Acute kidney injury and cardiovascular outcomes in acute severe hypertension.

PubMed

Szczech, Lynda A; Granger, Christopher B; Dasta, Joseph F; Amin, Alpesh; Peacock, W Frank; McCullough, Peter A; Devlin, John W; Weir, Matthew R; Katz, Jason N; Anderson, Frederick A; Wyman, Allison; Varon, Joseph

2010-05-25

Little is known about the association of kidney dysfunction and outcome in acute severe hypertension. This study aimed to measure the association between baseline chronic kidney disease (estimated glomerular filtration rate), acute kidney injury (AKI, decrease in estimated glomerular filtration rate > or =25% from baseline) and outcome in patients hospitalized with acute severe hypertension. The Studying the Treatment of Acute Hypertension (STAT) registry enrolled patients with acute severe hypertension, defined as > or =1 blood pressure measurement >180 mm Hg systolic and/or >110 mm Hg diastolic and treated with intravenous antihypertensive therapy. Data were compared across groups categorized by admission estimated glomerular filtration rate and AKI during admission. On admission, 79% of the cohort (n=1566) had at least mild chronic kidney disease (estimated glomerular filtration rate <60 mL/min in 46%, <30 mL/min in 22%). Chronic kidney disease patients were more likely to develop heart failure (P<0.0001), non-ST-elevation myocardial infarction (P=0.003), and AKI (P<0.007). AKI patients were at greater risk of heart failure and cardiac arrest (P< or =0.0001 for both). Subjects with AKI experienced higher mortality at 90 days (P=0.003). Any acute loss of estimated glomerular filtration rate during hospitalization was independently associated with an increased risk of death (odds ratio, 1.05; P=0.03 per 10-mL/min decline). Other independent predictors of mortality included increasing age (P<0.0001), male gender (P=0.016), white versus black race (P=0.003), and worse baseline kidney function (P=0.003). Chronic kidney disease is a common comorbidity among patients admitted with acute severe hypertension, and AKI is a frequent form of acute target organ dysfunction, particularly in those with baseline chronic kidney disease. Any degree of AKI is associated with a greater risk of morbidity and mortality.

Determination of glomerular function in advanced renal failure.

PubMed Central

Manz, F; Alatas, H; Kochen, W; Lutz, P; Rebien, W; Schärer, K

1977-01-01

In 15 children with advanced chronic renal failure, glomerular filtration rate was determined by different methods. Inulin clearance correlated well with the mean of creatinine and urea clearance, and also with 51-chromium edetic acid (EDTA) clearance measured over 24 hours. The absolute values of creatinine clearance and of 51Cr-EDTA clearance measured up to 8 hours were higher than inulin clearance. In advanced renal failure both the 51Cr-EDTA clearance measured over 24 hours, and the mean of creatinine and urea clearance, provide acceptable estimates of true glomerular filtration rate. PMID:411426

The synthetic triterpenoid, RTA405, increases glomerular filtration rate and reduces angiotensin II-induced contraction of glomerular mesangial cells

PubMed Central

Ding, Yanfeng; Stidham, Rhesa; Bumeister, Ron; Trevino, Isaac; Winters, Ali; Sprouse, Marc; Ding, Min; Ferguson, Deborah A.; Meyer, Colin J.; Wigley, W. Christian; Ma, Rong

2012-01-01

Bardoxolone methyl, a synthetic triterpenoid, improves the estimated glomerular filtration rate (GFR) in patients with chornic kidney disease and type 2 diabetes. Since the contractile activity of mesangial cells may influence glomerular filtration, we evaluated the effect of the synthetic triterpenoid RTA405 with structural similarity to bardoxolone methyl, on GFR in rats and on mesangial cell contractility in freshly isolated glomeruli. In rats, RTA 405 increased basal GFR, assessed by inulin clearance, and attenuated the angiotensin II-induced decline in GFR. RTA 405 increased the filtration fraction, but did not affect arterial blood pressure or renal plasma flow. Glomeruli from RTA 405-treated rats were resistant to angiotensin II-induced volume reduction ex vivo. In cultured mesangial cells, angiotensin II-stimulated contraction was attenuated by RTA 405, in a dose- and time-dependent fashion. Further, Nrf2 targeted gene transcription (regulates antioxidant, anti-inflammatory, and cytoprotective responses) in mesangial cells was associated with decreased basal and reduced angiotensin II-stimulated hydrogen peroxide and calcium ion levels. These mechanisms contribute to the GFR increase that occurs following treatment with RTA 405 in rats and may underlie the effect of bardoxolone methyl on the estimated GFR in patients. PMID:23235569

The synthetic triterpenoid, RTA 405, increases the glomerular filtration rate and reduces angiotensin II-induced contraction of glomerular mesangial cells.

PubMed

Ding, Yanfeng; Stidham, Rhesa D; Bumeister, Ron; Trevino, Isaac; Winters, Ali; Sprouse, Marc; Ding, Min; Ferguson, Deborah A; Meyer, Colin J; Wigley, W Christian; Ma, Rong

2013-05-01

Bardoxolone methyl, a synthetic triterpenoid, improves the estimated glomerular filtration rate (GFR) in patients with chronic kidney disease and type 2 diabetes. Since the contractile activity of mesangial cells may influence glomerular filtration, we evaluated the effect of the synthetic triterpenoid RTA 405, with structural similarity to bardoxolone methyl, on GFR in rats and on mesangial cell contractility in freshly isolated glomeruli. In rats, RTA 405 increased basal GFR, assessed by inulin clearance, and attenuated the angiotensin II-induced decline in GFR. RTA 405 increased the filtration fraction, but did not affect arterial blood pressure or renal plasma flow. Glomeruli from RTA 405-treated rats were resistant to angiotensin II-induced volume reduction ex vivo. In cultured mesangial cells, angiotensin II-stimulated contraction was attenuated by RTA 405, in a dose- and time-dependent fashion. Further, Nrf2-targeted gene transcription (regulates antioxidant, anti-inflammatory, and cytoprotective responses) in mesangial cells was associated with decreased basal and reduced angiotensin II-stimulated hydrogen peroxide and calcium ion levels. These mechanisms contribute to the GFR increase that occurs following treatment with RTA 405 in rats and may underlie the effect of bardoxolone methyl on the estimated GFR in patients.

Maremar, prevalence of chronic kidney disease, how to avoid over-diagnosis and under-diagnosis.

PubMed

De Broe, Marc E; Gharbi, Mohammed Benghanem; Elseviers, Monique

2016-04-01

Chronic kidney disease is considered as a major public health problem. Recent studies mention a prevalence rate between 8%-12%. Several editorials, comments, short reviews described the weaknesses (lack of confirmation of proteinuria, and of chronicity of decreased estimated glomerular filtration rate) of a substantial number of studies and the irrational of using a single arbitrary set point, i.e. diagnosis of chronic kidney disease whenever the estimated glomerular filtration rate is less than 60mL/min/1.73m(2). Maremar (Maladies rénales chroniques au Maroc) is a prevalence study of chronic kidney disease, hypertension, diabetes and obesity in a randomized, representative, high response rate (85%), sample of the adult population of Morocco, strictly applying the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Compared to the vast majority of the available studies, Maremar has a low prevalence of chronic kidney disease (2.9% adjusted to the actual adult population of Morocco). The population pyramid, and particularly the confirmation of proteinuria and "chronicity" of the decreased estimated glomerular filtration rate are the main reasons for this low prevalence of chronic kidney disease. The choice of arbitrary single threshold of estimated glomerular filtration rate for classifying stage 3-5 chronic kidney disease inevitably leads to "over-diagnosis" (false positives) of the disease in the elderly, particularly those without proteinuria, hematuria or hypertension, and to "under-diagnosed" (false negatives) in younger individuals with an estimated glomerular filtration rate above 60mL/min/1.73m(2) and below the 3rd percentile of their age/gender category. There is an urgent need for quality studies using in a correct way the recent KDIGO guidelines when investigating the prevalence of chronic kidney disease, in order to avoid a 50 to 100% overestimation of a disease state with potential dramatic consequences. The combination of the general population screening encompassing four different major health problems in the same screening procedure, using the correct methodologies and procedures, combined with a prevention/follow-up program results in a clinically/scientifically relevant program. Copyright © 2016 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Two-year analysis for predicting renal function and contralateral hypertrophy after robot-assisted partial nephrectomy: A three-dimensional segmentation technology study.

PubMed

Kim, Dae Keun; Jang, Yujin; Lee, Jaeseon; Hong, Helen; Kim, Ki Hong; Shin, Tae Young; Jung, Dae Chul; Choi, Young Deuk; Rha, Koon Ho

2015-12-01

To analyze long-term changes in both kidneys, and to predict renal function and contralateral hypertrophy after robot-assisted partial nephrectomy. A total of 62 patients underwent robot-assisted partial nephrectomy, and renal parenchymal volume was calculated using three-dimensional semi-automatic segmentation technology. Patients were evaluated within 1 month preoperatively, and postoperatively at 6 months, 1 year and continued up to 2-year follow up. Linear regression models were used to identify the factors predicting variables that correlated with estimated glomerular filtration rate changes and contralateral hypertrophy 2 years after robot-assisted partial nephrectomy. The median global estimated glomerular filtration rate changes were -10.4%, -11.9%, and -2.4% at 6 months, 1 and 2 years post-robot-assisted partial nephrectomy, respectively. The ipsilateral kidney median parenchymal volume changes were -24%, -24.4%, and -21% at 6 months, 1 and 2 years post-robot-assisted partial nephrectomy, respectively. The contralateral renal volume changes were 2.3%, 9.6% and 12.9%, respectively. On multivariable linear analysis, preoperative estimated glomerular filtration rate was the best predictive factor for global estimated glomerular filtration rate change on 2 years post-robot-assisted partial nephrectomy (B -0.452; 95% confidence interval -0.84 to -0.14; P = 0.021), whereas the parenchymal volume loss rate (B -0.43; 95% confidence interval -0.89 to -0.15; P = 0.017) and tumor size (B 5.154; 95% confidence interval -0.11 to 9.98; P = 0.041) were the significant predictive factors for the degree of contralateral renal hypertrophy on 2 years post-robot-assisted partial nephrectomy. Preoperative estimated glomerular filtration rate significantly affects post-robot-assisted partial nephrectomy renal function. Renal mass size and renal parenchyma volume loss correlates with compensatory hypertrophy of the contralateral kidney. Contralateral hypertrophy of the renal parenchyma compensates for the functional loss of the ipsilateral kidney. © 2015 The Japanese Urological Association.

Serum uric acid to creatinine ratio: A predictor of incident chronic kidney disease in type 2 diabetes mellitus patients with preserved kidney function.

PubMed

Gu, Liubao; Huang, Liji; Wu, Haidi; Lou, Qinglin; Bian, Rongwen

2017-05-01

Serum uric acid has shown to be a predictor of renal disease progression in most but not all studies. This study aims to test whether renal function-normalized serum uric acid is superior to serum uric acid as the predictor of incident chronic kidney disease in type 2 diabetes mellitus patients. In this study, 1339 type 2 diabetes mellitus patients with estimated glomerular filtration rate ⩾60 mL/min/1.73 m 2 and normouricemia were included. Renal function-normalized serum uric acid was calculated using serum uric acid/creatinine. Cox regression analysis was used to estimate the association between serum uric acid, renal function-normalized serum uric acid and incident chronic kidney disease. In total, 74 (5.53%) patients developed to chronic kidney disease 3 or greater during a median follow-up of 4 years, with older ages, longer diabetes duration and lower estimated glomerular filtration rate at baseline. The decline rate of estimated glomerular filtration rate was positively correlated with serum uric acid/creatinine ( r = 0.219, p < 0.001), but not serum uric acid ( r = 0.005, p = 0.858). Moreover, multivariate analysis revealed that serum uric acid was not an independent risk factor for incident chronic kidney disease ( p = 0.055), whereas serum uric acid to creatinine ratio was significantly associated with incident chronic kidney disease independently of potential confounders including baseline estimated glomerular filtration rate. serum uric acid to creatinine ratio might be a better predictor of incident chronic kidney disease in type 2 diabetes mellitus patients.

A 68-year old male presenting with rhabdomyolysis-associated acute kidney injury following concomitant use of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate and pravastatin/fenofibrate: a case report.

PubMed

Suttels, Veronique; Florence, Eric; Leys, John; Vekemans, Marc; Van den Ende, Jef; Vlieghe, Erika; Kenyon, Chris

2015-09-08

We present what we believe to be the first case in the literature of rhabdomyolysis-induced renal failure caused by a probable drug interaction between elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) and pravastatin/fenofibrate. A 68-year old Caucasian man presented with progressive pain in both legs two weeks after commencing treatment with EVG/COBI/FTC/TDF. He was found to have biochemical evidence of rhabdomyolysis and acute renal failure. We emphasize the need for post marketing surveillance of adverse effects of new products. Pharmacokinetic studies are necessary to investigate the levels of pravastatin in patients taking COBI and fenofibrate with and without other comorbidities. Meanwhile, we suggest that creatine kinase levels should be monitored and patients advised to report myalgias when using concomitant EVG/COBI/FTC/TDF and pravastatin/fenofibrate. This case serves as an important reminder to use estimated glomerular filtration rates rather than serum creatinine levels when choosing new medications. If potentially nephrotoxic combinations are started in patients with borderline estimated glomerular filtration rates, it may be prudent to check these filtration rates more frequently than usual. In patients with reduced estimated glomerular filtration rates, potentially nephrotoxic combinations should be avoided wherever possible.

Glomerular filtration rate and kidney size in type 2 (non-insulin-dependent) diabetes mellitus.

PubMed

Wirta, O R; Pasternack, A I

1995-07-01

The objective of the present study was to estimate glomerular filtration rate and kidney size in recently diagnosed and long-term type 2 (non-insulin-dependent) diabetic subjects. The study design comprised of a population-based controlled cross-sectional survey of middle-aged type 2 diabetic subjects in the City of Tampere, Southwest Finland. One hundred and fifty consecutive recently diagnosed and 146 long-term middle-aged type 2 diabetic subjects with a disease duration of at least five years and one hundred and fifty age- and sex-matched (to recent diabetic subjects) non-diabetic control subjects were recruited. The glomerular filtration rate by single-shot 51Cr-EDTA clearance and kidney size by native X-ray tomography were measured. The glomerular filtration rate (ml/min/1.73 m2) was increased in both recently diagnosed (males 121 [27] and females 112 [27]) and long-term (males 123 [24] and females 102 [36]) diabetic subjects (corrected for age) compared to control subjects (males 111 [26] and females 93 [17]). The kidney areas (cm2) were greater in both recent diabetic (males 116.6 [15.4] and females 99.1 [15.3] and long-term diabetic (males 118.3 [15.8] and females 100.4 [15.2]) subjects than in the control group (males 104.3 [12.0] and females 88.6 [12.0]). All differences between diabetic subjects and non-diabetic subjects were statistically significant (p < 0.05), except that between long-term diabetic and non-diabetic females for glomerular filtration rate (p = 0.07). Analyzed by linear regression glomerular filtration rate was related to kidney area in all study groups and to hemoglobin A1c in long-term diabetic males.(ABSTRACT TRUNCATED AT 250 WORDS)

Association of the cystatin C/creatinine ratio with the renally cleared hormones parathyroid hormone (PTH) and brain natriuretic peptide (BNP) in primary care patients: a cross-sectional study.

PubMed

Risch, Martin; Risch, Lorenz; Purde, Mette-Triin; Renz, Harald; Ambühl, Patrice; Szucs, Thomas; Tomonaga, Yuki

2016-09-01

The ratio of cystatin C to creatinine (cysC/crea) is regarded as a marker of glomerular filtration quality and predicts mortality. It has been hypothesized that increased mortality may be mediated by the retention of biologically active substances due to shrinking glomerular pores. The present study investigated whether cysC/crea is independently associated with the levels of two renally cleared hormones, which have been linked to increased mortality. We conducted a multicenter, cross-sectional study with a random selection of general practitioners (GPs) from all GP offices in seven Swiss cantons. Markers of glomerular filtration quality were investigated together with estimated glomerular filtration rate (eGFR), albuminuria and urinary neutrophil gelatinase associated lipocalin (uNGAL) as well as two renally cleared low-molecular-weight protein hormones (i.e. BNP and PTH), Morbidity was assessed with the Charlson Comorbidity Index (CCI). A total of 1000 patients (433 males; mean age 57 ± 17 years) were included. There was a significant univariate association of BNP (r = 0.36, p < 0.001) and PTH (r = 0.18, p < 0.001) with cysC/crea. An adjusted model that accounted for kidney function (eGFR), altered glomerular structure (albuminuria), renal stress (uNGAL), and CCI showed that BNP and PTH were independently associated with cysC/crea as well as with the ratio of cystatin C-based to creatinine-based eGFR. In conclusion, in primary care patients, BNP and PTH are independently associated both with markers of glomerular filtration quality and eGFR regardless of structural kidney damage or renal stress. These findings offer an explanation, how altered glomerular filtration quality could contribute to increased mortality.

Addition of vitamin D reverses the decline in GFR following treatment with ACE inhibitors/angiotensin receptor blockers in patients with chronic kidney disease.

PubMed

Soares, Abel Esteves; Maes, Michael; Godeny, Paula; Matsumoto, Andressa Keiko; Barbosa, Décio Sabbatini; da Silva, Taysa Antonia F; Souza, Flávio Henrique M O; Delfino, Vinicius Daher Alvares

2017-12-15

Vitamin D has anti-inflammatory, anti-fibrotic effect, and may block the intrarenal renin-angiotensin system. Adequate vitamin D levels in conjunction with the use of Angiotensin-converting Enzyme Inhibitors/Angiotensin Receptor Blockers may help to slow down chronic kidney disease progression. To study a possible beneficial effect of vitamin D supplementation in chronic kidney disease patients using angiotensin-converting enzyme inhibitors/angiotensin receptor blockers on chronic kidney disease progression we performed a clinical study involving vitamin D supplementation in patients with deficiency of this vitamin. This study was conducted in two chronic kidney disease clinics in the city of Londrina, Brazil, from October 2010 to December 2012. It was involved stage 3 and 4 chronic kidney disease (estimated glomerular filtration rate between 60 and 15mL/min/1.73m 2 ) patients with and without vitamin D deficiency. The patients ingested six-month cholecalciferol 50,000IU oral supplementation to chronic kidney disease patients with vitamin D deficiency. We hypothesize changes in estimated glomerular filtration rate over study period. Our data demonstrate reservation of estimated glomerular filtration with cholecalciferol supplementation to chronic kidney disease patients taking angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. The combination treatment of angiotensin converting enzyme inhibitors/angiotensin receptor blockers with cholecalciferol prevents the decline in estimated glomerular filtration in patients with chronic kidney disease following treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and may represent a valid approach to reduce renal disease progression in chronic kidney disease patients with vitamin D deficiency. This result needs confirmation in prospective controlled clinical trials. Copyright © 2017. Published by Elsevier Inc.

Association of Pulse Wave Velocity With Chronic Kidney Disease Progression and Mortality: Findings From the CRIC Study (Chronic Renal Insufficiency Cohort).

PubMed

Townsend, Raymond R; Anderson, Amanda Hyre; Chirinos, Julio A; Feldman, Harold I; Grunwald, Juan E; Nessel, Lisa; Roy, Jason; Weir, Matthew R; Wright, Jackson T; Bansal, Nisha; Hsu, Chi-Yuan

2018-06-01

Patients with chronic kidney diseases (CKDs) are at risk for further loss of kidney function and death, which occur despite reasonable blood pressure treatment. To determine whether arterial stiffness influences CKD progression and death, independent of blood pressure, we conducted a prospective cohort study of CKD patients enrolled in the CRIC study (Chronic Renal Insufficiency Cohort). Using carotid-femoral pulse wave velocity (PWV), we examined the relationship between PWV and end-stage kidney disease (ESRD), ESRD or halving of estimated glomerular filtration rate, or death from any cause. The 2795 participants we enrolled had a mean age of 60 years, 56.4% were men, 47.3% had diabetes mellitus, and the average estimated glomerular filtration rate at entry was 44.4 mL/min per 1.73 m 2 During follow-up, there were 504 ESRD events, 628 ESRD or halving of estimated glomerular filtration rate events, and 394 deaths. Patients with the highest tertile of PWV (>10.3 m/s) were at higher risk for ESRD (hazard ratio [95% confidence interval], 1.37 [1.05-1.80]), ESRD or 50% decline in estimated glomerular filtration rate (hazard ratio [95% confidence interval], 1.25 [0.98-1.58]), or death (hazard ratio [95% confidence interval], 1.72 [1.24-2.38]). PWV is a significant predictor of CKD progression and death in people with impaired kidney function. Incorporation of PWV measurements may help define better the risks for these important health outcomes in patients with CKDs. Interventions that reduce aortic stiffness deserve study in people with CKD. © 2018 American Heart Association, Inc.

Clinical and Biochemical Characteristics of Brain-Dead Donors as Predictors of Early- and Long-Term Renal Function After Transplant.

PubMed

Kwiatkowska, Ewa; Domański, Leszek; Bober, Joanna; Safranow, Krzysztof; Pawlik, Andrzej; Ciechanowski, Kazimierz; Wiśniewska, Magda; Kędzierska, Karolina

2017-08-01

Organs from brain-dead donors are the main source of allografts for transplant. Comparisons between living-donor and brain-dead donor kidneys show that the latter are more likely to demonstrate delayed graft function and lower long-term survival. This study aimed to assess the effects of various clinical and biochemical factors of donors on early- and long-term renal function after transplant. We analyzed data from kidney recipients treated between 2006 and 2008 who received organs from brain-dead donors. Data from 54 donors and 89 recipients were analyzed. No relation was observed between donor sodium concentration and the presence of delayed graft function. Donor height was positively correlated with creatinine clearance in recipients in the 1 to 3 months after renal transplant. Donor diastolic blood pressure was negatively correlated with estimated glomerular filtration rate throughout the observation period. Donor age was negatively correlated with the allograft recipient's estimated glomerular filtration rate throughout 4 years of observation. Donor estimated glomerular filtration rate was positively correlated with that of the recipient throughout 3 years of observation. The results of this study indicate that various factors associated with allograft donors may influence graft function.

Superiority of Serum Cystatin C Over Creatinine in Prediction of Long-Term Prognosis at Discharge From ICU.

PubMed

Ravn, Bo; Prowle, John R; Mårtensson, Johan; Martling, Claes-Roland; Bell, Max

2017-09-01

Renal outcomes after critical illness are seldom assessed despite strong correlation between chronic kidney disease and survival. Outside hospital, renal dysfunction is more strongly associated with mortality when assessed by serum cystatin C than by creatinine. The relationship between creatinine and longer term mortality might be particularly weak in survivors of critical illness. Retrospective observational cohort study. In 3,077 adult ICU survivors, we compared ICU discharge cystatin C and creatinine and their association with 1-year mortality. Exclusions were death within 72 hours of ICU discharge, ICU stay less than 24 hours, and end-stage renal disease. None. During ICU admission, serum cystatin C and creatinine diverged, so that by ICU discharge, almost twice as many patients had glomerular filtration rate less than 60 mL/min/1.73 m when estimated from cystatin C compared with glomerular filtration rate estimated from creatinine, 44% versus 26%. In 743 patients without acute kidney injury, where ICU discharge renal function should reflect ongoing baseline, discharge glomerular filtration rate estimated from creatinine consistently overestimated follow-up glomerular filtration rate estimated from creatinine, whereas ICU discharge glomerular filtration rate estimated from cystatin C well matched follow-up chronic kidney disease status. By 1 year, 535 (17.4%) had died. In survival analysis adjusted for age, sex, and comorbidity, cystatin C was near-linearly associated with increased mortality, hazard ratio equals to 1.78 (95% CI, 1.46-2.18), 75th versus 25th centile. Conversely, creatinine demonstrated a J-shaped relationship with mortality, so that in the majority of patients, there was no significant association with survival, hazard ratio equals to 1.03 (0.87-1.2), 75th versus 25th centile. After adjustment for both creatinine and cystatin C levels, higher discharge creatinine was then associated with lower long-term mortality. In contrast to creatinine, cystatin C consistently associated with long-term mortality, identifying patients at both high and low risk, and better correlated with follow-up renal function. Conversely, lower creatinine relative to cystatin C appeared to confer adverse prognosis, confounding creatinine interpretation in isolation. Cystatin C warrants further investigation as a more meaningful measure of renal function after critical illness.

Identification and characterization of kidney transplants with good glomerular filtration rate at 1 year but subsequent progressive loss of renal function.

PubMed

Park, Walter D; Larson, Timothy S; Griffin, Matthew D; Stegall, Mark D

2012-11-15

After the first year after kidney transplantation, 3% to 5% of grafts fail each year but detailed studies of how grafts progress to failure are lacking. This study aimed to analyze the functional stability of kidney transplants between 1 and 5 years after transplantation and to identify initially well-functioning grafts with progressive decline in allograft function. The study included 788 adult conventional kidney transplants performed at the Mayo Clinic Rochester between January 2000 and December 2005 with a minimum graft survival and follow-up of 2.6 years. The modification of diet in renal disease equation for estimating glomerular filtration rate (eGFR(MDRD)) was used to calculate the slope of renal function over time using all available serum creatinine values between 1 and 5 years after transplantation. Most transplants demonstrated good function (eGFR(MDRD) ≥40 mL/min) at 1 year with positive eGFR(MDRD) slope between 1 and 5 years after transplantation. However, a subset of grafts with 1-year eGFR(MDRD) ≥40 mL/min exhibited strongly negative eGFR(MDRD) slope between 1 and 5 years suggestive of progressive loss of graft function. Forty-one percent of this subset reached graft failure during follow-up, accounting for 69% of allograft failures occurring after 2.5 years after transplantation. This pattern of progressive decline in estimated glomerular filtration rate despite good early function was associated with but not fully attributable to factors suggestive of enhanced antidonor immunity. Longitudinal analysis of serial estimated glomerular filtration ratemeasurements identifies initially well-functioning kidney transplants at high risk for subsequent graft loss. For this subset, further studies are needed to identify modifiable causes of functional decline.

Impact of proteinuria and glomerular filtration rate on risk of ischaemic and intracerebral hemorrhagic stroke: a result from the Kailuan study.

PubMed

Li, Z; Wang, A; Cai, J; Gao, X; Zhou, Y; Luo, Y; Wu, S; Zhao, X

2015-02-01

Persons with chronic kidney disease, defined by a reduced estimated glomerular filtration rate and proteinuria, have an increased risk of cardiovascular disease including stroke. However, data from developing countries are limited. Our aim was to assess the relationship between chronic kidney disease and risk of stroke and its subtypes in a community-based population in China. The study was based on 92,013 participants (18-98 years old; 73,248 men and 18,765 women) of the Kailuan study who at baseline were free from stroke and myocardial infarction and had undergone tests for serum creatinine or proteinuria. Glomerular filtration rate was estimated using the Chronic Kidney Disease Epidemiology Collaboration formula and proteinuria by the urine dipstick result in laboratory databases. The primary outcome was the first occurrence of stroke. Data were analyzed using Cox proportional hazards models adjusted for relevant confounders and results are presented as hazard ratios (HRs) with 95% confidence intervals (CIs). During a follow-up of 4 years, 1575 stroke events (1128 ischaemic, 406 intracerebral hemorrhagic and 41 subarachnoid hemorrhagic strokes) occurred. After adjustment for variable confounders, patients with proteinuria were found to have increased HRs for the total and subtypes of stroke events (HR 1.61; 95% CI 1.35-1.92 for total stroke; HR 1.53; 95% CI 1.24-1.89 for ischaemic stroke; and HR 1.90; 95% CI 1.35-2.67 for hemorrhagic stroke). However, estimated glomerular filtration rate was not associated with incident stroke after adjustment for established cardiovascular risk factors. Proteinuria increased the risk of stroke in a general Chinese population. © 2014 EAN.

Retinopathy and chronic kidney disease in the Chronic Renal Insufficiency Cohort (CRIC) study.

PubMed

Grunwald, Juan E; Alexander, Judith; Ying, Gui-Shuang; Maguire, Maureen; Daniel, Ebenezer; Whittock-Martin, Revell; Parker, Candace; McWilliams, Kathleen; Lo, Joan C; Go, Alan; Townsend, Raymond; Gadegbeku, Crystal A; Lash, James P; Fink, Jeffrey C; Rahman, Mahboob; Feldman, Harold; Kusek, John W; Xie, Dawei; Jaar, Bernard G

2012-09-01

To investigate the association between retinopathy and chronic kidney disease. In this observational, cross-sectional study, 2605 patients of the Chronic Renal Insufficiency Cohort (CRIC) study, a multicenter study of chronic kidney disease, were offered participation. Nonmydriatic fundus photographs of the disc and macula in both eyes were obtained in 1936 of these subjects. The photographs were reviewed in a masked fashion at a central photograph reading center using standard protocols. Presence and severity of retinopathy (diabetic, hypertensive, or other) and vessel diameter caliber were assessed by trained graders and a retinal specialist using protocols developed for large epidemiologic studies. Kidney function measurements and information on traditional and nontraditional risk factors for decreased kidney function were obtained from the CRIC study. Greater severity of retinopathy was associated with lower estimated glomerular filtration rate after adjustment for traditional and nontraditional risk factors. The presence of vascular abnormalities usually associated with hypertension was also associated with lower estimated glomerular filtration rate. We found no strong direct relationship between estimated glomerular filtration rate and average arteriolar or venular calibers. Our findings show a strong association between severity of retinopathy and its features and level of kidney function after adjustment for traditional and nontraditional risk factors for chronic kidney disease, suggesting that retinovascular pathology reflects renal disease.

Resistant Hypertension, Time-Updated Blood Pressure Values and Renal Outcome in Type 2 Diabetes Mellitus.

PubMed

Viazzi, Francesca; Piscitelli, Pamela; Ceriello, Antonio; Fioretto, Paola; Giorda, Carlo; Guida, Pietro; Russo, Giuseppina; De Cosmo, Salvatore; Pontremoli, Roberto

2017-09-22

Apparent treatment resistant hypertension (aTRH) is highly prevalent in patients with type 2 diabetes mellitus (T2D) and entails worse cardiovascular prognosis. The impact of aTRH and long-term achievement of recommended blood pressure (BP) values on renal outcome remains largely unknown. We assessed the role of aTRH and BP on the development of chronic kidney disease in patients with T2D and hypertension in real-life clinical practice. Clinical records from a total of 29 923 patients with T2D and hypertension, with normal baseline estimated glomerular filtration rate and regular visits during a 4-year follow-up, were retrieved and analyzed. The association between time-updated BP control (ie, 75% of visits with BP <140/90 mm Hg) and the occurrence of estimated glomerular filtration rate <60 and/or a reduction ≥30% from baseline was assessed. At baseline, 17% of patients had aTRH. Over the 4-year follow-up, 19% developed low estimated glomerular filtration rate and 12% an estimated glomerular filtration rate reduction ≥30% from baseline. Patients with aTRH showed an increased risk of developing both renal outcomes (adjusted odds ratio, 1.31 and 1.43; P <0.001 respectively), as compared with those with non-aTRH. No association was found between BP control and renal outcomes in non-aTRH, whereas in aTRH, BP control was associated with a 30% ( P =0.036) greater risk of developing the renal end points. ATRH entails a worse renal prognosis in T2D with hypertension. BP control is not associated with a more-favorable renal outcome in aTRH. The relationship between time-updated BP and renal function seems to be J-shaped, with optimal systolic BP values between 120 and 140 mm Hg. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Estimated glomerular filtration rate is an early biomarker of cardiac surgery-associated acute kidney injury.

PubMed

Candela-Toha, Ángel; Pardo, María Carmen; Pérez, Teresa; Muriel, Alfonso; Zamora, Javier

2018-04-20

and objective Acute kidney injury (AKI) diagnosis is still based on serum creatinine and diuresis. However, increases in creatinine are typically delayed 48h or longer after injury. Our aim was to determine the utility of routine postoperative renal function blood tests, to predict AKI one or 2days in advance in a cohort of cardiac surgery patients. Using a prospective database, we selected a sample of patients who had undergone major cardiac surgery between January 2002 and December 2013. The ability of the parameters to predict AKI was based on Acute Kidney Injury Network serum creatinine criteria. A cohort of 3,962 cases was divided into 2groups of similar size, one being exploratory and the other a validation sample. The exploratory group was used to show primary objectives and the validation group to confirm results. The ability to predict AKI of several kidney function parameters measured in routine postoperative blood tests, was measured with time-dependent ROC curves. The primary endpoint was time from measurement to AKI diagnosis. AKI developed in 610 (30.8%) and 623 (31.4%) patients in the exploratory and validation samples, respectively. Estimated glomerular filtration rate using the MDRD-4 equation showed the best AKI prediction capacity, with values for the AUC ROC curves between 0.700 and 0.946. We obtained different cut-off values for estimated glomerular filtration rate depending on the degree of AKI severity and on the time elapsed between surgery and parameter measurement. Results were confirmed in the validation sample. Postoperative estimated glomerular filtration rate using the MDRD-4 equation showed good ability to predict AKI following cardiac surgery one or 2days in advance. Copyright © 2018 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Urinary albumin excretion is associated with nocturnal systolic blood pressure in resistant hypertensives.

PubMed

Oliveras, Anna; Armario, Pedro; Martell-Clarós, Nieves; Ruilope, Luis M; de la Sierra, Alejandro

2011-03-01

Microalbuminuria is a known marker of subclinical organ damage. Its prevalence is higher in patients with resistant hypertension than in subjects with blood pressure at goal. On the other hand, some patients with apparently well-controlled hypertension still have microalbuminuria. The current study aimed to determine the relationship between microalbuminuria and both office and 24-hour ambulatory blood pressure. A cohort of 356 patients (mean age 64 ± 11 years; 40.2% females) with resistant hypertension (blood pressure ≥ 140 and/or 90 mm Hg despite treatment with ≥ 3 drugs, diuretic included) were selected from Spanish hypertension units. Patients with estimated glomerular filtration rate <30 mL/min/1.73 m(2) were excluded. All patients underwent clinical and demographic evaluation, complete laboratory analyses, and good technical-quality 24-hour ambulatory blood pressure monitoring. Urinary albumin/creatinine ratio was averaged from 3 first-morning void urine samples. Microalbuminuria (urinary albumin/creatinine ratio ≥ 2.5 mg/mmol in males or ≥ 3.5 mg/mmol in females) was detected in 46.6%, and impaired renal function (estimated glomerular filtration rate <60 mL/min/1.73 m(2)) was detected in 26.8%. Bivariate analyses showed significant associations of microalbuminuria with older age, reduced estimated glomerular filtration rate, increased nighttime systolic blood pressure, and elevated daytime, nighttime, and 24-hour diastolic blood pressure. In a logistic regression analysis, after age and sex adjustment, elevated nighttime systolic blood pressure (multivariate odds ratio, 1.014 [95% CI, 1.001 to 1.026]; P=0.029) and reduced estimated glomerular filtration rate (multivariate odds ratio, 2.79 [95% CI, 1.57 to 4.96]; P=0.0005) were independently associated with the presence of microalbuminuria. We conclude that microalbuminuria is better associated with increased nighttime systolic blood pressure than with any other office and 24-hour ambulatory blood pressure monitoring parameters.

Compensatory Structural and Functional Adaptation after Radical Nephrectomy for Renal Cell Carcinoma According to Preoperative Stage of Chronic Kidney Disease.

PubMed

Choi, Don Kyoung; Jung, Se Bin; Park, Bong Hee; Jeong, Byong Chang; Seo, Seong Il; Jeon, Seong Soo; Lee, Hyun Moo; Choi, Han-Yong; Jeon, Hwang Gyun

2015-10-01

We investigated structural hypertrophy and functional hyperfiltration as compensatory adaptations after radical nephrectomy in patients with renal cell carcinoma according to the preoperative chronic kidney disease stage. We retrospectively identified 543 patients who underwent radical nephrectomy for renal cell carcinoma between 1997 and 2012. Patients were classified according to preoperative glomerular filtration rate as no chronic kidney disease--glomerular filtration rate 90 ml/minute/1.73 m(2) or greater (230, 42.4%), chronic kidney disease stage II--glomerular filtration rate 60 to less than 90 ml/minute/1.73 m(2) (227, 41.8%) and chronic kidney disease stage III--glomerular filtration rate 30 to less than 60 ml/minute/1.73 m(2) (86, 15.8%). Computerized tomography performed within 2 months before surgery and 1 year after surgery was used to assess functional renal volume for measuring the degree of hypertrophy of the remnant kidney, and the preoperative and postoperative glomerular filtration rate per unit volume of functional renal volume was used to calculate the degree of hyperfiltration. Among all patients (mean age 56.0 years) mean preoperative glomerular filtration rate, functional renal volume and glomerular filtration rate/functional renal volume were 83.2 ml/minute/1.73 m(2), 340.6 cm(3) and 0.25 ml/minute/1.73 m(2)/cm(3), respectively. The percent reduction in glomerular filtration rate was statistically significant according to chronic kidney disease stage (no chronic kidney disease 31.2% vs stage II 26.5% vs stage III 12.8%, p <0.001). However, the degree of hypertrophic functional renal volume in the remnant kidney was not statistically significant (no chronic kidney disease 18.5% vs stage II 17.3% vs stage III 16.5%, p=0.250). The change in glomerular filtration rate/functional renal volume was statistically significant (no chronic kidney disease 18.5% vs stage II 20.1% vs stage III 45.9%, p <0.001). Factors that increased glomerular filtration rate/functional renal volume above the mean value were body mass index (p=0.012), diabetes mellitus (p=0.023), hypertension (p=0.015) and chronic kidney disease stage (p <0.001). Patients with a lower preoperative glomerular filtration rate had a smaller reduction in postoperative renal function than those with a higher preoperative glomerular filtration rate due to greater degrees of functional hyperfiltration. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Transport of Spherical Particles Through Fibrous Media and a Row of Parallel Cylinders: Applications to Glomerular Filtration.

PubMed

Punyaratabandhu, Numpong; Kongoup, Pimkhwan; Dechadilok, Panadda; Katavetin, Pisut; Triampo, Wannapong

2017-12-01

Viewed in renal physiology as a refined filtration device, the glomerulus filters large volumes of blood plasma while keeping proteins within blood circulation. Effects of macromolecule size and macromolecule hydrodynamic interaction with the nanostructure of the cellular layers of the glomerular capillary wall on the glomerular size selectivity are investigated through a mathematical simulation based on an ultrastructural model. The epithelial slit, a planar arrangement of fibers connecting the epithelial podocytes, is represented as a row of parallel cylinders with nonuniform spacing between adjacent fibers. The mean and standard deviation of gap half-width between its fibers are based on values recently reported from electron microscopy. The glomerular basement membrane (GBM) is represented as a fibrous medium containing fibers of two different sizes: the size of type IV collagens and that of glycosaminoglycans (GAGs). The endothelial cell layer is modeled as a layer full of fenestrae that are much larger than solute size and filled with GAGs. The calculated total sieving coefficient agrees well with the sieving coefficients of ficolls obtained from in vivo urinalysis in humans, whereas the computed glomerular hydraulic permeability also falls within the range estimated from human glomerular filtration rate (GFR). Our result indicates that the endothelial cell layer and GBM significantly contribute to solute and fluid restriction of the glomerular barrier, whereas, based on the structure of the epithelial slit obtained from electron microscopy, the contribution of the epithelial slit could be smaller than previously believed.

The Dynamics of Glomerular Ultrafiltration in the Rat

PubMed Central

Brenner, Barry M.; Troy, Julia L.; Daugharty, Terrance M.

1971-01-01

Using a unique strain of Wistar rats endowed with glomeruli situated directly on the renal cortical surface, we measured glomerular capillary pressures using servo-nulling micropipette transducer techniques. Pressures in 12 glomerular capillaries from 7 rats averaged 60 cm H2O, or approximately 50% of mean systemic arterial values. Wave form characteristics for these glomerular capillaries were found to be remarkably similar to those of the central aorta. From similarly direct estimates of hydrostatic pressures in proximal tubules, and colloid osmotic pressures in systemic and efferent arteriolar plasmas, the net driving force for ultrafiltration was calculated. The average value of 14 cm H2O is lower by some two-thirds than the majority of estimates reported previously based on indirect techniques. Single nephron GFR (glomerular filtration rate) was also measured in these rats, thereby permitting calculation of the glomerular capillary ultrafiltration coefficient. The average value of 0.044 nl sec−1 cm H2O−1 glomerulus−1 is at least fourfold greater than previous estimates derived from indirect observations. PMID:5097578

The impact of tabalumab on the kidney in systemic lupus erythematosus: results from two phase 3 randomized, clinical trials.

PubMed

Rovin, B H; Dooley, M A; Radhakrishnan, J; Ginzler, E M; Forrester, T D; Anderson, P W

2016-12-01

Tabalumab is a monoclonal antibody that neutralizes membrane and soluble B-cell activating factor. Two 52-week, randomized, double-blind, placebo controlled phase 3 trials evaluated the safety and efficacy of tabalumab in systemic lupus erythematosus. Patients with moderate to severe active systemic lupus erythematosus (without severe active lupus nephritis) were randomly assigned 1:1:1 to receive tabalumab (120 mg subcutaneously every 2 or 4 weeks) or placebo for 52 weeks. Serum creatinine concentration, estimated glomerular filtration rate, urine protein/creatinine ratio, renal flares and renal adverse events were determined monthly. Data were analyzed for the intent-to-treat population and for intent-to-treat patients with baseline urine protein/creatinine ratio >20 mg/mmol (intent-to-treat plus urine protein/creatinine ratio). The trials enrolled 2262 patients. At baseline, demographics, systemic lupus erythematosus disease activity, serum creatinine concentration, estimated glomerular filtration rate and urine protein/creatinine ratio were similar among the treatment arms (with the exception of disease duration). In the intent-to-treat and intent-to-treat plus urine protein/creatinine ratio populations, there were no differences between the arms in the baseline-to-endpoint change in serum creatinine concentration, glomerular filtration rate, urine protein/creatinine ratio, or renal flare rates. Tabalumab resulted in a significant B-cell reduction and decreased immunoglobulin G levels at both doses. Compared to placebo, tabalumab did not significantly affect the serum creatinine concentration, glomerular filtration rate, urine protein/creatinine ratio, or renal flare rates over 1 year in intent-to-treat or intent-to-treat plus urine protein/creatinine ratio patients. There were no significant renal safety signals.ClinicalTrials.gov identifiers: NCT01205438 and NCT01196091 Lupus (2016) 25, 1597-1601. © The Author(s) 2016.

Prevalence of and risk factors for reduced serum bicarbonate in chronic kidney disease.

PubMed

Raphael, Kalani L; Zhang, Yingying; Ying, Jian; Greene, Tom

2014-10-01

The prevalence of metabolic acidosis increases as glomerular filtration rate falls. However, most patients with stage 4 chronic kidney disease have normal serum bicarbonate concentration while some with stage 3 chronic kidney disease have low serum bicarbonate, suggesting that other factors contribute to generation of acidosis. The purpose of this study is to identify risk factors, other than reduced glomerular filtration rate, for reduced serum bicarbonate in chronic kidney disease. This is a cross-sectional analysis of baseline data from the Chronic Renal Insufficiency Cohort Study. Multivariable logistic and linear regression models were used to relate predictor variables to the odds of low serum bicarbonate (< 22 mM) compared with normal serum bicarbonate (22-30 mM) and the coefficients of Δ serum bicarbonate concentration. The prevalence of low serum bicarbonate at baseline was 17.3%. Lower estimated glomerular filtration rate had the strongest relationship with low serum bicarbonate. Factors associated with higher odds of low serum bicarbonate, independent of estimated glomerular filtration rate, were urinary albumin/creatinine ≥ 10 mg/g, smoking, anaemia, hyperkalaemia, non-diuretic use and higher serum albumin. These and younger age, higher waist circumference, and use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers associated with negative Δ serum bicarbonate in linear regression models. Several factors not typically considered to associate with reduced serum bicarbonate in chronic kidney disease were identified including albuminuria ≥ 10 mg/g, anaemia, smoking, higher serum albumin, higher waist circumference, and use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers. Future studies should explore the longitudinal effect of these factors on serum bicarbonate concentration. © 2014 Asian Pacific Society of Nephrology.

Impact of Sofosbuvir-Based Regimens for the Treatment of Hepatitis C After Liver Transplant on Renal Function: Results of a Canadian National Retrospective Study.

PubMed

Faisal, Nabiha; Bilodeau, Marc; Aljudaibi, Bandar; Hirch, Geri; Yoshida, Eric M; Hussaini, Trana; Ghali, Maged P; Congly, Stephen E; Ma, Mang M; Lilly, Leslie B

2018-04-04

We assessed the impact of sofosbuvir-based regimens on renal function in liver transplant recipients with recurrent hepatitis C virus and the role of renal function on the efficacy and safety of these regimens. In an expanded pan-Canadian cohort, 180 liver transplant recipients were treated with sofosbuvir-based regimens for hepatitis C virus recurrence from January 2014 to May 2015. Mean age was 58 ± 6.85 years, and 50% had F3/4 fibrosis. Patients were stratified into 4 groups based on baseline estimated glomerular filtration rate (calculated by the Modification of Diet in Renal Disease formula): < 30, 30 to 45, 46 to 60, and > 60 mL/min/173 m2. The primary outcome was posttreatment changes in renal function from baseline. Secondary outcomes included sustained virologic response at 12 weeks posttreatment and anemia-related and serious adverse events. Posttreatment renal function was improved in most patients (58%). Renal function declined in 22% of patients, which was more marked in those with estimated glomerular filtration rate < 30 mL/min/173 m2, advanced cirrhosis (P = .05), and aggressive hepatitis C virus/fibrosing cholestatic hepatitis (P < .05). High rates (80%-88%) of sustained virologic response at 12 weeks posttreatment were seen across all renal function strata. Cirrhotic patients with glomerular filtration rates < 30 mL/min/173 m2 had sustained virologic response rates at 12 weeks posttreatment comparable to the overall patient group. Rates of anemia-related adverse events and transfusion requirements increased across decreasing estimated glomerular filtration rate groups, with notably more occurrences with ribavirin-based regimens. Sofosbuvir-based regimens improved overall renal function in liver transplant recipients, with sustained virologic response, suggesting an association of subclinical hepatitis C virus-related renal disease. Sustained virologic response rates at 12 weeks posttreatment (80%-88%) were comparable regardless of baseline renal function but lower in cirrhosis.

Herpes

MedlinePlus

... Testing Epstein-Barr Virus (EBV) Antibody Tests Erythrocyte Sedimentation Rate (ESR) Erythropoietin Estimated Glomerular Filtration Rate (eGFR) ... Available online at http://health.lifestyle.yahoo.ca/channel_section_details.asp?text_id=1364&channel_id= ...

Assessing the cost effectiveness of using prognostic biomarkers with decision models: case study in prioritising patients waiting for coronary artery surgery

PubMed Central

Henriksson, Martin; Palmer, Stephen; Chen, Ruoling; Damant, Jacqueline; Fitzpatrick, Natalie K; Abrams, Keith; Hingorani, Aroon D; Stenestrand, Ulf; Janzon, Magnus; Feder, Gene; Keogh, Bruce; Shipley, Martin J; Kaski, Juan-Carlos; Timmis, Adam; Sculpher, Mark

2010-01-01

Objective To determine the effectiveness and cost effectiveness of using information from circulating biomarkers to inform the prioritisation process of patients with stable angina awaiting coronary artery bypass graft surgery. Design Decision analytical model comparing four prioritisation strategies without biomarkers (no formal prioritisation, two urgency scores, and a risk score) and three strategies based on a risk score using biomarkers: a routinely assessed biomarker (estimated glomerular filtration rate), a novel biomarker (C reactive protein), or both. The order in which to perform coronary artery bypass grafting in a cohort of patients was determined by each prioritisation strategy, and mean lifetime costs and quality adjusted life years (QALYs) were compared. Data sources Swedish Coronary Angiography and Angioplasty Registry (9935 patients with stable angina awaiting coronary artery bypass grafting and then followed up for cardiovascular events after the procedure for 3.8 years), and meta-analyses of prognostic effects (relative risks) of biomarkers. Results The observed risk of cardiovascular events while on the waiting list for coronary artery bypass grafting was 3 per 10 000 patients per day within the first 90 days (184 events in 9935 patients). Using a cost effectiveness threshold of £20 000-£30 000 (€22 000-€33 000; $32 000-$48 000) per additional QALY, a prioritisation strategy using a risk score with estimated glomerular filtration rate was the most cost effective strategy (cost per additional QALY was <£410 compared with the Ontario urgency score). The impact on population health of implementing this strategy was 800 QALYs per 100 000 patients at an additional cost of £245 000 to the National Health Service. The prioritisation strategy using a risk score with C reactive protein was associated with lower QALYs and higher costs compared with a risk score using estimated glomerular filtration rate. Conclusion Evaluating the cost effectiveness of prognostic biomarkers is important even when effects at an individual level are small. Formal prioritisation of patients awaiting coronary artery bypass grafting using a routinely assessed biomarker (estimated glomerular filtration rate) along with simple, routinely collected clinical information was cost effective. Prioritisation strategies based on the prognostic information conferred by C reactive protein, which is not currently measured in this context, or a combination of C reactive protein and estimated glomerular filtration rate, is unlikely to be cost effective. The widespread practice of using only implicit or informal means of clinically ordering the waiting list may be harmful and should be replaced with formal prioritisation approaches. PMID:20085988

Urine podocyte mRNAs mark disease activity in IgA nephropathy

PubMed Central

Fukuda, Akihiro; Sato, Yuji; Iwakiri, Takashi; Komatsu, Hiroyuki; Kikuchi, Masao; Kitamura, Kazuo; Wiggins, Roger C.; Fujimoto, Shouichi

2015-01-01

Background Podocyte depletion is a major mechanism driving glomerulosclerosis. We and others have previously projected from model systems that podocyte-specific mRNAs in the urine pellet might serve as glomerular disease markers. We evaluated IgA nephropathy (IgAN) to test this concept. Methods From 2009 to 2013, early morning voided urine samples and kidney biopsies from IgAN patients (n = 67) were evaluated in comparison with urine samples from healthy age-matched volunteers (n = 28). Urine podocyte (podocin) mRNA expressed in relation to either urine creatinine concentration or a kidney tubular marker (aquaporin 2) was tested as markers. Results Urine podocyte mRNAs were correlated with the severity of active glomerular lesions (segmental glomerulosclerosis and acute extracapillary proliferation), but not with non-glomerular lesions (tubular atrophy/interstitial fibrosis) or with clinical parameters of kidney injury (serum creatinine and estimated glomerular filtration rate), or with degree of accumulated podocyte loss at the time of biopsy. In contrast, proteinuria correlated with all histological and clinical markers. Glomerular tuft podocyte nuclear density (a measure of cumulative podocyte loss) correlated with tubular atrophy/interstitial fibrosis, estimated-glomerular filtration rate and proteinuria, but not with urine podocyte markers. In a subset of the IgA cohort (n = 19, median follow-up period = 37 months), urine podocyte mRNAs were significantly decreased after treatment, in contrast to proteinuria which was not significantly changed. Conclusions Urine podocyte mRNAs reflect active glomerular injury at a given point in time, and therefore provide both different and additional clinical information that can complement proteinuria in the IgAN decision-making paradigm. PMID:25956757

Hyperkalemia After Initiating Renin-Angiotensin System Blockade: The Stockholm Creatinine Measurements (SCREAM) Project.

PubMed

Bandak, Ghassan; Sang, Yingying; Gasparini, Alessandro; Chang, Alex R; Ballew, Shoshana H; Evans, Marie; Arnlov, Johan; Lund, Lars H; Inker, Lesley A; Coresh, Josef; Carrero, Juan-Jesus; Grams, Morgan E

2017-07-19

Concerns about hyperkalemia limit the use of angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARBs), but guidelines conflict regarding potassium-monitoring protocols. We quantified hyperkalemia monitoring and risks after ACE-I/ARB initiation and developed and validated a hyperkalemia susceptibility score. We evaluated 69 426 new users of ACE-I/ARB therapy in the Stockholm Creatinine Measurements (SCREAM) project with medication initiation from January 1, 2007 to December 31, 2010, and follow-up for 1 year thereafter. Three fourths (76%) of SCREAM patients had potassium checked within the first year. Potassium >5 and >5.5 mmol/L occurred in 5.6% and 1.7%, respectively. As a comparison, we propensity-matched new ACE-I/ARB users to 20 186 new β-blocker users in SCREAM: 64% had potassium checked. The occurrence of elevated potassium levels was similar between new β-blocker and ACE-I/ARB users without kidney disease; only at estimated glomerular filtration rate <60 mL/min per 1.73 m 2 were risks higher among ACE-I/ARB users. We developed a hyperkalemia susceptibility score that incorporated estimated glomerular filtration rate, baseline potassium level, sex, diabetes mellitus, heart failure, and the concomitant use of potassium-sparing diuretics in new ACE-I/ARB users; this score accurately predicted 1-year hyperkalemia risk in the SCREAM cohort (area under the curve, 0.845, 95% CI: 0.840-0.869) and in a validation cohort from the US-based Geisinger Health System (N=19 524; area under the curve, 0.818, 95% CI: 0.794-0.841), with good calibration. Hyperkalemia within the first year of ACE-I/ARB therapy was relatively uncommon among people with estimated glomerular filtration rate >60 mL/min per 1.73 m 2 , but rates were much higher with lower estimated glomerular filtration rate. Use of the hyperkalemia susceptibility score may help guide laboratory monitoring and prescribing strategies. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

[Why? How? What for? We must measure the glomerular filtration].

PubMed

Treviño-Becerra, Alejandro

2010-01-01

The measurement of the glomerular filtration shows the degree of the functional qualities and the proficiency of the renal system. Despite new technologies, at present the best accepted technique for measuring the glomerular filtration in most countries is the clearance of creatinine in 24 hour urine. The clearance of creatinine has the advantage that it is confident, easy to reproduce, without technical limitations and low cost.

Fluid balance, glomerular filtration rate, and urine output in dogs anesthetized for an orthopedic surgical procedure.

PubMed

Boscan, Pedro; Pypendop, Bruno H; Siao, Kristine T; Francey, Thierry; Dowers, Kristy; Cowgill, Larry; Ilkiw, Jan E

2010-05-01

To determine fluid retention, glomerular filtration rate, and urine output in dogs anesthetized for a surgical orthopedic procedure. 23 dogs treated with a tibial plateau leveling osteotomy. 12 dogs were used as a control group. Cardiac output was measured in 5 dogs, and 6 dogs received carprofen for at least 14 days. Dogs received oxymorphone, atropine, propofol, and isoflurane for anesthesia (duration, 4 hours). Urine and blood samples were obtained for analysis every 30 minutes. Lactated Ringer's solution was administered at 10 mL/kg/h. Urine output was measured and glomerular filtration rate was estimated. Fluid retention was measured by use of body weight, fluid balance, and bioimpedance spectroscopy. No difference was found among control, cardiac output, or carprofen groups, so data were combined. Median urine output and glomerular filtration rate were 0.46 mL/kg/h and 1.84 mL/kg/min. Dogs retained a large amount of fluids during anesthesia, as indicated by increased body weight, positive fluid balance, increased total body water volume, and increased extracellular fluid volume. The PCV, total protein concentration, and esophageal temperature decreased in a linear manner. Dogs anesthetized for a tibial plateau leveling osteotomy retained a large amount of fluids, had low urinary output, and had decreased PCV, total protein concentration, and esophageal temperature. Evaluation of urine output alone in anesthetized dogs may not be an adequate indicator of fluid balance.

Alternatives for the Bedside Schwartz Equation to Estimate Glomerular Filtration Rate in Children.

PubMed

Pottel, Hans; Dubourg, Laurence; Goffin, Karolien; Delanaye, Pierre

2018-01-01

The bedside Schwartz equation has long been and still is the recommended equation to estimate glomerular filtration rate (GFR) in children. However, this equation is probably best suited to estimate GFR in children with chronic kidney disease (reduced GFR) but is not optimal for children with GFR >75 mL/min/1.73 m 2 . Moreover, the Schwartz equation requires the height of the child, information that is usually not available in the clinical laboratory. This makes automatic reporting of estimated glomerular filtration rate (eGFR) along with serum creatinine impossible. As the majority of children (even children referred to nephrology clinics) have GFR >75 mL/min/1.73 m 2 , it might be interesting to evaluate possible alternatives to the bedside Schwartz equation. The pediatric form of the Full Age Spectrum (FAS) equation offers an alternative to Schwartz, allowing automatic reporting of eGFR since height is not necessary. However, when height is involved in the FAS equation, the equation is essentially equal to the Schwartz equation for children, but there are large differences for adolescents. Combining standardized biomarkers increases the prediction performance of eGFR equations for children, reaching P10 ≈ 45% and P30 ≈ 90%. There are currently good and simple alternatives to the bedside Schwartz equation, but the more complex equations combining serum creatinine, serum cystatin C, and height show the highest accuracy and precision. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Relationship between renal function and renal volume in autosomal dominant polycystic kidney disease: cross-sectional study.

PubMed

Torres-Sánchez, M J; Ávila-Barranco, E; Esteban de la Rosa, R J; Fernández-Castillo, R; Esteban, M A; Carrero, J J; García-Valverde, M; Bravo-Soto, J A

2016-03-01

To determine in patients with autosomal dominant polycystic kidney disease the relationship between total renal volume (the sum of both kidneys, TRV) as measured by magnetic resonance and renal function; and its behaviour according to sex and the presence of arterial hypertension, hypercholesterolaemia and hyperglycemia. Cross-sectional study including patients with autosomal dominant polycystic kidney disease who underwent periodic reviews at Nephrology external consultations at Hospital de las Nieves de Granada, and who underwent an magnetic resonance to estimate renal volume between January 2008 and March 2011. We evaluated 67 patients (59.7% women, average age of 48±14.4 years) and found a significant positive association between TRV and serum creatinine or urea, which was reversed compared with estimated glomerular filtration by MDRD-4 and Cockcroft-Gault. Women showed an average serum creatinine level and a significantly lower TRV level compared with males. Subgroups affected by arterial hypertension and hyperuricemia presented average values for serum creatinine and urea, higher for TRV and lower for estimated glomerular filtration. The hypercholesterolaemia subgroup showed higher average values for urea and lower for estimated glomerular filtration, without detecting significant differences compared with TRV. The volume of polycystic kidneys measured by magnetic resonance is associated with renal function, and can be useful as a complementary study to monitor disease progression. The presence of arterial hypertension, hyperuricemia or hypercholesterolaemia is associated with a poorer renal function. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Prediction of cardiovascular outcome by estimated glomerular filtration rate and estimated creatinine clearance in the high-risk hypertension population of the VALUE trial.

PubMed

Ruilope, Luis M; Zanchetti, Alberto; Julius, Stevo; McInnes, Gordon T; Segura, Julian; Stolt, Pelle; Hua, Tsushung A; Weber, Michael A; Jamerson, Ken

2007-07-01

Reduced renal function is predictive of poor cardiovascular outcomes but the predictive value of different measures of renal function is uncertain. We compared the value of estimated creatinine clearance, using the Cockcroft-Gault formula, with that of estimated glomerular filtration rate (GFR), using the Modification of Diet in Renal Disease (MDRD) formula, as predictors of cardiovascular outcome in 15 245 high-risk hypertensive participants in the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial. For the primary end-point, the three secondary end-points and for all-cause death, outcomes were compared for individuals with baseline estimated creatinine clearance and estimated GFR < 60 ml/min and > or = 60 ml/min using hazard ratios and 95% confidence intervals. Coronary heart disease, left ventricular hypertrophy, age, sex and treatment effects were included as covariates in the model. For each end-point considered, the risk in individuals with poor renal function at baseline was greater than in those with better renal function. Estimated creatinine clearance (Cockcroft-Gault) was significantly predictive only of all-cause death [hazard ratio = 1.223, 95% confidence interval (CI) = 1.076-1.390; P = 0.0021] whereas estimated GFR was predictive of all outcomes except stroke. Hazard ratios (95% CIs) for estimated GFR were: primary cardiac end-point, 1.497 (1.332-1.682), P < 0.0001; myocardial infarction, 1.501 (1.254-1.796), P < 0.0001; congestive heart failure, 1.699 (1.435-2.013), P < 0.0001; stroke, 1.152 (0.952-1.394) P = 0.1452; and all-cause death, 1.231 (1.098-1.380), P = 0.0004. These results indicate that estimated glomerular filtration rate calculated with the MDRD formula is more informative than estimated creatinine clearance (Cockcroft-Gault) in the prediction of cardiovascular outcomes.

Assessment of glomerular filtration rate and effective renal plasma flow in cystic fibrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spino, M.; Chai, R.P.; Isles, A.F.

1985-07-01

A study was conducted to examine renal function in 10 healthy control subjects and eight patients with cystic fibrosis in stable condition. Sequential bolus injections of /sup 99m/Tc-DTPA and /sup 125/I-OIH were administered to assess glomerular filtration rate and effective renal plasma flow, respectively. Blood was subsequently collected for 3 hours, and urine for 24 hours. Renal clearances of both radioisotope markers were virtually identical in patients and controls. Inasmuch as neither glomerular filtration rate nor effective renal plasma flow was enhanced in patients with cystic fibrosis, increased clearance of drugs in these patients is unlikely to be the resultmore » of enhanced glomerular filtration or tubular secretion.« less

Population based screening for chronic kidney disease: cost effectiveness study.

PubMed

Manns, Braden; Hemmelgarn, Brenda; Tonelli, Marcello; Au, Flora; Chiasson, T Carter; Dong, James; Klarenbach, Scott

2010-11-08

To determine the cost effectiveness of one-off population based screening for chronic kidney disease based on estimated glomerular filtration rate. Cost utility analysis of screening with estimated glomerular filtration rate alone compared with no screening (with allowance for incidental finding of cases of chronic kidney disease). Analyses were stratified by age, diabetes, and the presence or absence of proteinuria. Scenario and sensitivity analyses, including probabilistic sensitivity analysis, were performed. Costs were estimated in all adults and in subgroups defined by age, diabetes, and hypertension. Publicly funded Canadian healthcare system. Large population based laboratory cohort used to estimate mortality rates and incidence of end stage renal disease for patients with chronic kidney disease over a five year follow-up period. Patients had not previously undergone assessment of glomerular filtration rate. Lifetime costs, end stage renal disease, quality adjusted life years (QALYs) gained, and incremental cost per QALY gained. Compared with no screening, population based screening for chronic kidney disease was associated with an incremental cost of $C463 (Canadian dollars in 2009; equivalent to about £275, €308, US $382) and a gain of 0.0044 QALYs per patient overall, representing a cost per QALY gained of $C104 900. In a cohort of 100 000 people, screening for chronic kidney disease would be expected to reduce the number of people who develop end stage renal disease over their lifetime from 675 to 657. In subgroups of people with and without diabetes, the cost per QALY gained was $C22 600 and $C572 000, respectively. In a cohort of 100 000 people with diabetes, screening would be expected to reduce the number of people who develop end stage renal disease over their lifetime from 1796 to 1741. In people without diabetes with and without hypertension, the cost per QALY gained was $C334 000 and $C1 411 100, respectively. Population based screening for chronic kidney disease with assessment of estimated glomerular filtration rate is not cost effective overall or in subgroups of people with hypertension or older people. Targeted screening of people with diabetes is associated with a cost per QALY that is similar to that accepted in other interventions funded by public healthcare systems.

Simultaneous assessment of glomerular filtration and barrier function in live zebrafish

PubMed Central

Kotb, Ahmed M.; Müller, Tobias; Xie, Jing; Anand-Apte, Bela; Endlich, Nicole

2014-01-01

The zebrafish pronephros is a well-established model to study glomerular development, structure, and function. A few methods have been described to evaluate glomerular barrier function in zebrafish larvae so far. However, there is a need to assess glomerular filtration as well. In the present study, we extended the available methods by simultaneously measuring the intravascular clearances of Alexa fluor 647-conjugated 10-kDa dextran and FITC-conjugated 500-kDa dextran as indicators of glomerular filtration and barrier function, respectively. After intravascular injection of the dextrans, mean fluorescence intensities of both dextrans were measured in the cardinal vein of living zebrafish (4 days postfertilization) by confocal microscopy over time. We demonstrated that injected 10-kDa dextran was rapidly cleared from the circulation, became visible in the lumen of the pronephric tubule, quickly accumulated in tubular cells, and was detectably excreted at the cloaca. In contrast, 500-kDa dextran could not be visualized in the tubule at any time point. To check whether alterations in glomerular function can be quantified by our method, we injected morpholino oligonucleotides (MOs) against zebrafish nonmuscle myosin heavy chain IIA (zMyh9) or apolipoprotein L1 (zApol1). While glomerular filtration was reduced in zebrafish nonmuscle myosin heavy chain IIA MO-injected larvae, glomerular barrier function remained intact. In contrast, in zebrafish apolipoprotein L1 MO-injected larvae, glomerular barrier function was compromised as 500-kDa dextran disappeared from the circulation and became visible in tubular cells. In summary, we present a novel method that allows to simultaneously assess glomerular filtration and barrier function in live zebrafish. PMID:25298528

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miyamori, I.; Yasuhara, S.; Takeda, Y.

The effects of captopril on effective renal plasma flow and glomerular filtration rate were studied using a noninvasive radioisotopic method on individual kidneys in eight patients with renovascular hypertension and 12 patients with essential hypertension with various renin levels. Four patients with renovascular hypertension had unilateral while three had bilateral renal artery stenosis. The effective renal plasma flow and glomerular filtration rate were determined by using /sup 131/I-iodohippurate sodium and /sup 99m/Tc-diethylenetriamine pentaacetic acid, respectively. Glomerular filtration rate and effective renal plasma flow were significantly reduced in the stenotic kidneys of patients with renovascular hypertension compared with values in nonstenoticmore » kidneys (p less than 0.01). Treatment with captopril, 37.5 to 75 mg/day for 1 to 48 weeks, further reduced the glomerular filtration rate only in stenotic kidneys, and effective renal plasma flow increased in both kidney types. In two of the three renal hypertensive patients with bilateral renal artery stenosis, captopril produced a reversible azotemia that was unrelated to the fall in blood pressure, as evidenced by the lack of azotemia seen after a moderate blood pressure reduction induced by other antihypertensive medications. These results indicate that endogenous angiotensin II is essential in maintaining the glomerular filtration rate in stenotic kidneys and suggest that a reduction in glomerular filtration rate during captopril administration could indicate the presence of renal artery stenosis.« less

Proteinuria and Reduced Estimated Glomerular Filtration Rate Independently Predict Risk for Acute Myocardial Infarction: Findings from a Population-Based Study in Keelung, Taiwan.

PubMed

Chang, Shu-Hsuan; Tsai, Chia-Ti; Yen, Amy Ming-Fang; Lei, Meng-Huan; Chen, Hsiu-Hsi; Tseng, Chuen-Den

2015-03-01

The aim of this study was to evaluate the independent roles of proteinuria and reduced estimated glomerular filtration rate (GFR) in the development of acute myocardial infarction in a northern Taiwanese population. We conducted a community-based prospective cohort study in Keelung, the northernmost county of Taiwan. A total of 63,129 subjects (63% women) ≥ 20 years of age who had no history of coronary heart disease were recruited and followed-up. Univariate and multivariate proportional hazards regression analysis was performed to assess the association between proteinuria and estimated GFR and the risk of acute myocardial infarction. There were 305 new cases of acute myocardial infarction (114 women and 191 men) documented during a four-year follow-up period. After adjustment of potential confounding covariates, heavier proteinuria (dipstick urinalysis reading 3+) and estimated GFR of less than 60 ml/min/1.73 m(2) independently predicted increased risk of developing acute myocardial infarction. The adjusted hazard ratio (aHR) of heavier proteinuria for occurrence of acute myocardial infarction was 1.85 [95% confidence intervals (CI), 1.17-2.91, p < 0.01] (vs. the reference group: negative dipstick proteinuria). The aHR of estimated GFR of 30-59 ml/min/1.73 m(2) for occurrence of acute myocardial infarction was 2.4 (95% CI, 1.31-4.38, p < 0.01) (vs. the reference group: estimated GFR ≥ 90 ml/ min/1.73 m(2)), and that of estimated GFR of 15-29 ml/min/1.73 m(2) was 5.26 (95% CI, 2.26-12.26, p < 0.01). We demonstrated that both heavier proteinuria and lower estimated GFR are significant independent predictors of developing future acute myocardial infarction in a northern Taiwanese population. Acute myocardial infarction; Estimated glomerular filtration rate; Proteinuria.

Nocturnal polyuria is related to absent circadian rhythm of glomerular filtration rate.

PubMed

De Guchtenaere, A; Vande Walle, C; Van Sintjan, P; Raes, A; Donckerwolcke, R; Van Laecke, E; Hoebeke, P; Vande Walle, J

2007-12-01

Monosymptomatic nocturnal enuresis is frequently associated with nocturnal polyuria and low urinary osmolality during the night. Initial studies found decreased vasopressin levels associated with low urinary osmolality overnight. Together with the documented desmopressin response, this was suggestive of a primary role for vasopressin in the pathogenesis of enuresis in the absence of bladder dysfunction. Recent studies no longer confirm this primary role of vasopressin. Other pathogenetic factors such as disordered renal sodium handling, hypercalciuria, increased prostaglandins and/or osmotic excretion might have a role. So far, little attention has been given to abnormalities in the circadian rhythm of glomerular filtration rate. We evaluated the circadian rhythm of glomerular filtration rate and diuresis in children with desmopressin resistant monosymptomatic nocturnal enuresis and nocturnal polyuria. We evaluated 15 children (9 boys) 9 to 14 years old with monosymptomatic nocturnal enuresis and nocturnal polyuria resistant to desmopressin treatment. The control group consisted of 25 children (12 boys) 9 to 16 years old with monosymptomatic nocturnal enuresis without nocturnal polyuria. Compared to the control population, children with nocturnal polyuria lost their circadian rhythm not only for diuresis and sodium excretion but also for glomerular filtration rate. Patients with monosymptomatic nocturnal enuresis and nocturnal polyuria lack a normal circadian rhythm for diuresis and sodium excretion, and the circadian rhythm of glomerular filtration rate is absent. This absence of circadian rhythm of glomerular filtration rate and/or sodium handling cannot be explained by a primary role of vasopressin, but rather by a disorder in circadian rhythm of renal glomerular and/or tubular functions.

Relationship of glomerular filtration rate based on serum iodixanol clearance to IRIS staging in cats with chronic kidney disease.

PubMed

Iwama, Ryosuke; Sato, Tsubasa; Katayama, Masaaki; Shimamura, Shunsuke; Satoh, Hiroshi; Ichijo, Toshihiro; Furuhama, Kazuhisa

2015-08-01

We examined the correlation between the glomerular filtration rate (GFR) estimated from an equation based on the serum iodixanol clearance technique and International Renal Interest Society (IRIS) stages of chronic kidney disease (CKD) in cats. The equation included the injection dose, sampling time, serum concentration and estimated volume of distribution (Vd) of the isotonic, nonionic, contrast medium iodixanol as a test tracer. The percent changes in the median basal GFR values calculated from the equation in CKD cats resembled those of IRIS stages 1-3. These data validate the association between the GFR derived from the simplified equation and IRIS stages based on the serum creatinine concentration in cats with CKD. They describe the GFR ranges determined using single-sample iodixanol clearance for healthy cats and cats with various IRIS stages of CKD.

[Bioimpedometry and its utilization in dialysis therapy].

PubMed

Lopot, František

2016-01-01

Measurement of living tissue impedance - bioimpedometry - started to be used in medicine some 50 years ago, first exclusively for estimation of extracellular and intracellular compartment volumes. Its most simple single frequency (50 kHz) version works directly with the measured impedance vector. Technically more sophisticated versions convert the measured impedance in values of volumes of different compartments of body fluids and calculate also principal markers of nutritional status (lean body mass, adipose tissue mass). The latest version specifically developed for application in dialysis patients includes body composition modelling and provides even absolute value of overhydration (excess fluid). Still in experimental phase is the bioimpedance exploitation for more precise estimation of residual glomerular filtration. Not yet standardized is also segmental bioimpedance measurement which should enable separate assessment of hydration status of the trunk segment and ultrafiltration capacity of peritoneum in peritoneal dialysis patients.Key words: assessment - bioimpedance - excess fluid - fluid status - glomerular filtration - haemodialysis - nutritional status - peritoneal dialysis.

Effect of Mannitol on Glomerular Ultrafiltration in the Hydropenic Rat

PubMed Central

Blantz, Roland C.

1974-01-01

The effect of mannitol upon glomerular ultrafiltration was examined in hydropenic Munich-Wistar rats. Superficial nephron filtration rate (sngfr) rose from 32.0±0.9 nl/min/g kidney wt to 42.0±1.6 (P < 0.001) in eight rats. Hydrostatic pressure gradients acting across the glomerular capillary (ΔP) were measured in glomerular capillaries and Bowman's space with a servo-nulling device, systemic (πA) and efferent arteriolar oncotic pressures (πE) were determined by microprotein analysis. These data were applied to a computer-based mathematical model of glomerular ultrafiltration to determine the profile of effective filtration pressure (EFP = ΔP — π) and total glomerular permeability (LpA) in both states. Filtration equilibrium obtained in hydropenia (LpA ≥ 0.099±0.006 nl/s/g kidney wt/mm Hg) and sngfr rose because EFP increased from a maximum value of 4.2±1.1 to 12.8±0.5 mm Hg after mannitol (P <0.01). This increase was due to both increased nephron plasma flow and decreased πA. Computer analysis of these data revealed that more than half (>58%) of this increase was due to decreased πA, consequent to dilution of protein. Since EFP was disequilibrated after mannitol, LpA could be calculated accurately (0.065 ± 0.003 nl/s/g kidney wt/mm Hg) and was significantly lower than the minimum estimate in hydropenia. Therefore, sngfr does increase with mannitol and this increase is not wholly dependent upon an increase in nephron plasma flow since the major factor increasing EFP was decreased πA. PMID:4418509

Comparison of estimated glomerular filtration rate equations for dosing new oral anticoagulants in patients with atrial fibrillation.

PubMed

Manzano-Fernández, Sergio; Andreu-Cayuelas, José M; Marín, Francisco; Orenes-Piñero, Esteban; Gallego, Pilar; Valdés, Mariano; Vicente, Vicente; Lip, Gregory Y H; Roldán, Vanessa

2015-06-01

New oral anticoagulants require dosing adjustment according to renal function. We aimed to determine discordance in hypothetical recommended dosing of these drugs using different estimated glomerular filtration rate equations in patients with atrial fibrillation. Cross-sectional analysis of 910 patients with atrial fibrillation and an indication for oral anticoagulation. The glomerular filtration rate was estimated using the Cockcroft-Gault, Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration equations. For dabigatran, rivaroxaban, and apixaban we identified dose discordance when there was disagreement in the recommended dose based on different equations. Among the overall population, relative to Cockcroft-Gault, discordance in dabigatran dosage was 11.4% for Modification of Diet in Renal Disease and 10% for Chronic Kidney Disease Epidemiology Collaboration, discordance in rivaroxaban dosage was 10% for Modification of Diet in Renal Disease and 8.5% for the Chronic Kidney Disease Epidemiology Collaboration. The lowest discordance was observed for apixaban: 1.4% for Modification of Diet in Renal Disease and 1.5% for the Chronic Kidney Disease Epidemiology Collaboration. In patients with Cockcroft-Gault<60mL/min or elderly patients, discordances in dabigatran and rivaroxaban dosages were higher, ranging from 13.2% to 30.4%. Discordance in apixaban dosage remained<5% in these patients. Discordance in new oral anticoagulation dosages using different equations is frequent, especially among elderly patients with renal impairment. This discordance was higher in dabigatran and rivaroxaban dosages than in apixaban dosages. Further studies are needed to clarify the clinical importance of these discordances and the optimal anticoagulant dosages depending on the use of different equations to estimate renal function. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Association of Kidney Function and Early Kidney Injury With Incident Hypertension in HIV-Infected Women.

PubMed

Ascher, Simon B; Scherzer, Rebecca; Peralta, Carmen A; Tien, Phyllis C; Grunfeld, Carl; Estrella, Michelle M; Abraham, Alison; Gustafson, Deborah R; Nowicki, Marek; Sharma, Anjali; Cohen, Mardge H; Butch, Anthony W; Young, Mary A; Bennett, Michael R; Shlipak, Michael G

2017-02-01

Subclinical kidney disease is associated with developing hypertension in the general population, but data are lacking among HIV-infected people. We examined associations of kidney function and injury with incident hypertension in 823 HIV-infected and 267 HIV-uninfected women in the Women's Interagency HIV Study, a multicenter, prospective cohort of HIV-infected and uninfected women in the United States. Baseline kidney biomarkers included estimated glomerular filtration rate using cystatin C, urine albumin-to-creatinine ratio, and 7 urine biomarkers of tubular injury: α-1-microglobulin, interleukin-18, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, liver fatty acid-binding protein, N-acetyl-β-d-glucosaminidase, and α1-acid-glycoprotein. We used multivariable Poisson regression to evaluate associations of kidney biomarkers with incident hypertension, defined as 2 consecutive visits of antihypertensive medication use. During a median follow-up of 9.6 years, 288 HIV-infected women (35%) developed hypertension. Among the HIV-infected women, higher urine albumin-to-creatinine ratio was independently associated with incident hypertension (relative risk =1.13 per urine albumin-to-creatinine ratio doubling, 95% confidence interval, 1.07-1.20), as was lower estimated glomerular filtration rate (relative risk =1.10 per 10 mL/min/1.73 m 2 lower estimated glomerular filtration rate; 95% confidence interval, 1.04-1.17). No tubular injury and dysfunction biomarkers were independently associated with incident hypertension in HIV-infected women. In contrast, among the HIV-uninfected women, urine albumin-to-creatinine ratio was not associated with incident hypertension, whereas higher urine interleukin-18, α1-acid-glycoprotein, and N-acetyl-β-d-glucosaminidase levels were significantly associated with incident hypertension. These findings suggest that early glomerular injury and kidney dysfunction may be involved in the pathogenesis of hypertension in HIV-infected people. The associations of tubular markers with hypertension in HIV-uninfected women should be validated in other studies. © 2016 American Heart Association, Inc.

Clinical dehydration and glomerular filtration rate in acute paediatric gastroenteritis.

PubMed

Milani, Gregorio P; Fossali, Emilio F; Perri, Alessandra; Vettori, Arianna; Grillo, Paolo; Agostoni, Carlo

2013-08-01

To evaluate changes in glomerular filtration rate in acute gastroenteritis. The correlation between two clinical diagnostic scales and glomerular filtration rate has been investigated in 113 children with acute gastroenteritis in a paediatric emergency setting. A significant reduction of GFR was found in 10% children less than, and 5% children higher than, 2 years of age with acute gastroenteritis. The differences observed as for risk of renal hypoperfusion suggests to consider the age of children as an important determinant to consider the dehydration status in acute gastroenteritis. ©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Comparison between a serum creatinine-and a cystatin C-based glomerular filtration rate equation in patients receiving amphotericin B.

PubMed

Karimzadeh, Iman; Khalili, Hossein

2016-06-06

Serum cystatin C (Cys C) has a number of advantages over serum creatinine in the evaluation of kidney function. Apart from Cys C level itself, several formulas have also been introduced in different clinical settings for the estimation of glomerular filtration rate (GFR) based upon serum Cys C level. The aim of the present study was to compare a serum Cys C-based equation with Cockcroft-Gault serum creatinine-based formula, both used in the calculation of GFR, in patients receiving amphotericin B. Fifty four adult patients with no history of acute or chronic kidney injury having been planned to receive conventional amphotericin B for an anticipated duration of at least 1 week for any indication were recruited. At three time points during amphotericin B treatment, including days 0, 7, and 14, serum cystatin C as well as creatinine levels were measured. GFR at the above time points was estimated by both creatinine (Cockcroft-Gault) and serum Cys C based equations. There was significant correlation between creatinine-based and Cys C-based GFR values at days 0 (R = 0.606, P = 0.001) and 7 (R = 0.714, P < 0.001). In contrast to GFR estimated by the Cockcroft-Gault equation, the mean (95 % confidence interval) Cys C-based GFR values at different studied time points were comparable within as well as between patients with and without amphotericin B nephrotoxicity. Our results suggested that the Gentian Cys C-based GFR equation correlated significantly with the Cockcroft-Gault formula at least at the early time period of treatment with amphotericin B. Graphical abstract Comparison between a serum creatinine-and a cystatin C-based glomerular filtration rate equation in patients receiving amphotericin B.

Prognostic Nutritional Index and the Risk of Mortality in Patients With Acute Heart Failure.

PubMed

Cheng, Yu-Lun; Sung, Shih-Hsien; Cheng, Hao-Min; Hsu, Pai-Feng; Guo, Chao-Yu; Yu, Wen-Chung; Chen, Chen-Huan

2017-06-25

Nutritional status has been related to clinical outcomes in patients with heart failure. We assessed the association between nutritional status, indexed by prognostic nutritional index (PNI), and survival in patients hospitalized for acute heart failure. A total of 1673 patients (age 76±13 years, 68% men) hospitalized for acute heart failure in a tertiary medical center were analyzed. PNI was calculated as 10×serum albumin (g/dL)+0.005×total lymphocyte count (per mm 3 ). National Death Registry was linked to identify the clinical outcomes of all-cause and cardiovascular death. With increasing tertiles of PNI, age and N-terminal probrain natriuretic peptide decreased, and body mass index, estimated glomerular filtration rate, and hemoglobin increased. During a mean follow-up duration of 31.5 months, a higher PNI tertile was related to better survival free from all-cause and cardiovascular mortality in the total study population and in participants with either reduced or preserved left ventricular ejection fraction. After accounting for age, sex, estimated glomerular filtration rate, left ventricular ejection fraction, serum sodium level, and on-admission systolic blood pressure, PNI was independently associated with cardiovascular death and total mortality (hazard ratio per 1 SD of the natural logarithm of the PNI: 0.76 [95% CI, 0.66-0.87] and 0.79 [95% CI, 0.73-0.87], respectively). In subgroup analyses stratified by age, sex, left ventricular ejection fraction, body mass index, or estimated glomerular filtration rate, PNI was consistently related to mortality. PNI is independently associated with long-term survival in patients hospitalized for acute heart failure with either reduced or preserved left ventricular ejection fraction. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Performance in Measurement of Serum Cystatin C by Laboratories Participating in the College of American Pathologists 2014 CYS Survey.

PubMed

Eckfeldt, John H; Karger, Amy B; Miller, W Greg; Rynders, Gregory P; Inker, Lesley A

2015-07-01

Cystatin C is becoming an increasingly popular biomarker for estimating glomerular filtration rate, and accurate measurements of cystatin C concentrations are necessary for accurate estimates of glomerular filtration rate. To assess the accuracy of cystatin C concentration measurements in laboratories participating in the College of American Pathologists CYS Survey. Two fresh frozen serum pools, the first from apparently healthy donors and the second from patients with chronic kidney disease, were prepared and distributed to laboratories participating in the CYS Survey along with the 2 usual processed human plasma samples. Target values were established for each pool by using 2 immunoassays and ERM DA471/IFCC international reference material. For the normal fresh frozen pool (ERM-DA471/IFCC-traceable target of 0.960 mg/L), the all-method mean (SD, % coefficient of variation [CV]) reported by all of the 123 reporting laboratories was 0.894 mg/L (0.128 mg/L, 14.3%). For the chronic kidney disease pool (ERM-DA471/IFCC-traceable target of 2.37 mg/L), the all-method mean (SD, %CV) was 2.258 mg/L (0.288 mg/L, 12.8%). There were substantial method-specific biases (mean milligram per liter reported for the normal pool was 0.780 for Siemens, 0.870 for Gentian, 0.967 for Roche, 1.061 for Diazyme, and 0.970 for other/not specified reagents; and mean milligram per liter reported for the chronic kidney disease pool was 2.052 for Siemens, 2.312 for Gentian, 2.247 for Roche, 2.909 for Diazyme, and 2.413 for other/not specified reagents). Manufacturers need to improve the accuracy of cystatin C measurement procedures if cystatin C is to achieve its full potential as a biomarker for estimating glomerular filtration rate.

Omega-3 fatty acid supplementation as an adjunctive therapy in the treatment of chronic kidney disease: a meta-analysis.

PubMed

Hu, Jing; Liu, Zuoliang; Zhang, Hao

2017-01-01

The aim of this study was to evaluate the benefits and risks of omega-3 fatty acid supplementation in patients with chronic kidney disease. A systematic search of articles in PubMed, Embase, the Cochrane Library, and reference lists was performed to find relevant literature. All eligible studies assessed proteinuria, the serum creatinine clearance rate, the estimated glomerular filtration rate, or the occurrence of end-stage renal disease. Standard mean differences with 95% confidence intervals for continuous data were used to estimate the effects of omega-3 fatty acid supplementation on renal function, as reflected by the serum creatinine clearance rate, proteinuria, the estimated glomerular filtration rate, and relative risk. Additionally, a random-effects model was used to estimate the effect of omega-3 fatty acid supplementation on the risk of end-stage renal disease. Nine randomized controlled trials evaluating 444 patients with chronic kidney disease were included in the study. The follow-up duration ranged from 2 to 76.8 months. Compared with no or low-dose omega-3 fatty acid supplementation, any or high-dose omega-3 fatty acid supplementation, respectively, was associated with a lower risk of proteinuria (SMD: -0.31; 95% CI: -0.53 to -0.10; p=0.004) but had little or no effect on the serum creatinine clearance rate (SMD: 0.22; 95% CI: -0.40 to 0.84; p=0.482) or the estimated glomerular filtration rate (SMD: 0.14; 95% CI: -0.13 to 0.42; p=0.296). However, this supplementation was associated with a reduced risk of end-stage renal disease (RR: 0.49; 95% CI: 0.24 to 0.99; p=0.047). In sum, omega-3 fatty acid supplementation is associated with a significantly reduced risk of end-stage renal disease and delays the progression of this disease.

Assessment of Plasma and NGAL for the Early Prediction of Acute Kidney Injury After Cardiac Surgery in Adults Study

ClinicalTrials.gov

2017-04-24

Acute Kidney Injury (AKI); Chronic Kidney Disease (CKD); End Stage Renal Disease (ESRD); Estimated Glomerular Filtration Rate (eGFR); Neutrophil Gelatinase-associated Lipocalin (NGAL); Serum Creatinine (SCr); Urine Creatinine (UCr); Urine Albumin (UAlb)

Excess Podocyte Semaphorin-3A Leads to Glomerular Disease Involving PlexinA1–Nephrin Interaction

PubMed Central

Reidy, Kimberly J.; Aggarwal, Pardeep K.; Jimenez, Juan J.; Thomas, David B.; Veron, Delma; Tufro, Alda

2014-01-01

Semaphorin-3A (Sema3a), a guidance protein secreted by podocytes, is essential for normal kidney patterning and glomerular filtration barrier development. Here, we report that podocyte-specific Sema3a gain-of-function in adult mice leads to proteinuric glomerular disease involving the three layers of the glomerular filtration barrier. Reversibility of the glomerular phenotype upon removal of the transgene induction provided proof-of-principle of the cause-and-effect relationship between podocyte Sema3a excess and glomerular disease. Mechanistically, excess Sema3a induces dysregulation of nephrin, matrix metalloproteinase 9, and αvβ3 integrin in vivo. Sema3a cell-autonomously disrupts podocyte shape. We identified a novel direct interaction between the Sema3a signaling receptor plexinA1 and nephrin, linking extracellular Sema3a signals to the slit-diaphragm signaling complex. We conclude that Sema3a functions as an extracellular negative regulator of the structure and function of the glomerular filtration barrier in the adult kidney. Our findings demonstrate a crosstalk between Sema3a and nephrin signaling pathways that is functionally relevant both in vivo and in vitro. PMID:23954273

Efficient reporting of the estimated glomerular filtration rate without height in pediatric patients with cancer.

PubMed

Jeong, Tae-Dong; Cho, Eun-Jung; Lee, Woochang; Chun, Sail; Hong, Ki-Sook; Min, Won-Ki

2017-10-26

The updated bedside Schwartz equation requires constant, serum creatinine concentration and height measurements to calculate the estimated glomerular filtration rate (eGFR) in pediatric patients. Unlike the serum creatinine levels, obtaining height information from the laboratory information system (LIS) is not always possible in a clinical laboratory. Recently, the height-independent eGFR equation, the full age spectrum (FAS) equation, has been introduced. We evaluated the performance of height-independent eGFR equation in Korean children with cancer. A total of 250 children who underwent chromium-51-ethylenediamine tetra acetic-acid (51Cr-EDTA)-based glomerular filtration rate (GFR) measurements were enrolled. The 51Cr-EDTA GFR was used as the reference GFR. The bias (eGFR - measured GFR), precision (root mean square error [RMSE]) and accuracy (P30) of the FAS equations were compared to those of the updated Schwartz equation. P30 was defined as the percentage of patients whose eGFR was within ±30% of the measured GFR. The FAS equation showed significantly lower bias (mL/min/1.73 m2) than the updated Schwartz equation (4.2 vs. 8.7, p<0.001). The RMSE and P30 were: updated Schwartz of 43.8 and 64.4%, respectively, and FAS of 42.7 and 66.8%, respectively. The height-independent eGFR-FAS equation was less biased and as accurate as the updated Schwartz equation in Korean children. The use of the height-independent eGFR equation will allow for efficient reporting of eGFR through the LIS in clinical laboratories.

Novel routes of albumin passage across the glomerular filtration barrier.

PubMed

Castrop, H; Schießl, I M

2017-03-01

Albuminuria is a hallmark of kidney diseases of various aetiologies and an unambiguous symptom of the compromised integrity of the glomerular filtration barrier. Furthermore, there is increasing evidence that albuminuria per se aggravates the development and progression of chronic kidney disease. This review covers new aspects of the movement of large plasma proteins across the glomerular filtration barrier in health and disease. Specifically, this review focuses on the role of endocytosis and transcytosis of albumin by podocytes, which constitutes a new pathway of plasma proteins across the filtration barrier. Thus, we summarize what is known about the mechanisms of albumin endocytosis by podocytes and address the fate of the endocytosed albumin, which is directed to lysosomal degradation or transcellular movement with subsequent vesicular release into the urinary space. We also address the functional consequences of overt albumin endocytosis by podocytes, such as the formation of pro-inflammatory cytokines, which might eventually result in a deterioration of podocyte function. Finally, we consider the diagnostic potential of podocyte-derived albumin-containing vesicles in the urine as an early marker of a compromised glomerular barrier function. In terms of new technical approaches, the review covers how our knowledge of the movement of albumin across the glomerular filtration barrier has expanded by the use of new intravital imaging techniques. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Renal Blood Flow, Glomerular Filtration Rate, and Renal Oxygenation in Early Clinical Septic Shock.

PubMed

Skytte Larsson, Jenny; Krumbholz, Vitus; Enskog, Anders; Bragadottir, Gudrun; Redfors, Bengt; Ricksten, Sven-Erik

2018-06-01

Data on renal hemodynamics, function, and oxygenation in early clinical septic shock are lacking. We therefore measured renal blood flow, glomerular filtration rate, renal oxygen consumption, and oxygenation in patients with early septic shock. Prospective comparative study. General and cardiothoracic ICUs. Patients with norepinephrine-dependent early septic shock (n = 8) were studied within 24 hours after arrival in the ICU and compared with postcardiac surgery patients without acute kidney injury (comparator group, n = 58). None. Data on systemic hemodynamics and renal variables were obtained during two 30-minute periods. Renal blood flow was measured by the infusion clearance of para-aminohippuric acid, corrected for renal extraction of para-aminohippuric acid. Renal filtration fraction was measured by renal extraction of chromium-51 labeled EDTA. Renal oxygenation was estimated from renal oxygen extraction. Renal oxygen delivery (-24%; p = 0.037) and the renal blood flow-to-cardiac index ratio (-21%; p = 0.018) were lower, renal vascular resistance was higher (26%; p = 0.027), whereas renal blood flow tended to be lower (-19%; p = 0.068) in the septic group. Glomerular filtration rate (-32%; p = 0.006) and renal sodium reabsorption (-29%; p = 0.014) were both lower in the septic group. Neither renal filtration fraction nor renal oxygen consumption differed significantly between groups. Renal oxygen extraction was significantly higher in the septic group (28%; p = 0.022). In the septic group, markers of tubular injury were elevated. In early clinical septic shock, renal function was lower, which was accompanied by renal vasoconstriction, a lower renal oxygen delivery, impaired renal oxygenation, and tubular sodium reabsorption at a high oxygen cost compared with controls.

Magnetic Resonance Imaging-Derived Renal Oxygenation and Perfusion During Continuous, Steady-State Angiotensin-II Infusion in Healthy Humans.

PubMed

van der Bel, René; Coolen, Bram F; Nederveen, Aart J; Potters, Wouter V; Verberne, Hein J; Vogt, Liffert; Stroes, Erik S G; Krediet, C T Paul

2016-03-28

The role of kidney hypoxia is considered pivotal in the progression of chronic kidney disease. A widely used method to assess kidney oxygenation is blood oxygen level dependent (BOLD)-magnetic resonance imaging (MRI), but its interpretation remains problematic. The BOLD-MRI signal is the result of kidney oxygen consumption (a proxy of glomerular filtration) and supply (ie, glomerular perfusion). Therefore, we hypothesized that with pharmacological modulation of kidney blood flow, renal oxygenation, as assessed by BOLD-MRI, correlates to filtration fraction (ie, glomerular filtration rate/effective renal plasma flow) in healthy humans. Eight healthy volunteers were subjected to continuous angiotensin-II infusion at 0.3, 0.9, and 3.0 ng/kg per minute. At each dose, renal oxygenation and blood flow were assessed using BOLD and phase-contrast MRI. Subsequently, "gold standard" glomerular filtration rate/effective renal plasma flow measurements were performed under the same conditions. Renal plasma flow decreased dose dependently from 660±146 to 467±103 mL/min per 1.73 m(2) (F[3, 21]=33.3, P<0.001). Glomerular filtration rate decreased from 121±23 to 110±18 mL/min per 1.73 m(2) (F[1.8, 2.4]=6.4, P=0.013). Cortical transverse relaxation rate (R2*; increases in R2* represent decreases in oxygenation) increased by 7.2±3.8% (F[3, 21]=7.37, P=0.001); medullar R2* did not change. Cortical R2* related to filtration fraction (R(2) 0.46, P<0.001). By direct comparison between "gold standard" kidney function measurements and BOLD MRI, we showed that cortical oxygenation measured by BOLD MRI relates poorly to glomerular filtration rate but is associated with filtration fraction. For future studies, there may be a need to include renal plasma flow measurements when employing renal BOLD-MRI. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Renal functional and perioperative outcomes of off-clamp versus clamped robot-assisted partial nephrectomy: matched cohort study.

PubMed

Tanagho, Youssef S; Bhayani, Sam B; Sandhu, Gurdarshan S; Vaughn, Nicholas P; Nepple, Kenneth G; Figenshau, R Sherburne

2012-10-01

To evaluate the potential benefit of performing off-clamp robot-assisted partial nephrectomy as it relates to renal functional outcomes, while assessing the safety profile of this unconventional surgical approach. Twenty-nine patients who underwent off-clamp robot-assisted partial nephrectomy for suspected renal cell carcinoma at Washington University between March 2008 and September 2011 (group 1) were matched to 29 patients with identical nephrometry scores and comparable baseline renal function who underwent robot-assisted partial nephrectomy with hilar clamping during the same period (group 2). The matched cohorts' perioperative and renal functional outcomes were compared at a mean 9-month follow-up. Mean estimated blood loss was 146.4 mL in group 1, versus 103.9 mL in group 2 (P = .039). Mean hilar clamp time was 0 minutes in group 1 and 14.7 minutes in group 2. No perioperative complications were encountered in group 1; 1 Clavien-2 complication (3.4%) occurred in group 2 (P = 1.000). At 9-month follow-up, mean estimated glomerular filtration rate in group 1 was 79.9 versus 84.8 mL/min/1.73 m(2) preoperatively (P = .013); mean estimated glomerular filtration rate in group 2 was 74.1 versus 85.8 mL/min/1.73 m(2) preoperatively (P < .001). Hence, estimated glomerular filtration rate declined by a mean of 4.9 mL/min/1.73 m(2) in group 1 versus 11.7 mL/min/1.73 m(2) in group 2 (P = .033). Off-clamp robot-assisted partial nephrectomy is associated with a favorable morbidity profile and relatively greater renal functional preservation compared to clamped robot-assisted partial nephrectomy. Nevertheless, the benefit is small in renal functional terms and may have very limited clinical relevance. Copyright © 2012 Elsevier Inc. All rights reserved.

Associations of blood lead with estimated glomerular filtration rate using MDRD, CKD-EPI and serum cystatin C-based equations

PubMed Central

Spector, June T.; Navas-Acien, Ana; Fadrowski, Jeffrey; Guallar, Eliseo; Jaar, Bernard

2011-01-01

Background. Low-level lead exposure is widespread and has been implicated as a chronic kidney disease (CKD) risk factor. However, studies evaluating associations of lead dose with newer, potentially more accurate, estimates of kidney function, in participants with a wide range of glomerular filtration rates (GFRs), are scarce. Methods. We compared associations of blood lead and estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and cystatin C single variable, multivariable and combined creatinine/cystatin C equations in 3941 adults who participated in the 1999–2002 National Health and Nutrition Examination Survey cystatin C subsample. Results. Geometric mean blood lead was 1.7 μg/dL. After multivariable adjustment, differences [95% confidence interval (CI)] in mean eGFR for a doubling of blood lead were −1.9 (−3.2, −0.7), −1.7 (−3.0, −0.5) and −1.4 (−2.3, −0.5) mL/min/1.73 m2, using the cystatin C single variable, multivariable and combined creatinine/cystatin C equations, respectively, reflecting lower eGFR with increased blood lead. The corresponding differences (95% CI) were −0.9 (−1.9, 0.02) and −0.9 (−1.8, 0.01) using the creatinine-based MDRD and CKD-EPI equations, respectively. In participants aged ≥60 years, differences in mean eGFR ranged from −3.0 to −4.5 mL/min/1.73 m2, and odds of reduced eGFR (<60 mL/min/1.73 m2) were increased for all estimates of GFR. Conclusions. These results support the inclusion of cystatin C-based eGFR in future lead research and provide additional evidence for environmental lead exposure as a CKD risk factor. PMID:21248295

A Mathematical Method to Calculate Tumor Contact Surface Area: An Effective Parameter to Predict Renal Function after Partial Nephrectomy.

PubMed

Hsieh, Po-Fan; Wang, Yu-De; Huang, Chi-Ping; Wu, Hsi-Chin; Yang, Che-Rei; Chen, Guang-Heng; Chang, Chao-Hsiang

2016-07-01

We proposed a mathematical formula to calculate contact surface area between a tumor and renal parenchyma. We examined the applicability of using contact surface area to predict renal function after partial nephrectomy. We performed this retrospective study in patients who underwent partial nephrectomy between January 2012 and December 2014. Based on abdominopelvic computerized tomography or magnetic resonance imaging, we calculated the contact surface area using the formula (2*π*radius*depth) developed by integral calculus. We then evaluated the correlation between contact surface area and perioperative parameters, and compared contact surface area and R.E.N.A.L. (Radius/Exophytic/endophytic/Nearness to collecting system/Anterior/Location) score in predicting a reduction in renal function. Overall 35, 26 and 45 patients underwent partial nephrectomy with open, laparoscopic and robotic approaches, respectively. Mean ± SD contact surface area was 30.7±26.1 cm(2) and median (IQR) R.E.N.A.L. score was 7 (2.25). Spearman correlation analysis showed that contact surface area was significantly associated with estimated blood loss (p=0.04), operative time (p=0.04) and percent change in estimated glomerular filtration rate (p <0.001). On multivariate analysis contact surface area and R.E.N.A.L. score independently affected percent change in estimated glomerular filtration rate (p <0.001 and p=0.03, respectively). On ROC curve analysis contact surface area was a better independent predictor of a greater than 10% change in estimated glomerular filtration rate compared to R.E.N.A.L. score (AUC 0.86 vs 0.69). Using this simple mathematical method, contact surface area was associated with surgical outcomes. Compared to R.E.N.A.L. score, contact surface area was a better predictor of functional change after partial nephrectomy. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Measuring residual renal function for hemodialysis adequacy: Is there an easier option?

PubMed

Davenport, Andrew

2017-10-01

Most patients starting hemodialysis (HD) have residual renal function. As such, there has been increased interest in starting patients with less frequent and shorter dialysis session times. However, for this incremental approach to be successful, patients require regular monitoring of residual renal function, so that as residual renal function declines, the amount of HD is appropriately increased. Currently most dialysis centers rely on interdialytic urine collections. However, many patients find these inconvenient and there may be marked intrapatient variability due to compliance issues. Thus, alternative markers of residual renal function are required for routine clinical practice. Currently three middle sized molecules; cystatin C, β2 microglobulin, and βtrace protein have been investigated as potential endogenous markers of glomerular filtration. Although none is ideal, combinations of these markers have been proposed to provide a more accurate estimation of glomerular clearance, and in particular cut offs for minimal residual renal function. However, in patients with low levels of residual renal function it remains unclear as to whether the benefits of residual renal function equally apply to glomerular filtration or tubular function. © 2017 International Society for Hemodialysis.

Influence of kidney function on risk of supratherapeutic international normalized ratio-related hemorrhage in warfarin users: a prospective cohort study

USDA-ARS?s Scientific Manuscript database

Background: Anticoagulation management is difficult in chronic kidney disease, with frequent supratherapeutic international normalized ratios (INRs >/= 4) increasing hemorrhagic risk. We evaluated whether the interaction of INR and lower estimated glomerular filtration rate (eGFR) increases hemorrha...

Lifestyle factors and indices of kidney function in the Framingham Heart Study

USDA-ARS?s Scientific Manuscript database

Background and objectives: Lifestyle characteristics are modifiable factors that could be targeted as part of chronic kidney disease (CKD) prevention. We sought to determine the association of lifestyle characteristics with incident estimated glomerular filtration rate (eGFR)<60mL/min/1.73m2 and rap...

Associations of blood lead, cadmium, and mercury with estimated glomerular filtration rate in the Korean general population: Analysis of 2008-2010 Korean National Health and Nutrition Examination Survey data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Yangho; Lee, Byung-Kook, E-mail: bklee@sch.ac.kr

Introduction: The objective of this study was to evaluate associations between blood lead, cadmium, and mercury levels with estimated glomerular filtration rate in a general population of South Korean adults. Methods: This was a cross-sectional study based on data obtained in the Korean National Health and Nutrition Examination Survey (KNHANES) (2008-2010). The final analytical sample consisted of 5924 participants. Estimated glomerular filtration rate (eGFR) was calculated using the MDRD Study equation as an indicator of glomerular function. Results: In multiple linear regression analysis of log2-transformed blood lead as a continuous variable on eGFR, after adjusting for covariates including cadmium andmore » mercury, the difference in eGFR levels associated with doubling of blood lead were -2.624 mL/min per 1.73 m Superscript-Two (95% CI: -3.803 to -1.445). In multiple linear regression analysis using quartiles of blood lead as the independent variable, the difference in eGFR levels comparing participants in the highest versus the lowest quartiles of blood lead was -3.835 mL/min per 1.73 m Superscript-Two (95% CI: -5.730 to -1.939). In a multiple linear regression analysis using blood cadmium and mercury, as continuous or categorical variables, as independent variables, neither metal was a significant predictor of eGFR. Odds ratios (ORs) and 95% CI values for reduced eGFR calculated for log2-transformed blood metals and quartiles of the three metals showed similar trends after adjustment for covariates. Discussion: In this large, representative sample of South Korean adults, elevated blood lead level was consistently associated with lower eGFR levels and with the prevalence of reduced eGFR even in blood lead levels below 10 {mu}g/dL. In conclusion, elevated blood lead level was associated with lower eGFR in a Korean general population, supporting the role of lead as a risk factor for chronic kidney disease.« less

Measuring dynamic kidney function in an undergraduate physiology laboratory.

PubMed

Medler, Scott; Harrington, Frederick

2013-12-01

Most undergraduate physiology laboratories are very limited in how they treat renal physiology. It is common to find teaching laboratories equipped with the capability for high-resolution digital recordings of physiological functions (muscle twitches, ECG, action potentials, respiratory responses, etc.), but most urinary laboratories still rely on a "dipstick" approach of urinalysis. Although this technique can provide some basic insights into the functioning of the kidneys, it overlooks the dynamic processes of filtration, reabsorption, and secretion. In the present article, we provide a straightforward approach of using renal clearance measurements to estimate glomerular filtration rate, fractional water reabsorption, glucose clearance, and other physiologically relevant parameters. The estimated values from our measurements in laboratory are in close agreement with those anticipated based on textbook parameters. For example, we found glomerular filtration rate to average 124 ± 45 ml/min, serum creatinine to be 1.23 ± 0.4 mg/dl, and fractional water reabsorption to be ∼96.8%. Furthermore, analyses for the class data revealed significant correlations between parameters like fractional water reabsorption and urine concentration, providing opportunities to discuss urine concentrating mechanisms and other physiological processes. The procedures outlined here are general enough that most undergraduate physiology laboratory courses should be able to implement them without difficulty.

The mechanism of the increase in glomerular filtration rate in the twelve-day pregnant rat.

PubMed Central

Baylis, C

1980-01-01

1. Whole kidney and micropuncture techniques were employed to investigate the determinants of glomerular ultrafiltration in virgin and 12-day pregnant rats. 2. A significant increase in whole kidney glomerular filtration rate (g.f.r.) and superficial cortical single nephron g.f.r. was noted in pregnant rats compared to virgins. 3. Increases in whole kidney and glomerular plasma flow rate also occurred in pregnancy which were in proportion to the increase in rate of filtration. No differences were noted in the hydrostatic and oncotic pressures which influence formation of glomerular ultrafiltrate in the superficial nephron population. 4. Reduction in arterial haematocrit and no change in mean red cell volume indicate that a plasma volume expansion has occurred by day 12 of pregnancy in the rat. 5. It is concluded that the increased g.f.r. seen in 12-day pregnant rats is exclusively the result of an increase in renal plasma flow rate (r.p.f.) since the other determinants of glomerular ultrafiltration are unaffected by pregnancy. The plasma volume expansion which also occurs must be, at least in part, responsible for the increase in r.p.f. PMID:7441561

Effects of levosimendan on glomerular filtration rate, renal blood flow, and renal oxygenation after cardiac surgery with cardiopulmonary bypass: a randomized placebo-controlled study.

PubMed

Bragadottir, Gudrun; Redfors, Bengt; Ricksten, Sven-Erik

2013-10-01

Acute kidney injury develops in a large proportion of patients after cardiac surgery because of the low cardiac output syndrome. The inodilator levosimendan increases cardiac output after cardiac surgery with cardiopulmonary bypass, but a detailed analysis of its effects on renal perfusion, glomerular filtration, and renal oxygenation in this group of patients is lacking. We therefore evaluated the effects of levosimendan on renal blood flow, glomerular filtration rate, renal oxygen consumption, and renal oxygen demand/supply relationship, i.e., renal oxygen extraction, early after cardiac surgery with cardiopulmonary bypass. Prospective, placebo-controlled, and randomized trial. Cardiothoracic ICU of a tertiary center. Postcardiac surgery patients (n=30). The patients were randomized to receive levosimendan, 0.1 µg/kg/min after a loading dose of 12 µg/kg (n=15), or placebo (n=15). The experimental procedure started 4-6 hours after surgery in the ICU during propofol sedation and mechanical ventilation. Systemic hemodynamic were evaluated by a pulmonary artery thermodilution catheter. Renal blood flow and glomerular filtration rate were measured by the renal vein retrograde thermodilution technique and by renal extraction of Cr-EDTA, respectively. Central venous pressure was kept constant by colloid/crystalloid infusion. Compared to placebo, levosimendan increased cardiac index (22%), stroke volume index (15%), and heart rate (7%) and decreased systemic vascular resistance index (21%), whereas mean arterial pressure was not affected. Levosimendan induced significant increases in renal blood flow (12%, p<0.05) and glomerular filtration rate (21%, p<0.05), decreased renal vascular resistance (18%, p<0.05) but caused no significant changes in filtration fraction, renal oxygen consumption, or renal oxygen extraction, compared to placebo. After cardiac surgery with cardiopulmonary bypass, levosimendan induces a vasodilation, preferentially of preglomerular resistance vessels, increasing both renal blood flow and glomerular filtration rate without jeopardizing renal oxygenation. Due to its pharmacodynamic profile, levosimendan might be an interesting alternative for treatment of postoperative heart failure complicated by acute kidney injury in postcardiac surgery patients.

Determination of the best method to estimate glomerular filtration rate from serum creatinine in adult patients with sickle cell disease: a prospective observational cohort study.

PubMed

Arlet, Jean-Benoît; Ribeil, Jean-Antoine; Chatellier, Gilles; Eladari, Dominique; De Seigneux, Sophie; Souberbielle, Jean-Claude; Friedlander, Gérard; de Montalembert, Marianne; Pouchot, Jacques; Prié, Dominique; Courbebaisse, Marie

2012-08-06

Sickle cell disease (SCD) leads to tissue hypoxia resulting in chronic organ dysfunction including SCD associated nephropathy. The goal of our study was to determine the best equation to estimate glomerular filtration rate (GFR) in SCD adult patients. We conducted a prospective observational cohort study. Since 2007, all adult SCD patients in steady state, followed in two medical departments, have had their GFR measured using iohexol plasma clearance (gold standard). The Cockcroft-Gault, MDRD-v4, CKP-EPI and finally, MDRD and CKD-EPI equations without adjustment for ethnicity were tested to estimate GFR from serum creatinine. Estimated GFRs were compared to measured GFRs according to the graphical Bland and Altman method. Sixty-four SCD patients (16 men, median age 27.5 years [range 18.0-67.5], 41 with SS-genotype were studied. They were Sub-Saharan Africa and French West Indies natives and predominantly lean (median body mass index: 22 kg/m2 [16-33]). Hyperfiltration (defined as measured GFR >110 mL/min/1.73 m2) was detected in 53.1% of patients. Urinary albumin/creatinine ratio was higher in patients with hyperfiltration than in patients with normal GFR (4.05 mg/mmol [0.14-60] versus 0.4 mg/mmol [0.7-81], p = 0.01). The CKD-EPI equation without adjustment for ethnicity had both the lowest bias and the greatest precision. Differences between estimated GFRs using the CKP-EPI equation and measured GFRs decreased with increasing GFR values, whereas it increased with the Cockcroft-Gault and MDRD-v4 equations. We confirm that SCD patients have a high rate of glomerular hyperfiltration, which is frequently associated with microalbuminuria or macroalbuminuria. In non-Afro-American SCD patients, the best method for estimating GFR from serum creatinine is the CKD-EPI equation without adjustment for ethnicity. This equation is particularly accurate to estimate high GFR values, including glomerular hyperfiltration, and thus should be recommended to screen SCD adult patients at high risk for SCD nephropathy.

Urotensin-II System in Genetic Control of Blood Pressure and Renal Function

PubMed Central

Debiec, Radoslaw; Christofidou, Paraskevi; Denniff, Matthew; Bloomer, Lisa D.; Bogdanski, Pawel; Wojnar, Lukasz; Musialik, Katarzyna; Charchar, Fadi J.; Thompson, John R.; Waterworth, Dawn; Song, Kijoung; Vollenweider, Peter; Waeber, Gerard; Zukowska-Szczechowska, Ewa; Samani, Nilesh J.; Lambert, David; Tomaszewski, Maciej

2013-01-01

Urotensin-II controls ion/water homeostasis in fish and vascular tone in rodents. We hypothesised that common genetic variants in urotensin-II pathway genes are associated with human blood pressure or renal function. We performed family-based analysis of association between blood pressure, glomerular filtration and genes of the urotensin-II pathway (urotensin-II, urotensin-II related peptide, urotensin-II receptor) saturated with 28 tagging single nucleotide polymorphisms in 2024 individuals from 520 families; followed by an independent replication in 420 families and 7545 unrelated subjects. The expression studies of the urotensin-II pathway were carried out in 97 human kidneys. Phylogenetic evolutionary analysis was conducted in 17 vertebrate species. One single nucleotide polymorphism (rs531485 in urotensin-II gene) was associated with adjusted estimated glomerular filtration rate in the discovery cohort (p = 0.0005). It showed no association with estimated glomerular filtration rate in the combined replication resource of 8724 subjects from 6 populations. Expression of urotensin-II and its receptor showed strong linear correlation (r = 0.86, p<0.0001). There was no difference in renal expression of urotensin-II system between hypertensive and normotensive subjects. Evolutionary analysis revealed accumulation of mutations in urotensin-II since the divergence of primates and weaker conservation of urotensin-II receptor in primates than in lower vertebrates. Our data suggest that urotensin-II system genes are unlikely to play a major role in genetic control of human blood pressure or renal function. The signatures of evolutionary forces acting on urotensin-II system indicate that it may have evolved towards loss of function since the divergence of primates. PMID:24391740

Efficacy of nebivolol-valsartan single-pill combination in obese and nonobese patients with hypertension.

PubMed

Mende, Christian W; Giles, Thomas D; Bharucha, David B; Ferguson, William G; Mallick, Madhuja; Patel, Mehul D

2017-06-01

Antihypertensive efficacy of single-pill combinations (SPCs) consisting of a β 1 -selective adrenergic blocker with vasodilatory properties via β 3 -agonism (nebivolol) and an angiotensin II receptor blocker (valsartan) was demonstrated in an 8-week phase 3 trial (NCT01508026). In this post hoc analysis, seated blood pressure, heart rate, 24-hour ambulatory blood pressure monitoring, plasma aldosterone, estimated glomerular filtration rate, and safety measures were assessed in obese (body mass index >32 kg/m 2 ; n=1823) and nonobese (body mass index <27 kg/m 2 ; n=847) adults with hypertension (stage I or II) treated with nebivolol-valsartan SPCs, nebivolol or valsartan monotherapy, or placebo. At week 8, reductions from baseline in blood pressure and ambulatory blood pressure monitoring were greater with SPCs and most nebivolol and valsartan monotherapy doses vs placebo regardless of obesity status. Aldosterone declined with all active treatments and estimated glomerular filtration rate remained steady. The nebivolol-valsartan 5/80 mg/d SPC was efficacious regardless of degree of obesity. © 2017 The Authors. The Journal of Clinical Hypertension Published by Wiley Periodicals, Inc.

Sodium-glucose co-transporter type 2 inhibitors reduce evening home blood pressure in type 2 diabetes with nephropathy.

PubMed

Takenaka, Tsuneo; Kishimoto, Miyako; Ohta, Mari; Tomonaga, Osamu; Suzuki, Hiromichi

2017-05-01

The effects of sodium-glucose co-transporter type 2 inhibitors on home blood pressure were examined in type 2 diabetes with nephropathy. The patients with diabetic nephropathy were screened from medical records in our hospitals. Among them, 52 patients who measured home blood pressure and started to take sodium-glucose co-transporter type 2 inhibitors were selected. Clinical parameters including estimated glomerular filtration rate, albuminuria and home blood pressure for 6 months were analysed. Sodium-glucose co-transporter type 2 inhibitors (luseogliflozin 5 mg/day or canagliflozin 100 mg/day) reduced body weight, HbA1c, albuminuria, estimated glomerular filtration rate and office blood pressure. Although sodium-glucose co-transporter type 2 inhibitors did not alter morning blood pressure, it reduced evening systolic blood pressure. Regression analyses revealed that decreases in evening blood pressure predicted decrements in albuminuria. The present data suggest that sodium-glucose co-transporter type 2 inhibitors suppress sodium overload during daytime to reduce evening blood pressure and albuminuria.

Impact of albuminuria on the incidence of periprocedural myocardial injury in patients undergoing elective coronary stent implantation.

PubMed

Osugi, Naohiro; Suzuki, Susumu; Ishii, Hideki; Yasuda, Yoshinari; Shibata, Yohei; Tatami, Yosuke; Ota, Tomoyuki; Kawamura, Yoshihiro; Okumura, Satoshi; Tanaka, Akihito; Inoue, Yosuke; Matsuo, Seiichi; Murohara, Toyoaki

2014-07-01

Albuminuria has traditionally been associated with an elevated risk of cardiovascular events. However, few studies have examined the potential relation between albuminuria and periprocedural risk in percutaneous coronary intervention (PCI). The aim of this study was to evaluate the impact of albuminuria on the incidence of periprocedural myocardial injury (PMI) in patients who underwent PCI. The study included 252 consecutive patients who underwent PCI. The incidence of PMI was significantly higher in patients with albuminuria than in those with normoalbuminuria (31.9% vs 43.3%, respectively, p = 0.014). Even after adjustment for confounders, the presence of albuminuria predicted PMI (odds ratio 2.07, 95% confidence interval 1.08 to 3.97, p = 0.029). Furthermore, patients with albuminuria and preserved estimated glomerular filtration rate had a 4.2-fold higher risk for PMI than did patients with normoalbuminuria and preserved estimated glomerular filtration rate. In conclusion, albuminuria was a strong predictor of PMI in patients who underwent PCI. Copyright © 2014 Elsevier Inc. All rights reserved.

Robot-assisted laparoscopic versus open partial nephrectomy in patients with chronic kidney disease: A propensity score-matched comparative analysis of surgical outcomes.

PubMed

Takagi, Toshio; Kondo, Tsunenori; Tachibana, Hidekazu; Iizuka, Junpei; Omae, Kenji; Kobayashi, Hirohito; Yoshida, Kazuhiko; Tanabe, Kazunari

2017-07-01

To compare surgical outcomes between robot-assisted laparoscopic partial nephrectomy and open partial nephrectomy in patients with chronic kidney disease. Of 550 patients who underwent partial nephrectomy between 2012 and 2015, 163 patients with T1-2 renal tumors who had an estimated glomerular filtration rate between 30 and 60 mL/min/1.73 m 2 , and underwent robot-assisted laparoscopic partial nephrectomy or open partial nephrectomy were retrospectively analyzed. To minimize selection bias between the two surgical methods, patient variables were adjusted by 1:1 propensity score matching. The present study included 75 patients undergoing robot-assisted laparoscopic partial nephrectomy and 88 undergoing open partial nephrectomy. After propensity score matching, 40 patients were included in each operative group. The mean preoperative estimated glomerular filtration rate was 49 mL/min/1.73 m 2 . The mean ischemia time was 21 min in robot-assisted laparoscopic partial nephrectomy (warm ischemia) and 35 min in open partial nephrectomy (cold ischemia). Preservation of the estimated glomerular filtration rate 3-6 months postoperatively was not significantly different between robot-assisted laparoscopic partial nephrectomy and open partial nephrectomy (92% vs 91%, P = 0.9348). Estimated blood loss was significantly lower in the robot-assisted laparoscopic partial nephrectomy group than in the open partial nephrectomy group (104 vs 185 mL, P = 0.0025). The postoperative length of hospital stay was shorter in the robot-assisted laparoscopic partial nephrectomy group than in the open partial nephrectomy group (P < 0.0001). The prevalence of Clavien-Dindo grade 3 complications and a negative surgical margin status were not significantly different between the two groups. In our experience, robot-assisted laparoscopic partial nephrectomy and open partial nephrectomy provide similar outcomes in terms of functional preservation and perioperative complications among patients with chronic kidney disease. However, a lower estimated blood loss and shorter postoperative length of hospital stay can be obtained with robot-assisted laparoscopic partial nephrectomy. © 2017 The Japanese Urological Association.

Benefits, Harms, and Costs of Osteoporosis Screening in Male Veterans

DTIC Science & Technology

2015-10-01

K Lyles, J LaFleur, C VanHoutven, C Pieper – accepted to American Geriatrics Society Annual Meeting, May 2016 Background: Practice guidelines...Veterans. Rasheeda K. Hall, Richard Sloane, Carl Pieper, Cathleen Colón-Emeric. – accepted to American Geriatrics Society Annual Meeting, May 2016...who had no prior diagnoses of fracture or osteoporosis therapy . Estimated glomerular filtration rate (eGFR) was estimated using baseline creatinine

The applicability of eGFR equations to different populations.

PubMed

Delanaye, Pierre; Mariat, Christophe

2013-09-01

The Cockcroft-Gault equation for estimating glomerular filtration rate has been learnt by every generation of medical students over the decades. Since the publication of the Modification of Diet in Renal Disease (MDRD) study equation in 1999, however, the supremacy of the Cockcroft-Gault equation has been relentlessly disputed. More recently, the Chronic Kidney Disease Epidemiology (CKD-EPI) consortium has proposed a group of novel equations for estimating glomerular filtration rate (GFR). The MDRD and CKD-EPI equations were developed following a rigorous process, are expressed in a way in which they can be used with standardized biomarkers of GFR (serum creatinine and/or serum cystatin C) and have been evaluated in different populations of patients. Today, the MDRD Study equation and the CKD-EPI equation based on serum creatinine level have supplanted the Cockcroft-Gault equation. In many regards, these equations are superior to the Cockcroft-Gault equation and are now specifically recommended by international guidelines. With their generalized use, however, it has become apparent that those equations are not infallible and that they fail to provide an accurate estimate of GFR in certain situations frequently encountered in clinical practice. After describing the processes that led to the development of the new GFR-estimating equations, this Review discusses the clinical situations in which the applicability of these equations is questioned.

Arterial stiffness, body fat compartments, central hemodynamics, renal function and left atrial size.

PubMed

Katulska, Katarzyna; Milewska, Agata; Wykretowicz, Mateusz; Krauze, Tomasz; Przymuszala, Dagmara; Piskorski, Jaroslaw; Stajgis, Marek; Guzik, Przemyslaw; Wysocki, Henryk; Wykrętowicz, Andrzej

2013-10-01

Left atrial (LA) size is an important predictor of stroke, death, and atrial fibrillation. It was demonstrated recently that body fat, arterial stiffness and renal functions are associated with LA diameter. However, data are lacking for comprehensive assessments of all these risk factors in a single population. Therefore, the aim of the present study was to investigate the association between LA size and different fat descriptors, central hemodynamics, arterial stiffness, and renal function in healthy subjects. To this end, body fat percentage, abdominal, subcutaneous fat, and general descriptors of body fat were estimated in 162 healthy subjects (mean age 51 years). Echocardiography was performed to assess LA diameter. Arterial stiffness and peripheral and central hemodynamics were estimated by digital volume pulse analysis and pulse wave analysis. Glomerular filtration rate was estimated by MDRD formula. There were significant (p < 0.05) bivariate correlations between LA diameter and all descriptors of body fat (except subcutaneous fat). Arterial stiffness and estimated glomerular filtration rate (eGFR) were also significantly correlated with LA size. Multiple regression analysis including all significant confounders, such as sex, mean arterial pressure, arterial stiffness, eGFR and body fat descriptors, explained 35% of variance in LA diameter. In conclusion, the present study reveals significant, independent relationships between body fat, arterial stiffness, and LA size.

Podocytes from the diagnostic and therapeutic point of view.

PubMed

Müller-Deile, Janina; Schiffer, Mario

2017-08-01

The central role of podocytes in glomerular diseases makes this cell type an interesting diagnostic tool as well as a therapeutic target. In this review, we discuss the current literature on the use of podocytes and podocyte-specific markers as non-invasive diagnostic tools in different glomerulopathies. Furthermore, we highlight the direct effects of drugs currently used to treat primary glomerular diseases and describe their direct cellular effects on podocytes. A new therapeutic potential is seen in drugs targeting the podocytic actin cytoskeleton which is essential for podocyte foot process structure and function. Incubation of cultured human podocyte cell lines with sera from patients with active glomerular diseases is currently also used to identify novel circulating factors with pathophysiological relevance for the glomerular filtration barrier. In addition, treatment of detached urinary podocytes from patients with substances that restore their cytoskeleton might serve as a novel personalized tool to estimate their potential for podocyte recovery ex vivo.

Incidence, determinants, and prognostic significance of hyperkalemia and worsening renal function in patients with heart failure receiving the mineralocorticoid receptor antagonist eplerenone or placebo in addition to optimal medical therapy: results from the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF).

PubMed

Rossignol, Patrick; Dobre, Daniela; McMurray, John J V; Swedberg, Karl; Krum, Henry; van Veldhuisen, Dirk J; Shi, Harry; Messig, Michael; Vincent, John; Girerd, Nicolas; Bakris, George; Pitt, Bertram; Zannad, Faiez

2014-01-01

Mineralocorticoid receptor antagonists improve outcomes in patients with systolic heart failure but may induce worsening of renal function (WRF) and hyperkalemia (HK). We assessed the risk factors for mineralocorticoid receptor antagonist-related WRF and for HK, as well as the association between HK and WRF with clinical outcomes in the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF). Serial changes in estimated glomerular filtration rate and in serum potassium were available in 2737 patients during a median 21-month follow-up. HK variably defined as serum K>4.5, 5, or 5.5 mmol/L occurred in 74.7%, 32.5%, and 8.9% patients enrolled in EMPHASIS-HF, respectively. WRF defined as a decrease in estimated glomerular filtration rate>20% or >30% from baseline occurred in 27% and 14% of patients, respectively. Patients assigned eplerenone displayed modest and early but significant and persistent (1) rise in serum potassium and (2) reduction in estimated glomerular filtration rate when compared with those assigned placebo. In multivariate analyses, eplerenone was associated with a higher incidence of WRF and HK, which were interrelated and also associated with baseline patient characteristics (eg, age≥75 years, hypertension, diabetes mellitus, nonwhite race, ejection fraction<30%, and treatment with an antiarrythmics drug or loop diuretic). Eplerenone retained its survival benefits without any significant interaction with the association between HK>5.5 mmol/L only and WRF and worse outcomes. In patients with heart failure receiving optimal therapy, WRF and HK were more frequent when eplerenone was added, but their occurrence did not eliminate the survival benefit of eplerenone. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00232180.

Randomized Trial of Studer Pouch versus T-Pouch Orthotopic Ileal Neobladder in Patients with Bladder Cancer.

PubMed

Skinner, Eila C; Fairey, Adrian S; Groshen, Susan; Daneshmand, Siamak; Cai, Jie; Miranda, Gus; Skinner, Donald G

2015-08-01

The need to prevent reflux in the construction of an orthotopic ileal neobladder is controversial. We designed the USC-STAR trial to determine whether the T-pouch neobladder that included an antireflux mechanism was superior to the Studer pouch in patients with bladder cancer undergoing radical cystectomy. This single center, randomized, controlled trial recruited patients with clinically nonmetastatic bladder cancer scheduled to undergo radical cystectomy with neobladder. Eligible patients were randomly assigned to undergo T-pouch or Studer ileal orthotopic neobladder. Treatment assignment was not masked. The primary end point was change in renal function from baseline to 3 years. The CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation was used to calculate the estimated glomerular filtration rate. Between February 2002 and November 2009, 237 patients were randomly assigned to T-pouch ileal orthotopic neobladder and 247 to Studer ileal orthotopic neobladder. Baseline characteristics did not differ between the groups. Between baseline and 3 years the estimated glomerular filtration rate decreased by 6.4 ml/minute/1.73 m(2) in the Studer group and 6.6 ml/minute/1.73 m(2) in the T-pouch group (p=0.35). Multivariable analysis showed that type of ileal orthotopic neobladder was not independently associated with 3-year renal function (p=0.63). However, baseline estimated glomerular filtration rate, age and urinary tract obstruction were independently associated with 3-year decline in renal function. Cumulative risk of urinary tract infection and overall late complications were not different between the groups, but the T-pouch was associated with an increased risk of secondary diversion related surgeries. T-pouch ileal orthotopic neobladder with an antireflux mechanism did not prevent a moderate reduction in renal function observed at 3 years compared to the Studer pouch, but did result in an increase in diversion related secondary surgical procedures. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Association of Race With Mortality and Cardiovascular Events in a Large Cohort of US Veterans.

PubMed

Kovesdy, Csaba P; Norris, Keith C; Boulware, L Ebony; Lu, Jun L; Ma, Jennie Z; Streja, Elani; Molnar, Miklos Z; Kalantar-Zadeh, Kamyar

2015-10-20

In the general population, blacks experience higher mortality than their white peers, attributed in part to their lower socioeconomic status, reduced access to care, and possibly intrinsic biological factors. Patients with kidney disease are a notable exception, among whom blacks experience lower mortality. It is unclear if similar differences affecting outcomes exist in patients with no kidney disease but with equal or similar access to health care. We compared all-cause mortality, incident coronary heart disease, and incident ischemic stroke using multivariable-adjusted Cox models in a nationwide cohort of 547 441 black and 2 525 525 white patients with baseline estimated glomerular filtration rate ≥ 60 mL·min⁻¹·1.73 m⁻² receiving care from the US Veterans Health Administration. In parallel analyses, we compared outcomes in black versus white individuals in the National Health and Nutrition Examination Survey (NHANES) 1999 to 2004. After multivariable adjustments in veterans, black race was associated with 24% lower all-cause mortality (adjusted hazard ratio, 0.76; 95% confidence interval, 0.75-0.77; P<0.001) and 37% lower incidence of coronary heart disease (adjusted hazard ratio, 0.63; 95% confidence interval, 0.62-0.65; P<0.001) but a similar incidence of ischemic stroke (adjusted hazard ratio, 0.99; 95% confidence interval, 0.97-1.01; P=0.3). Black race was associated with a 42% higher adjusted mortality among individuals with estimated glomerular filtration rate ≥ 60 mL·min⁻¹·1.73 m⁻² in NHANES (adjusted hazard ratio, 1.42; 95% confidence interval, 1.09-1.87). Black veterans with normal estimated glomerular filtration rate and equal access to healthcare have lower all-cause mortality and incidence of coronary heart disease and a similar incidence of ischemic stroke. These associations are in contrast to the higher mortality experienced by black individuals in the general US population. © 2015 American Heart Association, Inc.

Chronic Kidney Disease Is Associated With White Matter Hyperintensity Volume

PubMed Central

Khatri, Minesh; Wright, Clinton B.; Nickolas, Thomas L.; Yoshita, Mitsuhiro; Paik, Myunghee C.; Kranwinkel, Grace; Sacco, Ralph L.; DeCarli, Charles

2010-01-01

Background and Purpose White matter hyperintensities have been associated with increased risk of stroke, cognitive decline, and dementia. Chronic kidney disease is a risk factor for vascular disease and has been associated with inflammation and endothelial dysfunction, which have been implicated in the pathogenesis of white matter hyperintensities. Few studies have explored the relationship between chronic kidney disease and white matter hyperintensities. Methods The Northern Manhattan Study is a prospective, community-based cohort of which a subset of stroke-free participants underwent MRIs. MRIs were analyzed quantitatively for white matter hyperintensities volume, which was log-transformed to yield a normal distribution (log-white matter hyperintensity volume). Kidney function was modeled using serum creatinine, the Cockcroft-Gault formula for creatinine clearance, and the Modification of Diet in Renal Disease formula for estimated glomerular filtration rate. Creatinine clearance and estimated glomerular filtration rate were trichotomized to 15 to 60 mL/min, 60 to 90 mL/min, and >90 mL/min (reference). Linear regression was used to measure the association between kidney function and log-white matter hyperintensity volume adjusting for age, gender, race–ethnicity, education, cardiac disease, diabetes, homocysteine, and hypertension. Results Baseline data were available on 615 subjects (mean age 70 years, 60% women, 18% whites, 21% blacks, 62% Hispanics). In multivariate analysis, creatinine clearance 15 to 60 mL/min was associated with increased log-white matter hyperintensity volume (β 0.322; 95% CI, 0.095 to 0.550) as was estimated glomerular filtration rate 15 to 60 mL/min (β 0.322; 95% CI, 0.080 to 0.564). Serum creatinine, per 1-mg/dL increase, was also positively associated with log-white matter hyperintensity volume (β 1.479; 95% CI, 1.067 to 2.050). Conclusions The association between moderate–severe chronic kidney disease and white matter hyperintensity volume highlights the growing importance of kidney disease as a possible determinant of cerebrovascular disease and/or as a marker of microangiopathy. PMID:17962588

Clinical application of calculated split renal volume using computed tomography-based renal volumetry after partial nephrectomy: Correlation with technetium-99m dimercaptosuccinic acid renal scan data.

PubMed

Lee, Chan Ho; Park, Young Joo; Ku, Ja Yoon; Ha, Hong Koo

2017-06-01

To evaluate the clinical application of computed tomography-based measurement of renal cortical volume and split renal volume as a single tool to assess the anatomy and renal function in patients with renal tumors before and after partial nephrectomy, and to compare the findings with technetium-99m dimercaptosuccinic acid renal scan. The data of 51 patients with a unilateral renal tumor managed by partial nephrectomy were retrospectively analyzed. The renal cortical volume of tumor-bearing and contralateral kidneys was measured using ImageJ software. Split estimated glomerular filtration rate and split renal volume calculated using this renal cortical volume were compared with the split renal function measured with technetium-99m dimercaptosuccinic acid renal scan. A strong correlation between split renal function and split renal volume of the tumor-bearing kidney was observed before and after surgery (r = 0.89, P < 0.001 and r = 0.94, P < 0.001). The preoperative and postoperative split estimated glomerular filtration rate of the operated kidney showed a moderate correlation with split renal function (r = 0.39, P = 0.004 and r = 0.49, P < 0.001). The correlation between reductions in split renal function and split renal volume of the operated kidney (r = 0.87, P < 0.001) was stronger than that between split renal function and percent reduction in split estimated glomerular filtration rate (r = 0.64, P < 0.001). The split renal volume calculated using computed tomography-based renal volumetry had a strong correlation with the split renal function measured using technetium-99m dimercaptosuccinic acid renal scan. Computed tomography-based split renal volume measurement before and after partial nephrectomy can be used as a single modality for anatomical and functional assessment of the tumor-bearing kidney. © 2017 The Japanese Urological Association.

Renal function assessment in atrial fibrillation: Usefulness of chronic kidney disease epidemiology collaboration vs re-expressed 4 variable modification of diet in renal disease.

PubMed

Abumuaileq, Rami Riziq-Yousef; Abu-Assi, Emad; López-López, Andrea; Raposeiras-Roubin, Sergio; Rodríguez-Mañero, Moisés; Martínez-Sande, Luis; García-Seara, Francisco Javier; Fernandez-López, Xesus Alberte; González-Juanatey, Jose Ramón

2015-10-26

To compare the performance of the re-expressed Modification of Diet in Renal Disease equation vs the new Chronic Kidney Disease Epidemiology Collaboration equation in patients with non-valvular atrial fibrillation. We studied 911 consecutive patients with non-valvular atrial fibrillation on vitamin-K antagonist. The performance of the re-expressed Modification of Diet in Renal Disease equation vs the new Chronic Kidney Disease Epidemiology Collaboration equation in patients with non-valvular atrial fibrillation with respect to either a composite endpoint of major bleeding, thromboembolic events and all-cause mortality or each individual component of the composite endpoint was assessed using continuous and categorical ≥ 60, 59-30, and < 30 mL/min per 1.73 m(2) estimated glomerular filtration rate. During 10 ± 3 mo, the composite endpoint occurred in 98 (10.8%) patients: 30 patients developed major bleeding, 18 had thromboembolic events, and 60 died. The new equation provided lower prevalence of renal dysfunction < 60 mL/min per 1.73 m(2) (32.9%), compared with the re-expressed equation (34.1%). Estimated glomerular filtration rate from both equations was independent predictor of composite endpoint (HR = 0.98 and 0.97 for the re-expressed and the new equation, respectively; P < 0.0001) and all-cause mortality (HR = 0.98 for both equations, P < 0.01). Strong association with thromboembolic events was observed only when estimated glomerular filtration rate was < 30 mL/min per 1.73 m(2): HR is 5.1 for the re-expressed equation, and HR = 5.0 for the new equation. No significant association with major bleeding was observed for both equations. The new equation reduced the prevalence of renal dysfunction. Both equations performed similarly in predicting major adverse outcomes.

New optical probes for the continuous monitoring of renal function

NASA Astrophysics Data System (ADS)

Dorshow, Richard B.; Asmelash, Bethel; Chinen, Lori K.; Debreczeny, Martin P.; Fitch, Richard M.; Freskos, John N.; Galen, Karen P.; Gaston, Kimberly R.; Marzan, Timothy A.; Poreddy, Amruta R.; Rajagopalan, Raghavan; Shieh, Jeng-Jong; Neumann, William L.

2008-02-01

The ability to continuously monitor renal function via the glomerular filtration rate (GFR) in the clinic is currently an unmet medical need. To address this need we have developed a new series of hydrophilic fluorescent probes designed to clear via glomerular filtration for use as real time optical monitoring agents at the bedside. The ideal molecule should be freely filtered via the glomerular filtration barrier and be neither reabsorbed nor secreted by the renal tubule. In addition, we have hypothesized that a low volume of distribution into the interstitial space could also be advantageous. Our primary molecular design strategy employs a very small pyrazine-based fluorophore as the core unit. Modular chemistry for functionalizing these systems for optimal pharmacokinetics (PK) and photophysical properties have been developed. Structure-activity relationship (SAR) and pharmacokinetic (PK) studies involving hydrophilic pyrazine analogues incorporating polyethylene glycol (PEG), carbohydrate, amino acid and peptide functionality have been a focus of this work. Secondary design strategies for minimizing distribution into the interstitium while maintaining glomerular filtration include enhancing molecular volume through PEG substitution. In vivo optical monitoring experiments with advanced candidates have been correlated with plasma PK for measurement of clearance and hence GFR.

Podocyte-associated talin1 is critical for glomerular filtration barrier maintenance

PubMed Central

Tian, Xuefei; Kim, Jin Ju; Monkley, Susan M.; Gotoh, Nanami; Nandez, Ramiro; Soda, Keita; Inoue, Kazunori; Balkin, Daniel M.; Hassan, Hossam; Son, Sung Hyun; Lee, Yashang; Moeckel, Gilbert; Calderwood, David A.; Holzman, Lawrence B.; Critchley, David R.; Zent, Roy; Reiser, Jochen; Ishibe, Shuta

2014-01-01

Podocytes are specialized actin-rich epithelial cells that line the kidney glomerular filtration barrier. The interface between the podocyte and the glomerular basement membrane requires integrins, and defects in either α3 or β1 integrin, or the α3β1 ligand laminin result in nephrotic syndrome in murine models. The large cytoskeletal protein talin1 is not only pivotal for integrin activation, but also directly links integrins to the actin cytoskeleton. Here, we found that mice lacking talin1 specifically in podocytes display severe proteinuria, foot process effacement, and kidney failure. Loss of talin1 in podocytes caused only a modest reduction in β1 integrin activation, podocyte cell adhesion, and cell spreading; however, the actin cytoskeleton of podocytes was profoundly altered by the loss of talin1. Evaluation of murine models of glomerular injury and patients with nephrotic syndrome revealed that calpain-induced talin1 cleavage in podocytes might promote pathogenesis of nephrotic syndrome. Furthermore, pharmacologic inhibition of calpain activity following glomerular injury substantially reduced talin1 cleavage, albuminuria, and foot process effacement. Collectively, these findings indicate that podocyte talin1 is critical for maintaining the integrity of the glomerular filtration barrier and provide insight into the pathogenesis of nephrotic syndrome. PMID:24531545

Ultrastructural Characterization of the Glomerulopathy in Alport Mice by Helium Ion Scanning Microscopy (HIM).

PubMed

Tsuji, Kenji; Suleiman, Hani; Miner, Jeffrey H; Daley, James M; Capen, Diane E; Păunescu, Teodor G; Lu, Hua A Jenny

2017-09-15

The glomerulus exercises its filtration barrier function by establishing a complex filtration apparatus consisting of podocyte foot processes, glomerular basement membrane and endothelial cells. Disruption of any component of the glomerular filtration barrier leads to glomerular dysfunction, frequently manifested as proteinuria. Ultrastructural studies of the glomerulus by transmission electron microscopy (TEM) and conventional scanning electron microscopy (SEM) have been routinely used to identify and classify various glomerular diseases. Here we report the application of newly developed helium ion scanning microscopy (HIM) to examine the glomerulopathy in a Col4a3 mutant/Alport syndrome mouse model. Our study revealed unprecedented details of glomerular abnormalities in Col4a3 mutants including distorted podocyte cell bodies and disorganized primary processes. Strikingly, we observed abundant filamentous microprojections arising from podocyte cell bodies and processes, and presence of unique bridging processes that connect the primary processes and foot processes in Alport mice. Furthermore, we detected an altered glomerular endothelium with disrupted sub-endothelial integrity. More importantly, we were able to clearly visualize the complex, three-dimensional podocyte and endothelial interface by HIM. Our study demonstrates that HIM provides nanometer resolution to uncover and rediscover critical ultrastructural characteristics of the glomerulopathy in Col4a3 mutant mice.

The Effect of Health Literacy in Low Estimated Glomerular Filtration Rates and Diabetes

ERIC Educational Resources Information Center

Johnston, Nicklett

2017-01-01

Health literacy is widespread, but its potential is not recognized. By not recognizing health literacy, patients have the burden of coping with diabetes with renal complications without full knowledge of their responsibility to their health. The focus of the project was to assess participants with diabetes with low health literacy and low mean…

Aldosterone and glomerular filtration--observations in the general population.

PubMed

Hannemann, Anke; Rettig, Rainer; Dittmann, Kathleen; Völzke, Henry; Endlich, Karlhans; Nauck, Matthias; Wallaschofski, Henri

2014-03-10

Increasing evidence suggests that aldosterone promotes renal damage. Since data on the association between aldosterone and renal function in the general population are sparse, we chose to address this issue. We investigated the associations between the plasma aldosterone concentration (PAC) or the aldosterone-to-renin ratio (ARR) and the estimated glomerular filtration rate (eGFR) in a sample of adult men and women from Northeast Germany. A study population of 1921 adult men and women who participated in the first follow-up of the Study of Health in Pomerania was selected. None of the subjects used drugs that alter PAC or ARR. The eGFR was calculated according to the four-variable Modification of Diet in Renal Disease formula. Chronic kidney disease (CKD) was defined as an eGFR < 60 ml/min/1.73 m2. Linear regression models, adjusted for sex, age, waist circumference, diabetes mellitus, smoking status, systolic and diastolic blood pressures, serum triglyceride concentrations and time of blood sampling revealed inverse associations of PAC or ARR with eGFR (ß-coefficient for log-transformed PAC -3.12, p < 0.001; ß-coefficient for log-transformed ARR -3.36, p < 0.001). Logistic regression models revealed increased odds for CKD with increasing PAC (odds ratio for a one standard deviation increase in PAC: 1.35, 95% confidence interval: 1.06-1.71). There was no statistically significant association between ARR and CKD. Our study demonstrates that PAC and ARR are inversely associated with the glomerular filtration rate in the general population.

Glomerular Filtration Rate is Unchanged By Ultramarathon.

PubMed

Wołyniec, Wojciech; Ratkowski, Wojciech; Kasprowicz, Katarzyna; Jastrzębski, Zbigniew; Małgorzewicz, Sylwia; Witek, Konrad; Grzywacz, Tomasz; Żmijewski, Piotr; Renke, Marcin

2017-12-27

Acute kidney injury (AKI) is reported as a common complication of marathon and ultramarathon running. In previous studies AKI was diagnosed on the basis of the creatinine level in serum and estimated glomerular filtration rate (eGFR). In the present study we calculated eGFR and also measured creatinine clearance after every 25 km of a 100 km run. 20 healthy, amateur runners (males, mean age 40.75 ± 7.15 years, mean weight 76.87 ± 8.39 kg) took part in a 100 km run on a track. Blood and urine were collected before the run, after every 25 km and 12 hours after the run. 17 runners completed the study. There was increase in creatinine, urea and uric acid observed after 100 km (p < 0.05). The mean increase in creatinine was 0.21 mg/dl (24.53%). 5 runners fulfilled the Acute Kidney Injury Network (AKIN) criteria of AKI. The eGFR according to the MDRD (modification of diet in renal disease), CKD-EPI (chronic kidney disease epidemiology collaboration) and Cockcroft-Gault formulas was significantly decreased after the run (p < 0.05). Otherwise, creatinine clearance calculated from creatinine level in both serum and urine remained stable. In contrast to the majority of previous studies, we did not observe any decrease in the kidney function during an ultramarathon. In this study the creatinine clearance, which is the best routine laboratory method to determine glomerular filtration rate was used. There is no evidence that long running is harmful for kidney.

A Comprehensive Software and Database Management System for Glomerular Filtration Rate Estimation by Radionuclide Plasma Sampling and Serum Creatinine Methods.

PubMed

Jha, Ashish Kumar

2015-01-01

Glomerular filtration rate (GFR) estimation by plasma sampling method is considered as the gold standard. However, this method is not widely used because the complex technique and cumbersome calculations coupled with the lack of availability of user-friendly software. The routinely used Serum Creatinine method (SrCrM) of GFR estimation also requires the use of online calculators which cannot be used without internet access. We have developed user-friendly software "GFR estimation software" which gives the options to estimate GFR by plasma sampling method as well as SrCrM. We have used Microsoft Windows(®) as operating system and Visual Basic 6.0 as the front end and Microsoft Access(®) as database tool to develop this software. We have used Russell's formula for GFR calculation by plasma sampling method. GFR calculations using serum creatinine have been done using MIRD, Cockcroft-Gault method, Schwartz method, and Counahan-Barratt methods. The developed software is performing mathematical calculations correctly and is user-friendly. This software also enables storage and easy retrieval of the raw data, patient's information and calculated GFR for further processing and comparison. This is user-friendly software to calculate the GFR by various plasma sampling method and blood parameter. This software is also a good system for storing the raw and processed data for future analysis.

Serum uric acid concentration is associated with early changes of glomerular filtration rate in patients with diabetes type 1 without increased albumin excretion.

PubMed

Spaleniak, Sebastian; Korzeniewska-Dyl, Irmina; Moczulski, Dariusz

2014-10-01

The early loss of renal function in patients with type 1 diabetes may begin before proteinuria. Only 30% of patients with diabetes manifest overt proteinuria. According to the previous studies, increased urinary albumin excretion, which is considered a classic marker of progression of diabetic kidney disease, can regress to normal urine albumin excretion. The current studies conducted in patients with type 1 diabetes without increased urine albumin excretion showed that the uric acid concentration was an independent factor for the development of diabetic kidney disease. The aim of study was to assess the impact of uric acid concentration and to identify risk factors of the early glomerular filtration loss in patients with type 1 diabetes and normal urinary albumin excretion. 147 patients (61 women and 86 men) with type 1 diabetes without increased urine albumin excretion were analysed. GFR (gromerular filtration rate) was estimated based on the serum cystatin C concentration. Centile charts were used to determine the variation of uric acid concentration depending on GFR and gender. The mean value of the filtration rate for the study group was 117 ml/min/m2. The uric acid level above 90th percentile in relation to GFR was diagnosed in 8.2% of women and 0% of men, between 90th and 50th percentile in 44.3 % of women and 5.8% of men and below 50th percentile in 47.5% of women and 94.2% of men. Contrary to men in women higher serum acid concentration was strongly associated with higher glomerular filtration rate. Hyperfiltraion was diagnosed in 15 of women and 19 of men. The high normal uric acid concentration in women with type 1 diabetes might play a crucial role in development of hyperfiltration.

Assessment of glomerular filtration rate measurement with plasma sampling: a technical review.

PubMed

Murray, Anthony W; Barnfield, Mark C; Waller, Michael L; Telford, Tania; Peters, A Michael

2013-06-01

This article reviews available radionuclide-based techniques for glomerular filtration rate (GFR) measurement, focusing on clinical indications for GFR measurement, ideal GFR radiopharmaceutical tracer properties, and the 2 most common tracers in clinical use. Methods for full, 1-compartment, and single-sample renal clearance characterization are discussed. GFR normalization and the role of GFR measurement in chemotherapy dosing are also considered.

Albuminuria and Glomerular Filtration Rate in Individuals with Type 1 Diabetes Mellitus: Contribution of Metabolic Syndrome.

PubMed

Uribe-Wiechers, Ana Cecilia; Janka-Zires, Marcela; Almeda-Valdés, Paloma; López-Gutiérrez, Joel; Gómez-Pérez, Francisco J

2015-01-01

The development of metabolic syndrome has been described in patients with type 1 diabetes mellitus as the disease progresses over time. The purpose of this study is to assess the relationship between metabolic syndrome, albuminuria, and glomerular filtration rate, as well as to determine the prevalence of metabolic syndrome, in a group of Mexican patients with type 1 diabetes mellitus. We conducted a cross-sectional study that included patients with type 1 diabetes mellitus who were diagnosed over 10 years ago and who are seen at the Diabetes Intensive Control Clinic of the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran in Mexico City. The presence of metabolic syndrome was determined by using the National Cholesterol Education Program-Adult Treatment Panel III (ATP III) criteria. A total of 81 individuals were studied. The prevalence of metabolic syndrome was 18.5% (n = 15). A higher albuminuria was found in subjects with metabolic syndrome (34.9 mg/24 hours; 8.3-169.3) than in those without metabolic syndrome (9.0 mg/24 hours; 5.0-27.0; p = 0.02). Glomerular filtration rate was lower in patients with metabolic syndrome (95.3 ml/minute; [64.9-107.2] vs. 110.2 ml/minute [88.1-120.3]; p = 0.04). After classifying the population according to the number of metabolic syndrome criteria, a progressive increase in albuminuria and a progressive decrease in glomerular filtration rate were found with each additional metabolic syndrome criterion (p = 0.008 and p = 0.032, respectively). After adjusting for age, time from diagnosis, systolic blood pressure, triglycerides, HDL-cholesterol, and treatment with angiotensin receptor blockers or angiotensin converting enzyme inhibitors, we found that age, time from diagnosis, triglycerides, and HDL-cholesterol were independent factors associated with glomerular filtration rate (R2 = 0.286; p < 0.001). Metabolic syndrome was associated with a higher albuminuria and a reduction in glomerular filtration rate in patients with type 1 diabetes mellitus. Metabolic syndrome was present in 18.5% of this group of Mexican individuals with type 1 diabetes mellitus.

External Validation of Contact Surface Area as a Predictor of Postoperative Renal Function in Patients Undergoing Partial Nephrectomy.

PubMed

Haifler, Miki; Ristau, Benjamin T; Higgins, Andrew M; Smaldone, Marc C; Kutikov, Alexander; Zisman, Amnon; Uzzo, Robert G

2017-09-20

We sought to externally validate a mathematical formula for tumor contact surface area as a predictor of postoperative renal function in patients undergoing partial nephrectomy for renal cell carcinoma. We queried a prospectively maintained kidney cancer database for patients who underwent partial nephrectomy between 2014 and 2016. Contact surface area was calculated using data obtained from preoperative cross-sectional imaging. The correlation between contact surface area and perioperative variables was examined. The correlation between postoperative renal functional outcomes, contact surface area and the R.E.N.A.L. (radius, exophytic/endophytic properties, nearness of tumor to collecting system or sinus, anterior/posterior, location relative to polar lines and tumor touches main renal artery or vein) nephrometry score was also assessed. A total of 257 patients who underwent partial nephrectomy had sufficient data to enter the study. Median contact surface area was 14.5 cm 2 (IQR 6.2-36) and the median nephrometry score was 9 (IQR 7-10). Spearman correlation analysis showed that contact surface area correlated with estimated blood loss (r s = 0.42, p <0.001), length of stay (r s = 0.18, p = 0.005), and percent and absolute change in the estimated glomerular filtration rate (r s = -0.77 and -0.78, respectively, each p <0.001). On multivariable analysis contact surface area and nephrometry score were independent predictors of the absolute change in the estimated glomerular filtration rate (each p <0.001). ROC curve analysis revealed that contact surface area was a better predictor of a greater than 20% postoperative decline in the estimated glomerular filtration rate compared with the nephrometry score (AUC 0.94 vs 0.80). Contact surface area correlated with the change in postoperative renal function after partial nephrectomy. It can be used in conjunction with the nephrometry score to counsel patients about the risk of renal functional decline after partial nephrectomy. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Renal function in the fetus and neonate - the creatinine enigma.

PubMed

Kastl, Justin T

2017-04-01

The use of serum creatinine levels to estimate glomerular function in infants is admittedly fraught with inherent inaccuracies which are both physiological and methodological in nature. This characteristic can understandably reduce the neonatal clinician's confidence in the ability of serum creatinine levels to provide useful information relevant to their patients' medical care. The aim of this review is to provide further insight into the peculiarities of serum creatinine trends in both premature and term infants with special focus on the maturational and developmental changes occurring in the kidney during this crucial time-period. Though newer markers of glomerular function are gaining increasing traction in the clinical realm, the most prominent of which is currently cystatin C, creatinine nonetheless remains an important player in the scientific evolution of glomerular filtration rate (GFR) estimation. Not only do its limitations provide a level of distinction for newer markers of GFR, but its advantages persist in refining the precision of newer GFR formulae which incorporate multiple patient characteristics. Copyright © 2017 Elsevier Ltd. All rights reserved.

Circadian Rhythm of Glomerular Filtration and Solute Handling Related to Nocturnal Enuresis.

PubMed

Dossche, L; Raes, A; Hoebeke, P; De Bruyne, P; Vande Walle, J

2016-01-01

Although nocturnal polyuria in patients with monosymptomatic enuresis can largely be explained by the decreased nocturnal vasopressin secretion hypothesis, other circadian rhythms in the kidney also seem to have a role. We recently documented an absent day/night rhythm in a subgroup of desmopressin refractory cases. We explore the importance of abnormal circadian rhythm of glomerular filtration and tubular (sodium, potassium) parameters in patients with monosymptomatic enuresis. In this retrospective study of a tertiary enuresis population we collected data subsequent to a standardized screening (International Children's Continence Society questionnaire), 14-day diary for nocturnal enuresis and diuresis, and 24-hour concentration profile. The study population consisted of 139 children with nocturnal enuresis who were 5 years or older. Children with nonmonosymptomatic nocturnal enuresis were used as controls. There was a maintained circadian rhythm of glomerular filtration, sodium, osmotic excretion and diuresis rate in children with monosymptomatic and nonmonosymptomatic nocturnal enuresis, and there was no difference between the 2 groups. Secondary analysis revealed that in patients with nocturnal polyuria (with monosymptomatic or nonmonosymptomatic nocturnal enuresis) circadian rhythm of glomerular filtration, sodium and osmotic excretion, and diuresis rate was diminished in contrast to those without nocturnal polyuria (p <0.001). Circadian rhythm of the kidney does not differ between patients with nonmonosymptomatic and monosymptomatic enuresis. However, the subgroup with enuresis and nocturnal polyuria has a diminished circadian rhythm of nocturnal diuresis, sodium excretion and glomerular filtration in contrast to children without nocturnal polyuria. This observation cannot be explained by the vasopressin theory alone. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The relation of Complementary-Alternative Medicine use with glomerular filtration rate and depression in patients with chronic kidney disease at predialysis stage.

PubMed

Esen, Bennur; Atay, Ahmet Engin; Gokmen, Emel Saglam; Karakoc, Ayten; Sari, Hakan; Sarisakal, Samprie; Kahvecioglu, Serdar; Kayabasi, Hasan; Sit, Dede

2015-05-08

Complementary and alternative medicine is a broad field of health including all health care practices and methods; and their accompanying theories and beliefs. In the present study, we aimed to examine the frequency of complementary-alternative medicine use, and its relation with glomerular filtration rate and depression in patients with chronic kidney disease at predialysis stage. A total of 1053 predialysis patients; 518 female and 535 male, that were followed up with chronic kidney disease for at least 3 months were enrolled into the study. Demographic features, biochemical parameters and findings of physical examination were recorded. Their compliance to diet, and knowledge about disease were questioned. Beck depression inventory and questionnaire regarding to complementary-alternative medicine use were performed. The overall frequency of complementary-alternative medicine use was 40.3% . Total ratio of herbal products was 46%. Complementary-alternative medicine use was significantly more frequent in female or single patients, and patients that informed about chronic kidney disease or under strict diet (p:0.007, p:0.016, p:0.02, p:0.016; respectively). When glomerular filtration rate of participants were considered, complementary-alternative medicine use was similar in different stages of kidney disease. Depression was observed in 41.9% of patients and significantly frequent in patients with alternative method use (p:0.002). Depression score was higher as creatinine increases and glomerular filtration rate decreases (p:0.002; r: 0,093). We determined that complementary-alternative medicine use gradually increases at predialysis stage as glomerular filtration rate decreases and there is a strict relation between complementary-alternative medicine use and depression or female gender. Disorder related stressors may lead to seeking of alternative methods. This article is protected by copyright. All rights reserved.

Interaction of the renin-angiotensin system and the renal nerves in the regulation of rat kidney function.

PubMed Central

Handa, R K; Johns, E J

1985-01-01

Stimulation of the renal sympathetic nerves in pentobarbitone anaesthetized rats achieved a 13% reduction in renal blood flow, did not change glomerular filtration rate, but reduced urine flow by 37%, absolute sodium excretion by 37%, and fractional sodium excretion by 34%. Following inhibition of converting enzyme with captopril (0.38 mmol kg-1 h-1), similar nerve stimulation reduced both renal blood flow and glomerular filtration rate by 16%, and although urine flow and absolute sodium excretion fell by 32 and 31%, respectively, the 18% fall in fractional sodium excretion was significantly less than that observed in the absence of captopril. Renal nerve stimulation at low levels, which did not change either renal blood flow or glomerular filtration rate, reduced urine flow, and absolute and fractional sodium excretions by 25, 26 and 23%, respectively. In animals receiving captopril at 0.38 mmol kg-1 h-1, low-level nerve stimulation caused small increases in glomerular filtration rate of 7% and urine flow of 12%, but did not change either absolute or fractional sodium excretions. At one-fifth the dose of captopril (0.076 mmol kg-1 h-1), low-level nerve stimulation did not change renal haemodynamics but decreased urine flow, and absolute and fractional sodium excretions by 10, 10 and 8%, respectively. These results showed that angiotensin II production was necessary for regulation of glomerular filtration rate in the face of modest neurally induced reductions in renal blood flow and was compatible with an intra-renal site of action of angiotensin II preferentially at the efferent arteriole. They also demonstrated that in the rat the action of the renal nerves to decrease sodium excretion was dependent on angiotensin II. PMID:3005558

A Review of Podocyte Biology.

PubMed

Garg, Puneet

2018-05-31

Podocyte biology is a developing science that promises to help improve understanding of the mechanistic nature of multiple diseases associated with proteinuria. Proteinuria in nephrotic syndrome has been linked to mechanistic dysfunctions in the renal glomerulus involving the function of podocyte epithelial cells, including podocyte foot process effacement. Developments in imaging technology are improving knowledge of the detailed structure of the human renal glomerulus and cortex. Podocyte foot processes attach themselves to the glomerular capillaries at the glomerular basement membrane (GBM) forming intercellular junctions that form slit diaphragm filtration barriers that help maintain normal renal function. Damage in this area has been implicated in glomerular disease. Injured podocytes undergo effacement whereby they lose their structure and spread out, leading to a reduction in filtration barrier function. Effacement is typically associated with the presence of proteinuria in focal segmental glomerulosclerosis, minimal change disease, and diabetes. It is thought to be due to a breakdown in the actin cytoskeleton of the foot processes, complex contractile apparatuses that allow podocytes to dynamically reorganize according to changes in filtration requirements. The process of podocyte depletion correlates with the development of glomerular sclerosis and chronic kidney disease. Focal adhesion complexes that interact with the underlying GBM bind the podocytes within the glomerular structure and prevent their detachment. Key Messages: Knowledge of glomerular podocyte biology is helping to advance our understanding of the science and mechanics of the glomerular filtering process, opening the way to a variety of new potential applications for clinical targeting. © 2018 S. Karger AG, Basel.

Ceftazidime dosing in the elderly: economic implications.

PubMed

Vlasses, P H; Bastion, W A; Behal, R; Sirgo, M A

1993-01-01

This study evaluated the prevalence and resulting costs of ceftazidime dosing in excess of product labeling recommendations in elderly hospitalized patients. Ceftazidime is a beta-lactam antibiotic excreted via glomerular filtration. According to product labeling, ceftazidime dosing can frequently be decreased in the elderly because glomerular filtration declines with age. A multicenter, retrospective utilization audit involving 11 US academic medical centers examined 221 medical records of patients 65 years of age or older receiving ceftazidime (any brand, any indication). The creatinine clearance of each patient was estimated using the Cockcroft-Gault formula. Renal insufficiency, defined as an estimated creatinine clearance of less than 50 mL/min, was present in 111 of the patients (50 percent). Ceftazidime dosing in excess of product labeling recommendations was noted in 75 of those 111 (68 percent). The cost of excess ceftazidime dosing for those 75 patients (i.e., extra drug acquisition, preparation, administration) was $13,822.50. Although the dosage of ceftazidime required in a specific patient is based on many factors, ceftazidime is frequently overdosed in the elderly because renal function is not considered. Ceftazidime dose-adjustment in the elderly, based on the estimated creatinine clearance, can lead to cost savings. In the US, where hospital reimbursement by Medicare is based on diagnosis, institutions can realize direct cost savings.

Integrin beta1-mediated matrix assembly and signaling are critical for the normal development and function of the kidney glomerulus.

PubMed

Kanasaki, Keizo; Kanda, Yoshiko; Palmsten, Kristin; Tanjore, Harikrishna; Lee, Soo Bong; Lebleu, Valerie S; Gattone, Vincent H; Kalluri, Raghu

2008-01-15

The human kidneys filter 180 l of blood every day via about 2.5 million glomeruli. The three layers of the glomerular filtration apparatus consist of fenestrated endothelium, specialized extracellular matrix known as the glomerular basement membrane (GBM) and the podocyte foot processes with their modified adherens junctions known as the slit diaphragm (SD). In this study we explored the contribution of podocyte beta1 integrin signaling for normal glomerular function. Mice with podocyte specific deletion of integrin beta1 (podocin-Cre beta1-fl/fl mice) are born normal but cannot complete postnatal renal development. They exhibit detectable proteinuria on day 1 and die within a week. The kidneys of podocin-Cre beta1-fl/fl mice exhibit normal glomerular endothelium but show severe GBM defects with multilaminations and splitting including podocyte foot process effacement. The integrin linked kinase (ILK) is a downstream mediator of integrin beta1 activity in epithelial cells. To further explore whether integrin beta1-mediated signaling facilitates proper glomerular filtration, we generated mice deficient of ILK in the podocytes (podocin-Cre ILK-fl/fl mice). These mice develop normally but exhibit postnatal proteinuria at birth and die within 15 weeks of age due to renal failure. Collectively, our studies demonstrate that podocyte beta1 integrin and ILK signaling is critical for postnatal development and function of the glomerular filtration apparatus.

Estimation of residual glomerular filtration rate in peritoneal dialysis patients using cystatin C: comparison with 51Cr-EDTA clearance.

PubMed

Carter, Joanne L; Lane, Catherine E; Fan, Stanley L; Lamb, Edmund J

2011-11-01

Measuring glomerular filtration rate (GFR) is an important assessment in peritoneal dialysis patients. In clinical practice, it is commonly measured by calculating the mean of the urinary clearance of urea and creatinine (GFR(UrCl)) but this process is time consuming and unreliable. We wished to compare several estimates of GFR including residual GFR estimated from cystatin C (GFR(CysC)) using a published equation (Hoek), GFR(UrCl) and (51)Cr-ethylenediaminetetraacetic acid (EDTA) clearance, in peritoneal dialysis patients. GFR(CysC), GFR(UrCl) and (51)Cr-EDTA clearance were measured in 28 patients undergoing peritoneal dialysis in a single dialysis unit. GFR(CysC) was related to GFR(UrCl) (Spearman's rank correlation coefficient r(s) = 0.44; P = 0.0185) and to (51)Cr-EDTA clearance (r(s) = 0.48; P = 0.0099). GFR(CysC) values were significantly (P = 0.0077) lower than (51)Cr-EDTA clearance results (mean bias -19.7%). However, GFR(CysC) did not differ significantly (P > 0.05) from GFR(UrCl). GFR(CysC) is related to GFR(UrCl) but has a significant negative bias against (51)Cr-EDTA. Given the known limitations of (51)Cr-EDTA in estimating GFR in renal failure, this study provides additional validation suggesting that cystatin C-estimated rGFR (GFR(CysC)) gives a reasonable estimation of GFR without the clinical problems associated with 24 h urine collections.

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

PubMed

Pattaro, Cristian; Teumer, Alexander; Gorski, Mathias; Chu, Audrey Y; Li, Man; Mijatovic, Vladan; Garnaas, Maija; Tin, Adrienne; Sorice, Rossella; Li, Yong; Taliun, Daniel; Olden, Matthias; Foster, Meredith; Yang, Qiong; Chen, Ming-Huei; Pers, Tune H; Johnson, Andrew D; Ko, Yi-An; Fuchsberger, Christian; Tayo, Bamidele; Nalls, Michael; Feitosa, Mary F; Isaacs, Aaron; Dehghan, Abbas; d'Adamo, Pio; Adeyemo, Adebowale; Dieffenbach, Aida Karina; Zonderman, Alan B; Nolte, Ilja M; van der Most, Peter J; Wright, Alan F; Shuldiner, Alan R; Morrison, Alanna C; Hofman, Albert; Smith, Albert V; Dreisbach, Albert W; Franke, Andre; Uitterlinden, Andre G; Metspalu, Andres; Tonjes, Anke; Lupo, Antonio; Robino, Antonietta; Johansson, Åsa; Demirkan, Ayse; Kollerits, Barbara; Freedman, Barry I; Ponte, Belen; Oostra, Ben A; Paulweber, Bernhard; Krämer, Bernhard K; Mitchell, Braxton D; Buckley, Brendan M; Peralta, Carmen A; Hayward, Caroline; Helmer, Catherine; Rotimi, Charles N; Shaffer, Christian M; Müller, Christian; Sala, Cinzia; van Duijn, Cornelia M; Saint-Pierre, Aude; Ackermann, Daniel; Shriner, Daniel; Ruggiero, Daniela; Toniolo, Daniela; Lu, Yingchang; Cusi, Daniele; Czamara, Darina; Ellinghaus, David; Siscovick, David S; Ruderfer, Douglas; Gieger, Christian; Grallert, Harald; Rochtchina, Elena; Atkinson, Elizabeth J; Holliday, Elizabeth G; Boerwinkle, Eric; Salvi, Erika; Bottinger, Erwin P; Murgia, Federico; Rivadeneira, Fernando; Ernst, Florian; Kronenberg, Florian; Hu, Frank B; Navis, Gerjan J; Curhan, Gary C; Ehret, George B; Homuth, Georg; Coassin, Stefan; Thun, Gian-Andri; Pistis, Giorgio; Gambaro, Giovanni; Malerba, Giovanni; Montgomery, Grant W; Eiriksdottir, Gudny; Jacobs, Gunnar; Li, Guo; Wichmann, H-Erich; Campbell, Harry; Schmidt, Helena; Wallaschofski, Henri; Völzke, Henry; Brenner, Hermann; Kroemer, Heyo K; Kramer, Holly; Lin, Honghuang; Leach, I Mateo; Ford, Ian; Guessous, Idris; Rudan, Igor; Prokopenko, Inga; Borecki, Ingrid; Heid, Iris M; Kolcic, Ivana; Persico, Ivana; Jukema, J Wouter; Wilson, James F; Felix, Janine F; Divers, Jasmin; Lambert, Jean-Charles; Stafford, Jeanette M; Gaspoz, Jean-Michel; Smith, Jennifer A; Faul, Jessica D; Wang, Jie Jin; Ding, Jingzhong; Hirschhorn, Joel N; Attia, John; Whitfield, John B; Chalmers, John; Viikari, Jorma; Coresh, Josef; Denny, Joshua C; Karjalainen, Juha; Fernandes, Jyotika K; Endlich, Karlhans; Butterbach, Katja; Keene, Keith L; Lohman, Kurt; Portas, Laura; Launer, Lenore J; Lyytikäinen, Leo-Pekka; Yengo, Loic; Franke, Lude; Ferrucci, Luigi; Rose, Lynda M; Kedenko, Lyudmyla; Rao, Madhumathi; Struchalin, Maksim; Kleber, Marcus E; Cavalieri, Margherita; Haun, Margot; Cornelis, Marilyn C; Ciullo, Marina; Pirastu, Mario; de Andrade, Mariza; McEvoy, Mark A; Woodward, Mark; Adam, Martin; Cocca, Massimiliano; Nauck, Matthias; Imboden, Medea; Waldenberger, Melanie; Pruijm, Menno; Metzger, Marie; Stumvoll, Michael; Evans, Michele K; Sale, Michele M; Kähönen, Mika; Boban, Mladen; Bochud, Murielle; Rheinberger, Myriam; Verweij, Niek; Bouatia-Naji, Nabila; Martin, Nicholas G; Hastie, Nick; Probst-Hensch, Nicole; Soranzo, Nicole; Devuyst, Olivier; Raitakari, Olli; Gottesman, Omri; Franco, Oscar H; Polasek, Ozren; Gasparini, Paolo; Munroe, Patricia B; Ridker, Paul M; Mitchell, Paul; Muntner, Paul; Meisinger, Christa; Smit, Johannes H; Kovacs, Peter; Wild, Philipp S; Froguel, Philippe; Rettig, Rainer; Mägi, Reedik; Biffar, Reiner; Schmidt, Reinhold; Middelberg, Rita P S; Carroll, Robert J; Penninx, Brenda W; Scott, Rodney J; Katz, Ronit; Sedaghat, Sanaz; Wild, Sarah H; Kardia, Sharon L R; Ulivi, Sheila; Hwang, Shih-Jen; Enroth, Stefan; Kloiber, Stefan; Trompet, Stella; Stengel, Benedicte; Hancock, Stephen J; Turner, Stephen T; Rosas, Sylvia E; Stracke, Sylvia; Harris, Tamara B; Zeller, Tanja; Zemunik, Tatijana; Lehtimäki, Terho; Illig, Thomas; Aspelund, Thor; Nikopensius, Tiit; Esko, Tonu; Tanaka, Toshiko; Gyllensten, Ulf; Völker, Uwe; Emilsson, Valur; Vitart, Veronique; Aalto, Ville; Gudnason, Vilmundur; Chouraki, Vincent; Chen, Wei-Min; Igl, Wilmar; März, Winfried; Koenig, Wolfgang; Lieb, Wolfgang; Loos, Ruth J F; Liu, Yongmei; Snieder, Harold; Pramstaller, Peter P; Parsa, Afshin; O'Connell, Jeffrey R; Susztak, Katalin; Hamet, Pavel; Tremblay, Johanne; de Boer, Ian H; Böger, Carsten A; Goessling, Wolfram; Chasman, Daniel I; Köttgen, Anna; Kao, W H Linda; Fox, Caroline S

2016-01-21

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

PubMed Central

Pattaro, Cristian; Teumer, Alexander; Gorski, Mathias; Chu, Audrey Y.; Li, Man; Mijatovic, Vladan; Garnaas, Maija; Tin, Adrienne; Sorice, Rossella; Li, Yong; Taliun, Daniel; Olden, Matthias; Foster, Meredith; Yang, Qiong; Chen, Ming-Huei; Pers, Tune H.; Johnson, Andrew D.; Ko, Yi-An; Fuchsberger, Christian; Tayo, Bamidele; Nalls, Michael; Feitosa, Mary F.; Isaacs, Aaron; Dehghan, Abbas; d'Adamo, Pio; Adeyemo, Adebowale; Dieffenbach, Aida Karina; Zonderman, Alan B.; Nolte, Ilja M.; van der Most, Peter J.; Wright, Alan F.; Shuldiner, Alan R.; Morrison, Alanna C.; Hofman, Albert; Smith, Albert V.; Dreisbach, Albert W.; Franke, Andre; Uitterlinden, Andre G.; Metspalu, Andres; Tonjes, Anke; Lupo, Antonio; Robino, Antonietta; Johansson, Åsa; Demirkan, Ayse; Kollerits, Barbara; Freedman, Barry I.; Ponte, Belen; Oostra, Ben A.; Paulweber, Bernhard; Krämer, Bernhard K.; Mitchell, Braxton D.; Buckley, Brendan M.; Peralta, Carmen A.; Hayward, Caroline; Helmer, Catherine; Rotimi, Charles N.; Shaffer, Christian M.; Müller, Christian; Sala, Cinzia; van Duijn, Cornelia M.; Saint-Pierre, Aude; Ackermann, Daniel; Shriner, Daniel; Ruggiero, Daniela; Toniolo, Daniela; Lu, Yingchang; Cusi, Daniele; Czamara, Darina; Ellinghaus, David; Siscovick, David S.; Ruderfer, Douglas; Gieger, Christian; Grallert, Harald; Rochtchina, Elena; Atkinson, Elizabeth J.; Holliday, Elizabeth G.; Boerwinkle, Eric; Salvi, Erika; Bottinger, Erwin P.; Murgia, Federico; Rivadeneira, Fernando; Ernst, Florian; Kronenberg, Florian; Hu, Frank B.; Navis, Gerjan J.; Curhan, Gary C.; Ehret, George B.; Homuth, Georg; Coassin, Stefan; Thun, Gian-Andri; Pistis, Giorgio; Gambaro, Giovanni; Malerba, Giovanni; Montgomery, Grant W.; Eiriksdottir, Gudny; Jacobs, Gunnar; Li, Guo; Wichmann, H-Erich; Campbell, Harry; Schmidt, Helena; Wallaschofski, Henri; Völzke, Henry; Brenner, Hermann; Kroemer, Heyo K.; Kramer, Holly; Lin, Honghuang; Leach, I. Mateo; Ford, Ian; Guessous, Idris; Rudan, Igor; Prokopenko, Inga; Borecki, Ingrid; Heid, Iris M.; Kolcic, Ivana; Persico, Ivana; Jukema, J. Wouter; Wilson, James F.; Felix, Janine F.; Divers, Jasmin; Lambert, Jean-Charles; Stafford, Jeanette M.; Gaspoz, Jean-Michel; Smith, Jennifer A.; Faul, Jessica D.; Wang, Jie Jin; Ding, Jingzhong; Hirschhorn, Joel N.; Attia, John; Whitfield, John B.; Chalmers, John; Viikari, Jorma; Coresh, Josef; Denny, Joshua C.; Karjalainen, Juha; Fernandes, Jyotika K.; Endlich, Karlhans; Butterbach, Katja; Keene, Keith L.; Lohman, Kurt; Portas, Laura; Launer, Lenore J.; Lyytikäinen, Leo-Pekka; Yengo, Loic; Franke, Lude; Ferrucci, Luigi; Rose, Lynda M.; Kedenko, Lyudmyla; Rao, Madhumathi; Struchalin, Maksim; Kleber, Marcus E.; Cavalieri, Margherita; Haun, Margot; Cornelis, Marilyn C.; Ciullo, Marina; Pirastu, Mario; de Andrade, Mariza; McEvoy, Mark A.; Woodward, Mark; Adam, Martin; Cocca, Massimiliano; Nauck, Matthias; Imboden, Medea; Waldenberger, Melanie; Pruijm, Menno; Metzger, Marie; Stumvoll, Michael; Evans, Michele K.; Sale, Michele M.; Kähönen, Mika; Boban, Mladen; Bochud, Murielle; Rheinberger, Myriam; Verweij, Niek; Bouatia-Naji, Nabila; Martin, Nicholas G.; Hastie, Nick; Probst-Hensch, Nicole; Soranzo, Nicole; Devuyst, Olivier; Raitakari, Olli; Gottesman, Omri; Franco, Oscar H.; Polasek, Ozren; Gasparini, Paolo; Munroe, Patricia B.; Ridker, Paul M.; Mitchell, Paul; Muntner, Paul; Meisinger, Christa; Smit, Johannes H.; Abecasis, Goncalo R.; Adair, Linda S.; Alexander, Myriam; Altshuler, David; Amin, Najaf; Arking, Dan E.; Arora, Pankaj; Aulchenko, Yurii; Bakker, Stephan J. L.; Bandinelli, Stefania; Barroso, Ines; Beckmann, Jacques S.; Beilby, John P.; Bergman, Richard N.; Bergmann, Sven; Bis, Joshua C.; Boehnke, Michael; Bonnycastle, Lori L.; Bornstein, Stefan R.; Bots, Michiel L.; Bragg-Gresham, Jennifer L.; Brand, Stefan-Martin; Brand, Eva; Braund, Peter S.; Brown, Morris J.; Burton, Paul R.; Casas, Juan P.; Caulfield, Mark J.; Chakravarti, Aravinda; Chambers, John C.; Chandak, Giriraj R.; Chang, Yen-Pei C.; Charchar, Fadi J.; Chaturvedi, Nish; Shin Cho, Yoon; Clarke, Robert; Collins, Francis S.; Collins, Rory; Connell, John M.; Cooper, Jackie A.; Cooper, Matthew N.; Cooper, Richard S.; Corsi, Anna Maria; Dörr, Marcus; Dahgam, Santosh; Danesh, John; Smith, George Davey; Day, Ian N. M.; Deloukas, Panos; Denniff, Matthew; Dominiczak, Anna F.; Dong, Yanbin; Doumatey, Ayo; Elliott, Paul; Elosua, Roberto; Erdmann, Jeanette; Eyheramendy, Susana; Farrall, Martin; Fava, Cristiano; Forrester, Terrence; Fowkes, F. Gerald R.; Fox, Ervin R.; Frayling, Timothy M.; Galan, Pilar; Ganesh, Santhi K.; Garcia, Melissa; Gaunt, Tom R.; Glazer, Nicole L.; Go, Min Jin; Goel, Anuj; Grässler, Jürgen; Grobbee, Diederick E.; Groop, Leif; Guarrera, Simonetta; Guo, Xiuqing; Hadley, David; Hamsten, Anders; Han, Bok-Ghee; Hardy, Rebecca; Hartikainen, Anna-Liisa; Heath, Simon; Heckbert, Susan R.; Hedblad, Bo; Hercberg, Serge; Hernandez, Dena; Hicks, Andrew A.; Hilton, Gina; Hingorani, Aroon D.; Bolton, Judith A Hoffman; Hopewell, Jemma C.; Howard, Philip; Humphries, Steve E.; Hunt, Steven C.; Hveem, Kristian; Ikram, M. Arfan; Islam, Muhammad; Iwai, Naoharu; Jarvelin, Marjo-Riitta; Jackson, Anne U.; Jafar, Tazeen H.; Janipalli, Charles S.; Johnson, Toby; Kathiresan, Sekar; Khaw, Kay-Tee; Kim, Hyung-Lae; Kinra, Sanjay; Kita, Yoshikuni; Kivimaki, Mika; Kooner, Jaspal S.; Kumar, M. J. Kranthi; Kuh, Diana; Kulkarni, Smita R.; Kumari, Meena; Kuusisto, Johanna; Kuznetsova, Tatiana; Laakso, Markku; Laan, Maris; Laitinen, Jaana; Lakatta, Edward G.; Langefeld, Carl D.; Larson, Martin G.; Lathrop, Mark; Lawlor, Debbie A.; Lawrence, Robert W.; Lee, Jong-Young; Lee, Nanette R.; Levy, Daniel; Li, Yali; Longstreth, Will T.; Luan, Jian'an; Lucas, Gavin; Ludwig, Barbara; Mangino, Massimo; Mani, K. Radha; Marmot, Michael G.; Mattace-Raso, Francesco U. S.; Matullo, Giuseppe; McArdle, Wendy L.; McKenzie, Colin A.; Meitinger, Thomas; Melander, Olle; Meneton, Pierre; Meschia, James F.; Miki, Tetsuro; Milaneschi, Yuri; Mohlke, Karen L.; Mooser, Vincent; Morken, Mario A.; Morris, Richard W.; Mosley, Thomas H.; Najjar, Samer; Narisu, Narisu; Newton-Cheh, Christopher; Nguyen, Khanh-Dung Hoang; Nilsson, Peter; Nyberg, Fredrik; O'Donnell, Christopher J.; Ogihara, Toshio; Ohkubo, Takayoshi; Okamura, Tomonori; Ong, RickTwee-Hee; Ongen, Halit; Onland-Moret, N. Charlotte; O'Reilly, Paul F.; Org, Elin; Orru, Marco; Palmas, Walter; Palmen, Jutta; Palmer, Lyle J.; Palmer, Nicholette D.; Parker, Alex N.; Peden, John F.; Peltonen, Leena; Perola, Markus; Pihur, Vasyl; Platou, Carl G. P.; Plump, Andrew; Prabhakaran, Dorairajan; Psaty, Bruce M.; Raffel, Leslie J.; Rao, Dabeeru C.; Rasheed, Asif; Ricceri, Fulvio; Rice, Kenneth M.; Rosengren, Annika; Rotter, Jerome I.; Rudock, Megan E.; Sõber, Siim; Salako, Tunde; Saleheen, Danish; Salomaa, Veikko; Samani, Nilesh J.; Schwartz, Steven M.; Schwarz, Peter E. H.; Scott, Laura J.; Scott, James; Scuteri, Angelo; Sehmi, Joban S.; Seielstad, Mark; Seshadri, Sudha; Sharma, Pankaj; Shaw-Hawkins, Sue; Shi, Gang; Shrine, Nick R. G.; Sijbrands, Eric J. G.; Sim, Xueling; Singleton, Andrew; Sjögren, Marketa; Smith, Nicholas L.; Artigas, Maria Soler; Spector, Tim D.; Staessen, Jan A.; Stancakova, Alena; Steinle, Nanette I.; Strachan, David P.; Stringham, Heather M.; Sun, Yan V.; Swift, Amy J.; Tabara, Yasuharu; Tai, E-Shyong; Talmud, Philippa J.; Taylor, Andrew; Terzic, Janos; Thelle, Dag S.; Tobin, Martin D.; Tomaszewski, Maciej; Tripathy, Vikal; Tuomilehto, Jaakko; Tzoulaki, Ioanna; Uda, Manuela; Ueshima, Hirotsugu; Uiterwaal, Cuno S. P. M.; Umemura, Satoshi; van der Harst, Pim; van der Schouw, Yvonne T.; van Gilst, Wiek H.; Vartiainen, Erkki; Vasan, Ramachandran S.; Veldre, Gudrun; Verwoert, Germaine C.; Viigimaa, Margus; Vinay, D. G.; Vineis, Paolo; Voight, Benjamin F.; Vollenweider, Peter; Wagenknecht, Lynne E.; Wain, Louise V.; Wang, Xiaoling; Wang, Thomas J.; Wareham, Nicholas J.; Watkins, Hugh; Weder, Alan B.; Whincup, Peter H.; Wiggins, Kerri L.; Witteman, Jacqueline C. M.; Wong, Andrew; Wu, Ying; Yajnik, Chittaranjan S.; Yao, Jie; Young, J. H.; Zelenika, Diana; Zhai, Guangju; Zhang, Weihua; Zhang, Feng; Zhao, Jing Hua; Zhu, Haidong; Zhu, Xiaofeng; Zitting, Paavo; Zukowska-Szczechowska, Ewa; Okada, Yukinori; Wu, Jer-Yuarn; Gu, Dongfeng; Takeuchi, Fumihiko; Takahashi, Atsushi; Maeda, Shiro; Tsunoda, Tatsuhiko; Chen, Peng; Lim, Su-Chi; Wong, Tien-Yin; Liu, Jianjun; Young, Terri L.; Aung, Tin; Teo, Yik-Ying; Kim, Young Jin; Kang, Daehee; Chen, Chien-Hsiun; Tsai, Fuu-Jen; Chang, Li-Ching; Fann, S. -J. Cathy; Mei, Hao; Hixson, James E.; Chen, Shufeng; Katsuya, Tomohiro; Isono, Masato; Albrecht, Eva; Yamamoto, Kazuhiko; Kubo, Michiaki; Nakamura, Yusuke; Kamatani, Naoyuki; Kato, Norihiro; He, Jiang; Chen, Yuan-Tsong; Tanaka, Toshihiro; Reilly, Muredach P; Schunkert, Heribert; Assimes, Themistocles L.; Hall, Alistair; Hengstenberg, Christian; König, Inke R.; Laaksonen, Reijo; McPherson, Ruth; Thompson, John R.; Thorsteinsdottir, Unnur; Ziegler, Andreas; Absher, Devin; Chen, Li; Cupples13, L. Adrienne; Halperin, Eran; Li, Mingyao; Musunuru, Kiran; Preuss, Michael; Schillert, Arne; Thorleifsson, Gudmar; Wells, George A.; Holm, Hilma; Roberts, Robert; Stewart, Alexandre F. R.; Fortmann, Stephen; Go, Alan; Hlatky, Mark; Iribarren, Carlos; Knowles, Joshua; Myers, Richard; Quertermous, Thomas; Sidney, Steven; Risch, Neil; Tang, Hua; Blankenberg, Stefan; Schnabel, Renate; Sinning, Christoph; Lackner, Karl J.; Tiret, Laurence; Nicaud, Viviane; Cambien, Francois; Bickel, Christoph; Rupprecht, Hans J.; Perret, Claire; Proust, Carole; Münzel, Thomas F.; Barbalic, Maja; Chen, Ida Yii-Der; Demissie-Banjaw, Serkalem; Folsom, Aaron; Lumley, Thomas; Marciante, Kristin; Taylor, Kent D.; Volcik, Kelly; Gretarsdottir, Solveig; Gulcher, Jeffrey R.; Kong, Augustine; Stefansson, Kari; Thorgeirsson, Gudmundur; Andersen, Karl; Fischer, Marcus; Grosshennig, Anika; Linsel-Nitschke, Patrick; Stark, Klaus; Schreiber, Stefan; Aherrahrou, Zouhair; Bruse, Petra; Doering, Angela; Klopp, Norman; Diemert, Patrick; Loley, Christina; Medack, Anja; Nahrstedt, Janja; Peters, Annette; Wagner, Arnika K.; Willenborg, Christina; Böhm, Bernhard O.; Dobnig, Harald; Grammer, Tanja B.; Hoffmann, Michael M.; Meinitzer, Andreas; Winkelmann, Bernhard R.; Pilz, Stefan; Renner, Wilfried; Scharnagl, Hubert; Stojakovic, Tatjana; Tomaschitz, Andreas; Winkler, Karl; Guiducci, Candace; Burtt, Noel; Gabriel, Stacey B.; Dandona, Sonny; Jarinova, Olga; Qu, Liming; Wilensky, Robert; Matthai, William; Hakonarson, Hakon H.; Devaney, Joe; Burnett, Mary Susan; Pichard, Augusto D.; Kent, Kenneth M.; Satler, Lowell; Lindsay, Joseph M.; Waksman, Ron; Knouff, Christopher W.; Waterworth, Dawn M.; Walker, Max C.; Epstein, Stephen E.; Rader, Daniel J.; Nelson, Christopher P.; Wright, Benjamin J.; Balmforth, Anthony J.; Ball, Stephen G.; Loehr, Laura R.; Rosamond, Wayne D.; Benjamin, Emelia; Haritunians, Talin; Couper, David; Murabito, Joanne; Wang, Ying A.; Stricker, Bruno H.; Chang, Patricia P.; Willerson, James T.; Felix, Stephan B.; Watzinger, Norbert; Aragam, Jayashri; Zweiker, Robert; Lind, Lars; Rodeheffer, Richard J.; Greiser, Karin Halina; Deckers, Jaap W.; Stritzke, Jan; Ingelsson, Erik; Kullo, Iftikhar; Haerting, Johannes; Reffelmann, Thorsten; Redfield, Margaret M.; Werdan, Karl; Mitchell, Gary F.; Arnett, Donna K.; Gottdiener, John S.; Blettner, Maria; Friedrich, Nele; Kovacs, Peter; Wild, Philipp S.; Froguel, Philippe; Rettig, Rainer; Mägi, Reedik; Biffar, Reiner; Schmidt, Reinhold; Middelberg, Rita P. S.; Carroll, Robert J.; Penninx, Brenda W.; Scott, Rodney J.; Katz, Ronit; Sedaghat, Sanaz; Wild, Sarah H.; Kardia, Sharon L. R.; Ulivi, Sheila; Hwang, Shih-Jen; Enroth, Stefan; Kloiber, Stefan; Trompet, Stella; Stengel, Benedicte; Hancock, Stephen J.; Turner, Stephen T.; Rosas, Sylvia E.; Stracke, Sylvia; Harris, Tamara B.; Zeller, Tanja; Zemunik, Tatijana; Lehtimäki, Terho; Illig, Thomas; Aspelund, Thor; Nikopensius, Tiit; Esko, Tonu; Tanaka, Toshiko; Gyllensten, Ulf; Völker, Uwe; Emilsson, Valur; Vitart, Veronique; Aalto, Ville; Gudnason, Vilmundur; Chouraki, Vincent; Chen, Wei-Min; Igl, Wilmar; März, Winfried; Koenig, Wolfgang; Lieb, Wolfgang; Loos, Ruth J. F.; Liu, Yongmei; Snieder, Harold; Pramstaller, Peter P.; Parsa, Afshin; O'Connell, Jeffrey R.; Susztak, Katalin; Hamet, Pavel; Tremblay, Johanne; de Boer, Ian H.; Böger, Carsten A.; Goessling, Wolfram; Chasman, Daniel I.; Köttgen, Anna; Kao, W. H. Linda; Fox, Caroline S.

2016-01-01

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways. PMID:26831199

Skin Autofluorescence and Subclinical Atherosclerosis in Mild to Moderate Chronic Kidney Disease: A Case-Control Study.

PubMed

Sánchez, Enric; Betriu, Àngels; Arroyo, David; López, Carolina; Hernández, Marta; Rius, Ferran; Fernández, Elvira; Lecube, Albert

2017-01-01

Advanced glycation end-products (AGEs) are increased and predict mortality in patients with chronic kidney disease (CKD) who are undergoing hemodialysis, irrespective of the presence of type 2 diabetes. However, little information exits about the relationship between AGEs and subclinical atherosclerosis at the early stages of CKD. A case-control study was performed including 87 patients with mild-to-moderate stages of CKD (glomerular filtration rate from 89 to 30 ml/min/per 1.73m2) and 87 non-diabetic non-CKD subjects matched by age, gender, body mass index, and waist circumference. Skin autofluorescence (AF), a non-invasive assessment of AGEs, was measured. The presence of atheromatous disease in carotid and femoral arteries was evaluated using vascular ultrasound, and vascular age and SCORE risk were estimated. Patients with mild-to-moderate stages of CKD showed an increase in skin AF compared with control subjects (2.5±0.6 vs. 2.2±0.4 AU, p<0.001). A skin AF value >2.0 AU was accompanied by a 3-fold increased risk of detecting the presence of an atheromathous plaque (OR 3.0, 95% CI 1.4-6.5, p = 0.006). When vascular age was assessed through skin AF, subjects with CKD were almost 12 years older than control subjects (70.3±25.5 vs. 58.5±20.2 years, p = 0.001). Skin AF was negatively correlated with glomerular filtration rate (r = -0.354, p<0.001) and LDL-cholesterol (r = -0.269, p = 0.001), and positively correlated with age (r = 0.472, p<0.001), pulse pressure (r = 0.238, p = 0.002), and SCORE risk (r = 0.451, p<0.001). A stepwise multivariate regression analysis showed that age and glomerular filtration rate independently predicted skin AF (R2 = 0.289, p<0.001). Skin AF is elevated in patients with mild-to-moderate CKD compared with control subjects. This finding may be independently associated with the glomerular filtration rate and the presence of subclinical atheromatous disease. Therefore, the use of skin AF may help to accurately evaluate the real cardiovascular risk at the early stages of CKD.

Immunoadsorption in Anti-GBM Glomerulonephritis: Case Report in a Child and Literature Review.

PubMed

Dorval, Guillaume; Lion, Mathilde; Guérin, Sophie; Krid, Saoussen; Galmiche-Rolland, Louise; Salomon, Rémi; Boyer, Olivia

2017-11-01

Antiglomerular basement membrane glomerulonephritis (anti-GBM GN) is a rare autoimmune disease that is characterized by rapidly progressive glomerulonephritis that may be associated with pulmonary hemorrhage. Anti-GBM GN is caused by autoantibodies (classically type G immunoglobulin) directed against the α3 subunit of type IV collagen. Without any appropriate treatment, the disease is generally fulminant, and patient and kidney survival is poor. The current guidelines recommend the use of plasma exchanges and immunosuppressive drugs. Immunoadsorption (IA) can remove pathogenic IgGs from the circulation and do not require plasma infusions, contrary to plasma exchanges. IA has seldom been used in adult patients with good tolerance and efficiency. We report herein the first pediatric case successfully treated with IA combined with immunosuppressive drugs in a 7-year-old girl who presented acute kidney injury (estimated glomerular filtration rate 38 mL/minute/1.73 m 2 ). A kidney biopsy revealed numerous >80% glomerular crescents and linear IgG deposits along the glomerular basement membrane. Ten IA sessions led to rapid and sustained clearance of autoantibodies and improvement of kidney function until 21 months after onset (glomerular filtration rate 87 mL/minute/1.73 m 2 ). No adverse effect was noted. This report adds to the growing body of evidence suggesting IA as a therapeutic alternative to plasma exchanges in anti-GBM GN. The other 27 published pediatric cases of anti-GBM GN are reviewed. Copyright © 2017 by the American Academy of Pediatrics.

Protecting Podocytes: A Key Target for Therapy of Focal Segmental Glomerulosclerosis.

PubMed

Campbell, Kirk N; Tumlin, James A

2018-05-31

Focal segmental glomerulosclerosis (FSGS) is a histologic pattern of injury demonstrated by renal biopsy that can arise from a diverse range of causes and mechanisms. It has an estimated incidence of 7 per 1 million and is the most common primary glomerular disorder leading to end-stage renal disease in the United States. This review focuses on damage to the podocyte and the consequences of this injury in patients with FSGS, the genetics of FSGS, and approaches to treatment with a focus on the effects on podocytes. The podocyte is central to the glomerular filtration barrier and is particularly vulnerable because of its highly differentiated post-mitotic phenotype. The progressive structural changes involved in the pathology of FSGS include podocyte foot process effacement, death of podocytes and exposure of the glomerular basement membrane, filtration of nonspecific plasma proteins, expansion of capillaries, misdirected filtration at points of synechiae, and mesangial matrix proliferation. Although damage to and death of podocytes can result from single-gene disorders, evidence also suggests a role for soluble factors, such as soluble urokinase-type plasminogen activator receptor, cardiotrophin-like cytokine-1, and anti-CD40 antibodies, that promote FSGS recurrence post transplant. Several classes of medications, including corticosteroids, calcineurin inhibitors, endothelin receptor antagonists, adrenocorticotropic hormone, and rituximab, have been shown to be effective for the treatment of FSGS and have been demonstrated to have significant protective effects on podocytes. Key Messages: Greater understanding of podocyte biology is essential to the identification of new treatment targets and medications for the management of patients with FSGS. © 2018 S. Karger AG, Basel.

Aldosterone and glomerular filtration – observations in the general population

PubMed Central

2014-01-01

Background Increasing evidence suggests that aldosterone promotes renal damage. Since data on the association between aldosterone and renal function in the general population are sparse, we chose to address this issue. We investigated the associations between the plasma aldosterone concentration (PAC) or the aldosterone-to-renin ratio (ARR) and the estimated glomerular filtration rate (eGFR) in a sample of adult men and women from Northeast Germany. Methods A study population of 1921 adult men and women who participated in the first follow-up of the Study of Health in Pomerania was selected. None of the subjects used drugs that alter PAC or ARR. The eGFR was calculated according to the four-variable Modification of Diet in Renal Disease formula. Chronic kidney disease (CKD) was defined as an eGFR <60 ml/min/1.73 m2. Results Linear regression models, adjusted for sex, age, waist circumference, diabetes mellitus, smoking status, systolic and diastolic blood pressures, serum triglyceride concentrations and time of blood sampling revealed inverse associations of PAC or ARR with eGFR (ß-coefficient for log-transformed PAC −3.12, p < 0.001; ß-coefficient for log-transformed ARR −3.36, p < 0.001). Logistic regression models revealed increased odds for CKD with increasing PAC (odds ratio for a one standard deviation increase in PAC: 1.35, 95% confidence interval: 1.06-1.71). There was no statistically significant association between ARR and CKD. Conclusion Our study demonstrates that PAC and ARR are inversely associated with the glomerular filtration rate in the general population. PMID:24612948

Novel Filtration Markers for GFR Estimation

PubMed Central

Inker, Lesley A.; Coresh, Josef; Levey, Andrew S.; Eckfeldt, John H.

2017-01-01

Creatinine-based glomerular filtration rate estimation (eGFRcr) has been improved and refined since the 1970s through both the Modification of Diet in Renal Disease (MDRD) Study equation in 1999 and the CKD Epidemiology Collaboration (CKD-EPI) equation in 2009, with current clinical practice dependent primarily on eGFR for accurate assessment of GFR. However, researchers and clinicians have recognized limitations of relying on creatinine as the only filtration marker, which can lead to inaccurate GFR estimates in certain populations due to the influence of non-GFR determinants of serum or plasma creatinine. Therefore, recent literature has proposed incorporation of multiple serum or plasma filtration markers into GFR estimation to improve precision and accuracy and decrease the impact of non-GFR determinants for any individual biomarker. To this end, the CKD-EPI combined creatinine-cystatin C equation (eGFRcr-cys) was developed in 2012 and demonstrated superior accuracy to equations relying on creatinine or cystatin C alone (eGFRcr or eGFRcys). Now, the focus has broadened to include additional novel filtration markers to further refine and improve GFR estimation. Beta-2-microglobulin (B2M) and beta-trace-protein (BTP) are two filtration markers with established assays that have been proposed as candidates for improving both GFR estimation and risk prediction. GFR estimating equations based on B2M and BTP have been developed and validated, with the CKD-EPI combined BTP-B2M equation (eGFRBTP-B2M) demonstrating similar performance to eGFR and eGFR. Additionally, several studies have demonstrated that both B2M and BTP are associated with outcomes in CKD patients, including cardiovascular events, ESRD and mortality. This review will primarily focus on these two biomarkers, and will highlight efforts to identify additional candidate biomarkers through metabolomics-based approaches. PMID:29333147

Generation of a new cystatin C-based estimating equation for glomerular filtration rate by use of 7 assays standardized to the international calibrator.

PubMed

Grubb, Anders; Horio, Masaru; Hansson, Lars-Olof; Björk, Jonas; Nyman, Ulf; Flodin, Mats; Larsson, Anders; Bökenkamp, Arend; Yasuda, Yoshinari; Blufpand, Hester; Lindström, Veronica; Zegers, Ingrid; Althaus, Harald; Blirup-Jensen, Søren; Itoh, Yoshi; Sjöström, Per; Nordin, Gunnar; Christensson, Anders; Klima, Horst; Sunde, Kathrin; Hjort-Christensen, Per; Armbruster, David; Ferrero, Carlo

2014-07-01

Many different cystatin C-based equations exist for estimating glomerular filtration rate. Major reasons for this are the previous lack of an international cystatin C calibrator and the nonequivalence of results from different cystatin C assays. Use of the recently introduced certified reference material, ERM-DA471/IFCC, and further work to achieve high agreement and equivalence of 7 commercially available cystatin C assays allowed a substantial decrease of the CV of the assays, as defined by their performance in an external quality assessment for clinical laboratory investigations. By use of 2 of these assays and a population of 4690 subjects, with large subpopulations of children and Asian and Caucasian adults, with their GFR determined by either renal or plasma inulin clearance or plasma iohexol clearance, we attempted to produce a virtually assay-independent simple cystatin C-based equation for estimation of GFR. We developed a simple cystatin C-based equation for estimation of GFR comprising only 2 variables, cystatin C concentration and age. No terms for race and sex are required for optimal diagnostic performance. The equation, [Formula: see text] is also biologically oriented, with 1 term for the theoretical renal clearance of small molecules and 1 constant for extrarenal clearance of cystatin C. A virtually assay-independent simple cystatin C-based and biologically oriented equation for estimation of GFR, without terms for sex and race, was produced. © 2014 The American Association for Clinical Chemistry.

[Consensus document: recommendations for the use of equations to estimate glomerular filtration rate in children].

PubMed

Montañés Bermúdez, R; Gràcia Garcia, S; Fraga Rodríguez, G M; Escribano Subias, J; Diez de Los Ríos Carrasco, M J; Alonso Melgar, A; García Nieto, V

2014-05-01

The appearance of the K/DOQI guidelines in 2002 on the definition, evaluation and staging of chronic kidney disease (CKD) have led to a major change in how to assess renal function in adults and children. These guidelines, recently updated, recommended that the study of renal function is based, not only on measuring the serum creatinine concentration, but this must be accompanied by the estimation of glomerular filtration rate (GFR) obtained by an equation. However, the implementation of this recommendation in the clinical laboratory reports in the paediatric population has been negligible. Numerous studies have appeared in recent years on the importance of screening and monitoring of patients with CKD, the emergence of new equations for estimating GFR, and advances in clinical laboratories regarding the methods for measuring plasma creatinine and cystatin C, determined by the collaboration between the departments of paediatrics and clinical laboratories to establish recommendations based on the best scientific evidence on the use of equations to estimate GFR in this population. The purpose of this document is to provide recommendations on the evaluation of renal function and the use of equations to estimate GFR in children from birth to 18 years of age. The recipients of these recommendations are paediatricians, nephrologists, clinical biochemistry, clinical analysts, and all health professionals involved in the study and evaluation of renal function in this group of patients. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Evaluation of equations that estimate glomerular filtration rate in renal transplant recipients.

PubMed

De Alencastro, M G; Veronese, F V; Vicari, A R; Gonçalves, L F; Manfro, R C

2014-03-01

The accuracy of equations that estimate the glomerular filtration rate (GFR) in renal transplant patients has not been established; thus their performance was assessed in stable renal transplant patients. Renal transplant patients (N.=213) with stable graft function were enrolled. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used as the reference method and compared with the Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), Mayo Clinic (MC) and Nankivell equations. Bias, accuracy and concordance rates were determined for all equation relative to CKD-EPI. Mean estimated GFR values of the equations differed significantly from the CKD-EPI values, though the correlations with the reference method were significant. Values of MDRD differed from the CG, MC and Nankivell estimations. The best agreement to classify the chronic kidney disease (CKD) stages was for the MDRD (Kappa=0.649, P<0.001), and for the other equations the agreement was moderate. The MDRD had less bias and narrower agreement limits but underestimated the GFR at levels above 60 mL/min/1.73 m2. Conversely, the CG, MC and Nankivell equations overestimated the GFR, and the Nankivell equation had the worst performance. The MDRD equation P15 and P30 values were higher than those of the other equations (P<0.001). Despite their correlations, equations estimated the GFR and CKD stage differently. The MDRD equation was the most accurate, but the sub-optimal performance of all the equations precludes their accurate use in clinical practice.

Technical note: Use of a simplified equation for estimating glomerular filtration rate in beef cattle.

PubMed

Murayama, I; Miyano, A; Sasaki, Y; Hirata, T; Ichijo, T; Satoh, H; Sato, S; Furuhama, K

2013-11-01

This study was performed to clarify whether a formula (Holstein equation) based on a single blood sample and the isotonic, nonionic, iodine contrast medium iodixanol in Holstein dairy cows can apply to the estimation of glomerular filtration rate (GFR) for beef cattle. To verify the application of iodixanol in beef cattle, instead of the standard tracer inulin, both agents were coadministered as a bolus intravenous injection to identical animals at doses of 10 mg of I/kg of BW and 30 mg/kg. Blood was collected 30, 60, 90, and 120 min after the injection, and the GFR was determined by the conventional multisample strategies. The GFR values from iodixanol were well consistent with those from inulin, and no effects of BW, age, or parity on GFR estimates were noted. However, the GFR in cattle weighing less than 300 kg, aged<1 yr old, largely fluctuated, presumably due to the rapid ruminal growth and dynamic changes in renal function at young adult ages. Using clinically healthy cattle and those with renal failure, the GFR values estimated from the Holstein equation were in good agreement with those by the multisample method using iodixanol (r=0.89, P=0.01). The results indicate that the simplified Holstein equation using iodixanol can be used for estimating the GFR of beef cattle in the same dose regimen as Holstein dairy cows, and provides a practical and ethical alternative.

Cystatin C-based glomerular filtration rate associates more closely with mortality than creatinine-based or combined glomerular filtration rate equations in unselected patients.

PubMed

Helmersson-Karlqvist, Johanna; Ärnlöv, Johan; Larsson, Anders

2016-10-01

Decreased glomerular filtration rate (GFR) is an important cardiovascular risk factor, but estimated GFR (eGFR) may differ depending on whether it is based on creatinine or cystatin C. A combined creatinine/cystatin C equation has recently been shown to best estimate GFR; however, the benefits of using the combined equation for risk prediction in routine clinical care have been less studied. This study compares mortality risk prediction by eGFR using the combined creatinine/cystatin C equation (CKD-EPI), a sole creatinine equation (CKD-EPI) and a sole cystatin C equation (CAPA), respectively, using assays that are traceable to international calibrators. All patients analysed for both creatinine and cystatin C from the same blood sample tube (n = 13,054) during 2005-2007 in Uppsala University Hospital Laboratory were divided into eGFR risk categories>60, 30-60 and <30 mL/min/1.73 m(2) by each eGFR equation. During follow-up (median 4.6 years), 4398 participants died, of which 1396 deaths were due to cardiovascular causes. Reduced eGFR was significantly associated with death as assessed by all eGFR equations. The net reclassification improvement (NRI) for the combination equation compared with the sole creatinine equation was 0.10 (p < 0.001) for all-cause mortality and 0.08 (p < 0.001) for cardiovascular mortality, indicating improved reclassification. In contrast, NRI for the combination equation, compared with the sole cystatin C equation, was -0.06 (p < 0.001) for all-cause mortality and -0.02 (p = 0.032) for cardiovascular mortality, indicating a worsened reclassification. In routine clinical care, cystatin C-based eGFR was more closely associated with mortality compared with both creatinine-based eGFR and creatinine/cystatin C-based eGFR. © The European Society of Cardiology 2016.

Urine neutrophil gelatinase-associated lipocalin and risk of cardiovascular disease and death in CKD: results from the Chronic Renal Insufficiency Cohort (CRIC) Study.

PubMed

Liu, Kathleen D; Yang, Wei; Go, Alan S; Anderson, Amanda H; Feldman, Harold I; Fischer, Michael J; He, Jiang; Kallem, Radhakrishna R; Kusek, John W; Master, Stephen R; Miller, Edgar R; Rosas, Sylvia E; Steigerwalt, Susan; Tao, Kaixiang; Weir, Matthew R; Hsu, Chi-Yuan

2015-02-01

Chronic kidney disease is common and is associated with increased cardiovascular disease risk. Currently, markers of renal tubular injury are not used routinely to describe kidney health and little is known about the risk of cardiovascular events and death associated with these biomarkers independent of glomerular filtration-based markers (such as serum creatinine or albuminuria). Cohort study, CRIC (Chronic Renal Insufficiency Cohort) Study. 3,386 participants with estimated glomerular filtration rate of 20 to 70mL/min/1.73m(2) enrolled from June 2003 through August 2008. Urine neutrophil gelatinase-associated lipocalin (NGAL) concentration. Adjudicated heart failure event, ischemic atherosclerotic event (myocardial infarction, ischemic stroke, or peripheral artery disease), and death through March 2011. Urine NGAL measured at baseline with a 2-step assay using chemiluminescent microparticle immunoassay technology on an ARCHITECT i2000SR (Abbott Laboratories). There were 428 heart failure events (during 16,383 person-years of follow-up), 361 ischemic atherosclerotic events (during 16,584 person-years of follow-up), and 522 deaths (during 18,214 person-years of follow-up). In Cox regression models adjusted for estimated glomerular filtration rate, albuminuria, demographics, traditional cardiovascular disease risk factors, and cardiac medications, higher urine NGAL levels remained associated independently with ischemic atherosclerotic events (adjusted HR for the highest [>49.5ng/mL] vs lowest [≤6.9ng/mL] quintile, 1.83 [95% CI, 1.20-2.81]; HR per 0.1-unit increase in log urine NGAL, 1.012 [95% CI, 1.001-1.023]), but not heart failure events or deaths. Urine NGAL was measured only once. Among patients with chronic kidney disease, urine levels of NGAL, a marker of renal tubular injury, were associated independently with future ischemic atherosclerotic events, but not with heart failure events or deaths. Copyright © 2015 National Kidney Foundation, Inc. All rights reserved.

Chronic Kidney Disease Screening Methods and Its Implication for Malaysia: An in Depth Review

PubMed Central

Almualm, Yasmin; Huri, Hasniza Zaman

2015-01-01

Chronic Kidney Disease has become a public health problem, imposing heath, social and human cost on societies worldwide. Chronic Kidney Disease remains asymptomatic till late stage when intervention cannot stop the progression of the disease. Therefore, there is an urgent need to detect the disease early. Despite the high prevalence of Chronic Kidney Disease in Malaysia, screening is still lacking behind. This review discusses the strengths and limitations of current screening methods for Chronic Kidney Disease from a Malaysian point of view. Diabetic Kidney Disease was chosen as focal point as Diabetes is the leading cause of Chronic Kidney Disease in Malaysia. Screening for Chronic Kidney Disease in Malaysia includes a urine test for albuminuria and a blood test for serum creatinine. Recent literature indicates that albuminuria is not always present in Diabetic Kidney Disease patients and serum creatinine is only raised after substantial kidney damage has occurred. Recently, cystatin C was proposed as a potential marker for kidney disease but this has not been studied thoroughly in Malaysia. Glomerular Filtration Rate is the best method for measuring kidney function and is widely estimated using the Modification of Diet for Renal Disease equation. Another equation, the Chronic Kidney Disease Epidemiology Collaboration Creatinine equation was introduced in 2009. The new equation retained the precision and accuracy of the Modification of Diet for Renal Disease equation at GFR < 60ml/min/1.73m2, showed less bias and improved precision at GFR>60ml/min/1.73m2. In Asian countries, adding an ethnic coefficient to the equation enhanced its performance. In Malaysia, a multi-ethnic Asian population, the Chronic Kidney Disease Epidemiology Collaboration equation should be validated and the Glomerular Filtration Rate should be reported whenever serum creatinine is ordered. Reporting estimated Glomerular Filtration Rate will help diagnose patients who would have been otherwise missed if only albuminuria and serum creatinine are measured. PMID:25946939

Chronic kidney disease screening methods and its implication for Malaysia: an in depth review.

PubMed

Almualm, Yasmin; Zaman Huri, Hasniza

2015-01-01

Chronic Kidney Disease has become a public health problem, imposing heath, social and human cost on societies worldwide. Chronic Kidney Disease remains asymptomatic till late stage when intervention cannot stop the progression of the disease. Therefore, there is an urgent need to detect the disease early. Despite the high prevalence of Chronic Kidney Disease in Malaysia, screening is still lacking behind. This review discusses the strengths and limitations of current screening methods for Chronic Kidney Disease from a Malaysian point of view. Diabetic Kidney Disease was chosen as focal point as Diabetes is the leading cause of Chronic Kidney Disease in Malaysia. Screening for Chronic Kidney Disease in Malaysia includes a urine test for albuminuria and a blood test for serum creatinine. Recent literature indicates that albuminuria is not always present in Diabetic Kidney Disease patients and serum creatinine is only raised after substantial kidney damage has occurred.  Recently, cystatin C was proposed as a potential marker for kidney disease but this has not been studied thoroughly in Malaysia.  Glomerular Filtration Rate is the best method for measuring kidney function and is widely estimated using the Modification of Diet for Renal Disease equation. Another equation, the Chronic Kidney Disease Epidemiology Collaboration Creatinine equation was introduced in 2009. The new equation retained the precision and accuracy of the Modification of Diet for Renal Disease equation at GFR < 60ml/min/1.73m2, showed less bias and improved precision at GFR>60ml/min/1.73m2. In Asian countries, adding an ethnic coefficient to the equation enhanced its performance. In Malaysia, a multi-ethnic Asian population, the Chronic Kidney Disease Epidemiology Collaboration equation should be validated and the Glomerular Filtration Rate should be reported whenever serum creatinine is ordered. Reporting estimated Glomerular Filtration Rate will help diagnose patients who would have been otherwise missed if only albuminuria and serum creatinine are measured.

Microalbuminuria and plasma aldosterone levels in nondiabetic treatment-naïve patients with hypertension.

PubMed

Catena, Cristiana; Colussi, GianLuca; Martinis, Flavia; Novello, Marileda; Sechi, Leonardo A

2017-12-01

Identification of factors that contribute to urinary albumin losses in hypertensive nephropathy is crucial for prevention of renal deterioration. The aim of this study was to investigate the relationship of low-grade albuminuria with plasma aldosterone levels in treatment-naïve hypertensive patients free of additional comorbidities that might affect renal function. In 242 newly diagnosed patients with uncomplicated primary hypertension, we obtained duplicate 24-h urine collections for measurement of urinary albumin/creatinine ratio (UACR) and measured plasma aldosterone levels. Patients with diabetes, overt proteinuria (>300 mg/day), glomerular filtration rate less than 30 ml/min per 1.73 m, and previous renal diseases were excluded. Increasing UACR was associated with significantly and progressively higher blood pressure (BP), HDL-cholesterol, and plasma aldosterone levels, and with lower glomerular filtration. Microalbuminuria (30-300 mg/day) was detected in 41 (17%) of 242 hypertensive patients, and these patients had significantly higher BP and plasma aldosterone levels (178 ± 113 vs. 128 ± 84 pg/ml; P = 0.001), and lower glomerular filtration than patients without microalbuminuria. UACR was directly and independently correlated with BP and plasma aldosterone levels. In a logistic regression model, presence of microalbuminuria was associated with plasma aldosterone levels independently of glomerular filtration and demographic, anthropometric, and metabolic variables. In nondiabetic, treatment-naïve patients with hypertension, low-grade albuminuria is independently associated with elevated plasma aldosterone. These findings suggest a contribution of aldosterone to the early glomerular changes occurring in hypertensive nephropathy.

Abdominal Aortic Calcifications Influences the Systemic and Renal Hemodynamic Response to Renal Denervation in the DENERHTN (Renal Denervation for Hypertension) Trial.

PubMed

Courand, Pierre-Yves; Pereira, Helena; Del Giudice, Costantino; Gosse, Philippe; Monge, Matthieu; Bobrie, Guillaume; Delsart, Pascal; Mounier-Vehier, Claire; Lantelme, Pierre; Denolle, Thierry; Dourmap, Caroline; Halimi, Jean Michel; Girerd, Xavier; Rossignol, Patrick; Zannad, Faiez; Ormezzano, Olivier; Vaisse, Bernard; Herpin, Daniel; Ribstein, Jean; Bouhanick, Beatrice; Mourad, Jean-Jacques; Ferrari, Emile; Chatellier, Gilles; Sapoval, Marc; Azarine, Arshid; Azizi, Michel

2017-10-10

The DENERHTN (Renal Denervation for Hypertension) trial confirmed the efficacy of renal denervation (RDN) in lowering daytime ambulatory systolic blood pressure when added to standardized stepped-care antihypertensive treatment (SSAHT) for resistant hypertension at 6 months. This post hoc exploratory analysis assessed the impact of abdominal aortic calcifications (AAC) on the hemodynamic and renal response to RDN at 6 months. In total, 106 patients with resistant hypertension were randomly assigned to RDN plus SSAHT or to the same SSAHT alone (control group). Total AAC volume was measured, with semiautomatic software and blind to randomization, from the aortic hiatus to the iliac bifurcation using the prerandomization noncontrast abdominal computed tomography scans of 90 patients. Measurements were expressed as tertiles. The baseline-adjusted difference in the change in daytime ambulatory systolic blood pressure from baseline to 6 months between the RDN and control groups was -10.1 mm Hg ( P =0.0462) in the lowest tertile and -2.5 mm Hg ( P =0.4987) in the 2 highest tertiles of AAC volume. Estimated glomerular filtration rate remained stable at 6 months for the patients in the lowest tertile of AAC volume who underwent RDN (+2.5 mL/min per 1.73 m 2 ) but decreased in the control group (-8.0 mL/min per 1.73 m 2 , P =0.0148). In the 2 highest tertiles of AAC volume, estimated glomerular filtration rate decreased similarly in the RDN and control groups ( P =0.2640). RDN plus SSAHT resulted in a larger decrease in daytime ambulatory systolic blood pressure than SSAHT alone in patients with a lower AAC burden than in those with a higher AAC burden. This larger decrease in daytime ambulatory systolic blood pressure was not associated with a decrease in estimated glomerular filtration rate. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01570777. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Comparing Zero Ischemia Laparoscopic Radio Frequency Ablation Assisted Tumor Enucleation and Laparoscopic Partial Nephrectomy for Clinical T1a Renal Tumor: A Randomized Clinical Trial.

PubMed

Huang, Jiwei; Zhang, Jin; Wang, Yanqing; Kong, Wen; Xue, Wei; Liu, Dongming; Chen, YongHui; Huang, Yiran

2016-06-01

We evaluated the functional outcome, safety and efficacy of zero ischemia laparoscopic radio frequency ablation assisted tumor enucleation compared with conventional laparoscopic partial nephrectomy. A prospective randomized controlled trial was conducted from April 2013 to March 2015 in patients with cT1a renal tumor scheduled for laparoscopic nephron sparing surgery. All patients were followed for at least 12 months. Patients in the laparoscopic radio frequency ablation assisted tumor enucleation group underwent tumor enucleation after radio frequency ablation without hilar clamping. The primary outcome was the change in glomerular filtration rate of the affected kidney by renal scintigraphy at 12 months. Secondary outcomes included changes in estimated glomerular filtration rate, estimated blood loss, operative time, hospital stay, postoperative complications and oncologic outcomes. The Pearson chi-square or Fisher exact, Student t-test and Wilcoxon rank sum tests were used. The trial ultimately enrolled 89 patients, of whom 44 were randomized to the laparoscopic radio frequency ablation assisted tumor enucleation group and 45 to the laparoscopic partial nephrectomy group. In the laparoscopic partial nephrectomy group 1 case was converted to radical nephrectomy. Compared with the laparoscopic partial nephrectomy group, patients in the laparoscopic radio frequency ablation assisted tumor enucleation group had a smaller decrease in glomerular filtration rate of the affected kidney at 3 months (10.2% vs 20.5%, p=0.001) and 12 months (7.6% vs 16.2%, p=0.002). Patients in the laparoscopic radio frequency ablation assisted tumor enucleation group had a shorter operative time (p=0.002), lower estimated blood loss (p <0.001) and a shorter hospital stay (p=0.029) but similar postoperative complications (p=1.000). There were no positive margins or local recurrence in this study. Zero ischemia laparoscopic radio frequency ablation assisted tumor enucleation enables tumor excision with better renal function preservation compared to conventional laparoscopic partial nephrectomy. Less blood loss and a shorter operative time were achieved with similar postoperative complication rates. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Body Mass Index Is Associated with Increased Creatinine Clearance by a Mechanism Independent of Body Fat Distribution

PubMed Central

Gerchman, Fernando; Tong, Jenny; Utzschneider, Kristina M.; Zraika, Sakeneh; Udayasankar, Jayalakshmi; McNeely, Marguerite J.; Carr, Darcy B.; Leonetti, Donna L.; Young, Bessie A.; de Boer, Ian H.; Boyko, Edward J.; Fujimoto, Wilfred Y.; Kahn, Steven E.

2009-01-01

Context: Although obesity has been, in general, associated with glomerular hyperfiltration, visceral adiposity has been suggested to be associated with reduced glomerular filtration. Objective: The aim of the study was to evaluate the differential effects of obesity and body fat distribution on glomerular filtration. Design and Setting: We conducted a cross-sectional study of the Japanese-American community in Seattle, Washington. Participants: We studied a representative sample of second-generation Japanese-American men and women with normal glucose tolerance (n = 124) and impaired glucose metabolism (impaired fasting glucose and/or impaired glucose tolerance) (n = 144) residing in King County, Washington. Main Outcome Measures: Glomerular filtration rate was estimated by 24-h urinary creatinine clearance, body size by body mass index (BMI), and intra-abdominal fat (IAF), sc fat (SCF), and lean thigh areas by CT scan. Results: Creatinine clearance was positively correlated with BMI (r = 0.429; P < 0.001), fasting glucose (r = 0.198; P = 0.001), and insulin levels (r = 0.125; P = 0.042), as well as IAF (r = 0.239; P < 0.001), SCF (r = 0.281; P < 0.001), and lean thigh (r = 0.353; P < 0.001) areas. The association between creatinine clearance and BMI remained significant after adjustments for IAF, SCF areas, and fasting insulin levels (r = 0.337; P < 0.001); whereas IAF and SCF areas were not independently associated with creatinine clearance after adjusting for BMI. Creatinine clearance increased with increasing BMI after adjusting for fasting insulin, fasting glucose, IAF and SCF areas in subjects with normal glucose tolerance (r = 0.432; P < 0.001) and impaired glucose metabolism (r = 0.471; P < 0.001). Conclusions: BMI rather than body fat distribution is an independent determinant of creatinine clearance in nondiabetic subjects. Lean body mass, rather than adiposity, may explain this association. PMID:19584179

The effects of weight change on glomerular filtration rate.

PubMed

Chang, Alex; Greene, Tom H; Wang, Xuelei; Kendrick, Cynthia; Kramer, Holly; Wright, Jackson; Astor, Brad; Shafi, Tariq; Toto, Robert; Lewis, Julia; Appel, Lawrence J; Grams, Morgan

2015-11-01

Little is known about the effect of weight loss/gain on kidney function. Analyses are complicated by uncertainty about optimal body surface indexing strategies for measured glomerular filtration rate (mGFR). Using data from the African-American Study of Kidney Disease and Hypertension (AASK), we determined the association of change in weight with three different estimates of change in kidney function: (i) unindexed mGFR estimated by renal clearance of iodine-125-iothalamate, (ii) mGFR indexed to concurrently measured BSA and (iii) GFR estimated from serum creatinine (eGFR). All models were adjusted for baseline weight, time, randomization group and time-varying diuretic use. We also examined whether these relationships were consistent across a number of subgroups, including tertiles of baseline 24-h urine sodium excretion. In 1094 participants followed over an average of 3.6 years, a 5-kg weight gain was associated with a 1.10 mL/min/1.73 m(2) (95% CI: 0.87 to 1.33; P < 0.001) increase in unindexed mGFR. There was no association between weight change and mGFR indexed for concurrent BSA (per 5 kg weight gain, 0.21; 95% CI: -0.02 to 0.44; P = 0.1) or between weight change and eGFR (-0.09; 95% CI: -0.32 to 0.14; P = 0.4). The effect of weight change on unindexed mGFR was less pronounced in individuals with higher baseline sodium excretion (P = 0.08 for interaction). The association between weight change and kidney function varies depending on the method of assessment. Future clinical trials should examine the effect of intentional weight change on measured GFR or filtration markers robust to changes in muscle mass. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

The effects of weight change on glomerular filtration rate

PubMed Central

Chang, Alex; Greene, Tom H.; Wang, Xuelei; Kendrick, Cynthia; Kramer, Holly; Wright, Jackson; Astor, Brad; Shafi, Tariq; Toto, Robert; Lewis, Julia; Appel, Lawrence J.; Grams, Morgan

2015-01-01

Background Little is known about the effect of weight loss/gain on kidney function. Analyses are complicated by uncertainty about optimal body surface indexing strategies for measured glomerular filtration rate (mGFR). Methods Using data from the African-American Study of Kidney Disease and Hypertension (AASK), we determined the association of change in weight with three different estimates of change in kidney function: (i) unindexed mGFR estimated by renal clearance of iodine-125-iothalamate, (ii) mGFR indexed to concurrently measured BSA and (iii) GFR estimated from serum creatinine (eGFR). All models were adjusted for baseline weight, time, randomization group and time-varying diuretic use. We also examined whether these relationships were consistent across a number of subgroups, including tertiles of baseline 24-h urine sodium excretion. Results In 1094 participants followed over an average of 3.6 years, a 5-kg weight gain was associated with a 1.10 mL/min/1.73 m2 (95% CI: 0.87 to 1.33; P < 0.001) increase in unindexed mGFR. There was no association between weight change and mGFR indexed for concurrent BSA (per 5 kg weight gain, 0.21; 95% CI: −0.02 to 0.44; P = 0.1) or between weight change and eGFR (−0.09; 95% CI: −0.32 to 0.14; P = 0.4). The effect of weight change on unindexed mGFR was less pronounced in individuals with higher baseline sodium excretion (P = 0.08 for interaction). Conclusion The association between weight change and kidney function varies depending on the method of assessment. Future clinical trials should examine the effect of intentional weight change on measured GFR or filtration markers robust to changes in muscle mass. PMID:26085555

Determination of the glomerular filtration rate (GFR): methodological problems, age-dependence, consequences of various surgical interventions, and the influence of different drugs and toxic substances.

PubMed

Fleck, C

1999-01-01

Determinations of renal clearance of fluorescein isothiocyanate (FITC)-inulin were used for assessing the glomerular filtration rate (GFR) in rats and to characterize factors influencing the glomerular filtration capacity. In anesthetized rats, GFR develops after birth up to day 30. Thereafter, GFR remains relatively constant for up to 3 months of age and drops continuously until the 8th month. GFR can be determined in utero, already one day before birth, however, only at a very low level. It increases significantly on the first day of life. Even at this time the effect of furosemide on GFR can be proven. After reduction of renal mass, GFR is decreased in dependence on the extent of kidney tissue removal. However, within 2 days after unilateral nephrectomy (NX) or one week after 5/6 NX, GFR reaches values about 3/4 of the controls with two intact kidneys. Furthermore, the compensation of GFR after renal ischemia reaches 80% of baseline values after one week. On the other hand, GFR is enhanced after bile duct ligation as a model of hepato-renal failure. It has been shown in previous experiments that pretreatment with hormones can stimulate renal tubular transport processes. Pretreatment with dexamethasone or triiodothyronine after 5/6 NX improves glomerular filtration capacity whereas in animals with ligated bile ducts dexamethasone seems to prevent the increase in GFR. After subchronic treatment with epidermal growth factor (EGF) GFR is significantly reduced. A continuous infusion of amino acids does not change GFR in the controls but enhances the filtration capacity in EGF-treated rats. But immediately after bolus injection of amino acids GFR also increases significantly in the controls. Diuretics such as furosemide, most nephrotoxic agents (cyclosporine A [CsA], heavy metals) and imidazole reduce the GFR significantly. Diltiazem reported to act nephroprotectively in CsA nephrotoxicity in human beings was without beneficial effect in rats. This could be due to species differences in GFR because the rat is one of the species with the highest glomerular filtration capacity.

A study of the role of renal nerves in the renal responses to 60° head-up tilt in the anaesthetized dog

PubMed Central

DiBona, G. F.; Johns, E. J.

1980-01-01

1. Renal responses to 10 min of 60° head-up tilt were measured in anaesthetized dogs in which renal perfusion pressure was maintained at a relatively constant value. 2. Tilting was associated with a fall in systemic blood pressure and an increase in heart rate. Renal blood flow and glomerular filtration rate remained constant while there was a significant decrease in both absolute and fractional excretion of sodium. 3. Animals which had undergone acute renal denervation were tilted. The cardiovascular responses were similar to intact animals. A fall in renal blood flow was observed but the glomerular filtration rate was maintained at a steady value during tilting. The decreased renal tubular excretion of sodium measured in intact animals was abolished. 4. Alpha-adrenergic blockade of the kidney was achieved by infusion of phentolamine into the renal artery. Tilting of these animals caused cardiovascular changes similar to those observed in control animals but renal blood flow, glomerular filtration rate and sodium handling remained unchanged. 5. Animals in which both carotid sinuses had been acutely denervated were tilted. Systemic blood pressure fell as in intact animals, but the rise in heart rate was significantly less. Renal blood flow, glomerular filtration rate and the rate of sodium excretion were unchanged. 6. A 10 min period of 60° head-up tilt in anaesthetized dogs resulted in an unchanged renal blood flow and glomerular filtration rate which was associated with a decrease in both fractional excretion of sodium and sodium excretion. The renal sympathetic nerves were shown to be responsible for these changes in tubular sodium handling which appeared to exert their action via renal tubular α-adrenergic receptors. This activation of the renal nerves appeared to be mediated by the carotid sinus baroreceptor reflex. PMID:7381761

Relationship between estimated glomerular filtration rate, albuminuria, and oxidant status in the Japanese population

PubMed Central

2013-01-01

Background In the general population, reported levels of oxidative stress and antioxidant potential seem to vary. The aim of this study was to investigate the levels of oxidant status markers in relation to estimated glomerular filtration rate (eGFR) and albuminuria in Japanese population. Methods Data were analyzed from 8335 individuals who underwent a general health screening test. For the estimation of albuminuria, urinary albumin-to-creatinine ratio (UAER) was calculated. Oxidant status was determined by assessing derivatives of reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP). Results After adjusting for age, high blood pressure, depressor agent use, CRP, smoking status, multivariate logistic regression analysis showed that the lowest eGFR quartile was associated negatively with the top d-ROM quartile in men (odds ratio 0.78 [95% CI 0.62-0.98, P = 0.034]) and the highest UAER was associated with the top d-ROM in men (odds ratio 1.68) [95% CI 1.35-2.10, P < 0.001]. In addition, both the first eGFR quartile and the fourth UAER quartile showed significant positive association with low BAP levels in men, but not in women. Conclusions Among men who underwent general health screening, lower eGFR and increased albuminuria was negatively and positively, respectively, associated with higher oxidative stress levels, whereas both conditions were positively associated with lower antioxidant potential levels. PMID:24016221

Childhood Estimates of Glomerular Filtration Rate Based on Creatinine and Cystatin C: Importance of Body Composition.

PubMed

Miliku, Kozeta; Bakker, Hanneke; Dorresteijn, Eiske M; Cransberg, Karlien; Franco, Oscar H; Felix, Janine F; Jaddoe, Vincent W V

2017-01-01

Creatinine and cystatin C concentrations are commonly used to estimate glomerular filtration rate (eGFR) in clinical practice and epidemiological studies. To estimate the influence of different body composition measures on eGFR from creatinine and cystatin C blood concentrations, we compared the associations of different anthropometric and body composition measures with eGFR derived from creatinine (eGFRcreat) and cystatin C (eGFRcystC) blood concentrations. In a population-based cohort study among 4,305 children aged 6.0 years (95% range 5.7-8.0), we measured weight and height and calculated body mass index (BMI) and body surface area (BSA), and lean and fat mass using dual-energy X-ray absorptiometry. At the same age, we measured creatinine and cystatin C blood concentrations and estimated the GFR. Correlation between eGFR based on creatinine and cystatin C concentrations was r = 0.40 (p value <0.01). Higher BMI was associated with lower eGFRcystC but not with eGFRcreat. Higher BSA was associated with higher eGFRcreat and lower eGFRcystC (p value <0.05). Lean and fat mass percentages were associated with eGFRcreat but not with eGFRcystC. Our findings suggest that both eGFRcreat and eGFRcystC are influenced by BMI and BSA. eGFRcreat is more strongly influenced by body composition than eGFRcystC. © 2017 S. Karger AG, Basel.

Insulin induces the correlation between renal blood flow and glomerular filtration rate in diabetes: implications for mechanisms causing hyperfiltration.

PubMed

Pihl, Liselotte; Persson, Patrik; Fasching, Angelica; Hansell, Peter; DiBona, Gerald F; Palm, Fredrik

2012-07-01

Glomerular filtration rate (GFR) and renal blood flow (RBF) are normally kept constant via renal autoregulation. However, early diabetes results in increased GFR and the potential mechanisms are debated. Tubuloglomerular feedback (TGF) inactivation, with concomitantly increased RBF, is proposed but challenged by the finding of glomerular hyperfiltration in diabetic adenosine A(1) receptor-deficient mice, which lack TGF. Furthermore, we consistently find elevated GFR in diabetes with only minor changes in RBF. This may relate to the use of a lower streptozotocin dose, which produces a degree of hyperglycemia, which is manageable without supplemental suboptimal insulin administration, as has been used by other investigators. Therefore, we examined the relationship between RBF and GFR in diabetic rats with (diabetes + insulin) and without suboptimal insulin administration (untreated diabetes). As insulin can affect nitric oxide (NO) release, the role of NO was also investigated. GFR, RBF, and glomerular filtration pressures were measured. Dynamic RBF autoregulation was examined by transfer function analysis between arterial pressure and RBF. Both diabetic groups had increased GFR (+60-67%) and RBF (+20-23%) compared with controls. However, only the diabetes + insulin group displayed a correlation between GFR and RBF (R(2) = 0.81, P < 0.0001). Net filtration pressure was increased in untreated diabetes compared with both other groups. The difference between untreated and insulin-treated diabetic rats disappeared after administering N(ω)-nitro-l-arginine methyl ester to inhibit NO synthase and subsequent NO release. In conclusion, mechanisms causing diabetes-induced glomerular hyperfiltration are animal model-dependent. Supplemental insulin administration results in a RBF-dependent mechanism, whereas elevated GFR in untreated diabetes is mediated primarily by a tubular event. Insulin-induced NO release partially contributes to these differences.

Differential diagnosis of Bartter syndrome, Gitelman syndrome, and pseudo-Bartter/Gitelman syndrome based on clinical characteristics.

PubMed

Matsunoshita, Natsuki; Nozu, Kandai; Shono, Akemi; Nozu, Yoshimi; Fu, Xue Jun; Morisada, Naoya; Kamiyoshi, Naohiro; Ohtsubo, Hiromi; Ninchoji, Takeshi; Minamikawa, Shogo; Yamamura, Tomohiko; Nakanishi, Koichi; Yoshikawa, Norishige; Shima, Yuko; Kaito, Hiroshi; Iijima, Kazumoto

2016-02-01

Phenotypic overlap exists among type III Bartter syndrome (BS), Gitelman syndrome (GS), and pseudo-BS/GS (p-BS/GS), which are clinically difficult to distinguish. We aimed to clarify the differences between these diseases, allowing accurate diagnosis based on their clinical features. A total of 163 patients with genetically defined type III BS (n = 30), GS (n = 90), and p-BS/GS (n = 43) were included. Age at diagnosis, sex, body mass index, estimated glomerular filtration rate, and serum and urine electrolyte concentrations were determined. Patients with p-BS/GS were significantly older at diagnosis than those with type III BS and GS. Patients with p-BS/GS included a significantly higher percentage of women and had a lower body mass index and estimated glomerular filtration rate than did patients with GS. Although hypomagnesemia and hypocalciuria were predominant biochemical findings in patients with GS, 17 and 23% of patients with type III BS and p-BS/GS, respectively, also showed these abnormalities. Of patients with type III BS, GS, and p-BS/GS, 40, 12, and 63%, respectively, presented with chronic kidney disease. This study clarified the clinical differences between BS, GS, and p-BS/GS for the first time, which will help clinicians establish differential diagnoses for these three conditions.

Single-sample method for the estimation of glomerular filtration rate in children

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tauxe, W.N.; Bagchi, A.; Tepe, P.G.

1987-03-01

A method for the determination of the glomerular filtration rate (GFR) in children which involves the use of a single-plasma sample (SPS) after the injection of a radioactive indicator such as radioiodine labeled diatrizoate (Hypaque) has been developed. This is analogous to previously published SPS techniques of effective renal plasma flow (ERPF) in adults and children and GFR SPS techniques in adults. As a reference standard, GFR has been calculated from compartment analysis of injected radiopharmaceuticals (Sapirstein Method). Theoretical volumes of distribution were calculated at various times after injection (Vt) by dividing the total injected counts (I) by the plasmamore » concentration (Ct) expressed in liters, determined by counting an aliquot of plasma in a well type scintillation counter. Errors of predicting GFR from the various Vt values were determined as the standard error of estimate (Sy.x) in ml/min. They were found to be relatively high early after injection and to fall to a nadir of 3.9 ml/min at 91 min. The Sy.x Vt relationship was examined in linear, quadratic, and exponential form, but the simpler linear relationship was found to yield the lowest error. Other data calculated from the compartment analysis of the reference plasma disappearance curves are presented, but at this time have apparently little clinical relevance.« less

Assessing the kidney function parameters glomerular filtration rate and effective renal plasma flow with dynamic FDG-PET/MRI in healthy subjects.

PubMed

Geist, Barbara K; Baltzer, Pascal; Fueger, Barbara; Hamboeck, Martina; Nakuz, Thomas; Papp, Laszlo; Rasul, Sazan; Sundar, Lalith Kumar Shiyam; Hacker, Marcus; Staudenherz, Anton

2018-05-09

A method was developed to assess the kidney parameters glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) from 2-deoxy-2-[ 18 F]fluoro-D-glucose (FDG) concentration behavior in kidneys, measured with positron emission tomography (PET) scans. Twenty-four healthy adult subjects prospectively underwent dynamic simultaneous PET/magnetic resonance imaging (MRI) examination. Time activity curves (TACs) were obtained from the dynamic PET series, with the guidance of MR information. Patlak analysis was performed to determine the GFR, and based on integrals, ERPF was calculated. Results were compared to intra-individually obtained reference values determined from venous blood samples. Total kidney GFR and ERPF as estimated by dynamic PET/MRI were highly correlated to their reference values (r = 0.88/p < 0.0001 and r = 0.82/p < 0.0001, respectively) with no significant difference between their means. The study is a proof of concept that GFR and ERPF can be assessed with dynamic FDG PET/MRI scans in healthy kidneys. This has advantages for patients getting a routine scan, where additional examinations for kidney function estimation could be avoided. Further studies are required for transferring this PET/MRI method to PET/CT applications.

SGLT2 Inhibition for the Prevention and Treatment of Diabetic Kidney Disease: A Review.

PubMed

Alicic, Radica Z; Johnson, Emily J; Tuttle, Katherine R

2018-06-01

Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease in the United States and the world alike, and there is a great unmet need for treatments to reduce DKD development and progression. Inhibition of sodium/glucose co-transporter 2 (SGLT2) in the proximal tubule of the kidney has emerged as an effective antihyperglycemic treatment, leading to regulatory approval of several first-generation SGLT2 inhibitors for the treatment of type 2 diabetes. In follow-on clinical trials for the cardiovascular safety of the SGLT2 inhibitors, secondary effects to prevent or reduce albuminuria and decline in estimated glomerular filtration rate spurred further investigation into their potential application in DKD. This review summarizes the current understanding of mechanisms by which SGLT2 inhibitors block glucose reabsorption in the proximal tubule and improve systemic glucose homeostasis, the hypothesized mechanisms for kidney-protective effects of SGLT2 inhibition, and current recommendations for use of this class of antihyperglycemic agents in diabetic patients with low estimated glomerular filtration rates. Results of ongoing clinical trials in patients with DKD are eagerly awaited to expand knowledge of how SGLT2 inhibitors might be used for prevention and treatment. Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Dietary patterns and chronic kidney disease: a cross-sectional association in the Irish Nun Eye Study.

PubMed

Paterson, Euan N; Neville, Charlotte E; Silvestri, Giuliana; Montgomery, Shannon; Moore, Evelyn; Silvestri, Vittorio; Cardwell, Christopher R; MacGillivray, Tom J; Maxwell, Alexander P; Woodside, Jayne V; McKay, Gareth J

2018-04-27

Associations between dietary patterns and chronic kidney disease are not well established, especially in European populations. We conducted a cross-sectional study of 1033 older Irish women (age range 56-100 years) with a restricted lifestyle. Dietary intake was assessed using a food frequency questionnaire. Renal function was determined by estimated glomerular filtration rate. Two dietary patterns were identified within the study population using factor analysis. A significant negative association was found between unhealthy dietary pattern adherence and renal function in both unadjusted and adjusted models controlling for potential confounding variables (p for trend <0.001), with a mean difference in estimated glomerular filtration rate of -6 ml/min/1.73 m 2 between those in the highest fifth of adherence to the unhealthy dietary pattern compared to the lowest, in the fully adjusted model. Chronic kidney disease risk was significantly greater for the highest fifth, compared to the lowest fifth of unhealthy dietary pattern adherence in adjusted models (adjusted odds ratio = 2.62, p < 0.001). Adherence to the healthy dietary pattern was not associated with renal function or chronic kidney disease in adjusted models. In this cohort, an unhealthy dietary pattern was associated with lower renal function and greater prevalence of chronic kidney disease.

Effect of picric acid and enzymatic creatinine on the efficiency of the glomerular filtration rate predicator formula.

PubMed

Qiu, Ling; Guo, Xiuzhi; Zhu, Yan; Shou, Weilin; Gong, Mengchun; Zhang, Lin; Han, Huijuan; Quan, Guoqiang; Xu, Tao; Li, Hang; Li, Xuewang

2013-01-01

To investigate the impact of serum creatinine measurement on the applicability of glomerular filtration rate (GFR) evaluation equations. 99mTc-DTPA plasma clearance rate was used as GFR reference (rGFR) in patients with chronic kidney disease (CKD). Serum creatinine was measureded using enzymatic or picric acid creatinine reagent. The GFR of the patients were estimated using the Cockcroft-Gault equation corrected for body surface area, simplified Modification of Diet in Renal Disease (MDRD) equation, simplified MDRD equation corrected to isotopes dilution mass spectrometry, the CKD epidemiology collaborative research equation, and two Chinese simplified MDRD equations. Significant differences in the eGFR results estimated through enzymatic and picric acid methods were observed for the same evaluation equation. The intraclass correlation coefficient (ICC) of eGFR when the creatinine was measured by the picric acid method was significantly lower than that of the enzymatic method. The assessment accuracy of every equation using the enzymatic method to measure creatinine was significantly higher than that measured by the picric acid method when rGFR was > or = 60 mL/min/1.73m2. A significant difference was demonstrated in the same GFR evaluation equation using the picric acid and enzymatic methods. The enzymatic creatinine method was better than the picric acid method.

Comparison of mathematic models for assessment of glomerular filtration rate with electron-beam CT in pigs.

PubMed

Daghini, Elena; Juillard, Laurent; Haas, John A; Krier, James D; Romero, Juan C; Lerman, Lilach O

2007-02-01

To prospectively compare in pigs three mathematic models for assessment of glomerular filtration rate (GFR) on electron-beam (EB) computed tomographic (CT) images, with concurrent inulin clearance serving as the reference standard. This study was approved by the institutional animal care and use committee. Inulin clearance was measured in nine pigs (18 kidneys) and compared with single-kidney GFR assessed from renal time-attenuation curves (TACs) obtained with EB CT before and after infusion of the vasodilator acetylcholine. CT-derived GFR was calculated with the original and modified Patlak methods and with previously validated extended gamma variate modeling of first-pass cortical TACs. Statistical analysis was performed to assess correlation between CT methods and inulin clearance for estimation of GFR with least-squares regression analysis and Bland-Altman graphical representation. Comparisons within groups were performed with a paired t test. GFR assessed with the original Patlak method indicated poor correlation with inulin clearance, whereas GFR assessed with the modified Patlak method (P < .001, r = 0.75) and with gamma variate modeling (P < .001, r = 0.79) correlated significantly with inulin clearance and indicated an increase in response to acetylcholine. CT-derived estimates of GFR can be significantly improved by modifications in image analysis methods (eg, use of a cortical region of interest). (c) RSNA, 2007.

Estimating glomerular filtration rate (GFR) in children. The average between a cystatin C- and a creatinine-based equation improves estimation of GFR in both children and adults and enables diagnosing Shrunken Pore Syndrome.

PubMed

Leion, Felicia; Hegbrant, Josefine; den Bakker, Emil; Jonsson, Magnus; Abrahamson, Magnus; Nyman, Ulf; Björk, Jonas; Lindström, Veronica; Larsson, Anders; Bökenkamp, Arend; Grubb, Anders

2017-09-01

Estimating glomerular filtration rate (GFR) in adults by using the average of values obtained by a cystatin C- (eGFR cystatin C ) and a creatinine-based (eGFR creatinine ) equation shows at least the same diagnostic performance as GFR estimates obtained by equations using only one of these analytes or by complex equations using both analytes. Comparison of eGFR cystatin C and eGFR creatinine plays a pivotal role in the diagnosis of Shrunken Pore Syndrome, where low eGFR cystatin C compared to eGFR creatinine has been associated with higher mortality in adults. The present study was undertaken to elucidate if this concept can also be applied in children. Using iohexol and inulin clearance as gold standard in 702 children, we studied the diagnostic performance of 10 creatinine-based, 5 cystatin C-based and 3 combined cystatin C-creatinine eGFR equations and compared them to the result of the average of 9 pairs of a eGFR cystatin C and a eGFR creatinine estimate. While creatinine-based GFR estimations are unsuitable in children unless calibrated in a pediatric or mixed pediatric-adult population, cystatin C-based estimations in general performed well in children. The average of a suitable creatinine-based and a cystatin C-based equation generally displayed a better diagnostic performance than estimates obtained by equations using only one of these analytes or by complex equations using both analytes. Comparing eGFR cystatin and eGFR creatinine may help identify pediatric patients with Shrunken Pore Syndrome.

Differential associations between glomerular filtration rate and duration of obesity depending on the presence or absence of left ventricular diastolic dysfunction.

PubMed

Ybarra, Juan; Sánchez-Hernández, Joan; Vilallonga, Ramon; Romeo, June H

2016-07-01

A robust and consistent association between increasing body mass index (BMI) and chronic kidney disease (CKD) has been reported in several observational studies. Obesity remains the main preventable risk factor for CKD because it largely mediates diabetes and hypertension, the 2 most common etiologies for end-stage kidney disease (ESKD). Obesity is associated weakly with early stages of kidney disease but strongly with kidney progression to ESKD, even after adjustment for hypertension and diabetes. To assess the relationship between estimated glomerular filtration rate (eGFR) and trans-thoracic echocardiography left ventricular function parameters in a cohort of patients with obesity. Cross-sectional study involving 324 obese (BMI=44.0±2.2Kg/m(2)) apparently healthy asymptomatic patients with an eGFR >60ml/min/1.73m(2). Each patient underwent transthoracic echocardiography and a blood testing. The eGFR was addressed by the CKD-EPI formula. All patients had a normal systolic function whereas 24.5% disclosed diastolic dysfunction (DD). Hypertension and type 2 diabetes mellitus prevalence were 34.5% and 4.5% (respectively). All patients disclosed an eGFR >60ml/min while none of them disclosed hyperfiltration (eGFR >120ml/min). eGFR correlated inversely with BMI and the duration of obesity and positively with diastolic function parameters (P<0.001 for all, respectively). Patients with diastolic dysfunction displayed lower eGFR (P<0.0005) and longer duration of obesity (P<0.0005). Obesity and its duration are likely to impose hemodynamic changes affecting simultaneously both heart (diastolic dysfunction) and kidney (decreased glomerular filtration rate). Larger prospective studies are warranted. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Impact of Proteinuria and Glomerular Filtration Rate on Risk of Thromboembolism in Atrial Fibrillation: the ATRIA Study

PubMed Central

Go, Alan S.; Fang, Margaret C.; Udaltsova, Natalia; Chang, Yuchiao; Pomernacki, Niela K.; Borowsky, Leila; Singer, Daniel E.

2009-01-01

Background Atrial fibrillation (AF) substantially increases the risk of ischemic stroke but this risk varies among individual patients with AF. Existing risk stratification schemes have limited predictive ability. Chronic kidney disease is a major cardiovascular risk factor, but whether it independently increases the risk for ischemic stroke in persons with AF is unknown. Methods and Results We examined how chronic kidney disease (reduced glomerular filtration rate or proteinuria) affects risk of thromboembolism off anticoagulation in patients with AF. We estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease equation and proteinuria from urine dipstick results found in laboratory databases. Patient characteristics, warfarin use, and thromboembolic events were ascertained from clinical databases, with validation of thromboembolism by chart review. Results During 33,165 person-years off anticoagulation among 10,908 patients with atrial fibrillation, we observed 676 incident thromboembolic events. After adjustment for known risk factors for stroke and other confounders, proteinuria increased the risk of thromboembolism by 54% (relative risk [RR] 1.54, 1.29 to 1.85) and there was a graded, increased risk of stroke associated with progressively lower level of eGFR compared with eGFR ≥60 (in units of ml/min/1.73 m2): RR 1.16 (95% CI: 0.95−1.40) for eGFR 45−59 and RR 1.39 (95% CI: 1.13−1.71) for eGFR <45 (P=0.0082 for trend). Conclusions . Chronic kidney disease increases the risk of thromboembolism in AF independent of other risk factors. Knowing the level of kidney function and presence of proteinuria may improve risk stratification for decision-making about the use of antithrombotic therapy for stroke prevention in AF. PMID:19255343

[Management of chronic kidney disease guided by the theory of Traditional Chinese Medicine: an experimental study].

PubMed

Wen, Ji; Xie, Xi-Sheng; Zhang, Ming-Hua; Mao, Nan; Zhang, Cheng-Long; Xie, Lin-Shen; Cheng, Yuan; Zhang, Zi-Yuan; Fan, Jun-Ming

2014-01-01

To determine the impact of Traditional Chinese Medicine on patients with chronic kidney disease (CKD). A total of 225 CKD patients in an outpatient department were recruited for this study, among whom 170 received regular Western and Chinese medicine treatments (control group) and 55 received treatments guided by the theory of Traditional Chinese Medicine (experimental group). The effectiveness of the treatments was determined through a pre-post comparison. Significant pre-intervention differences in age (P < 0.01), stage of glomerular filtration rate (GFR) (P = 0.007) and urine protein (P < 0.01) were found between the two groups of patients. But age, gender and proteinuria were not significant predictors on clinical outcomes of the patients in the multivariate regression models. The experimental group had a greater level of decrease in blood urea nitrogen (P < 0.01) and serum creatine (P < 0. 01) than the control group. No significant differences between the groups were found in changes of uric acid (P = 0.475), urine protein (P = 0.058), urine red cells (P = 0.577), and urine white cells (P = 0.01). A greater level of increase in estimated glomerular filtration rate was found in the experimental group compared with the control (P < 0.001). The multivariate linear regression analysis identified group (B = 0.395, P < 0.001) and stage of GFR (B = 0.165, P = 0.008) as significant predictors on the outcomes of treatment. The treatment of CKD patients guided by the theory of Traditional Chinese Medicine can improve renal function through influencing glomerular filtration rate. The effect is more prominent than the regular treatment regime.

Glomerular Filtration Rate in Patients with Multiple Sclerosis Undergoing Stem Cell Transplantation and Treated With Cyclophosphamide.

PubMed

Ruiz-Argüelles, Alejandro; Gastélum-Cano, Jose M; Méndez-Huerta, Mariana A; Rodríguez-Gallegos, Alma B; Ruiz-Argüelles, Guillermo J

2018-06-15

Glomerular filtration rate (GFR) is partially impaired in patients with multiple sclerosis (MS). When given chemotherapy before receiving hematopoietic stem-cell transplantation, GFR might be further deteriorated. To measure the effect of cyclophosphamide on GFR in patients with MS who undergo chemotherapy. We estimated GFR based on creatinine and cystatin C plasma concentrations in patients undergoing autologous hematopoietic stem-cell transplantation to treat their MS. Baseline GFR values were lower in the 28 patients with MS than in the 20 healthy individuals. Also, according to the Chronic Kidney Disease-Epidemiology Collaborative Group (CKD-EPI) 2012 Creat-CysC equation criteria, 4 of 28 patients were classified as having chronic kidney disease (CKD) before receiving the chemotherapy drugs. After receiving 4 × 50 mg per kg body weight cyclophosphamide, abnormal GFR results were recorded in 12 of 28 patients. Renal function must be monitored in patients with MS undergoing autologous stem-cell transplantation. Also, chemotherapy should be constrained as much as possible to prevent further deterioration of renal function.

Longitudinal development of renal damage and renal function in infants with high grade vesicoureteral reflux.

PubMed

Sjöström, Sofia; Jodal, Ulf; Sixt, Rune; Bachelard, Marc; Sillén, Ulla

2009-05-01

We sought to study renal abnormality and renal function through time in infants with high grade vesicoureteral reflux. This prospective observational study included 115 infants (80 boys and 35 girls) younger than 1 year with grade III to V vesicoureteral reflux. The diagnosis was made after prenatal ultrasound in 26% of the patients and after urinary tract infection in 71%. Patients were followed by renal scintigraphy, 51chromium edetic acid clearance and video cystometry. Median followup was 62 months. Renal abnormality, which was found in 90% of the children at followup, was generalized in 71% and focal in 29%. The abnormality was bilateral in 28% of the affected patients. Total glomerular filtration rate was less than 80% of expected in 30% of the patients. Single kidney function was less than 40% of expected total glomerular filtration rate in 71% of the patients. Renal status (parenchymal abnormality and function) remained unchanged through time in 84 of 108 available cases (78%), improved in 5 (5%) and deteriorated in 19 (18%). Predictive factors for deterioration were recurrent febrile urinary tract infection, bilateral abnormality and reduced total glomerular filtration rate. Deteriorated renal status was more common in cases diagnosed prenatally than in those detected after urinary tract infection. Among these infants with high grade vesicoureteral reflux renal abnormality was frequent and was associated with subnormal filtration of one of the kidneys. Decreased total glomerular filtration rate was seen in about a third of the patients. Overall deterioration of renal status was seen in only a fifth of the patients. Infection control seems to be an important factor to minimize the risk.

Current use of equations for estimating glomerular filtration rate in Spanish laboratories.

PubMed

Gràcia-Garcia, Sílvia; Montañés-Bermúdez, Rosario; Morales-García, Luis J; Díez-de Los Ríos, M José; Jiménez-García, Juan Á; Macías-Blanco, Carlos; Martínez-López, Rosalina; Ruiz-Altarejos, Joaquín; Ruiz-Martín, Guadalupe; Sanz-Hernández, Sonia; Ventura-Pedret, Salvador

2012-07-17

In 2006 the Spanish Society of Clinical Biochemistry and Molecular Pathology (SEQC) and the Spanish Society of Nephrology (S.E.N.) developed a consensus document in order to facilitate the diagnosis and monitoring of chronic kidney disease with the incorporation of equations for estimating glomerular filtration rate (eGFR) into laboratory reports. The current national prevalence of eGFR reporting and the degree of adherence to these recommendations among clinical laboratories is unknown. We administered a national survey in 2010-11 to Spanish clinical laboratories. The survey was through e-mail or telephone to laboratories that participated in the SEQC’s Programme for External Quality Assurance, included in the National Hospitals Catalogue 2010, including both primary care and private laboratories. A total of 281 laboratories answered to the survey. Of these, 88.2% reported on the eGFR, with 61.9% reporting on the MDRD equation and 31.6% using the MDRD-IDMS equation. A total of 42.5% of laboratories always reported serum creatinine values, and other variables only when specifically requested. Regarding the way results were presented, 46.2% of laboratories reported the exact numerical value only when the filtration rate was below 60mL/min/1.73m2, while 50.6% reported all values regardless. In 56.3% of the cases reporting eGFR, an interpretive commentary of it was enclosed. Although a high percentage of Spanish laboratories have added eGFR in their reports, this metric is not universally used. Moreover, some aspects, such as the equation used and the correct expression of eGFR results, should be improved.

Renal dysfunction in early adulthood following birth asphyxia in male spiny mice, and its amelioration by maternal creatine supplementation during pregnancy.

PubMed

Ellery, Stacey J; LaRosa, Domenic A; Cullen-McEwen, Luise A; Brown, Russell D; Snow, Rod J; Walker, David W; Kett, Michelle M; Dickinson, Hayley

2017-04-01

Acute kidney injury affects ~70% of asphyxiated newborns, and increases their risk of developing chronic kidney disease later in life. Acute kidney injury is driven by renal oxygen deprivation during asphyxia, thus we hypothesized that creatine administered antenatally would protect the kidney from the long-term effects of birth asphyxia. Pregnant spiny mice were fed standard chow or chow supplemented with 5% creatine from 20-d gestation (midgestation). One day prior to term (37-d gestation), pups were delivered by caesarean or subjected to intrauterine asphyxia. Litters were allocated to one of two time-points. Kidneys were collected at 1 mo of age to estimate nephron number (stereology). Renal function (excretory profile and glomerular filtration rate) was measured at 3 mo of age, and kidneys then collected for assessment of glomerulosclerosis. Compared with controls, at 1 mo of age male (but not female) birth-asphyxia offspring had 20% fewer nephrons (P < 0.05). At 3 mo of age male birth-asphyxia offspring had 31% lower glomerular filtration rate (P < 0.05) and greater glomerular collagen IV content (P < 0.01). Antenatal creatine prevented these renal injuries arising from birth asphyxia. Maternal creatine supplementation during pregnancy may be an effective prophylactic to prevent birth asphyxia induced acute kidney injury and the emergence of chronic kidney disease.

Estimation of Glomerular Filtration Rate Based on Serum Cystatin C versus Creatinine in a Uruguayan Population

PubMed Central

Lujambio, Inés; Sottolano, Mariana; Robaina, Sebastián; Carusso, Florencia; da Rosa, Alicia; Ríos, Ana Carina; Olascoaga, Alicia; Gadola, Liliana; Noboa, Oscar; Staessen, Jan A.; Boggia, José

2014-01-01

Background. Estimation of glomerular filtration rate (eGFR) from biomarkers has evolved and multiple equations are available to estimate renal function at bedside. Methods. In a random sample of 119 Uruguayans (54.5% women; 56.2 years (mean)), we used Bland and Altman's method and Cohen's kappa statistic to assess concordance on a continuous or categorical (eGFR < 60 versus ≥60 mL/min/1.73 m2) scale between eGFRcys (reference) and eGFR derived from serum creatinine according to the Modification of Diet in Renal Disease (eGFRmdrd) or the Chronic Kidney Disease Epidemiology Collaboration equations (eGFRepi) or from both serum cystatin C and creatinine (eGFRmix). Results. In all participants, eGFRmdrd, eGFRepi, and eGFRmix were, respectively, 9.7, 11.5, and 5.6 mL/min/1.73 m2 higher (P < 0.0001) than eGFRcys. The prevalence of eGFR <60 mL/min/1.73 m2 was the highest for eGFRcys (21.8%), intermediate for eGFRmix (11.8%), and the lowest for eGFRmdrd (5.9%) and eGFRepi (3.4%). Using eGFRcys as reference, we found only fair agreement with the equations based on creatinine (Cohen's kappa statistic 0.15 to 0.23). Conclusion. Using different equations we reached clinically significant differences in the estimation of renal function. eGFRcys provides lower estimates, resulting in higher prevalence of eGFR <60 mL/min/1.73 m2. PMID:25215234

Skin Autofluorescence and Subclinical Atherosclerosis in Mild to Moderate Chronic Kidney Disease: A Case-Control Study

PubMed Central

Sánchez, Enric; Betriu, Àngels; Arroyo, David; López, Carolina; Hernández, Marta; Rius, Ferran; Fernández, Elvira

2017-01-01

Advanced glycation end-products (AGEs) are increased and predict mortality in patients with chronic kidney disease (CKD) who are undergoing hemodialysis, irrespective of the presence of type 2 diabetes. However, little information exits about the relationship between AGEs and subclinical atherosclerosis at the early stages of CKD. A case-control study was performed including 87 patients with mild-to-moderate stages of CKD (glomerular filtration rate from 89 to 30 ml/min/per 1.73m2) and 87 non-diabetic non-CKD subjects matched by age, gender, body mass index, and waist circumference. Skin autofluorescence (AF), a non-invasive assessment of AGEs, was measured. The presence of atheromatous disease in carotid and femoral arteries was evaluated using vascular ultrasound, and vascular age and SCORE risk were estimated. Patients with mild-to-moderate stages of CKD showed an increase in skin AF compared with control subjects (2.5±0.6 vs. 2.2±0.4 AU, p<0.001). A skin AF value >2.0 AU was accompanied by a 3-fold increased risk of detecting the presence of an atheromathous plaque (OR 3.0, 95% CI 1.4–6.5, p = 0.006). When vascular age was assessed through skin AF, subjects with CKD were almost 12 years older than control subjects (70.3±25.5 vs. 58.5±20.2 years, p = 0.001). Skin AF was negatively correlated with glomerular filtration rate (r = -0.354, p<0.001) and LDL-cholesterol (r = -0.269, p = 0.001), and positively correlated with age (r = 0.472, p<0.001), pulse pressure (r = 0.238, p = 0.002), and SCORE risk (r = 0.451, p<0.001). A stepwise multivariate regression analysis showed that age and glomerular filtration rate independently predicted skin AF (R2 = 0.289, p<0.001). Skin AF is elevated in patients with mild-to-moderate CKD compared with control subjects. This finding may be independently associated with the glomerular filtration rate and the presence of subclinical atheromatous disease. Therefore, the use of skin AF may help to accurately evaluate the real cardiovascular risk at the early stages of CKD. PMID:28141808

Performance of three glomerular filtration rate estimation equations in a population of sub-Saharan Africans with Type 2 diabetes.

PubMed

Agoons, D D; Balti, E V; Kaze, F F; Azabji-Kenfack, M; Ashuntantang, G; Kengne, A P; Sobngwi, E; Mbanya, J C

2016-09-01

We evaluated the performance of the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Cockcroft-Gault (CG) equations against creatinine clearance (CrCl) to estimate glomerular filtration rate (GFR) in 51 patients with Type 2 diabetes. The CrCl value was obtained from the average of two consecutive 24-h urine samples. Results were adjusted for body surface area using the Dubois formula. Serum creatinine was measured using the kinetic Jaffe method and was calibrated to standardized levels. Bland-Altman analysis and kappa statistic were used to examine agreement between measured and estimated GFR. Estimates of GFR from the CrCl, MDRD, CKD-EPI and CG equations were similar (overall P = 0.298), and MDRD (r = 0.58; 95% CI: 0.36-0.74), CKD-EPI (r = 0.55; 95% CI: 0.33-0.72) and CG (r = 0.61; 95% CI: 0.39-0.75) showed modest correlation with CrCl (all P < 0.001). Bias was -0.3 for MDRD, 1.7 for CKD-EPI and -5.4 for CG. All three equations showed fair-to-moderate agreement with CrCl (kappa: 0.38-0.51). The c-statistic for all three equations ranged between 0.75 and 0.77 with no significant difference (P = 0.639 for c-statistic comparison). The MDRD equation seems to have a modest advantage over CKD-EPI and CG in estimating GFR and detecting impaired renal function in sub-Saharan African patients with Type 2 diabetes. The overall relatively modest correlation with CrCl, however, suggests the need for context-specific estimators of GFR or context adaptation of existing estimators. © 2015 Diabetes UK.

Estimating glomerular filtration rate in black South Africans by use of the modification of diet in renal disease and Cockcroft-Gault equations.

PubMed

van Deventer, Hendrick E; George, Jaya A; Paiker, Janice E; Becker, Piet J; Katz, Ivor J

2008-07-01

The 4-variable Modification of Diet in Renal Disease (4-v MDRD) and Cockcroft-Gault (CG) equations are commonly used for estimating glomerular filtration rate (GFR); however, neither of these equations has been validated in an indigenous African population. The aim of this study was to evaluate the performance of the 4-v MDRD and CG equations for estimating GFR in black South Africans against measured GFR and to assess the appropriateness for the local population of the ethnicity factor established for African Americans in the 4-v MDRD equation. We enrolled 100 patients in the study. The plasma clearance of chromium-51-EDTA ((51)Cr-EDTA) was used to measure GFR, and serum creatinine was measured using an isotope dilution mass spectrometry (IDMS) traceable assay. We estimated GFR using both the reexpressed 4-v MDRD and CG equations and compared it to measured GFR using 4 modalities: correlation coefficient, weighted Deming regression analysis, percentage bias, and proportion of estimated GFR within 30% of measured GFR (P(30)). The Spearman correlation coefficient between measured and estimated GFR for both equations was similar (4-v MDRD R(2) = 0.80 and CG R(2) = 0.79). Using the 4-v MDRD equation with the ethnicity factor of 1.212 as established for African Americans resulted in a median positive bias of 13.1 (95% CI 5.5 to 18.3) mL/min/1.73 m(2). Without the ethnicity factor, median bias was 1.9 (95% CI -0.8 to 4.5) mL/min/1.73 m(2). The 4-v MDRD equation, without the ethnicity factor of 1.212, can be used for estimating GFR in black South Africans.

Glomerular hemodynamic alterations during acute hyperinsulinemia in normal and diabetic rats

NASA Technical Reports Server (NTRS)

Tucker, B. J.; Anderson, C. M.; Thies, R. S.; Collins, R. C.; Blantz, R. C.

1992-01-01

Treatment of insulin dependent diabetes invariably requires exogenous insulin to control blood glucose. Insulin treatment, independent of other factors associated with insulin dependent diabetes, may induce changes that affect glomerular function. Due to exogenous delivery of insulin in insulin dependent diabetes entering systemic circulation prior to the portal vein, plasma levels of insulin are often in excess of that observed in non-diabetics. The specific effects of hyperinsulinemia on glomerular hemodynamics have not been previously examined. Micropuncture studies were performed in control (non-diabetic), untreated diabetic and insulin-treated diabetic rats 7 to 10 days after administration of 65 mg/kg body weight streptozotocin. After the first period micropuncture measurements were obtained, 5 U of regular insulin (Humulin-R) was infused i.v., and glucose clamped at euglycemic values (80 to 120 mg/dl). Blood glucose concentration in non-diabetic controls was 99 +/- 6 mg/dl. In control rats, insulin infusion and glucose clamp increased nephron filtration rate due to decreases in both afferent and efferent arteriolar resistance (afferent greater than efferent) resulting in increased plasma flow and increased glomerular hydrostatic pressure gradient. However, insulin infusion and glucose clamp produced the opposite effect in both untreated and insulin-treated diabetic rats with afferent arteriolar vasoconstriction resulting in decreases in plasma flow, glomerular hydrostatic pressure gradient and nephron filtration rate. Thromboxane A2 (TX) synthetase inhibition partially decreased the vasoconstrictive response due to acute insulin infusion in diabetic rats preventing the decrease in nephron filtration rate.(ABSTRACT TRUNCATED AT 250 WORDS).

Glomerular filtration rate estimation from plasma creatinine after inhibition of tubular secretion: relevance of the creatinine assay.

PubMed

Kemperman, F A; Silberbusch, J; Slaats, E H; van Zanten, A P; Weber, J A; Krediet, R T; Arisz, L

1999-05-01

Estimation of glomerular filtration rate (GFR) from plasma creatinine concentration after inhibition of tubular creatinine secretion with cimetidine provides a good assessment in patients with various nephropathies and with non-insulin-dependent diabetes mellitus (NIDDM). The aim of this study was to compare cimetidine-aided GFR estimations using various creatinine assays. In 30 outpatients with NIDDM GFR was measured as the urinary clearance of continuously infused [125I]iothalamate. Plasma creatinine concentration was analysed after oral cimetidine with an alkaline picrate (AP) method, with an enzymatic (PAP) assay and with HPLC. GFR estimations were calculated with the Cockcroft Gault formula (CG). AP creatinine concentrations were significantly higher than PAP or HPLC values. GFR estimations by AP (CG(AP) 66 +/- 19 ml/min/1.73 m2, mean SD) were significantly lower than GFR (89 +/- 30), whereas CG(PAP) (85 +/- 30) and CG(HPLC) (84 +/- 34 ml/min/1.73 m2) were not. Bland and Altman analysis showed a difference between CG(AP) and GFR of -22.4 +/- 17.7 ml/min/1.73 m2; this difference becomes larger when the GFR increases. The difference between CG and GFR was only -3.8 +/- 14.8 ml/min/1.73 m2 for PAP and -4.4 +/- 17.5 ml/min/1.73 m2 for HPLC, without any systematic difference. A good assessment of the GFR from plasma creatinine after cimetidine administration is possible when creatinine is measured with an enzymatic assay or with the less convenient HPLC method. The more widespread and cheaper alkaline picrate assay is not suitable for GFR-estimation.

Renal hemodynamics and renin-angiotensin system activity in humans with multifocal renal artery fibromuscular dysplasia.

PubMed

van Twist, Daan J L; Houben, Alphons J H M; de Haan, Michiel W; de Leeuw, Peter W; Kroon, Abraham A

2016-06-01

Fibromuscular dysplasia (FMD) is the second most common cause of renovascular hypertension. Nonetheless, knowledge on the renal microvasculature and renin-angiotensin system (RAS) activity in kidneys with FMD is scarce. Given the fairly good results of revascularization, we hypothesized that the renal microvasculature and RAS are relatively spared in kidneys with FMD. In 58 hypertensive patients with multifocal renal artery FMD (off medication) and 116 matched controls with essential hypertension, we measured renal blood flow (Xenon washout method) per kidney and drew blood samples from the aorta and both renal veins to determine renin secretion and glomerular filtration rate per kidney. We found that renal blood flow and glomerular filtration rate in FMD were comparable to those in controls. Although systemic renin levels were somewhat higher in FMD, renal renin secretion was not elevated. Moreover, in patients with unilateral FMD, no differences between the affected and unaffected kidney were observed with regard to renal blood flow, glomerular filtration rate, or renin secretion. In men, renin levels and renin secretion were higher as compared with women. The renal blood flow response to RAS modulation (by intrarenal infusion of angiotensin II, angiotensin-(1-7), an angiotensin II type 1 receptor blocker, or a nitric oxide synthase blocker) was also comparable between FMD and controls. Renal blood flow, glomerular filtration, and the response to vasoactive substances in kidneys with multifocal FMD are comparable to patients with essential hypertension, suggesting that microvascular function is relatively spared. Renin secretion was not increased and the response to RAS modulation was not affected in kidneys with FMD.

Proteomic analysis of the kidney filtration barrier--Problems and perspectives.

PubMed

Rinschen, Markus M; Benzing, Thomas; Limbutara, Kavee; Pisitkun, Trairak

2015-12-01

Diseases of the glomerular filter of the kidney are a leading cause of end-stage renal failure. The kidney filter is localized within the renal glomeruli, small microvascular units that are responsible for ultrafiltration of about 180 liters of primary urine every day. The renal filter consists of three layers, fenestrated endothelial cells, glomerular basement membrane, and the podocytes, terminally differentiated, arborized epithelial cells. This review demonstrates the use of proteomics to generate insights into the regulation of the renal filtration barrier at a molecular level. The advantages and disadvantages of different glomerular purification methods are examined, and the technical limitations that have been significantly improved by in silico or biochemical approaches are presented. We also comment on phosphoproteomic studies that have generated considerable molecular-level understanding of the physiological regulation of the kidney filter. Lastly, we conclude with an analysis of urinary exosomes as a potential filter-derived resource for the noninvasive discovery of glomerular disease mechanisms. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

CKD-EPI equation: A suitable Glomerular Filtration Rate estimate for drug dosing in HIV-infected patients.

PubMed

Gagneux-Brunon, A; Botelho-Nevers, E; Delanaye, P; Lucht, F; Frésard, A; Cazorla, C; Guglielminotti, C; Fafin, C; Mariat, C; Moranne, O

2017-06-01

To evaluate concordance between glomerular filtration rate (GFR) estimates (Cockcroft and Gault, modification of diet in renal diseases, chronic kidney disease epidemiology study group equations) for drug dosing in HIV-infected patients. We performed a monocentric study. GFR was measured using the gold standard method (plasma clearance of iohexol) in 230 HIV-infected patients. Concordance rate was evaluated between measured GFR (mGFR) and estimated GFR (eGFR) for different GFR categories (GFR>90 mL/min, GFR<90 mL/min, GFR>70 mL/min, and GFR<70 mL/min). MDRD and CKD-EPI were used with and without indexation to body surface area (BSA). Mean age was 48±10 years, mean mGFR was 101±26 mL/min. Concordance between mGFR and eGFR estimated with CG, CKD-EPI (indexed and not indexed to BSA), or MDRD equations (not indexed to BSA) was similar (73%, 73%, 74%, and 73% respectively) for a breakpoint value of 90 mL/min for GFR. At this value, the concordance rate between mGFR and MDRD indexed to BSA was significantly lower (65%, P<0.05). Using 70 mL/min of GFR as the breakpoint value, all equations had similar concordance rates with mGFR (with or without indexation to BSA). CKD-EPI equation has the same concordance with GFR and with CG when used for drug dosing. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Involvement of Renal Corpuscle microRNA Expression on Epithelial-to-Mesenchymal Transition in Maternal Low Protein Diet in Adult Programmed Rats

PubMed Central

Sene, Letícia de Barros; Mesquita, Flávia Fernandes; de Moraes, Leonardo Nazário; Santos, Daniela Carvalho; Carvalho, Robson; Gontijo, José Antônio Rocha; Boer, Patrícia Aline

2013-01-01

Prior study shows that maternal protein-restricted (LP) 16-wk-old offspring have pronounced reduction of nephron number and arterial hypertension associated with unchanged glomerular filtration rate, besides enhanced glomerular area, which may be related to glomerular hyperfiltration/overflow and which accounts for the glomerular filtration barrier breakdown and early glomerulosclerosis. In the current study, LP rats showed heavy proteinuria associated with podocyte simplification and foot process effacement. TGF-β1 glomerular expression was significantly enhanced in LP. Isolated LP glomeruli show a reduced level of miR-200a, miR-141, miR-429 and ZEB2 mRNA and upregulated collagen 1α1/2 mRNA expression. By western blot analyzes of whole kidney tissue, we found significant reduction of both podocin and nephrin and enhanced expression of mesenchymal protein markers such as desmin, collagen type I and fibronectin. From our present knowledge, these are the first data showing renal miRNA modulation in the protein restriction model of fetal programming. The fetal-programmed adult offspring showed pronounced structural glomerular disorders with an accentuated and advanced stage of fibrosis, which led us to state that the glomerular miR-200 family would be downregulated by TGF-β1 action inducing ZEB 2 expression that may subsequently cause glomeruli epithelial-to-mesenchymal transition. PMID:23977013

Pathophysiologic Implications of Reduced Podocyte Number in a Rat Model of Progressive Glomerular Injury

PubMed Central

Macconi, Daniela; Bonomelli, Maria; Benigni, Ariela; Plati, Tiziana; Sangalli, Fabio; Longaretti, Lorena; Conti, Sara; Kawachi, Hiroshi; Hill, Prue; Remuzzi, Giuseppe; Remuzzi, Andrea

2006-01-01

Changes in podocyte number or density have been suggested to play an important role in renal disease progression. Here, we investigated the temporal relationship between glomerular podocyte number and development of proteinuria and glomerulosclerosis in the male Munich Wistar Fromter (MWF) rat. We also assessed whether changes in podocyte number affect podocyte function and focused specifically on the slit diaphragm-associated protein nephrin. Age-matched Wistar rats were used as controls. Estimation of podocyte number per glomerulus was determined by digital morphometry of WT1-positive cells. MWF rats developed moderate hypertension, massive proteinuria, and glomerulosclerosis with age. Glomerular hypertrophy was already observed at 10 weeks of age and progressively increased thereafter. By contrast, mean podocyte number per glomerulus was lower than normal in young animals and further decreased with time. As a consequence, the capillary tuft volume per podocyte was more than threefold increased in older rats. Electron microscopy showed important changes in podocyte structure of MWF rats, with expansion of podocyte bodies surrounding glomerular filtration membrane. Glomerular nephrin expression was markedly altered in MWF rats and inversely correlated with both podocyte loss and proteinuria. Our findings suggest that reduction in podocyte number is an important determinant of podocyte dysfunction and progressive impairment of the glomerular permselectivity that lead to the development of massive proteinuria and ultimately to renal scarring. PMID:16400008

Renal Insufficiency After Contrast Media Administration Trial II (REMEDIAL II): RenalGuard System in high-risk patients for contrast-induced acute kidney injury.

PubMed

Briguori, Carlo; Visconti, Gabriella; Focaccio, Amelia; Airoldi, Flavio; Valgimigli, Marco; Sangiorgi, Giuseppe Massimo; Golia, Bruno; Ricciardelli, Bruno; Condorelli, Gerolama

2011-09-13

The RenalGuard System, which creates high urine output and fluid balancing, may be beneficial in preventing contrast-induced acute kidney injury. The Renal Insufficiency After Contrast Media Administration Trial II (REMEDIAL II) trial is a randomized, multicenter, investigator-driven trial addressing the prevention of contrast-induced acute kidney injury in high-risk patients. Patients with an estimated glomerular filtration rate ≤30 mL · min(-1) · 1.73 m(-2) and/or a risk score ≥11 were randomly assigned to sodium bicarbonate solution and N-acetylcysteine (control group) or hydration with saline and N-acetylcysteine controlled by the RenalGuard System and furosemide (RenalGuard group). The primary end point was an increase of ≥0.3 mg/dL in the serum creatinine concentration at 48 hours after the procedure. The secondary end points included serum cystatin C kinetics and rate of in-hospital dialysis. Contrast-induced acute kidney injury occurred in 16 of 146 patients in the RenalGuard group (11%) and in 30 of 146 patients in the control group (20.5%; odds ratio, 0.47; 95% confidence interval, 0.24 to 0.92). There were 142 patients (48.5%) with an estimated glomerular filtration rate ≤30 mL · min(-1) · 1.73 and 149 patients (51.5%) with only a risk score ≥11. Subgroup analysis according to inclusion criteria showed a similarly lower risk of adverse events (estimated glomerular filtration rate ≤30 mL · min(-1) · 1.73 m(-2): odds ratio, 0.44; risk score ≥11: odds ratio, 0.45; P for interaction=0.97). Changes in cystatin C at 24 hours (0.02±0.32 versus -0.08±0.26; P=0.002) and 48 hours (0.12±0.42 versus 0.03±0.31; P=0.001) and the rate of in-hospital dialysis (4.1% versus 0.7%; P=0.056) were higher in the control group. RenalGuard therapy is superior to sodium bicarbonate and N-acetylcysteine in preventing contrast-induced acute kidney injury in high-risk patients. URL: http://www.clinicaltrial.gov. Unique identifier: NCT01098032.

Efficacy and safety of febuxostat in the treatment of hyperuricemia in stable kidney transplant recipients

PubMed Central

Sofue, Tadashi; Inui, Masashi; Hara, Taiga; Nishijima, Yoko; Moriwaki, Kumiko; Hayashida, Yushi; Ueda, Nobufumi; Nishiyama, Akira; Kakehi, Yoshiyuki; Kohno, Masakazu

2014-01-01

Background Post-transplant hyperuricemia (PTHU), defined as serum uric acid concentration ≥7.0 mg/dL or need for treatment with allopurinol or benzbromarone, reduces long-term allograft survival in kidney transplant recipients. Febuxostat, a new nonpurine selective xanthine oxidase inhibitor, is well tolerated in patients with moderate renal impairment. However, its efficacy and safety in kidney recipients with PTHU is unclear. We therefore assessed the efficacy and safety of febuxostat in stable kidney transplant recipients with PTHU. Methods Of 93 stable adult kidney transplant recipients, 51 were diagnosed with PTHU (PTHU group) and 42 were not (NPTHU group). Of the 51 patients with PTHU, 26 were treated with febuxostat (FX group) and 25 were not (NFX group), at the discretion of each attending physician. One-year changes in serum uric acid concentrations, rates of achievement of target uric acid (<6.0 mg/dL), estimated glomerular filtration rates in allografts, and adverse events were retrospectively analyzed in the FX, NFX, and NPTHU groups. Results The FX group showed significantly greater decreases in serum uric acid (−2.0±1.1 mg/dL versus 0.0±0.8 mg/dL per year, P<0.01) and tended to show a higher rate of achieving target uric acid levels (50% versus 24%; odds ratio 3.17 [95% confidence interval 0.96–10.5], P=0.08) than the NFX group. Although baseline allograft estimated glomerular filtration rates tended to be lower in the FX group than in the NFX group (40±14 mL/min/1.73 m2 versus 47±19 mL/min/1.73 m2), changes in allograft estimated glomerular filtration rate were similar (+1.0±4.9 mL/min/1.73 m2 versus −0.2±6.9 mL/min/1.73 m2 per year, P=0.50). None of the patients in the FX group experienced any severe adverse effects, such as pancytopenia or attacks of gout, throughout the entire study period. Nephrologists were more likely than urologists to start febuxostat in kidney transplant recipients with PTHU (69% versus 8%). Conclusion Treatment with febuxostat sufficiently lowered uric acid levels without severe adverse effects in stable kidney transplant recipients with PTHU. PMID:24600205

Efficacy and safety of febuxostat in the treatment of hyperuricemia in stable kidney transplant recipients.

PubMed

Sofue, Tadashi; Inui, Masashi; Hara, Taiga; Nishijima, Yoko; Moriwaki, Kumiko; Hayashida, Yushi; Ueda, Nobufumi; Nishiyama, Akira; Kakehi, Yoshiyuki; Kohno, Masakazu

2014-01-01

Post-transplant hyperuricemia (PTHU), defined as serum uric acid concentration ≥7.0 mg/dL or need for treatment with allopurinol or benzbromarone, reduces long-term allograft survival in kidney transplant recipients. Febuxostat, a new nonpurine selective xanthine oxidase inhibitor, is well tolerated in patients with moderate renal impairment. However, its efficacy and safety in kidney recipients with PTHU is unclear. We therefore assessed the efficacy and safety of febuxostat in stable kidney transplant recipients with PTHU. Of 93 stable adult kidney transplant recipients, 51 were diagnosed with PTHU (PTHU group) and 42 were not (NPTHU group). Of the 51 patients with PTHU, 26 were treated with febuxostat (FX group) and 25 were not (NFX group), at the discretion of each attending physician. One-year changes in serum uric acid concentrations, rates of achievement of target uric acid (<6.0 mg/dL), estimated glomerular filtration rates in allografts, and adverse events were retrospectively analyzed in the FX, NFX, and NPTHU groups. The FX group showed significantly greater decreases in serum uric acid (-2.0±1.1 mg/dL versus 0.0±0.8 mg/dL per year, P<0.01) and tended to show a higher rate of achieving target uric acid levels (50% versus 24%; odds ratio 3.17 [95% confidence interval 0.96-10.5], P=0.08) than the NFX group. Although baseline allograft estimated glomerular filtration rates tended to be lower in the FX group than in the NFX group (40±14 mL/min/1.73 m(2) versus 47±19 mL/min/1.73 m(2)), changes in allograft estimated glomerular filtration rate were similar (+1.0±4.9 mL/min/1.73 m(2) versus -0.2±6.9 mL/min/1.73 m(2) per year, P=0.50). None of the patients in the FX group experienced any severe adverse effects, such as pancytopenia or attacks of gout, throughout the entire study period. Nephrologists were more likely than urologists to start febuxostat in kidney transplant recipients with PTHU (69% versus 8%). Treatment with febuxostat sufficiently lowered uric acid levels without severe adverse effects in stable kidney transplant recipients with PTHU.

Glomerular hyperfiltration is strongly correlated with age in Congolese children with sickle cell anaemia.

PubMed

Aloni, Michel Ntetani; Ngiyulu, René Makuala; Ekulu, Pépé Mfutu; Mbutiwi, Fiston IkwaNdol; Makulo, Jean Robert; Gini-Ehungu, Jean Lambert; Nseka, Nazaire Mangani; Lepira, François Bompeka

2017-05-01

Glomerular hyperfiltration is an early marker of sickle cell nephropathy and can lead to microalbuminuria and renal failure. Our aim was to identify the associated risk factors, as these could be of preventative importance. We recruited 150 children with sickle cell anaemia (SCA), aged two to 18 years and living in Kinshasa, the Democratic Republic of Congo. Hyperfiltration and microalbuminuria were defined as an estimated glomerular filtration rate of less than 140 mL/min/1.73 m² and an albumin creatinine ratio of between 30 and 299 mg/g, respectively. Independent determinants of hyperfiltration were assessed using logistic regression analysis. Glomerular hyperfiltration was observed in 60 (40%) children, who were significantly older (10.2 ± 4.1 versus 7.9 ± 4.3 years, p = 0.001) and had a lower body mass index level (14.7 ± 2.3 versus 15.0 ± 2.3 kg/m 2 ) than the 60% without. A higher proportion had microalbuminuria (25.0 versus 13.3%), but the difference was not statistically significant (p>0.05). Increased age and decreased body mass index were the main independent factors associated with glomerular hyperfiltration in the multivariate analysis. A quarter (25%) of the 60 children with SCA with glomerular hyperfiltration had microalbuminuria. Glomerular hyperfiltration was a common finding in this study and was significantly associated with age. ©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Effects of bombesin on erythropoietin production in the anaesthetized dog.

PubMed

Melchiorri, P; Sopranzi, N; Roseghini, M

1976-08-01

Bombesin, a tetradecapeptide isolated from the skin of some European discoglossid frogs, has been reported previously to reduce renal blood flow and glomerular filtration rate and to increase plasma renin activity in anaesthetized dogs. In the present study bombesin was infused intravenously in anaesthetized dogs at dose levels of 3, 6 and 12 ng/kg/min for 6 h and renal blood flow, glomerular filtration rate, oxygen consumption, oxygen extraction by the kidney tissue, as well as plasma erythropoietin levels (ESF) and plasma renin activity were measured. Plasma levels of ESF increased during bombesin infusion only when renal blood flow was reduced to a level of 1 ml/g/min or less. In this situation glomerular filtration was blocked, renal oxygen consumption was decreased to 10% of normal and oxygen extraction by the kidney was increased by 2 times. No correlation was found between plasma renin activity and ESF concentrations during bombesin infusion. It is concluded that the stimulant action of bombesin on ESF production is a consequence of the renal hypoxia induced by the reduction in renal blood flow.

Documentation of angiotensin II receptors in glomerular epithelial cells

NASA Technical Reports Server (NTRS)

Sharma, M.; Sharma, R.; Greene, A. S.; McCarthy, E. T.; Savin, V. J.; Cowley, A. W. (Principal Investigator)

1998-01-01

Angiotensin II decreases glomerular filtration rate, renal plasma flow, and glomerular capillary hydraulic conductivity. Although angiotensin II receptors have been demonstrated in mesangial cells and proximal tubule cells, the presence of angiotensin II receptors in glomerular epithelial cells has not previously been shown. Previously, we have reported that angiotensin II caused an accumulation of cAMP and a reorganization of the actin cytoskeleton in cultured glomerular epithelial cells. Current studies were conducted to verify the presence of angiotensin II receptors by immunological and non-peptide receptor ligand binding techniques and to ascertain the activation of intracellular signal transduction in glomerular epithelial cells in response to angiotensin II. Confluent monolayer cultures of glomerular epithelial cells were incubated with angiotensin II, with or without losartan and/or PD-123,319 in the medium. Membrane vesicle preparations were obtained by homogenization of washed cells followed by centrifugation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of membrane proteins followed by multiscreen immunoblotting was used to determine the presence of angiotensin II receptor type 1 (AT1) or type 2 (AT2). Angiotensin II-mediated signal transduction in glomerular epithelial cells was studied by measuring the levels of cAMP, using radioimmunoassay. Results obtained in these experiments showed the presence of both AT1 and AT2 receptor types in glomerular epithelial cells. Angiotensin II was found to cause an accumulation of cAMP in glomerular epithelial cells, which could be prevented only by simultaneous use of losartan and PD-123,319, antagonists for AT1 and AT2, respectively. The presence of both AT1 and AT2 receptors and an increase in cAMP indicate that glomerular epithelial cells respond to angiotensin II in a manner distinct from that of mesangial cells or proximal tubular epithelial cells. Our results suggest that glomerular epithelial cells participate in angiotensin II-mediated control of the glomerular filtration barrier.

GFR Estimation: From Physiology to Public Health

PubMed Central

Levey, Andrew S.; Inker, Lesley A.; Coresh, Josef

2014-01-01

Estimating glomerular filtration rate (GFR) is essential for clinical practice, research, and public health. Appropriate interpretation of estimated GFR (eGFR) requires understanding the principles of physiology, laboratory medicine, epidemiology and biostatistics used in the development and validation of GFR estimating equations. Equations developed in diverse populations are less biased at higher GFR than equations developed in CKD populations and are more appropriate for general use. Equations that include multiple endogenous filtration markers are more precise than equations including a single filtration marker. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations are the most accurate GFR estimating equations that have been evaluated in large, diverse populations and are applicable for general clinical use. The 2009 CKD-EPI creatinine equation is more accurate in estimating GFR and prognosis than the 2006 Modification of Diet in Renal Disease (MDRD) Study equation and provides lower estimates of prevalence of decreased eGFR. It is useful as a “first” test for decreased eGFR and should replace the MDRD Study equation for routine reporting of serum creatinine–based eGFR by clinical laboratories. The 2012 CKD-EPI cystatin C equation is as accurate as the 2009 CKD-EPI creatinine equation in estimating eGFR, does not require specification of race, and may be more accurate in patients with decreased muscle mass. The 2012 CKD-EPI creatinine–cystatin C equation is more accurate than the 2009 CKD-EPI creatinine and 2012 CKD-EPI cystatin C equations and is useful as a confirmatory test for decreased eGFR as determined by an equation based on serum creatinine. Further improvement in GFR estimating equations will require development in more broadly representative populations, including diverse racial and ethnic groups, use of multiple filtration markers, and evaluation using statistical techniques to compare eGFR to “true GFR”. PMID:24485147

The Rac-specific exchange factors Dock1 and Dock5 are dispensable for the establishment of the glomerular filtration barrier in vivo

PubMed Central

Laurin, Mélanie; Dumouchel, Annie; Fukui, Yoshinori; Côté, Jean-François

2013-01-01

Podocytes are specialized kidney cells that form the kidney filtration barrier through the connection of their foot processes. Nephrin and Neph family transmembrane molecules at the surface of podocytes interconnect to form a unique type of cell-cell junction, the slit diaphragm, which acts as a molecular sieve. The cytoplasmic tails of Nephrin and Neph mediate cytoskeletal rearrangement that contributes to the maintenance of the filtration barrier. Nephrin and Neph1 orthologs are essential to regulate cell-cell adhesion and Rac-dependent actin rearrangement during Drosophila myoblast fusion. We hypothesized here that molecules regulating myoblast fusion in Drosophila could contribute to signaling downstream of Nephrin and Neph1 in podocytes. We found that Nephrin engagement promoted recruitment of the Rac exchange factor Dock1 to the membrane. Furthermore, Nephrin overexpression led to lamellipodia formation that could be blocked by inhibiting Rac1 activity. We generated in vivo mouse models to investigate whether Dock1 and Dock5 contribute to the formation and maintenance of the kidney filtration barrier. Our results indicate that while Dock1 and Dock5 are expressed in podocytes, their functions are not essential for the development of the glomerular filtration barrier. Furthermore, mice lacking Dock1 were not protected from LPS-induced podocyte effacement. Our data suggest that Dock1 and Dock5 are not the important exchange factors regulating Rac activity during the establishment and maintenance of the glomerular barrier. PMID:24365888

Open-Label, Randomized Study of Transition From Tacrolimus to Sirolimus Immunosuppression in Renal Allograft Recipients

PubMed Central

Tedesco-Silva, Helio; Peddi, V. Ram; Sánchez-Fructuoso, Ana; Marder, Brad A.; Russ, Graeme R.; Diekmann, Fritz; Flynn, Alison; Hahn, Carolyn M.; Li, Huihua; Tortorici, Michael A.; Schulman, Seth L.

2016-01-01

Background Calcineurin inhibitor–associated nephrotoxicity and other adverse events have prompted efforts to minimize/eliminate calcineurin inhibitor use in kidney transplant recipients. Methods This open-label, randomized, multinational study evaluated the effect of planned transition from tacrolimus to sirolimus on kidney function in renal allograft recipients. Patients received tacrolimus-based immunosuppression and then were randomized 3 to 5 months posttransplantation to transition to sirolimus or continue tacrolimus. The primary end point was percentage of patients with 5 mL/min per 1.73 m2 or greater improvement in estimated glomerular filtration rate from randomization to month 24. Results The on-therapy population included 195 patients (sirolimus, 86; tacrolimus, 109). No between-group difference was noted in percentage of patients with 5 mL/min per 1.73 m2 or greater estimated glomerular filtration rate improvement (sirolimus, 34%; tacrolimus, 42%; P = 0.239) at month 24. Sirolimus patients had higher rates of biopsy-confirmed acute rejection (8% vs 2%; P = 0.02), treatment discontinuation attributed to adverse events (21% vs 3%; P < 0.001), and lower rates of squamous cell carcinoma of the skin (0% vs 5%; P = 0.012). Conclusions Our findings suggest that renal function improvement at 24 months is similar for patients with early conversion to sirolimus after kidney transplantation versus those remaining on tacrolimus. PMID:27500260

Association between serum bilirubin levels and decline in estimated glomerular filtration rate among patients with type 2 diabetes.

PubMed

Wang, Jing; Li, Yaru; Han, Xu; Hu, Hua; Wang, Fei; Yu, Caizheng; Li, Xiulou; Yang, Kun; Yuan, Jing; Yao, Ping; Miao, Xiaoping; Wei, Sheng; Wang, Youjie; Chen, Weihong; Liang, Yuan; Zhang, Xiaomin; Guo, Huan; Pan, An; Yang, Handong; Wu, Tangchun; He, Meian

2016-01-01

Studies indicate that elevated serum total bilirubin (TBil) levels are associated with lower risk of diabetic kidney disease (DKD). Few studies examined the associations of direct bilirubin (DBil) and indirect bilirubin (IBil) with the development of DKD. Type 2 diabetes patients (n=2,958) with estimated glomerular filtration (eGFR)≥60mlmin(-1) 1.73m(-2) from the Dongfeng-Tongji cohort were selected and followed up for 5years. Development of DKD was defined as decline in eGFR≥30% during follow-up. Generalize linear model was used to assess the associations of bilirubin levels with DKD development. Compared with those in the first tertile of serum TBil, the relative risks (RRs) and 95% confidence intervals (CIs) of incident eGFR decline for tertile 2 to 3 were 0.83 (0.64-1.09) and 0.74 (0.56-0.98), Ptrend=0.04. The counterpart RRs (95% CIs) in IBil were 0.74 (0.57-0.97) and 0.75 (0.57-0.98), Ptrend=0.04. No significant associations were observed in DBil. Moreover, TBil and IBil interacted with smoking, the bilirubin-DKD associations were evident in ever smokers. Our findings suggest that elevation of serum TBil or IBil levels are independent protective factors for development of DKD, particularly in smokers. Copyright © 2016 Elsevier Inc. All rights reserved.

Clinical observation of patients with Fabry disease after switching from agalsidase beta (Fabrazyme) to agalsidase alfa (Replagal).

PubMed

Tsuboi, Kazuya; Yamamoto, Hiroshi

2012-09-01

Fabry disease is a rare, X-linked, inherited lysosomal storage disorder that can be treated with the enzymes agalsidase alfa (Replagal) and agalsidase beta (Fabrazyme). Currently, there is a global shortage of agalsidase beta, and this has increased global demand for agalsidase alfa. We assess the feasibility of switching patients on agalsidase beta treatment to agalsidase alfa instead. This analysis is part of an ongoing observational study involving 11 patients with Fabry disease in whom the treatment was switched from agalsidase beta (1 mg/kg every other week) to agalsidase alfa (0.2 mg/kg every other week). Data were collected for a minimum of 36 months: 24 months before and 12 months after the switch. Serial data were evaluated with respect to renal function, cardiac mass, pain, quality of life, and tolerability/safety. Indexes of renal function (estimated glomerular filtration rate) and cardiac mass (left-ventricular mass index), pain (Brief Pain Inventory), and quality of life (EuroQoL-Dimensions) clearly showed that, in patients switched to agalsidase alfa, Fabry disease stabilized during the 12 months of follow-up. Despite the limitations of this preliminary observational study, it was found that all the patients maintained disease stability when treated with agalsidase alfa, as evidenced by estimated glomerular filtration rate, left-ventricular mass index, pain scores, and quality-of-life indexes, throughout 12 months of follow-up.

Clinical observation of patients with Fabry disease after switching from agalsidase beta (Fabrazyme) to agalsidase alfa (Replagal).

PubMed

Tsuboi, Kazuya; Yamamoto, Hiroshi

2012-09-01

Fabry disease is a rare, X-linked, inherited lysosomal storage disorder that can be treated with the enzymes agalsidasealfa (Replagal) and agalsidase beta (Fabrazyme). Currently, there is a global shortage of agalsidase beta, and this has increased global demand for agalsidase alfa. We assess the feasibility of switching patients on agalsidase beta treatment to agalsidase alfa instead. This analysis is part of an ongoing observational study involving 11 patients with Fabry disease in whom the treatment was switched from agalsidase beta (1 mg/kg every other week) to agalsidase alfa (0.2 mg/kg every other week). Data were collected for a minimum of 36 months: 24 months before and 12 months after the switch. Serial data were evaluated with respect to renal function, cardiac mass, pain, quality of life, and tolerability/safety. Indexes of renal function (estimated glomerular filtration rate) and cardiac mass (left-ventricular mass index), pain (Brief Pain Inventory), and quality of life (EuroQoL-Dimensions) clearly showed that, in patients switched to agalsidase alfa, Fabry disease stabilized during the 12 months of follow-up. Despite the limitations of this preliminary observational study, it was found that all the patients maintained disease stability when treated with agalsidase alfa, as evidenced by estimated glomerular filtration rate, left-ventricular mass index,pain scores, and quality-of-life indexes, throughout 12 months of follow-up.

Kidney and bladder outcomes in children with hemorrhagic cystitis and BK virus infection after allogeneic hematopoietic stem cell transplantation.

PubMed

Oshrine, Benjamin; Bunin, Nancy; Li, Yimei; Furth, Susan; Laskin, Benjamin L

2013-12-01

BK virus (BKV) infection is associated with hemorrhagic cystitis (HC) in hematopoietic stem cell transplantation (HSCT) recipients and nephropathy after kidney transplantation. We assessed the association between BKV and kidney and bladder complications in children developing HC by retrospectively reviewing 221 consecutive pediatric allogeneic HSCT recipients at the Children's Hospital of Philadelphia from 2005 to 2011. We included all patients with BKV PCR testing performed for clinical indication from day 0 until 1 year post-HSCT (N = 68). We assessed the association of any BKV infection (urine and/or blood) or peak BK viremia ≥ 10,000 copies/mL (high viremia) with severe HC (defined as grade IV-bladder catheterization or surgical intervention); the need for dialysis; serum creatinine-estimated glomerular filtration rate at the time of BKV testing, day 100, and day 365; and death. Children with high viremia more likely developed severe HC compared with those with peak viremia < 10,000 copies/mL (21% versus 2%; P = .02). BKV infection of the blood or urine was not associated with the need for dialysis, change in estimated glomerular filtration rate, or mortality. BKV infection is common after pediatric allogeneic HSCT, and plasma testing in those with HC may predict patients who will develop severe bladder injury. Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Estimated Glomerular Filtration Rate; Laboratory Implementation and Current Global Status.

PubMed

Miller, W Greg; Jones, Graham R D

2018-01-01

In 2002, the Kidney Disease Outcomes Quality Initiative guidelines for identifying and treating CKD recommended that clinical laboratories report estimated glomerular filtration rate (eGFR) with every creatinine result to assist clinical practitioners to identify people with early-stage CKD. At that time, the original Modification of Diet in Renal Disease (MDRD) Study equation based on serum creatinine measurements was recommended for calculating eGFR. Because the MDRD Study equation was developed using a nonstandardized creatinine method, a Laboratory Working Group of the National Kidney Disease Education program was formed and implemented standardized calibration traceability for all creatinine methods from global manufacturers by approximately 2010. A modified MDRD Study equation for use with standardized creatinine was developed. The Chronic Kidney Disease Epidemiology Collaboration developed a new equation in 2009 that was more accurate than the MDRD Study equation at values above 60 mL/min/1.73 m 2 . As of 2017, reporting eGFR with creatinine is almost universal in many countries. A reference system for cystatin C became available in 2010, and manufacturers are in the process to standardize cystatin C assays. Equations for eGFR based on standardized cystatin C alone and with creatinine are now available from the Chronic Kidney Disease Epidemiology Collaboration and other groups. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Comparison of glomerular filtration rate determined by use of single-slice dynamic computed tomography and scintigraphy in cats.

PubMed

Schmidt, David M; Scrivani, Peter V; Dykes, Nathan L; Goldstein, Richard M; Erb, Hollis N; Reeves, Anthony P

2012-04-01

To compare estimation of glomerular filtration rate determined via conventional methods (ie, scintigraphy and plasma clearance of technetium Tc 99m pentetate) and dynamic single-slice computed tomography (CT). 8 healthy adult cats. Scintigraphy, plasma clearance testing, and dynamic CT were performed on each cat on the same day; order of examinations was randomized. Separate observers performed GFR calculations for scintigraphy, plasma clearance testing, or dynamic CT. Methods were compared via Bland-Altman plots and considered interchangeable and acceptable when the 95% limits of agreement (mean difference between methods ± 1.96 SD of the differences) were ≤ 0.7 mL/min/kg. Global GFR differed < 0.7 mL/min/kg in 5 of 8 cats when comparing plasma clearance testing and dynamic CT; the limits of agreement were 1.4 and -1.7 mL/min/kg. The mean ± SD difference was -0.2 ± 0.8 mL/min/kg, and the maximum difference was 1.6 mL/min/kg. The mean ± SD difference (absolute value) for percentage filtration by individual kidneys was 2.4 ± 10.5% when comparing scintigraphy and dynamic CT; the maximum difference was 20%, and the limits of agreement were 18% and 23% (absolute value). GFR estimation via dynamic CT exceeded the definition for acceptable clinical use, compared with results for conventional methods, which was likely attributable to sample size and preventable technical complications. Because 5 of 8 cats had comparable values between methods, further investigation of dynamic CT in a larger sample population with a wide range of GFR values should be performed.

Effects of serum creatinine calibration on estimated renal function in african americans: the Jackson heart study.

PubMed

Wang, Wei; Young, Bessie A; Fülöp, Tibor; de Boer, Ian H; Boulware, L Ebony; Katz, Ronit; Correa, Adolfo; Griswold, Michael E

2015-05-01

The calibration to isotope dilution mass spectrometry-traceable creatinine is essential for valid use of the new Chronic Kidney Disease Epidemiology Collaboration equation to estimate the glomerular filtration rate. For 5,210 participants in the Jackson Heart Study (JHS), serum creatinine was measured with a multipoint enzymatic spectrophotometric assay at the baseline visit (2000-2004) and remeasured using the Roche enzymatic method, traceable to isotope dilution mass spectrometry in a subset of 206 subjects. The 200 eligible samples (6 were excluded, 1 for failure of the remeasurement and 5 for outliers) were divided into 3 disjoint sets-training, validation and test-to select a calibration model, estimate true errors and assess performance of the final calibration equation. The calibration equation was applied to serum creatinine measurements of 5,210 participants to estimate glomerular filtration rate and the prevalence of chronic kidney disease (CKD). The selected Deming regression model provided a slope of 0.968 (95% confidence interval [CI], 0.904-1.053) and intercept of -0.0248 (95% CI, -0.0862 to 0.0366) with R value of 0.9527. Calibrated serum creatinine showed high agreement with actual measurements when applying to the unused test set (concordance correlation coefficient 0.934, 95% CI, 0.894-0.960). The baseline prevalence of CKD in the JHS (2000-2004) was 6.30% using calibrated values compared with 8.29% using noncalibrated serum creatinine with the Chronic Kidney Disease Epidemiology Collaboration equation (P < 0.001). A Deming regression model was chosen to optimally calibrate baseline serum creatinine measurements in the JHS, and the calibrated values provide a lower CKD prevalence estimate.

Estimating equations for glomerular filtration rate in the era of creatinine standardization: a systematic review.

PubMed

Earley, Amy; Miskulin, Dana; Lamb, Edmund J; Levey, Andrew S; Uhlig, Katrin

2012-06-05

Clinical laboratories are increasingly reporting estimated glomerular filtration rate (GFR) by using serum creatinine assays traceable to a standard reference material. To review the performance of GFR estimating equations to inform the selection of a single equation by laboratories and the interpretation of estimated GFR by clinicians. A systematic search of MEDLINE, without language restriction, between 1999 and 21 October 2011. Cross-sectional studies in adults that compared the performance of 2 or more creatinine-based GFR estimating equations with a reference GFR measurement. Eligible equations were derived or reexpressed and validated by using creatinine measurements traceable to the standard reference material. Reviewers extracted data on study population characteristics, measured GFR, creatinine assay, and equation performance. Eligible studies compared the MDRD (Modification of Diet in Renal Disease) Study and CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations or modifications thereof. In 12 studies in North America, Europe, and Australia, the CKD-EPI equation performed better at higher GFRs (approximately >60 mL/min per 1.73 m(2)) and the MDRD Study equation performed better at lower GFRs. In 5 of 8 studies in Asia and Africa, the equations were modified to improve their performance by adding a coefficient derived in the local population or removing a coefficient. Methods of GFR measurement and study populations were heterogeneous. Neither the CKD-EPI nor the MDRD Study equation is optimal for all populations and GFR ranges. Using a single equation for reporting requires a tradeoff to optimize performance at either higher or lower GFR ranges. A general practice and public health perspective favors the CKD-EPI equation. Kidney Disease: Improving Global Outcomes.

Cuff-Based Oscillometric Central and Brachial Blood Pressures Obtained Through ABPM are Similarly Associated with Renal Organ Damage in Arterial Hypertension.

PubMed

Fernández-Llama, Patricia; Pareja, Júlia; Yun, Sergi; Vázquez, Susana; Oliveras, Anna; Armario, Pedro; Blanch, Pedro; Calero, Francesca; Sierra, Cristina; de la Sierra, Alejandro

2017-01-01

Central blood pressure (BP) has been suggested to be a better estimator of hypertension-associated risks. We aimed to evaluate the association of 24-hour central BP, in comparison with 24-hour peripheral BP, with the presence of renal organ damage in hypertensive patients. Brachial and central (calculated by an oscillometric system through brachial pulse wave analysis) office BP and ambulatory BP monitoring (ABPM) data and aortic pulse wave velocity (PWV) were measured in 208 hypertensive patients. Renal organ damage was evaluated by means of the albumin to creatinine ratio and the estimated glomerular filtration rate. Fifty-four patients (25.9%) were affected by renal organ damage, displaying either microalbuminuria (urinary albumin excretion ≥30 mg/g creatinine) or an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2. Compared to those without renal abnormalities, hypertensive patients with kidney damage had higher values of office brachial systolic BP (SBP) and pulse pressure (PP), and 24-h, daytime, and nighttime central and brachial SBP and PP. They also had a blunted nocturnal decrease in both central and brachial BP, and higher values of aortic PWV. After adjustment for age, gender, and antihypertensive treatment, only ABPM-derived BP estimates (both central and brachial) showed significant associations with the presence of renal damage. Odds ratios for central BP estimates were not significantly higher than those obtained for brachial BP. Compared with peripheral ABPM, cuff-based oscillometric central ABPM does not show a closer association with presence of renal organ damage in hypertensive patients. More studies, however, need to be done to better identify the role of central BP in clinical practice. © 2017 The Author(s). Published by S. Karger AG, Basel.

Measurement of glomerular filtration rate, renal plasma flow, and endogenous creatinine clearance in cheetahs (Acinonyx jubatus jubatus).

PubMed

Holder, Erin Hall; Citino, Scott B; Businga, Nancy; Cartier, Leslie; Brown, Scott A

2004-06-01

Glomerular filtration rate (GFR), renal plasma flow (RPF), and the endogenous creatinine clearance (CCr) rate were determined in 13 captive cheetahs, Acinonyx jubatus jubatus (seven females and six males, 1.5-7.5 yr of age, x = 5.02 yr), during general anesthesia with Telazol and isoflurane by measuring the urinary clearances of inulin, para-aminohipppuric acid, and endogenous creatinine, respectively. Methods to determine GFR, RPF, and endogenous CCr in captive cheetahs were evaluated, and the relationship between GFR and CCr for this species was determined. The GFR and the RPF were stable during the procedure, with mean values of 1.59+/-0.17 ml/min/kg body weight and 5.12+/-1.15 ml/min/kg body weight, respectively. Although the mean value for CCr (1.47+/-0.20 ml/min/kg body weight) was significantly less than the corresponding value for GFR, the mean difference (0.11+/-0.02 ml/min/kg weight) between the two measurements was slight, and the values were highly correlated (R2 = 0.928; P < 0.0001). The measurement of CCr in cheetahs should provide a reliable estimate of GFR, facilitating the early detection of renal disease in this species.

Cystatin C– and Creatinine-Based Estimated Glomerular Filtration Rate, Vascular Disease, and Mortality in Persons With Diabetes in the U.S.

PubMed Central

Tsai, Ching-Wei; Grams, Morgan E.; Inker, Lesley A.; Coresh, Josef; Selvin, Elizabeth

2014-01-01

OBJECTIVE Serum cystatin C is an alternative to serum creatinine for estimating glomerular filtration rate (GFR), since cystatin C is less influenced by age and muscle mass. Among persons with diabetes, we compared the performance of GFR estimated using cystatin C (eGFRcys) with that using creatinine (eGFRcr) for the identification of reduced kidney function and its association with diabetes complications. RESEARCH DESIGN AND METHODS We analyzed data from adult participants from the 1999–2002 National Health and Nutrition Examination Survey with available cystatin C (N = 4,457). Kidney function was dichotomized as preserved (eGFR ≥60 mL/min/1.73 m2) or reduced (eGFR <60 mL/min/1.73 m2) using the 2012 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) cystatin C and the 2009 CKD-EPI creatinine equations. RESULTS Among 778 persons with diabetes, the prevalence of reduced kidney function was 16.5% using eGFRcr and 22.0% using eGFRcys. More persons with diabetes were reclassified from preserved kidney function by eGFRcr to reduced kidney function by eGFRcys than persons without diabetes (odds ratio 3.1 [95% CI 1.9–4.9], P < 0.001). The associations between lower eGFR and higher prevalence of albuminuria, retinopathy, peripheral arterial disease, and coronary artery disease were robust regardless of filtration marker. Similarly, the risk of all-cause mortality increased with lower eGFRcr and eGFRcys. Only lower eGFRcys was significantly associated with cardiovascular mortality. CONCLUSIONS More persons with diabetes had reduced kidney function by eGFRcys than by eGFRcr, and lower eGFRcys was strongly associated with diabetes complications. Whether eGFRcys is superior to eGFRcr in approximating true kidney function in a diabetic population requires additional study. PMID:24271191

Office and 24-hour heart rate and target organ damage in hypertensive patients

PubMed Central

2012-01-01

Background We investigated the association between heart rate and its variability with the parameters that assess vascular, renal and cardiac target organ damage. Methods A cross-sectional study was performed including a consecutive sample of 360 hypertensive patients without heart rate lowering drugs (aged 56 ± 11 years, 64.2% male). Heart rate (HR) and its standard deviation (HRV) in clinical and 24-hour ambulatory monitoring were evaluated. Renal damage was assessed by glomerular filtration rate and albumin/creatinine ratio; vascular damage by carotid intima-media thickness and ankle/brachial index; and cardiac damage by the Cornell voltage-duration product and left ventricular mass index. Results There was a positive correlation between ambulatory, but not clinical, heart rate and its standard deviation with glomerular filtration rate, and a negative correlation with carotid intima-media thickness, and night/day ratio of systolic and diastolic blood pressure. There was no correlation with albumin/creatinine ratio, ankle/brachial index, Cornell voltage-duration product or left ventricular mass index. In the multiple linear regression analysis, after adjusting for age, the association of glomerular filtration rate and intima-media thickness with ambulatory heart rate and its standard deviation was lost. According to the logistic regression analysis, the predictors of any target organ damage were age (OR = 1.034 and 1.033) and night/day systolic blood pressure ratio (OR = 1.425 and 1.512). Neither 24 HR nor 24 HRV reached statistical significance. Conclusions High ambulatory heart rate and its variability, but not clinical HR, are associated with decreased carotid intima-media thickness and a higher glomerular filtration rate, although this is lost after adjusting for age. Trial Registration ClinicalTrials.gov: NCT01325064 PMID:22439900

Prolonged Baroreflex Activation Abolishes Salt-Induced Hypertension After Reductions in Kidney Mass.

PubMed

Hildebrandt, Drew A; Irwin, Eric D; Lohmeier, Thomas E

2016-12-01

Chronic electric activation of the carotid baroreflex produces sustained reductions in sympathetic activity and arterial pressure and is currently being evaluated for therapy in patients with resistant hypertension. However, patients with significant impairment of renal function have been largely excluded from clinical trials. Thus, there is little information on blood pressure and renal responses to baroreflex activation in subjects with advanced chronic kidney disease, which is common in resistant hypertension. Changes in arterial pressure and glomerular filtration rate were determined in 5 dogs after combined unilateral nephrectomy and surgical excision of the poles of the remaining kidney to produce ≈70% reduction in renal mass. After control measurements, sodium intake was increased from ≈45 to 450 mol/d. While maintained on high salt, animals experienced increases in mean arterial pressure from 102±4 to 121±6 mm Hg and glomerular filtration rate from 40±2 to 45±2 mL/min. During 7 days of baroreflex activation, the hypertension induced by high salt was abolished (103±6 mm Hg) along with striking suppression of plasma norepinephrine concentration from 139±21 to 81±9 pg/mL, but despite pronounced blood pressure lowering, there were no significant changes in glomerular filtration rate (43±2 mL/min). All variables returned to prestimulation values during a recovery period. These findings indicate that after appreciable nephron loss, chronic suppression of central sympathetic outflow by baroreflex activation abolishes hypertension induced by high salt intake. The sustained antihypertensive effects of baroreflex activation occur without significantly compromising glomerular filtration rate in remnant nephrons. © 2016 American Heart Association, Inc.

Evaluation of Gentian cystatin C reagent on Abbott Ci8200 and calculation of glomerular filtration rate expressed in mL/min/1.73 m(2) from the cystatin C values in mg/L.

PubMed

Flodin, M; Jonsson, A-S; Hansson, L-O; Danielsson, L-A; Larsson, A

2007-01-01

Estimation of the glomerular filtration rate (GFR) is essential when evaluating patients with kidney disease and treating patients with drugs eliminated from the circulation by the kidneys. Cystatin C has been shown in several studies to be superior to creatinine in the estimation of GFR. At our hospitals, there is an increasing demand for cystatin C and at present we perform approximately 1500 cystatin C analyses a month. We thus need the assay available 24 h/day and to have it on our routine chemistry instrument to minimize handling time per test and time to reported test results. We have evaluated a new cystatin C immunoassay from Gentian (Gentian, Moss, Norway) on Architect ci8200 (Abbott Laboratories, Abbott Park, Ill., USA). A prerequisite at our hospital is that cystatin C results are reported as a calculated GFR in mL/min/1.73 m(2), so we also made a comparison with iohexol clearance. The Gentian cystatin C assay showed good agreement with the corresponding assay from Dade Behring (Deerfield, Ill., USA) and good inter-laboratory concordance. The assay has very low total imprecision, good linearity and strong correlation with iohexol clearance (R (2) = 0.956). The equation for the correlation curve is: y = 79.901x(-1.4389). There was low inter-laboratory variation between the three laboratories involved in the cystatin C evaluation, and thus all three laboratories can use the same equation for calculating the estimated GFR.

Enzymatic creatinine assays allow estimation of glomerular filtration rate in stages 1 and 2 chronic kidney disease using CKD-EPI equation.

PubMed

Kuster, Nils; Cristol, Jean-Paul; Cavalier, Etienne; Bargnoux, Anne-Sophie; Halimi, Jean-Michel; Froissart, Marc; Piéroni, Laurence; Delanaye, Pierre

2014-01-20

The National Kidney Disease Education Program group demonstrated that MDRD equation is sensitive to creatinine measurement error, particularly at higher glomerular filtration rates. Thus, MDRD-based eGFR above 60 mL/min/1.73 m² should not be reported numerically. However, little is known about the impact of analytical error on CKD-EPI-based estimates. This study aimed at assessing the impact of analytical characteristics (bias and imprecision) of 12 enzymatic and 4 compensated Jaffe previously characterized creatinine assays on MDRD and CKD-EPI eGFR. In a simulation study, the impact of analytical error was assessed on a hospital population of 24084 patients. Ability using each assay to correctly classify patients according to chronic kidney disease (CKD) stages was evaluated. For eGFR between 60 and 90 mL/min/1.73 m², both equations were sensitive to analytical error. Compensated Jaffe assays displayed high bias in this range and led to poorer sensitivity/specificity for classification according to CKD stages than enzymatic assays. As compared to MDRD equation, CKD-EPI equation decreases impact of analytical error in creatinine measurement above 90 mL/min/1.73 m². Compensated Jaffe creatinine assays lead to important errors in eGFR and should be avoided. Accurate enzymatic assays allow estimation of eGFR until 90 mL/min/1.73 m² with MDRD and 120 mL/min/1.73 m² with CKD-EPI equation. Copyright © 2013 Elsevier B.V. All rights reserved.

Repeated serum creatinine measurement in primary care: Not all patients have chronic renal failure.

PubMed

Gentille Lorente, Delicia; Gentille Lorente, Jorge; Salvadó Usach, Teresa

2015-01-01

To assess the prevalence of kidney failure in patients from a primary care centre in a basic healthcare district with laboratory availability allowing serum creatinine measurements. An observational descriptive cross-sectional study. A basic healthcare district serving 23,807 people aged ≥ 18 years. Prevalence of kidney failure among 17,240 patients having at least one laboratory measurement available was 8.5% (mean age 77.6 ± 12.05 years). In 33.2% of such patients an occult kidney failure was found (98.8% were women). Prevalence of chronic kidney failure among 10,011 patients having at least 2 laboratory measurements available (≥ 3 months apart) was 5.5% with mean age being 80.1 ± 10.0 years (most severely affected patients were those aged 75 to 84); 59.7% were men and 76.3% of cases were in stage 3. An occult kidney failure was found in 5.3% of patients with women being 86.2% of them (a glomerular filtration rate<60 ml/min was estimated for plasma creatinine levels of 0.9 mg/dl or higher). Comparison of present findings to those previously reported demonstrates the need for further studies on the prevalence of overall (chronic and acute) kidney failure in Spain in order to estimate the real scope of the disease. Primary care physicians play a critical role in disease detection, therapy, control and recording (in medical records). MDRD equation is useful and practical to estimate glomerular filtration rate. Copyright © 2015 The Authors. Published by Elsevier España, S.L.U. All rights reserved.

Determinants of urinary albumin excretion reduction in essential hypertension: A long-term follow-up study.

PubMed

Pascual, Jose Maria; Rodilla, Enrique; Miralles, Amparo; Gonzalez, Carmen; Redon, Josep

2006-11-01

The objective of the present study was to assess factors related to long-term changes in urinary albumin excretion (UAE) of nondiabetic microalbuminuric (n = 252) or proteinuric hypertensive individuals (n = 58) in a prospective follow-up. After enrollment, patients were placed on usual care including nonpharmacological treatment and/or treatment with an antihypertensive drug regime to achieve blood pressure < 135/85 mmHg. Periodic UAE measurements were performed until regression or significant reduction (defined when UAE dropped > 50% from the initial values, plus reduction of UAE to < 30 mg/24 h for microalbuminuric patients and < 300 mg/24 h for proteinuric patients). Among the microalbuminuric patients, 113 (44.8%) significantly reduced UAE after a mean follow-up of 18 months (range 12-69 months), 20.3/100 patients per year. Among the proteinuric patients, 29 (50%) significantly reduced UAE after a mean follow-up of 25 months (range 12-51 months), 20.2/100 patients per year. The baseline glomerular filtration rate, diastolic blood pressure and fasting glucose during follow-up were independent factors related to the regression or significant reduction in a Cox proportional hazard model. Regression of UAE was independently related to initial estimated glomerular filtration rate < or = 60 ml/min per 1.73 m (hazard ratio, 0.57; 95% confidence interval, 0.38-0.86; P = 0.001) and DBP > or = 90 mmHg achieved during the follow-up (hazard ratio, 0.57; 95% confidence interval, 0.38-0.86; P = 0.001), even when adjusted for age, gender, body mass index, fasting glucose, presence of treatment at the beginning of the study and treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers during the follow-up. The reduction of urinary albumin excretion was linked to the preserved glomerular filtration rate and to adequate blood pressure control.

24 h urinary free cortisol in large-scale epidemiological studies: short-term and long-term stability and sources of variability.

PubMed

Rosmalen, Judith G M; Kema, Ido P; Wüst, Stefan; van der Ley, Claude; Visser, Sipke T; Snieder, Harold; Bakker, Stephan J L

2014-09-01

Function of the hypothalamus-pituitary-adrenal (HPA) axis has been associated with several somatic and psychiatric health problems. The amount of free cortisol excreted in the urine during 24h (24-h UFC) has often been used as a proxy for HPA-axis function. Reference values for 24-h UFC and their stability in the short and long term, as well as sources of variability, are largely lacking. This study was performed in a general population cohort. Participants collected 24-h UFC on two consecutive days (T1), and repeated this collection approximately 2 years later (T2). Cortisol in urine was measured using LC-MS/MS. Height and weight were measured at the research facilities; glomerular filtration rate was estimated using creatinine clearance. Psychological distress (General Health Questionnaire), smoking, alcohol use and exercise were measured by means of questionnaires. 24-h UFC stability on a day-to-day basis was 0.69 (T1, N=1192) and 0.72 (T2, N=963) (both p<0.001). Long-term stability as indicated by correlation between 2-day averages of T1 and T2 was 0.60 (N=972, p<0.001). Multivariable linear regression analysis revealed that 24-h UFC was predicted by urine volume (standardized beta 0.282 (T1, N=1556) and 0.276 (T2, N=1244); both p<0.001) and glomerular filtration rate (standardized beta 0.137 (T1) and 0.179 (T2); both p<0.001), while also sex explained a small part (standardized beta for female sex -0.057 (T1) and -0.080 (T2); both p<0.05). 24-h UFC is moderately stable both in the short and the long term. The effects of urine volume and glomerular filtration rate on 24-h UFC are much stronger than those of sex. Copyright © 2014 Elsevier Ltd. All rights reserved.

Patients with type 2 diabetes having higher glomerular filtration rate showed rapid renal function decline followed by impaired glomerular filtration rate: Japan Diabetes Complications Study.

PubMed

Moriya, Tatsumi; Tanaka, Shiro; Sone, Hirohito; Ishibashi, Shun; Matsunaga, Satoshi; Ohashi, Yasuo; Akanuma, Yasuo; Haneda, Masakazu; Katayama, Shigehiro

2017-02-01

The Japan Diabetes Complications Study (JDCS), a nation-wide, multicenter, prospective study of patients with type 2 diabetes, reported that hemoglobin A 1c (HbA 1c ), systolic blood pressure, and smoking were risk factors for the onset of macroalbuminuria. This study explored the risk factors for glomerular filtration rate (GFR) decline in the JDCS patients. We examined the 1407 JDCS patients (667 women, mean age 59years, 974 normoalbuminuria, 433 microalbuminuria) whose urinary albumin-to-creatinine ratio (UACR) and estimated GFR (eGFR) were determined at baseline with an 8-year follow-up. We divided all the patients into four groups according to baseline eGFR: G1 (120≤eGFR), G2 (90≤eGFR<120), G3 (60≤eGFR<90), G4 (eGFR<60). The eGFRs in groups G1 and G2 decreased at follow-up compared to those at the baseline. The risk of annual eGFR decline rate≥3ml/min/1.73m 2 (rapid decliners) increased as the baseline eGFR increased. Advanced age, high HbA 1c , and UACR, or diabetic retinopathy at baseline were risk factors for the rapid decliners. Especially the G1 group had a significant risk for the rapid decliners. The frequency of the patients with GFR<60ml/min/1.73m 2 at the follow-up amounted to 31.1% in the rapid decliners, which was higher than 12% in the non-rapid decliners. In normo- and microalbuminuric patients with type 2 diabetes, extra careful attention should be paid to patients with eGFR ≥120ml/min/1.73m 2 to detect cases with rapidly decreased GFR under the normal range. Copyright © 2016 Elsevier Inc. All rights reserved.

Improving precision of glomerular filtration rate estimating model by ensemble learning.

PubMed

Liu, Xun; Li, Ningshan; Lv, Linsheng; Fu, Yongmei; Cheng, Cailian; Wang, Caixia; Ye, Yuqiu; Li, Shaomin; Lou, Tanqi

2017-11-09

Accurate assessment of kidney function is clinically important, but estimates of glomerular filtration rate (GFR) by regression are imprecise. We hypothesized that ensemble learning could improve precision. A total of 1419 participants were enrolled, with 1002 in the development dataset and 417 in the external validation dataset. GFR was independently estimated from age, sex and serum creatinine using an artificial neural network (ANN), support vector machine (SVM), regression, and ensemble learning. GFR was measured by 99mTc-DTPA renal dynamic imaging calibrated with dual plasma sample 99mTc-DTPA GFR. Mean measured GFRs were 70.0 ml/min/1.73 m 2 in the developmental and 53.4 ml/min/1.73 m 2 in the external validation cohorts. In the external validation cohort, precision was better in the ensemble model of the ANN, SVM and regression equation (IQR = 13.5 ml/min/1.73 m 2 ) than in the new regression model (IQR = 14.0 ml/min/1.73 m 2 , P < 0.001). The precision of ensemble learning was the best of the three models, but the models had similar bias and accuracy. The median difference ranged from 2.3 to 3.7 ml/min/1.73 m 2 , 30% accuracy ranged from 73.1 to 76.0%, and P was > 0.05 for all comparisons of the new regression equation and the other new models. An ensemble learning model including three variables, the average ANN, SVM, and regression equation values, was more precise than the new regression model. A more complex ensemble learning strategy may further improve GFR estimates.

Glomerular hyperfiltration and metabolic syndrome: results from the FIrenze-BAgno A Ripoli (FIBAR) Study.

PubMed

Monami, Matteo; Pala, Laura; Bardini, Gianluca; Francesconi, Paolo; Cresci, Barbara; Marchionni, Niccolò; Rotella, Carlo Maria; Mannucci, Edoardo

2009-09-01

Metabolic syndrome (MS) has been associated with microalbuminuria and kidney disease. In the present cohort study, different methods for the estimation of glomerular filtration rate (GFR) on the basis of serum creatinine were compared with respect to their association with MS and their predictive value for incident diabetes mellitus. The present analysis was performed on the cohort of subjects enrolled in the FIBAR study, a screening program for diabetes. GFR was estimated (eGFR) using three different methods: Cockroft-Gault (CG) formula, using actual body weight (CAW), CG formula using ideal body weight (CIW), and Modification of Diet in Renal Disease formula (M). The study was performed on 2,694 nondiabetic subjects, without history of renal insufficiency or serum creatinine at baseline >1.5 mg/dl. Mean follow-up was 27.8 +/- 11.5 months. Elevated eGFR, estimated with different methods, was associated with increased prevalence of most components of MS; however, an association between elevated clearance and MS was observed only when using CAW, which overestimates filtration in obese subjects. During follow-up, 40 new cases of diabetes were recorded (0.5/100 patient*years). After adjusting for age and sex, the HR (with 95% confidence intervals) for diabetes for patients in the highest quintile of eGFR was 1.14 [0.44-2.99], 0.89 [0.31-2.51], and 1.01 [0.42-2.41] for formula CAW, CIW, and M, respectively (all p > 0.7). Elevated eGFR, estimated through methods which do not produce a systematic overestimate in obese subjects, is not associated with the diagnosis of MS, and does not predict diabetes.

Prevalence of augmented renal clearance and performance of glomerular filtration estimates in Indigenous Australian patients requiring intensive care admission.

PubMed

Tsai, D; Udy, A A; Stewart, P C; Gourley, S; Morick, N M; Lipman, J; Roberts, J A

2018-01-01

Augmented renal clearance (ARC) refers to the enhanced renal excretion of circulating solute commonly demonstrated in numerous critically ill subgroups. This study aimed to describe the prevalence of ARC in critically ill Indigenous Australian patients and explore the accuracy of commonly employed mathematical estimates of glomerular filtration. We completed a single-centre, prospective, observational study in the intensive care unit (ICU), Alice Springs Hospital, Central Australia. Participants were critically ill adult Indigenous and non-Indigenous Australian patients with a urinary catheter in situ. Exclusion criteria were anuria, pregnancy or the requirement for renal replacement therapy. Daily eight-hour measured creatinine clearances (CrCL_m) were collected throughout the ICU stay. ARC was defined by a CrCL_m ≥130 ml/min/1.73 m². The Cockcroft-Gault and Chronic Kidney Disease Epidemiology Collaboration equations were also used to calculate mathematical estimates for comparison. In total, 131 patients were recruited (97 Indigenous, 34 non-Indigenous) and 445 samples were collected. The median (range) CrCL_m was 93.0 (5.14 to 205.2) and 90.4 (18.7 to 206.8) ml/min/1.73 m² in Indigenous and non-Indigenous patients, respectively. Thirty-one of 97 (32%) Indigenous patients manifested ARC, compared to 7 of 34 (21%) non-Indigenous patients (P=0.21). Younger age, major surgery, higher baseline renal function and an absence of diabetes were all associated with ARC. Both mathematical estimates manifest limited accuracy. ARC was prevalent in critically ill Indigenous patients, which places them at significant risk of underdosing with renally excreted drugs. CrCL_m should be obtained wherever possible to ensure accurate dosing.

Assessing Glomerular Filtration Rate in Hospitalized Patients: A Comparison Between CKD-EPI and Four Cystatin C-Based Equations

PubMed Central

de la Torre, Judith; Ramos, Natalia; Quiroz, Augusto; Garjau, Maria; Torres, Irina; Azancot, M. Antonia; López, Montserrat; Sobrado, Ana

2011-01-01

Summary Background and objectives A specific method is required for estimating glomerular filtration rate GFR in hospitalized patients. Our objective was to validate the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and four cystatin C (CysC)–based equations in this setting. Design, setting, participants, & measurements This was an epidemiologic, cross-sectional study in a random sample of hospitalized patients (n = 3114). We studied the accuracy of the CKD-EPI and four CysC-based equations—based on (1) CysC alone or (2) adjusted by gender; (3) age, gender, and race; and (4) age, gender, race, and creatinine, respectively—compared with GFR measured by iohexol clearance (mGFR). Clinical, biochemical, and nutritional data were also collected. Results The CysC equation 3 significantly overestimated the GFR (bias of 7.4 ml/min per 1.73 m2). Most of the error in creatinine-based equations was attributable to calculated muscle mass, which depended on patient's nutritional status. In patients without malnutrition or reduced body surface area, the CKD-EPI equation adequately estimated GFR. Equations based on CysC gave more precise mGFR estimates when malnutrition, extensive reduction of body surface area, or loss of muscle mass were present (biases of 1 and 1.3 ml/min per 1.73 m2 for equations 2 and 4, respectively, versus 5.9 ml/min per 1.73 m2 for CKD-EPI). Conclusions These results suggest that the use of equations based on CysC and gender, or CysC, age, gender, and race, is more appropriate in hospitalized patients to estimate GFR, since these equations are much less dependent on patient's nutritional status or muscle mass than the CKD-EPI equation. PMID:21852668

Estimating Glomerular Filtration Rate in Kidney Transplant Recipients: Comparing a Novel Equation With Commonly Used Equations in this Population

PubMed Central

Salvador, Cathrin L.; Hartmann, Anders; Åsberg, Anders; Bergan, Stein; Rowe, Alexander D.; Mørkrid, Lars

2017-01-01

Background Assessment of glomerular filtration rate (GFR) is important in kidney transplantation. The aim was to develop a kidney transplant specific equation for estimating GFR and evaluate against published equations commonly used for GFR estimation in these patients. Methods Adult kidney recipients (n = 594) were included, and blood samples were collected 10 weeks posttransplant. GFR was measured by 51Cr-ethylenediaminetetraacetic acid clearance. Patients were randomized into a reference group (n = 297) to generate a new equation and a test group (n = 297) for comparing it with 7 alternative equations. Results Two thirds of the test group were males. The median (2.5-97.5 percentile) age was 52 (23-75) years, cystatin C, 1.63 (1.00-3.04) mg/L; creatinine, 117 (63-220) μmol/L; and measured GFR, 51 (29-78) mL/min per 1.73 m2. We also performed external evaluation in 133 recipients without the use of trimethoprim, using iohexol clearance for measured GFR. The Modification of Diet in Renal Disease equation was the most accurate of the creatinine-equations. The new equation, estimated GFR (eGFR) = 991.15 × (1.120sex/([age0.097] × [cystatin C0.306] × [creatinine0.527]); where sex is denoted: 0, female; 1, male, demonstrating a better accuracy with a low bias as well as good precision compared with reference equations. Trimethoprim did not influence the performance of the new equation. Conclusions The new equation demonstrated superior accuracy, precision, and low bias. The Modification of Diet in Renal Disease equation was the most accurate of the creatinine-based equations. PMID:29536033

Physical Activity Is not Associated with Estimated Glomerular Filtration Rate among Young and Middle-Aged Adults: Results from the Population-Based Longitudinal Doetinchem Study

PubMed Central

Herber-Gast, Gerrie-Cor M.; Hulsegge, Gerben; Hartman, Linda; Verschuren, W. M. Monique; Stehouwer, Coen D. A.; Gansevoort, Ron T.; Bakker, Stephan J. L.; Spijkerman, Annemieke M. W.

2015-01-01

There is debate as to whether physical inactivity is associated with reduced kidney function. We studied the prospective association of (changes in) physical activity with estimated glomerular filtration rate (eGFR) in adult men and women. We included 3,935 participants aged 26 to 65 years from the Doetinchem Cohort study, examined every 5 years for 15 years. Physical activity was assessed at each round using the Cambridge Physical Activity Index. Using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation, GFR was estimated from routinely measured cystatin C concentrations, examining all available samples per participant in one assay run. We determined the association between 1) physical activity and eGFR and 2) 5-year changes in physical activity (becoming inactive, staying inactive, staying active, becoming active) and eGFR, using time-lagged generalized estimating equation analyses. At baseline, 3.6% of the participants were inactive, 18.5% moderately inactive, 26.0% moderately active, and 51.9% active. The mean (± SD) eGFR was 107.9 (± 14.5) mL/min per 1.73 m2. Neither physical activity nor 5-year changes in physical activity were associated with eGFR at the subsequent round. The multivariate adjusted βeGFR was 0.57 mL/min per 1.73 m2 (95% Confidence Interval (CI) -1.70, 0.56) for inactive compared to active participants. Studying changes in physical activity between rounds, the adjusted βeGFR was -1.10 mL/min per 1.73 m2 (95% CI -4.50, 2.30) for those who stayed inactive compared with participants who became active. Physical activity was not associated with eGFR in this population-based study of adults. PMID:26465150

Accuracy and reproducibility of a new contrast clearance method for the determination of glomerular filtration rate.

PubMed Central

O'Reilly, P H; Brooman, P J; Martin, P J; Pollard, A J; Farah, N B; Mason, G C

1986-01-01

A new method for determining the glomerular filtration rate was analysed prospectively. The method uses an x ray fluorescence technique to measure disappearance from the plasma of injected non-ionic iodinated contrast media. Eighty seven patients were studied. Fifty four had an intravenous dose of 100 ml iohexol (Omnipaque) and 33 had 50 ml iohexol. Clearances of chromium-51 labelled edetic acid (51Cr-EDTA) were measured simultaneously. In the patients given 100 ml iohexol there was excellent correlation with 51Cr-EDTA clearance (r = 0.90). The correlation using 50 ml iohexol was also good (r = 0.85). Correlation between creatinine clearance and clearance of 51Cr-EDTA in 33 patients was less satisfactory (r = 0.69). There were no adverse reactions to the contrast media. The equipment used for measuring contrast clearance was robust and simple to operate. Freezing plasma samples in 10 studies and re-examining them weekly for six weeks showed no significant variation in results; hence reproducibility was good. This new and accurate method for determining the glomerular filtration rate merits further study and might find a useful place in routine clinical practice. Images FIG 1 PMID:3089467

Renal function, renal volume, and blood pressure in infants with antecedent of antenatal steroids.

PubMed

Carballo-Magdaleno, Deyanira; Guízar-Mendoza, Juan M; Amador-Licona, Norma; Domínguez-Domínguez, Víctor

2011-10-01

Steroids have been used for more than 20 years in preterm infants to induce pulmonary maturity; however, some long-term effects have been reported, such as insulin resistance and elevation of blood pressure. The aim of our study was to compare renal volume, renal function, and blood pressure in infants between 12-36 months of age with and without antecedent of antenatal steroid treatment. This was a cross-sectional study comprised of three groups of infants (n = 30, respectively): preterm infants with and without antecedent of receiving antenatal steroids, respectively, and full-term infants. Blood pressure, renal volume, glomerular filtration rate, and tubular function were measured. Blood pressure and cystatin C levels and glomerular filtration rate were higher in both groups of preterm infants than in the control group (p < 0.01). However, no difference in any of the tested variables between the steroid and non-steroid group of preterm infants. Renal volume was similar in preterm and control infants. Based on these results, we conclude that prematurity independent of antenatal steroid use is associated with higher cystatin C and blood pressure levels and a higher glomerular filtration rate in infants between 12-36 months of age.

Optimization of protein and peptide drugs based on the mechanisms of kidney clearance.

PubMed

Huang, Jiaguo; Wu, Huizi

2018-05-30

Development of proteins and peptides into drugs has been considered as a promising strategy to target certain diseases. However, only few proteins and peptides has been approved as new drugs into the market each year. One major problem is that proteins and peptides often exhibit short plasma half-life times, which limits the application for their clinical use. In most cases a short half-life time is not effective to deliver sufficient amount of drugs to the target organs and tissues, which is generally caused by fast renal clearance and low plasma stability due to proteolytic degradation during systemic circulation, because the most common clearance pathway of small proteins and peptides is through glomerular filtration by the kidneys. In this review, enzymatic degradation of proteins and peptides were discussed. Furthermore, several approaches to lengthen the half-life of peptides and proteins drugs based on the unique structures of glomerular capillary wall and the mechanisms of glomerular filtration were summarized, such as increasing the size and hydrodynamic diameter; increasing the negative charge to delay the filtration; increasing plasma protein binding to decrease plasma clearance. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Relationship between dietary protein intake and the changes in creatinine clearance and glomerular cross-sectional area in patients with IgA nephropathy.

PubMed

Wada, Toshikazu; Nakao, Toshiyuki; Matsumoto, Hiroshi; Okada, Tomonari; Nagaoka, Yume; Iwasawa, Hideaki; Gondo, Asako; Niwata, Ami; Kanno, Yoshihiko

2015-08-01

Dietary protein intake (PI) induces glomerular hyperfiltration and reduced dietary PI can be effective in preserving kidney function. However, there is limited information regarding the relationship between dietary PI and glomerular histological changes in chronic kidney disease. We investigated the relationship between changes in dietary PI and both the changes in creatinine clearance and glomerular histomorphometry in adult patients with IgA nephropathy (IgAN). A total of 24 consecutive adult patients with biopsy-confirmed IgAN were enrolled and glomerular histomorphometric variables and clinical variables were investigated. The main clinical variables were differences in creatinine clearance (Ccr) (dCcr) and in PI (dPI) which were calculated by subtracting PI and Ccr values in patients on a controlled diet during hospitalization for kidney biopsy from the respective values in patients on daily diets as outpatients. These values of PI were estimated from urinary urea excretion measured by 24-h urine collection. The main renal histomorphometric variable was glomerular tuft area (GTA) (μm(2)). dCcr positively correlated with dPI (r = 0.726, P < 0.001). GTA correlated positively with dPI (r = 0.556, P = 0.013). Multiple regression analysis showed that dPI was independently associated with both dCcr and GTA. Additionally, GTA positively correlated with dietary PI as outpatients (r = 0.457, P = 0.043). Changes in dietary PI were associated with the changes in glomerular filtration rate. Furthermore, histomorphometric findings suggested that a greater dietary PI can affect the glomerular size at the time of the initial diagnostic biopsy for IgAN.

Cell biology of mesangial cells: the third cell that maintains the glomerular capillary.

PubMed

Kurihara, Hidetake; Sakai, Tatsuo

2017-03-01

The renal glomerulus consists of glomerular endothelial cells, podocytes, and mesangial cells, which cooperate with each other for glomerular filtration. We have produced monoclonal antibodies against glomerular cells in order to identify different types of glomerular cells. Among these antibodies, the E30 clone specifically recognizes the Thy1.1 molecule expressed on mesangial cells. An injection of this antibody into rats resulted in mesangial cell-specific injury within 15 min, and induced mesangial proliferative glomerulonephritis in a reproducible manner. We examined the role of mesangial cells in glomerular function using several experimental tools, including an E30-induced nephritis model, mesangial cell culture, and the deletion of specific genes. Herein, we describe the characterization of E30-induced nephritis, formation of the glomerular capillary network, mesangial matrix turnover, and intercellular signaling between glomerular cells. New molecules that are involved in a wide variety of mesangial cell functions are also introduced.

Metal accumulation and nephron heterogeneity in mercuric chloride-induced acute renal failure.

PubMed

Wilks, M F; Gregg, N J; Bach, P H

1994-01-01

The present study was designed to assess the effects of mercury on glomerular integrity during the early phase of acute renal failure. The silver amplification method showed distribution of mercury in midcortical and juxtamedullary glomeruli and on the brush border of the S2 segment of the proximal tubule 15 min after treatment. At 30 min, there was a decrease in glomerular staining and increased mercury in the proximal tubule. After 3 hr, mercury was no longer detectable in glomeruli but was widespread in the lumen of the proximal tubule. By 24 hr, mercury was prominent in all proximal tubular segments throughout the cortex. The presence of mercury in glomeruli was not related to hemodynamic changes, as there was no evidence for blood redistribution toward juxtamedullary glomeruli as assessed by the filling of the microvascular system with Monastral Blue B. The reduced activity of horseradish peroxidase (administered i.v. 90 sec and 10 min before sacrifice) in juxtamedullary glomeruli 30 min after mercury administration suggests a decreased uptake of horseradish peroxidase or an increased glomerular protein filtration. These data support glomerular filtration as the predominant excretory route for mercury, highlight the marked nephron heterogeneity in the distribution of this metal, and show that impairment of glomerular integrity occurs before necrosis of the proximal tubules and acute renal failure.

Prevalence of glomerular hyperfiltration and nephromegaly in normo- and microalbuminuric type 2 diabetic patients.

PubMed

Gragnoli, G; Signorini, A M; Tanganelli, I; Fondelli, C; Borgogni, P; Borgogni, L; Vattimo, A; Ferrari, F; Guercia, M

1993-01-01

Glomerular hyperfiltration, correlated with nephromegaly, is a frequent finding in type 1 (insulin-dependent) diabetes. In type 2 (non-insulin-dependent) diabetes, very few studies have been performed, and the results have been inconclusive. Glomerular filtration rate (GFR) and kidney volume, using 99mTc-DTPA scintigraphy and ultrasonography, respectively, were evaluated in 58 control subjects and 163 type 2 diabetic patients; 79 of whom were normoalbuminuric and 84 microalbuminuric. In the two groups of patients, these parameters did not differ significantly from those of controls, even when hypertensive subjects were excluded. Glomerular hyperfiltration was observed in 10 cases; all were normotensive (9.8%), of whom 7 were normoalbuminuric and 3 microalbuminuric. Nephromegaly was observed in 3 other normotensive microalbuminuric diabetic patients. Hypertensive subjects showed a lower GFR than normotensive patients and control subjects. Multivariate analysis showed a negative correlation between glomerular filtrate and systolic blood pressure (BP) in the overall population of patients and in normo- and microalbuminuric patients taken separately. It is concluded that the relationship between these variables forms a continuum in our type 2 diabetic patients; it may also be important in determining the low prevalence of hyperfiltration and nephromegaly found in our patients, who had BP levels higher than those of controls.

Comparison of CKD-EPI and MDRD to estimate baseline renal function in HIV-positive patients.

PubMed

Ibrahim, Fowzia; Hamzah, Lisa; Jones, Rachael; Nitsch, Dorothea; Sabin, Caroline; Post, Frank A

2012-06-01

Renal dysfunction is common in HIV-positive patients, and guidelines suggest regular monitoring of renal function with estimated glomerular filtration rate (eGFR) and urinalysis. It is unknown whether Chronic Kidney Disease Epidemiological Collaboration (CKD-EPI) or Modification of Diet in Renal Disease (MDRD) provide better estimates of glomerular filtration rate (GFR) in this population. We compared the CKD-EPI and MDRD equations to estimate GFR at baseline in 20,132 HIV-positive individuals in the UK CHIC cohort. Kappa statistics and Bland-Altman plots were used to assess agreement between the two estimates and Kaplan-Meier plots and Cox regression analysis to describe mortality patterns. At baseline, median eGFR was 100 (87, 112) (CKD-EPI) and 94 (83, 108) (MDRD) (mL/min/1.73 m(2)). Good overall agreement between CKD-EPI- and MDRD-defined eGFR bands was observed (Kappa = 0.71, 95% confidence interval: 0.70-0.72). Of the 367 patients with eGFR MDRD 30-59, 57 (15.5%) were categorized as eGFR 60-89 by CKD-EPI. After adjustment for covariates, eGFR <60 (CKD-EPI), eGFR <30 (MDRD) and eGFR ≥105 (both formulae) were significantly associated with an increased risk of death. Mortality in patients classified as having eGFR 60-89 by CKD-EPI and eGFR 30-59 by MDRD more closely resembled mortality of patients who had eGFR 60-89 by both formulae. MDRD and CKD-EPI equations showed a high degree of agreement in stratifying patients by baseline eGFR. CKD-EPI estimates of GFR <60 at baseline are more strongly associated with mortality than MDRD estimates of GFR <60, supporting the concept that MDRD may have overestimated the severity of renal impairment in these patients. Our findings support the use of CKD-EPI in HIV-positive individuals.

Clinical observation of patients with Fabry disease after switching from agalsidase beta (Fabrazyme) to agalsidase alfa (Replagal)

PubMed Central

Tsuboi, Kazuya; Yamamoto, Hiroshi

2012-01-01

Purpose: Fabry disease is a rare, X-linked, inherited lysosomal storage disorder that can be treated with the enzymes agalsidase alfa (Replagal) and agalsidase beta (Fabrazyme). Currently, there is a global shortage of agalsidase beta, and this has increased global demand for agalsidase alfa. We assess the feasibility of switching patients on agalsidase beta treatment to agalsidase alfa instead. Methods: This analysis is part of an ongoing observational study involving 11 patients with Fabry disease in whom the treatment was switched from agalsidase beta (1 mg/kg every other week) to agalsidase alfa (0.2 mg/kg every other week). Data were collected for a minimum of 36 months: 24 months before and 12 months after the switch. Serial data were evaluated with respect to renal function, cardiac mass, pain, quality of life, and tolerability/safety. Results: Indexes of renal function (estimated glomerular filtration rate) and cardiac mass (left-ventricular mass index), pain (Brief Pain Inventory), and quality of life (EuroQoL-Dimensions) clearly showed that, in patients switched to agalsidase alfa, Fabry disease stabilized during the 12 months of follow-up. Conclusion: Despite the limitations of this preliminary observational study, it was found that all the patients maintained disease stability when treated with agalsidase alfa, as evidenced by estimated glomerular filtration rate, left-ventricular mass index, pain scores, and quality-of-life indexes, throughout 12 months of follow-up. PMID:22498845

Clinician’s use of automated reports of estimated glomerular filtration rate: A qualitative study

PubMed Central

2012-01-01

Background There is a growing awareness in primary care of the importance of identifying patients with chronic kidney disease (CKD) so that they can receive appropriate clinical care; one method that has been widely embraced is the use of automated reporting of estimated glomerular filtration rate (eGFR) by clinical laboratories. We undertook a qualitative study to examine how clinicians use eGFR in clinical decision making, patient communication issues, barriers to use of eGFR, and suggestions to improve the clinical usefulness of eGFR reports. Methods Our study used qualitative methods with structured interviews among primary care clinicians including both physicians and allied health providers, recruited from Kaiser Permanente Northwest, a non-profit health maintenance organization. Results We found that clinicians generally held favorable views toward eGFR reporting but did not use eGFR to replace serum creatinine in their clinical decision-making. Clinicians used eGFR as a tool to help identify CKD, educate patients about their kidney function and make treatment decisions. Barriers noted by several clinicians included a desire for greater education regarding care for patients with CKD and tools to facilitate discussion of eGFR findings with patients. Conclusions The manner in which clinicians use eGFRs appears to be more complex than previously understood, and our study illustrates some of the efforts that might be usefully undertaken (e.g. specific clinician education) when encouraging further promulgation of eGFR reporting and usage. PMID:23173944

QT dispersion increases with low glomerular filtration rate in patients with coronary artery disease

PubMed Central

Celik, Murat; Yuksel, UygarCagdas; Gokoglan, Yalcin; Bugan, Baris; Yalcinkaya, Emre; Unal, HilmiUmut; Celik, Turgay; Iyisoy, Atila; Kilic, Selim

2014-01-01

Objective: We aimed to evaluate the relationship between estimated glomerular filtration rate (eGFR) and QT dispersion (QTd) in patients with coronary artery disease (CAD). Methods: Sixty patients(mean age 62.72 ± 12.48 years) included 46 male, (mean age 60.89 ± 12.70 years)and 14 female (mean age 68.71± 9.86 years) were enrolled in this study. Patients were divided into 2 groups according to their eGFR using the 6 variable MDRD equation. Group 1 consisted of patients with estimated eGFR<60 ml/min/1.73m2 and Group 2 consisted of patients witheGFR ≥ 60 ml/min/1.73m2. Results: Baseline patient characteristics were homogeneous in both groups except for age, gender and smoking.Also, the extent of CAD was similar in both groups (p > 0.05) QTd values were found higher in group 1 than those of group 2 (57.23 ± 40.65 ms vs. 31.23 ± 14.47 ms, p = 0.002). After adjustment for age, gender and smoking using one-way ANCOVA test, statistically significant difference in QTd still existedbetween the groups (p=0.038). Conclusion:QTd tends to be higher in patients with poor renal function independent of severity of angiographical CAD. QTd may be a potentially useful non-invasive test in the management of patients with poor renal function, especially those with CAD. PMID:24772124

Periodontitis associated with chronic kidney disease among Mexican Americans.

PubMed

Ioannidou, Effie; Hall, Yoshio; Swede, Helen; Himmelfarb, Jonathan

2013-01-01

In comparison to non-Hispanic whites, a number of health-care disparities, including poor oral health, have been identified among Hispanics in general and Mexican Americans in particular. We hypothesized that Mexican Americans with chronic kidney disease (CKD) would have higher prevalence of chronic periodontitis compared with Mexican Americans with normal kidney function, and that the level of kidney function would be inversely related to the prevalence of periodontal disease. We examined this hypothesis using the National Health and Nutrition Examination Survey 1988-1994 (NHANES III) data set. We followed the American Academy of Periodontology/Center for Disease Control and Prevention case definition for periodontitis. Glomerular filtration rate was estimated using the CKD-Epidemiology equation for Hispanic populations. The classification to CKD stages was based on the National Kidney Foundation Kidney Disease Outcomes Quality Initiative. Periodontitis prevalence increased across the kidney function groups showing a statistically significant dose-response association (P<0.001). Mexican Americans with reduced kidney function were twofold more likely to have periodontitis compared with Mexican Americans with normal kidney function after adjusting for potential confounders such as smoking, diabetes, and socioeconomic status. Multivariate adjusted odds ratio for periodontitis significantly increased with 1, 5, and 10 mL/minute estimated glomerular filtration rate reduction from the mean. This is the first report, to the best our knowledge, that showed an increase of periodontitis prevalence with decreased kidney function in this population. © 2012 American Association of Public Health Dentistry.

Kidney transplantation after desensitization in sensitized patients: a Korean National Audit.

PubMed

Huh, Kyu Ha; Kim, Beom Seok; Yang, Jaeseok; Ahn, Jeongmyung; Kim, Myung-Gyu; Park, Jae Berm; Kim, Jong Man; Chung, Byung-Ha; Kim, Joong Kyung; Kong, Jin Min

2012-10-01

The number of end-stage renal disease (ESRD) patients with preformed antibodies waiting for a kidney transplant has been increasing lately. We conducted a nationwide study on the outcomes of kidney transplantation after desensitization in Korea. Six transplant centers have run desensitization programs. The patients who underwent living donor kidney transplantation after desensitization from 2002 to 2010 were retrospectively analyzed. A total of 86 cases were enrolled. Thirty-five of these were cases of re-transplantation (40.7 %). Indications of desensitization were positive complement-dependent cytotoxicity (CDC) cross-match responses (CDC(+), 36.0 %), positive flow-cytometric cross-match responses (FCX(+), 54.7 %), and positive donor-specific antibodies (DSA(+), 8.1 %). The desensitization protocols used pre-transplant plasmapheresis (95.3 %), intravenous immunoglobulin (62.8 %), and rituximab (67.4 %). Acute rejection occurred in 18 patients (20.9 %), graft failure occurred in 4 patients, and the 3-year graft survival rate was 93.8 %. The presence of DSA increased the acute rejection rate (P = 0.015) and decreased the 1-year post-transplant estimated glomerular filtration rate (P = 0.006). Although rejection-free survival rates did not differ significantly between the CDC(+) and FCX(+) groups, the 1-year estimated glomerular filtration rate was lower in the CDC(+) group (P = 0.010). Infectious and significant bleeding complications occurred in 15.5 % and 4.7 % of cases, respectively. Kidney transplantation after desensitization had good graft outcomes and tolerable complications in Korea, and therefore, this therapy can be recommended for sensitized ESRD patients.

A Simple Method to Detect Recovery of Glomerular Filtration Rate following Acute Kidney Injury

PubMed Central

Pickering, John W.

2014-01-01

In acute kidney injury (AKI), elevated plasma creatinine is diagnostic of an earlier loss of glomerular filtration rate (GFR) but not of the concomitant GFR. Only subsequent creatinine changes will inform if GFR had already recovered or not. We hypothesized that the creatinine excretion rate to production rate ratio would provide this information. A retrospective analysis of 482 critically ill patients from two intensive care units (ICU) is shown. Plasma creatinine was measured on ICU entry and 12 hours later. Four-hour creatinine excretion rates (E) were measured on entry. Creatinine production rates were estimated (eG). The ability of the ratio E/eG to predict a decrease in plasma creatinine concentration, identify recovered AKI (≥0.3 mg/dL decrease), and predict AKI (≥0.3 mg/dL increase) was assessed by the area under the receiver operator characteristic curves (AUC). There was a linear relationship between reduced creatinine concentration and E/eG (r 2 = 0.15; P < 0.0001). E/eG predicted a decrease in creatinine (AUC 0.70 (0.65 to 0.74)), identified recovered AKI (0.75 (0.67 to 0.84)), and predicted AKI (0.80 (0.73 to 0.86)). A ratio of the rates of creatinine excretion to estimated production much less than 1 indicated a concomitant GFR below baseline, whereas a ratio much more than 1 indicated a recovering or recovered GFR. PMID:24982893

The reproducibility and predictive value on outcome of renal biopsies from expanded criteria donors.

PubMed

Azancot, M Antonieta; Moreso, Francesc; Salcedo, Maite; Cantarell, Carme; Perello, Manel; Torres, Irina B; Montero, Angeles; Trilla, Enric; Sellarés, Joana; Morote, Joan; Seron, Daniel

2014-05-01

Reproducibility and predictive value on outcome are the main criteria to evaluate the utility of histological scores. Here we analyze the reproducibility of donor biopsy assessment by different on-call pathologists and the retrospective evaluation by a single renal pathologist blinded to clinical outcomes. We also evaluate the predictive value on graft outcome of both evaluations. A biopsy was performed in donors with any of the following: age≥55 years, hypertension, diabetes, creatinine>1.5 mg/dl, or stroke. Glomerulosclerosis, interstitial fibrosis, tubular atrophy, intimal thickening, and arteriolar hyalinosis evaluated according to the Banff criteria were added to obtain a chronic score. Biopsies were classified as mild (≥3), intermediate (4-5), or advanced (6-7) damage, and unacceptable (≥8) for transplantation of 127 kidneys biopsied. Weighted κ value between both readings was 0.41 (95% CI: 0.28-0.54). Evaluation of biopsies by the renal pathologist was significantly and independently associated with estimated 12-month glomerular filtration rate and a significant composite outcome variable, including death-censored graft survival and time to reach an estimated glomerular filtration rate<30 ml/min per 1.73 m2. Thus, there was no association between readings of on-call pathologists and outcome. The lack of association between histological scores obtained by the on-call pathologists and graft outcome suggests that a specific training on renal pathology is recommended to optimize the use of kidneys retrieved from expanded criteria donors.

Impact of estimated glomerular filtration rate on diabetic macular edema.

PubMed

Temkar, Shreyas; Karuppaiah, Nishanthini; Takkar, Brijesh; Bhowmik, Dipankar; Tripathi, Manjari; Ramakrishnan, Sivasubramanian; Sharma, Yog Raj; Vohra, Rajpal; Chawla, Rohan; Venkatesh, Pradeep

2018-06-01

Diabetic macular edema (DME) is a major cause of visual impairment in patients with diabetes and is influenced by various systemic factors. This study evaluates the effect of renal status on DME using estimated glomerular filtration rate (eGFR) as a study marker. This was a prospective observational cross-sectional study. One hundred and ninety-five patients of diabetic retinopathy (DR) were included. Group 1 had patients of DR without DME (n = 100), and group 2 had patients of DR with DME (n = 95). All patients were evaluated for DR/DME-related risk factors. eGFR was calculated in all patients. Spectral domain optical coherence tomography (SDOCT) was done to identify the various patterns and severity of DME. Group 2 patients had significantly higher comorbidities than those in group 1 (p < 0.001). Hba1c, total cholesterol, triglycerides, LDL/HDL ratio, systolic and diastolic blood pressures were significantly higher in group II (p < 0.001 in each). There was no significant difference between the groups in terms of blood urea, serum creatinine or eGFR. eGFR did not show a significant association with a specific SDOCT pattern or severity of DME. Comorbidities are more common and more severe in patients with DME. However, eGFR as a marker was not useful in predicting either the severity or pattern of DME. eGFR, in its present form, may not be useful in the evaluation and management of patients with DME.

Renal BOLD-MRI relates to kidney function and activity of the renin-angiotensin-aldosterone system in hypertensive patients.

PubMed

Vink, Eva E; de Boer, Anneloes; Hoogduin, Hans J M; Voskuil, Michiel; Leiner, Tim; Bots, Michiel L; Joles, Jaap A; Blankestijn, Peter J

2015-03-01

The renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system are key factors in the pathophysiology of hypertension. Renal hypoxia is the putative mechanism stimulating both systems. Blood oxygen level-dependent MRI (BOLD-MRI) provides a noninvasive tool to determine renal oxygenation in humans. The aim of the current study was to investigate the relation between blood pressure (BP) and kidney function with renal BOLD-MRI. Moreover, the relation between direct and indirect variables of the RAAS and sympathetic nervous system and renal BOLD-MRI was studied. Seventy-five hypertensive patients (38 men) were included. Antihypertensive medication was temporarily stopped. Patients collected urine during 24 h (sodium, catecholamines), blood samples were taken (creatinine, renin, aldosterone), a captopril challenge test was performed, and ambulatory BP was measured. Mean age was 58 (±11) years, day-time BP was 167 (±19)/102 (±16) mmHg, and estimated glomerular filtration rate was 75 (±18) ml/min per 1.73 m). In multivariable regression analysis, renal medullary R2*-values inversely related to estimated glomerular filtration rate (P = 0.02). Moreover, the BP-lowering effect of captopril positively related to cortical (P = 0.02) and medullary (P = 0.008) R2*-values, as well as to P90 (P = 0.02). In patients with hypertension, kidney function relates to medullary R2*-values. Activation of the RAAS is also positively related to the renal R2*-values.

Clinical characteristics and predictive factors of subclinical diabetic nephropathy.

PubMed

Zhang, Y; Yang, J; Zheng, M; Wang, Y; Ren, H; Xu, Y; Yang, Y; Cheng, J; Han, F; Yang, X; Chen, L; Shan, C; Chang, B

2015-02-01

To investigate the clinical characteristics and predictive factors of subclinical diabetic nephropathy in type 2 diabetes patients. A total of 298 type 2 diabetes patients were divided into 3 groups based on 24-h urinary microalbumin and estimated glomerular filtration rate: patients with normal albuminuria and glomerular filtration rate (NC), patients with normoalbuminuria and glomerular hyperfiltration (SDN) and patients with microalbuminuria (EDN). The renal size, tubular injury markers and ambulatory blood pressure were analyzed. Renal size increased in the SDN and EDN groups compared to the NC group (P<0.05), while renal length in the SDN group was greater than the EDN group (P<0.05). Patients in the SDN and EDN groups had higher level of urine retinol binding protein and N-acetyl-β-D-glucosaminidase and most of them developed proximal tubular dysfunction. The SDN group had higher 24-h mean and nocturnal diastolic blood pressure than the NC group (P<0.05), while the EDN group had higher systolic blood pressure and pulse pressure than the SDN group (P<0.01). More patients developed abnormal blood pressure rhythm in the SDN and EDN groups. The likelihood of a decrease in nocturnal systolic blood pressure was lower as the microalbuminuria increased. Increased renal size, more abnormal tubular injury markers and higher 24-h mean and nocturnal blood pressure were all risk factors of subclinical diabetic nephropathy. Patients with subclinical diabetic nephropathy had increased renal size, abnormal tubular injury markers, high blood pressure and abnormal circadian rhythm. © Georg Thieme Verlag KG Stuttgart · New York.

High sodium intake increases blood pressure and alters renal function in intrauterine growth-retarded rats.

PubMed

Sanders, Marijke W; Fazzi, Gregorio E; Janssen, Ger M J; Blanco, Carlos E; De Mey, Jo G R

2005-07-01

A suboptimal fetal environment increases the risk to develop cardiovascular disease in the adult. We reported previously that intrauterine stress in response to reduced uteroplacental blood flow in the pregnant rat limits fetal growth and compromises renal development, leading to an altered renal function in the adult offspring. Here we tested the hypothesis that high dietary sodium intake in rats with impaired renal development attributable to intrauterine stress, results in increased blood pressure, altered renal function, and organ damage. In rats, intrauterine stress was induced by bilateral ligation of the uterine arteries at day 17 of pregnancy. At the age of 12 weeks, the offspring was given high-sodium drinking water (2% sodium chloride). At the age of 16 weeks, rats were instrumented for monitoring of blood pressure and renal function. After intrauterine stress, litter size and birth weight were reduced, whereas hematocrit at birth was increased. Renal blood flow, glomerular filtration rate, and the glomerular filtration fraction were increased significantly after intrauterine stress. High sodium intake did not change renal function and blood pressure in control animals. However, during high sodium intake in intrauterine stress offspring, renal blood flow, glomerular filtration rate, and the filtration fraction were decreased, and blood pressure was increased. In addition, these animals developed severe albuminuria, an important sign of renal dysfunction. Thus, a suboptimal fetal microenvironment, which impairs renal development, results in sodium-dependent hypertension and albuminuria.

Basement Membrane Defects in Genetic Kidney Diseases

PubMed Central

Chew, Christine; Lennon, Rachel

2018-01-01

The glomerular basement membrane (GBM) is a specialized structure with a significant role in maintaining the glomerular filtration barrier. This GBM is formed from the fusion of two basement membranes during development and its function in the filtration barrier is achieved by key extracellular matrix components including type IV collagen, laminins, nidogens, and heparan sulfate proteoglycans. The characteristics of specific matrix isoforms such as laminin-521 (α5β2γ1) and the α3α4α5 chain of type IV collagen are essential for the formation of a mature GBM and the restricted tissue distribution of these isoforms makes the GBM a unique structure. Detailed investigation of the GBM has been driven by the identification of inherited abnormalities in matrix proteins and the need to understand pathogenic mechanisms causing severe glomerular disease. A well-described hereditary GBM disease is Alport syndrome, associated with a progressive glomerular disease, hearing loss, and lens defects due to mutations in the genes COL4A3, COL4A4, or COL4A5. Other proteins associated with inherited diseases of the GBM include laminin β2 in Pierson syndrome and LMX1B in nail patella syndrome. The knowledge of these genetic mutations associated with GBM defects has enhanced our understanding of cell–matrix signaling pathways affected in glomerular disease. This review will address current knowledge of GBM-associated abnormalities and related signaling pathways, as well as discussing the advances toward disease-targeted therapies for patients with glomerular disease. PMID:29435440

Transcutaneous measurement of glomerular filtration rate in conscious laboratory animals: state of the art and future perspectives

NASA Astrophysics Data System (ADS)

Friedemann, Jochen; Schock-Kusch, Daniel; Shulhevich, Yury

2017-02-01

Transcutaneous measurement of Glomerular Filtration Rate (tGFR) is now frequently used in preclinical in vivo animal studies. tGFR allows consecutive measurements on the same animal, including multiple measurements on a daily basis. A description of the measurement device and its many applications, along with examples from the recent literature will be given. We will highlight the fields of interest in which the system is used and give an overview about its performance versus endogenous and other exogenous methods of GFR measurement. A special focus will be put on the precision of tGFR compared to standard measurements employed in the research setting.

Verification on the use of the Inoue method for precisely determining glomerular filtration rate in Philippine pediatrics

NASA Astrophysics Data System (ADS)

Magcase, M. J. D. J.; Duyan, A. Q.; Carpio, J.; Carbonell, C. A.; Trono, J. D.

2015-06-01

The objective of this study is to validate the Inoue method so that it would be the preferential choice in determining glomerular filtration rate (GFR) in Philippine pediatrics. The study consisted of 36 patients ranging from ages 2 months to 19 years old. The subjects used were those who were previously subjected to in-vitro method. The scintigrams of the invitro method was obtained and processed for split percentage uptake and for parameters needed to obtain Inoue GFR. The result of this paper correlates the Inoue GFR and In-vitro method (r = 0.926). Thus, Inoue method is a viable, simple, and practical technique in determining GFR in pediatric patients.

Association Between Contrast Media Volume-Glomerular Filtration Rate Ratio and Contrast-Induced Acute Kidney Injury After Primary Percutaneous Coronary Intervention.

PubMed

Celik, Omer; Ozturk, Derya; Akin, Fatih; Ayca, Burak; Yalcın, Ahmet Arif; Erturk, Mehmet; Bıyık, Ismail; Ayaz, Ahmet; Akturk, Ibrahim Faruk; Enhos, Asım; Aslan, Serkan

2015-07-01

We hypothesized that contrast media volume-estimated glomerular filtration rate (CV-e-GFR) ratio may be a predictor of contrast media-induced acute kidney injury (CI-AKI). We investigated the associations between CV-e-GFR ratio and CI-AKI in 597 patients undergoing primary percutaneous coronary intervention (pPCI). An absolute ≥0.3 mg/dL increase in serum creatinine compared with baseline levels within 48 hours after the procedure was considered as CI-AKI; 78 (13.1%) of the 597 patients experienced CI-AKI. The amount of contrast during procedure was higher in the CI-AKI group than in those without CI-AKI (153 vs 135 mL, P = .003). The CV-e-GFR ratio was significantly higher in patients with CI-AKI than without (2.3 vs 1.5, P < .001). In multivariate analysis, independent predictors of CI-AKI were low left ventricular ejection fraction (P = .018, odds ratio [OR] = 0.966), e-GFR <60 mL/min (P = .012, OR = 2.558), and CV-e-GFR >2 (P < .001, OR = 5.917). In conclusion, CV-e-GFR ratio is significantly associated with CI-AKI after pPCI. © The Author(s) 2014.

Coffee and tea consumption in relation to estimated glomerular filtration rate: results from the population-based longitudinal Doetinchem Cohort Study.

PubMed

Herber-Gast, Gerrie-Cor M; van Essen, Hanneke; Verschuren, Wm Monique; Stehouwer, Coen DA; Gansevoort, Ron T; Bakker, Stephan Jl; Spijkerman, Annemieke Mw

2016-05-01

Although coffee consumption and tea consumption have been linked to diabetes, the relation with kidney function is less clear and is underresearched. We investigated the prospective associations of coffee and tea consumption with estimated glomerular filtration rate (eGFR). We included 4722 participants aged 26-65 y from the Doetinchem Cohort Study who were examined every 5 y for 15 y. Coffee and tea consumption (in cups/d) were assessed at each round. eGFR was assessed by using the Chronic Kidney Disease Epidemiology Collaboration equation based on both plasma creatinine and cystatin C. We determined the association between categories of coffee and tea intake and 1) eGFR and 2) subsequent annual changes in eGFR by using generalized estimating equation analyses. Baseline mean ± SD eGFR was 108.0 ± 14.7 mL · min(-1) · 1.73 m(-2) Tea consumption was not associated with eGFR. Those individuals who drank >6 cups coffee/d had a 1.33 (95% CI: 0.24, 2.43) mL · min(-1) · 1.73 m(-2) higher eGFR than those who drank <1 cup/d (P-trend = 0.02). This association was most apparent among those with a median age of ≥46 y at baseline, with eGFR being 2.47 (95% CI: 0.42, 4.51) mL · min(-1) · 1.73 m(-2) higher in participants drinking >6 cups/d compared with <1 cup/d (P-trend = 0.02). Adjustment for biological risk factors and coffee constituents did not attenuate the associations. Neither coffee nor tea consumption was associated with changes in eGFR. Coffee consumption was associated with a slightly higher eGFR, particularly in those aged ≥46 y. The absence of an association with eGFR changes suggests that the higher eGFR among coffee consumers is unlikely to be a result of glomerular hyperfiltration. Therefore, low to moderate coffee consumption is not expected to be a concern for kidney health in the general population. © 2016 American Society for Nutrition.

[Determination of homeostatic kidney function in the diagnosis of chronic glomerulonephritis].

PubMed

Ratner, M J

1977-12-01

The latent and hypertonic forms of the course of compensated nephritides more frequently make difficulties concerning the differential diagnosis between a chronic glomerulonephritis and a chronic pyelonephritis. According to the results achieved the determination of the renal processes furthering homoeostasis gives the possibility to demarcate the two diseases. A certain reduction of the creatinine clearance (to less than 90 ml/min) and of the maximum water diuresis (to less than 10.0 per 100 ml glomerular filtrate) is suitable for the latent form of the chronic glomerulonephritis. On the other hand, a reduction of the ammonia secretion (to less than 35 per 100 ml glomerular (filtrate) and of the total H+-ion secretion (to less than 50 per 100 ml glomerular filtrate) in the determination after Alkinton is characteristic for the chronic pyelonephritis. In the hypertensive form of the course of the chronic glomerulonephritis in contrast to the same form in chronic pyelonephritis a reduction of the maximum water diuresis to less than 7.5, of the clearance of the "osmotically free" water to less than 6.0, of the titrable acidity to less than 25 is the result. Here the ammonia quotient transgresses 45%. In chronic pyelonephritis the titrable acidity in considerably increased and the ammonia genesis relatively decreased (to less than 45%).

Proenkephalin, Neutrophil Gelatinase-Associated Lipocalin, and Estimated Glomerular Filtration Rates in Patients With Sepsis.

PubMed

Kim, Hanah; Hur, Mina; Lee, Seungho; Marino, Rossella; Magrini, Laura; Cardelli, Patrizia; Struck, Joachim; Bergmann, Andreas; Hartmann, Oliver; Di Somma, Salvatore

2017-09-01

Proenkephalin (PENK) has been suggested as a novel biomarker for kidney function. We investigated the diagnostic and prognostic utility of plasma PENK in comparison with neutrophil gelatinase-associated lipocalin (NGAL) and estimated glomerular filtration rates (eGFR) in septic patients. A total of 167 septic patients were enrolled: 99 with sepsis, 37 with septic shock, and 31 with suspected sepsis. PENK and NGAL concentrations were measured and GFR was estimated by using the isotope dilution mass spectrometry traceable-Modification of Diet in Renal Disease (MDRD) Study and three Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations: CKD-EPI(Cr), CDK-EPI(CysC), and CKD-EPI(Cr-CysC). The PENK, NGAL, and eGFR results were compared according to sepsis severity, presence or absence of acute kidney injury (AKI), and clinical outcomes. The PENK, NGAL, and eGFR results were significantly associated with sepsis severity and differed significantly between patients with and without AKI only in the sepsis group (all P<0.05). PENK was superior to NGAL in predicting AKI (P=0.022) and renal replacement therapy (RRT) (P=0.0085). Regardless of the variable GFR category by the different eGFR equations, PENK showed constant and significant associations with all eGFR equations. Unlike NGAL, PENK was not influenced by inflammation and predicted the 30-day mortality. PENK is a highly sensitive and objective biomarker of AKI and RRT and is useful for prognosis prediction in septic patients. With its diagnostic robustness and predictive power for survival, PENK constitutes a promising biomarker in critical care settings including sepsis. © The Korean Society for Laboratory Medicine

Skin autofluorescence associates with vascular calcification in chronic kidney disease.

PubMed

Wang, Angela Yee-Moon; Wong, Chun-Kwok; Yau, Yat-Yin; Wong, Sharon; Chan, Iris Hiu-Shuen; Lam, Christopher Wai-Kei

2014-08-01

This study aims to evaluate the relationship between tissue advanced glycation end products, as reflected by skin autofluorescence, and vascular calcification in chronic kidney disease. Three hundred patients with stage 3 to 5 chronic kidney disease underwent multislice computed tomography to estimate total coronary artery calcium score (CACS) and had tissue advanced glycation end product assessed using a skin autofluorescence reader. Intact parathyroid hormone (P<0.001) displaced estimated glomerular filtration rate as third most significant factor associated with skin autofluorescence after age (P<0.001) and diabetes mellitus (P<0.001) in multiple regression analysis. On univariate multinomial logistic regression analysis, every 1-U increase in skin autofluorescence was associated with a 7.43-fold (95% confidence intervals, 3.59-15.37; P<0.001) increased odds of having CACS ≥400 compared with those with zero CACS. Skin autofluorescence retained significance in predicting CACS ≥400 (odds ratio, 3.63; 95% confidence intervals, 1.44-9.18; P=0.006) when adjusting for age, sex, serum calcium, phosphate, albumin, C-reactive protein, lipids, blood pressure, estimated glomerular filtration rate, and intact parathyroid hormone but marginally lost significance when additionally adjusting for diabetes mellitus (odds ratio, 2.23; 95% confidence intervals, 0.81-6.14; P=0.1). Combination of diabetes mellitus and higher intact parathyroid hormone was associated with greater skin autofluorescence and CACS versus those without diabetes mellitus and having lower intact parathyroid hormone. Tissue advanced glycation end product, as reflected by skin autofluorescence, showed a significant novel association with vascular calcification in chronic kidney disease. These data suggest that increased tissue advanced glycation end product may contribute to vascular calcification in chronic kidney disease and diabetes mellitus and warrant further experimental investigation. © 2014 American Heart Association, Inc.

[Diagnostic ability of Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease-4 equations to estimate glomerular filtration rate in with multimorbidity patients].

PubMed

Cabrerizo-García, José Luis; Díez-Manglano, Jesús; García-Arilla, Ernesto; Revillo-Pinilla, Paz; Ramón-Puertas, José; Sebastián-Royo, Mariano

2015-01-06

The Modification of Diet in Renal Disease (MDRD) equation is recommended by most scientific societies to calculate the estimated glomerular filtration rate (GFR). Recently the group Chronic Kidney Disease Epidemiology Collaboration (CKP-EPI) has published a new, more precise and accurate equation. We have analyzed its behavior in a group of polypathological patients (PP) and compared it with the classic MDRD-4.version Multicenter, observational, descriptive and transversal study. We calculated GFR by MDRD-4 and CKD-EPI in 425 PP. Each stage was assigned according to the GFR: 1:>90; 2: 60-89; 3: 30-59; 4: 15-29; and 5 < 15 ml/min/1.73m(2). We analyzed the correlation between both and the patients reclassified by CKD-EPI. Mean age was (mean [SD]) 81.7 (7.9) years. 55.3% were women. The mean estimated GFR was 58.6 (26.3) ml/min/1,73m(2) by MDRD-4 and 52.7 (23.0) ml/min/1.73m(2) by CKD-EPI (P<.001; Spearman's Rho correlation and Lin concordance coefficients: 0.993 and 0.948). The Bland-Altman plots reflected lower values for GFR for CKD-EPI equation. In the stage 2, 21.2% were reclassified by CKD-EPI to the stage 3, with women older than 83 years being the more disadvantaged subgroup with 27.3% or reclassification. CKD-EPI equation applied to PP worsens the results of MDRD-4. In general, it originates low values of GFR and increases the degree of renal insufficiency, especially in older women. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Predictors of postoperative decline in estimated glomerular filtration rate in patients undergoing robotic partial nephrectomy.

PubMed

Wiener, Scott; Kiziloz, Halil; Dorin, Ryan P; Finnegan, Kyle; Shichman, Steven S; Meraney, Anoop

2014-07-01

To identify prognostic indicators of estimated glomerular filtration rate (eGFR) following robotic partial nephrectomy (RPN). In a retrospective study of RPN patients, we examined data describing age, gender, eGFR, body mass index (BMI), tumor size (TS), length of stay, and estimated blood loss (EBL). Changes in eGFR (i.e., renal function trajectory [RFT]) and chronic kidney disease (CKD) stage shift were analyzed with mixed model linear and logistic regression analyses, Chi-squared, and t-tests. Changes in eGFR (RFT) were determined in 122 patients at baseline and at 6- and 12-month follow-up visits. Mean age, TS, and Charlson comorbidity index (CCI) were 62±11 years, 3±1.2 cm, and 4.8±1.8, respectively. The pre- and postoperative eGFR was lower in patients >60 years. Preoperative eGFR was unrelated to gender, BMI>30 kg/m(2), histopathology, nuclear grade, and TS. Univariate analyses determined that age, BMI>30, EBL>200 mL, CCI>5, and TS were associated with greater declines in eGFR. Reduced eGFR was also associated with warm ischemia time ≥22 minutes, while age was associated with a ≥1 worsening of British CKD classification. Using multivariate analysis, only age was significantly associated with a decline in eGFR, which was greater in patients with a normal preoperative eGFR. Patient age, BMI>30, EBL>200 mL, CCI>5, and TS were predictors of greater postoperative declines in eGFR. Although a decline in eGFR was proportionally greater in low stage CKD, postoperative changes are associated with advancing age.

Gallium-68 EDTA PET/CT for Renal Imaging.

PubMed

Hofman, Michael S; Hicks, Rodney J

2016-09-01

Nuclear medicine renal imaging provides important functional data to assist in the diagnosis and management of patients with a variety of renal disorders. Physiologically stable metal chelates like ethylenediaminetetraacetic acid (EDTA) and diethylenetriamine penta-acetate (DTPA) are excreted by glomerular filtration and have been radiolabelled with a variety of isotopes for imaging glomerular filtration and quantitative assessment of glomerular filtration rate. Gallium-68 ((68)Ga) EDTA PET usage predates Technetium-99m ((99m)Tc) renal imaging, but virtually disappeared with the widespread adoption of gamma camera technology that was not optimal for imaging positron decay. There is now a reemergence of interest in (68)Ga owing to the greater availability of PET technology and use of (68)Ga to label other radiotracers. (68)Ga EDTA can be used a substitute for (99m)Tc DTPA for wide variety of clinical indications. A key advantage of PET for renal imaging over conventional scintigraphy is 3-dimensional dynamic imaging, which is particularly helpful in patients with complex anatomy in whom planar imaging may be nondiagnostic or difficult to interpret owing to overlying structures containing radioactive urine that cannot be differentiated. Other advantages include accurate and absolute (rather than relative) camera-based quantification, superior spatial and temporal resolution and integrated multislice CT providing anatomical correlation. Furthermore, the (68)Ga generator enables on-demand production at low cost, with no additional patient radiation exposure compared with conventional scintigraphy. Over the past decade, we have employed (68)Ga EDTA PET/CT primarily to answer difficult clinical questions in patients in whom other modalities have failed, particularly when it was envisaged that dynamic 3D imaging would be of assistance. We have also used it as a substitute for (99m)Tc DTPA if unavailable owing to supply issues, and have additionally examined the role of (68)Ga EDTA PET/CT for measuring glomerular filtration rate and split renal function. Copyright © 2016 Elsevier Inc. All rights reserved.

Limitations of analyses based on achieved blood pressure: lessons from the African American study of kidney disease and hypertension trial.

PubMed

Davis, Esa M; Appel, Lawrence J; Wang, Xuelei; Greene, Tom; Astor, Brad C; Rahman, Mahboob; Toto, Robert; Lipkowitz, Michael S; Pogue, Velvie A; Wright, Jackson T

2011-06-01

Blood pressure (BP) guidelines that set target BP levels often rely on analyses of achieved BP from hypertension treatment trials. The objective of this article was to compare the results of analyses of achieved BP to intention-to-treat analyses on renal disease progression. Participants (n=1094) in the African-American Study of Kidney Disease and Hypertension Trial were randomly assigned to either usual BP goal defined by a mean arterial pressure goal of 102 to 107 mm Hg or lower BP goal defined by a mean arterial pressure goal of ≤92 mm Hg. Median follow-up was 3.7 years. Primary outcomes were rate of decline in measured glomerular filtration rate and a composite of a decrease in glomerular filtration rate by >50% or >25 mL/min per 1.73 m(2), requirement for dialysis, transplantation, or death. Intention-to-treat analyses showed no evidence of a BP effect on either the rate of decline in glomerular filtration rate or the clinical composite outcome. In contrast, the achieved BP analyses showed that each 10-mm Hg increment in mean follow-up achieved mean arterial pressure was associated with a 0.35 mL/min per 1.73 m(2) (95% CI: 0.08 to 0.62 mL/min per 1.73 m(2); P=0.01) faster mean glomerular filtration rate decline and a 17% (95% CI: 5% to 32%; P=0.006) increased risk of the clinical composite outcome. Analyses based on achieved BP lead to markedly different inferences than traditional intention-to-treat analyses, attributed in part to confounding of achieved BP with comorbidities, disease severity, and adherence. Clinicians and policy makers should exercise caution when making treatment recommendations based on analyses relating outcomes to achieved BP.

Role of humoral mediators in, and influence of a liposomal formulation on, acute amphotericin B nephrotoxicity.

PubMed

Sabra, R; Zeinoun, N; Sharaf, L H; Ghali, R; Beshara, G; Serhal, H

2001-04-01

The mechanisms responsible for amphotericin B nephrotoxicity remain incompletely understood, but clearly involve reduction in renal blood flow and glomerular filtration rate. Both direct effects of amphotericin B on contractile vascular cells, and indirect effects, due to humoural mediators, have been proposed. This study examines the role of nitric oxide, endothelin and angiotensin II in the acute nephrotoxic effects of amphotericin B in rats, and compares the anti-fungal and nephrotoxic effects of liposomal amphotericin B and amphotericin B-deoxycholate. Anaesthetized rats were given infusions of amphotericin B-deoxycholate in the presence or absence of N-nitro-L-arginine, PD 145065, a non-specific endothelin receptor antagonist, and L-158809, an angiotensin II type I receptor antagonist, or increasing doses of liposomal amphotericin B. Amphotericin B-deoxycholate (0.03 mg/kg/min intravenously) caused a significant 44% reduction in glomerular filtration rate and 65% maximal fall in renal blood flow. N-Nitro-L-arginine-treated rats had a lower renal blood flow and glomerular filtration rate at baseline, but sustained similar reduction of 53% and 75% in these parameters, respectively. PD145065 and L-158809 did not modify these effects either. Increasing doses of liposomal amphotericin B (from 0.01 up to 0.50 mg/kg/min.) induced no change in either glomerular filtration rate or renal blood flow. In vitro susceptibility tests revealed similar potency for liposomal amphotericin B and amphotericin B-deoxycholate in their fungistatic effects and slightly higher potency for amphotericin B-deoxycholate in their fungicidal effect. These results suggest that endogenous endothelin, angiotensin II or nitric oxide systems are not involved in the nephrotoxic effects of amphotericin B. The liposomal amphotericin B results suggest that amphotericin B nephrotoxicity is due to a direct interaction of amphotericin B with renal cells that is prevented by its encapsulation in liposomes.

Renal parameter estimates in unrestrained dogs

NASA Technical Reports Server (NTRS)

Rader, R. D.; Stevens, C. M.

1974-01-01

A mathematical formulation has been developed to describe the hemodynamic parameters of a conceptualized kidney model. The model was developed by considering regional pressure drops and regional storage capacities within the renal vasculature. Estimation of renal artery compliance, pre- and postglomerular resistance, and glomerular filtration pressure is feasible by considering mean levels and time derivatives of abdominal aortic pressure and renal artery flow. Changes in the smooth muscle tone of the renal vessels induced by exogenous angiotensin amide, acetylcholine, and by the anaesthetic agent halothane were estimated by use of the model. By employing totally implanted telemetry, the technique was applied on unrestrained dogs to measure renal resistive and compliant parameters while the dogs were being subjected to obedience training, to avoidance reaction, and to unrestrained caging.

Creatinine Clearance and Estimated Glomerular Filtration Rate--When are they Interchangeable.

PubMed

Simetić, Lucija; Zibar, Lada; Drmić, Sandra; Begić, Ivana; Serić, Vatroslav

2015-09-01

Study goal was to examine which of glomerular rate equations is most suitable for prediction of creatinine clearance (CrCl). Using a retrospective review of data from 500 hospital patients we calculated glomerular filtration rate according to Cockcroft-Gault equation (C-G), Modification of Diet in Renal Disease Study equation (MDRD) and Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI). We determined if results of these equations were compatible with CrCl, and does stage of kidney disease, body-mass index (BMI), diabetes or old age have an impact on their ability to predict creatinine clearance. All of the equations showed high correlations with CrCl, regardless of diabetes, overweight or old age. There was no significant difference (p<0.05) between diagnostic accuracy when comparing ROC plots for MDRD and CKD-EPIat CrCl cut offs of 60 ml/min/1.73 m2 and 90 ml/min/1.73 m2 when analyzing data for all patients, older patients (>65 years) and diabetics. The percentage of overweight patients (BMI > or = 25) in patients with normal CrCl and decreased GFR was 64.81% for C-G, 92.04% for MDRD and 91.36% for CKD-EPI. Large number of overweight patients with normal CrCl and decreased GFR would indicate that CrCl overestimates GFR in overweight patients. The simple correction in CrCl for obese subjects is purposed. Passing-Bablok regression showed agreement between CrCl and MDRD and CrCl and CKD-EPI only in cases of severely decreased GFR (G4 and G5 stage of chronic kidney disease). Only in these stages of chronic kidney disease can CrCl and MDRD or CrCl and CKD-EPI be used simultaneously.

The Variability of Estimated Glomerular Filtration Rate Decline in Alport Syndrome.

PubMed

Langsford, David; Tang, Mila; Djurdjev, Ognjenka; Er, Lee; Levin, Adeera

2016-01-01

A progressive trajectory toward renal failure is common in patients with Alport syndrome. Genotype-phenotype correlations have been well described; however, the natural history of the trajectory toward renal failure is not well described. The objective of this study is to describe the natural history of renal function decline in a cohort of Alport syndrome patients. Retrospective observational cohort study. British Columbia, Canada, chronic renal disease registry 1995-2012. 37 biopsy proven Alport syndrome or hematuria with family history of Alport syndrome. Serial estimated glomerular filtration rate (eGFR) Trajectory of renal decline described graphically by fitting a cubic smoothing spline to patient's eGFR measures. Various time points within a trajectory were indexed, randomly sampled, and followed for 2 years to estimate portion of progressors (>5 mL/min/1.73 m2 /y decline), stable state (0-2 mL/min/1.73 m2 /y decline), and regressors (>2 mL/min/1.73 m2 /y incline). In this retrospective observational cohort study, participants were identified through a chronic renal disease registry in British Columbia, Canada, from 1995 to 2012. Inclusion criteria were biopsy proven or hematuria with a family history of Alport syndrome. Individual patients and family group members were studied. Trajectory of renal decline described graphically by fitting a cubic smoothing spline to patient's serial estimated glomerular filtration rate (eGFR) measures. Various time points within a trajectory were indexed, randomly sampled, and followed for 2 years to estimate portion of progressors (>5 mL/min/1.73 m 2 /y decline), stable state (0-2 mL/min/1.73 m 2 /y decline), and regressors (>2 mL/min/1.73 m 2 /y incline). Histological or genetic evidence of Alport syndrome is not available in all patients. Median follow-up time was 48.2 months of 37 patients (78% male), with a median age of 36 (interquartile range [IQR], 18-47) and a median age of renal replacement therapy commencement (n = 23) of 38 (IQR = 20-52). Renal function changes were found to be heterogeneous overall, intra-individual and within families. Portion of progressors in eGFR 45-60 mL/min/1.73 m 2 was 73.7% (SD, 10.3), whereas 23.6% (SD, 11.0) remained stable. Within eGFR 30-45 mL/min/1.73 m 2 , 45.6% (SD, 7.0) were progressors, whereas 53.4% (SD, 7.4) remained stable. A large portion of eGFR 15-30 mL/min/1.73 m 2 patients were stable (54.8%; SD, 8.4), whereas 25.7% (SD, 7.1) progressed and 19.5% (SD, 5.6) regressed. The renal decline in Alport syndrome patients is heterogeneous which has implications for designing clinical trials of interventions.

The Variability of Estimated Glomerular Filtration Rate Decline in Alport Syndrome

PubMed Central

Langsford, David; Tang, Mila; Djurdjev, Ognjenka; Er, Lee; Levin, Adeera

2016-01-01

Background: A progressive trajectory toward renal failure is common in patients with Alport syndrome. Genotype-phenotype correlations have been well described; however, the natural history of the trajectory toward renal failure is not well described. Objective: The objective of this study is to describe the natural history of renal function decline in a cohort of Alport syndrome patients. Design: Retrospective observational cohort study. Setting: British Columbia, Canada, chronic renal disease registry 1995-2012. Patients: 37 biopsy proven Alport syndrome or hematuria with family history of Alport syndrome. Measurements: Serial estimated glomerular filtration rate (eGFR) Trajectory of renal decline described graphically by fitting a cubic smoothing spline to patient’s eGFR measures. Various time points within a trajectory were indexed, randomly sampled, and followed for 2 years to estimate portion of progressors (>5 mL/min/1.73 m2 /y decline), stable state (0-2 mL/min/1.73 m2 /y decline), and regressors (>2 mL/min/1.73 m2 /y incline). Methods: In this retrospective observational cohort study, participants were identified through a chronic renal disease registry in British Columbia, Canada, from 1995 to 2012. Inclusion criteria were biopsy proven or hematuria with a family history of Alport syndrome. Individual patients and family group members were studied. Trajectory of renal decline described graphically by fitting a cubic smoothing spline to patient’s serial estimated glomerular filtration rate (eGFR) measures. Various time points within a trajectory were indexed, randomly sampled, and followed for 2 years to estimate portion of progressors (>5 mL/min/1.73 m2/y decline), stable state (0-2 mL/min/1.73 m2/y decline), and regressors (>2 mL/min/1.73 m2/y incline). Limitations: Histological or genetic evidence of Alport syndrome is not available in all patients. Results: Median follow-up time was 48.2 months of 37 patients (78% male), with a median age of 36 (interquartile range [IQR], 18-47) and a median age of renal replacement therapy commencement (n = 23) of 38 (IQR = 20-52). Renal function changes were found to be heterogeneous overall, intra-individual and within families. Portion of progressors in eGFR 45-60 mL/min/1.73 m2 was 73.7% (SD, 10.3), whereas 23.6% (SD, 11.0) remained stable. Within eGFR 30-45 mL/min/1.73 m2, 45.6% (SD, 7.0) were progressors, whereas 53.4% (SD, 7.4) remained stable. A large portion of eGFR 15-30 mL/min/1.73 m2 patients were stable (54.8%; SD, 8.4), whereas 25.7% (SD, 7.1) progressed and 19.5% (SD, 5.6) regressed. Conclusions: The renal decline in Alport syndrome patients is heterogeneous which has implications for designing clinical trials of interventions. PMID:28781883

Correlation between cystatin C-based formulas, Schwartz formula and urinary creatinine clearance for glomerular filtration rate estimation in children with kidney disease.

PubMed

Safaei-Asl, Afshin; Enshaei, Mercede; Heydarzadeh, Abtin; Maleknejad, Shohreh

2016-01-01

Assessment of glomerular filtration rate (GFR) is an important tool for monitoring renal function. Regarding to limitations in available methods, we intended to calculate GFR by cystatin C (Cys C) based formulas and determine correlation rate of them with current methods. We studied 72 children (38 boys and 34 girls) with renal disorders. The 24 hour urinary creatinine (Cr) clearance was the gold standard method. GFR was measured with Schwartz formula and Cys C-based formulas (Grubb, Hoek, Larsson and Simple). Then correlation rates of these formulas were determined. Using Pearson correlation coefficient, a significant positive correlation between all formulas and the standard method was seen (R(2) for Schwartz, Hoek, Larsson, Grubb and Simple formula was 0.639, 0.722, 0.705, 0.712, 0.722, respectively) (P<0.001). Cys C-based formulas could predict the variance of standard method results with high power. These formulas had correlation with Schwarz formula by R(2) 0.62-0.65 (intermediate correlation). Using linear regression and constant (y-intercept), it revealed that Larsson, Hoek and Grubb formulas can estimate GFR amounts with no statistical difference compared with standard method; but Schwartz and Simple formulas overestimate GFR. This study shows that Cys C-based formulas have strong relationship with 24 hour urinary Cr clearance. Hence, they can determine GFR in children with kidney injury, easier and with enough accuracy. It helps the physician to diagnosis of renal disease in early stages and improves the prognosis.

Diminished disease progression rate in a chronic kidney disease population following the replacement of dietary water source with quality drinking water: A pilot study.

PubMed

Siriwardhana, Edirisinghe Arachchige Ranga Iroshanie Edirisinghe; Perera, Ponnamperuma Aratchige Jayasumana; Sivakanesan, Ramiah; Abeysekara, Tilak; Nugegoda, Danaseela Bandara; Weerakoon, Kosala; Siriwardhana, Dunusingha Asitha Surandika

2018-05-01

Environmental toxin/s is alleged to be the contributory factor for the chronic kidney disease of unknown aetiology (CKDu) in Sri Lanka. The potential of drinking water as a medium for the nephrotoxic agents in the affected subjects has been comprehensively discoursed in the recent past. The present study was aimed to assess the effect of replacing the habitual drinking water on the kidney function of CKDu patients residing in the North Central Province of Sri Lanka: METHODS: An interventional study was carried out to assess the disease progression rate of a CKDu population whose habitual drinking water was replaced by bottled spring water certified by Sri Lanka Standard (SLS) for a period of 18 month along with a population of CKDu patients who continued with their usual drinking water. Kidney function of subjects in both groups were monitored in terms of blood pressure, serum creatinine, serum calcium, serum phosphorus, hemoglobin, estimated glomerular filtration rate and urinary protein at 6 months intervals during the intervention and follow up periods. Diminished disease progression rate was observed in CKDu patients in the intervention group when compared with the non- intervention group based on serum creatinine, Hb, estimated glomerular filtration rate and urinary protein levels. Extensive interventional studies are required to generalize effect of drinking water on CKDu population. The habitual drinking water is likely to be a contributory factor towards the progression of the disease. © 2017 Asian Pacific Society of Nephrology.

Analysis of Advanced Glycation End Products in the DHS Mind Study

PubMed Central

Adams, Jeremy N.; Martelle, Susan E.; Raffield, Laura M.; Freedman, Barry I.; Langefeld, Carl D.; Hsu, Fang-Chi; Maldjian, Joseph A.; Williamson, Jeff D.; Hugenschmidt, Christina E.; Carr, J. Jeffery; Cox, Amanda J.; Bowden, Donald W.

2016-01-01

Aims Human studies of links between advanced glycation end-products (AGEs) and disease phenotypes are less common than studies of animal and cell models. Here, we examined the association of total AGEs with diabetes risk factors in a predominately type 2 diabetes (T2D) affected cohort. Methods AGEs were measured using an enzyme linked immunosorbant assay in 816 individuals from the DHS Mind Study (n=709 T2D affected), and association analyses were completed. Results Total AGEs were associated with estimated glomerular filtration rate (p= 0.0054; β= −0.1291) and coronary artery calcification (p= 0.0352; β= 1.1489) in the entire cohort. No significant associations were observed when individuals with T2D were analyzed separately. In individuals without T2D, increased circulating AGEs were associated with increased BMI (p= 0.02, β = 0.138), low density lipoproteins (p=0.046, β = 17.07) and triglycerides (p= 0.0004, β = 0.125), and decreased carotid artery calcification (p= 0.0004, β = −1.2632) and estimated glomerular filtration rate (p= 0.0018, β = −0.1405). Strong trends were also observed for an association between AGEs and poorer cognitive performance on the digit symbol substitution test (p=0.046, β = −6.64) and decreased grey matter volume (p=0.037, β = −14.87). Conclusions AGEs may play an important role in a number of phenotypes and diseases, although not necessarily in interindividual variation in people with T2D. Further evaluation of specific AGE molecules may shed more light on these relationships. PMID:26739237

Impact of estimated glomerular filtration rate based on plasma cystatin C and serum creatinine levels before allogeneic hematopoietic cell transplantation.

PubMed

Wada, Hidenori; Kanda, Junya; Akahoshi, Yu; Nakano, Hirofumi; Ugai, Tomotaka; Yamasaki, Ryoko; Ishihara, Yuko; Kawamura, Koji; Sakamoto, Kana; Ashizawa, Masahiro; Sato, Miki; Terasako-Saito, Kiriko; Kimura, Shun-Ichi; Kikuchi, Misato; Nakasone, Hideki; Yamazaki, Rie; Kako, Shinichi; Tanihara, Aki; Nishida, Junji; Kanda, Yoshinobu

2018-06-01

No standard method for measuring renal function has been established in allogeneic hematopoietic cell transplantation (allo-HCT). We retrospectively analyzed 80 patients with hematological diseases who underwent allo-HCT at our center. We assessed renal function using creatinine clearance (Ccr), estimated glomerular filtration rate (eGFR) based on creatinine (eGFRcre), eGFR based on cystatin C (eGFRcys), and the average of eGFRcre and eGFRcys (eGFRave). We then evaluated the impact of pre-transplant renal function on the exacerbation of renal function and non-relapse mortality after transplantation. There was a significant correlation between Ccr and eGFRcre, eGFRcys, and eGFRave. eGFRave best predicted the exacerbation of renal function according to the area under the receiver-operating characteristic curve. The cumulative incidence of renal function exacerbation at 1 year was higher in the lower eGFRave group (<90 ml/min/1.73 m 2 ) than in the higher eGFRave group (≥90 ml/min/1.73 m 2 ; 0.85 vs. 0.39, p < 0.001), which was confirmed by a multivariate analysis (HR 2.75, p = 0.001). A lower eGFRave value was a marginally significant factor for non-relapse mortality (HR 3.29, p = 0.076). Among the four parameters, eGFRave best predicted the exacerbation of renal function in allo-HCT. Further, the marginal association between low eGFRave and high non-relapse mortality warrants further study in a prospective study in allo-HCT.

Using Mathematical Algorithms to Modify Glomerular Filtration Rate Estimation Equations

PubMed Central

Zhu, Bei; Wu, Jianqing; Zhu, Jin; Zhao, Weihong

2013-01-01

Background The equations provide a rapid and low-cost method of evaluating glomerular filtration rate (GFR). Previous studies indicated that the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease-Epidemiology (CKD-EPI) and MacIsaac equations need further modification for application in Chinese population. Thus, this study was designed to modify the three equations, and compare the diagnostic accuracy of the equations modified before and after. Methodology With the use of 99 mTc-DTPA renal dynamic imaging as the reference GFR (rGFR), the MDRD, CKD-EPI and MacIsaac equations were modified by two mathematical algorithms: the hill-climbing and the simulated-annealing algorithms. Results A total of 703 Chinese subjects were recruited, with the average rGFR 77.14±25.93 ml/min. The entire modification process was based on a random sample of 80% of subjects in each GFR level as a training sample set, the rest of 20% of subjects as a validation sample set. After modification, the three equations performed significant improvement in slop, intercept, correlated coefficient, root mean square error (RMSE), total deviation index (TDI), and the proportion of estimated GFR (eGFR) within 10% and 30% deviation of rGFR (P10 and P30). Of the three modified equations, the modified CKD-EPI equation showed the best accuracy. Conclusions Mathematical algorithms could be a considerable tool to modify the GFR equations. Accuracy of all the three modified equations was significantly improved in which the modified CKD-EPI equation could be the optimal one. PMID:23472113

Diabetes and Trajectories of Estimated Glomerular Filtration Rate: A Prospective Cohort Analysis of the Atherosclerosis Risk in Communities Study.

PubMed

Warren, Bethany; Rebholz, Casey M; Sang, Yingying; Lee, Alexandra K; Coresh, Josef; Selvin, Elizabeth; Grams, Morgan E

2018-06-01

Long-term kidney disease trajectories in persons with and without diabetes in a general population are largely uncharacterized. We classified 15,517 participants in the community-based Atherosclerosis Risk in Communities (ARIC) study by diabetes status at baseline (1987-1989; no diabetes, undiagnosed diabetes, and diagnosed diabetes). We used linear mixed models with random intercepts and slopes to quantify estimated glomerular filtration rate (eGFR) trajectories at four visits over 26 years. Adjusted mean eGFR decline over the full study period among participants without diabetes was -1.4 mL/min/1.73 m 2 /year (95% CI -1.5 to -1.4); with undiagnosed diabetes was -1.8 mL/min/1.73 m 2 /year (95% CI -2.0 to -1.7) (difference vs. no diabetes, P < 0.001); and with diagnosed diabetes was -2.5 mL/min/1.73 m 2 /year (95% CI -2.6 to -2.4) (difference vs. no diabetes, P < 0.001). Among participants with diagnosed diabetes, risk factors for steeper eGFR decline included African American race, APOL1 high-risk genotype, systolic blood pressure ≥140 mmHg, insulin use, and higher HbA 1c . Diabetes is an important risk factor for kidney function decline. Those with diagnosed diabetes declined almost twice as rapidly as those without diabetes. Among people with diagnosed diabetes, steeper declines were seen in those with modifiable risk factors, including hypertension and glycemic control, suggesting areas for continued targeting in kidney disease prevention. © 2018 by the American Diabetes Association.

Plasma creatinine levels, estimated glomerular filtration rate and carotid intima media thickness in middle-aged women: a population based cohort study.

PubMed

Gentile, M; Panico, S; Mattiello, A; de Michele, M; Iannuzzi, A; Jossa, F; Marotta, G; Rubba, P

2014-06-01

The relationships between high Creatinine (Cr) levels or low estimated Glomerular Filtration Rate (eGFR) and common carotid Intima Media thickness (IMT) have been evaluated in a population-based cohort study in women, aged 30-69 (Progetto ATENA). Serum Cr and eGFR were measured in 310 women, as a part of 5.062. In this group carotid ultrasound examination (B-Mode imaging) was performed and mean max IMT was calculated. Women were classified by Cr levels >1 mg/dL or eGFR < 56 ml/min. Women with Cr > 1 mg/dL (90th percentile of creatinine distribution) or eGFR less than 56 ml/min (5th percentile of eGFR distribution) had relatively more carotid plaques as compared to the rest of the cohort. Multivariate logistic analysis, after adjustment for age, demonstrated a significant association between Cr (>1 mg/dL) and IMT (≥1.2 mm): OR 4.12 (C.I 1.22-13.86), p = 0.022; or eGFR (<56 ml/min) and IMT (≥1.2 mm): OR 4.31 (C.I 1.27-14.66), p = 0.019. These findings on an independent relationship between Cr and common carotid plaques in this population of middle aged women, independently of age, suggest the value of screening for early carotid disease in asymptomatic middle aged-women with mild renal insufficiency, in order to predict those at relatively higher risk for future cardiovascular events. Copyright © 2013 Elsevier B.V. All rights reserved.

Nocturia in men is a chaotic condition dominated by nocturnal polyuria.

PubMed

Fujimura, Tetsuya; Yamada, Yuta; Sugihara, Toru; Azuma, Takeshi; Suzuki, Motofumi; Fukuhara, Hiroshi; Nakagawa, Tohru; Kume, Haruki; Igawa, Yasuhiko; Homma, Yukio

2015-05-01

To characterize nocturia in men based on frequency volume chart data and symptom profiles assessed using the Core Lower Urinary Tract Symptom Score and Athens Insomnia Scale questionnaires. The Core Lower Urinary Tract Symptom Score and Athens Insomnia Scale questionnaires were administered to 299 consecutive treatment naïve men with nocturia (≥one time per night). Frequency volume chart data were recorded for 2 days. Correlations between nocturia and clinical characteristics including symptom scores, clinical diagnosis, Charlson Comorbidity Index, estimated glomerular filtration rate, uroflowmetry and prostate volume were analyzed. Patients were divided into five groups: one time (n = 36), two times (n = 65), three times (n = 85), four times (n = 78) and five times (n = 34) of nocturia. Age, prevalence or severity of chronic kidney disease, hyperlipidemia, low bladder capacity, nocturnal polyuria, urgency, bladder pain and sleep disorders were significantly correlated with the severity of nocturia. The Spearman correlation analysis identified eight possible independent factors for nocturia: age, estimated glomerular filtration rate, urgency, bladder pain, sleep quality, sleepiness during the day, average voided volume and nocturnal volume divided by body weight. Logistic regression analysis showed that nocturnal volume divided by body weight was the strongest factor of nocturia, and ≥7, 9 and 9.7 mL/kg were practical cut-off values of three, four and five times per night of nocturia, respectively. Nocturia in men is a chaotic condition dominated by nocturnal polyuria, and related to multiple factors including age, renal function, urgency, bladder pain, insomnia and bladder volume. © 2015 The Japanese Urological Association.

Types of vicarious learning experienced by pre-dialysis patients.

PubMed

McCarthy, Kate; Sturt, Jackie; Adams, Ann

2015-01-01

Haemodialysis and peritoneal dialysis renal replacement treatment options are in clinical equipoise, although the cost of haemodialysis to the National Health Service is £16,411/patient/year greater than peritoneal dialysis. Treatment decision-making takes place during the pre-dialysis year when estimated glomerular filtration rate drops to between 15 and 30 mL/min/1.73 m(2). Renal disease can be familial, and the majority of patients have considerable health service experience when they approach these treatment decisions. Factors affecting patient treatment decisions are currently unknown. The objective of this article is to explore data from a wider study in specific relation to the types of vicarious learning experiences reported by pre-dialysis patients. A qualitative study utilised unstructured interviews and grounded theory analysis during the participant's pre-dialysis year. The interview cohort comprised 20 pre-dialysis participants between 24 and 80 years of age. Grounded theory design entailed thematic sampling and analysis, scrutinised by secondary coding and checked with participants. Participants were recruited from routine renal clinics at two local hospitals when their estimated glomerular filtration rate was between 15 and 30 mL/min/1.73 m(2). Vicarious learning that contributed to treatment decision-making fell into three main categories: planned vicarious leaning, unplanned vicarious learning and historical vicarious experiences. Exploration and acknowledgement of service users' prior vicarious learning, by healthcare professionals, is important in understanding its potential influences on individuals' treatment decision-making. This will enable healthcare professionals to challenge heuristic decisions based on limited information and to encourage analytic thought processes.

Pneumocystis pneumonia outbreak among renal transplant recipients at a North American transplant center: Risk factors and implications for infection control.

PubMed

Mulpuru, Sunita; Knoll, Greg; Weir, Colleen; Desjardins, Marc; Johnson, Daniel; Gorn, Ivan; Fairhead, Todd; Bissonnette, Janice; Bruce, Natalie; Toye, Baldwin; Suh, Kathryn; Roth, Virginia

2016-04-01

Pneumocystis pneumonia is a severe opportunistic fungal infection. Outbreaks among renal transplant recipients have been reported in Europe and Japan, but never in North America. We conducted a retrospective case-control study among adult renal transplant recipients at a Canadian center, using a 3:1 matching scheme. Ten cases and 30 controls were matched based on initial transplantation date, and all patients received prophylaxis with trimethoprim-sulfamethoxazole for 1 year posttransplantation. The median time between transplantation and infection was 10.2 years, and all patients survived. Compared with controls, case patients had statistically lower estimated glomerular filtration rate (29.3 mL/min vs 66.3 mL/min; P = .028) and lymphopenia (0.51 × 10(9)/L vs 1.25 × 10(9)/L; P = .002). Transmission mapping revealed significant overlap in the clinic and laboratory visits among case vs control patients (P = .0002). One hundred percent of patients (4 out of 4) successfully genotyped had the same strain of Pneumocystis jirovecii. Our study demonstrated an outbreak of pneumocystis more than 10 years following initial transplantation, despite using recommended initial prophylaxis. We identified low estimated glomerular filtration rate and lymphopenia as risk factors for infection. Overlapping ambulatory care visits were identified as important potential sources of infection transmission, suggesting that institutions should re-evaluate policy and infrastructure strategies to interrupt transmission of respiratory pathogens. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Use of Readily Accessible Inflammatory Markers to Predict Diabetic Kidney Disease.

PubMed

Winter, Lauren; Wong, Lydia A; Jerums, George; Seah, Jas-Mine; Clarke, Michele; Tan, Sih Min; Coughlan, Melinda T; MacIsaac, Richard J; Ekinci, Elif I

2018-01-01

Diabetic kidney disease is a common complication of type 1 and type 2 diabetes and is the primary cause of end-stage renal disease in developed countries. Early detection of diabetic kidney disease will facilitate early intervention aimed at reducing the rate of progression to end-stage renal disease. Diabetic kidney disease has been traditionally classified based on the presence of albuminuria. More recently estimated glomerular filtration rate has also been incorporated into the staging of diabetic kidney disease. While albuminuric diabetic kidney disease is well described, the phenotype of non-albuminuric diabetic kidney disease is now widely accepted. An association between markers of inflammation and diabetic kidney disease has previously been demonstrated. Effector molecules of the innate immune system including C-reactive protein, interleukin-6, and tumor necrosis factor-α are increased in patients with diabetic kidney disease. Furthermore, renal infiltration of neutrophils, macrophages, and lymphocytes are observed in renal biopsies of patients with diabetic kidney disease. Similarly high serum neutrophil and low serum lymphocyte counts have been shown to be associated with diabetic kidney disease. The neutrophil-lymphocyte ratio is considered a robust measure of systemic inflammation and is associated with the presence of inflammatory conditions including the metabolic syndrome and insulin resistance. Cross-sectional studies have demonstrated a link between high levels of the above inflammatory biomarkers and diabetic kidney disease. Further longitudinal studies will be required to determine if these readily available inflammatory biomarkers can accurately predict the presence and prognosis of diabetic kidney disease, above and beyond albuminuria, and estimated glomerular filtration rate.

Prevalence of kidney disease in anaemia differs by GFR-estimating method: The Third National Health and Nutrition Examination Survey (1988–94)

PubMed Central

Estrella, Michelle M.; Astor, Brad C.; Köttgen, Anna; Selvin, Elizabeth; Coresh, Josef; Parekh, Rulan S.

2010-01-01

Background. Anaemia worsens as kidney function declines. Both conditions are associated with increased mortality. Serum cystatin C is purportedly a more sensitive marker of kidney disease and a better predictor of mortality than serum creatinine. However, studies suggest that extrarenal factors also influence cystatin C levels. Methods. We determined whether estimates of glomerular filtration rate [estimated glomerular filtration rate (eGFR)] based on serum cystatin C alone or in combination with serum creatinine were superior to those based on serum creatinine in recognizing impaired kidney function in the setting of anaemia in a sub-sample of the Third National Health and Nutrition Examination Survey of the USA consisting of 6734 participants, 20 years or older. Results. The prevalence of moderate to severe kidney disease (eGFR 15–59 mL/min/1.73 m2) among anaemic persons was 15–16% when based on serum creatinine alone (eGFRSCR) or combined with cystatin C (eGFRSCR + CYSC); this estimate increased to nearly 25% when kidney function was estimated by cystatin C (eGFRCYSC). The adjusted odds ratios of kidney disease in anaemic versus non-anaemic persons were slightly higher with eGFRCYSC than eGFRSCR and eGFRSCR + CYSC in younger adults [odds ratio (OR) = 5.22, 95% confidence interval (CI): 2.23, 12.17], women (OR = 5.34, 95% CI: 2.36, 12.06) and those with elevated C-reactive protein (CRP) (OR = 7.36, 95% CI: 1.98–27.36). Conclusions. Impaired kidney function was common in individuals with anaemia. Among anaemic individuals, the prevalence estimate for kidney disease was notably higher when kidney function was estimated by cystatin C alone compared with the estimations by serum creatinine alone or in combination with serum cystatin C. eGFRCYSC may be particularly helpful in identifying kidney disease in the setting of anaemia among younger persons, women and those with elevated CRP. Regardless of which renal biomarker is used, our study suggests that an evaluation for underlying kidney disease should be considered in the standard workup of anaemia. PMID:20176612

Molecular understanding of the slit diaphragm.

PubMed

Grahammer, Florian; Schell, Christoph; Huber, Tobias B

2013-10-01

Glomerular filtration has always attracted the interest of nephrologists and renal researchers alike. Although several key questions on the structure and function of the kidney filter may have been answered within the last 40 years of intense research, there still remain crucial questions to be solved. The following article attempts to give a brief overview of recent developments in glomerular research highlighting particular advances in our understanding of the slit diaphragm.

Studies of the permeation properties of glomerular basement membrane: cross-linking renders glomerular basement membrane permeable to protein.

PubMed

Walton, H A; Byrne, J; Robinson, G B

1992-03-20

Cross-linking glomerular basement membrane (GBM) has been shown to render it more permeable to protein. Isolated pig GBM was cross-linked with dimethylmalonimidate which reacts selectively with lysine epsilon-NH2 groups or with glutaraldehyde, a less selective cross-linking agent. Studies of the ultrafiltration properties of these materials in vitro using cytochrome c, myoglobin, bovine serum albumin and immunoglobulin showed that cross-linking had markedly increased solvent and protein fluxes as compared with native membranes particularly at higher pressures. Filtration studies with serum demonstrated that the cross-linked membranes were more permeable to serum proteins. Thickness measurements under pressure indicated that cross-linked membrane was less compressed than native membrane as pressure was increased. Pore theory did not provide a suitable model for analysis of the results, but analysis of the results using the fibre-matrix hypothesis indicated that cross-linking had the effect of bundling together the fibres (type IV collagen) in the GBM matrix. The effect of cross-linking on filtration could be explained by a combination of contraction of the membrane, fibre bundling and increased rigidity compared with native membrane. Cross-linking of GBM might lead to long-term damage of the glomerular capillary wall in nephritis, so promoting proteinuria.

Proximal Tubules Have the Capacity to Regulate Uptake of Albumin.

PubMed

Wagner, Mark C; Campos-Bilderback, Silvia B; Chowdhury, Mahboob; Flores, Brittany; Lai, Xianyin; Myslinski, Jered; Pandit, Sweekar; Sandoval, Ruben M; Wean, Sarah E; Wei, Yuan; Satlin, Lisa M; Wiggins, Roger C; Witzmann, Frank A; Molitoris, Bruce A

2016-02-01

Evidence from multiple studies supports the concept that both glomerular filtration and proximal tubule (PT) reclamation affect urinary albumin excretion rate. To better understand these roles of glomerular filtration and PT uptake, we investigated these processes in two distinct animal models. In a rat model of acute exogenous albumin overload, we quantified glomerular sieving coefficients (GSC) and PT uptake of Texas Red-labeled rat serum albumin using two-photon intravital microscopy. No change in GSC was observed, but a significant decrease in PT albumin uptake was quantified. In a second model, loss of endogenous albumin was induced in rats by podocyte-specific transgenic expression of diphtheria toxin receptor. In these albumin-deficient rats, exposure to diphtheria toxin induced an increase in albumin GSC and albumin filtration, resulting in increased exposure of the PTs to endogenous albumin. In this case, PT albumin reabsorption was markedly increased. Analysis of known albumin receptors and assessment of cortical protein expression in the albumin overload model, conducted to identify potential proteins and pathways affected by acute protein overload, revealed changes in the expression levels of calreticulin, disabled homolog 2, NRF2, angiopoietin-2, and proteins involved in ATP synthesis. Taken together, these results suggest that a regulated PT cell albumin uptake system can respond rapidly to different physiologic conditions to minimize alterations in serum albumin level. Copyright © 2016 by the American Society of Nephrology.

Proximal Tubules Have the Capacity to Regulate Uptake of Albumin

PubMed Central

Wagner, Mark C.; Campos-Bilderback, Silvia B.; Chowdhury, Mahboob; Flores, Brittany; Lai, Xianyin; Myslinski, Jered; Pandit, Sweekar; Sandoval, Ruben M.; Wean, Sarah E.; Wei, Yuan; Satlin, Lisa M.; Wiggins, Roger C.; Witzmann, Frank A.

2016-01-01

Evidence from multiple studies supports the concept that both glomerular filtration and proximal tubule (PT) reclamation affect urinary albumin excretion rate. To better understand these roles of glomerular filtration and PT uptake, we investigated these processes in two distinct animal models. In a rat model of acute exogenous albumin overload, we quantified glomerular sieving coefficients (GSC) and PT uptake of Texas Red-labeled rat serum albumin using two-photon intravital microscopy. No change in GSC was observed, but a significant decrease in PT albumin uptake was quantified. In a second model, loss of endogenous albumin was induced in rats by podocyte-specific transgenic expression of diphtheria toxin receptor. In these albumin-deficient rats, exposure to diphtheria toxin induced an increase in albumin GSC and albumin filtration, resulting in increased exposure of the PTs to endogenous albumin. In this case, PT albumin reabsorption was markedly increased. Analysis of known albumin receptors and assessment of cortical protein expression in the albumin overload model, conducted to identify potential proteins and pathways affected by acute protein overload, revealed changes in the expression levels of calreticulin, disabled homolog 2, NRF2, angiopoietin-2, and proteins involved in ATP synthesis. Taken together, these results suggest that a regulated PT cell albumin uptake system can respond rapidly to different physiologic conditions to minimize alterations in serum albumin level. PMID:26054544

Morphine induces albuminuria by compromising podocyte integrity.

PubMed

Lan, Xiqian; Rai, Partab; Chandel, Nirupama; Cheng, Kang; Lederman, Rivka; Saleem, Moin A; Mathieson, Peter W; Husain, Mohammad; Crosson, John T; Gupta, Kalpna; Malhotra, Ashwani; Singhal, Pravin C

2013-01-01

Morphine has been reported to accelerate the progression of chronic kidney disease. However, whether morphine affects slit diaphragm (SD), the major constituent of glomerular filtration barrier, is still unclear. In the present study, we examined the effect of morphine on glomerular filtration barrier in general and podocyte integrity in particular. Mice were administered either normal saline or morphine for 72 h, then urine samples were collected and kidneys were subsequently isolated for immunohistochemical studies and Western blot. For in vitro studies, human podocytes were treated with morphine and then probed for the molecular markers of slit diaphragm. Morphine-receiving mice displayed a significant increase in albuminuria and showed effacement of podocyte foot processes. In both in vivo and in vitro studies, the expression of synaptopodin, a molecular marker for podocyte integrity, and the slit diaphragm constituting molecules (SDCM), such as nephrin, podocin, and CD2-associated protein (CD2AP), were decreased in morphine-treated podocytes. In vitro studies indicated that morphine modulated podocyte expression of SDCM through opiate mu (MOR) and kappa (KOR) receptors. Since morphine also enhanced podocyte oxidative stress, the latter seems to contribute to decreased SDCM expression. In addition, AKT, p38, and JNK pathways were involved in morphine-induced down regulation of SDCM in human podocytes. These findings demonstrate that morphine has the potential to alter the glomerular filtration barrier by compromising the integrity of podocytes.

Requirement for Class II Phosphoinositide 3-Kinase C2α in Maintenance of Glomerular Structure and Function▿

PubMed Central

Harris, David P.; Vogel, Peter; Wims, Marie; Moberg, Karen; Humphries, Juliane; Jhaver, Kanchan G.; DaCosta, Christopher M.; Shadoan, Melanie K.; Xu, Nianhua; Hansen, Gwenn M.; Balakrishnan, Sanjeevi; Domin, Jan; Powell, David R.; Oravecz, Tamas

2011-01-01

An early lesion in many kidney diseases is damage to podocytes, which are critical components of the glomerular filtration barrier. A number of proteins are essential for podocyte filtration function, but the signaling events contributing to development of nephrotic syndrome are not well defined. Here we show that class II phosphoinositide 3-kinase C2α (PI3KC2α) is expressed in podocytes and plays a critical role in maintaining normal renal homeostasis. PI3KC2α-deficient mice developed chronic renal failure and exhibited a range of kidney lesions, including glomerular crescent formation and renal tubule defects in early disease, which progressed to diffuse mesangial sclerosis, with reduced podocytes, widespread effacement of foot processes, and modest proteinuria. These findings were associated with altered expression of nephrin, synaptopodin, WT-1, and desmin, indicating that PI3KC2α deficiency specifically impacts podocyte morphology and function. Deposition of glomerular IgA was observed in knockout mice; importantly, however, the development of severe glomerulonephropathy preceded IgA production, indicating that nephropathy was not directly IgA mediated. PI3KC2α deficiency did not affect immune responses, and bone marrow transplantation studies also indicated that the glomerulonephropathy was not the direct consequence of an immune-mediated disease. Thus, PI3KC2α is critical for maintenance of normal glomerular structure and function by supporting normal podocyte function. PMID:20974805

Fully automatic region of interest selection in glomerular filtration rate estimation from 99mTc-DTPA renogram.

PubMed

Lin, Kun-Ju; Huang, Jia-Yann; Chen, Yung-Sheng

2011-12-01

Glomerular filtration rate (GFR) is a common accepted standard estimation of renal function. Gamma camera-based methods for estimating renal uptake of (99m)Tc-diethylenetriaminepentaacetic acid (DTPA) without blood or urine sampling have been widely used. Of these, the method introduced by Gates has been the most common method. Currently, most of gamma cameras are equipped with a commercial program for GFR determination, a semi-quantitative analysis by manually drawing region of interest (ROI) over each kidney. Then, the GFR value can be computed from the scintigraphic determination of (99m)Tc-DTPA uptake within the kidney automatically. Delineating the kidney area is difficult when applying a fixed threshold value. Moreover, hand-drawn ROIs are tedious, time consuming, and dependent highly on operator skill. Thus, we developed a fully automatic renal ROI estimation system based on the temporal changes in intensity counts, intensity-pair distribution image contrast enhancement method, adaptive thresholding, and morphological operations that can locate the kidney area and obtain the GFR value from a (99m)Tc-DTPA renogram. To evaluate the performance of the proposed approach, 30 clinical dynamic renograms were introduced. The fully automatic approach failed in one patient with very poor renal function. Four patients had a unilateral kidney, and the others had bilateral kidneys. The automatic contours from the remaining 54 kidneys were compared with the contours of manual drawing. The 54 kidneys were included for area error and boundary error analyses. There was high correlation between two physicians' manual contours and the contours obtained by our approach. For area error analysis, the mean true positive area overlap is 91%, the mean false negative is 13.4%, and the mean false positive is 9.3%. The boundary error is 1.6 pixels. The GFR calculated using this automatic computer-aided approach is reproducible and may be applied to help nuclear medicine physicians in clinical practice.

New Model for Estimating Glomerular Filtration Rate in Patients With Cancer

PubMed Central

Janowitz, Tobias; Williams, Edward H.; Marshall, Andrea; Ainsworth, Nicola; Thomas, Peter B.; Sammut, Stephen J.; Shepherd, Scott; White, Jeff; Mark, Patrick B.; Lynch, Andy G.; Jodrell, Duncan I.; Tavaré, Simon; Earl, Helena

2017-01-01

Purpose The glomerular filtration rate (GFR) is essential for carboplatin chemotherapy dosing; however, the best method to estimate GFR in patients with cancer is unknown. We identify the most accurate and least biased method. Methods We obtained data on age, sex, height, weight, serum creatinine concentrations, and results for GFR from chromium-51 (51Cr) EDTA excretion measurements (51Cr-EDTA GFR) from white patients ≥ 18 years of age with histologically confirmed cancer diagnoses at the Cambridge University Hospital NHS Trust, United Kingdom. We developed a new multivariable linear model for GFR using statistical regression analysis. 51Cr-EDTA GFR was compared with the estimated GFR (eGFR) from seven published models and our new model, using the statistics root-mean-squared-error (RMSE) and median residual and on an internal and external validation data set. We performed a comparison of carboplatin dosing accuracy on the basis of an absolute percentage error > 20%. Results Between August 2006 and January 2013, data from 2,471 patients were obtained. The new model improved the eGFR accuracy (RMSE, 15.00 mL/min; 95% CI, 14.12 to 16.00 mL/min) compared with all published models. Body surface area (BSA)–adjusted chronic kidney disease epidemiology (CKD-EPI) was the most accurate published model for eGFR (RMSE, 16.30 mL/min; 95% CI, 15.34 to 17.38 mL/min) for the internal validation set. Importantly, the new model reduced the fraction of patients with a carboplatin dose absolute percentage error > 20% to 14.17% in contrast to 18.62% for the BSA-adjusted CKD-EPI and 25.51% for the Cockcroft-Gault formula. The results were externally validated. Conclusion In a large data set from patients with cancer, BSA-adjusted CKD-EPI is the most accurate published model to predict GFR. The new model improves this estimation and may present a new standard of care. PMID:28686534

New Model for Estimating Glomerular Filtration Rate in Patients With Cancer.

PubMed

Janowitz, Tobias; Williams, Edward H; Marshall, Andrea; Ainsworth, Nicola; Thomas, Peter B; Sammut, Stephen J; Shepherd, Scott; White, Jeff; Mark, Patrick B; Lynch, Andy G; Jodrell, Duncan I; Tavaré, Simon; Earl, Helena

2017-08-20

Purpose The glomerular filtration rate (GFR) is essential for carboplatin chemotherapy dosing; however, the best method to estimate GFR in patients with cancer is unknown. We identify the most accurate and least biased method. Methods We obtained data on age, sex, height, weight, serum creatinine concentrations, and results for GFR from chromium-51 ( 51 Cr) EDTA excretion measurements ( 51 Cr-EDTA GFR) from white patients ≥ 18 years of age with histologically confirmed cancer diagnoses at the Cambridge University Hospital NHS Trust, United Kingdom. We developed a new multivariable linear model for GFR using statistical regression analysis. 51 Cr-EDTA GFR was compared with the estimated GFR (eGFR) from seven published models and our new model, using the statistics root-mean-squared-error (RMSE) and median residual and on an internal and external validation data set. We performed a comparison of carboplatin dosing accuracy on the basis of an absolute percentage error > 20%. Results Between August 2006 and January 2013, data from 2,471 patients were obtained. The new model improved the eGFR accuracy (RMSE, 15.00 mL/min; 95% CI, 14.12 to 16.00 mL/min) compared with all published models. Body surface area (BSA)-adjusted chronic kidney disease epidemiology (CKD-EPI) was the most accurate published model for eGFR (RMSE, 16.30 mL/min; 95% CI, 15.34 to 17.38 mL/min) for the internal validation set. Importantly, the new model reduced the fraction of patients with a carboplatin dose absolute percentage error > 20% to 14.17% in contrast to 18.62% for the BSA-adjusted CKD-EPI and 25.51% for the Cockcroft-Gault formula. The results were externally validated. Conclusion In a large data set from patients with cancer, BSA-adjusted CKD-EPI is the most accurate published model to predict GFR. The new model improves this estimation and may present a new standard of care.

Glomerular filtration rate estimated using creatinine, cystatin C or both markers and the risk of clinical events in HIV-infected individuals.

PubMed

Lucas, G M; Cozzi-Lepri, A; Wyatt, C M; Post, F A; Bormann, A M; Crum-Cianflone, N F; Ross, M J

2014-02-01

The accuracy and precision of glomerular filtration rate (GFR) estimating equations based on plasma creatinine (GFR(cr)), cystatin C (GFR(cys)) and the combination of these markers (GFR(cr-cys)) have recently been assessed in HIV-infected individuals. We assessed the associations of GFR, estimated by these three equations, with clinical events in HIV-infected individuals. We compared the associations of baseline GFR(cr), GFR(cys) and GFR(cr-cys) [using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations] with mortality, cardiovascular events (CVEs) and opportunistic diseases (ODs) in the Strategies for the Management of Antiretroviral Therapy (SMART) study. We used Cox proportional hazards models to estimate unadjusted and adjusted hazard ratios per standard deviation (SD) change in GFR. A total of 4614 subjects from the SMART trial with available baseline creatinine and cystatin C data were included in this analysis. Of these, 99 died, 111 had a CVE and 121 had an OD. GFR(cys) was weakly to moderately correlated with HIV RNA, CD4 cell count, high-sensitivity C-reactive protein, interleukin-6, and D-dimer, while GFR(cr) had little or no correlation with these factors. GFR(cys) had the strongest associations with the three clinical outcomes, followed closely by GFR(cr-cys), with GFR(cr) having the weakest associations with clinical outcomes. In a model adjusting for demographics, cardiovascular risk factors, HIV-related factors and inflammation markers, a 1-SD lower GFR(cys) was associated with a 55% [95% confidence interval (CI) 27-90%] increased risk of mortality, a 21% (95% CI 0-47%) increased risk of CVE, and a 22% (95% CI 0-48%) increased risk of OD. Of the three CKD-EPI GFR equations, GFR(cys) had the strongest associations with mortality, CVE and OD. © 2013 British HIV Association.

Factors associated with renal function compensation after donor nephrectomy.

PubMed

Burballa, Carla; Crespo, Marta; Redondo-Pachón, Dolores; Pérez-Sáez, María José; Arias-Cabrales, Carlos; Mir, Marisa; Francés, Albert; Fumadó, Lluís; Cecchini, Lluís; Pascual, Julio

2018-05-14

Kidney transplant donors lose 50% of their renal mass after nephrectomy. The remaining kidney compensates for this loss and it is estimated that 70% of the baseline renal function prior to donation is recovered. Factors associated with post-donation renal compensation are not well understood. Retrospective study of 66 consecutive kidney donors (mean age 48.8 years, 74.2% women). We analysed the potential factors associated with the compensatory mechanisms of the remaining kidney by comparing donors according to their renal compensation rate (RCR) (Group A, infra-compensation [<70%]; Group B, normal compensation [>70%]). We compared Group A (n=38) and group B (n=28). Predictors for RCR>70% were higher baseline creatinine (A vs B: 0.73±0.14 vs 0.82±0.11; P=.03) and a lower baseline glomerular filtration rate (GFR), estimated both by MDRD-4 (A vs B: 97.7±18.8 vs 78.6±9.6ml/min; P<.001) and CKD-EPI (A vs B: 101.7±15 vs. 88.3±11.7ml/min; P≤.001). Age, gender, smoking, hypertension and GFR measured by Tc-DTPA did not show any correlation with the RCR. The multivariate analysis confirmed baseline estimated glomerular filtration rate (eGFR) to be a predictor of compensation: the higher the baseline eGFR, the lower the likelihood of >70% compensation (MDRD-4, OR=0.94 [95% CI 0.8-0.9], P=.01). The compensation rate decreased by 0.4% (P<.001) and 0.3% (P=.006) for every ml/min increase in baseline eGFR estimated by MDRD-4 and CKD-EPI, respectively. One year after living donor nephrectomy, the remaining kidney partially compensates baseline renal function. In our experience, baseline eGFR is inversely proportional to the one-year renal compensation rate. Copyright © 2018 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Effect of experimental hypothyroidism on glomerular filtration rate and plasma creatinine concentration in dogs.

PubMed

Panciera, D L; Lefebvre, H P

2009-01-01

Hypothyroidism affects renal function in a manner opposite the effects of hyperthyroidism. To evaluate the effects of experimentally induced hypothyroidism on glomerular filtration rate (GFR) and basal plasma creatinine concentration in dogs. Sixteen anestrous, female dogs. Hypothyroidism was induced by administration of (131)I in 8 dogs, and 8 healthy euthyroid dogs acted as controls. Exogenous plasma creatinine clearance (an estimate of GFR) was measured in all dogs before (control period) and 43-50 weeks after induction of hypothyroidism (posttreatment period). Other pharmacokinetic parameters of creatinine were also determined. No significant difference was observed for basal plasma creatinine concentration and creatinine clearance between control and hypothyroid dogs in the control period. In the posttreatment period, mean + or - SD creatinine clearance in the hypothyroid group (2.13 + or - 0.48 mL/min/kg) was lower (P < .001) than that of the control group (3.20 + or - 0.42 mL/kg/min). Nevertheless, basal plasma creatinine concentrations were not significantly different between the hypothyroid and control groups (0.74 + or - 0.18 versus 0.70 + or - 0.08 mg/dL, respectively) because endogenous production of creatinine was decreased in hypothyroid dogs (22 + or - 3 versus 32 + or - 5 mg/kg/d, P=.001). Hypothyroidism causes a substantial decrease in GFR without altering plasma creatinine concentrations, indicating that GFR evaluation is needed to identify renal dysfunction in such patients.

Peritumoral Artery Scoring System: a Novel Scoring System to Predict Renal Function Outcome after Laparoscopic Partial Nephrectomy.

PubMed

Zhang, Ruiyun; Wu, Guangyu; Huang, Jiwei; Shi, Oumin; Kong, Wen; Chen, Yonghui; Xu, Jianrong; Xue, Wei; Zhang, Jin; Huang, Yiran

2017-06-06

The present study aimed to assess the impact of peritumoral artery characteristics on renal function outcome prediction using a novel Peritumoral Artery Scoring System based on computed tomography arteriography. Peritumoral artery characteristics and renal function were evaluated in 220 patients who underwent laparoscopic partial nephrectomy and then validate in 51 patients with split and total glomerular filtration rate (GFR). In particular, peritumoral artery classification and diameter were measured to assign arteries into low, moderate, and high Peritumoral Artery Scoring System risk categories. Univariable and multivariable logistic regression analyses were then used to determine risk factors for major renal functional decline. The Peritumoral Artery Scoring System and four other nephrometry systems were compared using receiver operating characteristic curve analysis. The Peritumoral Artery Scoring System was significantly superior to the other systems for predicting postoperative renal function decline (p < 0.001). In receiver operating characteristic analysis, our category system was a superior independent predictor of estimated glomerular filtration rate (eGFR) decline (area-under-the-curve = 0.865, p < 0.001) and total GFR decline (area-under-the-curve = 0.796, p < 0.001), and split GFR decline (area-under-the-curve = 0.841, p < 0.001). Peritumoral artery characteristics were independent predictors of renal function outcome after laparoscopic partial nephrectomy.

[Renal excretion of methylene-diphosphate-technium-99m. Preliminary observations].

PubMed

Vattimo, A; Martini, G

1983-11-30

The purpose of this study is to elucidate the mechanism of the renal excretion of 99mTc-MDP in man. We compared the renal clearance of 99mTc-MDP and 51Cr-EDTA (glomerular filtration rate agent). Since the 99mTc-MDP is bound to the plasma protein, the free fraction was calculated by dialysis. The clearances were obtained by single-injection technique. The plasma disappearance of the tracers was resolved into three exponential functions and area was calculated. The clearance was calculated by dividing the amount of the tracers excreted during the first four hours and the plasma area. In this study no difference was found in the clearance of the two agents. These findings suggest that the renal excretion of diphosphonate is related to the glomerular filtration rate.

An overview of glomerular filtration rate testing in dogs and cats

PubMed Central

Von Hendy-Willson, Vanessa E.; Pressler, Barrak M.

2010-01-01

Determination of glomerular filtration rate (GFR) is a valuable, yet underused, diagnostic tool for evaluating renal function in dogs and cats. This article first reviews the hormonal and hemodynamic factors which contribute to GFR, followed by a description of considerations when selecting a pharmacokinetic model and methods of animal-to-animal standardization. The best-characterized existing GFR markers, including creatinine, radiolabeled markers, and iohexol, are reviewed in depth, as well as alternative but lesser-used techniques. A weighted means analysis of reported GFR measurements in healthy dogs and cats and a review of selected studies that have examined GFR alterations in animals with naturally-occurring and experimental diseases provide the reader with preliminary guidelines on expected GFR results in these species and disease conditions. PMID:20541957

Dual renin-angiotensin-aldosterone system blockade for diabetic kidney disease.

PubMed

Pichler, Raimund H; de Boer, Ian H

2010-08-01

Blockade of the renin-angiotensin-aldosterone system (RAAS) prevents the development and progression of diabetic kidney disease (DKD). It is controversial whether the simultaneous use of two RAAS inhibitors (ie, dual RAAS blockade) further improves renal outcomes. This review examines the scientific rationale and current clinical evidence addressing the use of dual RAAS blockade to prevent and treat DKD. It is concluded that dual RAAS blockade should not be routinely applied to patients with low or moderate risk of progressive kidney disease (normoalbuminuria or microalbuminuria with preserved glomerular filtration rate). For patients with high risk of progressive kidney disease (substantial albuminuria or impaired glomerular filtration rate), clinicians should carefully weigh the potential risks and benefits of dual RAAS blockade on an individual basis until ongoing clinical trials provide further insight.

Effects of a supplemented hypoproteic diet in chronic kidney disease.

PubMed

Mircescu, Gabriel; Gârneaţă, Liliana; Stancu, Simona Hildegard; Căpuşă, Cristina

2007-05-01

We assessed the effect of a severe hypoproteic diet supplemented with ketoanalogues (SVLPD) for 48 weeks on certain metabolic disorders of chronic kidney disease (CKD). We performed a prospective, open-label, parallel, randomized, controlled trial. The study took place in the Nephrology Department at the Dr Carol Davila Teaching Hospital of Nephrology, Bucharest, Romania. A total of 53 nondiabetic patients with CKD with an estimated glomerular filtration rate less than 30 mL/min/1.73 m(2) (Modification of Diet in Renal Disease formula), proteinuria less than 1 g/g urinary creatinine, good nutritional status, and anticipated good compliance with the diet were randomly assigned to two groups. Group I (n = 27) received the SVLPD (0.3 g/kg/d of vegetable proteins and ketoanalogues, 1 capsule for every 5 kg of ideal body weight per day). Group II (n = 26) continued a conventional low mixed protein diet (0.6 g/kg/d). Nitrogen waste products retention and calcium-phosphorus and acid-base disturbances were primary efficacy parameters, and "death" of the kidney or the patient and the estimated glomerular filtration rate were secondary efficacy parameters. The nutritional status and compliance with the diet were predefined as safety variables. There were no differences between groups in any parameter at baseline. In the SVLPD group, serum urea significantly decreased (56 +/- 7.9 mmol/L vs. 43.2 +/- 10 mmol/L), and significant improvements in serum bicarbonate (23.4 +/- 2.1 mmol/L vs. 18.1 +/- 1.5 mmol/L), serum calcium (1.10 +/- 0.17 mmol/L vs. 1.00 +/- 0.15 mmol/L at baseline), serum phosphates (1.45 +/- 0.66 mmol/L vs. 1.91 +/- 0.68 mmol/L), and calcium-phosphorus product (1.59 +/- 0.11 mmol(2)/L(2) vs. 1.91 +/- 0.10 mmol(2)/L(2)) were noted after 48 weeks. No death was registered in any group. Significantly lower percentages of patients in group I required renal replacement therapy initiation (4% vs. 27%). After 48 weeks, estimated glomerular filtration rate did not significantly change in patients receiving SVLPD (0.26 +/- 0.08 mL/s vs. 0.31 +/- 0.08 mL/s at baseline), but significantly decreased in controls (0.22 +/- 0.09 mL/s vs. 0.30 +/- 0.07 mL/s). The compliance with the keto-diet was good in enrolled patients. No significant changes in any of the parameters of the nutritional status and no adverse reactions were noted. SVLPD seems to ameliorate the nitrogen waste products retention and acid-base and calcium-phosphorus metabolism disturbances and to postpone the renal replacement therapy initiation, preserving the nutritional status in patients with CKD.

Quantifying Glomerular Permeability of Fluorescent Macromolecules Using 2-Photon Microscopy in Munich Wistar Rats

PubMed Central

Sandoval, Ruben M.; Molitoris, Bruce A.

2013-01-01

Kidney diseases involving urinary loss of large essential macromolecules, such as serum albumin, have long been thought to be caused by alterations in the permeability barrier comprised of podocytes, vascular endothelial cells, and a basement membrane working in unison. Data from our laboratory using intravital 2-photon microscopy revealed a more permeable glomerular filtration barrier (GFB) than previously thought under physiologic conditions, with retrieval of filtered albumin occurring in an early subset of cells called proximal tubule cells (PTC)1,2,3. Previous techniques used to study renal filtration and establishing the characteristic of the filtration barrier involved micropuncture of the lumen of these early tubular segments with sampling of the fluid content and analysis4. These studies determined albumin concentration in the luminal fluid to be virtually non-existent; corresponding closely to what is normally detected in the urine. However, characterization of dextran polymers with defined sizes by this technique revealed those of a size similar to serum albumin had higher levels in the tubular lumen and urine; suggesting increased permeability5. Herein is a detailed outline of the technique used to directly visualize and quantify glomerular fluorescent albumin permeability in vivo. This method allows for detection of filtered albumin across the filtration barrier into Bowman's space (the initial chamber of urinary filtration); and also allows quantification of albumin reabsorption by proximal tubules and visualization of subsequent albumin transcytosis6. The absence of fluorescent albumin along later tubular segments en route to the bladder highlights the efficiency of the retrieval pathway in the earlier proximal tubule segments. Moreover, when this technique was applied to determine permeability of dextrans having a similar size to albumin virtually identical permeability values were reported2. These observations directly support the need to expand the focus of many proteinuric renal diseases to included alterations in proximal tubule cell reclamation. PMID:23628966

Measurement of glomerular filtration rate using dynamic magnetic resonance imaging in patients with chronic kidney disease.

PubMed

Artunc, Ferruh; Yildiz, Serdar; Boss, Andreas; Frenzel, Thomas; Schlemmer, Heinz-Peter; Schick, Fritz; Risler, Teut; Häring, Hans-Ulrich; Rossi, Cristina

2011-01-01

Determination of glomerular filtration rate (GFR) using plasma disappearance curves requires the injection of a filtration marker and repeated timed blood collections. Gadolinium-containing contrast media are excreted exclusively by glomerular filtration and could provide a novel approach to quantifying GFR using magnetic resonance (MR) imaging. The aim of this study was to demonstrate the feasibility of measuring GFR by the clearance of gadolinium-containing contrast medium in patients with chronic kidney disease (CKD). Informed consent was obtained from stable CKD patients in stages 1, 2 or 3 (n=16; 5 women, 11 men; median age 54 years). GFR was measured after a bolus injection of gadobutrol (4 mL, approximately 0.05 mmol/kg) and calculated from the washout of the signal intensity obtained over the liver. The obtained MR-GFR was compared with simultaneously measured plasma clearance of inulin and gadobutrol. Technical failure occurred in 2 patients. The mean obtained MR-GFR was 71 ± 25 (SD) mL/min per 1.73 m² and agreed well with the mean inulin-GFR (70 ± 24 mL/min per 1.73 m²). Pearson's correlation coefficient was r=0.91. The mean of the paired differences was 1 ± 10 mL/min per 1.73 m² and not significantly different from zero. GFR obtained from gadobutrol plasma clearance also agreed well with inulin-GFR and MR-GFR (r=0.92 and r=0.75, respectively). We describe a novel method of determining GFR from MR imaging using a low dose of gadobutrol in patients with reduced GFR that enables the absolute quantification of GFR after routine contrast-enhanced MR imaging.

Associations of Perfluoroalkyl Substances (PFAS) with Lower Birth Weight: An Evaluation of Potential Confounding by Glomerular Filtration Rate Using a Physiologically Based Pharmacokinetic Model (PBPK)

PubMed Central

Loccisano, Anne E.; Morken, Nils-Halvdan; Yoon, Miyoung; Wu, Huali; McDougall, Robin; Maisonet, Mildred; Marcus, Michele; Kishi, Reiko; Miyashita, Chihiro; Chen, Mei-Huei; Hsieh, Wu-Shiun; Andersen, Melvin E.; Clewell, Harvey J.; Longnecker, Matthew P.

2015-01-01

Background Prenatal exposure to perfluoroalkyl substances (PFAS) has been associated with lower birth weight in epidemiologic studies. This association could be attributable to glomerular filtration rate (GFR), which is related to PFAS concentration and birth weight. Objectives We used a physiologically based pharmacokinetic (PBPK) model of pregnancy to assess how much of the PFAS–birth weight association observed in epidemiologic studies might be attributable to GFR. Methods We modified a PBPK model to reflect the association of GFR with birth weight (estimated from three studies of GFR and birth weight) and used it to simulate PFAS concentrations in maternal and cord plasma. The model was run 250,000 times, with variation in parameters, to simulate a population. Simulated data were analyzed to evaluate the association between PFAS levels and birth weight due to GFR. We compared simulated estimates with those from a meta-analysis of epidemiologic data. Results The reduction in birth weight for each 1-ng/mL increase in simulated cord plasma for perfluorooctane sulfonate (PFOS) was 2.72 g (95% CI: –3.40, –2.04), and for perfluorooctanoic acid (PFOA) was 7.13 g (95% CI: –8.46, –5.80); results based on maternal plasma at term were similar. Results were sensitive to variations in PFAS level distributions and the strength of the GFR–birth weight association. In comparison, our meta-analysis of epidemiologic studies suggested that each 1-ng/mL increase in prenatal PFOS and PFOA levels was associated with 5.00 g (95% CI: –21.66, –7.78) and 14.72 g (95% CI: –8.92, –1.09) reductions in birth weight, respectively. Conclusion Results of our simulations suggest that a substantial proportion of the association between prenatal PFAS and birth weight may be attributable to confounding by GFR and that confounding by GFR may be more important in studies with sample collection later in pregnancy. Citation Verner MA, Loccisano AE, Morken NH, Yoon M, Wu H, McDougall R, Maisonet M, Marcus M, Kishi R, Miyashita C, Chen MH, Hsieh WS, Andersen ME, Clewell HJ III, Longnecker MP. 2015. Associations of perfluoroalkyl substances (PFAS) with lower birth weight: an evaluation of potential confounding by glomerular filtration rate using a physiologically based pharmacokinetic model (PBPK). Environ Health Perspect 123:1317–1324; http://dx.doi.org/10.1289/ehp.1408837 PMID:26008903

About Chronic Kidney Disease

MedlinePlus

... Donate A to Z Health Guide About Chronic Kidney Disease Tweet Share Print Email Chronic kidney disease ( ... about Glomerular Filtration Rate (GFR) What is chronic kidney disease (CKD)? Chronic kidney disease includes conditions that ...

The renal response to electrical stimulation of renal efferent sympathetic nerves in the anaesthetized greyhound.

PubMed Central

Poucher, S M; Karim, F

1991-01-01

1. The effect of direct electrical stimulation of the renal efferent nerves upon renal haemodynamics and function was studied in greyhounds anaesthetized with chloralose and artificially ventilated. The left kidney was neurally and vascularly isolated, and perfused with blood from one of the femoral arteries at a constant pressure of 99 +/- 1 mmHg. Renal blood flow was measured with a cannulating electromagnetic flow probe placed in the perfusion circuit, glomerular filtration rate by creatinine clearance, urinary sodium excretion by flame photometry and solute excretion by osmometry. Beta-Adrenergic receptor activation was blocked by the infusion of dl-propranolol (17 micrograms kg-1 min-1). The peripheral ends of the ligated renal nerves were stimulated at 0.5, 1.0, 1.5 and 2.0 Hz. 2. At 0.5 Hz frequency only osmolar excretion was significantly reduced (10.3 +/- 3.2%, P less than 0.05, n = 6). Reductions in sodium excretion (53.6 +/- 8.5%, P less than 0.01, n = 6) and water excretion (26.9 +/- 8.0%, P less than 0.05, n = 6) and further reductions of osmolar excretion (20.7 +/- 3.7%, P less than 0.01, n = 6) were observed at 1.0 Hz; however, these were observed in the absence of significant changes in renal blood flow and glomerular filtration rate. Significant reductions were observed in glomerular filtration rate at 1.5 Hz (16.3 +/- 4.1%, P less than 0.02, n = 5) and in renal blood flow at 2.0 Hz (13.1 +/- 4.0%, P less than 0.05, n = 5). Further reductions in urine flow and sodium excretion were also observed at these higher frequencies. 3. These results clearly show that significant changes in renal tubular function can occur in the absence of changes in renal blood flow and glomerular filtration rate when the renal nerves are stimulated electrically from a zero baseline activity up to a frequency of 1.5 Hz. Higher frequencies caused significant changes in both renal haemodynamics and function. PMID:2023113

Tumstatin peptide, an inhibitor of angiogenesis, prevents glomerular hypertrophy in the early stage of diabetic nephropathy.

PubMed

Yamamoto, Yoshihiko; Maeshima, Yohei; Kitayama, Hiroyuki; Kitamura, Shinji; Takazawa, Yuki; Sugiyama, Hitoshi; Yamasaki, Yasushi; Makino, Hirofumi

2004-07-01

In the early stage of diabetic nephropathy (one of the major microvascular complications of diabetes) glomerular hyperfiltration and hypertrophy are observed. It is clinically important to regulate glomerular hypertrophy for preventing glomerulosclerosis. The number of glomerular endothelial cells is known to be increased in diabetic nephropathy associated with enlarged glomerular tufts, suggesting that the mechanism is similar to that of angiogenesis. Tumstatin peptide is an angiogenesis inhibitor derived from type IV collagen and inhibits in vivo neovascularization induced by vascular endothelial growth factor (VEGF), one of the mediators of glomerular hypertrophy in diabetic nephropathy. Here, we show the effect of tumstatin peptide in inhibiting alterations in early diabetic nephropathy. Glomerular hypertrophy, hyperfiltration, and albuminuria were suppressed by tumstatin peptide (1 mg/kg) in streptozotocin-induced diabetic mice. Glomerular matrix expansion, the increase of total glomerular cell number and glomerular endothelial cells (CD31 positive), and monocyte/macrophage accumulation was inhibited by tumstatin peptide. Increase in renal expression of VEGF, flk-1, and angiopoietin-2, an antagonist of angiopoietin-1, was inhibited by tumstatin treatment in diabetic mice. Alteration of glomerular nephrin expression, a podocyte protein crucial for maintaining glomerular filtration barrier, was recovered by tumstatin in diabetic mice. Taken together, these results demonstrate the potential use of antiangiogenic tumstatin peptide as a novel therapeutic agent in early diabetic nephropathy.

Using the Drosophila Nephrocyte to Model Podocyte Function and Disease

PubMed Central

Helmstädter, Martin; Huber, Tobias B.; Hermle, Tobias

2017-01-01

Glomerular disorders are a major cause of end-stage renal disease and effective therapies are often lacking. Nephrocytes are considered to be part of the Drosophila excretory system and form slit diaphragms across cellular membrane invaginations. Nehphrocytes have been shown to share functional, morphological, and molecular features with podocytes, which form the glomerular filter in vertebrates. Here, we report the progress and the evolving tool-set of this model system. Combining a functional, accessible slit diaphragm with the power of the genetic tool-kit in Drosophila, the nephrocyte has the potential to greatly advance our understanding of the glomerular filtration barrier in health and disease. PMID:29270398

Kidney Function in Obesity-Challenges in Indexing and Estimation.

PubMed

Chang, Alex R; Zafar, Waleed; Grams, Morgan E

2018-01-01

As the prevalence of obesity continues to increase worldwide, an increasing number of people are at risk for kidney disease. Thus, there is a critical need to understand how best to assess kidney function in this population, and several challenges exist. The convention of indexing glomerular filtration rate (GFR) to body surface area (BSA) attempts to normalize exposure to metabolic wastes across populations of differing body size. In obese individuals, this convention results in a significantly lower indexed GFR than unindexed GFR, which has practical implications for drug dosing. Recent data suggest that "unindexing" estimated GFR (multiplying by BSA/1.73 m 2 ) for drug dosing may be acceptable, but pharmocokinetic data to support this practice are lacking. Beyond indexing, biomarkers commonly used for estimating GFR may induce bias. Creatinine is influenced by muscle mass, whereas cystatin C correlates with fat mass, both independent of kidney function. Further research is needed to evaluate the performance of estimating equations and other filtration markers in obesity, and determine whether unindexed GFR might better predict optimal drug dosing and clinical outcomes in patients whose BSA is very different than the conventional normalized value of 1.73 m 2 . Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Phase 1 trial of adalimumab in Focal Segmental Glomerulosclerosis (FSGS): II. Report of the FONT (Novel Therapies for Resistant FSGS) study group.

PubMed

Joy, Melanie S; Gipson, Debbie S; Powell, Leslie; MacHardy, Jacqueline; Jennette, J Charles; Vento, Suzanne; Pan, Cynthia; Savin, Virginia; Eddy, Allison; Fogo, Agnes B; Kopp, Jeffrey B; Cattran, Daniel; Trachtman, Howard

2010-01-01

Patients with primary focal segmental glomerulosclerosis (FSGS) resistant to current treatment regimens are at high risk of progression to end-stage kidney disease. Antifibrotic agents, such as tumor necrosis factor alpha antagonists, are a promising strategy to slow or halt the decline in renal function, based on preclinical and clinical data. Phase 1 clinical trial to assess the pharmacokinetics, tolerability, and safety of adalimumab, a human monoclonal antibody to tumor necrosis factor alpha. 10 patients (4 male and 6 female) aged 16.8 +/- 9.0 years with an estimated glomerular filtration rate of 105 +/- 50 mL/min/1.73 m(2) were studied. Adalimumab, 24 mg/m(2), every 14 days for 16 weeks (total, 9 doses). Pharmacokinetic assessment, tolerability, and safety. Estimated glomerular filtration rate, proteinuria, and pharmacokinetic assessment after initial dosing and steady state. Pharmacokinetic evaluation indicated that the area under the curve was decreased by 54% (P < 0.001) and clearance was increased by 160% (P < 0.01) in patients with resistant FSGS compared with healthy controls and patients with rheumatoid arthritis. Adalimumab was well tolerated with no serious adverse events or infectious complications attributable to the drug. Proteinuria decreased by > or = 50% in 4 of 10 treated patients. Insufficient power to assess the safety or efficacy of adalimumab therapy for patients with resistant FSGS. Pharmacokinetic assessment showed increased clearance of adalimumab in patients with resistant primary FSGS and validated the need to evaluate the disposition of novel therapies for this disease to define appropriate dosing regimens. The study provides a rationale to evaluate the efficacy of adalimumab as an antifibrotic agent for resistant FSGS in phase 2/3 clinical trials. Copyright 2009 National Kidney Foundation, Inc. All rights reserved.

Long-term Outcome of 1-step Kidney Transplantation and Bladder Augmentation Procedure in Pediatric Patients.

PubMed

Cleper, Roxana; Ben Meir, David; Krause, Irit; Livne, Pinchas; Mor, Eitan; Davidovits, Miriam; Dagan, Amit

2018-06-01

Guidelines for bladder augmentation (BA) in kidney transplantation (KT) recipients are not well-defined. In our center, simultaneous BA with KT (BA-KT) is performed. We assessed transplantation outcomes of this unique extensive procedure. A case-control single center retrospective study. Transplantation outcomes were compared with those of KT recipients who did not need BA. Compared with 22 patients who underwent KT only, for 9 who underwent BA-KT, surgical complications and the need for revision in the early posttransplantation period were similar; early graft function was better: estimated glomerular filtration rate, 96.5 ± 17.1 versus 79.4 ± 16.6 mL/min at 0 to 6 months (P = 0.02); posttransplantation clean intermittent catheterization was more often needed: by 78% (7/9) versus 13% (3/22); and asymptomatic bacteriuria was more common: 100% versus 9% during the first 6 months (P < 0.001), 55% versus 9% (P = 0.02) and 66.6% versus 9% during the first and second years, respectively (P = 0.004). Urinary tract infection (UTI) incidence was also higher: 100% versus 23% during the first 6 months and 44% versus 9% during the second year posttransplantation. Graft function deteriorated significantly in the BA-KT group by the fifth posttransplantation year: estimated glomerular filtration rate was 47.7 ± 39.7 mL/min versus 69 ± 21.3 mL/min, with only 6 (66%) of 9 functioning grafts versus 100% in the KT only group. Causes of graft loss were noncompliance with drug therapy in 2 patients and recurrent UTIs in 2 patients. Excellent short-term outcome for simultaneous BA-KT is threatened by graft loss due to a high prevalence of UTIs and patient noncompliance with the demanding complex posttransplantation therapy.

Recent trends in the prevalence of chronic kidney disease: not the same old song.

PubMed

Hsu, Raymond K; Powe, Neil R

2017-05-01

We aim to review recent updates on the epidemiology of chronic kidney disease (CKD). Recent analyses from the National Health and Nutritional Examination survey describe the temporal trend in CKD prevalence in US adults. The overall prevalence of estimated glomerular filtration rate less than 60 ml/min/1.73 m increased from 4.8% in 1988-1994 to 6.9% in 2003-2004, but has since stabilized at 6.4-6.9% up to 2011-2012. Prevalence of CKD stages 1-4 has also stabilized at ∼14% of adults since 2003-2004. The prevalence of diabetic kidney disease - defined as estimated glomerular filtration rate less than 60 ml/min/1.73 m and/or microalbuminuria among adults with diabetes - has similarly plateaued since the early to mid-2000s at ∼26-27%. There is continued rise in CKD and diabetic kidney disease prevalence among blacks and Mexican-Americans, however, in the last decade. Worldwide, a similar pattern of stable prevalence of CKD since the early 2000s is seen in England, Norway, and Korea. Despite these optimistic findings, there are several emerging at-risk populations. Rapid increases in diabetes and hypertension in China may signal an impending growth in CKD. In parts of Central America, there is emergence of very high CKD prevalence among agricultural workers - suspected to be due to occupational and environmental exposures. Collective efforts to undermine risk factors, such as better control of hypertension and diabetes, have likely helped to abate the growth in CKD in several developed countries within the last decade. More worldwide high-quality and geographically granular data collection on CKD would help to monitor the epidemiology of CKD and potentially assist in identifying impactful interventions.

Chronic kidney disease in patients at high risk of cardiovascular disease in the United Arab Emirates: A population-based study.

PubMed

Al-Shamsi, S; Regmi, D; Govender, R D

2018-01-01

Chronic kidney disease has become an increasingly significant clinical and public health issue, accounting for 1.1 million deaths worldwide. Information on the epidemiology of chronic kidney disease and associated risk factors is limited in the United Arab Emirates. Therefore, this study aimed to evaluate the incidence and causes of chronic kidney disease stages 3-5 in adult United Arab Emirates nationals with or at high risk of cardiovascular disease. This retrospective study included 491 adults with or at high risk of cardiovascular disease (diabetes mellitus or associated clinical disease) who attended outpatient clinics at a tertiary care hospital in Al-Ain, United Arab Emirates. Estimated glomerular filtration rate was assessed every 3 months from baseline to June 30, 2017. Chronic kidney disease stages 3-5 were defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m2 for ≥ 3 months. Multivariable Cox's proportional hazards analysis was used to determine the independent risk factors associated with developing chronic kidney disease stages 3-5. The cumulative incidence of chronic kidney disease stages 3-5 over a 9-year period was 11.4% (95% confidence interval 8.6, 14.0). The incidence rate of these disease stages was 164.8 (95% confidence interval 121.6, 207.9) per 10,000 person-years. The independent risk factors for developing chronic kidney disease stages 3-5 were older age, history of coronary heart disease, history of diabetes mellitus, and history of smoking. These data may be useful to develop effective strategies to prevent chronic kidney disease development in high-risk United Arab Emirates nationals.

AKIGUARD (Acute Kidney Injury GUARding Device) trial: in-hospital and one-year outcomes.

PubMed

Usmiani, Tullio; Andreis, Alessandro; Budano, Carlo; Sbarra, Pierluigi; Andriani, Monica; Garrone, Paolo; Fanelli, Anna Laura; Calcagnile, Chiara; Bergamasco, Laura; Biancone, Luigi; Marra, Sebastiano

2016-07-01

Contrast-induced acute kidney injury (CIAKI) in patients with chronic kidney disease undergoing coronary angiography or percutaneous coronary intervention is a common iatrogenic complication associated with increased morbidity and mortality. This study compares sodium bicarbonate/isotonic saline/N-acetylcysteine/vitamin C prophylaxis (BS-NAC) against high-volume forced diuresis with matched hydration in CIAKI prevention. One-hundred and thirty-three consecutive patients undergoing coronary angiography or percutaneous coronary intervention with estimated glomerular filtration rate less than 60 mL/min/1.73m were randomized to the study group receiving matched hydration (MHG) or to the control group receiving BS-NAC. MHG received in vein (i.v.) 250 mL isotonic saline bolus, followed by a 0.5 mg/kg furosemide i.v. bolus to forced diuresis. A dedicated device automatically matched the isotonic saline i.v. infusion rate to the urinary output for 1 h before, during and 4 h after the procedure. MHG had the lowest incidence of CIAKI (7 vs. 25%, P = 0.01), major adverse cardiac and cerebrovascular events at 1 year (7 vs. 32%, P < 0.01) and readmissions to cardiology/nephrology departments (8 vs. 25%, P = 0.03; hospitalization days 1.0 ± 3.8 vs. 4.9 ± 12.5, P = 0.01). Three months after the procedure the decrease in the estimated glomerular filtration rate was 0.02% for MHG versus 15% for the control group. Matched hydration was more effective than BS-NAC in CIAKI prevention. One-year follow-up showed that matched hydration was associated also with limited chronic kidney disease progression, major adverse cardiac and cerebrovascular events and hospitalizations.

Effects of a Multicomponent Life-Style Intervention on Weight, Glycemic Control, Depressive Symptoms, and Renal Function in Low-Income, Minority Patients With Type 2 Diabetes: Results of the Community Approach to Lifestyle Modification for Diabetes Randomized Controlled Trial.

PubMed

Moncrieft, Ashley E; Llabre, Maria M; McCalla, Judith Rey; Gutt, Miriam; Mendez, Armando J; Gellman, Marc D; Goldberg, Ronald B; Schneiderman, Neil

2016-09-01

Few interventions have combined life-style and psychosocial approaches in the context of Type 2 diabetes management. The purpose of this study was to determine the effect of a multicomponent behavioral intervention on weight, glycemic control, renal function, and depressive symptoms in a sample of overweight/obese adults with Type 2 diabetes and marked depressive symptoms. A sample of 111 adults with Type 2 diabetes were randomly assigned to a 1-year intervention (n = 57) or usual care (n = 54) in a parallel groups design. Primary outcomes included weight, glycosylated hemoglobin, and Beck Depression Inventory II score. Estimated glomerular filtration rate served as a secondary outcome. All measures were assessed at baseline and 6 and 12 months after randomization by assessors blind to randomization. Latent growth modeling was used to examine intervention effects on each outcome. The intervention resulted in decreased weight (mean [M] = 0.322 kg, standard error [SE] = 0.124 kg, p = .010) and glycosylated hemoglobin (M = 0.066%, SE = 0.028%, p = .017), and Beck Depression Inventory II scores (M = 1.009, SE = 0.226, p < .001), and improved estimated glomerular filtration rate (M = 0.742 ml·min·1.73 m, SE = 0.318 ml·min·1.73 m, p = .020) each month during the first 6 months relative to usual care. Multicomponent behavioral interventions targeting weight loss and depressive symptoms as well as diet and physical activity are efficacious in the management of Type 2 diabetes. This study is registered at Clinicaltrials.gov ID: NCT01739205.

Association between Metformin Use and Risk of Lactic Acidosis or Elevated Lactate Concentration in Type 2 Diabetes.

PubMed

Lee, Eun Young; Hwang, Sena; Lee, Yong Ho; Lee, Seo Hee; Lee, Young Mi; Kang, Hua Pyong; Han, Eugene; Lee, Woonhyoung; Lee, Byung Wan; Kang, Eun Seok; Cha, Bong Soo; Lee, Hyun Chul

2017-03-01

Metformin can reduce diabetes-related complications and mortality. However, its use is limited because of potential lactic acidosis-associated adverse effects, particularly in renal impairment patients. We aimed to investigate the association of metformin use with lactic acidosis and hyperlactatemia in patients with type 2 diabetes. This was a cross-sectional study from a tertiary university-affiliated medical center. A total of 1954 type 2 diabetes patients were recruited in 2007-2011, and stratified according to the estimated glomerular filtration rate of 60 mL/min/1.73 m². Lactic acidosis was defined as plasma lactate levels >5 mmol/L and arterial pH <7.35. Metformin was used in 61.4% of the patients with type 2 diabetes mellitus. Plasma lactate levels were not different in the patients with and without metformin use. There was no difference in prevalence of hyperlactatemia and lactic acidosis between the patients with and without metformin use (18.9% vs. 18.7%, p=0.905 for hyperlactatemia and 2.8% vs. 3.3%, p=0.544 for lactic acidosis). Similar results were observed in the patients with estimated glomerular filtration rate <60 mL/min/1.73 m². Most patients with lactic acidosis had at least one condition related to hypoxia or poor tissue perfusion. Multiple regression analysis indicated no association between metformin use and lactic acidosis, whereas tissue hypoxia was an independent risk factor for lactic acidosis [odds ratio 4.603 (95% confidence interval, 1.327-15.965)]. Metformin use was not associated with hyperlactatemia or lactic acidosis in patients with type 2 diabetes.

Effect of losartan on proteinuria and urinary angiotensinogen excretion in non-diabetic patients with chronic kidney disease.

PubMed

Lee, Yu-Ji; Cho, Seong; Kim, Sung Rok; Jang, Hye Ryoun; Lee, Jung Eun; Huh, Wooseong; Kim, Dae Joong; Oh, Ha Young; Kim, Yoon-Goo

2011-10-01

Activation of the rennin-angiotensin system (RAS) is thought to contribute to hypertension and proteinuria, and eventually to the progression of chronic kidney disease (CKD). Recent evidence suggests that urinary angiotensinogen (UAGT) excretion reflects activation of the intrarenal RAS. This study was performed to determine the effect of losartan on proteinuria and UAGT excretion in non-diabetic patients with CKD with non-nephrotic-range proteinuria. Thirty-two patients with non-nephrotic-range proteinuria (0.045-0.23 g/mmol creatinine) and normal renal function between April 2005 and April 2006 were randomised to a losartan (n=17) or a control (n=15) group. Patients in the losartan group received losartan 50 mg/day, and the doses were titrated up to 100 mg/day after 6 weeks. Serum and urinary angiotensinogen concentrations were measured by sandwich ELISA. The primary end point was the percentage change in proteinuria. The secondary end points were changes in estimated glomerular filtration rate and UAGT excretion. The follow-up period was 24 months. Baseline characteristics in the two groups were similar. After 24 months, losartan had reduced urinary protein excretion by 43% (from mean±SD 0.13±0.04 to 0.073±0.03 g/mmol, p<0.0001), but proteinuria had not changed in the control group. The percentage change in mean arterial pressure did not differ between the groups. Losartan decreased logarithmically converted UAGT excretion (from 1.58±0.47 to 1.00±0.52, p=0.001). Estimated glomerular filtration rate decreased significantly only in the control group. Losartan significantly decreased proteinuria and UAGT excretion, and preserved renal function in non-diabetic patients with CKD.

Arteriovenous fistula creation may slow estimated glomerular filtration rate trajectory

PubMed Central

Golper, Thomas A.; Hartle, Phillip Matthew; Bian, Aihua

2015-01-01

Background We practice the timely placement of an arteriovenous fistula (AVF) in patients facing chronic hemodialysis. We have anecdotally observed after AVF creation that there appears to be a slowing of the decline in kidney function as measured by the estimated glomerular filtration rate (eGFR). There are physiologically plausible explanations as to how an AVF might alter kidney function, but this clinical observation has been attributed to improved compliance and/or other practices. The present retrospective observational analysis was performed to assess the possibility that a successfully created AVF could be associated with the slowing of the eGFR trajectory. Methods We identified 123 patients between 2005 and 2010 with at least two eGFR determinations for 2 years before and up to 2 years after AVF creation. Inclusion eligibility was that the fistula was maturing by the nephrologists' initial post-creation examination. Termination events were death, starting dialysis or transplantation. Each subject served as their own control for the pre- and post-AVF-creation eGFR measurements. Results Subjects' median age was 68 years and 56% were diabetic. The rate of change of the eGFR for the 2 years prior to AVF creation was −5.9 mL/min/year (95% CI: −5.3, −6.5) and after AVF creation −0.5 mL/min/year (95% CI: −1.1, 0.1) (interaction (P < 0.001). Conclusions A functioning AVF may be associated with a slowing of the eGFR decline. Agreeing to timely AVF creation selects patients in an otherwise typical population and other confounders have not yet been eliminated. To do so a thorough prospective observational study is indicated. PMID:25888388

Arteriovenous fistula creation may slow estimated glomerular filtration rate trajectory.

PubMed

Golper, Thomas A; Hartle, Phillip Matthew; Bian, Aihua

2015-12-01

We practice the timely placement of an arteriovenous fistula (AVF) in patients facing chronic hemodialysis. We have anecdotally observed after AVF creation that there appears to be a slowing of the decline in kidney function as measured by the estimated glomerular filtration rate (eGFR). There are physiologically plausible explanations as to how an AVF might alter kidney function, but this clinical observation has been attributed to improved compliance and/or other practices. The present retrospective observational analysis was performed to assess the possibility that a successfully created AVF could be associated with the slowing of the eGFR trajectory. We identified 123 patients between 2005 and 2010 with at least two eGFR determinations for 2 years before and up to 2 years after AVF creation. Inclusion eligibility was that the fistula was maturing by the nephrologists' initial post-creation examination. Termination events were death, starting dialysis or transplantation. Each subject served as their own control for the pre- and post-AVF-creation eGFR measurements. Subjects' median age was 68 years and 56% were diabetic. The rate of change of the eGFR for the 2 years prior to AVF creation was -5.9 mL/min/year (95% CI: -5.3, -6.5) and after AVF creation -0.5 mL/min/year (95% CI: -1.1, 0.1) (interaction (P < 0.001). A functioning AVF may be associated with a slowing of the eGFR decline. Agreeing to timely AVF creation selects patients in an otherwise typical population and other confounders have not yet been eliminated. To do so a thorough prospective observational study is indicated. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Flexible ureterorenoscopy is safe and efficient for the treatment of kidney stones in patients with chronic kidney disease.

PubMed

Yuruk, Emrah; Binbay, Murat; Ozgor, Faruk; Erbin, Akif; Berberoglu, Yalcin; Muslumanoglu, Ahmet Y

2014-12-01

To evaluate the outcomes of kidney stone treatment using flexible ureterorenoscopy (f-URS) among patients with chronic kidney disease (CKD). Data of patients who underwent f-URS between January 2009 and December 2012 were collected. Patients were staged according to estimated glomerular filtration rate. Patients with stage ≥ 3 were accepted as having CKD (study group). These patients were matched with a group of patients without CKD (control group). Operative characteristics, complication rates, and third-month success rates were compared. Overall, 339 patients underwent f-URS and 62 (18.28%) had CKD. Control group constituted of 87 patients. Having a solitary kidney (17.4% vs 3.5%; P = .003) and history of stone intervention (51.6% vs 23%; P = .001) were more common in the CKD group. Similarly, access sheath was more commonly used among patients with CKD (87.1% vs 70.22%; P = .015). Both perioperative (19.35% vs 19.54; P = .372) and postoperative (22.6% vs 16.1%; P = .214) complication rates were similar in patients with and without CKD. Hospitalization time was 25.70 ± 25.62 and 24.5 ± 25 hours (P = .871) for patients with and without CKD, respectively. Although mean third postoperative estimated glomerular filtration rate of patients with CKD did not change significantly (48.16 ± 8.72 vs 49.08 ± 9.26; P = .431), CKD stage of 13 patients shifted from 3 to 2. At the third postoperative month, stone free rate in patients with and without CKD was 87.1% vs 86.2% (P = .875). f-URS is a safe and effective procedure in patients with CKD and it is associated with improved overall kidney function. Copyright © 2014 Elsevier Inc. All rights reserved.

Urinary Liver Type Fatty Acid Binding Protein Is Negatively Associated With Estimated Glomerular Filtration Rate in Renal Transplant Recipients With Graft Loss.

PubMed

Huang, Y-C; Chang, Y-S; Chen, C-C; Tsai, S-F; Yu, T-M; Wu, M-J; Chen, C-H

2018-05-01

Liver type fatty acid binding protein (L-FABP) is abundant not only in the liver but also in the kidney and is excreted in urine. Its primary function is to facilitate intracellular long chain fatty acid transport and it might also act as an endogenous antioxidant molecular. The purpose of this study was to investigate whether plasma or urinary L-FABP levels were associated with graft function in renal transplant recipients. Sixty-seven renal transplant recipients with a mean age of 48.8 years were recruited. The mean duration of renal transplantation was 4131 days. Recipients were divided into 2 groups based on their estimated glomerular filtration rate (eGFR) values: moderate graft function (eGFR ≥60 mL/min/1.73 m 2 ) and low graft function (eGFR <60 mL/min/1.73 m 2 ). Fasting plasma and urinary L-FABP levels were measured. There was no significant difference in plasma L-FABP level between the 2 groups, although recipients in the low graft function group had significantly lower urinary L-FABP level when compared with recipients in the moderate graft function group. Plasma and urinary L-FABP levels were not associated with eGFR in the 67 recipients; however, urinary L-FABP level (β = -1.24, P = .037) and level adjusted by urinary creatinine (β = -0.75, P = .046) were significantly negatively associated with eGFR in recipients with low graft function after adjusting for potential confounders. Increased urinary L-FABP level seems to be a significant indicator of decreased graft function in renal transplant recipients with loss of graft function. Copyright © 2018 Elsevier Inc. All rights reserved.

Survival among older adults with kidney failure is better in the first three years with chronic dialysis treatment than not.

PubMed

Tam-Tham, Helen; Quinn, Robert R; Weaver, Robert G; Zhang, Jianguo; Ravani, Pietro; Liu, Ping; Thomas, Chandra; King-Shier, Kathryn; Fruetel, Karen; James, Matt T; Manns, Braden J; Tonelli, Marcello; Murtagh, Fliss E M; Hemmelgarn, Brenda R

2018-05-23

Comparisons of survival between dialysis and nondialysis care for older adults with kidney failure have been limited to those managed by nephrologists, and are vulnerable to lead and immortal time biases. So we compared time to all-cause mortality among older adults with kidney failure treated vs. not treated with chronic dialysis. Our retrospective cohort study used linked administrative and laboratory data to identify adults aged 65 or more years of age in Alberta, Canada, with kidney failure (2002-2012), defined by two or more consecutive outpatient estimated glomerular filtration rates less than 10 mL/min/1.73m 2 , spanning 90 or more days. We used marginal structural Cox models to assess the association between receipt of dialysis and all-cause mortality by allowing control for both time-varying and baseline confounders. Overall, 838 patients met inclusion criteria (mean age 79.1; 48.6% male; mean estimated glomerular filtration rate 7.8 mL/min/1.73m 2 ). Dialysis treatment (vs. no dialysis) was associated with a significantly lower risk of death for the first three years of follow-up (hazard ratio 0.59 [95% confidence interval 0.46-0.77]), but not thereafter (1.22 [0.69-2.17]). However, dialysis was associated with a significantly higher risk of hospitalization (1.40 [1.16-1.69]). Thus, among older adults with kidney failure, treatment with dialysis was associated with longer survival up to three years after reaching kidney failure, though with a higher risk of hospital admissions. These findings may assist shared decision-making about treatment of kidney failure. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

Low Estimated Glomerular Filtration Rate Is Prevalent among North Korean Refugees in South Korea

PubMed Central

Song, Young-Soo

2018-01-01

Background The number of North Korean refugees entering South Korea is rising. Few studies have investigated the risk of non-communicable disease in North Korean refugees. Moreover, kidney insufficiency, a risk factor for cardiovascular disease, has not been studied in this population. We compared the prevalence of non-communicable disease and kidney function in North Korean refugees and South Koreans. Methods Our study was conducted using a case-control design. We enrolled 118 North Korean refugees from the Hana Center and selected 472 randomly sampled South Korean individuals as controls, who were age- and sex-matched with the North Korean refugees in a ratio of 1:4, from the 2014 Korea National Health and Nutrition Examination Survey database. Results The prevalence of non-communicable disease did not differ significantly between the groups; however, a low estimated glomerular filtration rate (eGFR; <90 mL/min per 1.73 m2) was more prevalent in the North Korean refugees than in the South Korean population (52.1% vs. 29.9%, P<0.001). After adjusting for covariates and weight gain after escape, the prevalence of a low eGFR was associated with the length of residence in South Korea (odds ratio, 2.84; 95% confidence interval, 1.02–7.89). Conclusion The prevalence of non-communicable disease did not differ between North Korean refugees and the South Korean population, while a low eGFR was more prevalent in North Korean refugees than in South Koreans. Moreover, after adjusting for other covariates, the prevalence of a low eGFR in North Korean refugees was associated with the length of residence in South Korea. PMID:29788704

White coat hypertension is more risky than prehypertension: important role of arterial wave reflections.

PubMed

Sung, Shih-Hsien; Cheng, Hao-Min; Wang, Kang-Ling; Yu, Wen-Chung; Chuang, Shao-Yuan; Ting, Chih-Tai; Lakatta, Edward G; Yin, Frank C P; Chou, Pesus; Chen, Chen-Huan

2013-06-01

Arterial aging may link cardiovascular risk to white coat hypertension (WCH). The aims of the present study were to investigate the role of arterial aging in the white coat effect, defined as the difference between office and 24-hour ambulatory systolic blood pressures, and to compare WCH with prehypertension (PH) with respect to target organ damage and long-term cardiovascular mortality. A total of 1257 never-been-treated volunteer subjects from a community-based survey were studied. WCH and PH were defined by office and 24-hour ambulatory blood pressures. Left ventricular mass index, carotid intima-media thickness, estimated glomerular filtration rate, carotid-femoral pulse wave velocity, carotid augmentation index, amplitude of the reflection pressure wave, and 15-year cardiovascular mortality were determined. Subjects with WCH were significantly older and had greater body mass index, blood pressure values, intima-media thickness, carotid-femoral pulse wave velocity, augmentation index, amplitude of the backward pressure wave, and a lower estimated glomerular filtration rate than PH. Amplitude of the backward pressure wave was the most important independent correlate of the white coat effect in multivariate analysis (model r(2)=0.451; partial r(2)/model r(2)=90.5%). WCH had significantly greater cardiovascular mortality than PH (hazard ratio, 2.94; 95% confidence interval, 1.09-7.91), after accounting for age, sex, body mass index, smoking, fasting plasma glucose, and total cholesterol/high-density lipoprotein-cholesterol ratio. Further adjustment of the model for amplitude of the backward pressure wave eliminated the statistical significance of the WCH effect. In conclusion, the white coat effect is mainly caused by arterial aging. WCH carries higher risk for cardiovascular mortality than PH, probably via enhanced wave reflections that accompany arterial aging.

Does bariatric surgery really prevent deterioration of renal function?

PubMed

Kim, Eun Young; Kim, Yong Jin

2016-05-01

Obesity is related to impaired renal function; bariatric surgery is associated with an improvement in renal function. We investigated obesity-related changes in renal function after bariatric surgery and identified related clinical factors. Soonchunhyang University Seoul Hospital, Korea. From December 2011 to February 2014, 493 consecutive patients who met the criteria underwent bariatric surgery. Of these patients, 136 patients were enrolled. The exclusion criteria were as follows: revisional bariatric surgery, laparoscopic adjustable gastric banding, significant chronic kidney disease, macroalbuminuria, nephrotic range proteinuria, and absence of laboratory data on renal function. Overall, there were 126 patients with Roux-en-Y gastric bypass and 10 with sleeve gastrectomy. Preoperative and postoperative 1-year renal function was evaluated by the estimated glomerular filtration rate, urinary albumin-to-creatinine ratio (UACR), and urinary protein-to-creatinine ratio (UPCR). Of 136 patients, 101 were women, and the mean age was 35.9±11.2 years. UACR was significantly lower postoperatively than preoperatively (27.0±47.2 versus 9.0±8.6 mg/g; P<.001). Microalbuminuria was present in 22.1% of patients preoperatively, decreasing to 4.4% 1-year postoperatively. A significant reduction was observed in the UPCR (90.7±101.2 versus 64.6±34.8 mg/g; P = .004). The mean value of estimated glomerular filtration rate improved from 117.8 to 119.6 mL/min/1.73 m(2), although this was not significant. In obese patients, bariatric surgery significantly improves microalbuminuria and decreases the UACR and UPCR. Therefore, bariatric surgery should be considered as an early treatment for obesity with renal impairment and may prevent the progression to overt disease. Copyright © 2016 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Acoustic radiation force impulse elastography of the kidneys: is shear wave velocity affected by tissue fibrosis or renal blood flow?

PubMed

Asano, Kenichiro; Ogata, Ai; Tanaka, Keiko; Ide, Yoko; Sankoda, Akiko; Kawakita, Chieko; Nishikawa, Mana; Ohmori, Kazuyoshi; Kinomura, Masaru; Shimada, Noriaki; Fukushima, Masaki

2014-05-01

The aim of this study was to identify the main influencing factor of the shear wave velocity (SWV) of the kidneys measured by acoustic radiation force impulse elastography. The SWV was measured in the kidneys of 14 healthy volunteers and 319 patients with chronic kidney disease. The estimated glomerular filtration rate was calculated by the serum creatinine concentration and age. As an indicator of arteriosclerosis of large vessels, the brachial-ankle pulse wave velocity was measured in 183 patients. Compared to the degree of interobserver and intraobserver deviation, a large variance of SWV values was observed in the kidneys of the patients with chronic kidney disease. Shear wave velocity values in the right and left kidneys of each patient correlated well, with high correlation coefficients (r = 0.580-0.732). The SWV decreased concurrently with a decline in the estimated glomerular filtration rate. A low SWV was obtained in patients with a high brachial-ankle pulse wave velocity. Despite progression of renal fibrosis in the advanced stages of chronic kidney disease, these results were in contrast to findings for chronic liver disease, in which progression of hepatic fibrosis results in an increase in the SWV. Considering that a high brachial-ankle pulse wave velocity represents the progression of arteriosclerosis in the large vessels, the reduction of elasticity succeeding diminution of blood flow was suspected to be the main influencing factor of the SWV in the kidneys. This study indicates that diminution of blood flow may affect SWV values in the kidneys more than the progression of tissue fibrosis. Future studies for reducing data variance are needed for effective use of acoustic radiation force impulse elastography in patients with chronic kidney disease.

Abnormal glomerular filtration rate in children, adolescents and young adults starts below 75 mL/min/1.73 m(2).

PubMed

Pottel, Hans; Hoste, Liesbeth; Delanaye, Pierre

2015-05-01

The chronic kidney disease (CKD) classification system for children is similar to that for adults, with both mainly based on estimated glomerular filtration rate (eGFR) combined with fixed cut-off values. The main cut-off eGFR value used to define CKD is 60 mL/min/1.73 m(2), a value that is also applied for children older than 2 years of age, adolescents and young adults. Based on a literature search, we evaluated inclusion criteria for eGFR in clinical trials or research studies on CKD for children. We also collected information on direct measurements of GFR (mGFR) in children and adolescents, with the aim to estimate the normal reference range for GFR. Using serum creatinine (Scr) normal reference values and Scr-based eGFR-equations, we also evaluated the correspondence between Scr normal reference values and (e)GFR normal reference values. Based on our literature search, the inclusion of children in published CKD studies has been based on cut-off values for eGFR of >60 mL/min/1.73 m(2). The lower reference limits for mGFR far exceed this adult threshold. Using eGFR values calculated using Scr-based formulas, we found that abnormal Scr levels in children already correspond to eGFR values that are below a cut-off of 75 mL/min/1.73 m(2). Abnormal GFR in children, adolescents and young adults starts below 75 mL/min/1.73 m(2), and as abnormality is a sign of disease, we recommend referring children, adolescents and young adults with an (e)GFR of <75 mL/min/1.73 m(2) for further clinical assessment.

Cardiac Amyloid Load: A Prognostic and Predictive Biomarker in Patients With Light-Chain Amyloidosis.

PubMed

Kristen, Arnt V; Brokbals, Eva; Aus dem Siepen, Fabian; Bauer, Ralf; Hein, Selina; Aurich, Matthias; Riffel, Johannes; Behrens, Hans-Michael; Krüger, Sandra; Schirmacher, Peter; Katus, Hugo A; Röcken, Christoph

2016-07-05

Cardiac amyloid load has not been analyzed for its effect on mortality in patients with amyloid light-chain (AL) cardiac amyloidosis. This study retrospectively compared histological amyloid load with common clinical predictors of mortality. This study assessed 216 patients with histologically confirmed cardiac amyloidosis at a single center with electrocardiography, echocardiography, and laboratory testing. AL amyloid deposits were usually distributed in a reticular/pericellular pattern, whereas transthyretin amyloid (ATTR) more commonly showed patchy deposits. Median amyloid load was 30.5%; no amyloid load was above 70%. During follow-up (median 19.1 months), 112 patients died. Chemotherapy had a significant effect on overall survival in AL amyloidosis (16.2 months vs. 1.4 months; p = 0.003). Patients with <20% AL amyloid load who responded to chemotherapy showed significantly better survival than nonresponders. According to univariate analysis, predictors of survival in AL amyloidosis included sex, Karnofsky index, New York Heart Association (NYHA) functional class, diastolic blood pressure, estimated glomerular filtration rate, N-terminal pro-B-type natriuretic peptide, mineralocorticoid receptor antagonists, low voltage, ineligibility for chemotherapy, response to chemotherapy, and amyloid load. Independent predictors of mortality by multivariate analysis included NYHA functional class (III vs. II), estimated glomerular filtration rate, responders to chemotherapy, and amyloid load. In ATTR amyloidosis, survival correlated with NYHA functional class, diastolic blood pressure, and use of diuretic agents. Following Cox regression analysis, NYHA functional class (III vs. II; p < 0.05) remained the only independent predictor of patient survival in ATTR amyloidosis. Early identification of subjects with AL amyloid is essential given that in late-stage disease with extensive amyloid load, our data suggested that outcomes are not affected by administration of chemotherapy. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Low Estimated Glomerular Filtration Rate Is Prevalent among North Korean Refugees in South Korea.

PubMed

Song, Young-Soo; Choi, Seong-Woo

2018-05-01

The number of North Korean refugees entering South Korea is rising. Few studies have investigated the risk of non-communicable disease in North Korean refugees. Moreover, kidney insufficiency, a risk factor for cardiovascular disease, has not been studied in this population. We compared the prevalence of non-communicable disease and kidney function in North Korean refugees and South Koreans. Our study was conducted using a case-control design. We enrolled 118 North Korean refugees from the Hana Center and selected 472 randomly sampled South Korean individuals as controls, who were age- and sex-matched with the North Korean refugees in a ratio of 1:4, from the 2014 Korea National Health and Nutrition Examination Survey database. The prevalence of non-communicable disease did not differ significantly between the groups; however, a low estimated glomerular filtration rate (eGFR; <90 mL/min per 1.73 m 2 ) was more prevalent in the North Korean refugees than in the South Korean population (52.1% vs. 29.9%, P<0.001). After adjusting for covariates and weight gain after escape, the prevalence of a low eGFR was associated with the length of residence in South Korea (odds ratio, 2.84; 95% confidence interval, 1.02-7.89). The prevalence of non-communicable disease did not differ between North Korean refugees and the South Korean population, while a low eGFR was more prevalent in North Korean refugees than in South Koreans. Moreover, after adjusting for other covariates, the prevalence of a low eGFR in North Korean refugees was associated with the length of residence in South Korea.

Disease management programs for CKD patients: the potential and pitfalls.

PubMed

Rocco, Michael V

2009-03-01

Disease management describes the use of a number of approaches to identify and treat patients with chronic health conditions, especially those that are expensive to treat. Disease management programs have grown rapidly in the United States in the past several years. These programs have been established for patients with chronic kidney disease (CKD), but some have been discontinued because of the high cost of the program. Disease management programs for CKD face unique challenges. Identification of patients with CKD is hampered by incomplete use of the International Classification of Diseases, Ninth Revision (ICD-9) codes for CKD by physicians and the less than universal use of estimated glomerular filtration rate from serum creatinine measurements to identify patients with an estimated glomerular filtration rate less than 60 mL/min/1.73 m(2). CKD affects multiple organ systems. Thus, a comprehensive disease management program will need to manage each of these aspects of CKD. These multiple interventions likely will make a CKD disease management program more costly than similar disease management programs designed for patients with diabetes mellitus, congestive heart failure, or other chronic diseases. The lack of data that can be used to develop effective disease management programs in CKD makes it difficult to determine goals for the management of each organ system affected by CKD. Finally, long periods of observation will be needed to determine whether a particular disease management program is effective in not only improving patient outcomes, but also decreasing both resource use and health care dollars. This long-term observation period is contrary to how most disease management contracts are written, which usually are based on meeting goals during a 1- to 3-year period. Until these challenges are resolved, it likely will be difficult to maintain effective disease management programs for CKD.

Predictive Factors of Chronic Kidney Disease in Patients with Vesicoureteral Reflux Treated Surgically and Followed after Puberty.

PubMed

Kang, Minyong; Lee, Jung Keun; Im, Young Jae; Choi, Hwang; Park, Kwanjin

2016-04-01

We delineated clinical features and determined predictors of chronic kidney disease during long-term postpubertal followup in patients with vesicoureteral reflux treated surgically. We analyzed the data of 101 patients who were surgically treated for vesicoureteral reflux and had gone through puberty. Patients underwent preoperative and postoperative voiding cystourethrography to assess reflux status, and dimercaptosuccinic acid scan to assess renal cortical defects. We compared several variables preoperatively and postpubertally, including body mass index; blood urea nitrogen, creatinine and uric acid levels; estimated glomerular filtration rate; microalbuminuria; blood pressure; renal function and renal scarring. Kaplan-Meier analysis was used to predict chronic kidney disease-free survival rates throughout the followup periods. Cox regression model was adopted to identify independent predictors of chronic kidney disease. We defined chronic kidney disease as estimated glomerular filtration rate less than 60 ml/minute/1.73 m(2). Median followup was 100.0 months (IQR 69.0 to 136.5). Median age was 16 years at last followup (IQR 14 to 18). A total of 11 patients (10.9%) were diagnosed with de novo chronic kidney disease during postpubertal followup. It is noteworthy that serum uric acid levels (HR 1.96) and presence of high grade reflux (HR 7.40) were significant predictors of chronic kidney disease on multivariate analysis. In children who were treated surgically for vesicoureteral reflux preoperative uric acid levels and high grade reflux were independent predictors of de novo chronic kidney disease during postpubertal followup. Our results offer valuable information for predicting long-term renal outcomes in patients with vesicoureteral reflux treated surgically. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Early Outcomes of the New UK Deceased Donor Kidney Fast-Track Offering Scheme.

PubMed

Callaghan, Chris J; Mumford, Lisa; Pankhurst, Laura; Baker, Richard J; Bradley, J Andrew; Watson, Christopher J E

2017-12-01

The UK Kidney Fast-Track Scheme (KFTS) was introduced in 2012 to identify kidneys at high risk of discard and to rapidly facilitate transplantation. A retrospective analysis of kidneys transplanted through the KFTS was undertaken. UK Transplant Registry data were collected on deceased donor kidneys implanted between November 1, 2012, and April 30, 2015, (donation after brain death [DBD] donors) and March 1, 2013, and April 30, 2015 (donation after circulatory death [DCD] donors). Posttransplant outcomes included 1-year estimated glomerular filtration rate and death-censored graft survival (DCGS). Over the study period, 523 deceased donor kidneys were transplanted through the KFTS and 4174 via the standard National Kidney Allocation Scheme (NKAS). Kidneys in the KFTS were more likely to be from older diabetic donors, had a higher frequency of poor ex vivo perfusion, had longer cold ischemic times, and were transplanted into older recipients. One-year DCGS of KFTS and NKAS DBD donor kidneys was similar (94% vs 95%; P = 0.70), but for DCD donor kidneys, DCGS was lower in those allocated via the KFTS (91% versus 95%; P = 0.04). Median 1-year estimated glomerular filtration rate for DBD donor kidneys was lower in those allocated via the KFTS (49 vs 52 mL/min per 1.73 m; P = 0.01), but for DCD kidneys, there was no difference (45 vs 48 mL/min per 1.73 m; P = 0.10). Although KFTS kidneys have less favorable donor, graft, and recipient risk factors than NKAS kidneys, short-term graft and patient outcomes are acceptable. National schemes that identify and rapidly offer kidneys at high risk of discard may contribute to minimizing the unnecessary discard of organs.

Plasma Creatinine Clearance in the Dog

ERIC Educational Resources Information Center

Frazier, Loy W.

1977-01-01

Lists materials and methods for an experiment that demonstrates the concept of glomerular filtration rate (GFR) using anesthesized dogs. In the dog, GFR is equivalent to the renal plasma clearance of exogenous creatinine. (CS)

Unilateral improvement in glomerular filtration rate after permanent drainage of a perinephric pseudocyst in a cat.

PubMed

McCord, Kelly; Steyn, Philip F; Lunn, Katharine F

2008-07-01

A 12-year-old, 6 kg, castrated male Siamese-cross cat was referred for investigation of an abdominal mass. The cat was found to have a left perinephric pseudocyst (PNP), accompanied by azotemia, with a small right kidney detected on ultrasound. Glomerular filtration rate (GFR) was determined by renal scintigraphy and was found to be low, with the left kidney contributing 64% of the total GFR. Percutaneous ultrasound-guided drainage of the PNP did not improve the GFR, and fluid reaccumulated within a short period of time. Laparoscopic fenestration of the cyst capsule was performed to allow for permanent drainage. The PNP did not recur, renal values progressively improved, and 8 months after the capsulotomy the GFR of the left kidney had increased by 50%, while renal function remained static on the right side.

Serum Creatinine: Not So Simple!

PubMed

Delanaye, Pierre; Cavalier, Etienne; Pottel, Hans

2017-01-01

Measuring serum creatinine is cheap and commonly done in daily practice. However, interpretation of serum creatinine results is not always easy. In this review, we will briefly remind the physiological limitations of serum creatinine due notably to its tubular secretion and the influence of muscular mass or protein intake on its concentration. We mainly focus on the analytical limitations of serum creatinine, insisting on important concept such as reference intervals, standardization (and IDMS traceability), analytical interferences, analytical coefficient of variation (CV), biological CV and critical difference. Because the relationship between serum creatinine and glomerular filtration rate is hyperbolic, all these CVs will impact not only the precision of serum creatinine but still more the precision of different creatinine-based equations, especially in low or normal-low creatinine levels (or high or normal-high glomerular filtration rate range). © 2017 S. Karger AG, Basel.

A meta-analysis on diagnostic value of serum cystatin C and creatinine for the evaluation of glomerular filtration function in renal transplant patients.

PubMed

Pan, Pan; Binjie, Hu; Min, Li; Lipei, Fan; Yanli, Ni; Junwen, Zhou; Xianghua, Shi

2014-12-01

This meta-analysis aimed to perform a systematic review on comparing the diagnostic value of serum cystatin C and creatinine for glomerular filtration rate in renal transplant patients. The data was extracted into 2×2 table after the articles were assessed by the tool of QUADAS and heterogeneity analysis. The SROC curve and meta-analysis were performed by MetaDisc1.4. Meta-analysis showed that the serum cystatin C had no heterogeneity (P=0.418, I2=2.2%, DOR=25.03), while creatinine heterogeneity was high (P=0.109, I2=37.5%, DOR=9.11). The values of SEN, SPE and SAUC were calculated as 0.86, 0.70 and 0.9015 for cystatin C, and 0.78, 0.73 and 0.8285 for creatinine individually. This study utilized GFR detection and subgroups analysis by cutoff. The PLR was 6.13 and the NLR was 0.12 for cystatin C, compared to SCr (3.72, 0.32). There was homogeneity among these studies using PENIA testing for cystatin C (χ2=2.61, P=0.4560, I2=0.0%. There were significant correlations among cystatin C , creatinine and glomerular filtration rate (GFR). Cystatin C had more sensitivity but less specificity than creatinine for evaluation of GFR. Cystatin C had strong ability in diagnosing renal function after renal transplant and ruling out diagnostic efficacy.

Prostaglandins and nonsteroidal anti-inflammatory drugs. Effects on renal hemodynamics.

PubMed

DiBona, G F

1986-01-17

Renal prostaglandins are important modulators of renal hemodynamic function. Their synthesis from arachidonic acid precursor is regulated by neurohumoral vasoactive substances as well as by intrarenal factors. Endogenous renal prostaglandins exert little influence on renal blood flow and glomerular filtration rate in the basal state. In contrast, inhibition of cyclooxygenase-dependent arachidonic acid metabolism with nonsteroidal anti-inflammatory drugs in states of decreased renal perfusion causes marked alterations in these variables. Thus, clinical states characterized by decreased intravascular volume (decreased effective blood volume) with decreased renal perfusion augment the activity of various neurohumoral vasoactive systems and result in an increased dependence of renal hemodynamics on endogenous renal prostaglandin synthesis, which is stimulated, in a compensatory manner, by these same systems. The development of newer drugs that undergo biotransformation in the kidney between active and inactive forms may permit a lesser degree of renal cyclooxygenase inhibition, with the possibility of a reduction in the adverse effects on renal blood flow and glomerular filtration rate. Appropriate clinical use of nonsteroidal anti-inflammatory drugs requires careful consideration of the potential deleterious consequences of prostaglandin synthesis inhibition. Prostaglandins are considered to be autacoids and, as such, they exert their physiologic actions close to or at the site of synthesis. Therefore, production of prostaglandins, thromboxanes, and, possibly, leukotrienes in the renal cortex by the constituent cells of the glomeruli and the arterioles would be anticipated to influence their hemodynamic functions, that is, glomerular filtration rate, renal blood flow, renal vascular resistance, and juxtaglomerular granular cell renin release.

Cystatin C-Based Equation Does Not Accurately Estimate the Glomerular Filtration in Japanese Living Kidney Donors.

PubMed

Tsujimura, Kazuma; Ota, Morihito; Chinen, Kiyoshi; Adachi, Takayuki; Nagayama, Kiyomitsu; Oroku, Masato; Nishihira, Morikuni; Shiohira, Yoshiki; Iseki, Kunitoshi; Ishida, Hideki; Tanabe, Kazunari

2017-06-23

BACKGROUND Precise evaluation of a living donor's renal function is necessary to ensure adequate residual kidney function after donor nephrectomy. Our aim was to evaluate the feasibility of estimating glomerular filtration rate (GFR) using serum cystatin-C prior to kidney transplantation. MATERIAL AND METHODS Using the equations of the Japanese Society of Nephrology, we calculated the GFR using serum creatinine (eGFRcre) and cystatin C levels (eGFRcys) for 83 living kidney donors evaluated between March 2010 and March 2016. We compared eGFRcys and eGFRcre values against the creatinine clearance rate (CCr). RESULTS The study population included 27 males and 56 females. The mean eGFRcys, eGFRcre, and CCr were, 91.4±16.3 mL/min/1.73 m² (range, 59.9-128.9 mL/min/1.73 m²), 81.5±14.2 mL/min/1.73 m² (range, 55.4-117.5 mL/min/1.73 m²) and 108.4±21.6 mL/min/1.73 m² (range, 63.7-168.7 mL/min/1.73 m²), respectively. eGFRcys was significantly lower than CCr (p<0.001). The correlation coefficient between eGFRcys and CCr values was 0.466, and the mean difference between the two values was -17.0 (15.7%), with a root mean square error of 19.2. Thus, eGFRcre was significantly lower than CCr (p<0.001). The correlation coefficient between eGFRcre and CCr values was 0.445, and the mean difference between the two values was -26.9 (24.8%), with a root mean square error of 19.5. CONCLUSIONS Although eGFRcys provided a better estimation of GFR than eGFRcre, eGFRcys still did not provide an accurate measure of kidney function in Japanese living kidney donors.

A semi-automated region of interest detection method in the scintigraphic glomerular filtration rate determination for patients with abnormal low renal function.

PubMed

Tian, Cancan; Zheng, Xiujuan; Han, Yuan; Sun, Xiaoguang; Chen, Kewei; Huang, Qiu

2013-11-01

This work presents a novel semi-automated renal region-of-interest (ROI) determination method that is user friendly, time saving, and yet provides a robust glomerular filtration rate (GFR) estimation highly consistent with the reference method. We reviewed data from 57 patients who underwent (99m)Tc-diethylenetriaminepentaacetic acid renal scintigraphy and were diagnosed with abnormal renal function. The renal and background ROIs were delineated by the proposed multi-step, semi-automated method, which integrates temporal/morphologic information via visual inspection and computer-aided calculations. The total GFR was estimated using the proposed method (sGFR) performed by 2 junior clinicians (A and B) with 1 and 3 years of experience, respectively (sGFR_a, sGFR_b), and compared with the reference total GFR (rGFR) estimated by a senior clinician with 20 years of experience who manually delineated the kidney and background ROIs. All GFR calculations herein were conducted using the Gates method. Data from 10 patients with unilateral or non-functioning kidneys were excluded from the analysis. For the remaining patients, sGFR correlated well with rGFR (r(s/rGFR_a) = 0.957, P < 0.001 and r(s/rGFR_b) = 0.951, P < 0.001) and sGFR_a correlated well with sGFR_b (r(a/b) = 0.997, P < 0.001). Moreover, the Bland-Altman plots for sGFR_a and sGFR_b confirm the high reproducibility of the proposed method between different operators. Finally, the proposed procedure is almost 3 times faster than the routinely used procedure in clinical practice. The results suggest that this method is easy to use, highly reproducible, and accurate in measuring the GFR of patients with low renal function. The method is being further extended to a fully automated procedure.

Correlation of the Glomerular Filtration Rate Measured With the Use of DTPA-Tc99m in Live Kidney Donors With Equations Based on Creatinine and Cystatin C.

PubMed

Garcia-Covarrubias, L; Barragan, J; Castro, I; Hernandez, K; Reding, A; Hinojosa, H; Prieto, P; Garcia, A; Alejandra, C; Ortuño, D; Carmona, M; Fernández, D; Diliz, H

2018-03-01

Renal donation leads to a risk of developing chronic kidney disease, with an incidence of 0.47%. To evaluate for its presence, formulas based on serum creatinine are used, but up to 80% of these formulas underestimate the glomerular filtration rate (GFR) in donors. The aim of this work was to confirm the highest correlation of the GFR as measured with the use of DTPA-Tc99m with the GFR as estimated by means of the formula based on serum cystatin C (CKD-EPI creatinine-cystatin C) in healthy kidney donors. In this observational, analytic, cross-sectional study, the GFR of kidney donors was determined ≥1 year after donation by means of DTPA gammagram and estimation with the use of conventional formulations and with cystatin C. Of 112 donors, 38 (34%) were included, 20 (60%) were female, with an overall average age of 40 years, 36.5 months after donation, and body mass index of 25.5 kg/m 2 . Correlation with the GFR as measured by means of DTPA gammagram was better with the use of CKD-EPI cystatin C (0.402; P = .020) and CKD-EPI creatinine-cystatin (0.549; P < .001) than the conventional formulas. Linear correlation with serum cystatin C was 0.825 (P < .001; 95% confidence interval, -105.3 to -63.2) for the CKD-EPI cystatin C formula, 0.77 (P < .001; -89.9 to -48.1) for the CKD-EPI creatinine-cystatin formula, and 0.525 (P = .002; -91.1 to -23.2) for DTPA-Tc99m scintigraphy. There is a strong correlation between estimate the GFR by equations based on cystatin C and the measurement of the GFR by DTPA-Tc99m gammagram. Copyright © 2017 Elsevier Inc. All rights reserved.

Incidence of Posttransplantation Diabetes Mellitus in De Novo Kidney Transplant Recipients Receiving Prolonged-Release Tacrolimus-Based Immunosuppression With 2 Different Corticosteroid Minimization Strategies: ADVANCE, A Randomized Controlled Trial.

PubMed

Mourad, Georges; Glyda, Maciej; Albano, Laetitia; Viklický, Ondrej; Merville, Pierre; Tydén, Gunnar; Mourad, Michel; Lõhmus, Aleksander; Witzke, Oliver; Christiaans, Maarten H L; Brown, Malcolm W; Undre, Nasrullah; Kazeem, Gbenga; Kuypers, Dirk R J

2017-08-01

ADVANCE (NCT01304836) was a phase 4, multicenter, prospectively randomized, open-label, 24-week study comparing the incidence of posttransplantation diabetes mellitus (PTDM) with 2 prolonged-release tacrolimus corticosteroid minimization regimens. All patients received prolonged-release tacrolimus, basiliximab, mycophenolate mofetil and 1 bolus of intraoperative corticosteroids (0-1000 mg) as per center policy. Patients in arm 1 received tapered corticosteroids, stopped after day 10, whereas patients in arm 2 received no steroids after the intraoperative bolus. The primary efficacy variable was the diagnosis of PTDM as per American Diabetes Association criteria (2010) at any point up to 24 weeks postkidney transplantation. Secondary efficacy variables included incidence of composite efficacy failure (graft loss, biopsy-proven acute rejection or severe graft dysfunction: estimated glomerular filtration rate (Modification of Diet in Renal Disease-4) <30 mL/min per 1.73 m), acute rejection and graft and patient survival. The full-analysis set included 1081 patients (arm 1: n = 528, arm 2: n = 553). Baseline characteristics and mean tacrolimus trough levels were comparable between arms. Week 24 Kaplan-Meier estimates of PTDM were similar for arm 1 versus arm 2 (17.4% vs 16.6%; P = 0.579). Incidence of composite efficacy failure, graft and patient survival, and mean estimated glomerular filtration rate were also comparable between arms. Biopsy-proven acute rejection and acute rejection were significantly higher in arm 2 versus arm 1 (13.6% vs 8.7%, P = 0.006 and 25.9% vs 18.2%, P = 0.001, respectively). Tolerability profiles were comparable between arms. A prolonged-release tacrolimus, basiliximab, and mycophenolate mofetil immunosuppressive regimen is efficacious, with a low incidence of PTDM and a manageable tolerability profile over 24 weeks of treatment. A lower incidence of biopsy-proven acute rejection was seen in patients receiving corticosteroids tapered over 10 days plus an intraoperative corticosteroid bolus versus those receiving an intraoperative bolus only.

Preliminary findings of serum creatinine and estimated glomerular filtration rate (eGFR) in adolescents with intellectual disabilities.

PubMed

Lin, Jin-Ding; Lin, Lan-Ping; Hsieh, Molly; Lin, Pei-Ying

2010-01-01

The present study aimed to describe the kidney function profile - serum creatinine and estimated glomerular filtration rate (eGFR), and to examine the relationships of predisposing factors to abnormal serum creatinine in people with intellectual disabilities (ID). Data were collected by a cross-sectional study of 827 aged 15-18 years adolescents with ID who participated in annual health examinations as they enrolled into special education schools in Taiwan. We used serum samples to determine participants' creatinine profiles, and the Cockcroft-Gault formula to calculate the data of eGFR to present the chronic kidney disease. The results found 22% of the participants have abnormal serum creatinine value (creatinine>1.0mg/dl) and 59.6%, 36.4% and 4.0% at chronic kidney disease (CKD) stage 1, 2 and 3 cases accordingly based on the Cockcroft-Gault formula. No CKD stage 4 and 5 cases in this study. That is, there were 4% CKD cases (eGFR <60 mL/min/1.73 m(2); CKD stage 3, 4 and 5) in adolescents with ID in this study. The results also indicated that gender and BMI could significantly predict abnormal creatinine condition in multivariate logistic regression analysis. Those boys with ID were more likely to have abnormal creatinine value than girls with ID (OR=10.13, 95% CI=5.96-17.23). In term of BMI, those underweight adolescents with ID were less likely to have high creatinine value compared to normal weight group (OR=0.45, 95% CI=0.28-0.72). In summary, this study provides the preliminary information of creatinine and estimated GFR in people with ID; we suggest the public health policy should initiate appropriate management strategies to monitor kidney function and to improve treatment outcomes of chronic kidney disease for this vulnerable population. Copyright © 2010 Elsevier Ltd. All rights reserved.

Feasibility and accuracy of computational robot-assisted partial nephrectomy planning by virtual partial nephrectomy analysis.

PubMed

Isotani, Shuji; Shimoyama, Hirofumi; Yokota, Isao; China, Toshiyuki; Hisasue, Shin-ichi; Ide, Hisamitsu; Muto, Satoru; Yamaguchi, Raizo; Ukimura, Osamu; Horie, Shigeo

2015-05-01

To evaluate the feasibility and accuracy of virtual partial nephrectomy analysis, including a color-coded three-dimensional virtual surgical planning and a quantitative functional analysis, in predicting the surgical outcomes of robot-assisted partial nephrectomy. Between 2012 and 2014, 20 patients underwent virtual partial nephrectomy analysis before undergoing robot-assisted partial nephrectomy. Virtual partial nephrectomy analysis was carried out with the following steps: (i) evaluation of the arterial branch for selective clamping by showing the vascular-supplied area; (ii) simulation of the optimal surgical margin in precise segmented three-dimensional model for prediction of collecting system opening; and (iii) detailed volumetric analyses and estimates of postoperative renal function based on volumetric change. At operation, the surgeon identified the targeted artery and determined the surgical margin according to the virtual partial nephrectomy analysis. The surgical outcomes between the virtual partial nephrectomy analysis and the actual robot-assisted partial nephrectomy were compared. All 20 patients had negative cancer surgical margins and no urological complications. The tumor-specific renal arterial supply areas were shown in color-coded three-dimensional model visualization in all cases. The prediction value of collecting system opening was 85.7% for sensitivity and 100% for specificity. The predicted renal resection volume was significantly correlated with actual resected specimen volume (r(2) = 0.745, P < 0.001). The predicted estimated glomerular filtration rate was significantly correlated with actual postoperative estimated glomerular filtration rate (r(2) = 0.736, P < 0.001). Virtual partial nephrectomy analysis is able to provide the identification of tumor-specific renal arterial supply, prediction of collecting system opening and prediction of postoperative renal function. This technique might allow urologists to compare various arterial clamping methods and resection margins with surgical outcomes in a non-invasive manner. © 2015 The Japanese Urological Association.

Comparison of Glomerular Filtration Rate Estimation from Serum Creatinine and Cystatin C in HNF1A-MODY and Other Types of Diabetes.

PubMed

Szopa, Magdalena; Kapusta, Maria; Matejko, Bartlomiej; Klupa, Tomasz; Koblik, Teresa; Kiec-Wilk, Beata; Borowiec, Maciej; Malecki, Maciej T

2015-01-01

We previously showed that in HNF1A-MODY the cystatin C-based glomerular filtration rate (GFR) estimate is higher than the creatinine-based estimate. Currently, we aimed to replicate this finding and verify its clinical significance. The study included 72 patients with HNF1A-MODY, 72 with GCK-MODY, 53 with type 1 diabetes (T1DM), 70 with type 2 diabetes (T2DM), and 65 controls. Serum creatinine and cystatin C levels were measured. GFR was calculated from creatinine and cystatin C using the CKD-EPI creatinine equation (eGRF-cr) and CKD-EPI cystatin C equation (eGFR-cys), respectively. Cystatin C levels were lower (p < 0.001) in the control (0.70 ± 0.13 mg/L), HNF1A (0.75 ± 0.21), and GCK (0.72 ± 0.16 mg/L) groups in comparison to those with either T1DM (0.87 ± 0.15 mg/L) or T2DM (0.9 ± 0.23 mg/L). Moreover, eGFR-cys was higher than eGRF-cr in HNF1A-MODY, GCK-MODY, and the controls (p = 0.004; p = 0.003; p < 0.0001). This corresponded to 8.9 mL/min/1.73 m2, 9.7 mL/min/1.73 m2, and 16.9 mL/min/1.73 m2 of difference. Additionally, T1DM patients had higher eGFR-cr than eGFR-cys (11.6 mL/min/1.73 m(2); p = 0.0004); no difference occurred in T2DM (p = 0.91). We confirmed that eGFR-cys values in HNF1A-MODY patients are higher compared to eGFR-cr. Some other differences were also described in diabetic groups. However, none of them appears to be clinically relevant.

Arterial wave reflections and kidney function decline among persons with preserved estimated glomerular filtration rate: the Multi-Ethnic Study of Atherosclerosis.

PubMed

Hsu, Jeffrey J; Katz, Ronit; Chirinos, Julio A; Jacobs, David R; Duprez, Daniel A; Peralta, Carmen A

2016-05-01

Differences in arterial wave reflections have been associated with increased risk for heart failure and mortality. Whether these measures are also associated with kidney function decline is not well established. Reflection magnitude (RM, defined as the ratio of the backward wave [Pb] to that of the forward wave [Pf]), augmentation index (AIx), and pulse pressure amplification (PPA) were derived from radial tonometry measures among 5232 participants free of cardiovascular disease who were enrolled in the Multiethnic Study of Atherosclerosis. Kidney function was estimated by creatinine and cystatin C measurements, as well as albumin-to-creatinine ratio. We evaluated the associations of Pb, Pf, RM, AIx, and PPA with annualized estimated glomerular filtration rate (eGFR) change and rapid kidney function decline over 5 years, using generalized linear mixed models and logistic regression, respectively. Of the study participants, 48% were male, mean age was 62 years, mean eGFR and median albumin-to-creatinine ratio at baseline were 84 mL/min/1.73 m(2) and 5.3 mg/g, respectively. In demographically adjusted models, both Pb and Pf had similarly strong associations with kidney function decline; compared to those in the lowest tertiles, the persons in the highest tertiles of Pb and Pf had a 1.01 and 0.99 mL/min/1.73 m(2)/year faster eGFR decline, respectively (P < .05). However, these associations were attenuated after adjustment for systolic blood pressure. We found no significant associations between RM, AIx, or PPA and kidney function decline. In conclusion, the reflected and forward wave components were similarly associated with kidney function decline, and these associations were explained by differences in systolic blood pressure. Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Glomerular filtration rate

MedlinePlus

... Some labs use different measurements or test different samples. Talk to your doctor about the meaning of your specific test results. What Abnormal Results Mean Levels below 60 mL/min/1.73 m 2 for 3 or more months ...

Anatomic and physiologic changes of the aging kidney.

PubMed

Karam, Zeina; Tuazon, Jennifer

2013-08-01

Aging is associated with structural and functional changes in the kidney. Structural changes include glomerulosclerosis, thickening of the basement membrane, increase in mesangial matrix, tubulointerstitial fibrosis and arteriosclerosis. Glomerular filtration rate is maintained until the fourth decade of life, after which it declines. Parallel reductions in renal blood flow occur with redistribution of blood flow from the cortex to the medulla. Other functional changes include an increase in glomerular basement permeability and decreased ability to dilute or concentrate urine. Copyright © 2013 Elsevier Inc. All rights reserved.

Multiple Factors Influence Glomerular Albumin Permeability in Rats

PubMed Central

Sandoval, Ruben M.; Wagner, Mark C.; Patel, Monica; Campos-Bilderback, Silvia B.; Rhodes, George J.; Wang, Exing; Wean, Sarah E.; Clendenon, Sherry S.

2012-01-01

Different laboratories recently reported incongruous results describing the quantification of albumin filtration using two-photon microscopy. We investigated the factors that influence the glomerular sieving coefficient for albumin (GSCA) in an effort to explain these discordant reports and to develop standard operating procedures for determining GSCA. Multiple factors influenced GSCA, including the kidney depth of image acquisition (10–20 μm was appropriate), the selection of fluorophore (probes emitting longer wavelengths were superior), the selection of plasma regions for fluorescence measurements, the size and molecular dispersion characteristics of dextran polymers if used, dietary status, and the genetic strain of rat. Fasting reduced the GSCA in Simonsen Munich Wistar rats from 0.035±0.005 to 0.016±0.004 (P<0.01). Frömter Munich Wistar rats had a much lower GSCA in both the fed and the fasted states. Finally, we documented extensive albumin transcytosis with vesicular and tubular delivery to and fusion with the basolateral membrane in S1 proximal tubule cells. In summary, these results help explain the previously conflicting microscopy and micropuncture data describing albumin filtration and highlight the dynamic nature of glomerular albumin permeability. PMID:22223875

Podocyte Glutamatergic Signaling Contributes to the Function of the Glomerular Filtration Barrier

PubMed Central

Giardino, Laura; Armelloni, Silvia; Corbelli, Alessandro; Mattinzoli, Deborah; Zennaro, Cristina; Guerrot, Dominique; Tourrel, Fabien; Ikehata, Masami; Li, Min; Berra, Silvia; Carraro, Michele; Messa, Piergiorgio

2009-01-01

Podocytes possess the complete machinery for glutamatergic signaling, raising the possibility that neuron-like signaling contributes to glomerular function. To test this, we studied mice and cells lacking Rab3A, a small GTPase that regulates glutamate exocytosis. In addition, we blocked the glutamate ionotropic N-methyl-d-aspartate receptor (NMDAR) with specific antagonists. In mice, the absence of Rab3A and blockade of NMDAR both associated with an increased urinary albumin/creatinine ratio. In humans, NMDAR blockade, obtained by addition of ketamine to general anesthesia, also had an albuminuric effect. In vitro, Rab3A-null podocytes displayed a dysregulated release of glutamate with higher rates of spontaneous exocytosis, explained by a reduction in Rab3A effectors resulting in freedom of vesicles from the actin cytoskeleton. In addition, NMDAR antagonism led to profound cytoskeletal remodeling and redistribution of nephrin in cultured podocytes; the addition of the agonist NMDA reversed these changes. In summary, these results suggest that glutamatergic signaling driven by podocytes contributes to the integrity of the glomerular filtration barrier and that derangements in this signaling may lead to proteinuric renal diseases. PMID:19578006

[Glomerular filtration and renal volume in type II diabetes (non-insulin-dependent): study in normal and microalbuminuria patients].

PubMed

Signorini, A M; Tanganelli, I; Fondelli, C; Vattimo, A; Ferrari, F; Borgogni, P; Borgogni, L; Gragnoli, G

1991-08-01

In type 2 diabetes elevated glomerular filtration rate (GFR) and increased renal volume (RV), often accompanied to normo or microalbuminuria, were demonstrated. This condition is considered a pathogenetic factor for clinical nephropathy. As this topic is little studied in type 2 diabetes, we have investigated 73 type 2 diabetic patients (34 normo and 39 microalbuminuric), looking for a correlation between GFR, RV, hypertension, duration of diabetes and indexes of metabolic control. GFR was measured by a scintigraphy, after infusion of 99Tc-DTPA. Renal volume was determined by ultrasound scanning. Between the groups GFR and RV weren't different; elevated GFR was demonstrated in 3 patients; increased RV in 1 patient. In the hypertensive group GFR was lower than in normotensive group and in controls. Multivariate analysis in stepwise demonstrated that GFR presents a negative correlation to systolic blood pressure as in normo as in microalbuminuric patients. In the normotensive group GFR didn't correlate to the other variables. The present data suggest that in type 2 diabetes there is a little prevalence of glomerular hyperfiltration and increased renal volume and that hypertension plays a role on GFR of hypertensive diabetic patients.

Improving the prognosis of patients with severely decreased glomerular filtration rate (CKD G4+): conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

PubMed Central

Eckardt, Kai-Uwe; Bansal, Nisha; Coresh, Josef; Evans, Marie; Grams, Morgan E.; Herzog, Charles A.; James, Matthew T.; Heerspink, Hiddo J.L.; Pollock, Carol A.; Stevens, Paul E.; Tamura, Manjula Kurella; Tonelli, Marcello A.; Wheeler, David C.; Winkelmayer, Wolfgang C.; Cheung, Michael; Hemmelgarn, Brenda R.

2018-01-01

Patients with severely decreased glomerular filtration rate (GFR) (i.e., chronic kidney disease [CKD] G4+) are at increased risk for kidney failure, cardiovascular disease (CVD) events (including heart failure), and death. However, little is known about the variability of outcomes and optimal therapeutic strategies, including initiation of kidney replacement therapy (KRT). Kidney Disease: Improving Global Outcomes (KDIGO) organized a Controversies Conference with an international expert group in December 2016 to address this gap in knowledge. In collaboration with the CKD Prognosis Consortium (CKD-PC) a global meta-analysis of cohort studies (n = 264,515 individuals with CKD G4+) was conducted to better understand the timing of clinical outcomes in patients with CKD G4+ and risk factors for different outcomes. The results confirmed the prognostic value of traditional CVD risk factors in individuals with severely decreased GFR, although the risk estimates vary for kidney and CVD outcomes. A 2- and 4-year model of the probability and timing of kidney failure requiring KRT was also developed. The implications of these findings for patient management were discussed in the context of published evidence under 4 key themes: management of CKD G4+, diagnostic and therapeutic challenges of heart failure, shared decision-making, and optimization of clinical trials in CKD G4+ patients. Participants concluded that variable prognosis of patients with advanced CKD mandates individualized, risk-based management, factoring in competing risks and patient preferences. PMID:29656903

Observations of a large Dent disease cohort.

PubMed

Blanchard, Anne; Curis, Emmanuel; Guyon-Roger, Tiphaine; Kahila, Diana; Treard, Cyrielle; Baudouin, Véronique; Bérard, Etienne; Champion, Gérard; Cochat, Pierre; Dubourg, Julie; de la Faille, Renaud; Devuyst, Olivier; Deschenes, Georges; Fischbach, Michel; Harambat, Jérôme; Houillier, Pascal; Karras, Alexandre; Knebelmann, Bertrand; Lavocat, Marie-Pierre; Loirat, Chantal; Merieau, Elodie; Niaudet, Patrick; Nobili, François; Novo, Robert; Salomon, Rémi; Ulinski, Tim; Jeunemaître, Xavier; Vargas-Poussou, Rosa

2016-08-01

Dent disease classically combines low-molecular-weight proteinuria, hypercalciuria with nephrocalcinosis, and renal failure. Nephrotic range proteinuria, normal calciuria, and hypokalemia have been rarely reported. It is unknown whether the changes in phenotype observed over time are explained by a decrease in glomerular filtration rate (GFR) or whether there is any phenotype-genotype relationship. To answer this we retrospectively analyzed data from 109 male patients with CLCN5 mutations (Dent-1) and 9 patients with mutation of the OCRL gene (Dent-2). In Dent-1 disease, the estimated GFR decreased with age, by 1.0 to 1.6 ml/min per 1.73 m(2)/yr in the absence and presence of nephrocalcinosis, respectively, with no significant difference. Median values of low-molecular-weight proteinuria were in the nephrotic range and remained at the same level even in late renal disease. End-stage renal disease occurred in 12 patients, at a median age of 40 years. Hypercalciuria decreased with glomerular filtration and was absent in 40% of the patients under 30 and 85% of those over the age of 30. Hypophosphatemia did not resolve with age and calcitriol concentrations were in the upper normal range. Kalemia decreased with age, with half of the patients over the age of 18 presenting with hypokalemia. Thus, no phenotype/genotype correlation was observed in this cohort of patients with Dent disease. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Acute kidney injury in HIV-infected children: comparison of patients according to the use of highly active antiretroviral therapy.

PubMed

Soares, Douglas de Sousa; Cavalcante, Malena Gadelha; Ribeiro, Samille Maria Vasconcelos; Leitão, Rayana Café; Vieira, Ana Patrícia Freitas; Pires Neto, Roberto da Justa; Silva Junior, Geraldo Bezerra da; Daher, Elizabeth de Francesco

To assess clinical and laboratory data, and acute kidney injury (AKI) in HIV-infected children using and not using highly active antiretroviral therapy (HAART) prior to admission. A retrospective study was conducted with HIV-infected pediatric patients (<16 years). Children who were using and not using HAART prior to admission were compared. Sixty-three patients were included. Mean age was 5.3±4.27 years; 55.6% were females. AKI was observed in 33 (52.3%) children. Patients on HAART presented lower levels of potassium (3.9±0.8 vs. 4.5±0.7mEq/L, p=0.019) and bicarbonate (19.1±4.9 vs. 23.5±2.2mEq/L, p=0.013) and had a higher estimated glomerular filtration rate (102.2±36.7 vs. 77.0±32.8mL/min/1.73m 2 , p=0.011) than those not on HAART. In the multivariate analysis, the use of HAART prior to the admission was a protective factor for AKI (p=0.036; OR=0.30; 95% CI=0.097-0.926). AKI is a common complication of pediatric HIV infection. Use of HAART prior to the admission preserved glomerular filtration and was a protective factor for AKI, but increased medication side effects, such as hypokalemia and renal metabolic acidosis. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

A different scintigraphic approach to evaluate the glomerular filtration rate.

PubMed

Haciosmanoglu, T; Karacalioglu, A O; Eyileten, T; Ince, S; Arslan, N

Multiple nuclear medicine techniques for measuring renal glomerular filtration rate (GFR) are available but some of them are not practical in daily routine use and others have some accuracy issues. Hence the aim of the study was to design a new camera-based approach to measure the GFR and to compare our results with other measured GFR (mGFR) and estimated GFRs (eGFRs) derived from available measurements and equations used in daily clinical practice. 34 patients were included in the study. ∼74MBq (2mCi) Technetium 99m diethylene-triamine-pentaacetic acid ( 99m Tc-DTPA) was administered to the patients during 5min. A simple formula based on a dilution principle was used to measure GFR (ScinGFR). Our formula provided similar mGFR results in narrower range as creatinine clearance did and our results correlated well with results derived from other equations. When ScinGFR values were compared to others, there was a significant difference among them (p=0.031) due to difference between the ScinGFR and Cockroft-Gault. When the results of the ScinGFR compared to others without Cockroft-Gault, the difference among them was not significant (p=0.164). A simple formula considering the extracellular fluid volume was used to predict the split and global kidney functions and despite some discrepancies, good correlation among our results and those derived from available formulas was detected. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Aging and physiological changes of the kidneys including changes in glomerular filtration rate.

PubMed

Musso, Carlos G; Oreopoulos, Dimitrios G

2011-01-01

In addition to the structural changes in the kidney associated with aging, physiological changes in renal function are also found in older adults, such as decreased glomerular filtration rate, vascular dysautonomia, altered tubular handling of creatinine, reduction in sodium reabsorption and potassium secretion, and diminished renal reserve. These alterations make aged individuals susceptible to the development of clinical conditions in response to usual stimuli that would otherwise be compensated for in younger individuals, including acute kidney injury, volume depletion and overload, disorders of serum sodium and potassium concentration, and toxic reactions to water-soluble drugs excreted by the kidneys. Additionally, the preservation with aging of a normal urinalysis, normal serum urea and creatinine values, erythropoietin synthesis, and normal phosphorus, calcium and magnesium tubular handling distinguishes decreased GFR due to normal aging from that due to chronic kidney disease. Copyright © 2011 S. Karger AG, Basel.

Renal manifestations in children with Alagille syndrome.

PubMed

Di Pinto, Diana; Adragna, Marta

2018-04-01

Alagille syndrome (AS) is a cholestatic disease secondary to scarcity of interlobular bile ducts. It is associated with extrahepatic manifestations, and renal involvement is frequent. To describe the prevalence, type and outcome of renal pathology in children with AS. The presence and outcome of renal pathology was retrospectively studied in 21 children who met AS criteria. Renal pathology was observed in 18 patients (85.7%): (1) ultrasound variations in 7 patients (6 cases of bilateral renal dysplasia and 1 case of renal agenesis); (2) distal renal tubular acidosis in 2 patients; (3) a drop in glomerular filtration and/or proteinuria in 16 patients. The frequency of a drop in glomerular filtration was similar between patients with and without pathological kidney ultrasound findings. Our study confirms a high prevalence of renal involvement, which enhances the importance of diagnosis and renal function follow-up in children with AS. Sociedad Argentina de Pediatría.

aPKCλ/ι and aPKCζ Contribute to Podocyte Differentiation and Glomerular Maturation

PubMed Central

Hartleben, Björn; Widmeier, Eugen; Suhm, Martina; Worthmann, Kirstin; Schell, Christoph; Helmstädter, Martin; Wiech, Thorsten; Walz, Gerd; Leitges, Michael; Schiffer, Mario

2013-01-01

Precise positioning of the highly complex interdigitating podocyte foot processes is critical to form the normal glomerular filtration barrier, but the molecular programs driving this process are unknown. The protein atypical protein kinase C (aPKC)—a component of the Par complex, which localizes to tight junctions and interacts with slit diaphragm proteins—may play a role. Here, we found that the combined deletion of the aPKCλ/ι and aPKCζ isoforms in podocytes associated with incorrectly positioned centrosomes and Golgi apparatus and mislocalized molecules of the slit diaphragm. Furthermore, aPKC-deficient podocytes failed to form the normal network of foot processes, leading to defective glomerular maturation with incomplete capillary formation and mesangiolysis. Our results suggest that aPKC isoforms orchestrate the formation of the podocyte processes essential for normal glomerular development and kidney function. Defective aPKC signaling results in a dramatically simplified glomerular architecture, causing severe proteinuria and perinatal death. PMID:23334392

Podocyte injury: the role of proteinuria, urinary plasminogen, and oxidative stress

PubMed Central

Tian, Runxia; Wong, Jenny S.; He, John C.; Campbell, Kirk N.

2016-01-01

Podocytes are the key target for injury in proteinuric glomerular diseases that result in podocyte loss, progressive focal segmental glomerular sclerosis (FSGS), and renal failure. Current evidence suggests that the initiation of podocyte injury and associated proteinuria can be separated from factors that drive and maintain these pathogenic processes leading to FSGS. In nephrotic urine aberrant glomerular filtration of plasminogen (Plg) is activated to the biologically active serine protease plasmin by urokinase-type plasminogen activator (uPA). In vivo inhibition of uPA mitigates Plg activation and development of FSGS in several proteinuric models of renal disease including 5/6 nephrectomy. Here, we show that Plg is markedly increased in the urine in two murine models of proteinuric kidney disease associated with podocyte injury: Tg26 HIV-associated nephropathy and the Cd2ap−/− model of FSGS. We show that human podocytes express uPA and three Plg receptors: uPAR, tPA, and Plg-RKT. We demonstrate that Plg treatment of podocytes specifically upregulates NADPH oxidase isoforms NOX2/NOX4 and increases production of mitochondrial-dependent superoxide anion (O2−) that promotes endothelin-1 synthesis. Plg via O2− also promotes expression of the B scavenger receptor CD36 and subsequent increased intracellular cholesterol uptake resulting in podocyte apoptosis. Taken together, our findings suggest that following disruption of the glomerular filtration barrier at the onset of proteinuric disease, podocytes are exposed to Plg resulting in further injury mediated by oxidative stress. We suggest that chronic exposure to Plg could serve as a “second hit” in glomerular disease and that Plg is potentially an attractive target for therapeutic intervention. PMID:27335373

Fluid flow shear stress over podocytes is increased in the solitary kidney

PubMed Central

Srivastava, Tarak; Celsi, Gianni E.; Sharma, Mukut; Dai, Hongying; McCarthy, Ellen T.; Ruiz, Melanie; Cudmore, Patricia A.; Alon, Uri S.; Sharma, Ram; Savin, Virginia A.

2014-01-01

Background Glomerular hyperfiltration is emerging as the key risk factor for progression of chronic kidney disease (CKD). Podocytes are exposed to fluid flow shear stress (FFSS) caused by the flow of ultrafiltrate within Bowman's space. The mechanism of hyperfiltration-induced podocyte injury is not clear. We postulated that glomerular hyperfiltration in solitary kidney increases FFSS over podocytes. Methods Infant Sprague–Dawley rats at 5 days of age and C57BL/6J 14-week-old adult mice underwent unilateral nephrectomy. Micropuncture and morphological studies were then performed on 20- and 60-day-old rats. FFSS over podocytes in uninephrectomized rats and mice was calculated using the recently published equation by Friedrich et al. which includes the variables—single nephron glomerular filtration rate (SNGFR), filtration fraction (f), glomerular tuft diameter (2RT) and width of Bowman's space (s). Results Glomerular hypertrophy was observed in uninephrectomized rats and mice. Uninephrectomized rats on Day 20 showed a 2.0-fold increase in SNGFR, 1.0-fold increase in 2RT and 2.1-fold increase in FFSS, and on Day 60 showed a 1.9-fold increase in SNGFR, 1.3-fold increase in 2RT and 1.5-fold increase in FFSS, at all values of modeled ‘s’. Similarly, uninephrectomized mice showed a 2- to 3-fold increase in FFSS at all values of modeled SNGFR. Conclusions FFSS over podocytes is increased in solitary kidneys in both infant rats and adult mice. This increase is a consequence of increased SNGFR. We speculate that increased FFSS caused by reduced nephron number contributes to podocyte injury and promotes the progression of CKD. PMID:24166460

Proton Pump Inhibitor Use and the Risk of Chronic Kidney Disease.

PubMed

Lazarus, Benjamin; Chen, Yuan; Wilson, Francis P; Sang, Yingying; Chang, Alex R; Coresh, Josef; Grams, Morgan E

2016-02-01

Proton pump inhibitors (PPIs) are among the most commonly used drugs worldwide and have been linked to acute interstitial nephritis. Less is known about the association between PPI use and chronic kidney disease (CKD). To quantify the association between PPI use and incident CKD in a population-based cohort. In total, 10,482 participants in the Atherosclerosis Risk in Communities study with an estimated glomerular filtration rate of at least 60 mL/min/1.73 m(2) were followed from a baseline visit between February 1, 1996, and January 30, 1999, to December 31, 2011. The data was analyzed from May 2015 to October 2015. The findings were replicated in an administrative cohort of 248,751 patients with an estimated glomerular filtration rate of at least 60 mL/min/1.73 m(2) from the Geisinger Health System. Self-reported PPI use in the Atherosclerosis Risk in Communities study or an outpatient PPI prescription in the Geisinger Health System replication cohort. Histamine2 (H2) receptor antagonist use was considered a negative control and active comparator. Incident CKD was defined using diagnostic codes at hospital discharge or death in the Atherosclerosis Risk in Communities Study, and by a sustained outpatient estimated glomerular filtration rate of less than 60 mL/min/1.73 m(2) in the Geisinger Health System replication cohort. Among 10,482 participants in the Atherosclerosis Risk in Communities study, the mean (SD) age was 63.0 (5.6) years, and 43.9% were male. Compared with nonusers, PPI users were more often of white race, obese, and taking antihypertensive medication. Proton pump inhibitor use was associated with incident CKD in unadjusted analysis (hazard ratio [HR], 1.45; 95% CI, 1.11-1.90); in analysis adjusted for demographic, socioeconomic, and clinical variables (HR, 1.50; 95% CI, 1.14-1.96); and in analysis with PPI ever use modeled as a time-varying variable (adjusted HR, 1.35; 95% CI, 1.17-1.55). The association persisted when baseline PPI users were compared directly with H2 receptor antagonist users (adjusted HR, 1.39; 95% CI, 1.01-1.91) and with propensity score-matched nonusers (HR, 1.76; 95% CI, 1.13-2.74). In the Geisinger Health System replication cohort, PPI use was associated with CKD in all analyses, including a time-varying new-user design (adjusted HR, 1.24; 95% CI, 1.20-1.28). Twice-daily PPI dosing (adjusted HR, 1.46; 95% CI, 1.28-1.67) was associated with a higher risk than once-daily dosing (adjusted HR, 1.15; 95% CI, 1.09-1.21). Proton pump inhibitor use is associated with a higher risk of incident CKD. Future research should evaluate whether limiting PPI use reduces the incidence of CKD.

Underlying renal insufficiency: the pivotal risk factor for Pneumocystis jirovecii pneumonia in immunosuppressed patients with non-transplant glomerular disease.

PubMed

Ye, Wen-Ling; Tang, Nan; Wen, Yu-Bing; Li, Hang; Li, Min-Xi; Du, Bin; Li, Xue-Mei

2016-11-01

Data on PCP in patients with glomerular disease are rare. The aim of this study was to assess the predictors of PCP development, the risk factors for mortality and the incidence of acute kidney injury (AKI) when high-dose trimethoprim-sulphamethoxazole (TMP-SMX) was used in patients with non-transplant glomerular disease. Forty-seven patients with PCP, as confirmed by positive results for Pneumocystis jirovecii DNA or Pneumocystis jirovecii cysts tested by a methenamine silver stain between January 1, 2003, and December 30, 2012, were retrospectively investigated. The baseline characteristics of glomerular disease, clinical findings of PCP and renal parameters after treatment were collected. Predictors for PCP development and risk factors for mortality were determined using a multivariate logistic regression analysis. All PCP patients exclusively received immunosuppressants. Baseline renal insufficiency [estimated glomerular filtration rate (eGFR) <60 mL/min·1.73 m 2 ] was present in 87.23 % of patients. The overall mortality rate was 29.79 %. A pulmonary coinfection and the need for mechanical ventilation were independently associated with PCP mortality. A lower eGFR, lower serum albumin level and a higher percentage of global glomerulosclerosis were independent predictors of PCP in patients with IgA nephropathy receiving immunosuppressants. AKI occurred in 60.47 % of patients who received TMP-SMX. After treatment cessation, 93.75 % of surviving patients showed a recovery of renal function to baseline values. PCP is a fatal complication in patients with glomerular disease, and the use of immunosuppressants may be a basic risk factor for this infection. Underlying renal insufficiency and high renal pathology chronicity are the key risk factors for PCP in IgA nephropathy. TMP-SMX therapy remains an ideal choice because of high treatment response and frequently reversible kidney injury.

Salt sensitivity of children with low birth weight.

PubMed

Simonetti, Giacomo D; Raio, Luigi; Surbek, Daniel; Nelle, Mathias; Frey, Felix J; Mohaupt, Markus G

2008-10-01

Compromised intrauterine fetal growth leading to low birth weight (<2500 g) is associated with adulthood renal and cardiovascular disease. The aim of this study was to assess the effect of salt intake on blood pressure (salt sensitivity) in children with low birth weight. White children (n=50; mean age: 11.3+/-2.1 years) born with low (n=35) or normal (n=15) birth weight and being either small or appropriate for gestational age (n=25 in each group) were investigated. The glomerular filtration rate was calculated using the Schwartz formula, and renal size was measured by ultrasound. Salt sensitivity was assigned if mean 24-hour blood pressure increased by >or=3 mm Hg on a high-salt diet as compared with a controlled-salt diet. Baseline office blood pressure was higher and glomerular filtration rate lower in children born with low birth weight as compared with children born at term with appropriate weight (P<0.05). Salt sensitivity was present in 37% and 47% of all of the low birth weight and small for gestational age children, respectively, higher even than healthy young adults from the same region. Kidney length and volume (both P<0.0001) were reduced in low birth weight children. Salt sensitivity inversely correlated with kidney length (r(2)=0.31; P=0.005) but not with glomerular filtration rate. We conclude that a reduced renal mass in growth-restricted children poses a risk for a lower renal function and for increased salt sensitivity. Whether the changes in renal growth are causative or are the consequence of the same abnormal "fetal programming" awaits clarification.

Glomerular filtration rate in evaluation of the effect of iodinated contrast media on renal function.

PubMed

Becker, Joshua; Babb, James; Serrano, Manuel

2013-04-01

The purpose of this study was to use measured glomerular filtration rate (GFR), the reference standard of renal function, to assess the deleterious effect of iodinated contrast media on renal function. Such an effect has been traditionally defined as a greater than 0.5-mg/dL increase in serum creatinine concentration or a 25% or greater increase 24-72 hours after the injection of iodinated contrast medium. This pilot investigation was focused on the consequences of clinically indicated IV injection of iodinated contrast media; intraarterial injection was excluded. One hundred thirteen patients with normal serum creatinine concentrations were enrolled in an approved protocol. At random, as chosen by one of the investigators, patients underwent imaging with one of three monomeric agents (iopamidol 300, iopromide 300, iohexol 300) and one dimeric agent (iodixanol 320). Measured GFR was determined immediately before CT and approximately 3 and 72 hours after the contrast injection for the CT examination. Iodinated contrast medium, a glomerular filtrate with no tubular excretion or reabsorption, was the GFR marker. Measured GFR was determined by x-ray fluorescence analysis with nonisotopic iodinated contrast media. Monomeric and dimeric contrast agents in diagnostic CT volumes (based on bodyweight and imaging protocol) did not induce a significant change in measured GFR (95% confidence by Wilcoxon test), suggesting that use of the evaluated contrast media will not lead to more than a 12% variation. The three monomeric agents studied and the one dimeric agent were equivalent in terms of lack of a significant effect on measured GFR when administered to patients with a normal GFR.

The Radiologist Is in, but Was it Worth the Wait? Radiology Resident Note Quality in an Outpatient Interventional Radiology Clinic.

PubMed

Abboud, Salim E; Soriano, Stephanie; Abboud, Rayan; Patel, Indravadan; Davidson, Jon; Azar, Nami R; Nakamoto, Dean A

Preprocedural evaluation of patients in an interventional radiology (IR) clinic is a complex synthesis of physical examination and imaging findings, and as IR transitions to an independent clinical specialty, such evaluations will become an increasingly critical component of a successful IR practice and quality patient care. Prior research suggests that preprocedural evaluations increased patient's perceived quality of care and may improve procedural technical success rates. Appropriate documentation of a preprocedural evaluation in the medical record is also paramount for an interventional radiologist to add value and function as an effective member of a larger IR service and multidisciplinary health care team. The purpose of this study is to examine the quality of radiology resident notes for patients seen in an outpatient IR clinic at a single academic medical center before and after the adoption of clinic note template with reminders to include platelet count, international normalized ratio, glomerular filtration rate, and plan for periprocedural coagulation status. Before adoption of the template, platelet count, international normalized ratio, glomerular filtration rate and an appropriate plan for periprocedural coagulation status were documented in 72%, 82%, 42%, and 33% of patients, respectively. After adoption of the template, appropriate documentation of platelet count, international normalized ratio, and glomerular filtration rate increased to 96%, and appropriate plan for periprocedural coagulation status was documented in 83% of patients. Patient evaluation and clinical documentation skills may not be adequately practiced during radiology residency, and tools such as templates may help increase documentation quality by radiology residents. Copyright © 2017 Elsevier Inc. All rights reserved.

Alport syndrome: its effects on the glomerular filtration barrier and implications for future treatment

PubMed Central

Savige, Judy

2014-01-01

The glomerular filtration barrier comprises a fenestrated capillary endothelium, glomerular basement membrane and podocyte slit diaphragm. Over the past decade we have come to realise that permselectivity depends on size and not necessarily charge, that the molecular sieve depends on the podocyte contractile apparatus and is highly dynamic, and that protein uptake by proximal tubular epithelial cells stimulates signalling and the production of transcription factors and inflammatory mediators. Alport syndrome is the second commonest monogenic cause of renal failure after autosomal dominant polycystic kidney disease. Eighty per cent of patients have X-linked disease caused by mutations in the COL4A5 gene. Most of these result in the replacement of the collagen IV α3α4α5 network with the α1α1α2 heterotrimer. Affected membranes also have ectopic laminin and increased matrix metalloproteinase levels, which makes them more susceptible to proteolysis. Mechanical stress, due to the less elastic membrane and hypertension, interferes with integrin-mediated podocyte–GBM adhesion. Proteinuria occurs when urinary levels exceed tubular reabsorption rates, and initiates tubulointerstitial fibrosis. The glomerular mesangial cells produce increased TGFβ and CTGF which also contribute to glomerulosclerosis. Currently there is no specific therapy for Alport syndrome. However treatment with angiotensin converting enzyme (ACE) inhibitors delays renal failure progression by reducing intraglomerular hypertension, proteinuria, and fibrosis. Our greater understanding of the mechanisms underlying the GBM changes and their consequences in Alport syndrome have provided us with further novel therapeutic targets. PMID:25107927

Endothelial cell and podocyte autophagy synergistically protect from diabetes-induced glomerulosclerosis

PubMed Central

Lenoir, Olivia; Jasiek, Magali; Hénique, Carole; Guyonnet, Léa; Hartleben, Björn; Bork, Tillmann; Chipont, Anna; Flosseau, Kathleen; Bensaada, Imane; Schmitt, Alain; Massé, Jean-Marc; Souyri, Michèle; Huber, Tobias B; Tharaux, Pierre-Louis

2015-01-01

The glomerulus is a highly specialized capillary tuft, which under pressure filters large amounts of water and small solutes into the urinary space, while retaining albumin and large proteins. The glomerular filtration barrier (GFB) is a highly specialized filtration interface between blood and urine that is highly permeable to small and midsized solutes in plasma but relatively impermeable to macromolecules such as albumin. The integrity of the GFB is maintained by molecular interplay between its 3 layers: the glomerular endothelium, the glomerular basement membrane and podocytes, which are highly specialized postmitotic pericytes forming the outer part of the GFB. Abnormalities of glomerular ultrafiltration lead to the loss of proteins in urine and progressive renal insufficiency, underlining the importance of the GFB. Indeed, albuminuria is strongly predictive of the course of chronic nephropathies especially that of diabetic nephropathy (DN), a leading cause of renal insufficiency. We found that high glucose concentrations promote autophagy flux in podocyte cultures and that the abundance of LC3B II in podocytes is high in diabetic mice. Deletion of Atg5 specifically in podocytes resulted in accelerated diabetes-induced podocytopathy with a leaky GFB and glomerulosclerosis. Strikingly, genetic alteration of autophagy on the other side of the GFB involving the endothelial-specific deletion of Atg5 also resulted in capillary rarefaction and accelerated DN. Thus autophagy is a key protective mechanism on both cellular layers of the GFB suggesting autophagy as a promising new therapeutic strategy for DN. PMID:26039325

Autonomic and Renal Alterations in the Offspring of Sleep-Restricted Mothers During Late Pregnancy.

PubMed

Raimundo, Joyce R S; Bergamaschi, Cassia T; Campos, Ruy R; Palma, Beatriz D; Tufik, Sergio; Gomes, Guiomar N

2016-09-01

Considering that changes in the maternal environment may result in changes in progeny, the aim of this study was to investigate the influence of sleep restriction during the last week of pregnancy on renal function and autonomic responses in male descendants at an adult age. After confirmation of pregnancy, female Wistar rats were randomly assigned to either a control or a sleep restriction group. The sleep-restricted rats were subjected to sleep restriction using the multiple platforms method for over 20 hours per day between the 14th and 20th day of pregnancy. After delivery, the litters were limited to 6 offspring that were designated as offspring from control and offspring from sleep-restricted mothers. Indirect measurements of systolic blood pressure (BPi), renal plasma flow, glomerular filtration rate, glomerular area and number of glomeruli per field were evaluated at three months of age. Direct measurements of cardiovascular function (heart rate and mean arterial pressure), cardiac sympathetic tone, cardiac parasympathetic tone, and baroreflex sensitivity were evaluated at four months of age. The sleep-restricted offspring presented increases in BPi, glomerular filtration rate and glomerular area compared with the control offspring. The sleep-restricted offspring also showed higher basal heart rate, increased mean arterial pressure, increased sympathetic cardiac tone, decreased parasympathetic cardiac tone and reduced baroreflex sensitivity. Our data suggest that reductions in sleep during the last week of pregnancy lead to alterations in cardiovascular autonomic regulation and renal morpho-functional changes in offspring, triggering increases in blood pressure.

Kidney function and urine protein composition in healthy volunteers during space station fitness tests.

PubMed

Fomina, Elena V; Lisova, Natalia Iu; Kireev, Kirill S; Tiys, Evgeny S; Kononikhin, Alexey S; Larina, Irina M

2015-05-01

There is a close physiological connection between muscular activity and kidney function. During physical exercise (PE) the qualitative and quantitative composition of urine changes. This paper explores the influence of moderate PE on urine protein composition. The study of urine protein composition will help to make corrections to the existing methods of countermeasures. There were 10 healthy men who exercised on a treadmill similar to the one onboard the International Space Station. We analyzed their urinary proteome composition, potassium level, sodium level, and their level of osmotically active substances before and after PE. After moderate PE, a small increase in urine flow speed and a constant glomerular filtration rate were noted. The average-group index of total protein excretion within the urine was reliably increased. From the 148 proteins identified in the urine, 64 were associated with known tissue origin. We found that protein penetration into the urine had a positive correlation with their tissue expression. Selectivity of the glomerular barrier during PE decreased and high-molecular weight proteins penetrated through the glomerular barrier more easily after PE. Performance of moderate intensity physical exercise of short duration did not lead to an increase in the glomerular filtration rate nor did diuresis increase above the limits of baseline variability. However, the protein excretion rate increased after PE. We also observed that protein composition drift indicated a change in the set of biological processes in which a given protein participated, in some cases activating, in some cases inactivating them.

External validation of the Revised Cardiac Risk Index and update of its renal variable to predict 30-day risk of major cardiac complications after non-cardiac surgery: rationale and plan for analyses of the VISION study.

PubMed

Roshanov, Pavel S; Walsh, Michael; Devereaux, P J; MacNeil, S Danielle; Lam, Ngan N; Hildebrand, Ainslie M; Acedillo, Rey R; Mrkobrada, Marko; Chow, Clara K; Lee, Vincent W; Thabane, Lehana; Garg, Amit X

2017-01-09

The Revised Cardiac Risk Index (RCRI) is a popular classification system to estimate patients' risk of postoperative cardiac complications based on preoperative risk factors. Renal impairment, defined as serum creatinine >2.0 mg/dL (177 µmol/L), is a component of the RCRI. The estimated glomerular filtration rate has become accepted as a more accurate indicator of renal function. We will externally validate the RCRI in a modern cohort of patients undergoing non-cardiac surgery and update its renal component. The Vascular Events in Non-cardiac Surgery Patients Cohort Evaluation (VISION) study is an international prospective cohort study. In this prespecified secondary analysis of VISION, we will test the risk estimation performance of the RCRI in ∼34 000 participants who underwent elective non-cardiac surgery between 2007 and 2013 from 29 hospitals in 15 countries. Using data from the first 20 000 eligible participants (the derivation set), we will derive an optimal threshold for dichotomising preoperative renal function quantified using the Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) glomerular filtration rate estimating equation in a manner that preserves the original structure of the RCRI. We will also develop a continuous risk estimating equation integrating age and CKD-Epi with existing RCRI risk factors. In the remaining (approximately) 14 000 participants, we will compare the risk estimation for cardiac complications of the original RCRI to this modified version. Cardiac complications will include 30-day non-fatal myocardial infarction, non-fatal cardiac arrest and death due to cardiac causes. We have examined an early sample to estimate the number of events and the distribution of predictors and missing data, but have not seen the validation data at the time of writing. The research ethics board at each site approved the VISION protocol prior to recruitment. We will publish our results and make our models available online at http://www.perioperativerisk.com. ClinicalTrials.gov NCT00512109. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The giraffe kidney tolerates high arterial blood pressure by high renal interstitial pressure and low glomerular filtration rate.

PubMed

Damkjaer, M; Wang, T; Brøndum, E; Østergaard, K H; Baandrup, U; Hørlyck, A; Hasenkam, J M; Smerup, M; Funder, J; Marcussen, N; Danielsen, C C; Bertelsen, M F; Grøndahl, C; Pedersen, M; Agger, P; Candy, G; Aalkjaer, C; Bie, P

2015-08-01

The tallest animal on earth, the giraffe (Giraffa camelopardalis) is endowed with a mean arterial blood pressure (MAP) twice that of other mammals. The kidneys reside at heart level and show no sign of hypertension-related damage. We hypothesized that a species-specific evolutionary adaption in the giraffe kidney allows normal for size renal haemodynamics and glomerular filtration rate (GFR) despite a MAP double that of other mammals. Fourteen anaesthetized giraffes were instrumented with vascular and bladder catheters to measure glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). Renal interstitial hydrostatic pressure (RIHP) was assessed by inserting a needle into the medullary parenchyma. Doppler ultrasound measurements provided renal artery resistive index (RI). Hormone concentrations as well as biomechanical, structural and histological characteristics of vascular and renal tissues were determined. GFR averaged 342 ± 99 mL min(-1) and ERPF 1252 ± 305 mL min(-1) . RIHP varied between 45 and 140 mmHg. Renal pelvic pressure was 39 ± 2 mmHg and renal venous pressure 32 ± 4 mmHg. A valve-like structure at the junction of the renal and vena cava generated a pressure drop of 12 ± 2 mmHg. RI was 0.27. The renal capsule was durable with a calculated burst pressure of 600 mmHg. Plasma renin and AngII were 2.6 ± 0.5 mIU L(-1) and 9.1 ± 1.5 pg mL(-1) respectively. In giraffes, GFR, ERPF and RI appear much lower than expected based on body mass. A strong renal capsule supports a RIHP, which is >10-fold that of other mammals effectively reducing the net filtration pressure and protecting against the high MAP. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Iothalamate versus estimated GFR in a Hispanic-dominant pediatric renal transplant population.

PubMed

Papez, Karen E; Barletta, Gina-Marie; Hsieh, Stephanie; Joseph, Mark; Morgenstern, Bruce Z

2013-12-01

Accurate knowledge of glomerular filtration rate (GFR) is essential to the practice of nephrology. Routine surveillance of GFR is most commonly executed using estimated GFR (eGFR) calculations, most often from serum creatinine measurements. However, cystatin C-based equations have demonstrated earlier sensitivity to decline in renal function. The literature regarding eGFR from cystatin C has few references that include transplant recipients. Additionally, for most of the published eGFR equations, patients of Hispanic ethnicity have not been enrolled in sufficient numbers. The applicability of several eGFR equations to the pediatric kidney transplant population at our center were compared in the context of determining whether Hispanic ethnicity was associated with equation performance. Updated Schwartz, CKiD, and Zappitelli eGFR estimation equations demonstrated the highest correlations. The authors recommend further prospective investigations to validate and identify factors contributing to these findings.

Patient-specific evolution of renal function in chronic heart failure patients dynamically predicts clinical outcome in the Bio-SHiFT study.

PubMed

Brankovic, Milos; Akkerhuis, K Martijn; van Boven, Nick; Anroedh, Sharda; Constantinescu, Alina; Caliskan, Kadir; Manintveld, Olivier; Cornel, Jan Hein; Baart, Sara; Rizopoulos, Dimitris; Hillege, Hans; Boersma, Eric; Umans, Victor; Kardys, Isabella

2018-04-01

Renal dysfunction is an important component of chronic heart failure (CHF), but its single assessment does not sufficiently reflect clinically silent progression of CHF prior to adverse clinical outcome. Therefore, we aimed to investigate temporal evolutions of glomerular and tubular markers in 263 stable patients with CHF, and to determine if their patient-specific evolutions during this clinically silent period can dynamically predict clinical outcome. We determined the risk of clinical outcome (composite endpoint of Heart Failure hospitalization, cardiac death, Left Ventricular Assist Device placement, and heart transplantation) in relation to marker levels, slopes and areas under their trajectories. In each patient, the trajectories were estimated using repeatedly measured glomerular markers: creatinine/estimated glomerular filtration rate (eGFR), cystatin C (CysC), and tubular markers: urinary N-acetyl-beta-D-glucosaminidase (NAG) and kidney injury molecule (KIM)-1, plasma and urinary neutrophil gelatinase-associated lipocalin (NGAL). During 2.2 years of follow-up, we collected on average 8 urine and 9 plasma samples per patient. All glomerular markers predicted the endpoint (univariable hazard ratio [95% confidence interval] per 20% increase: creatinine: 1.18[1.07-1.31], CysC: 2.41[1.81-3.41], and per 20% eGFR decrease: 1.13[1.05-1.23]). Tubular markers, NAG, and KIM-1 also predicted the endpoint (NAG: 1.06[1.01-1.11] and KIM-1: 1.08[1.04-1.11]). Larger slopes were the strongest predictors (creatinine: 1.57[1.39-1.84], CysC: 1.76[1.52-2.09], eGFR: 1.59[1.37-1.90], NAG: 1.26[1.11-1.44], and KIM-1: 1.64[1.38-2.05]). Associations persisted after multivariable adjustment for clinical characteristics. Thus, during clinically silent progression of CHF, glomerular and tubular functions deteriorate, but not simultaneously. Hence, patient-specific evolutions of these renal markers dynamically predict clinical outcome in patients with CHF. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

The eGFR-C study: accuracy of glomerular filtration rate (GFR) estimation using creatinine and cystatin C and albuminuria for monitoring disease progression in patients with stage 3 chronic kidney disease--prospective longitudinal study in a multiethnic population.

PubMed

Lamb, Edmund J; Brettell, Elizabeth A; Cockwell, Paul; Dalton, Neil; Deeks, Jon J; Harris, Kevin; Higgins, Tracy; Kalra, Philip A; Khunti, Kamlesh; Loud, Fiona; Ottridge, Ryan S; Sharpe, Claire C; Sitch, Alice J; Stevens, Paul E; Sutton, Andrew J; Taal, Maarten W

2014-01-14

Uncertainty exists regarding the optimal method to estimate glomerular filtration rate (GFR) for disease detection and monitoring. Widely used GFR estimates have not been validated in British ethnic minority populations. Iohexol measured GFR will be the reference against which each estimating equation will be compared. The estimating equations will be based upon serum creatinine and/or cystatin C. The eGFR-C study has 5 components: 1) A prospective longitudinal cohort study of 1300 adults with stage 3 chronic kidney disease followed for 3 years with reference (measured) GFR and test (estimated GFR [eGFR] and urinary albumin-to-creatinine ratio) measurements at baseline and 3 years. Test measurements will also be undertaken every 6 months. The study population will include a representative sample of South-Asians and African-Caribbeans. People with diabetes and proteinuria (ACR ≥30 mg/mmol) will comprise 20-30% of the study cohort.2) A sub-study of patterns of disease progression of 375 people (125 each of Caucasian, Asian and African-Caribbean origin; in each case containing subjects at high and low risk of renal progression). Additional reference GFR measurements will be undertaken after 1 and 2 years to enable a model of disease progression and error to be built.3) A biological variability study to establish reference change values for reference and test measures.4) A modelling study of the performance of monitoring strategies on detecting progression, utilising estimates of accuracy, patterns of disease progression and estimates of measurement error from studies 1), 2) and 3).5) A comprehensive cost database for each diagnostic approach will be developed to enable cost-effectiveness modelling of the optimal strategy.The performance of the estimating equations will be evaluated by assessing bias, precision and accuracy. Data will be modelled as a linear function of time utilising all available (maximum 7) time points compared with the difference between baseline and final reference values. The percentage of participants demonstrating large error with the respective estimating equations will be compared. Predictive value of GFR estimates and albumin-to-creatinine ratio will be compared amongst subjects that do or do not show progressive kidney function decline. The eGFR-C study will provide evidence to inform the optimal GFR estimate to be used in clinical practice. ISRCTN42955626.

Americans’ Use of Dietary Supplements That Are Potentially Harmful in CKD

PubMed Central

Grubbs, Vanessa; Plantinga, Laura C.; Tuot, Delphine S.; Hedgeman, Elizabeth; Saran, Rajiv; Saydah, Sharon; Rolka, Deborah; Powe, Neil R.

2013-01-01

Background The prevalence in the United States of dietary supplement use that may be harmful to those with chronic kidney disease (CKD) is unknown. We sought to characterize potentially harmful supplement use by individual CKD status. Study Design Cross-sectional national survey (National Health and Nutrition Examination Survey, 1999-2008) Setting & Participants Community-based survey of 21,169 non-pregnant, non-institutionalized U.S. civilian adults (≥20 years) Predictor CKD status (no CKD, at risk for CKD [presence of diabetes, hypertension and/or cardiovascular disease], stage 1/2 [albuminuria only (albumin-creatinine ratio ≥30 mg/g)], or stage 3/4 [estimated glomerular filtration rate of 15-59 ml/min/1.73 m2]). Outcome Self-reported use of dietary supplements containing any of 37 herbs the National Kidney Foundation identified as potentially harmful in the setting of CKD. Measurements Albuminuria and estimated glomerular filtration rate assessed from urine and blood samples; demographics and comorbid conditions assessed by standardized questionnaire. Results An estimated 8.0% of U.S. adults reported potentially harmful supplement use within the last 30 days. Lower crude estimated prevalence of potentially harmful supplement use was associated with higher CKD severity (no CKD, 8.5%; at risk, 8.0%; stage 1/2, 6.1%; and stage 3/4, 6.2%; p<0.001). However, after adjustment for confounders, those with or at risk for CKD were as likely to use a potentially harmful supplement as those without CKD: at-risk OR, 0.93 (95% CI, 0.79 -1.09); stage 1/2 OR, 0.83 (95% CI, 0.64 -1.08); stage 3/4 OR, 0.87 (95% CI, 0.63 -1.18); all vs. no CKD. Limitations Herb content was not available and the list of potentially harmful supplements examined is unlikely to be exhaustive. Conclusions The use of dietary supplements potentially harmful to people with CKD is common, regardless of CKD status. Healthcare providers should discuss the use and potential risks of supplements with patients with and at risk for CKD. PMID:23415417

Americans' use of dietary supplements that are potentially harmful in CKD.

PubMed

Grubbs, Vanessa; Plantinga, Laura C; Tuot, Delphine S; Hedgeman, Elizabeth; Saran, Rajiv; Saydah, Sharon; Rolka, Deborah; Powe, Neil R

2013-05-01

The prevalence in the United States of dietary supplement use that may be harmful to those with chronic kidney disease (CKD) is unknown. We sought to characterize potentially harmful supplement use by individual CKD status. Cross-sectional national survey (National Health and Nutrition Examination Survey, 1999-2008). Community-based survey of 21,169 nonpregnant noninstitutionalized US civilian adults (aged ≥20 years). CKD status (no CKD, at risk of CKD [presence of diabetes, hypertension, and/or cardiovascular disease], stages 1/2 [albuminuria only (albumin-creatinine ratio ≥30 mg/g)], or stages 3/4 [estimated glomerular filtration rate of 15-59 mL/min/1.73 m(2)]). Self-reported use of dietary supplements containing any of 37 herbs the National Kidney Foundation identified as potentially harmful in the setting of CKD. Albuminuria and estimated glomerular filtration rate assessed from urine and blood samples; demographics and comorbid conditions assessed by standardized questionnaire. An estimated 8.0% of US adults reported potentially harmful supplement use within the last 30 days. A lower crude estimated prevalence of potentially harmful supplement use was associated with higher CKD severity (no CKD, 8.5%; at risk, 8.0%; stages 1/2, 6.1%; and stages 3/4, 6.2%; P < 0.001). However, after adjustment for confounders, those with or at risk of CKD were as likely to use a potentially harmful supplement as those without CKD: at-risk OR, 0.93 (95% CI, 0.79-1.09); stages 1/2 OR, 0.83 (95% CI, 0.64-1.08); and stages 3/4 OR, 0.87 (95% CI, 0.63-1.18); all versus no CKD. Herb content was not available and the list of potentially harmful supplements examined is unlikely to be exhaustive. The use of dietary supplements potentially harmful to people with CKD is common regardless of CKD status. Health care providers should discuss the use and potential risks of supplements with patients with and at risk of CKD. Copyright © 2013 National Kidney Foundation, Inc. All rights reserved.

Effect of Tenofovir Disoproxil Fumarate on Incidence of Chronic Kidney Disease and Rate of Estimated Glomerular Filtration Rate Decrement in HIV-1-Infected Treatment-Naïve Asian Patients: Results from 12-Year Observational Cohort.

PubMed

Suzuki, Soichiro; Nishijima, Takeshi; Kawasaki, Yohei; Kurosawa, Takuma; Mutoh, Yoshikazu; Kikuchi, Yoshimi; Gatanaga, Hiroyuki; Oka, Shinichi

2017-03-01

Little evidence is available for the incidence of chronic kidney disease (CKD) and rate of estimated glomerular filtration rate (eGFR) decrement among Asians with low body weight who are susceptible to tenofovir disoproxil fumarate (TDF) nephrotoxicity. In this 12-year observational cohort in Tokyo, we examined 1383 treatment-naïve HIV-1-infected Asians [720 started TDF-containing (TDF group) and 663 started non-TDF-containing (control) combination antiretroviral therapy (cART)]. The CKD incidence was calculated, and the effect of TDF use on CKD development was estimated using logistic regression. The eGFR slopes, before and after cART initiation, were estimated using mixed-effects linear spline models. Most patients were males (median weight, 62.6 kg; 83% started ritonavir-boosted protease inhibitors; median observation duration, 5.08 years). CKD developed in 150 patients (10.8%), with an incidence of 20.6 per 1000 person-years [confidence interval (95% CI), 17.6-24.2]. None developed end-stage renal disease. TDF use was associated with CKD [odds ratio (OR), 1.8; 95% CI, 1.00-3.13; p = 0.052]. The cumulative mean loss in the TDF group, relative to the control, increased over time after 1, 4, and 8 years of TDF exposure (-3.8, -5.5, and -9.0 mL/min/1.73 m 2 , respectively; p < 0.0001). The eGFR rapidly declined during the first 3 months of cART, particularly in the TDF group (-26.4 vs. -7.4 mL/min/1.73 m 2 /year in the control). In the TDF group, cART introduction was significantly associated with a faster rate of eGFR decline (from -0.44 to -2.11 mL/min/1.73 m 2 /year; p = 0.010), whereas in the control, the difference was not significant. For HIV-1-infected Asian patients with low body weight, TDF-containing cART is associated with CKD and faster eGFR declines.

[Concordance in critical patients between the equations designed for the calculation of glomerular filtration rate and 24-hour creatinine clearance].

PubMed

Seller-Pérez, G; Herrera-Gutiérrez, M E; Banderas-Bravo, E; Olalla-Sánchez, R; Lozano-Sáez, R; Quesada-García, G

2010-01-01

To study the behavior of the different equations used to estimate glomerular filtration rate (GFR) applied to critical care patients compared to the standard method: 24-hour creatinine clearance (24-CrCl). Retrospective analysis of data base from a previous observational prospective study. Polyvalent ICU in a tertiary Hospital. All adult patients admitted to our Unit during the study who had a bladder catheter inserted. Anuric patients were excluded. We measured 24-CrCl and estimated GFR by MDRD, modified Jelliffe (JF), Mayo-Clinic (CM) and Cockroft-Gault (C-G) equations. To evaluate degree of agreement, we grouped patients regarding 24-CrCl as normal (>70), moderate dysfunction (69-50) or severe renal dysfunction (< 50 mL/min/1.73 m(2)). 307 patients, aged 54+/-18, 69.7% males. Measured 24-CrCl was 109.2+/-78.2 mL/min/1.73 m(2) and the estimate one 95.5+/-56.7 for JF, 87.4+/-53.4 for C-G, 86.9+/-55.9 for MDRD and 85.6+/-39.9 for CM. The difference was significant (p<0.001) for all estimates but lower for (13.7+/-53.2 mL/min/1.73 m(2)) than C-G (21.9+/-58.3), CM (23.6+/-59.6) or MDRD (22.3+/-60.4). Correlation coefficient was 0.73 for JF, 0.67 C-G or CM and 0.64 for MDRD. The degree of agreement was only fair for all measures (Kappa 0.55 for JF or MDRD, 0.51 for C-G and 0.5 for CM). Modified Jelliffe equation showed higher agreement with 24-CrCl than Cockroft-Gault, MDRD or Mayo-Clinic equations when used in critically ill patients. However, when exact measurement is needed, none of the equations can be considered adequate and in these cases, the CrCl should be calculated. Copyright (c) 2009 Elsevier España, S.L. y SEMICYUC. All rights reserved.

Application of 80-kVp scan and raw data-based iterative reconstruction for reduced iodine load abdominal-pelvic CT in patients at risk of contrast-induced nephropathy referred for oncological assessment: effects on radiation dose, image quality and renal function.

PubMed

Nagayama, Yasunori; Tanoue, Shota; Tsuji, Akinori; Urata, Joji; Furusawa, Mitsuhiro; Oda, Seitaro; Nakaura, Takeshi; Utsunomiya, Daisuke; Yoshida, Eri; Yoshida, Morikatsu; Kidoh, Masafumi; Tateishi, Machiko; Yamashita, Yasuyuki

2018-05-01

To evaluate the image quality, radiation dose, and renal safety of contrast medium (CM)-reduced abdominal-pelvic CT combining 80-kVp and sinogram-affirmed iterative reconstruction (SAFIRE) in patients with renal dysfunction for oncological assessment. We included 45 patients with renal dysfunction (estimated glomerular filtration rate  <45 ml per min per 1.73 m 2 ) who underwent reduced-CM abdominal-pelvic CT (360 mgI kg -1 , 80-kVp, SAFIRE) for oncological assessment. Another 45 patients without renal dysfunction (estimated glomerular filtration rate >60 ml per lmin per 1.73 m 2 ) who underwent standard oncological abdominal-pelvic CT (600 mgI kg -1 , 120-kVp, filtered-back projection) were included as controls. CT attenuation, image noise, and contrast-to-noise ratio (CNR) were compared. Two observers performed subjective image analysis on a 4-point scale. Size-specific dose estimate and renal function 1-3 months after CT were measured. The size-specific dose estimate and iodine load of 80-kVp protocol were 32 and 41%,, respectively, lower than of 120-kVp protocol (p < 0.01). CT attenuation and contrast-to-noise ratio of parenchymal organs and vessels in 80-kVp images were significantly better than those of 120-kVp images (p < 0.05). There were no significant differences in quantitative or qualitative image noise or subjective overall quality (p > 0.05). No significant kidney injury associated with CM administration was observed. 80-kVp abdominal-pelvic CT with SAFIRE yields diagnostic image quality in oncology patients with renal dysfunction under substantially reduced iodine and radiation dose without renal safety concerns. Advances in knowledge: Using 80-kVp and SAFIRE allows for 40% iodine load and 32% radiation dose reduction for abdominal-pelvic CT without compromising image quality and renal function in oncology patients at risk of contrast-induced nephropathy.

Clinical and genetic predictors of renal dysfunctions in sickle cell anaemia in Cameroon.

PubMed

Geard, Amy; Pule, Gift D; Chetcha Chemegni, Bernard; Ngo Bitoungui, Valentina J; Kengne, Andre P; Chimusa, Emile R; Wonkam, Ambroise

2017-08-01

Micro-albuminuria and glomerular hyperfiltration are primary indicators of renal dysfunctions in Sickle Cell Disease (SCD), with more severe manifestations previously associated with variants in APOL1 and HMOX1 among African Americans. We have investigated 413 SCD patients from Cameroon. Anthropometric variables, haematological indices, crude albuminuria, albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were measured. Patients were genotyped for 3·7 kb alpha-globin gene (HBA1/HBA2) deletion, and for variants in APOL1 (G1/G2; rs60910145, rs73885319, rs71785313) and HMOX1 (rs3074372, rs743811). The median age was 15 years; the majority presented with micro-albuminuria (60·9%; n = 248), and approximately half with glomerular hyperfiltration (49·5%; n = 200). Age, male sex, haemoglobin level, leucocyte count, mean corpuscular volume, blood pressure, body mass index and creatinine levels significantly affected albuminuria and/or eGFR. Co-inheritance of alpha-thalassaemia was protective against macro-albuminuria (P = 0·03). APOL1 G1/G2 risk variants were significantly associated with the ACR (P = 0·01) and borderline with eGFR (P = 0·07). HMOX1 - rs743811 was borderline associated with micro-albuminuria (P = 0·07) and macro-albuminuria (P = 0·06). The results revealed a high proportion of micro-albuminuria and glomerular hyperfiltration among Cameroonian SCD patients, and support the possible use of targeted genetic biomarkers for risks assessment. © 2017 John Wiley & Sons Ltd.

28 CFR 79.67 - Proof of chronic renal disease.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) Abnormal glomerular filtration rate (by either measured creatinine or iothalamate clearance or calculated... report; (5) Hospital discharge summary report; (6) Hospital admitting report; or (7) Death certificate, provided that it is signed by a physician at the time of death. ...

28 CFR 79.67 - Proof of chronic renal disease.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) Abnormal glomerular filtration rate (by either measured creatinine or iothalamate clearance or calculated... report; (5) Hospital discharge summary report; (6) Hospital admitting report; or (7) Death certificate, provided that it is signed by a physician at the time of death. ...

28 CFR 79.67 - Proof of chronic renal disease.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) Abnormal glomerular filtration rate (by either measured creatinine or iothalamate clearance or calculated... report; (5) Hospital discharge summary report; (6) Hospital admitting report; or (7) Death certificate, provided that it is signed by a physician at the time of death. ...

Numbers, Neurons and Tides, Oh My!

ERIC Educational Resources Information Center

Ortiz, Mary Theresa

2006-01-01

Mathematical applications to biology are presented in Anatomy & Physiology, General and Marine Biology. Body measurements and anatomical terminology are integrated, and problems involving neuron conduction speed, red blood cells, hemoglobin and glomerular filtration presented. General Biology applications include trans-membrane potential and…

Pregnancy Increases the Renal Secretion of N1-methylnicotinamide, an Endogenous Probe for Renal Cation Transporters, in Patients Prescribed Metformin.

PubMed

Bergagnini-Kolev, Mackenzie C; Hebert, Mary F; Easterling, Thomas R; Lin, Yvonne S

2017-03-01

N 1 -methylnicotinamide (1-NMN) has been investigated as an endogenous probe for the renal transporter activity of organic cation transporter 2 (OCT2) and multidrug and toxin extrusion proteins 1 and 2-K (MATE1 and MATE2-K). As pregnancy increased the renal secretion of metformin, a substrate for OCT2, MATE1, and MATE2-K, we hypothesized that the renal secretion of 1-NMN would be similarly affected. Blood and urine samples collected from women prescribed metformin for type 2 diabetes, gestational diabetes, and polycystic ovarian syndrome during early, mid, and late pregnancy ( n = 34 visits) and postpartum ( n = 14 visits) were analyzed for 1-NMN using liquid chromatography-mass spectrometry. The renal clearance and secretion clearance, using creatinine clearance to correct for glomerular filtration, were estimated for 1-NMN and correlated with metformin renal clearance. 1-NMN renal clearance was higher in both mid (504 ± 293 ml/min, P < 0.01) and late pregnancy (557 ± 305 ml/min, P < 0.01) compared with postpartum (240 ± 106 ml/min). The renal secretion of 1-NMN was 3.5-fold higher in mid pregnancy (269± 267, P < 0.05) and 4.5-fold higher in late pregnancy compared with postpartum (342 ± 283 versus 76 ± 92 ml/min, P < 0.01). Because creatinine is also a substrate of OCT2, MATE1, and MATE2-K, creatinine clearance likely overestimates filtration clearance, whereas the calculated 1-NMN secretion clearance is likely underestimated. Metformin renal clearance and 1-NMN renal clearance were positively correlated (r s = 0.68, P < 0.0001). 1-NMN renal clearance increases during pregnancy due to increased glomerular filtration and net secretion by renal transporters. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Effect of angiotensin converting enzyme inhibitor on glomerular hyperfiltration in patients with type 1 diabetes

PubMed Central

Naqvi, S. A. Jaffar; Ahsan, Shahid; Fawwad, Asher; Basit, Abdul; Shera, A Samad

2016-01-01

Objective: To assess the effect of angiotensin converting enzyme inhibition on glomerular filtration rate (GFR) in normotensive patient with type 1 diabetes. Methods: A two year non-placebo control prospective study was conducted after ethical approval at Diabetes Centre of Diabetic Association of Pakistan, a WHO collaborating centre in Karachi, Pakistan. All patients with type 1 diabetes visited the out-patients department from August 2009 till July 2011 and those who fulfilled the inclusion criteria were invited to participate. A total of 121 people aged ≥18 years and ≥ 5 years of diabetes were included. Pregnant and lactating woman and those aged <18 years were excluded. GFR was calculated by using CKD-EPI formula (eGFR) at baseline and after two year. On the basis of estimated GFR, patients at baseline were divided according to KDIGO classification of chronic kidney diseases into, hyperfiltration (eGFR ≥ 100 ml/min) and normal filtration group (eGFR < 100 ml/min). All subjects in hyperfiltration group received ACE inhibitor (treatment group) while patients with normal filtration did not receive ACE inhibitor (control group). Results: Fifty two patients (43%) were in the treatment and sixty nine (57%) were in the control group. At baseline eGFR, systolic and diastolic blood pressures between groups were non-significantly different. After two years, compared to baseline, eGFR of the treatment group declined and the control group increased significantly. No significant difference in systolic while diastolic blood pressure of the treatment group increased significantly after two years compared to baseline. In contrast both systolic and diastolic blood pressure of control group increased significantly after two years compared to their baseline values. Conclusion: Present study demonstrated that initiation of ACEI in hyperfiltration stage declined GFR and keep blood pressure within normal range. PMID:27375689

Effective Utilization of Oral Hypoglycemic Agents to Achieve Individualized HbA1c Targets in Patients with Type 2 Diabetes Mellitus.

PubMed

Bannister, Margaret; Berlanga, Jenny

2016-09-01

Type 2 diabetes is a progressive condition that may require the combination of three oral treatments to achieve optimal glycemic management to prevent microvascular and macrovascular complications whilst minimizing the risk of acute complications and side effects or adverse reactions to treatments. With the widening availability of treatment options and increasing importance of individualized treatment pathways, including personalized HbA1c targets, this article will explore the mode of action of currently available oral treatments, factors to consider when individualizing HbA1c targets, the relevance of estimated glomerular filtration rate assessment, and the importance of reviewing the clinical impact of all treatment decisions.

Strategies of the Brazilian chronic kidney disease prevention campaign (2003-2009).

PubMed

Mastroianni-Kirsztajn, Gianna; Bastos, Marcus G; Burdmann, Emmanuel A

2011-01-01

In Brazil, as in the rest of the world, the prevalence of chronic kidney disease (CKD) is increasing. In order to alert the population, health professionals and authorities to this risk, in 2003, the Brazilian Society of Nephrology launched a CKD prevention campaign called 'Previna-se'. In addition, since its onset, Brazil has participated in the World Kidney Day efforts and has developed several prevention strategies. Here, we summarize the main strategies adopted in this campaign (population screening, events and meetings, distribution of educational materials, routine report of estimated glomerular filtration rate) and our initial results, sharing practical experience that could be useful in other developing countries. Copyright © 2010 S. Karger AG, Basel.

Diabetes-Induced Reactive Oxygen Species: Mechanism of Their Generation and Role in Renal Injury

PubMed Central

Fakhruddin, Selim; Alanazi, Wael

2017-01-01

Diabetes induces the onset and progression of renal injury through causing hemodynamic dysregulation along with abnormal morphological and functional nephron changes. The most important event that precedes renal injury is an increase in permeability of plasma proteins such as albumin through a damaged glomerular filtration barrier resulting in excessive urinary albumin excretion (UAE). Moreover, once enhanced UAE begins, it may advance renal injury from progression of abnormal renal hemodynamics, increased glomerular basement membrane (GBM) thickness, mesangial expansion, extracellular matrix accumulation, and glomerulosclerosis to eventual end-stage renal damage. Interestingly, all these pathological changes are predominantly driven by diabetes-induced reactive oxygen species (ROS) and abnormal downstream signaling molecules. In diabetic kidney, NADPH oxidase (enzymatic) and mitochondrial electron transport chain (nonenzymatic) are the prominent sources of ROS, which are believed to cause the onset of albuminuria followed by progression to renal damage through podocyte depletion. Chronic hyperglycemia and consequent ROS production can trigger abnormal signaling pathways involving diverse signaling mediators such as transcription factors, inflammatory cytokines, chemokines, and vasoactive substances. Persistently, increased expression and activation of these signaling molecules contribute to the irreversible functional and structural changes in the kidney resulting in critically decreased glomerular filtration rate leading to eventual renal failure. PMID:28164134

[Impaired renal function: be aware of exogenous factors].

PubMed

van der Meijden, Wilbert A G; Smak Gregoor, Peter J H

2013-01-01

Renal function is currently estimated using the Modification of Diet in Renal Disease (MDRD) formula, which is partly based on the serum creatinine level. Patients with impaired renal function are referred to nephrologists in accordance with the Dutch national transmural agreement for 'Chronic renal impairment'. A 54-year-old woman without significant history was referred to analyse a coincidentally found decline in the estimated glomerular filtration rate (eGFR). The patient had no complaints and used no medication except creatine supplements. Additional diagnostic testing showed no abnormalities. After cessation of creatine supplementation, the calculated renal function normalized. Serum creatinine is a reflection of muscle mass. The use of creatine-containing dietary supplements, such as creatine ethyl ester, can influence serum creatinine levels and therefore the eGFR as calculated with the MDRD formula. The use of supplements deserves attention when taking the history.

A reassessment of soluble urokinase-type plasminogen activator receptor in glomerular disease

PubMed Central

Spinale, Joann M.; Mariani, Laura H.; Kapoor, Shiv; Zhang, Jidong; Weyant, Robert; Song, Peter X.; Wong, Hetty N.; Troost, Jonathan P.; Gadegbeku, Crystal A.; Gipson, Debbie S.; Kretzler, Matthias; Nihalani, Deepak; Holzman, Lawrence B.

2014-01-01

It has been suggested that soluble urokinase receptor (suPAR) is a causative circulating factor for and a biomarker of focal and segmental glomerulosclerosis (FSGS). Here we undertook validation of these assumptions in both mouse and human models. Injection of recombinant suPAR in wild-type mice did not induce proteinuria within 24 hours. Moreover, a disease phenotype was not seen in an inducible transgenic mouse model that maintained elevated suPAR concentrations for 6 weeks. Plasma and urine suPAR concentrations were evaluated as clinical biomarkers in 241 patients with glomerular disease from the prospective, longitudinal multi-center observational NEPTUNE cohort. The serum suPAR concentration at baseline inversely correlated with estimated glomerular filtration rate (eGFR) and the urine suPAR/creatinine ratio positively correlated with the urine protein/creatinine ratio. After adjusting for eGFR and urine protein, neither the serum nor urine suPAR level was an independent predictor of FSGS histopathology. A multivariable mixed-effects model of longitudinal data evaluated the association between the change in serum suPAR concentration from baseline with eGFR. After adjusting for baseline suPAR concentration, age, gender, proteinuria and time, the change in suPAR from baseline was associated with eGFR, but this association was not different for patients with FSGS as compared to other diagnoses. Thus, these results do not support a pathological role for suPAR in FSGS. PMID:25354239

A reassessment of soluble urokinase-type plasminogen activator receptor in glomerular disease.

PubMed

Spinale, Joann M; Mariani, Laura H; Kapoor, Shiv; Zhang, Jidong; Weyant, Robert; Song, Peter X; Wong, Hetty N; Troost, Jonathan P; Gadegbeku, Crystal A; Gipson, Debbie S; Kretzler, Matthias; Nihalani, Deepak; Holzman, Lawrence B

2015-03-01

It has been suggested that soluble urokinase receptor (suPAR) is a causative circulating factor for and a biomarker of focal and segmental glomerulosclerosis (FSGS). Here we undertook validation of these assumptions in both mouse and human models. Injection of recombinant suPAR in wild-type mice did not induce proteinuria within 24 h. Moreover, a disease phenotype was not seen in an inducible transgenic mouse model that maintained elevated suPAR concentrations for 6 weeks. Plasma and urine suPAR concentrations were evaluated as clinical biomarkers in 241 patients with glomerular disease from the prospective, longitudinal multicenter observational NEPTUNE cohort. The serum suPAR concentration at baseline inversely correlated with estimated glomerular filtration rate (eGFR) and the urine suPAR/creatinine ratio positively correlated with the urine protein/creatinine ratio. After adjusting for eGFR and urine protein, neither the serum nor urine suPAR level was an independent predictor of FSGS histopathology. A multivariable mixed-effects model of longitudinal data evaluated the association between the change in serum suPAR concentration from baseline with eGFR. After adjusting for baseline suPAR concentration, age, gender, proteinuria, and time, the change in suPAR from baseline was associated with eGFR, but this association was not different for patients with FSGS as compared with other diagnoses. Thus these results do not support a pathological role for suPAR in FSGS.

Risk factors for requirement of filtration surgery after vitrectomy in patients with proliferative diabetic retinopathy.

PubMed

Sakamoto, Masashi; Hashimoto, Ryuya; Yoshida, Izumi; Maeno, Takatoshi

2018-01-01

We retrospectively reviewed patients with postoperative neovascular glaucoma (NVG) after vitrectomy for proliferative diabetic retinopathy to investigate how variables assessed before, during, and after vitrectomy are associated with the requirement for filtration surgery. The subjects in this retrospective, observational, comparative study were 55 consecutive patients (61 eyes) who underwent vitrectomy for proliferative diabetic retinopathy at Toho University Sakura Medical Center between December 2011 and November 2016, were followed up for at least 6 months after surgery, and developed NVG within 2 years after surgery. They comprised 44 men and 11 women of mean age 52.4±9.1 years, who were followed up for a mean 7.1±6.1 months. We collected data on the following 16 variables: sex, age, history of panretinal photocoagulation completed within 3 months before vitrectomy, presence/absence of a lens, obvious iris/angle neovascularization, tractional retinal detachment, diabetic macular edema, vitreous hemorrhage, visual acuity and intraocular pressure before vitrectomy and at the onset of NVG, glycated hemoglobin, fasting blood glucose, estimated glomerular filtration rate, and use of intraoperative gas tamponade. Logistic regression analysis with the backward elimination method identified preoperative fasting hyperglycemia ( P =0.08), high intraocular pressure at the onset of NVG ( P =0.04), and use of gas tamponade during vitrectomy ( P =0.008) to be significant risk factors for requirement of filtration surgery. Preoperative fasting hyperglycemia, high intraocular pressure at the onset of NVG, and use of gas tamponade during vitrectomy predispose patients to require filtration surgery in the event of postoperative NVG.

Acute Kidney Injury Predicts Major Adverse Outcomes in Diabetes: Synergic Impact With Low Glomerular Filtration Rate and Albuminuria.

PubMed

Monseu, Mathilde; Gand, Elise; Saulnier, Pierre-Jean; Ragot, Stéphanie; Piguel, Xavier; Zaoui, Philippe; Rigalleau, Vincent; Marechaud, Richard; Roussel, Ronan; Hadjadj, Samy; Halimi, Jean-Michel

2015-12-01

Subjects with diabetes are prone to the development of cardiovascular and noncardiovascular complications. In separate studies, acute kidney injury (AKI), albuminuria, and low estimated glomerular filtration rate (eGFR) were shown to predict adverse outcomes, but, when considered together, their respective prognostic value is unknown. Patients with type 2 diabetes consecutively recruited in the SURDIAGENE cohort were prospectively followed up for major diabetes-related events, as adjudicated by an independent committee: death (with cause), major cardiovascular events (myocardial infarction, stroke, congestive heart failure, amputation, and arterial revascularization), and renal failure (i.e., sustained doubling of serum creatinine level or end-stage renal disease). Intrahospital AKI occurred in 411 of 1,371 patients during the median follow-up period of 69 months. In multivariate analyses, AKI was significantly associated with cardiovascular and noncardiovascular death, including cancer-related death. In multivariate analyses, AKI was a powerful predictor of major adverse cardiovascular events, heart failure requiring hospitalization, myocardial infarction, stroke, lower-limb amputation or revascularization, and carotid artery revascularization. AKI, eGFR, and albuminuria, even when simultaneously considered in multivariate models, predicted all-cause and cardiovascular deaths. All three renal biomarkers were also prognostic of most adverse outcomes and of the risk of renal failure. AKI, low eGFR, and elevated albuminuria, separately or together, are compelling biomarkers of major adverse outcomes and death in diabetes. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Range of therapeutic metformin concentrations in clinical blood samples and comparison to a forensic case with death due to lactic acidosis.

PubMed

Hess, C; Unger, M; Madea, B; Stratmann, B; Tschoepe, D

2018-05-01

Due to a lack of reference values for blood concentration of metformin in the literature, the forensic evaluation of metformin findings in blood samples is difficult. Interpretations with regard to the assessment of blood concentrations as well as an estimation of the ingested metformin amounts are often vague. Furthermore, post mortem evaluation of death due to lactic acidosis because of metformin is difficult since renal performance or lactate concentrations can not always reliably be determined after death. To describe a concentration range in clinical samples after chronic use of metformin, metformin serum concentrations were determined in serum samples of 95 diabetic patients receiving daily doses of 500mg-3000mg of metformin. The analyses of metformin was carried out using a validated high performance liquid chromatograph coupled to triple quadrupole mass spectrometry (LC-QQQ-MS). On average, metformin concentrations were 1846ng/mL (

Improving the prognosis of patients with severely decreased glomerular filtration rate (CKD G4+): conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

PubMed

Eckardt, Kai-Uwe; Bansal, Nisha; Coresh, Josef; Evans, Marie; Grams, Morgan E; Herzog, Charles A; James, Matthew T; Heerspink, Hiddo J L; Pollock, Carol A; Stevens, Paul E; Tamura, Manjula Kurella; Tonelli, Marcello A; Wheeler, David C; Winkelmayer, Wolfgang C; Cheung, Michael; Hemmelgarn, Brenda R

2018-06-01

Patients with severely decreased glomerular filtration rate (GFR) (i.e., chronic kidney disease [CKD] G4+) are at increased risk for kidney failure, cardiovascular disease (CVD) events (including heart failure), and death. However, little is known about the variability of outcomes and optimal therapeutic strategies, including initiation of kidney replacement therapy (KRT). Kidney Disease: Improving Global Outcomes (KDIGO) organized a Controversies Conference with an international expert group in December 2016 to address this gap in knowledge. In collaboration with the CKD Prognosis Consortium (CKD-PC) a global meta-analysis of cohort studies (n = 264,515 individuals with CKD G4+) was conducted to better understand the timing of clinical outcomes in patients with CKD G4+ and risk factors for different outcomes. The results confirmed the prognostic value of traditional CVD risk factors in individuals with severely decreased GFR, although the risk estimates vary for kidney and CVD outcomes. A 2- and 4-year model of the probability and timing of kidney failure requiring KRT was also developed. The implications of these findings for patient management were discussed in the context of published evidence under 4 key themes: management of CKD G4+, diagnostic and therapeutic challenges of heart failure, shared decision-making, and optimization of clinical trials in CKD G4+ patients. Participants concluded that variable prognosis of patients with advanced CKD mandates individualized, risk-based management, factoring in competing risks and patient preferences. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Evaluation of Serological Indicators and Glomerular Filtration Rate Equations in Chinese Cancer Patients

PubMed Central

Tong, Yingna; Liu, Xiaobin; Guan, Mingxiu; Wang, Meng; Zhang, Lufang; Dong, Dong; Niu, Ruifang; Zhang, Fei; Zhou, Yunli

2017-01-01

Background The performance of estimated glomerular filtration rate (eGFR) have been proved to vary according to the races of the target population. The eGFR equations have not been validated in the Chinese cancer population received chemotherapy. Meanwhile, serum cystatin C (CysC), urea, β2 microglobulin (β2-MG), and creatinine (SCr) were also evaluated in a cohort of Chinese cancer patients. Material/Methods A total of 1000 cancer patients undergoing combination chemotherapy and 108 healthy volunteers were included in this study, and their renal function parameters were evaluated. The eGFR values were compared with reference GFR (rGFR) according to correlation, consistency, precision, and accuracy. Receiver operating characteristic (ROC) curves were used to evaluate the discriminating ability of the GFR equations and serological indicators of renal function. Results (1) The equations contained CysC had the same varying tendency as rGFR in relation to the chemotherapeutic cycle. (2) eGFRscr+cysc and eGFRChinese scr+cysc worked better than the other equations, as indicated by a stronger correlation, less bias, improved precision, higher accuracy, and greater AUC. (3) CysC was more sensitive than the other serological indicators for identifying early renal injury. (4) Each parameter showed different characteristics in subgroups of Chinese cancer patients. Conclusions CysC was the most sensitive marker for early renal injury. Among the 8 most commonly used eGFR equations, the combination equation eGFRscr+cysc and eGFRChinese scr+cysc exhibited the best performance in the assessment of the renal function of Chinese cancer patients. PMID:28623247

Value of Nephrometry Score Constituents on Perioperative Outcomes and Split Renal Function in Patients Undergoing Minimally Invasive Partial Nephrectomy.

PubMed

Watts, Kara L; Ghosh, Propa; Stein, Solomon; Ghavamian, Reza

2017-01-01

To assess the relationship between individual nephrometry score (NS) constituents (RENAL) on perioperative outcomes and renal function of the surgical kidney in patients undergoing laparoscopic partial nephrectomy or robotic-assisted partial nephrectomy. Two hundred forty-five patients who underwent laparoscopic partial nephrectomy or robotic-assisted partial nephrectomy between 2005 and 2014 were retrospectively reviewed. Each renal mass' NS was calculated from preoperative computed tomography imaging. Multivariate regression analysis was used to evaluate the effect of NS variables on perioperative outcomes and change in overall renal function (as estimated by glomerular filtration rate) from preoperative to 1-year postoperative. A cohort analysis assessed the effect of NS variables on change in split renal function of the surgical kidney from pre- to postoperative based on nuclear medicine renal scintigraphy. Tumor radius (R), endophytic nature (E), and nearness to collecting system (N) variables significantly and incrementally predicted a longer operative time and warm ischemia time. Overall renal function based on glomerular filtration rate was not affected by any NS variable. However, percent function of the surgical kidney by renal scintigraphy significantly decreased postoperatively as R and E values increased. R, E, and N were associated with significant changes in warm ischemia time and operative time. R and E were associated with a significant decrease in split renal function of the surgical kidney at 1 year after surgery but not with overall renal function. R, E, and N are the NS constituents most relevant to perioperative outcomes and postoperative differential renal function after partial nephrectomy. Copyright © 2016. Published by Elsevier Inc.

Radiofrequency ablation of renal cell carcinoma: a follow up of outcomes.

PubMed

Curry, David; Yassin, Musaab; Thwaini, Ali; Pahuja, Ajay; Alanbuki, Ammar H; Rajan, Thiagarajan Nambi; Loan, Willie

2014-02-01

To present the oncological outcomes in a series of patients with cT1a renal cell carcinoma (RCC) treated with radiofrequency ablation (RFA) and its effect on the glomerular filtration rate (GFR). Forty-five patients (48 renal units) treated at the Belfast City Hospital, over 4 years. Average age is 61.5 years (range 41-80). Eighteen patients (22 renal units) were included with American Society of Anesthesiologists (ASA) II and III. The rest were ASA I. Average tumor size was 2.63 cm (range 1.2 cm-6 cm). Renal function before and after RFA was recorded by means of the estimated glomerular filtration rate (eGFR) and the changes are presented. Oncological outcomes were established from follow up imaging. A satisfactory response was defined by disappearance or a persistence of non-enhancing lesion of smaller size at follow up. A partial response was defined by a persistent but non-enhancing similar size lesion. A failed response was defined by enlarging or persistently enhancing lesions. Mean follow up was 30.6 months (4-60 months). A good response was found in 33 (74%) patients. A partial response was found in 3 (8%) patients and failed response was identified in 8 (18%) patients. The average reduction in eGFR was 11 mL/min. Two patients had a 50% reduction in their eGFR. No patient required dialysis following treatment. RFA presents safe treatment choice for patients with RCC, particularly those that are high risk surgical candidates and those who refuse surgery. Short term results suggest good oncological outcomes and preservation of renal function.

Safety of Iohexol Administration to Measure Glomerular Filtration Rate in Different Patient Populations: A 25-Year Experience.

PubMed

Gaspari, Flavio; Thakar, Surabhi; Carrara, Fabiola; Perna, Annalisa; Trillini, Matias; Aparicio, Maria Carolina; Diadei, Olimpia; Ferrari, Silvia; Cannata, Antonio; Stucchi, Nadia; Ruggenenti, Piero; Remuzzi, Giuseppe; Perico, Norberto

2018-05-17

In clinical research setting, accurate and precise measurement of glomerular filtration rate (GFR) is essential to overcome the limitations of GFR estimation with equations, which are often unreliable. In recent decades, a method for measuring GFR by plasma clearance of iohexol, a non-ionic radiocontrast agent, was developed. To evaluate the safety of the procedure, we aimed to review all immediate adverse reactions that could be related to iohexol administration in our group's 25 years worth of experience. We retrospectively reviewed all GFR investigations in 2,891 patients, between 1992 and 2016, as part of 37 clinical trials coordinated by our group. Subjects with disparate renal diseases, kidney transplant recipients, and living donors - all with different renal function categories - were included in the surveyed clinical trials. During 15,147 GFR measurements, only one treatment-related event of moderate intensity was identified. Flushing, urticaria, and itching were observed in a diabetic patient a few minutes after iohexol administration during the first GFR measurement. The event recovered without sequelae after intravenous injection of methylprednisolone sodium succinate. The patient was not hospitalized and the event was categorized as non-serious. Eight additional non-serious events observed closely following iohexol injection were considered as not related to treatment. Thus, independent of disease conditions and GFR categories, the overall rate of treatment-related events was 0.0066%. Iohexol administration for GFR measurement is a safe procedure, even in repeated investigations in the same subject, that should be adopted in clinical research and, when needed, also in clinical practice. © 2018 S. Karger AG, Basel.

Alteration of renal excretion pathways in gentamicin-induced renal injury in rats.

PubMed

Ma, Yan-Rong; Luo, Xuan; Wu, Yan-Fang; Zhang, Tiffany; Zhang, Fan; Zhang, Guo-Qiang; Wu, Xin-An

2018-07-01

The kidney plays a major part in the elimination of many drugs and their metabolites, and drug-induced kidney injury commonly alters either glomerular filtration or tubular transport, or both. However, the renal excretion pathway of drugs has not been fully elucidated at different stages of renal injury. This study aimed to evaluate the alteration of renal excretion pathways in gentamicin (GEN)-induced renal injury in rats. Results showed that serum cystatin C, creatinine and urea nitrogen levels were greatly increased by the exposure of GEN (100 mg kg -1 ), and creatinine concentration was increased by 39.7% by GEN (50 mg kg -1 ). GEN dose-dependently upregulated the protein expression of rOCT1, downregulated rOCT2 and rOAT1, but not affected rOAT2. Efflux transporters, rMRP2, rMRP4 and rBCRP expressions were significantly increased by GEN(100), and the rMATE1 level was markedly increased by GEN(50) but decreased by GEN(100). GEN(50) did not alter the urinary excretion of inulin, but increased metformin and furosemide excretion. However, GEN(100) resulted in a significant decrease of the urinary excretion of inulin, metformin and p-aminohippurate. In addition, urinary metformin excretions in vivo were significantly decreased by GEN(100), but slightly increased by GEN(50). These results suggested that GEN(50) resulted in the induction of rOCTs-rMATE1 and rOAT3-rMRPs pathway, but not changed the glomerular filtration rate, and GEN(100)-induced acute kidney injury caused the downregulated function of glomerular filtration -rOCTs-rMATE1 and -rOAT1-rMRPs pathway. Copyright © 2018 John Wiley & Sons, Ltd.

Nephrogenous Cyclic Adenosine Monophosphate as a Parathyroid Function Test

PubMed Central

Broadus, Arthur E.; Mahaffey, Jane E.; Bartter, Frederic C.; Neer, Robert M.

1977-01-01

Nephrogenous cyclic AMP (NcAMP), total cyclic AMP excretion (UcAMP), and plasma immunoreactive parathyroid hormone (iPTH), determined with a multivalent antiserum, were prospectively measured in 55 control subjects, 57 patients with primary hyperparathyroidism (1°HPT), and 10 patients with chronic hypoparathyroidism. In the group with 1° HPT, NcAMP was elevated in 52 patients (91%), and similar elevations were noted in subgroups of 26 patients with mild (serum calcium ≤10.7 mg/dl) or intermittent hypercalcemia, 19 patients with mild renal insufficiency (mean glomerular filtration rate, 64 ml/min), and 10 patients with moderate renal insufficiency (mean glomerular filtration rate, 43 ml/min). Plasma iPTH was increased in 41 patients (73%). The development of a parametric expression for UcAMP was found to be critically important in the clinical interpretation of results for total cAMP excretion. Because of renal impairment in a large number of patients, the absolute excretion rate of cAMP correlated poorly with the hyperparathyroid state. Expressed as a function of creatinine excretion, UcAMP was elevated in 81% of patients with 1° HPT, but the nonparametric nature of the expression led to a number of interpretive difficulties. The expression of cAMP excretion as a function of glomerular filtration rate was developed on the basis of the unique features of cAMP clearance in man, and this expression, which provided elevated values in 51 (89%) of the patients with 1° HPT, avoided entirely the inadequacies of alternative expressions. Results for NcAMP and UcAMP in nonazotemic and azotemic patients with hypoparathyroidism confirmed the validity of the measurements and the expressions employed. PMID:197123

Micropuncture studies of the recovery phase of myohemoglobinuric acute renal failure in the rat

PubMed Central

Oken, Donald E.; DiBona, Gerald F.; McDonald, Franklin D.

1970-01-01

Micropuncture studies of the recovery phase of glycerol-induced myohemoglobinuric acute renal failure were performed in rats whose blood urea nitrogen (BUN) had fallen at least 20% below its peak value. The glomerular filtration rate (GFR) of individual nephrons in a single kidney in the recovery period generally either was in the normal range or minimal. Each animal's BUN concentration at the time of the study was inversely related to the proportion of functioning surface nephrons, but did not correlate with individual nephron GFR values. Proximal tubule fractional water absorption was significantly depressed as manifested by both depressed inulin (TF/P) values and supernormal volumes of collections, a finding which, in the absence of a urea-induced osmotic diuresis, suggests impaired sodium transport by the damaged nephron. The mean proximal tubule hydrostatic pressure in recovery was normal and there was little variation in pressure among functioning nephrons. It is concluded that recovery from this model of acute renal failure reflects the progressive recruitment of increasing numbers of functioning nephrons. The recovery of individual nephron glomerular filtration, once begun, was rapid and complete. No evidence could be adduced that the gradual return of renal function towards normal reflects a slow release of tubular obstruction or repair of disrupted tubular epithelium. Rather, recovery appeared to be directly attributable to the return of an adequate effective glomerular filtration pressure. Significant limitation in proximal tubule water absorption persisted after individual nephron GFR had returned to normal or supernormal values in this model of experimental acute renal failure in the rat, a finding which readily accounts for the diuresis associated with the recovery phase of this syndrome. PMID:5443173

Glomerular filtration barrier in pediatric idiopathic nephrotic syndrome.

PubMed

Sharma, Alok; Gupta, Ruchika; Bagga, Arvind; Dinda, Amit K

2013-03-01

Nephrotic syndrome (NS) is a common proteinuric disorder with defect in the perm-selectivity of the glomerular filtration barrier (GFB). Ultrastructural morphometric evaluation of the GFB in pediatric NS has been attempted in only a few studies. This study was aimed at qualitative and quantitative evaluation of the alterations involving the GFB in pediatric idiopathic NS with an attempt to correlate these alterations with the clinico-laboratory data. For this study, renal biopsies from nine patients with NS and two children with interstitial nephritis were included. Relevant clinical and laboratory data, including degree of 24-h proteinuria and renal function tests, were recorded. Renal biopsies were reviewed for morphologic and electron microscopic diagnosis. Ultrastructural morphometry of the GFB was performed using image analysis software. The age at onset of NS, duration of illness, presence of hypertension, and renal function tests were comparable between the group of patients with minimal change disease (MCD) and those with mesangioproliferative glomerulonephritis (mesPGN)/focal segmental glomerulosclerosis (FSGS). However, the latter group showed higher 24-h proteinuria compared with the group with MCD. Among the detected ultra-structural changes, glomerular basement membrane thickness and foot process width were significantly different between the MCD and the mesPGN/FSGS groups. The slit pore diameter in the glomeruli showed a positive correlation with the degree of proteinuria. We conclude that our study demonstrated remarkable differences in certain parameters and the glomerular ultrastructural alterations in the various categories of NS. These differences might underlie the observed variation in response of these entities to various therapies.

Probability of reduced renal function after contrast-enhanced CT: a model based on serum creatinine level, patient age, and estimated glomerular filtration rate.

PubMed

Herts, Brian R; Schneider, Erika; Obuchowski, Nancy; Poggio, Emilio; Jain, Anil; Baker, Mark E

2009-08-01

The objectives of our study were to develop a model to predict the probability of reduced renal function after outpatient contrast-enhanced CT (CECT)--based on patient age, sex, and race and on serum creatinine level before CT or directly based on estimated glomerular filtration rate (GFR) before CT--and to determine the relationship between patients with changes in creatinine level that characterize contrast-induced nephropathy and patients with reduced GFR after CECT. Of 5,187 outpatients who underwent CECT, 963 (18.6%) had serum creatinine levels obtained within 6 months before and 4 days after CECT. The estimated GFR was calculated before and after CT using the four-variable Modification of Diet in Renal Disease (MDRD) Study equation. Pre-CT serum creatinine level, age, race, sex, and pre-CT estimated GFR were tested using multiple-variable logistic regression models to determine the probability of having an estimated GFR of < 60 and < 45 mL/min/1.73 m(2) after CECT. Two thirds of the patients were used to create and one third to test the models. We also determined discordance between patients who met standard definitions of contrast-induced nephropathy and those with a reduced estimated GFR after CECT. Significant (p < 0.002) predictors for a post-CT estimated GFR of < 60 mL/min/1.73 m(2) were age, race, sex, pre-CT serum creatinine level, and pre-CT estimated GFR. Sex, serum creatinine level, and pre-CT estimated GFR were significant factors (p < 0.001) for predicting a post-CT estimated GFR of < 45 mL/min/1.73 m(2). The probability is [exp(y) / (1 + exp(y))], where y = 6.21 - (0.10 x pre-CT estimated GFR) for an estimated GFR of < 60 mL/min/1.73 m(2), and y = 3.66 - (0.087 x pre-CT estimated GFR) for an estimated GFR of < 45 mL/min/1.73 m(2). A discrepancy between those who met contrast-induced nephropathy criteria by creatinine changes and those with a post-CT estimated GFR of < 60 mL/min/1.73 m(2) was detected in 208 of the 963 patients (21.6%). The probability of a reduced estimated GFR after CECT can be predicted by the pre-CT estimated GFR using the four-variable MDRD equation. Furthermore, standard criteria for contrast-induced nephropathy are poor predictors of poor renal function after CECT. Criteria need to be established for what is an acceptable risk to manage patients undergoing CECT.

Enhanced renal prostaglandin production in the dog. I. Effects on renal function.

PubMed

Tannenbaum, J; Splawinski, J A; Oates, J A; Nies, A S

1975-01-01

The changes in renal function produced by endogenous synthesis of prostaglandins by the kidney were evaluated by infusing sodium arachidonate, the prescursor of the prostaglandins, into one renal artery of the dog. These changes were compared with those produced by similar infusions on performed prostaglandin (PG) E2 and F2alpha.PGE2given at 0.01-0.3 mug/kg min--1 produced dose-related increases in urine flow, sodium and potassium excretion, free water clearance, and renal blood flow. The glomerular filtration rage increased only at the lowest dose and the calculated filtration fraction fell. Arachidonic acid at 1.0-30.0 mug/kg min--1 similarly produced dose-related increases in electrolyte excretion, but the increase in renal blood flow was much less than that produced by PGE2 and there were no changes in glomerular filtration rate, filtration fraction, or free water clearances. PGF2alpha had essentially no effects at infusion rates of 0.03-1.0 mug/kg min--1. All renal effects of arachidonic acid were inhibited by simultaneous infusions of an inhibitor of prostaglandin synthetase, 5, 8, 11,14-eicosatetraynoic acid (20:4). None of the effects produced by PGE2 were inhibited by 20:4. These results indicate that enhanced endogenous renal prostaglandin synthesis, which can be produced by arachidonate infusion, results in significant alterations of renal function. This finding strengthens the hypothesis that renal prostaglandins formed in vivo have physiological importance as regulators of renal function.

Kidney Response to the Spectrum of Diet-Induced Acid Stress

PubMed Central

Goraya, Nimrit; Wesson, Donald E.

2018-01-01

Chronic ingestion of the acid (H+)-producing diets that are typical of developed societies appears to pose a long-term threat to kidney health. Mechanisms employed by kidneys to excrete this high dietary H+ load appear to cause long-term kidney injury when deployed over many years. In addition, cumulative urine H+ excretion is less than the cumulative increment in dietary H+, consistent with H+ retention. This H+ retention associated with the described high dietary H+ worsens as the glomerular filtration rate (GFR) declines which further exacerbates kidney injury. Modest H+ retention does not measurably change plasma acid–base parameters but, nevertheless, causes kidney injury and might contribute to progressive nephropathy. Current clinical methods do not detect H+ retention in its early stages but the condition manifests as metabolic acidosis as it worsens, with progressive decline of the glomerular filtration rate. We discuss this spectrum of H+ injury, which we characterize as “H+ stress”, and the emerging evidence that high dietary H+ constitutes a threat to long-term kidney health. PMID:29751620

Triiodothyronine and thyroxine in urine. II. Renal handling, and effect of urinary protein.

PubMed

Burke, C W; Shakespear, R A

1976-03-01

Mean urinary clearances of T3 were 164 ml/min in normal subjects, 177 in pregnancy, 221 in thyrotoxicosis, 174 in hypothyroidism, and 194 in 3 persons with undetectable T4 but normal T3 levels. T4 clearances were 38 ml/min in normal subjects, 48 in thyrotoxicosis, and 138 in hypothyroidism. Low creatinine clearance was associated with low clearances of T4 and T3. The data suggest urinary excretion of T3 by glomerular filtration of serum unbound T3 with added tubular excretion; and T4 excretion by glomerular filtration of unbound T4 and tubular reabsorption. However, 3-9% of urinary T3 and 5-12% of urinary T4 were bound to urinary proteins, and increased protein excretion caused markedly increased T4 excretion. In addition, 52% of urinary T3 and 68% of urinary T4 were bound to other substances of approximate mol wt 500-2,000, which may influence tubular handling of T3 or T4.

Neural control of renal tubular sodium reabsorption of the dog.

PubMed

DiBona, G F

1978-04-01

The evidence supporting a role for direct neurogenic control of renal tubular sodium reabsorption is reviewed. Electron microscopic and fluorescence histochemical studies demonstrate adrenergic nerve terminals in direct contact with basement membranes of mammalian renal tubular epithelial cells. Low level direct or baroreceptor reflex stimulation of renal sympathetic nerves produces an increase in renal tubular sodium reabsorption without alterations in glomerular filtration rate, renal blood flow, or intrarenal distribution of blood flow. The antinatriuresis is prevented by prior treatment of the kidney with guanethidine or phenoxybenzamine. Possible indirect mediation of the antinatriuresis by other humoral agents known to be released from the kidney upon renal nerve stimulation (angiotensin II, prostaglandin) was excluded by experiments with appropriate blocking agents. Reflex diminutions in renal nerve activity (left atrial distention, stellate ganglion stimulation) produce a decrease in renal tubular sodium reabsorption independent of glomerular filtration rate or renal blood flow. The anatomically described adrenergic innervation of the renal tubules participates in the direct regulation of renal tubular sodium reabsorption.

Human pharmacokinetics of iohexol. A new nonionic contrast medium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Olsson, B.; Aulie, A.; Sveen, K.

1983-03-01

The pharmacokinetics of iohexol, a new nonionic, water-soluble contrast medium, have been determined after intravenous injection in 20 healthy volunteers, at four different dose levels (125-500 mg I/kg). The apparent volume of distribution was 0.27 1/kg, indicating distribution in the extracellular water. The biologic half-life was 121 minutes, comparable with that of other intravascular contrast media. Iohexol was excreted completely unmetabolized in the urine, with a 100% recovery 24 hours after injection. A comparison of iohexol and chromium-51 (/sup 51/Cr)-EDTA clearances indicates that iohexol is mainly excreted by glomerular filtration. The /sup 51/Cr-EDTA clearance was the same when injected separatelymore » and concomitantly with iohexol, indicating that glomerular filtration rate is not affected by iohexol. No dose dependency was observed in the investigated parameters t1/2 alpha, t1/2 beta, Vd, ClT or ClR. Iohexol pharmacokinetics are in correspondence with previously reported data on intravascular contrast media.« less

Sitagliptin reduces the urine albumin-to-creatinine ratio in type 2 diabetes through decreasing both blood pressure and estimated glomerular filtration rate.

PubMed

Kawasaki, Isao; Hiura, Yoshikazu; Tamai, Anna; Yoshida, Yoko; Yakusiji, Yosuke; Ikuno, Yoshiko; Okada, Megumi; Ueno, Hiroki; Tanaka, Nagaaki; Yamagami, Keiko; Fukumoto, Mariko; Hosoi, Masayuki

2015-01-01

We investigated the change in the urine albumin-to-creatinine ratio (ACR) to examine the effect of sitagliptin on diabetic nephropathy. Sitagliptin at a dose of 50 mg was administered to 247 outpatients with type 2 diabetes. Data were collected on the patients' laboratory results (including the ACR), blood pressure, and body weight. Clinical data were compared before and after 3 months' administration of sitagliptin. The ACR changed from 150.0 ± 538.6 mg/gCre to 148.3 ± 764.6 mg/gCre over 3 months. In the patients with micro- and macro-albuminuria, the ACR after 3 months significantly decreased compared with the baseline (P = 0.04 and P = 0.02, respectively). The subjects whose ACR decreased experienced significantly larger decreases over the 3-month period in blood pressure and estimated glomerular filtration rate (eGFR) than the other subjects. There was no significant correlation between change in ACR (ΔACR) and change in hemoglobin A1c (ΔHbA1c) during 3 months (r = 0.04, P = 0.59), but there was a significant correlation between change in ΔACR and change in systolic blood pressure (r = 0.16, P = 0.03). Multiple regression analysis revealed that the significant predictors for ΔACR were change in systolic blood pressure (β = 0.21, P = 0.016) and change in eGFR (β = 0.20, P = 0.024) over 3 months (r = 0.35, P = 0.04). Sitagliptin reduces the ACR through decreasing both blood pressure and eGFR, with no correlation with a decrease in HbA1c over a 3-month period. These results may reflect the direct action of sitagliptin on the kidneys. © 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Nutritional status and body composition in patients early after renal transplantation.

PubMed

Netto, M C A S; Alves-Filho, G; Mazzali, M

2012-10-01

After renal transplantation recovery in nutritional status occurs during the first year. We assessed the changes in nutritional status after transplantation in 145 transplant recipients (94 males, 51 females). Patients were evaluated immediately after renal transplant (baseline data) and at 6 months' follow-up. Analysis included body mass index (BMI), body composition (skin fold and arm circumference), and estimated body composition (calculated percent of fat, arm circumference, arm muscle circumference, and arm muscle area). Other data obtained from medical records included renal function (MDRD) serum albumin and lipid profile. At baseline evaluation (21 ± 15 days posttransplant), mean BMI was 23.9 ± 3.9 kg/m(2), serum albumin was 3.7 ± 0.7 g/dL, and lipid profile showed (cholesterol 158.5 ± 52.7 mg% and triglycerides 135.9 ± 91.8 mg%. Body composition analysis showed better adaptation of muscle mass in females [AC (91 ± 10.2 × 98 ± 14.6; male × female, P < .05) arm muscle circumference (92.6 ± 1.4 × 102.3% ± 2.9%, male × female, P < .05) and arm muscle area (87.1 ± 22.3 × 105.5% ± 25.9%, male × female, P < .05)]. Body fat was above the recommended levels in 80% of patients, especially females. After 6 months we divided the groups according to BMI, observing better renal function in the normal weight group compared with obese subjects (60 ± 17.2 × 39.5 ± 19.8 mL/min MDRD, P < .05), despite comparable estimated glomerular filtration rate at baseline. The nutritional assessment of patients with end-stage renal disease early after renal transplantation, showed inadequate body composition, with increased fat and reduced lean body mass. The lower glomerular filtration rate after 6 months may be attributed to relatively inadequate renal mass or to obesity-induced hyperfiltration. Copyright © 2012 Elsevier Inc. All rights reserved.

Clinical benefits of using inulin clearance and cystatin C for determining glomerular filtration rate in HIV-1-infected individuals treated with dolutegravir.

PubMed

Yukawa, Satomi; Watanabe, Dai; Uehira, Tomoko; Shirasaka, Takuma

2018-03-01

Dolutegravir may inhibit creatinine transporters in renal tubules and elevate serum creatinine levels. We investigated the usefulness of glomerular filtration rate (GFR) measured using inulin clearance (Cin), creatinine clearance (Ccr), and estimated GFR based on both serum creatinine (eGFRcre) and serum cystatin C (eGFRcys). HIV-1-infected Japanese patients with suppressed viremia and whose antiretroviral drug was switched to dolutegravir from other drugs were included (n = 108, Study 1). We compared eGFRcre and eGFRcys at the start and after 48 weeks of dolutegravir administration. For the patients providing consent, we measured Cin and Ccr (n = 15, Study 2). We assessed biases and accuracy and compared Cin with eGFRcre, eGFRcys, and Ccr. There were no differences in serum cystatin C and eGFRcys between baseline and at 48 weeks. Moreover, eGFRcre was significantly less accurate (within 30% of measured GFR) than both eGFRcys and Ccr (40% accuracy compared to 93% and 93%, respectively). eGFRcys was significantly less biased than eGFRcre and Ccr (p < 0.0001, p = 0.00036, respectively). No significant difference between Cin and eGFRcys was observed. eGFRcys was significantly correlated with Cin (γ = 0.85, p < 0.0001). eGFRcys provided the most precise estimate and most closely approximate Cin in HIV-1-infected Japanese patients with suppressed viremia treated with dolutegravir. We demonstrated clinical benefits of inulin clearance and eGFRcys. This is the first study performing inulin clearance for HIV-1-infected individuals and to show data for eGFRcys from a large cohort following a switch to dolutegravir from other antiretroviral agents. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Impact of uric acid levels on the risk of long-term cardiovascular mortality in patients with type 2 diabetes mellitus.

PubMed

Ilundain-González, Ana Isabel; Gimeno-Orna, José Antonio; Sáenz-Abad, Daniel; Pons-Dolset, Jordi; Cebollada-Del Hoyo, Jesús; Lahoza-Pérez, María Del Carmen

Hyperuricemia is associated to cardiovascular disease. However, the contribution of uric acid (UA) to cardiovascular mortality in diabetic patients is controversial. To assess the impact of UA levels on the risk of cardiovascular mortality risk in a cohort of patients with type 2 diabetes mellitus (T2DM). A prospective cohort study on outpatients with T2DM. The clinical endpoint was cardiovascular death. Anthropometric, demographic, clinical, and biochemical variables were collected, including UA levels, urinary albumin excretion and estimated glomerular filtration rate. The independent contribution of UA levels to cardiovascular mortality was assessed using multivariate Cox regression models, progressively adjusted for potential confounders. A total of 452 patients with a mean age of 65.9 (SD 9.5) years were enrolled. Mean UA level was 4.2mg/dL. Quartiles of UA levels were Q1 < 3.3; Q2: 3.3-4.2; Q3: 4.3-5.1; Q4 > 5.1mg/dL. UA levels significantly correlated with estimated glomerular filtration rate (Rho=-0.227; p<0.001). During a median follow-up time of 13 years, cardiovascular mortality rates were higher in Q4 of the UA distribution (Q1: 10.7; Q2: 11.7; Q3: 10.7; Q4: 21.6 per 1000 patient-years; p = 0.027). UA was a predictor of cardiovascular mortality in the univariate analysis (HR1mg/dL = 1.30; p=0.002), but not in a multivariate analysis adjusted for urinary albumin excretion and eGFR (HR1mg/dL=1.20; p=0.12). High UA levels are associated to cardiovascular mortality in patients with T2DM. However, the role of UA may be mediated by impaired kidney function in patients with hyperuricemia. Copyright © 2018 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

Estimation of glomerular filtration rate in cancer patients with abnormal body composition and relation with carboplatin toxicity.

PubMed

Bretagne, M; Jouinot, A; Durand, J P; Huillard, O; Boudou Rouquette, P; Tlemsani, C; Arrondeau, J; Sarfati, G; Goldwasser, F; Alexandre, J

2017-07-01

Carboplatin clearance is correlated with glomerular filtration rate (GFR) and usually estimated with creatinine clearance using Cockcroft-Gault (CG) formula. Because plasma creatinine level is highly correlated with muscle mass, we hypothesized that an abnormal body composition with a low lean body mass (LBM) percentage [(LBM/weight) × 100] may result in inadequate carboplatin dosing. Serum cystatin C is an alternative marker of GFR, not affected by muscle mass. We aimed to investigate the influence of total LBM and LBM percentage on GFR calculation, using creatinine (CrCl) or cystatin C (GFR cysC-creat ) in cancer patients. Pretreatment serum creatinine and cystatin C were prospectively measured in consecutive patients. CrCl (CG formula), GFR cysC-creat (CKD-EPI creatinine-cystatin equation), and LBM (CT scan) were calculated. Severe thrombocytopenia post-carboplatin were analyzed. In 131 patients without renal insufficiency, LBM was correlated with creatinine (r = 0.30, p < 0.005) but not with cystatin C (r = -0.07, p = 0.43). In patients with the lowest LBM percentage, the CrCl was significantly higher than GFR cysC-creat indicating an overestimation of GFR with creatinine (p = 0.0004). In 24 patients treated with carboplatin AUC 5 (mg/ml min) ± paclitaxel, the risk of severe thrombocytopenia was associated with lower LBM percentage (p = 0.0002) and higher CrCl/GFR cysC-creat ratio (p = 0.006). By ROC analysis, the CrCl/GFR cysC-creat ratio threshold predicting severe thrombocytopenia was 1.23. A low LBM percentage increases the risk of inadequate GFR calculation by CG formula, and carboplatin overdosage with severe thrombocytopenia. High CrCl/GFR cysC-creat ratio allows the identification of these patients.

Cystatin C is Better than Serum Creatinine for Estimating Glomerular Filtration Rate to Detect Osteopenia in Chronic Kidney Disease Patients.

PubMed

Kwon, Young Eun; Lee, Mi Jung; Park, Kyoung Sook; Han, Seung Hyeok; Yoo, Tae Hyun; Oh, Kook Hwan; Lee, Joongyub; Lee, Kyu Beck; Chung, Wookyung; Kim, Yeong Hoon; Ahn, Curie; Choi, Kyu Hun

2017-03-01

Recent studies have reported that loss of bone mass is associated with renal function decline and increased fracture risks in chronic kidney disease (CKD) patients. The aim of this study was to investigate the best estimated glomerular filtration rate (eGFR) equation to detect osteopenia in CKD patients. This was a cross-sectional study, and 780 patients aged 50 years or above were classified into normal bone mass or osteopenia groups according to the -1.0 of T-scores at total hip and femur neck. Comparisons of area under the receiver operating characteristic (ROC) curves (AUC) were performed to investigate significant differences among three eGFR formulas: Modification of Diet in Renal Disease, CKD-Epidemiology Collaboration (EPI) creatinine, and CKD-EPI cystatin C (CKD-EPI-Cys). The mean age was 61 years old and the proportion of females was 37.3%. The total hip osteopenia group showed lower CKD-EPI-Cys eGFR levels (osteopenia group, 33.3±19.0 mL/min/1.73 m²; normal group, 48.1±26.2 mL/min/1.73 m², p<0.001). In multiple logistic regression analysis, CKD-EPI-Cys eGFR was independently associated with osteopenia at the total hip (per 1 mL/min/1.73 m² increase, odds ratio 0.98, 95% confidence interval 0.97-0.99, p=0.004) after adjusting for confounding variables. ROC curve analyses indicated that CKD-EPI-Cys shows the largest AUC for osteopenia at the total hip (AUC=0.678, all p<0.01) and the femur neck (AUC=0.665, all p<0.05). Decreased renal function assessed by CKD-EPI-Cys equation correlates with osteopenia better than creatinine-based methods in CKD patients, and the CKD-EPI-Cys formula might be a useful tool to assess skeletal-related event risks.

Incomplete reversibility of estimated glomerular filtration rate decline following tenofovir disoproxil fumarate exposure.

PubMed

Jose, Sophie; Hamzah, Lisa; Campbell, Lucy J; Hill, Teresa; Fisher, Martin; Leen, Clifford; Gilson, Richard; Walsh, John; Nelson, Mark; Hay, Phillip; Johnson, Margaret; Chadwick, David; Nitsch, Dorothea; Jones, Rachael; Sabin, Caroline A; Post, Frank A

2014-08-01

Tenofovir disoproxil fumarate (TDF) has been linked to renal impairment, but the extent to which this impairment is reversible is unclear. We aimed to investigate the reversibility of renal decline during TDF therapy. Cox proportional hazards models assessed factors associated with discontinuing TDF in those with an exposure duration of >6 months. In those who discontinued TDF therapy, linear piecewise regression models estimated glomerular filtration rate (eGFR) slopes before initiation of, during, and after discontinuation of TDF therapy. Factors associated with not achieving eGFR recovery 6 months after discontinuing TDF were assessed using multivariable logistic regression. We observed declines in the eGFR during TDF exposure (mean slopes, -15.7 mL/minute/1.73 m(2)/year [95% confidence interval {CI}, -20.5 to -10.9] during the first 3 months and -3.1 mL/minute/1.73 m(2)/year [95% CI, -4.6 to -1.7] thereafter) and evidence of eGFR increases following discontinuation of TDF therapy (mean slopes, 12.5 mL/minute/1.73 m(2)/year [95% CI, 8.9-16.1] during the first 3 months and 0.8 mL/minute/1.73 m(2)/year [95% CI, .1-1.5] thereafter). Following TDF discontinuation, 38.6% of patients with a decline in the eGFR did not experience recovery. A higher eGFR at baseline, a lower eGFR after discontinuation of TDF therapy, and more-prolonged exposure to TDF were associated with an increased risk of incomplete recovery 6 months after discontinuation of TDF therapy. This study shows that a decline in the eGFR during TDF therapy was not fully reversible in one third of patients and suggests that prolonged TDF exposure at a low eGFR should be avoided. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Incomplete Reversibility of Estimated Glomerular Filtration Rate Decline Following Tenofovir Disoproxil Fumarate Exposure

PubMed Central

Jose, Sophie; Hamzah, Lisa; Campbell, Lucy J.; Hill, Teresa; Fisher, Martin; Leen, Clifford; Gilson, Richard; Walsh, John; Nelson, Mark; Hay, Phillip; Johnson, Margaret; Chadwick, David; Nitsch, Dorothea; Jones, Rachael; Sabin, Caroline A.; Post, Frank A.; Ainsworth, Jonathan; Anderson, Jane; Babiker, Abdel; Chadwick, David; Delpech, Valerie; Dunn, David; Fisher, Martin; Gazzard, Brian; Gilson, Richard; Gompels, Mark; Hay, Phillip; Hill, Teresa; Johnson, Margaret; Kegg, Stephen; Leen, Clifford; Nelson, Mark; Orkin, Chloe; Palfreeman, Adrian; Phillips, Andrew; Pillay, Deenan; Post, Frank; Sabin, Caroline; Sachikonye, Memory; Schwenk, Achim; Walsh, John; Hill, Teresa; Huntington, Susie; Josie, Sophie; Phillips, Andrew; Sabin, Caroline; Thornton, Alicia; Dunn, David; Glabay, Adam; Orkin, C.; Garrett, N.; Lynch, J.; Hand, J.; de Souza, C.; Fisher, M.; Perry, N.; Tilbury, S.; Churchill, D.; Gazzard, B.; Nelson, M.; Waxman, M.; Asboe, D.; Mandalia, S.; Delpech, V.; Anderson, J.; Munshi, S.; Korat, H.; Poulton, M.; Taylor, C.; Gleisner, Z.; Campbell, L.; Babiker, Abdel; Dunn, David; Glabay, Adam; Gilson, R.; Brima, N.; Williams, I.; Schwenk, A.; Ainsworth, J.; Wood, C.; Miller, S.; Johnson, M.; Youle, M.; Lampe, F.; Smith, C.; Grabowska, H.; Chaloner, C.; Puradiredja, D.; Walsh, J.; Weber, J.; Ramzan, F.; Mackie, N.; Winston, A.; Leen, C.; Wilson, A.; Gompels, M.; Allan, S.; Palfreeman, A.; Moore, A.; Chadwick, D.; Wakeman, K.; Kegg, Stephen; Main, Paul; Mitchell; Hunter; Sachikonye, Memory; Hay, Phillip; Dhillon, Mandip

2014-01-01

Background. Tenofovir disoproxil fumarate (TDF) has been linked to renal impairment, but the extent to which this impairment is reversible is unclear. We aimed to investigate the reversibility of renal decline during TDF therapy. Methods. Cox proportional hazards models assessed factors associated with discontinuing TDF in those with an exposure duration of >6 months. In those who discontinued TDF therapy, linear piecewise regression models estimated glomerular filtration rate (eGFR) slopes before initiation of, during, and after discontinuation of TDF therapy. Factors associated with not achieving eGFR recovery 6 months after discontinuing TDF were assessed using multivariable logistic regression. Results. We observed declines in the eGFR during TDF exposure (mean slopes, −15.7 mL/minute/1.73 m2/year [95% confidence interval {CI}, −20.5 to −10.9] during the first 3 months and −3.1 mL/minute/1.73 m2/year [95% CI, −4.6 to −1.7] thereafter) and evidence of eGFR increases following discontinuation of TDF therapy (mean slopes, 12.5 mL/minute/1.73 m2/year [95% CI, 8.9–16.1] during the first 3 months and 0.8 mL/minute/1.73 m2/year [95% CI, .1–1.5] thereafter). Following TDF discontinuation, 38.6% of patients with a decline in the eGFR did not experience recovery. A higher eGFR at baseline, a lower eGFR after discontinuation of TDF therapy, and more-prolonged exposure to TDF were associated with an increased risk of incomplete recovery 6 months after discontinuation of TDF therapy. Conclusions. This study shows that a decline in the eGFR during TDF therapy was not fully reversible in one third of patients and suggests that prolonged TDF exposure at a low eGFR should be avoided. PMID:24585896

Impact of ABCB1, ABCG2, and CYP3A5 polymorphisms on plasma trough concentrations of apixaban in Japanese patients with atrial fibrillation.

PubMed

Ueshima, Satoshi; Hira, Daiki; Fujii, Ryo; Kimura, Yuuma; Tomitsuka, Chiho; Yamane, Takuya; Tabuchi, Yohei; Ozawa, Tomoya; Itoh, Hideki; Horie, Minoru; Terada, Tomohiro; Katsura, Toshiya

2017-09-01

During anticoagulant therapy, major bleeding is one of the most severe adverse effects. This study aimed to evaluate the relationships between ABCB1, ABCG2, and CYP3A5 polymorphisms and plasma trough concentrations of apixaban, a direct inhibitor of coagulation factor X. A total of 70 plasma concentrations of apixaban from 44 Japanese patients with atrial fibrillation were analyzed. In these analyses, the plasma trough concentration/dose (C/D) ratio of apixaban was used as a pharmacokinetic index and all data were stratified according to the presence of ABCB1 (ABCB1 1236C>T, 2677G>T/A, and 3435C>T), ABCG2 (ABCG2 421C>A), and CYP3A5 (CYP3A5*3) polymorphisms. Influences of various clinical laboratory parameters (age, serum creatinine, estimated glomerular filtration rate, aspartate amino transferase, and alanine amino transferase) on the plasma trough C/D ratio of apixaban were included in analyses. Although no ABCB1 polymorphisms affected the plasma trough C/D ratio of apixaban, the plasma trough C/D ratio of apixaban was significantly higher in patients with the ABCG2 421A/A genotype than in patients with the ABCG2 421C/C genotype (P<0.01). The plasma trough C/D ratio of apixaban in patients with CYP3A5*1/*3 or *3/*3 genotypes was also significantly higher than that in patients with the CYP3A5*1/*1 genotype (P<0.05). Furthermore, the plasma trough C/D ratio of apixaban decreased with increased estimated glomerular filtration rate. These results indicate that ABCG2 421A/A and CYP3A5*3 genotypes and renal function are considered potential factors affecting trough concentrations of apixaban.

Association of HaeIII single nucleotide polymorphisms in the SLC2A1 gene with risk of diabetic nephropathy; evidence from Kurdish patients with type 2 diabetes mellitus.

PubMed

Amini, Sabrieh; Javanmardi, Mitra; Mokarizadeh, Aram; Maroofi, Farzad; Jalali, Chiya; Azadi, Namam-Ali; Mohammadi, Hamid; Abdi, Mohammad

2016-06-01

Given the growing rate of patients with type 2 diabetes mellitus, uncovering the effects of gene polymorphism on diabetes pathogenesis has attracted a lot of attention. Because glucose transporter 1 is involved in glucose uptake, the polymorphism of this gene may be an important risk factor in type 2 diabetes mellitus or in the progression of diabetes complications such as diabetic nephropathy. As far as the authors are concerned, this study is the first one aiming at evaluating the probable effects of solute carrier family 2 facilitated glucose transporter member 1 (SLC2A1) HaeIII polymorphism on clinical and laboratory outcomes of Kurdish patients with type 2 diabetes mellitus. This study was conducted involving 126 diabetic nephropathy patients and 150 diabetic patients without renal involvement. Serum levels of Cystatin C, fasting blood glucose, creatinine and urinary albumin; levels of glycated hemoglobin and estimated glomerular filtration rate were measured. Moreover, the Hae III polymorphism of SLC2A1 gene was determined by PCR-restriction fragment length polymorphism (RFLP). The rate of CC genotype was higher (37%) in patients with diabetic nephropathy compared with controls. There were a significant correlation between the CC genotype and risk of diabetic nephropathy. There were significant correlations between genotypes, serum Cystatin C and estimated glomerular filtration rate in patients with diabetic nephropathy. The results demonstrated the high frequency of C allele of SLC2A1 HaeIII in Kurdish patients with diabetic nephropathy. It was also found that this polymorphism is a significant risk factor for diabetic nephropathy. The effect of this polymorphism on clinical and laboratory characteristics of diabetic nephropathy patients was significant. © The Author 2015. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effects of Febuxostat on Oxidative Stress.

PubMed

Fukui, Toshiki; Maruyama, Mie; Yamauchi, Kazuhiro; Yoshitaka, Sumie; Yasuda, Tadashi; Abe, Youichi

2015-07-01

We previously examined factors that affect the measured derivatives of reactive oxygen metabolites (d-ROMs), an indicator of reactive oxygen species production, and biological antioxidant potential (BAP), an indicator of antioxidant capacity, in typical health checkup examinees and reported the usefulness of measuring both indicators simultaneously. In addition, a positive correlation reportedly exists between d-ROMs and the visceral fat area measured by using computed tomography. A recent study of the relationship between uric acid levels and various obesity-related factors found that visceral fat was the factor most strongly related to uric acid levels. Uric acid is itself a potent endogenous antioxidant, but because reactive oxygen species are produced during uric acid generation, it is suggested that uric acid may have opposing effects. The objective of this study was to analyze the effect of febuxostat, a novel xanthine oxidase inhibitor, on oxidative stress. Study subjects were 43 hyperuricemia outpatients receiving care in the internal medicine department of our institution. The subjects were divided into a new administration group (29 patients) and a switched administration group (14 patients); the latter were allopurinol-treated patients with hyperuricemia who were switched to febuxostat. In addition to measuring the patients' uric acid and creatinine levels and estimated glomerular filtration rate before and after treatment, their d-ROMs and BAP as well as the BAP/d-ROMs ratio were also measured. Both groups exhibited significant decreases in uric acid levels, as well as significant decreases in d-ROMs and BAP. No significant changes were observed in the BAP/dROMs ratio or renal function, including creatinine levels and estimated glomerular filtration rate. Febuxostat could significantly reduce d-ROMs. However, BAP levels were also significantly reduced concurrently. No changes were observed in the BAP/d-ROMs ratios. This regulatory mechanism is believed to have counteracted changes in the in vivo oxidative stress balance caused by febuxostat administration. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

Efficacy and safety of febuxostat in 73 gouty patients with stage 4/5 chronic kidney disease: A retrospective study of 10 centers.

PubMed

Juge, Pierre-Antoine; Truchetet, Marie-Elise; Pillebout, Evangeline; Ottaviani, Sébastien; Vigneau, Cécile; Loustau, Clotilde; Cornec, Divi; Pascart, Tristan; Snanoudj, Renaud; Bailly, Florian; Cornec-Le Gall, Emilie; Schaeverbeke, Thierry; Saraux, Alain; Dieudé, Philippe; Flipo, René-Marc; Richette, Pascal; Lioté, Frédéric; Bardin, Thomas; Chalès, Gérard; Ea, Hang-Korng

2017-10-01

The allopurinol dose is limited in chronic kidney disease, particularly stage 4/5 chronic kidney disease. Febuxostat has a hepatic metabolism and has been approved without dose adaptation in gouty patients with stage 1-3 chronic kidney disease. We aimed to study the safety and efficacy of febuxostat for stage 4/5 chronic kidney disease. In this retrospective study, we included patients with (1) a diagnosis of gout, (2) febuxostat treatment, (3) estimated glomerular filtration rate≤30mL/min/1.73m 2 (Modification of Diet in Renal Disease formula) at febuxostat initiation and (4) follow-up for at least 3 months after febuxostat initiation. Efficacy, safety and variation in estimated glomerular filtration rate were analyzed. We included 73 patients (mean age 70.2±11.8, 61 men, 31 with vascular chronic kidney disease and 18 renal transplantation) with gout (baseline serum uric acid level=9.86±2.85mg/dL, mean gout duration 6.2±7.0 years) from 10 academic centers. Comorbidities included cardiac failure (17.8%), hypertension (98.6%), diabetes mellitus (30.1%), dyslipidemia (64.8%) and history of cardiovascular events (38.4%). At the last visit (mean follow-up 68.5±64.8 weeks), the daily dose of febuxostat was 40mg for 7 patients (10.5%), 80mg for 50 (74.6%) and 120mg for 10 (14.9%). Serum uric acid level was<6mg/dL for 49 patients (67%). Renal function improved for 18 patients, was unchanged for 24 and worsened for 31; 19 patients experienced flares and 1 patient, limb edema. Febuxostat seemed efficient in gouty patients with stage 4/5 chronic kidney disease. However, safety data were not clear regarding renal function. Larger studies are needed to assess safety. Copyright © 2016 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Predicting timing of clinical outcomes in patients with chronic kidney disease and severely decreased glomerular filtration rate.

PubMed

Grams, Morgan E; Sang, Yingying; Ballew, Shoshana H; Carrero, Juan Jesus; Djurdjev, Ognjenka; Heerspink, Hiddo J L; Ho, Kevin; Ito, Sadayoshi; Marks, Angharad; Naimark, David; Nash, Danielle M; Navaneethan, Sankar D; Sarnak, Mark; Stengel, Benedicte; Visseren, Frank L J; Wang, Angela Yee-Moon; Köttgen, Anna; Levey, Andrew S; Woodward, Mark; Eckardt, Kai-Uwe; Hemmelgarn, Brenda; Coresh, Josef

2018-06-01

Patients with chronic kidney disease and severely decreased glomerular filtration rate (GFR) are at high risk for kidney failure, cardiovascular disease (CVD) and death. Accurate estimates of risk and timing of these clinical outcomes could guide patient counseling and therapy. Therefore, we developed models using data of 264,296 individuals in 30 countries participating in the international Chronic Kidney Disease Prognosis Consortium with estimated GFR (eGFR)s under 30 ml/min/1.73m 2 . Median participant eGFR and urine albumin-to-creatinine ratio were 24 ml/min/1.73m 2 and 168 mg/g, respectively. Using competing-risk regression, random-effect meta-analysis, and Markov processes with Monte Carlo simulations, we developed two- and four-year models of the probability and timing of kidney failure requiring kidney replacement therapy (KRT), a non-fatal CVD event, and death according to age, sex, race, eGFR, albumin-to-creatinine ratio, systolic blood pressure, smoking status, diabetes mellitus, and history of CVD. Hypothetically applied to a 60-year-old white male with a history of CVD, a systolic blood pressure of 140 mmHg, an eGFR of 25 ml/min/1.73m 2 and a urine albumin-to-creatinine ratio of 1000 mg/g, the four-year model predicted a 17% chance of survival after KRT, a 17% chance of survival after a CVD event, a 4% chance of survival after both, and a 28% chance of death (9% as a first event, and 19% after another CVD event or KRT). Risk predictions for KRT showed good overall agreement with the published kidney failure risk equation, and both models were well calibrated with observed risk. Thus, commonly-measured clinical characteristics can predict the timing and occurrence of clinical outcomes in patients with severely decreased GFR. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Estimating the glomerular filtration rate in the Spanish working population: chronic kidney disease prevalence and its association with risk factors.

PubMed

Sánchez-Chaparro, Miguel-Angel; Calvo-Bonacho, Eva; González-Quintela, Arturo; Cabrera, Martha; Quevedo-Aguado, Luis; Fernández-Labandera, Carlos; Ruiz-Moraga, Montserrat; Sainz-Gutiérrez, Juan Carlos; Gómez-Martínez, Pablo; Román-García, Javier; Felices, Pedro Valdivielso; Ruilope, Luis-Miguel; Zanchetti, Alberto

2014-10-01

This study aims to investigate the influence of estimated glomerular filtration rate (eGFR) with two equations (and by one or two separate measurements), on the prevalence of chronic kidney disease (CKD) and its association with blood pressure, and cardiovascular and metabolic risk factors. Between January 2010 and October 2011, the Ibermutuamur CArdiovascular RIsk Assessment project included 128 588 workers (77.2% men, mean age 39.3 years, range 16-75), who underwent two consecutive yearly medical check-ups and had information for eGFR according to the MDRD-IDMS and CKD-EPI equations (serum creatinine was measured by a isotope-dilution mass spectrometry traceable method in a single central laboratory). CKD was defined by an eGFR less than 60 ml/min per 1.73 m. Subclinical (occult) renal disease was defined as an eGFR less than 60 ml/min per 1.73 m in patients with serum creatinine below 1.3 mg/dl and below 1.2 mg/dl in men and women, respectively. In this working population, prevalence of CKD was very low, but two to six times lower when two separate eGFRs below 60 ml/min per 1.73 m were used. The prevalence of CKD was significantly lower with the CKD-EPI compared to the MDRD-IDMS equation. The same applies to occult CKD. In male workers, occult CKD was practically nonexistent.Multivariate analyses show that blood pressure, total serum cholesterol, and serum glucose (positively), and high-density lipoprotein and low-density lipoprotein (negatively) were associated with CKD, with both equations. Another metabolic factor (waist circumference) was only associated (positively) with CKD defined by the CKD-EPI equation, which appears to be associated with most components of the metabolic syndrome. The CKD-EPI formula, calculated on the basis of two reported blood samples, may provide the most specific definition of CKD.

Coffee Consumption and Incident Kidney Disease: Results From the Atherosclerosis Risk in Communities (ARIC) Study.

PubMed

Hu, Emily A; Selvin, Elizabeth; Grams, Morgan E; Steffen, Lyn M; Coresh, Josef; Rebholz, Casey M

2018-03-12

Moderate coffee consumption has been suggested to be associated with lower risk for chronic conditions such as diabetes, a major precursor to chronic kidney disease (CKD). However, the association between coffee and CKD has not been fully established. STUDY DESIGN: Prospective cohort study. 14,209 participants aged 45 to 64 years from the Atherosclerosis Risk in Communities (ARIC) Study. Coffee consumption (cups per day) was assessed at visits 1 (1987-1989) and 3 (1993-1995) using food frequency questionnaires. Incident CKD defined as estimated glomerular filtration rate < 60mL/min/1.73m 2 accompanied by ≥25% estimated glomerular filtration rate decline, CKD-related hospitalization or death, or end-stage renal disease. There were 3,845 cases of incident CKD over a median of 24 years of follow-up. Men, whites, current smokers, and participants without comorbid conditions were more likely to consume higher amounts of coffee per day. After adjustment for demographic, clinical, and dietary factors, higher categories of coffee consumption were associated with lower risk for incident CKD compared with those who never consumed coffee (HR for <1 cup per day, 0.90 [95% CI, 0.82-0.99]; 1-<2 cups per day, 0.90 [95% CI, 0.82-0.99]; 2-<3 cups per day, 0.87 [95% CI, 0.77-0.97]; and ≥3 cups per day, 0.84 [95% CI, 0.75-0.94]). In continuous analysis, for each additional cup of coffee consumed per day, risk for incident CKD was lower by 3% (HR, 0.97; 95% CI, 0.95-0.99; P<0.001). Self-reported coffee consumption and observational design. Participants who drank higher amounts of coffee had lower risk for incident CKD after adjusting for covariates. Coffee consumers may not be at adverse risk for kidney disease. Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Randomized Trial of Machine Perfusion Versus Cold Storage in Recipients of Deceased Donor Kidney Transplants With High Incidence of Delayed Graft Function.

PubMed

Tedesco-Silva, Helio; Mello Offerni, Juliano Chrystian; Ayres Carneiro, Vanessa; Ivani de Paula, Mayara; Neto, Elias David; Brambate Carvalhinho Lemos, Francine; Requião Moura, Lúcio Roberto; Pacheco E Silva Filho, Alvaro; de Morais Cunha, Mirian de Fátima; Francisco da Silva, Erica; Miorin, Luiz Antonio; Demetrio, Daniela Priscila; Luconi, Paulo Sérgio; da Silva Luconi, Waldere Tania; Bobbio, Savina Adriana; Kuschnaroff, Liz Milstein; Noronha, Irene Lourdes; Braga, Sibele Lessa; Barsante, Renata Cristina; Mendes Moreira, João Cezar; Fernandes-Charpiot, Ida Maria Maximina; Abbud-Filho, Mario; Modelli de Andrade, Luis Gustavo; Dalsoglio Garcia, Paula; Tanajura Santamaria Saber, Luciana; Fernandes Laurindo, Alan; Chocair, Pedro Renato; Cuvello Neto, Américo Lourenço; Zanocco, Juliana Aparecida; Duboc de Almeida Soares Filho, Antonio Jose; Ferreira Aguiar, Wilson; Medina Pestana, Jose

2017-05-01

This study compared the use of static cold storage versus continuous hypothermic machine perfusion in a cohort of kidney transplant recipients at high risk for delayed graft function (DGF). In this national, multicenter, and controlled trial, 80 pairs of kidneys recovered from brain-dead deceased donors were randomized to cold storage or machine perfusion, transplanted, and followed up for 12 months. The primary endpoint was the incidence of DGF. Secondary endpoints included the duration of DGF, hospital stay, primary nonfunction, estimated glomerular filtration rate, acute rejection, and allograft and patient survivals. Mean cold ischemia time was high but not different between the 2 groups (25.6 ± 6.6 hours vs 25.05 ± 6.3 hours, 0.937). The incidence of DGF was lower in the machine perfusion compared with cold storage group (61% vs. 45%, P = 0.031). Machine perfusion was independently associated with a reduced risk of DGF (odds ratio, 0.49; 95% confidence interval, 0.26-0.95). Mean estimated glomerular filtration rate tended to be higher at day 28 (40.6 ± 19.9 mL/min per 1.73 m 2 vs 49.0 ± 26.9 mL/min per 1.73 m 2 ; P = 0.262) and 1 year (48.3 ± 19.8 mL/min per 1.73 m 2 vs 54.4 ± 28.6 mL/min per 1.73 m 2 ; P = 0.201) in the machine perfusion group. No differences in the incidence of acute rejection, primary nonfunction (0% vs 2.5%), graft loss (7.5% vs 10%), or death (8.8% vs 6.3%) were observed. In this cohort of recipients of deceased donor kidneys with high mean cold ischemia time and high incidence of DGF, the use of continuous machine perfusion was associated with a reduced risk of DGF compared with the traditional cold storage preservation method.

Estimated glomerular filtration rate is associated with both arterial stiffness and N-terminal pro-brain natriuretic peptide in newly diagnosed hypertensive patients.

PubMed

Gür, Mustafa; Uçar, Hakan; Kuloğlu, Osman; Kıvrak, Ali; Şeker, Taner; Türkoğlu, Caner; Özaltun, Betül; Kaypaklı, Onur; Şahin, Durmuş Yıldıray; Elbasan, Zafer; Tanboğa, Halil İbrahim; Çaylı, Murat

2014-01-01

Even a slight decrease in the glomerular filtration rate (GFR) is an independent risk factor for cardiovascular disease. Arterial stiffness, left ventricular hypertrophy and N-terminal pro-brain natriuretic peptide (NT-proBNP) are independent risk factors for cardiovascular disease, which are particularly common in end-stage renal disease. We aimed to evaluate the association between GFR with arterial stiffness, left ventricle mass (LVM) and NT-proBNP in hypertensive subjects with normal to mildly impaired renal function. The study population consisted of 285 newly diagnosed hypertensive patients (mean age; 49.9 ± 11.8 years). GFR was estimated (eGFR) by the Modification of Diet in Renal Disease formula. Pulse wave velocity (PWV) and augmentation index (AIx), which reflects arterial stiffness, were calculated using the single-point method via the Mobil-O-Graph® ARCsolver algorithm. LVM was obtained by echocardiography. Plasma NT-proBNP was measured by electrochemiluminescence. The patients were divided into two groups according to the median eGFR value (eGFRlow group <101 ml/min/1.73 m(2) and eGFRhigh group ≥ 101 ml/min/1.73 m(2)). LVM and NT-proBNP values were higher in eGFRlow group compared with eGFRhigh group (p<0.05). Pulse wave velocity and augmentation index values were higher in eGFRlow group compared with eGFRhigh group (p<0.05, for all). Multiple linear regression analysis showed that eGFR was independently associated with PWV (β=-0.422, p<0.001) and NT-proBNP (β=-0.404, p<0.001). Present study showed that eGFR was independently associated with PWV and NT-proBNP values. Importantly, these findings may explain, in part, the increase in cardiovascular risk in with slightly impaired renal function.

Post-standardization of routine creatinine assays: are they suitable for clinical applications.

PubMed

Jassam, Nuthar; Weykamp, Cas; Thomas, Annette; Secchiero, Sandra; Sciacovelli, Laura; Plebani, Mario; Thelen, Marc; Cobbaert, Christa; Perich, Carmen; Ricós, Carmen; Paula, Faria A; Barth, Julian H

2017-05-01

Introduction Reliable serum creatinine measurements are of vital importance for the correct classification of chronic kidney disease and early identification of kidney injury. The National Kidney Disease Education Programme working group and other groups have defined clinically acceptable analytical limits for creatinine methods. The aim of this study was to re-evaluate the performance of routine creatinine methods in the light of these defined limits so as to assess their suitability for clinical practice. Method In collaboration with the Dutch External Quality Assurance scheme, six frozen commutable samples, with a creatinine concentration ranging from 80 to 239  μmol/L and traceable to isotope dilution mass spectrometry, were circulated to 91 laboratories in four European countries for creatinine measurement and estimated glomerular filtration rate calculation. Two out of the six samples were spiked with glucose to give high and low final concentrations of glucose. Results Results from 89 laboratories were analysed for bias, imprecision (%CV) for each creatinine assay and total error for estimated glomerular filtration rate. The participating laboratories used analytical instruments from four manufacturers; Abbott, Beckman, Roche and Siemens. All enzymatic methods in this study complied with the National Kidney Disease Education Programme working group recommended limits of bias of 5% above a creatinine concentration of 100  μmol/L. They also did not show any evidence of interference from glucose. In addition, they also showed compliance with the clinically recommended %CV of ≤4% across the analytical range. In contrast, the Jaffe methods showed variable performance with regard to the interference of glucose and unsatisfactory bias and precision. Conclusion Jaffe-based creatinine methods still exhibit considerable analytical variability in terms of bias, imprecision and lack of specificity, and this variability brings into question their clinical utility. We believe that clinical laboratories and manufacturers should work together to phase out the use of relatively non-specific Jaffe methods and replace them with more specific methods that are enzyme based.

Blood urea nitrogen/creatinine ratio identifies a high-risk but potentially reversible form of renal dysfunction in patients with decompensated heart failure.

PubMed

Brisco, Meredith A; Coca, Steven G; Chen, Jennifer; Owens, Anjali Tiku; McCauley, Brian D; Kimmel, Stephen E; Testani, Jeffrey M

2013-03-01

Identifying reversible renal dysfunction (RD) in the setting of heart failure is challenging. The goal of this study was to evaluate whether elevated admission blood urea nitrogen/creatinine ratio (BUN/Cr) could identify decompensated heart failure patients likely to experience improvement in renal function (IRF) with treatment. Consecutive hospitalizations with a discharge diagnosis of heart failure were reviewed. IRF was defined as ≥20% increase and worsening renal function as ≥20% decrease in estimated glomerular filtration rate. IRF occurred in 31% of the 896 patients meeting eligibility criteria. Higher admission BUN/Cr was associated with in-hospital IRF (odds ratio, 1.5 per 10 increase; 95% confidence interval [CI], 1.3-1.8; P<0.001), an association persisting after adjustment for baseline characteristics (odds ratio, 1.4; 95% CI, 1.1-1.8; P=0.004). However, higher admission BUN/Cr was also associated with post-discharge worsening renal function (odds ratio, 1.4; 95% CI, 1.1-1.8; P=0.011). Notably, in patients with an elevated admission BUN/Cr, the risk of death associated with RD (estimated glomerular filtration rate <45) was substantial (hazard ratio, 2.2; 95% CI, 1.6-3.1; P<0.001). However, in patients with a normal admission BUN/Cr, RD was not associated with increased mortality (hazard ratio, 1.2; 95% CI, 0.67-2.0; P=0.59; p interaction=0.03). An elevated admission BUN/Cr identifies decompensated patients with heart failure likely to experience IRF with treatment, providing proof of concept that reversible RD may be a discernible entity. However, this improvement seems to be largely transient, and RD, in the setting of an elevated BUN/Cr, remains strongly associated with death. Further research is warranted to develop strategies for the optimal detection and treatment of these high-risk patients.

Blood Urea Nitrogen/Creatinine Ratio Identifies a High-Risk but Potentially Reversible Form of Renal Dysfunction in Patients With Decompensated Heart Failure

PubMed Central

Brisco, Meredith A.; Coca, Steven G.; Chen, Jennifer; Owens, Anjali Tiku; McCauley, Brian D.; Kimmel, Stephen E.; Testani, Jeffrey M.

2014-01-01

Background Identifying reversible renal dysfunction (RD) in the setting of heart failure is challenging. The goal of this study was to evaluate whether elevated admission blood urea nitrogen/creatinine ratio (BUN/Cr) could identify decompensated heart failure patients likely to experience improvement in renal function (IRF) with treatment. Methods and Results Consecutive hospitalizations with a discharge diagnosis of heart failure were reviewed. IRF was defined as ≥20% increase and worsening renal function as ≥20% decrease in estimated glomerular filtration rate. IRF occurred in 31% of the 896 patients meeting eligibility criteria. Higher admission BUN/Cr was associated with inhospital IRF (odds ratio, 1.5 per 10 increase; 95% confidence interval [CI], 1.3–1.8; P<0.001), an association persisting after adjustment for baseline characteristics (odds ratio, 1.4; 95% CI, 1.1–1.8; P=0.004). However, higher admission BUN/Cr was also associated with post-discharge worsening renal function (odds ratio, 1.4; 95% CI, 1.1–1.8; P=0.011). Notably, in patients with an elevated admission BUN/Cr, the risk of death associated with RD (estimated glomerular filtration rate <45) was substantial (hazard ratio, 2.2; 95% CI, 1.6–3.1; P<0.001). However, in patients with a normal admission BUN/Cr, RD was not associated with increased mortality (hazard ratio, 1.2; 95% CI, 0.67–2.0; P=0.59; p interaction=0.03). Conclusions An elevated admission BUN/Cr identifies decompensated patients with heart failure likely to experience IRF with treatment, providing proof of concept that reversible RD may be a discernible entity. However, this improvement seems to be largely transient, and RD, in the setting of an elevated BUN/Cr, remains strongly associated with death. Further research is warranted to develop strategies for the optimal detection and treatment of these high-risk patients. PMID:23325460

Effects of renal denervation with a standard irrigated cardiac ablation catheter on blood pressure and renal function in patients with chronic kidney disease and resistant hypertension.

PubMed

Kiuchi, Márcio Galindo; Maia, George Luiz Marques; de Queiroz Carreira, Maria Angela Magalhães; Kiuchi, Tetsuaki; Chen, Shaojie; Andrea, Bruno Rustum; Graciano, Miguel Luis; Lugon, Jocemir Ronaldo

2013-07-01

Evaluation of the safety and efficacy of renal denervation with a standard irrigated cardiac ablation catheter (SICAC) in chronic kidney disease (CKD) patients with refractory hypertension. Twenty-four patients were included and treated with a SICAC. Denervation was performed by a single operator following the standard technique. Patients included with CKD were on stages 2 (n = 16), 3 (n = 4), and 4 (n = 4). Data were obtained at baseline and monthly until 180th day of follow-up. Baseline values of blood pressure (mean ± SD) were 186 ± 19 mmHg/108 ± 13 mmHg in the office, and 151 ± 18 mmHg/92 ± 11 mmHg by 24 h ambulatory blood pressure monitoring (ABPM). Office blood pressure values at 180th day after the procedure were 135 ± 13 mmHg/88 ± 7 mmHg (P < 0.0001, for both comparisons). The mean ABPM decreased to 132 ± 15 mmHg/85 ± 11 mmHg at the 180th day after the procedure (P < 0.0001 for systolic and P = 0.0015 for diastolic). Estimated glomerular filtration (mean ± SD) increased from baseline (64.4 ± 23.9 mL/min/1.73 m(2)) to the 180th day (85.4 ± 34.9 mL/min/1.73 m(2), P < 0.0001) of follow-up. The median urine albumin:creatinine ratio decreased from baseline (48.5, IQR: 35.8-157.2 mg/g) to the 180th day after ablation (ACR = 15.7, IQR: 10.3-34.2 mg/g, P = 0.0017). No major complications were seen. The procedure using SICAC seemed to be feasible, effective, and safe resulting in a better control of BP, a short-term increase in estimated glomerular filtration rate, and reduced albuminuria. Although encouraging, our data are preliminary and need to be validated in the long term.

Gender, renal function, and outcomes on the liver transplant waiting list: assessment of revised MELD including estimated glomerular filtration rate.

PubMed

Myers, Robert P; Shaheen, Abdel Aziz M; Aspinall, Alexander I; Quinn, Robert R; Burak, Kelly W

2011-03-01

The Model for End-Stage Liver Disease (MELD) allocation system for liver transplantation (LT) may present a disadvantage for women by including serum creatinine, which is typically lower in females. Our objectives were to investigate gender disparities in outcomes among LT candidates and to assess a revised MELD, including estimated glomerular filtration rate (eGFR), for predicting waiting list mortality. Adults registered for LT between 2002 and 2007 were identified using the UNOS database. We compared components of MELD, MDRD-derived eGFR, and the 3-month probability of LT and death between genders. Discrimination of MELD, MELDNa, and revised models including eGFR for mortality were compared using c-statistics. A total of 40,393 patients (36% female) met the inclusion criteria; 9% died and 24% underwent LT within 3 months of listing. Compared with men, women had lower median serum creatinine (0.9 vs. 1.0 mg/dl), eGFR (72 vs. 83 ml/min/1.73 m(2)), and mean MELD (16.5 vs. 17.2; all p <0.0005), but within most MELD strata, had higher bilirubin and INR. After adjusting for relevant covariates including creatinine and body weight, women were less likely than men to receive a LT (hazard ratio [HR] 0.85; 95% CI 0.79-0.87) and had greater 3-month mortality (HR 1.13; 95% CI 1.05-1.21). Revision of MELD and MELDNa to include eGFR did not improve discrimination for 3-month mortality (c-statistics: MELD 0.896, MELD-eGFR 0.894, MELDNa 0.911, MELDNa-eGFR 0.905). Women are disadvantaged under MELD potentially due to its inclusion of creatinine. However, since including eGFR in MELD does not improve mortality prediction, alternative refinements are necessary. Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Glomerular filtration rate is associated with free triiodothyronine in euthyroid subjects: Comparison between various equations to estimate renal function and creatinine clearance.

PubMed

Anderson, Josephine L C; Gruppen, Eke G; van Tienhoven-Wind, Lynnda; Eisenga, Michele F; de Vries, Hanne; Gansevoort, Ron T; Bakker, Stephan J L; Dullaart, Robin P F

2018-02-01

Effects of variations in thyroid function within the euthyroid range on renal function are unclear. Cystatin C-based equations to estimate glomerular filtration rate (GFR) are currently advocated for mortality and renal risk prediction. However, the applicability of cystatin C-based equations is discouraged in patients with overt thyroid dysfunction, since serum cystatin C and creatinine levels are oppositely affected by thyroid dysfunction. Here, we compared relationships of thyroid stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3) with various measures of kidney function in euthyroid subjects. Relationships of eGFR, based on creatinine (eGFRcrea), cystatin C (eGFRcysC), creatinine+cystatin C combined (eGFRcrea-cysC) and creatinine clearance (CrCl) with TSH, FT4 and FT3 were determined in 2180 euthyroid subjects (TSH, FT4 and FT3 all within the reference range; anti-thyroid peroxidase autoantibodies negative) who did not use thyroid hormones, anti-thyroid drugs, amiodarone or lithium carbonate. In multivariable models including TSH, FT3 and FT4 together, eGFRcrea, eGFRcysC and eGFRcrea-cysC and CrCl were all positively related to FT3 (P≤0.001), translating into a 2.61 to 2.83mL/min/1.73m 2 increase in eGFR measures and a 3.92mL/min increase in CrCl per 1pmol/L increment in FT3. These relationships with FT3 remained taking account of relevant covariates. In euthyroid subjects renal function is associated with thyroid function status, especially by serum FT3, irrespective of the eGFR equation applied. In the euthyroid state, cystatin C-based eGFR equations are appropriate to assess the relationship of renal function with variation in thyroid function status. Copyright © 2017 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Association between kidney function and telomere length: the Heart and Soul Study

PubMed Central

Bansal, Nisha; Whooley, Mary A.; Regan, Mathilda; McCulloch, Charles E.; Ix, Joachim H.; Epel, Elissa; Blackburn, Elizabeth; Lin, Jue; Hsu, Chi-yuan

2013-01-01

Background Telomere attrition is a novel risk factor for cardiovascular disease. Studies of telomere length in relation to kidney function are limited. We explored the association of kidney function with telomere length and telomere shortening. Methods The Heart and Soul study is a longitudinal study of patients with stable coronary heart disease (CHD). Measures of baseline kidney function included: serum creatinine, creatinine-derived estimated glomerular filtration rate (eGFRCKD-EPI), 24-hour urine measured creatinine clearance, cystatin C, cystatin C-derived estimated glomerular filtration rate (eGFRcys) and urine albumin to creatinine ratio. Telomere length was measured from peripheral blood leukocytes at baseline (N=954) and 5 years later (N=608). Linear regression models were used to test the association of kidney function with i) baseline telomere length and ii) change in telomere length over 5 years. Results At baseline, mean eGFRCKD-EPI was 72.6 (± 21.5) ml/min/1.73 m2, eGFRcys was 71.0 (± 23.1) ml/min/1.73 m2 and ACR was 8.6 (±12.3) mg/gm. Only lower baseline eGFRCKD-EPI was associated with shorter baseline telomere length (9.1 [95% CI 1.2–16.9] fewer base pairs for every 5 ml/min/1.73 m2 lower eGFRCKD-EPI). Lower baseline eGFRCKD-EPI (and all other measures of kidney function) predicted more rapid telomere shortening (10.8 [95% CI 4.3–17.3] decrease in base pairs over 5 years for every 5 ml/min/1.73 m2 lower eGFRCKD-EPI). After adjustment for age, these associations were no longer statistically significant. Conclusions In patients with CHD, reduced kidney function is associated with i) shorter baseline telomere length and ii) more rapid telomere shortening over 5 years, however these associations are entirely explained by older age. PMID:23108000

Association of ABCB1 genetic variants with renal function in Africans and in Caucasians

PubMed Central

Bochud, Murielle; Eap, Chin B; Maillard, Marc; Johnson, Toby; Vollenweider, Peter; Bovet, Pascal; Elston, Robert C; Bergmann, Sven; Beckmann, Jacques S; Waterworth, Dawn M; Mooser, Vincent; Gabriel, Anne; Burnier, Michel

2008-01-01

Background The P-glycoprotein, encoded by the ABCB1 gene, is expressed in human endothelial and mesangial cells, which contribute to control renal plasma flow and glomerular filtration rate. We investigated the association of ABCB1 variants with renal function in African and Caucasian subjects. Methods In Africans (290 subjects from 62 pedigrees), we genotyped the 2677G>T and 3435 C>T ABCB1 polymorphisms. Glomerular filtration rate (GFR) was measured using inulin clearance and effective renal plasma flow (ERPF) using para-aminohippurate clearance. In Caucasians (5382 unrelated subjects), we analyzed 30 SNPs located within and around ABCB1, using data from the Affymetrix 500 K chip. GFR was estimated using the simplified Modification of the Diet in Renal Disease (MDRD) and Cockcroft-Gault equations. Results In Africans, compared to the reference genotype (GG or CC), each copy of the 2677T and 3435T allele was associated, respectively, with: GFR higher by 10.6 ± 2.9 (P < 0.001) and 4.4 ± 2.3 (P = 0.06) mL/min; ERPF higher by 47.5 ± 11.6 (P < 0.001) and 28.1 ± 10.5 (P = 0.007) mL/min; and renal resistances lower by 0.016 ± 0.004 (P < 0.001) and 0.011 ± 0.004 (P = 0.004) mm Hg/mL/min. In Caucasians, we identified 3 polymorphisms in the ABCB1 gene that were strongly associated with all estimates of GFR (smallest P value = 0.0006, overall P = 0.014 after multiple testing correction). Conclusion Variants of the ABCB1 gene were associated with renal function in both Africans and Caucasians and may therefore confer susceptibility to nephropathy in humans. If confirmed in other studies, these results point toward a new candidate gene for nephropathy in humans. PMID:18518969

Pulmonary Hypertension Is Associated With a Higher Risk of Heart Failure Hospitalization and Mortality in Patients With Chronic Kidney Disease: The Jackson Heart Study.

PubMed

Selvaraj, Senthil; Shah, Sanjiv J; Ommerborn, Mark J; Clark, Cheryl R; Hall, Michael E; Mentz, Robert J; Qazi, Saadia; Robbins, Jeremy M; Skelton, Thomas N; Chen, Jiaying; Gaziano, J Michael; Djoussé, Luc

2017-06-01

African Americans develop chronic kidney disease and pulmonary hypertension (PH) at disproportionately high rates. Little is known whether PH heightens the risk of heart failure (HF) admission or mortality among chronic kidney disease patients, including patients with non-end-stage renal disease. We analyzed African Americans participants with chronic kidney disease (estimated glomerular filtration rate <60 mL/min per 1.73 m 2 or urine albumin/creatinine >30 mg/g) and available echocardiogram-derived pulmonary artery systolic pressure (PASP) from the Jackson Heart Study (N=408). We used Cox models to assess whether PH (PASP>35 mm Hg) was associated with higher rates of HF hospitalization and mortality. In a secondary, cross-sectional analysis, we examined the relationship between cystatin C (a marker of renal function) and PASP and potential mediators, including BNP (B-type natriuretic peptide) and endothelin-1. In our cohort, the mean age was 63±13 years, 70% were female, 78% had hypertension, and 22% had PH. Eighty-five percent of the participants had an estimated glomerular filtration rate >30 mL/min per 1.73 m 2 . During follow-up, 13% were hospitalized for HF and 27% died. After adjusting for potential confounders, including BNP, PH was found to be associated with HF hospitalization (hazard ratio, 2.37; 95% confidence interval, 1.15-4.86) and the combined outcome of HF hospitalization or mortality (hazard ratio, 1.84; confidence interval, 1.09-3.10). Log cystatin C was directly associated with PASP (adjusted β =2.5 [95% confidence interval, 0.8-4.1] per standard deviation change in cystatin C). Mediation analysis showed that BNP and endothelin-1 explained 56% and 40%, respectively, of the indirect effects between cystatin C and PASP. Among African Americans with chronic kidney disease, PH, which is likely pulmonary venous hypertension, was associated with a higher risk of HF admission and mortality. © 2017 American Heart Association, Inc.

Associations of Perfluoroalkyl Substances (PFAS) with Lower Birth Weight: An Evaluation of Potential Confounding by Glomerular Filtration Rate Using a Physiologically Based Pharmacokinetic Model (PBPK).

PubMed

Verner, Marc-André; Loccisano, Anne E; Morken, Nils-Halvdan; Yoon, Miyoung; Wu, Huali; McDougall, Robin; Maisonet, Mildred; Marcus, Michele; Kishi, Reiko; Miyashita, Chihiro; Chen, Mei-Huei; Hsieh, Wu-Shiun; Andersen, Melvin E; Clewell, Harvey J; Longnecker, Matthew P

2015-12-01

Prenatal exposure to perfluoroalkyl substances (PFAS) has been associated with lower birth weight in epidemiologic studies. This association could be attributable to glomerular filtration rate (GFR), which is related to PFAS concentration and birth weight. We used a physiologically based pharmacokinetic (PBPK) model of pregnancy to assess how much of the PFAS-birth weight association observed in epidemiologic studies might be attributable to GFR. We modified a PBPK model to reflect the association of GFR with birth weight (estimated from three studies of GFR and birth weight) and used it to simulate PFAS concentrations in maternal and cord plasma. The model was run 250,000 times, with variation in parameters, to simulate a population. Simulated data were analyzed to evaluate the association between PFAS levels and birth weight due to GFR. We compared simulated estimates with those from a meta-analysis of epidemiologic data. The reduction in birth weight for each 1-ng/mL increase in simulated cord plasma for perfluorooctane sulfonate (PFOS) was 2.72 g (95% CI: -3.40, -2.04), and for perfluorooctanoic acid (PFOA) was 7.13 g (95% CI: -8.46, -5.80); results based on maternal plasma at term were similar. Results were sensitive to variations in PFAS level distributions and the strength of the GFR-birth weight association. In comparison, our meta-analysis of epidemiologic studies suggested that each 1-ng/mL increase in prenatal PFOS and PFOA levels was associated with 5.00 g (95% CI: -21.66, -7.78) and 14.72 g (95% CI: -8.92, -1.09) reductions in birth weight, respectively. Results of our simulations suggest that a substantial proportion of the association between prenatal PFAS and birth weight may be attributable to confounding by GFR and that confounding by GFR may be more important in studies with sample collection later in pregnancy.

Albuminuria, but not estimated glomerular filtration rate, is associated with maladaptive arterial remodeling: the Hoorn Study.

PubMed

Hermans, Marc M H; Henry, Ronald M A; Dekker, Jaqueline M; Nijpels, Giel; Heine, Rob J; Stehouwer, Coen D A

2008-04-01

Arterial remodeling aims to maintain a constant circumferential wall stress (sigmac). A failing remodeling process is associated with stroke. Data on the relationship between chronic kidney disease and arterial remodeling are scarce. We investigated the association between a lower glomerular filtration rate (GFR) and microalbuminuria with arterial remodeling of the common carotid artery (CCA) in a population-based study of 806 patients. CCA properties including intima-media thickness and interadventitial diameter (IAD) were assessed. Lumen diameter, circumferential wall tension (CWT), and circumferential wall stress (sigmac) were calculated. GFR was estimated (eGFR) by the Modification of Diet in Renal Disease formula. Albuminuria was expressed as urinary albumin/creatinine ratio. Mean eGFR was 60.3 (+/-10.8) ml/min/1.73 m2; median urinary albumin/creatinine ratio was 0.57 (range 0.10-26.6 mg/mmol). After adjustment for age, sex, glucose tolerance status, and prevalent cardiovascular disease, eGFR was not independently associated with CCA properties. A greater urinary albumin/creatinine ratio (per quartile) was associated with a greater lumen diameter [regression coefficient beta with 95% confidence interval, 0.14 (0.08-0.20; P < 0.01)], IAD [0.15 (0.09-0.21; P < 0.01)], CWT [0.95 (0.52-1.38; P < 0.01)], and sigmac [1.7 (0.5-2.9; P < 0.01)] but not with a greater IMT [0.01 (-0.002-0.02; P = 0.12)]. Additional adjustments for mean arterial pressure, pulse pressure, and eGFR did not change the results. Greater albuminuria is independently associated with an increase in lumen diameter and IAD of the CCA. In addition, greater albuminuria is associated with a maladaptive carotid remodeling process as shown by an increase in CWT and sigmac. These findings may explain, why microalbuminuria is associated with a greater risk of cardiovascular disease and especially stroke.

Prognostic Value of Improved Kidney Function After Transcatheter Aortic Valve Implantation for Aortic Stenosis.

PubMed

Nijenhuis, Vincent Johan; Peper, Joyce; Vorselaars, Veronique M M; Swaans, Martin J; De Kroon, Thom; Van der Heyden, Jan A S; Rensing, Benno J W M; Heijmen, Robin; Bos, Willem-Jan W; Ten Berg, Jurrien M

2018-05-15

Transcatheter aortic valve implantation (TAVI) is associated with acute kidney injury (AKI), but can also improve the kidney function (IKF). We assessed the effects of kidney function changes in relation to baseline kidney function on 2-year clinical outcomes after TAVI. In total, 639 consecutive patients with aortic stenosis who underwent TAVI were stratified into 3 groups according to the ratio of serum creatinine post- to pre-TAVI: IKF (≤0.80; n = 95 [15%]), stable kidney function (0.80 to 1.5; n = 477 [75%]), and AKI (≥1.5; n = 67 [10%]). Different AKI risk scores were compared using receiving-operator characteristics. Median follow-up was 24 (8 to 44) months. At 3 months, the increase in estimated glomerular filtration rate in the IKF group remained, and the decreased estimated glomerular filtration rate in the AKI group recovered. Compared with a stable kidney function, AKI showed a higher 2-year mortality rate (adjusted hazard ratio [HR] 3.69, 95% confidence interval [CI] 2.43 to 5.62) and IKF a lower mortality rate (adjusted hazard ratio 0.53, 95% CI 0.30 to 0.93). AKI also predicted major and life-threatening bleeding (adjusted odds ratio 2.94, 95% CI 1.27 to 6.78). Independent predictors of AKI were chronic kidney disease and pulmonary hypertension. Independent predictors of IKF were female gender, a preserved kidney function, absence of atrial fibrillation, and hemoglobin level. Established AKI risk scores performed moderately and did not differentiate between AKI and IKF. In conclusion, AKI is transient and is independently associated with a higher mortality rate, whereas IKF is sustained and is associated with a lower mortality rate. These effects are independent of baseline kidney function. Further studies are warranted to investigate the role of IKF and generate a dedicated prediction model. Copyright © 2018 Elsevier Inc. All rights reserved.

Similar 5-Year Estimated Glomerular Filtration Rate Between Kidney Transplants From Uncontrolled and Controlled Donors After Circulatory Death—A Dutch Cohort Study

PubMed Central

Peters-Sengers, Hessel; Homan van der Heide, Jaap J.; Heemskerk, Martin B. A.; ten Berge, Ineke J. M.; Ultee, Fred C. W.; Idu, Mirza M.; Betjes, Michiel G. H.; van Zuilen, Arjan D.; Christiaans, Maarten H. L.; Hilbrands, Luuk H.; de Vries, Aiko P. J.; Nurmohamed, Azam S.; Berger, Stefan P.; Bemelman, Frederike J.

2017-01-01

Background Organ shortage persists despite a high rate of donation after circulatory death (DCD) in the Netherlands. The median waiting time for a deceased donor kidney in 2013 was 3.5 years. Most DCD kidneys are from controlled DCD (cDCD; Maastricht category III). Experience with uncontrolled donors after cardiac death (uDCD), that is, donors with an unexpected and irreversible cardiac arrest (Maastricht categories I and II), is increasing; and its effect on transplant outcomes needs evaluation. Methods We used the Dutch Organ Transplantation Registry to include recipients (≥18 years old) from all Dutch centers who received transplants from 2002 to 2012 with a first DCD kidney. We compared transplant outcome in uDCD (n = 97) and cDCD (n = 1441). Results Primary nonfunction in uDCD was higher than in the cDCD (19.6% vs 9.6%, P < 0.001, respectively). Delayed graft function was also higher in uDCD than in cDCD, but not significantly (73.7% vs 63.3%, P = .074, respectively). If censored for primary nonfunction, estimated glomerular filtration rates after 1 year and 5 years were comparable between uDCD and cDCD (1 year: uDCD, 44.3 (23.4) mL/min/m2 and cDCD, 45.8 (24.1) mL/min/m2; P = 0.621; 5 years: uDCD, 49.1 (25.6) mL/min/m2 and cDCD, 47.7 (21.7) mL/min/m2; P = 0.686). The differences in primary nonfunction between kidneys from uDCD and cDCD were explained by differences in the first warm ischemic period, cold ischemic time, and donor age. Conclusions We conclude that uDCD kidneys have potential for excellent function and can constitute a valuable extension of the donor pool. However, further efforts are necessary to address the high rate of primary nonfunction. PMID:27257998

Poverty, race, and CKD in a racially and socioeconomically diverse urban population.

PubMed

Crews, Deidra C; Charles, Raquel F; Evans, Michele K; Zonderman, Alan B; Powe, Neil R

2010-06-01

Low socioeconomic status (SES) and African American race are both independently associated with end-stage renal disease and progressive chronic kidney disease (CKD). However, despite their frequent co-occurrence, the effect of low SES independent of race has not been well studied in CKD. Cross-sectional study. 2,375 community-dwelling adults aged 30-64 years residing within 12 neighborhoods selected for both socioeconomic and racial diversity in Baltimore City, MD. Low SES (self-reported household income <125% of 2004 Department of Health and Human Services guideline), higher SES (> or =125% of guideline); white and African American race. CKD defined as estimated glomerular filtration rate <60 mL/min/1.73 m(2). Logistic regression used to calculate ORs for relationship between poverty and CKD, stratified by race. Of 2,375 participants, 955 were white (347 low SES and 608 higher SES) and 1,420 were African American (713 low SES and 707 higher SES). 146 (6.2%) participants had CKD. Overall, race was not associated with CKD (OR, 1.05; 95% CI, 0.57-1.96); however, African Americans had a much greater odds of advanced CKD (estimated glomerular filtration rate <30 mL/min/1.73 m(2)). Low SES was independently associated with 59% greater odds of CKD after adjustment for demographics, insurance status, and comorbid disease (OR, 1.59; 95% CI, 1.27-1.99). However, stratified by race, low SES was associated with CKD in African Americans (OR, 1.91; 95% CI, 1.54-2.38), but not whites (OR, 0.95; 95% CI, 0.58-1.55; P for interaction = 0.003). Cross-sectional design; findings may not be generalizable to non-urban populations. Low SES has a profound relationship with CKD in African Americans, but not whites, in an urban population of adults, and its role in the racial disparities seen in CKD is worthy of further investigation. Copyright 2010 National Kidney Foundation, Inc. All rights reserved.

CIN85 Deficiency Prevents Nephrin Endocytosis and Proteinuria in Diabetes

PubMed Central

Teng, Beina; Schroder, Patricia; Müller-Deile, Janina; Schenk, Heiko; Staggs, Lynne; Tossidou, Irini; Dikic, Ivan; Haller, Hermann

2016-01-01

Diabetic nephropathy (DN) is the major cause of end-stage renal disease worldwide. Podocytes are important for glomerular filtration barrier function and maintenance of size selectivity in protein filtration in the kidney. Podocyte damage is the basis of many glomerular diseases characterized by loss of interdigitating foot processes and decreased expression of components of the slit diaphragm. Nephrin, a podocyte-specific protein, is the main component of the slit diaphragm. Loss of nephrin is observed in human and rodent models of diabetic kidney disease. The long isoform of CIN85 (RukL) is a binding partner of nephrin that mediates nephrin endocytosis via ubiquitination in podocytes. Here we demonstrate that the loss of nephrin expression and the onset of proteinuria in diabetic mice correlate with an increased accumulation of ubiquitinated proteins and expression of CIN85/RukL in podocytes. CIN85/RukL deficiency preserved nephrin surface expression on the slit diaphragm and reduced proteinuria in diabetic mice, whereas overexpression of CIN85 in zebrafish induced severe edema and disruption of the filtration barrier. Thus, CIN85/RukL is involved in endocytosis of nephrin in podocytes under diabetic conditions, causing podocyte depletion and promoting proteinuria. CIN85/RukL expression therefore shows potential to be a novel target for antiproteinuric therapy in diabetes. PMID:27531950

Mortality Prediction in the Oldest Old with Five Different Equations to Estimate Glomerular Filtration Rate: The Health and Anemia Population-based Study

PubMed Central

Mandelli, Sara; Riva, Emma; Tettamanti, Mauro; Detoma, Paolo; Giacomin, Adriano; Lucca, Ugo

2015-01-01

Background Kidney function declines considerably with age, but little is known about its clinical significance in the oldest-old. Objectives To study the association between reduced glomerular filtration rate (GFR) estimated according to five equations with mortality in the oldest-old. Design Prospective population-based study. Setting Municipality of Biella, Piedmont, Italy. Participants 700 subjects aged 85 and older participating in the “Health and Anemia” Study in 2007–2008. Measurements GFR was estimated using five creatinine-based equations: the Cockcroft-Gault (C-G), Modification of Diet in Renal Disease (MDRD), MAYO Clinic, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Berlin Initiative Study-1 (BIS-1). Survival analysis was used to study mortality in subjects with reduced eGFR (<60 mL/min/1.73m2) compared to subjects with eGFR ≥60 mL/min/1.73m2. Results Prevalence of reduced GFR was 90.7% with the C-G, 48.1% with MDRD, 23.3% with MAYO, 53.6% with CKD-EPI and 84.4% with BIS-1. After adjustment for confounders, two-year mortality was significantly increased in subjects with reduced eGFR using BIS-1 and C-G equations (adjusted HRs: 2.88 and 3.30, respectively). Five-year mortality was significantly increased in subjects with eGFR <60 mL/min/1.73m2 using MAYO, CKD-EPI and, in a graduated fashion in reduced eGFR categories, MDRD. After 5 years, oldest old with an eGFR <30 mL/min/1.73m2 showed a significantly higher risk of death whichever equation was used (adjusted HRs between 2.04 and 2.70). Conclusion In the oldest old, prevalence of reduced eGFR varies noticeably depending on the equation used. In this population, risk of mortality was significantly higher for reduced GFR estimated with the BIS-1 and C-G equations over the short term. Though after five years the MDRD appeared on the whole a more consistent predictor, differences in mortality prediction among equations over the long term were less apparent. Noteworthy, subjects with a severely reduced GFR were consistently at higher risk of death regardless of the equation used to estimate GFR. PMID:26317988

Mortality Prediction in the Oldest Old with Five Different Equations to Estimate Glomerular Filtration Rate: The Health and Anemia Population-based Study.

PubMed

Mandelli, Sara; Riva, Emma; Tettamanti, Mauro; Detoma, Paolo; Giacomin, Adriano; Lucca, Ugo

2015-01-01

Kidney function declines considerably with age, but little is known about its clinical significance in the oldest-old. To study the association between reduced glomerular filtration rate (GFR) estimated according to five equations with mortality in the oldest-old. Prospective population-based study. Municipality of Biella, Piedmont, Italy. 700 subjects aged 85 and older participating in the "Health and Anemia" Study in 2007-2008. GFR was estimated using five creatinine-based equations: the Cockcroft-Gault (C-G), Modification of Diet in Renal Disease (MDRD), MAYO Clinic, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Berlin Initiative Study-1 (BIS-1). Survival analysis was used to study mortality in subjects with reduced eGFR (<60 mL/min/1.73 m(2)) compared to subjects with eGFR ≥ 60 mL/min/1.73 m(2). Prevalence of reduced GFR was 90.7% with the C-G, 48.1% with MDRD, 23.3% with MAYO, 53.6% with CKD-EPI and 84.4% with BIS-1. After adjustment for confounders, two-year mortality was significantly increased in subjects with reduced eGFR using BIS-1 and C-G equations (adjusted HRs: 2.88 and 3.30, respectively). Five-year mortality was significantly increased in subjects with eGFR <60 mL/min/1.73 m(2) using MAYO, CKD-EPI and, in a graduated fashion in reduced eGFR categories, MDRD. After 5 years, oldest old with an eGFR <30 mL/min/1.73 m(2) showed a significantly higher risk of death whichever equation was used (adjusted HRs between 2.04 and 2.70). In the oldest old, prevalence of reduced eGFR varies noticeably depending on the equation used. In this population, risk of mortality was significantly higher for reduced GFR estimated with the BIS-1 and C-G equations over the short term. Though after five years the MDRD appeared on the whole a more consistent predictor, differences in mortality prediction among equations over the long term were less apparent. Noteworthy, subjects with a severely reduced GFR were consistently at higher risk of death regardless of the equation used to estimate GFR.

Assessing glomerular filtration rate (GFR) in critically ill patients with acute kidney injury - true GFR versus urinary creatinine clearance and estimating equations

PubMed Central

2013-01-01

Introduction Estimation of kidney function in critically ill patients with acute kidney injury (AKI), is important for appropriate dosing of drugs and adjustment of therapeutic strategies, but challenging due to fluctuations in kidney function, creatinine metabolism and fluid balance. Data on the agreement between estimating and gold standard methods to assess glomerular filtration rate (GFR) in early AKI are lacking. We evaluated the agreement of urinary creatinine clearance (CrCl) and three commonly used estimating equations, the Cockcroft Gault (CG), the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, in comparison to GFR measured by the infusion clearance of chromium-ethylenediaminetetraacetic acid (51Cr-EDTA), in critically ill patients with early AKI after complicated cardiac surgery. Methods Thirty patients with early AKI were studied in the intensive care unit, 2 to 12 days after complicated cardiac surgery. The infusion clearance for 51Cr-EDTA obtained as a measure of GFR (GFR51Cr-EDTA) was calculated from the formula: GFR (mL/min/1.73m2) = (51Cr-EDTA infusion rate × 1.73)/(arterial 51Cr-EDTA × body surface area) and compared with the urinary CrCl and the estimated GFR (eGFR) from the three estimating equations. Urine was collected in two 30-minute periods to measure urine flow and urine creatinine. Urinary CrCl was calculated from the formula: CrCl (mL/min/1.73m2) = (urine volume × urine creatinine × 1.73)/(serum creatinine × 30 min × body surface area). Results The within-group error was lower for GFR51Cr-EDTA than the urinary CrCl method, 7.2% versus 55.0%. The between-method bias was 2.6, 11.6, 11.1 and 7.39 ml/min for eGFRCrCl, eGFRMDRD, eGFRCKD-EPI and eGFRCG, respectively, when compared to GFR51Cr-EDTA. The error was 103%, 68.7%, 67.7% and 68.0% for eGFRCrCl, eGFRMDRD, eGFRCKD-EPI and eGFRCG, respectively, when compared to GFR51Cr-EDTA. Conclusions The study demonstrated poor precision of the commonly utilized urinary CrCl method for assessment of GFR in critically ill patients with early AKI, suggesting that this should not be used as a reference method when validating new methods for assessing kidney function in this patient population. The commonly used estimating equations perform poorly when estimating GFR, with high biases and unacceptably high errors. PMID:23767877

Effect of Finerenone on Albuminuria in Patients With Diabetic Nephropathy: A Randomized Clinical Trial.

PubMed

Bakris, George L; Agarwal, Rajiv; Chan, Juliana C; Cooper, Mark E; Gansevoort, Ron T; Haller, Hermann; Remuzzi, Giuseppe; Rossing, Peter; Schmieder, Roland E; Nowack, Christina; Kolkhof, Peter; Joseph, Amer; Pieper, Alexander; Kimmeskamp-Kirschbaum, Nina; Ruilope, Luis M

2015-09-01

Steroidal mineralocorticoid receptor antagonists, when added to a renin-angiotensin system blocker, further reduce proteinuria in patients with chronic kidney disease but may be underused because of a high risk of adverse events. To evaluate the safety and efficacy of different oral doses of the nonsteroidal mineralocorticoid receptor antagonist finerenone, given for 90 days to patients with diabetes and high or very high albuminuria who are receiving an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Randomized, double-blind, placebo-controlled, parallel-group study conducted at 148 sites in 23 countries. Patients were recruited from June 2013 to February 2014 and the study was completed in August 2014. Of 1501 screened patients, 823 were randomized and 821 received study drug. Participants were randomly assigned to receive oral, once-daily finerenone (1.25 mg/d, n = 96; 2.5 mg/d, n = 92; 5 mg/d, n = 100; 7.5 mg/d, n = 97; 10 mg/d, n = 98; 15 mg/d, n = 125; and 25 mg/d, n = 119) or matching placebo (n = 94) for 90 days. The primary outcome was the ratio of the urinary albumin-creatinine ratio (UACR) at day 90 vs at baseline. Safety end points were changes from baseline in serum potassium and estimated glomerular filtration rate. The mean age of the participants was 64.2 years; 78% were male. At baseline, 36.7% of patients treated had very high albuminuria (UACR ≥300 mg/g) and 40.0% had an estimated glomerular filtration rate of 60 mL/min/1.73 m2 or lower. Finerenone demonstrated a dose-dependent reduction in UACR. The primary outcome, the placebo-corrected mean ratio of the UACR at day 90 relative to baseline, was reduced in the finerenone 7.5-, 10-, 15-, and 20-mg/d groups (for 7.5 mg/d, 0.79 [90% CI, 0.68-0.91; P = .004]; for 10 mg/d, 0.76 [90% CI, 0.65-0.88; P = .001]; for 15 mg/d, 0.67 [90% CI, 0.58-0.77; P<.001]; for 20 mg/d, 0.62 [90% CI, 0.54-0.72; P < .001]). The prespecified secondary outcome of hyperkalemia leading to discontinuation was not observed in the placebo and finerenone 10-mg/d groups; incidences in the finerenone 7.5-, 15-, and 20-mg/d groups were 2.1%, 3.2%, and 1.7%, respectively. There were no differences in the incidence of the prespecified secondary outcome of an estimated glomerular filtration rate decrease of 30% or more or in incidences of adverse events and serious adverse events between the placebo and finerenone groups. Among patients with diabetic nephropathy, most receiving an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker, the addition of finerenone compared with placebo resulted in improvement in the urinary albumin-creatinine ratio. Further trials are needed to compare finerenone with other active medications. clinicaltrials.gov Identifier: NCT1874431.

In vivo imaging of kidney glomeruli transplanted into the anterior chamber of the mouse eye

PubMed Central

Kistler, Andreas D.; Caicedo, Alejandro; Abdulreda, Midhat H.; Faul, Christian; Kerjaschki, Dontscho; Berggren, Per-Olof; Reiser, Jochen; Fornoni, Alessia

2014-01-01

Multiphoton microscopy enables live imaging of the renal glomerulus. However, repeated in vivo imaging of the same glomerulus over extended periods of time and the study of glomerular function independent of parietal epithelial and proximal tubular cell effects has not been possible so far. Here, we report a novel approach for non-invasive imaging of acapsular glomeruli transplanted into the anterior chamber of the mouse eye. After microinjection, glomeruli were capable of engrafting on the highly vascularized iris. Glomerular structure was preserved, as demonstrated by podocyte specific expression of cyan fluorescent protein and by electron microscopy. Injection of fluorescence-labeled dextrans of various molecular weights allowed visualization of glomerular filtration and revealed leakage of 70 kDa dextran in an inducible model of proteinuria. Our findings demonstrate functionality and long-term survival of glomeruli devoid of Bowman's capsule and provide a novel approach for non-invasive longitudinal in vivo study of glomerular physiology and pathophysiology. PMID:24464028

42 CFR 410.130 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... transplantation (glomerular filtration rate [GFR] 13-50 ml/min/1.73m2). Diabetes means diabetes mellitus, a... person with symptoms of uncontrolled diabetes. Episode of care means services covered in a 12-month time period when coordinated with initial diabetes self-management training (DSMT) and one calendar year for...

Case discussion: impaired renal function and tolerance to high altitude.

PubMed

2002-01-01

A 58-year-old woman who plans a trek in the Himalayas at altitudes from 4500 to 5000 m is known to have the loss of about 50% of renal function based on glomerular filtration studies and renal biopsy. Possible risks and management are discussed.

Combining Cystatin C and Creatinine Yields a Reliable Glomerular Filtration Rate Estimation in Older Adults in Contrast to β-Trace Protein and β2-Microglobulin.

PubMed

Werner, Karin; Pihlsgård, Mats; Elmståhl, Sölve; Legrand, Helen; Nyman, Ulf; Christensson, Anders

2017-01-01

The glomerular filtration rate (GFR) is the most important measure of kidney function and chronic kidney disease (CKD). This study aims to validate commonly used equations for estimated GFR (eGFR) based on creatinine (cr), cystatin C (cys), β-trace protein (BTP), and β2-microglobulin (B2M) in older adults. We conducted a validation study with 126 participants aged between 72 and 98 with a mean measured GFR (mGFR) by iohexol clearance of 54 mL/min/1.73 m2. The eGFR equations (CKD-Epidemiology collaboration [CKD-EPI], Berlin Initiative Study [BIS], Full Age Spectrum [FAS], Modification of Diet in Renal Disease [MDRD]cr, Caucasian-Asian-Pediatric-Adult [CAPA]cys, Lund-Malmö Revised [LM-REV]cr, and MEAN-LM-CAPAcr-cys), were assessed in terms of bias (median difference: eGFR-mGFR), precision (interquartile range of the differences), and accuracy (P30: percentage of estimates ±30% of mGFR). The equations were compared to a benchmark equation: CKD-EPIcr-cys. All cystatin C-based equations underestimated the GFR compared to mGFR, whereas bias was mixed for the equations based only on creatinine. Accuracy was the highest for CKD-EPIcr-cys (98%) and lowest for MDRD (82%). Below mGFR 45 mL/min/1.73 m2 only equations incorporating cystatin C reached P30 accuracy >90%. CKD-EPIcr-cys was not significantly more accurate than the other cystatin C-based equations. In contrast, CKD-EPIcr-cys was significantly more accurate than all creatinine-based equations except LM-REVcr. This study confirms that it is reasonable to use equations incorporating cystatin C and creatinine in older patients across a wide spectrum of GFR. However, the results call into question the use of creatinine alone below mGFR 45 mL/min/1.73 m2. B2M and BTP do not demonstrate additional value in eGFR determination in older adults. © 2017 S. Karger AG, Basel.

A genome-wide search for linkage of estimated glomerular filtration rate (eGFR) in the Family Investigation of Nephropathy and Diabetes (FIND).

PubMed

Thameem, Farook; Igo, Robert P; Freedman, Barry I; Langefeld, Carl; Hanson, Robert L; Schelling, Jeffrey R; Elston, Robert C; Duggirala, Ravindranath; Nicholas, Susanne B; Goddard, Katrina A B; Divers, Jasmin; Guo, Xiuqing; Ipp, Eli; Kimmel, Paul L; Meoni, Lucy A; Shah, Vallabh O; Smith, Michael W; Winkler, Cheryl A; Zager, Philip G; Knowler, William C; Nelson, Robert G; Pahl, Madeline V; Parekh, Rulan S; Kao, W H Linda; Rasooly, Rebekah S; Adler, Sharon G; Abboud, Hanna E; Iyengar, Sudha K; Sedor, John R

2013-01-01

Estimated glomerular filtration rate (eGFR), a measure of kidney function, is heritable, suggesting that genes influence renal function. Genes that influence eGFR have been identified through genome-wide association studies. However, family-based linkage approaches may identify loci that explain a larger proportion of the heritability. This study used genome-wide linkage and association scans to identify quantitative trait loci (QTL) that influence eGFR. Genome-wide linkage and sparse association scans of eGFR were performed in families ascertained by probands with advanced diabetic nephropathy (DN) from the multi-ethnic Family Investigation of Nephropathy and Diabetes (FIND) study. This study included 954 African Americans (AA), 781 American Indians (AI), 614 European Americans (EA) and 1,611 Mexican Americans (MA). A total of 3,960 FIND participants were genotyped for 6,000 single nucleotide polymorphisms (SNPs) using the Illumina Linkage IVb panel. GFR was estimated by the Modification of Diet in Renal Disease (MDRD) formula. The non-parametric linkage analysis, accounting for the effects of diabetes duration and BMI, identified the strongest evidence for linkage of eGFR on chromosome 20q11 (log of the odds [LOD] = 3.34; P = 4.4 × 10(-5)) in MA and chromosome 15q12 (LOD = 2.84; P = 1.5 × 10(-4)) in EA. In all subjects, the strongest linkage signal for eGFR was detected on chromosome 10p12 (P = 5.5 × 10(-4)) at 44 cM near marker rs1339048. A subsequent association scan in both ancestry-specific groups and the entire population identified several SNPs significantly associated with eGFR across the genome. The present study describes the localization of QTL influencing eGFR on 20q11 in MA, 15q21 in EA and 10p12 in the combined ethnic groups participating in the FIND study. Identification of causal genes/variants influencing eGFR, within these linkage and association loci, will open new avenues for functional analyses and development of novel diagnostic markers for DN.

Estimated Glomerular Filtration Rate, Cardiovascular Events and Mortality Across Age Groups Among Individuals Older Than 60 Years in Southern Europe.

PubMed

Salvador-González, Betlem; Gil-Terrón, Neus; Cerain-Herrero, M Jesús; Subirana, Isaac; Güell-Miró, Roser; Rodríguez-Latre, Luisa M; Cunillera-Puértolas, Oriol; Elosua, Roberto; Grau, Maria; Vila, Joan; Pascual-Benito, Luisa; Mestre-Ferrer, Jordi; Ramos, Rafel; Baena-Díez, José Miguel; Soler-Vila, Maria; Alonso-Bes, Eva; Ruipérez-Guijarro, Laura; Álvarez-Funes, Virtudes; Freixes-Villaró, Esther; Rodríguez-Pascual, Mercedes; Martínez-Castelao, Alberto

2018-06-01

Individuals with a decreased estimated glomerular filtration rate (eGFR) are at increased risk of all-cause (ACM) and cardiovascular mortality; there is ongoing debate about whether older individuals with eGFR 45 to 59mL/min/1.73 m 2 are also at increased risk. We evaluated the association between eGFR and ACM and cardiovascular events (CVE) in people aged 60 to 74 and ≥ 75 years in a population with a low coronary disease incidence. We conducted a retrospective cohort study by using primary care and hospital electronic records. We included 130 233 individuals aged ≥ 60 years with creatinine measurement between January 1, 2010 and December 31, 2011; eGFR was estimated by using the Chronic Kidney Disease Epidemiology Collaboration creatinine equation. The independent association between eGFR and the risk of ACM and hospital admission due to CVE were determined with Cox and Fine-Gray regressions, respectively. The median was age 70 years, and 56.1% were women; 13.5% had eGFR < 60 (69.7% eGFR 45-59). During a median follow-up of 38.2 months, 6474 participants died and 3746 had a CVE. For ACM and CVE, the HR in older individuals became significant at eGFR < 60. Fully adjusted HR for ACM in the eGFR 45 to 59 category were 1.61; 95%CI, 1.37-1.89 and 1.19; 95%CI, 1.10-1.28 in 60- to 74-year-olds and ≥ 75-year-olds, respectively; for CVE HR were 1.28; 95%CI, 1.08-1.51 and 1.12; 95%CI, 0.99-1.26. In a region with low coronary disease incidence, the risk of death and CVE increased with decreasing eGFR. In ≥ 75-year-olds, the eGFR 45 to 59 category, which had borderline risk for CVE, included many individuals without significant additional risk. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Association between vascular access creation and deceleration of estimated glomerular filtration rate decline in late-stage chronic kidney disease patients transitioning to end-stage renal disease.

PubMed

Sumida, Keiichi; Molnar, Miklos Z; Potukuchi, Praveen K; Thomas, Fridtjof; Lu, Jun Ling; Ravel, Vanessa A; Soohoo, Melissa; Rhee, Connie M; Streja, Elani; Yamagata, Kunihiro; Kalantar-Zadeh, Kamyar; Kovesdy, Csaba P

2017-08-01

Prior studies have suggested that arteriovenous fistula (AVF) or graft (AVG) creation may be associated with slowing of estimated glomerular filtration rate (eGFR) decline. It is unclear if this is attributable to the physiological benefits of a mature access on systemic circulation versus confounding factors. We examined a nationwide cohort of 3026 US veterans with advanced chronic kidney disease (CKD) transitioning to dialysis between 2007 and 2011 who had a pre-dialysis AVF/AVG and had at least three outpatient eGFR measurements both before and after AVF/AVG creation. Slopes of eGFR were estimated using mixed-effects models adjusted for fixed and time-dependent confounders, and compared separately for the pre- and post-AVF/AVG period overall and in patients stratified by AVF/AVG maturation. In all, 3514 patients without AVF/AVG who started dialysis with a catheter served as comparators, using an arbitrary 6-month index date before dialysis initiation to assess change in eGFR slopes. Of the 3026 patients with AVF/AVG (mean age 67 years, 98% male, 75% diabetic), 71% had a mature AVF/AVG at dialysis initiation. eGFR decline accelerated in the last 6 months prior to dialysis in patients with a catheter (median, from -6.0 to -16.3 mL/min/1.73 m2/year, P < 0.001), while a significant deceleration of eGFR decline was seen after vascular access creation in those with AVF/AVG (median, from -5.6 to -4.1 mL/min/1.73 m2/year, P < 0.001). Findings were independent of AVF/AVG maturation status and were robust in adjusted models. The creation of pre-dialysis AVF/AVG appears to be associated with eGFR slope deceleration and, consequently, may delay the onset of dialysis initiation in advanced CKD patients. Published by Oxford University Press on behalf of ERA-EDTA 2016. This work is written by US Government employees and is in the public domain in the US.

Comparison of creatinine and cystatin C based eGFR in the estimation of glomerular filtration rate in Indigenous Australians: The eGFR Study.

PubMed

Barr, Elizabeth Lm; Maple-Brown, Louise J; Barzi, Federica; Hughes, Jaquelyne T; Jerums, George; Ekinci, Elif I; Ellis, Andrew G; Jones, Graham Rd; Lawton, Paul D; Sajiv, Cherian; Majoni, Sandawana W; Brown, Alex Dh; Hoy, Wendy E; O'Dea, Kerin; Cass, Alan; MacIsaac, Richard J

2017-04-01

The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation that combines creatinine and cystatin C is superior to equations that include either measure alone in estimating glomerular filtration rate (GFR). However, whether cystatin C can provide any additional benefits in estimating GFR for Indigenous Australians, a population at high risk of end-stage kidney disease (ESKD) is unknown. Using a cross-sectional analysis from the eGFR Study of 654 Indigenous Australians at high risk of ESKD, eGFR was calculated using the CKD-EPI equations for serum creatinine (eGFRcr), cystatin C (eGFRcysC) and combined creatinine and cystatin C (eGFRcysC+cr). Reference GFR (mGFR) was determined using a non-isotopic iohexol plasma disappearance technique over 4h. Performance of each equation to mGFR was assessed by calculating bias, % bias, precision and accuracy for the total population, and according to age, sex, kidney disease, diabetes, obesity and c-reactive protein. Data were available for 542 participants (38% men, mean [sd] age 45 [14] years). Bias was significantly greater for eGFRcysC (15.0mL/min/1.73m 2 ; 95% CI 13.3-16.4, p<0.001) and eGFRcysC+cr (10.3; 8.8-11.5, p<0.001) compared to eGFRcr (5.4; 3.0-7.2). Accuracy was lower for eGFRcysC (80.3%; 76.7-83.5, p<0.001) but not for eGFRcysC+cr (91.9; 89.3-94.0, p=0.29) compared to eGFRcr (90.0; 87.2-92.4). Precision was comparable for all equations. The performance of eGFRcysC deteriorated across increasing levels of c-reactive protein. Cystatin C based eGFR equations may not perform well in populations with high levels of chronic inflammation. CKD-EPI eGFR based on serum creatinine remains the preferred equation in Indigenous Australians. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Changes in renal function after discontinuation of vitamin D analogues in advanced chronic kidney disease.

PubMed

Caravaca, Francisco; Caravaca-Fontán, Fernando; Azevedo, Lilia; Luna, Enrique

In routine clinical practice, the prescription of vitamin D analogues (VDA) in patients with chronic kidney disease (CKD) is often associated with a decline of the estimated renal function. The reason for this is not fully understood. To analyse the effects of VDA discontinuation in advanced CKD and to determine the factors associated with changes in renal function. Retrospective cohort study of adult patients with advanced CKD. The case subgroup was treated with VDA and this medication was discontinued at baseline (the first visit). The control subgroup was not treated with VDA and they were selected according to comparability principles for CKD progression by propensity score matching. The primary outcome measure was a change to both the estimated glomerular filtration rate (MDRD-GFR) and the measured glomerular filtration rate (mGFR by combined creatinine and urea clearances). Baseline parameters related to mineral metabolism and creatinine generation were analysed as potential determinants of renal function changes. The study sample consisted of 67 cases and 67 controls. Renal function improved in 67% of cases and worsened in 72% of controls (p<0.0001). Changes in MDRD-GFR for the case subgroup and the control subgroup were +0.455±0.997 vs. -0.436±1.103ml/min/1.73 m 2 /month (p<0.0001), respectively. Total creatinine excretion was slightly higher in cases than in controls but the difference was not significant. According to multivariate logistic and linear regression analyses, baseline total serum calcium was one of the best determinants of both renal function recovery (Odds ratio=3.49; p=0.001), and of the extent of renal function recovery (beta=0.276; p=0.001). Discontinuation of VDA treatment in CKD patients is associated with significant recovery of estimated renal function. The extent of these changes is mainly associated with baseline total serum calcium. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

A Genome-Wide Search for Linkage of Estimated Glomerular Filtration Rate (eGFR) in the Family Investigation of Nephropathy and Diabetes (FIND)

PubMed Central

Thameem, Farook; Igo, Robert P.; Freedman, Barry I.; Langefeld, Carl; Hanson, Robert L.; Schelling, Jeffrey R.; Elston, Robert C.; Duggirala, Ravindranath; Nicholas, Susanne B.; Goddard, Katrina A. B.; Divers, Jasmin; Guo, Xiuqing; Ipp, Eli; Kimmel, Paul L.; Meoni, Lucy A.; Shah, Vallabh O.; Smith, Michael W.; Winkler, Cheryl A.; Zager, Philip G.; Knowler, William C.; Nelson, Robert G.; Pahl, Madeline V.; Parekh, Rulan S.; Kao, W. H. Linda; Rasooly, Rebekah S.; Adler, Sharon G.; Abboud, Hanna E.; Iyengar, Sudha K.; Sedor, John R.

2013-01-01

Objective Estimated glomerular filtration rate (eGFR), a measure of kidney function, is heritable, suggesting that genes influence renal function. Genes that influence eGFR have been identified through genome-wide association studies. However, family-based linkage approaches may identify loci that explain a larger proportion of the heritability. This study used genome-wide linkage and association scans to identify quantitative trait loci (QTL) that influence eGFR. Methods Genome-wide linkage and sparse association scans of eGFR were performed in families ascertained by probands with advanced diabetic nephropathy (DN) from the multi-ethnic Family Investigation of Nephropathy and Diabetes (FIND) study. This study included 954 African Americans (AA), 781 American Indians (AI), 614 European Americans (EA) and 1,611 Mexican Americans (MA). A total of 3,960 FIND participants were genotyped for 6,000 single nucleotide polymorphisms (SNPs) using the Illumina Linkage IVb panel. GFR was estimated by the Modification of Diet in Renal Disease (MDRD) formula. Results The non-parametric linkage analysis, accounting for the effects of diabetes duration and BMI, identified the strongest evidence for linkage of eGFR on chromosome 20q11 (log of the odds [LOD] = 3.34; P = 4.4×10−5) in MA and chromosome 15q12 (LOD = 2.84; P = 1.5×10−4) in EA. In all subjects, the strongest linkage signal for eGFR was detected on chromosome 10p12 (P = 5.5×10−4) at 44 cM near marker rs1339048. A subsequent association scan in both ancestry-specific groups and the entire population identified several SNPs significantly associated with eGFR across the genome. Conclusion The present study describes the localization of QTL influencing eGFR on 20q11 in MA, 15q21 in EA and 10p12 in the combined ethnic groups participating in the FIND study. Identification of causal genes/variants influencing eGFR, within these linkage and association loci, will open new avenues for functional analyses and development of novel diagnostic markers for DN. PMID:24358131

Incidence of Posttransplantation Diabetes Mellitus in De Novo Kidney Transplant Recipients Receiving Prolonged-Release Tacrolimus-Based Immunosuppression With 2 Different Corticosteroid Minimization Strategies: ADVANCE, A Randomized Controlled Trial

PubMed Central

Mourad, Georges; Glyda, Maciej; Albano, Laetitia; Viklický, Ondrej; Merville, Pierre; Tydén, Gunnar; Mourad, Michel; Lõhmus, Aleksander; Witzke, Oliver; Christiaans, Maarten H. L.; Brown, Malcolm W.; Undre, Nasrullah; Kazeem, Gbenga; Kuypers, Dirk R. J.

2017-01-01

Background ADVANCE (NCT01304836) was a phase 4, multicenter, prospectively randomized, open-label, 24-week study comparing the incidence of posttransplantation diabetes mellitus (PTDM) with 2 prolonged-release tacrolimus corticosteroid minimization regimens. Methods All patients received prolonged-release tacrolimus, basiliximab, mycophenolate mofetil and 1 bolus of intraoperative corticosteroids (0-1000 mg) as per center policy. Patients in arm 1 received tapered corticosteroids, stopped after day 10, whereas patients in arm 2 received no steroids after the intraoperative bolus. The primary efficacy variable was the diagnosis of PTDM as per American Diabetes Association criteria (2010) at any point up to 24 weeks postkidney transplantation. Secondary efficacy variables included incidence of composite efficacy failure (graft loss, biopsy-proven acute rejection or severe graft dysfunction: estimated glomerular filtration rate (Modification of Diet in Renal Disease-4) <30 mL/min per 1.73 m2), acute rejection and graft and patient survival. Results The full-analysis set included 1081 patients (arm 1: n = 528, arm 2: n = 553). Baseline characteristics and mean tacrolimus trough levels were comparable between arms. Week 24 Kaplan–Meier estimates of PTDM were similar for arm 1 versus arm 2 (17.4% vs 16.6%; P = 0.579). Incidence of composite efficacy failure, graft and patient survival, and mean estimated glomerular filtration rate were also comparable between arms. Biopsy-proven acute rejection and acute rejection were significantly higher in arm 2 versus arm 1 (13.6% vs 8.7%, P = 0.006 and 25.9% vs 18.2%, P = 0.001, respectively). Tolerability profiles were comparable between arms. Conclusions A prolonged-release tacrolimus, basiliximab, and mycophenolate mofetil immunosuppressive regimen is efficacious, with a low incidence of PTDM and a manageable tolerability profile over 24 weeks of treatment. A lower incidence of biopsy-proven acute rejection was seen in patients receiving corticosteroids tapered over 10 days plus an intraoperative corticosteroid bolus versus those receiving an intraoperative bolus only. PMID:27547871

Age- and sex-specific reference limits for creatinine, cystatin C and the estimated glomerular filtration rate.

PubMed

Hannemann, Anke; Friedrich, Nele; Dittmann, Kathleen; Spielhagen, Christin; Wallaschofski, Henri; Völzke, Henry; Rettig, Rainer; Endlich, Karlhans; Lendeckel, Uwe; Stracke, Sylvia; Nauck, Matthias

2011-11-14

Early detection of patients with chronic kidney disease is of great importance. This study developed reference limits for serum creatinine and serum cystatin C concentrations and for the estimated glomerular filtration rate (eGFR) in healthy subjects from the general population aged 25-65 years. This study defined a reference population including 985 subjects from the first follow-up of the Study of Health in Pomerania. Serum creatinine was measured with a modified kinetic Jaffé method. Serum cystatin C was measured with a nephelometric assay. The eGFR was calculated from serum creatinine according to the Cockcroft-Gault (eGFR(CG)) and the Modification of Diet in Renal Disease (eGFR(MDRD)) equation, respectively, as well as from serum cystatin C according to the formula by Larsson (eGFR(Larsson)). Non-parametric quantile regression was used to estimate the reference limits. For serum creatinine and serum cystatin C the 95th percentile and for eGFR(CG), eGFR(MDRD) and eGFR(Larsson) the 5th percentile were selected as reference limits. All data was weighted to reflect the age- and sex-structure of the German population in 2008. The reference limits for serum creatinine (men: 1.11-1.23 mg/dL; women: 0.93-1.00 mg/dL) and serum cystatin C levels (men: 0.92-1.04 mg/L; women: 0.84-1.02 mg/L) increased with advancing age. The reference limits for eGFR decreased with increasing age (eGFR(CG) men: 106.0-64.7 mL/min, women 84.4-57.9 mL/min; eGFR(MDRD) men: 82.5-62.2 mL/min/1.73 m², women 75.0-58.2 mL/min/1.73 m²; eGFR(Larsson) men: 85.5-72.9 mL/min, women 94.5-75.7 mL/min). This study presents age- and sex-specific reference limits for five measures of renal function based on quantile regression models.

Increased plasma Kidney Injury Molecule-1 suggests early progressive renal decline in non-proteinuric patients with Type 1 diabetes

PubMed Central

Nowak, Natalia; Skupien, Jan; Niewczas, Monika A.; Yamanouchi, Masayuki; Major, Melissa; Croall, Stephanie; Smiles, Adam; Warram, James H.; Bonventre, Joseph V.; Krolewski, Andrzej S.

2015-01-01

Progressively decreasing glomerular filtration rate (GFR), or renal decline, is seen in patients with type 1 diabetes (T1D) and normoalbuminuria or microalbuminuria. Here we examined the associations of kidney injury molecule-1 (KIM-1) in plasma and urine with the risk of renal decline and determine whether those associations are independent of markers of glomerular damage. The study group comprised patients with T1D from the 2nd Joslin Kidney Study of which 259 had normoalbuminuria and 203 had microalbuminuria. Serial measurements over 4 to 10 years of follow-up (median 8 years) of serum creatinine and cystatin C were used jointly to estimate eGFRcr-cys slopes and time of onset of CKD stage 3 or higher. Baseline urinary excretion of IgG2 and albumin were used as markers of glomerular damage, and urinary excretion of KIM-1 and its plasma concentration were used as markers of proximal tubular damage. All patients had normal renal function at baseline. During follow-up, renal decline (eGFRcr-cys loss 3.3% or more per year) developed in 96 patients and 62 progressed to CKD stage 3. For both outcomes, the risk rose with increasing baseline levels of plasma KIM-1. In multivariable models, elevated baseline plasma KIM-1 was strongly associated with risk of early progressive renal decline, regardless of baseline clinical characteristics, serum TNFR1 or markers of glomerular damage. Thus, damage to proximal tubules may play an independent role in the development of early progressive renal decline in non-proteinuric patients with T1D. PMID:26509588

Congolese children with sickle cell trait may exhibit glomerular hyperfiltration: A case control study.

PubMed

Aloni, Michel Ntetani; Ngiyulu, René Makwala; Nsibu, Célestin Ndosimao; Ekulu, Pépé Mfutu; Makulo, Jean Robert; Gini-Ehungu, Jean-Lambert; Nseka, Nazaire Mangani; Lepira, François Bompeka

2017-11-01

The prevalence of sickle cell trait is extremely high in sub-Saharan Africa. Recent studies have reported the impact of sickle cell carriers on renal function. However, data on renal abnormalities in children with sickle cell trait in this part of the world are unknown. In this report, we assess the glomerular function of children with sickle cell trait (SCT). A case control study was conducted to assess the glomerular function in 43 Congolese children with sickle cell trait (Hb-AS) matched for age to 65 children with sickle cell anemia in steady state (Hb-SS) and 67 normal controls (Hb-AA). There was a significant difference in the blood pressure levels between the Hb-AS group vs Hb-SS group (P<.05). The estimated glomerular filtration rate (eGFR) corrected for body surface area was increased in Hb-AS group compared to Hb-AA group, but there was no significant difference between the two groups (P=.48). At the same time, the eGFR was decreased, but no significantly so, in the Hb-AS group compared to the Hb-SS group (P=.19). The proportion of children with Hb-AS (16.3%) who had hyperfiltration was higher compared to the proportion (6.1%) found in the Hb-AA group, but lower compared to the proportion found in the Hb-SS group (30%). However, in both situations, the difference was not statistically significant. No case of proteinuria was detected in children with Hb-AS. It appears that at least one of six children with SCT had hyperfiltration. The findings could form a basis for further studies on this renal physiology among SCT individuals in Africa. © 2017 Wiley Periodicals, Inc.

Interfering RNA against PKC-α inhibits TNF-α-induced IP3R1 expression and improves glomerular filtration rate in rats with fulminant hepatic failure.

PubMed

Wang, Dong-Lei; Dai, Wen-Ying; Wang, Wen; Wen, Ying; Zhou, Ying; Zhao, Yi-Tong; Wu, Jian; Liu, Pei

2018-05-01

We have reported that tumor necrosis factor-α (TNF-α) is critical for reduction of glomerular filtration rate (GFR) in rats with fulminant hepatic failure (FHF). The present study aims to evaluate the underlying mechanisms of decreased GFR during acute hepatic failure. Rats with FHF induced by d-galactosamine plus lipopolysaccharide (GalN/LPS) were injected intravenously with recombinant lentivirus harboring short hairpin RNA against the protein kinase C-α ( PKC-α) gene (Lenti-shRNA-PKC-α). GFR, serum levels of aminotransferases, creatinine, urea nitrogen, potassium, sodium, chloride, TNF-α, and endothelin-1 (ET-1), as well as type 1 inositol 1,4,5-trisphosphate receptor (IP 3 R1) expression in renal tissue were assessed. The effects of PKC-α silencing on TNF-α-induced IP 3 R1, specificity protein 1 (SP-1), and c-Jun NH 2 -terminal kinase (JNK) expression, as well as cytosolic calcium content were determined in glomerular mesangial cell (GMCs) with RNAi against PKC-α. Renal IP 3 R1 overexpression was abrogated by pre-treatment with Lenti-shRNA-PKC-α. The PKC-α silence significantly improved the compromised GFR, reduced Cr levels, and reversed the decrease in glomerular inulin space and the increase in glomerular calcium content in GalN/LPS-exposed rats. TNF-α treatment increased expression of PKC-α, IP 3 R1, specificity protein 1 (SP-1), JNK, and p-JNK in GMCs and increased Ca 2 + release and binding activity of SP-1 to the IP 3 R1 promoter. These effects were blocked by transfection of siRNA against the PKC-α gene, and the PKC-α gene silence also restored cytosolic Ca 2+ concentration. RNAi targeting PKC-α inhibited TNF-α-induced IP 3 R1 overexpression and in turn improved compromised GFR in the development of acute kidney injury during FHF in rats.

Contrast media controversies in 2015: imaging patients with renal impairment or risk of contrast reaction.

PubMed

Davenport, Matthew S; Cohan, Richard H; Ellis, James H

2015-06-01

The incidence and significance of complications related to intravascular contrast material administration have become increasingly controversial. This review will highlight current thinking regarding the imaging of patients with renal impairment and those at risk for an allergiclike contrast reaction. The risk of contrast-induced acute kidney injury remains uncertain for patients with an estimated glomerular filtration rate (GFR) less than 45 mL/min/1.73 m(2), but if there is a risk, it is greatest in those with estimated GFR less than 30 mL/min/1.73 m(2). In this population, low-risk gadolinium-based contrast agents appear to have a large safety margin. Corticosteroid prophylaxis remains the standard of care in the United States for patients identified to be at high risk of a contrast reaction, but it has an incomplete mitigating effect on contrast reaction rates and the number needed to treat is large.

Renal tubular ACE-mediated tubular injury is the major contributor to microalbuminuria in early diabetic nephropathy.

PubMed

Eriguchi, Masahiro; Lin, Mercury; Yamashita, Michifumi; Zhao, Tuantuan V; Khan, Zakir; Bernstein, Ellen A; Gurley, Susan B; Gonzalez-Villalobos, Romer A; Bernstein, Kenneth E; Giani, Jorge F

2018-04-01

Diabetic nephropathy is a major cause of end-stage renal disease in developed countries. While angiotensin-converting enzyme (ACE) inhibitors are used to treat diabetic nephropathy, how intrarenal ACE contributes to diabetic renal injury is uncertain. Here, two mouse models with different patterns of renal ACE expression were studied to determine the specific contribution of tubular vs. glomerular ACE to early diabetic nephropathy: it-ACE mice, which make endothelial ACE but lack ACE expression by renal tubular epithelium, and ACE 3/9 mice, which lack endothelial ACE and only express renal ACE in tubular epithelial cells. The absence of endothelial ACE normalized the glomerular filtration rate and endothelial injury in diabetic ACE 3/9 mice. However, these mice developed tubular injury and albuminuria and displayed low renal levels of megalin that were similar to those observed in diabetic wild-type mice. In diabetic it-ACE mice, despite hyperfiltration, the absence of renal tubular ACE greatly reduced tubulointerstitial injury and albuminuria and increased renal megalin expression compared with diabetic wild-type and diabetic ACE 3/9 mice. These findings demonstrate that endothelial ACE is a central regulator of the glomerular filtration rate while tubular ACE is a key player in the development of tubular injury and albuminuria. These data suggest that tubular injury, rather than hyperfiltration, is the main cause of microalbuminuria in early diabetic nephropathy.

Apparent renal disease due to elevated creatinine levels associated with the use of boldenone.

PubMed

Winnett, Georgia; Cranfield, Lesley; Almond, Michael

2011-02-01

The widespread use of reporting estimated glomerular filtration rate (eGFR) alongside serum creatinine has led to a heightened appreciation of renal disease. However, creatinine is recognized as an insensitive marker of true GFR and therefore can lead to misdiagnosis of renal dysfunction in the absence of true pathology. We report the case of a 37-year-old male referred due to abnormal eGFR and creatinine in the absence of clinical signs, symptoms or other biochemical abnormalities of renal disease. Subsequent investigations based on a high index of suspicion for exogenous substance abuse led to a novel observation of significantly raised creatinine due to the presence of boldenone, an equine anabolic steroid commonly abused in body building.

The Renal Renin-Angiotensin System

ERIC Educational Resources Information Center

Harrison-Bernard, Lisa M.

2009-01-01

The renin-angiotensin system (RAS) is a critical regulator of sodium balance, extracellular fluid volume, vascular resistance, and, ultimately, arterial blood pressure. In the kidney, angiotensin II exerts its effects to conserve salt and water through a combination of the hemodynamic control of renal blood flow and glomerular filtration rate and…

HYDROXYUREA TREATMENT DECREASES GLOMERULAR HYPERFILTRATION IN CHILDREN WITH SICKLE CELL ANEMIA

PubMed Central

Aygun, Banu; Mortier, Nicole A.; Smeltzer, Matthew P.; Shulkin, Barry L.; Hankins, Jane S.; Ware, Russell E.

2015-01-01

Background Glomerular hyperfiltration and microalbuminuria/proteinuria are early manifestations of sickle nephropathy. The effects of hydroxyurea therapy on these renal manifestations of sickle cell anemia (SCA) are not well defined. Objective To investigate the effects of hydroxyurea on glomerular filtration rate (GFR) measured by 99mTc-DTPA clearance, and on microalbuminuria/proteinuria in children with SCA. Study Design Hydroxyurea Study of Long-Term Effects (HUSTLE) is a prospective study (NCT00305175) with the goal of describing the long-term cellular, molecular, and clinical effects of hydroxyurea therapy in SCA. Glomerular filtration rate, urine microalbumin, and serum cystatin C were measured before initiating hydroxyurea therapy and then repeated after 3 years. Baseline and Year 3 values for HUSTLE subjects were compared using the Wilcoxon Signed Rank test. Associations between continuous variables were evaluated using Spearman correlation coefficient. Results Twenty-three children with SCA (median age 7.5 years, range 2.5–14.0 years) received hydroxyurea at maximum tolerated dose (MTD, 24.4 ± 4.5 mg/kg/day, range 15.3–30.6 mg/kg/day). After three years of treatment, GFR measured by 99mTc-DTPA decreased significantly from 167 ± 46 mL/min/1.73m2 to 145 ± 27 mL/min/1.73m2 (p=0.016). This decrease in GFR was significantly associated with increase in fetal hemoglobin (p= 0.042) and decrease in lactate dehydrogenase levels (p=0.035). Urine microalbumin and cystatin C levels did not change significantly. Conclusions Hydroxyurea at MTD is associated with a decrease in hyperfiltration in young children with SCA. PMID:23255310

[Considerations when using creatinine as a measure of kidney function].

PubMed

Drion, I Iefke; Fokkert, M J Marion; Bilo, H J G Henk

2013-01-01

Reported serum creatinine concentrations can sometimes vary considerably, even when the renal function does less so or even not. This variation is partly due to true changes in actual serum concentration, and partly due to interferences in the measurement technique, thus not reflecting a true change in concentration. Increased or decreased endogenous creatinine production, ingested creatinine sources through meat eating or certain creatine formulations, and interference by either browning of chromogenic substances in Jaffe measurement techniques or promotors and inhibitors of enzymatic reaction methods do play a role. Reliable serum creatinine measurements are needed for renal function estimating equations. In screening circumstances and daily practice, chronic kidney disease staging is based on these estimated glomerular filtration rate values. Given the possible influences on reported serum creatinine concentrations, it is important for health care workers to remain critical when interpreting outcomes of renal function estimating equations and to not see every reported result based on an equation as a true reflection of renal function.

Ethanol at low concentrations protects glomerular podocytes through alcohol dehydrogenase and 20-HETE.

PubMed

McCarthy, Ellen T; Zhou, Jianping; Eckert, Ryan; Genochio, David; Sharma, Rishi; Oni, Olurinde; De, Alok; Srivastava, Tarak; Sharma, Ram; Savin, Virginia J; Sharma, Mukut

2015-01-01

Clinical studies suggest cardiovascular and renal benefits of ingesting small amounts of ethanol. Effects of ethanol, role of alcohol dehydrogenase (ADH) or of 20-hydroxyeicosatetraenoic acid (20-HETE) in podocytes of the glomerular filtration barrier have not been reported. We found that mouse podocytes at baseline generate 20-HETE and express ADH but not CYP2e1. Ethanol at high concentrations altered the actin cytoskeleton, induced CYP2e1, increased superoxide production and inhibited ADH gene expression. Ethanol at low concentrations upregulated the expression of ADH and CYP4a12a. 20-HETE, an arachidonic acid metabolite generated by CYP4a12a, blocked the ethanol-induced cytoskeletal derangement and superoxide generation. Ethanol at high concentration or ADH inhibitor increased glomerular albumin permeability in vitro. 20-HETE and its metabolite produced by ADH activity, 20-carboxy-arachidonic acid, protected the glomerular permeability barrier against an ADH inhibitor, puromycin or FSGS permeability factor. We conclude that ADH activity is required for glomerular function, 20-HETE is a physiological substrate of ADH in podocytes and that podocytes are useful biosensors to understand glomeruloprotective effects of ethanol. Published by Elsevier Inc.

Ethanol at Low Concentrations Protects Glomerular Podocytes through Alcohol Dehydrogenase and 20-HETE

PubMed Central

McCarthy, Ellen T.; Zhou, Jianping; Eckert, Ryan; Genochio, David; Sharma, Rishi; Oni, Olurinde; De, Alok; Srivastava, Tarak; Sharma, Ram; Savin, Virginia J.; Sharma, Mukut

2014-01-01

Clinical studies suggest cardiovascular and renal benefits of ingesting small amounts of ethanol. Effects of ethanol, role of alcohol dehydrogenase (ADH) or of 20-hydroxyeicosatetraenoic acid (20-HETE) in podocytes of the glomerular filtration barrier have not been reported. We found that mouse podocytes at baseline generate 20-HETE and express ADH but not CYP2e1. Ethanol at high concentrations altered the actin cytoskeleton, induced CYP2e1, increased superoxide production and inhibited ADH gene expression. Ethanol at low concentrations upregulated the expression of ADH and CYP4a12a. 20-HETE, an arachidonic acid metabolite generated by CYP4a12a, blocked the ethanol-induced cytoskeletal derangement and superoxide generation. Ethanol at high concentration or ADH inhibitor increased glomerular albumin permeability in vitro. 20-HETE and its metabolite produced by ADH activity, 20-carboxy-arachidonic acid, protected the glomerular permeability barrier against an ADH inhibitor, puromycin or FSGS permeability factor. We conclude that ADH activity is required for glomerular function, 20-HETE is a physiological substrate of ADH in podocytes and that podocytes are useful biosensors to understand glomeruloprotective effects of ethanol. PMID:25447342

Neuronal proteins are novel components of podocyte major processes and their expression in glomerular crescents supports their role in crescent formation.

PubMed

Sistani, Laleh; Rodriguez, Patricia Q; Hultenby, Kjell; Uhlen, Mathias; Betsholtz, Christer; Jalanko, Hannu; Tryggvason, Karl; Wernerson, Annika; Patrakka, Jaakko

2013-01-01

The podocyte has a central role in the glomerular filtration barrier typified by a sophisticated morphology of highly organized primary (major) and secondary (foot) processes. The molecular makeup of foot processes is well characterized, but that of major processes is poorly known. Previously, we profiled the glomerular transcriptome through large-scale sequencing and microarray profiling. Unexpectedly, the survey found expression of three neuronal proteins (Huntingtin interacting protein 1 (Hip1), neurofascin (Nfasc), and olfactomedin-like 2a (Olfml2a)), all enriched in the glomerulus. These proteins were expressed exclusively by podocytes, wherein they localized to major processes as verified by RT-PCR, western blotting, immunofluorescence, and immunoelectron microscopy. During podocyte development, these proteins colocalized with vimentin, confirming their association with major processes. Using immunohistochemistry, we found coexpression of Hip1 and Olfml2a along with the recognized podocyte markers synaptopodin and Pdlim2 in glomerular crescents of human kidneys, indicating the presence of podocytes in these lesions. Thus, three neuronal proteins are highly expressed in podocyte major process. Using these new markers we found that podocytes contribute to the formation of glomerular crescents.

Update on the renal toxicity of iodinated contrast drugs used in clinical medicine

PubMed Central

Andreucci, Michele; Faga, Teresa; Serra, Raffaele; De Sarro, Giovambattista; Michael, Ashour

2017-01-01

An important side effect of diagnostic contrast drugs is contrast-induced acute kidney injury (CI-AKI; a sudden decrease in renal function) occurring 48–72 hours after injection of a contrast drug that cannot be attributed to other causes. Its existence has recently been challenged, because of some retrospective studies in which the incidence of AKI was not different between subjects who received a contrast drug and those who did not, even using propensity score matching to prevent selection bias. For some authors, only patients with estimated glomerular filtration rate <30 mL/min/1.73 m2 are at significant risk of CI-AKI. Most agree that when renal function is normal, there is no CI-AKI risk. Many experimental studies, however, are in favor of the existence of CI-AKI. Contrast drugs have been shown to cause the following changes: renal vasoconstriction, resulting in a rise in intrarenal resistance (decrease in renal blood flow and glomerular filtration rate and medullary hypoxia); epithelial vacuolization and dilatation and necrosis of proximal tubules; potentiation of angiotensin II effects, reducing nitric oxide (NO) and causing direct constriction of descending vasa recta, leading to formation of reactive oxygen species in isolated descending vasa recta of rats microperfused with a solution of iodixanol; increasing active sodium reabsorption in the thick ascending limbs of Henle’s loop (increasing O2 demand and consequently medullary hypoxia); direct cytotoxic effects on endothelial and tubular epithelial cells (decrease in release of NO in vasa recta); and reducing cell survival, due to decreased activation of Akt and ERK1/2, kinases involved in cell survival/proliferation. Prevention is mainly based on extracellular volume expansion, statins, and N-acetylcysteine; conflicting results have been obtained with nebivolol, furosemide, calcium-channel blockers, theophylline, and hemodialysis. PMID:28579836

Thyrotropin levels are associated with chronic kidney disease among healthy subjects in cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

PubMed

Peixoto de Miranda, Érique José F; Bittencourt, Márcio Sommer; Goulart, Alessandra C; Santos, Itamar S; de Oliveira Titan, Silvia Maria; Ladeira, Roberto Marini; Barreto, Sandhi Maria; Lotufo, Paulo A; Benseñor, Isabela Judith Martins

2017-12-01

Few studies have evaluated a possible relationship between thyrotropin levels and glomerular filtration rate (GFR) and albumin/creatinine ratio in euthyroid subjects. We aimed to analyze this association using baseline data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Cross-sectionally, we included subjects with normal thyroid function and with subclinical hypothyroidism (SCH). We excluded individuals using medications that affect thyroid function. Linear and logistic regression models evaluated GFR estimated by Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) and albuminuria/creatinine ratio as dependent variables and thyrotropin quartiles in individuals with euthyroidism and SCH as independent variables, adjusted for demographical characteristics and diseases related to CKD. We included 13,193 subjects with a median age of 51 years [interquartile range, (IQR): 45-58], 6840 (51.8%) women, 12,416 (94.1%) euthyroid, and 777 (5.9%) with SCH. SCH subjects were characterized by higher age, triglycerides, frequency of white race, cardiovascular disease, CKD, and former smokers. In adjusted models, log-transformed TSH in euthyroid subjects was inversely and strongly associated with CKD (β = -2.181, 95% CI -2.714 to -1.648), P < 0.0001 for glomerular filtration rate and 4.528 (1.190-7.865) for albuminuria/creatinine ratio. Multivariate logistic models for euthyroid subjects showed an OR of 1.45 (95% CI 1.15-1.83) for GFR and of 1.95 (95% CI 1.08-3.54) for albuminuria/creatinine ratio in the fourth quartile of TSH using the first as the reference. Thyrotropin levels are independently associated with CKD in euthyroid subjects.

Interorgan handling of fibroblast growth factor-23 in humans.

PubMed

Verzola, Daniela; Ansaldo, Francesca; Milanesi, Samantha; Parodi, Emanuele Luigi; Rosa, Gian Marco; Sofia, Antonella; Bonanni, Alice; Viazzi, Francesca; Balbi, Manrico; Garibotto, Giacomo

2017-02-01

Fibroblast growth factor-23 (FGF-23) accumulates in blood of patients with chronic kidney disease (CKD) and is associated both with cardiovascular complications and disease progression. However, our knowledge of the sites and mechanisms that regulate plasma FGF-23 is still incomplete. We measured plasma intact FGF-23 across the kidney, splanchnic organs, and lung in 11 patients [estimated glomerular filtration rate (eGFR) 60 ± 6 ml/min] during elective diagnostic cardiac catheterizations. In these patients FGF-23 was removed by the kidney, with a fractional extraction (FE) of ∼22%. The FE of FGF-23 across the kidney was similar to that of creatinine (∼17%, P = NS). In addition, the FGF-23 FE by the kidney was significantly directly related to eGFR (r = 0.709 P = 0.018) and to kidney creatinine FE (r = 0.736 P = 0.013) but only as a trend to plasma phosphate levels (r = 0.55, P = 0.18). There was no difference in FGF-23 levels in blood perfusing splanchnic organs and cardiopulmonary bed. However, the arterial-venous difference of FGF-23 across the lung was directly related to FGF-23 pulmonary artery levels, suggesting that the lung, and possibly the heart, participate in the homeostasis of plasma FGF-23 when its systemic levels are increased. Our data show that the human kidney is the only site for FGF-23 removal from blood and suggest that FGF-23 is predominantly removed by glomerular filtration. The kidney ability to remove FGF-23 from the circulation likely accounts for the early increase in blood of FGF-23 in patients with CKD. Copyright © 2017 the American Physiological Society.

Importance of glomerular filtration rate change as surrogate endpoint for the future incidence of end-stage renal disease in general Japanese population: community-based cohort study.

PubMed

Kanda, Eiichiro; Usui, Tomoko; Kashihara, Naoki; Iseki, Chiho; Iseki, Kunitoshi; Nangaku, Masaomi

2018-04-01

Because of the necessity for extended period and large costs until the event occurs, surrogate endpoints are indispensable for implementation of clinical studies to improve chronic kidney disease (CKD) patients' prognosis. Subjects with serum creatinine level for a baseline period over 1-3 years were enrolled (n = 69,238) in this community-based prospective cohort study in Okinawa, Japan, and followed up for 15 years. The endpoint was end-stage renal disease (ESRD). The percent of estimated glomerular filtration rate (%eGFR) change was calculated on the basis of the baseline period. Subjects had a mean ± SD age, 55.59 ± 14.69 years; eGFR, 80.15 ± 21.15 ml/min/1.73 m 2 . Among the subjects recruited, 15.81% had a low eGFR (<60 ml/min/1.73 m 2 ) and 36.1/100,000 person years developed ESRD. Cox proportional hazards models adjusted for baseline characteristics showed that the risk of ESRD tended to be high with high rates of decrease in %eGFR changes over 2 or 3 years in the high- and low-eGFR groups. The specificities and positive predictive values for ESRD based on a cutoff value of %eGFR change of less than -30% over 2 or 3 years were high in the high- and low-eGFR groups. %eGFR change tends to be associated with the risk of ESRD. %eGFR change of less than -30% over 2 or 3 years can be a candidate surrogate endpoint for ESRD in the general Japanese population.

Robotic partial nephrectomy with intracorporeal renal hypothermia using ice slush.

PubMed

Kaouk, Jihad H; Samarasekera, Dinesh; Krishnan, Jayram; Autorino, Riccardo; Acka, Oktay; Brando, Luis Felipe; Laydner, Humberto; Zargar, Homayoun

2014-09-01

To outline our technique for intracorporeal cooling with ice slush during robotic partial nephrectomy (RPN), with real-time parenchymal temperature monitoring. Eleven consecutive patients with enhancing solid renal masses suitable for treatment with RPN between September 2013 and January 2014 were included in the analysis. Institutional review board approval and informed consent were obtained. Preoperative patient characteristics, intraoperative surgical parameters including patient body temperature and ipsilateral kidney temperature with real-time monitoring, and short-term functional outcomes were analyzed. Median age was 55 years (range, 39-75 years) and American Society of Anesthesiologists score was 3 (range, 2-4). Median tumor size was 4 cm (range, 2.3-7.1) and RENAL nephrometry score was 9 (range, 5-11). One patient had a solitary kidney. During cooling, the lowest median renal parenchymal temperature was 17.05°C (range, 11°C-26°C) and cold ischemia time was 27.17 minutes (range, 18-49 minutes). Median time to latest postoperative estimated glomerular filtration rate was 12 days (range, 2-30 days). Median glomerular filtration rate preservation was 81% (range, 47.9%-126%). There was one positive margin. There were no postoperative complications, and no patients experienced a prolonged ileus. The limitations of this study include a small number of patients and short-term follow-up. RPN with renal hypothermia using intracorporeal ice slush is technically feasible. Our simplified method of introducing the ice slush was free of complications and highly reproducible. The use of a needle temperature probe allowed us to monitor in real time cooling of the renal parenchyma. Copyright © 2014 Elsevier Inc. All rights reserved.

Sex differences in serum CK activity but not in glomerular filtration rate after resistance exercise: is there a sex dependent renal adaptative response?

PubMed

Amorim, Mayra Z; Machado, Marco; Hackney, Anthony C; de Oliveira, Wilkes; Luz, Carla Patrícia Novais; Pereira, Rafael

2014-01-01

We investigated differences in sex responses in serum CK activity and renal function measured by glomerular filtration rate (GFR) after an exercise session. Twenty-two healthy and trained volunteers (11 males and 11 females) performed 17 resistance exercises with 3 × 12 repetitions in a circuit training fashion. Subjects provided blood samples prior to exercise session, and at 24, 48, and 72 h following exercise sessions for creatine kinase and creatinine. Twenty-four-hour urine samples were collected before and 72 h after the exercise. Estimate (e) GFR was obtained by using the Chronic Kidney Disease Epidemiology Collaboration equation adjusted for males and females. After the exercise session, males showed greater serum CK activity than females (p < 0.02), serum creatinine increased 31.3 % for males and 29.8 % for females, and urinary creatinine decreased on average 5.4 % for males and 0.6 % for females, with no significant differences (p > 0.05) between sex for serum and urinary creatinine. eGFR decreased significantly for males (~10 %) and females (~8 %), but also without a difference between the sexes (p > 0.05). The correlation between CK and eGFR was significant for males (r = -0.794; p = 0.003), and females (r = -0.8875; p < 0.001). A significant negative correlation between CK activity and the eGFR indice of renal function in both males and females was observed. Additionally, the renal function compromise was similar for both sexes, despite males presenting greater exercise-induced skeletal muscle damage when compared to females.

Tolerating increases in the serum creatinine following aggressive treatment of chronic kidney disease, hypertension and proteinuria: pre-renal success.

PubMed

Hirsch, Sheldon; Hirsch, Jackie; Bhatt, Udayan; Rovin, Brad H

2012-01-01

Blood pressure (BP) reduction in patients with chronic kidney disease (CKD), particularly with a renin-angiotensin system inhibitor (RASI), commonly leads to an initial decrease in glomerular filtration rate. The current clinical guideline, based on studies with single RASIs, is to tolerate an increase in the serum creatinine only up to 30%. This guideline has aptly guided CKD care for over a decade, but should be updated in the contemporary context of more aggressive RASI and diuretic use. This study is a retrospective review of 48 mostly African-American patients with CKD treated with multiple and/or high-dose renin-angiotensin system (RAS) inhibition and diuretics, targeting both low BP and reduction of urine protein. RASI was not reduced in response to initial increases in serum creatinine greater than 30%. A clinically well-tolerated increase in serum creatinine over 30% during the first year occurred in 41% of the patients. Treatment was unaltered, and target goals for BP and urine protein were typically achieved. After the point of maximal serum creatinine in the first year, these patients had minimal progression of disease over the next 6 years, with a long-term estimated glomerular filtration rate slope of only -0.52 ml/min/year/1.73 m(2). Only 25% progressed to end-stage renal disease or death. The 30% limitation to initial increases in the serum creatinine still pertains for single RASI at usual doses. However, favorable long-term outcomes suggest that initial increases over 30% should be tolerated in the context of dual goal-directed, more aggressive RASI and diuretic use. Copyright © 2012 S. Karger AG, Basel.

[Concordance of glomerular filtration rate with creatinine clearance in 24-hour urine and Schwartz and Schwartz updated].

PubMed

Salazar-Gutiérrez, María Luisa; Ochoa-Ponce, Cristina; Lona-Reyes, Juan Carlos; Gutiérrez-Íñiguez, Sara Ivonne

Reference methods for the quantification of the glomerular filtration rate (GFR) are difficult to use in clinical practice; formulas for evaluating GFR based on serum creatinine (SCr) and/or creatinine clearance are used. The aim of this study was to quantify the correlation and concordance of GFR with creatinine clearance in 24-hour urine (GFR24) and Schwartz and Schwartz updated formulas. Cross-sectional study involving healthy pediatric patients and with chronic kidney disease (CKD) from 5 to 16.9 years. Linear correlation between GFR 24 and two formulas was evaluated with the Pearson correlation coefficient (r) and intraclass correlation coefficient (ICC). We studied 134 patients, of which 59.7% were male. Mean age was 10.8 years. The average GFR24 was 140.34ml/min/1.73m 2 ; 34.3% (n=46) had GFR <90ml/min/1.73m 2 . Moderate linear correlation between GFR24 and Schwartz (r= 0.63) and Schwartz updated (r= 0.65) formulas was observed. There was good concordance between the GFR24 and Schwartz (ICC= 0.77) and updated Schwartz (ICC= 0.77) formulas. Schwartz classical formula in patients with GFR24 ≥ 90ml/min/1.73m 2 estimated higher values, while Schwartz updated underestimated values. There is moderate correlation and good concordance between the GFR24 and Schwartz and Schwartz updated formulas. The concordance was better in patients with obesity and lower in women, patients with hyperfiltration and normal weight. Copyright © 2016 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Initial formal toxicity evaluation of APC-2, a novel fluorescent tracer agent for real-time measurement of glomerular filtration rate in preparation for a first-in-man clinical trial

NASA Astrophysics Data System (ADS)

Bugaj, Joseph E.; Dorshow, Richard B.

2014-03-01

The fluorescent tracer agent 2,5-bis[N-(1-carboxy-2-hydroxy)]carbamoyl-3,6-diaminopyrazine, designated APC-2, has been developed with properties and attributes necessary for use as a direct measure of glomerular filtration rate (GFR). Comparison to known standard exogenous GFR agents in animal models has demonstrated an excellent correlation. A clinical trial to demonstrate this same correlation in humans is in preparation. A battery of formal toxicity tests necessary for regulatory clearance to proceed with a clinical trial has been recently completed on this new fluorescent tracer agent. These include single dose toxicity studies in rats and dogs to determine overall toxicity and toxicokinetics of the compound. Blood compatibility, mutation assay, chromosomal aberration assay, and several other assays were also completed. Toxicity assessments were based on mortality, clinical signs, body weight, food consumption and anatomical pathology. Blood samples were collected to assess pharmacokinetic parameters including half-life, area under the curve, and clearance. Urine samples were collected to assess distribution. Doses of up to 200-300 times the estimated human dose were administered. No test-article related effects were noted on body weight, food consumption, ophthalmic observations and no abnormal pathology was seen in either macroscopic or microscopic evaluations of any organs or tissues. All animals survived to scheduled sacrifice. Transient discoloration of skin and urine was noted at the higher dose levels in both species as expected from a highly fluorescent compound and was not considered pathological. Thus initial toxicology studies of this new fluorescent tracer agent APC-2 have resulted in no demonstrable pathological test article concerns.

The decline in kidney function with chromium exposure is exacerbated with co-exposure to lead and cadmium.

PubMed

Tsai, Tsung-Lin; Kuo, Chin-Chi; Pan, Wen-Harn; Chung, Yu-Teh; Chen, Chiu-Ying; Wu, Trong-Neng; Wang, Shu-Li

2017-09-01

Environmental factors contribute significantly to the pathogenesis of chronic kidney disease. However, these factors, and particularly the toxic effects of heavy metals, have not been completely evaluated. Chromium is a widespread industrial contaminant that has been linked to nephrotoxicity in animal and occupational population studies. Nevertheless, its role in population renal health and its potential interactions with other nephrotoxic metals, such as lead and cadmium, remain unknown. We assessed the association between exposure to chromium, lead, and cadmium with renal function using estimated glomerular filtration rate (eGFR) in an analysis of 360 Taiwanese adults aged 19-84 years from the National Nutrition and Health Survey in Taiwan (2005-2008). Doubling of urinary chromium or lead decreased the eGFR by -5.99 mL/min/1.73 m 2 (95% confidence interval -9.70, -2.27) and -6.61 (-9.71, -3.51), respectively, after adjusting for age, sex, body mass index, hypertension, diabetes, cigarette smoking, sodium intake, education, urinary volume, and other metals. For those in the highest tertile of cadmium exposure, the eGFR decreased by -12.68 mL/min/1.73 m 2 (95% confidence interval -20.44, -4.93) and -11.22 mL/min/1.73 m 2 (-17.01, -5.44), as urinary chromium or lead levels doubled, respectively. Thus, there is a significant and independent association between chromium exposure and decreased renal function. Furthermore, co-exposure to chromium with lead and cadmium is potentially associated with additional decline in the glomerular filtration rate in Taiwanese adults. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Food Insecurity, CKD, and Subsequent ESRD in US Adults.

PubMed

Banerjee, Tanushree; Crews, Deidra C; Wesson, Donald E; Dharmarajan, Sai; Saran, Rajiv; Ríos Burrows, Nilka; Saydah, Sharon; Powe, Neil R

2017-07-01

Poor access to food among low-income adults has been recognized as a risk factor for chronic kidney disease (CKD), but there are no data for the impact of food insecurity on progression to end-stage renal disease (ESRD). We hypothesized that food insecurity would be independently associated with risk for ESRD among persons with and without earlier stages of CKD. Longitudinal cohort study. 2,320 adults (aged ≥ 20 years) with CKD and 10,448 adults with no CKD enrolled in NHANES III (1988-1994) with household income ≤ 400% of the federal poverty level linked to the Medicare ESRD Registry for a median follow-up of 12 years. Food insecurity, defined as an affirmative response to the food-insecurity screening question. Development of ESRD. Demographics, income, diabetes, hypertension, estimated glomerular filtration rate, and albuminuria. Dietary acid load was estimated from 24-hour dietary recall. We used a Fine-Gray competing-risk model to estimate the relative hazard (RH) for ESRD associated with food insecurity after adjusting for covariates. 4.5% of adults with CKD were food insecure. Food-insecure individuals were more likely to be younger and have diabetes (29.9%), hypertension (73.9%), or albuminuria (90.4%) as compared with their counterparts (P<0.05). Median dietary acid load in the food-secure versus food-insecure group was 51.2 mEq/d versus 55.6 mEq/d, respectively (P=0.05). Food-insecure adults were more likely to develop ESRD (RH, 1.38; 95% CI, 1.08-3.10) compared with food-secure adults after adjustment for demographics, income, diabetes, hypertension, estimated glomerular filtration rate, and albuminuria. In the non-CKD group, 5.7% were food insecure. We did not find a significant association between food insecurity and ESRD (RH, 0.77; 95% CI, 0.40-1.49). Use of single 24-hour diet recall; lack of laboratory follow-up data and measure of changes in food insecurity over time; follow-up of cohort ended 10 years ago. Among adults with CKD, food insecurity was independently associated with a higher likelihood of developing ESRD. Innovative approaches to address food insecurity should be tested for their impact on CKD outcomes. Copyright © 2016 National Kidney Foundation, Inc. All rights reserved.

Existing creatinine-based equations overestimate glomerular filtration rate in Indians.

PubMed

Kumar, Vivek; Yadav, Ashok Kumar; Yasuda, Yoshinari; Horio, Masaru; Kumar, Vinod; Sahni, Nancy; Gupta, Krishan L; Matsuo, Seiichi; Kohli, Harbir Singh; Jha, Vivekanand

2018-02-01

Accurate estimation of glomerular filtration rate (GFR) is important for diagnosis and risk stratification in chronic kidney disease and for selection of living donors. Ethnic differences have required correction factors in the originally developed creatinine-based GFR estimation equations for populations around the world. Existing equations have not been validated in the vegetarian Indian population. We examined the performance of creatinine and cystatin-based GFR estimating equations in Indians. GFR was measured by urinary clearance of inulin. Serum creatinine was measured using IDMS-traceable Jaffe's and enzymatic assays, and cystatin C by colloidal gold immunoassay. Dietary protein intake was calculated by measuring urinary nitrogen appearance. Bias, precision and accuracy were calculated for the eGFR equations. A total of 130 participants (63 healthy kidney donors and 67 with CKD) were studied. About 50% were vegetarians, and the remainder ate meat 3.8 times every month. The average creatinine excretion were 14.7 mg/kg/day (95% CI: 13.5 to 15.9 mg/kg/day) and 12.4 mg/kg/day (95% CI: 11.2 to 13.6 mg/kg/day) in males and females, respectively. The average daily protein intake was 46.1 g/day (95% CI: 43.2 to 48.8 g/day). The mean mGFR in the study population was 51.66 ± 31.68 ml/min/1.73m 2 . All creatinine-based eGFR equations overestimated GFR (p < 0.01 for each creatinine based eGFR equation). However, eGFR by CKD-EPI Cys was not significantly different from mGFR (p = 0.38). The CKD-EPI Cys exhibited lowest bias [mean bias: -3.53 ± 14.70 ml/min/1.73m 2 (95% CI: -0.608 to -0.98)] and highest accuracy (P 30 : 74.6%). The GFR in the healthy population was 79.44 ± 20.19 (range: 41.90-134.50) ml/min/1.73m 2 . Existing creatinine-based GFR estimating equations overestimate GFR in Indians. An appropriately powered study is needed to develop either a correction factor or a new equation for accurate assessment of kidney function in the Indian population.

Effect of Tenofovir Disoproxil Fumarate on Incidence of Chronic Kidney Disease and Rate of Estimated Glomerular Filtration Rate Decrement in HIV-1–Infected Treatment-Naïve Asian Patients: Results from 12-Year Observational Cohort

PubMed Central

Suzuki, Soichiro; Kawasaki, Yohei; Kurosawa, Takuma; Mutoh, Yoshikazu; Kikuchi, Yoshimi; Gatanaga, Hiroyuki; Oka, Shinichi

2017-01-01

Abstract Little evidence is available for the incidence of chronic kidney disease (CKD) and rate of estimated glomerular filtration rate (eGFR) decrement among Asians with low body weight who are susceptible to tenofovir disoproxil fumarate (TDF) nephrotoxicity. In this 12-year observational cohort in Tokyo, we examined 1383 treatment-naïve HIV-1-infected Asians [720 started TDF-containing (TDF group) and 663 started non-TDF-containing (control) combination antiretroviral therapy (cART)]. The CKD incidence was calculated, and the effect of TDF use on CKD development was estimated using logistic regression. The eGFR slopes, before and after cART initiation, were estimated using mixed-effects linear spline models. Most patients were males (median weight, 62.6 kg; 83% started ritonavir-boosted protease inhibitors; median observation duration, 5.08 years). CKD developed in 150 patients (10.8%), with an incidence of 20.6 per 1000 person-years [confidence interval (95% CI), 17.6–24.2]. None developed end-stage renal disease. TDF use was associated with CKD [odds ratio (OR), 1.8; 95% CI, 1.00–3.13; p = 0.052]. The cumulative mean loss in the TDF group, relative to the control, increased over time after 1, 4, and 8 years of TDF exposure (−3.8, −5.5, and −9.0 mL/min/1.73 m2, respectively; p < 0.0001). The eGFR rapidly declined during the first 3 months of cART, particularly in the TDF group (−26.4 vs. −7.4 mL/min/1.73 m2/year in the control). In the TDF group, cART introduction was significantly associated with a faster rate of eGFR decline (from −0.44 to −2.11 mL/min/1.73 m2/year; p = 0.010), whereas in the control, the difference was not significant. For HIV-1-infected Asian patients with low body weight, TDF-containing cART is associated with CKD and faster eGFR declines. PMID:28282247

Troponin T as a Predictor of End-Stage Renal Disease and All-Cause Death in African Americans and Whites From Hypertensive Families.

PubMed

Hickson, LaTonya J; Rule, Andrew D; Butler, Kenneth R; Schwartz, Gary L; Jaffe, Allan S; Bartley, Adam C; Mosley, Thomas H; Turner, Stephen T

2015-11-01

To evaluate cardiac troponin T (cTnT) as a predictor of end-stage renal disease (ESRD) and death in a cohort of African American and white community-dwelling adults with hypertensive families. A total of 3050 participants (whites from Rochester, Minnesota; African Americans from Jackson, Mississippi) of the Genetic Epidemiology Network of Arteriopathy study were followed from baseline examination (June 1, 1996, through August 31, 2000) through January 22, 2010. Cox proportional hazards regression models were used to examine the association of cTnT with ESRD and death after adjusting for traditional risk factors. Cohort demographic characteristics and measurements included 1395 whites (45.7%), 2174 hypertensive (71.3%), 992 estimated glomerular filtration rate of less than 60 mL/min per 1.73 m(2) (32.5%), 1574 high-sensitivity C-reactive protein level of greater than 3 mg/L (51.6%), and 66 abnormal cTnT level of 0.01 ng/mL or higher (2.2%). The estimated cumulative incidence of ESRD at 10 years was 27.4% among those with abnormal cTnT levels compared with 1.3% for those with normal levels. Similarly, the estimated cumulative incidence of death at 10 years was 47% among those with abnormal cTnT compared with 7.3% among those with normal cTnT. Abnormal cTnT levels were strongly associated with ESRD and death. This effect was attenuated but was still highly significant after adjustment for demographic characteristics, estimated glomerular filtration rate, and traditional risk factors for ESRD (unadjusted hazard ratio [HR], 23.91; 95% CI, 12.9-44.2; adjusted HR, 2.81; 95% CI, 1.3-5.9) and death (unadjusted HR, 8.43; 95% CI, 6.0-11.9; adjusted HR, 3.46; 95% CI, 2.3-5.1). Cardiac troponin T makes an independent contribution to the prediction of ESRD and all-cause death in community-dwelling individuals beyond traditional risk markers. Further studies may be needed to determine whether cTnT screening in individuals with hypertension or in a subset of hypertensive individuals would help identify those at risk of ESRD and all-cause death. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

The Evolving Complexity of the Podocyte Cytoskeleton.

PubMed

Schell, Christoph; Huber, Tobias B

2017-11-01

Podocytes exhibit a unique cytoskeletal architecture that is fundamentally linked to their function in maintaining the kidney filtration barrier. The cytoskeleton regulates podocyte shape, structure, stability, slit diaphragm insertion, adhesion, plasticity, and dynamic response to environmental stimuli. Genetic mutations demonstrate that even slight impairment of the podocyte cytoskeletal apparatus results in proteinuria and glomerular disease. Moreover, mechanisms underpinning all acquired glomerular pathologies converge on disruption of the cytoskeleton, suggesting that this subcellular structure could be targeted for therapeutic purposes. This review summarizes our current understanding of the function of the cytoskeleton in podocytes and the associated implications for pathophysiology. Copyright © 2017 by the American Society of Nephrology.

[Effect of fasting-dietary therapy in patients with arterial hypertension and obesity].

PubMed

Murav'ev, S A; Okonechnikova, N S; Dmitrieva, O A; Makarova, G A

2010-01-01

35 patients with arterial hypertension and obesity against the background of fasting-diet therapy and after 1 and 6 months after treatment conducted daily monitoring of blood pressure, microalbuminuria and glomerular filtration rate, the study of color and contrast sensitivity of retinal eyes. Fasting-diet therapy within 11 days results in reliable reduced daily average AD and stabilization of load pressure indicators; reduction originally pathological microalbuminurii at 18%, increase in the number of patients with normal speed glomerular filtering 48%; improving of eyes function, these changes are saved within 1-6 months after treatment without the using of antihypertensive therapy.

Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality.

PubMed

Coresh, Josef; Turin, Tanvir Chowdhury; Matsushita, Kunihiro; Sang, Yingying; Ballew, Shoshana H; Appel, Lawrence J; Arima, Hisatomi; Chadban, Steven J; Cirillo, Massimo; Djurdjev, Ognjenka; Green, Jamie A; Heine, Gunnar H; Inker, Lesley A; Irie, Fujiko; Ishani, Areef; Ix, Joachim H; Kovesdy, Csaba P; Marks, Angharad; Ohkubo, Takayoshi; Shalev, Varda; Shankar, Anoop; Wen, Chi Pang; de Jong, Paul E; Iseki, Kunitoshi; Stengel, Benedicte; Gansevoort, Ron T; Levey, Andrew S

2014-06-25

The established chronic kidney disease (CKD) progression end point of end-stage renal disease (ESRD) or a doubling of serum creatinine concentration (corresponding to a change in estimated glomerular filtration rate [GFR] of −57% or greater) is a late event. To characterize the association of decline in estimated GFR with subsequent progression to ESRD with implications for using lesser declines in estimated GFR as potential alternative end points for CKD progression. Because most people with CKD die before reaching ESRD, mortality risk also was investigated. Individual meta-analysis of 1.7 million participants with 12,344 ESRD events and 223,944 deaths from 35 cohorts in the CKD Prognosis Consortium with a repeated measure of serum creatinine concentration over 1 to 3 years and outcome data. Transfer of individual participant data or standardized analysis of outputs for random-effects meta-analysis conducted between July 2012 and September 2013, with baseline estimated GFR values collected from 1975 through 2012. End-stage renal disease (initiation of dialysis or transplantation) or all-cause mortality risk related to percentage change in estimated GFR over 2 years, adjusted for potential confounders and first estimated GFR. The adjusted hazard ratios (HRs) of ESRD and mortality were higher with larger estimated GFR decline. Among participants with baseline estimated GFR of less than 60 mL/min/1.73 m2, the adjusted HRs for ESRD were 32.1 (95% CI, 22.3-46.3) for changes of −57% in estimated GFR and 5.4 (95% CI, 4.5-6.4) for changes of −30%. However, changes of −30% or greater (6.9% [95% CI, 6.4%-7.4%] of the entire consortium) were more common than changes of −57% (0.79% [95% CI, 0.52%-1.06%]). This association was strong and consistent across the length of the baseline period (1 to 3 years), baseline estimated GFR, age, diabetes status, or albuminuria. Average adjusted 10-year risk of ESRD (in patients with a baseline estimated GFR of 35 mL/min/1.73 m2) was 99% (95% CI, 95%-100%) for estimated GFR change of −57%, was 83% (95% CI, 71%-93%) for estimated GFR change of −40%, and was 64% (95% CI, 52%-77%) for estimated GFR change of −30% vs 18% (95% CI, 15%-22%) for estimated GFR change of 0%. Corresponding mortality risks were 77% (95% CI, 71%-82%), 60% (95% CI, 56%-63%), and 50% (95% CI, 47%-52%) vs 32% (95% CI, 31%-33%), showing a similar but weaker pattern. Declines in estimated GFR smaller than a doubling of serum creatinine concentration occurred more commonly and were strongly and consistently associated with the risk of ESRD and mortality, supporting consideration of lesser declines in estimated GFR (such as a 30% reduction over 2 years) as an alternative end point for CKD progression.

Effect of injected rotenone on the production and composition of urine from the rainbow trout (Salmo gairdneri)

USGS Publications Warehouse

Erickson, D.A.; Gingerich, W.H.

1986-01-01

Renal function was evaluated in adult rainbow trout (Salmo gairdneri) dosed i.a. with rotenone at 225 and 275 μg/kg. The chemical composition of urine samples and urine flow rates collected over a 5-h pretreatment period were compared with hourly urine samples collected over a 5-h posttreatment period. Significant increases in osmolality and in concentrations of sodium, potassium, chloride, glucose, and total protein were observed in the urine of treated fish. Urine solute concentrations reached maximum values within 1 to 3 h after treatment and decreased thereafter, indicating that the effects were reversible. Concentrations of sodium and chloride were highly correlated in 2-h posttreatment urine samples at the low (r = 0.922) and high (r = 0.981) rotenone treatments. Urine flow rates were reduced in trout at each dose of rotenone but the decrease in volume of urine voided was not dose-dependent. In a separate study, [14C]polyethylene glycol was used as a filtration marker to determine the effect of rotenone treatment (225 &mu:g/kg) on urine flow rate, glomerular filtration rate, and renal water reabsorption. We showed that posttreatment urine flow rates were reduced partly by reduced glomerular filtration and partly by increased water reabsorption. Transient increases in plasma osmolality and hematocrit also were observed 0.5 h after rotenone treatment.

Differential glomerular filtration rate in diagnosis of renovascular hypertension and follow-up of balloon angioplasty

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lamki, L.; Spence, J.D.; MacDonald, A.C.

Two hundred nine hypertensive patients with high stimulated plasma renin levels were screened for renovascular hypertension using Tc-99m DTPA renal scintigraphy. Differential glomerular filtration rate (Diff-GFR) was obtained by integrating the area under the background-subtracted renogram of each kidney between 1 and 3 minutes. 50 patients who also had undergone selective renal angiography were divided into four groups according to Diff-GFR contribution by one of the kidneys. If one kidney contributed 45-50% of total GFR, this was regarded as normal. A Diff-GFR of less than 45% was very considered to be very suggestive of renovascular hypertension in the appropriate clinicalmore » setting, while a Diff-GFR of less than 20% indicated that the renal artery might not be amenable to successful balloon angioplasty. Diff-GFR following balloon angioplasty closely reflected the early clinical response of the patients--and in some cases progressive Diff-GFR improvement was observed several months later. Diff-GFR as a scintigraphic criterion for renovascular hypertension has a sensitivity of 93%, specificity of 74%, and accuracy of 85%.« less

Developmental changes in renal tubular transport - An overview

PubMed Central

Gattineni, Jyothsna; Baum, Michel

2013-01-01

The adult kidney maintains a constant volume and composition of extracellular fluid despite changes in water and salt intake. The neonate is born with a kidney that has a small fraction of the glomerular filtration rate of the adult and immature tubules that function at a lower capacity than that of the mature animal. None the less, the neonate is also able to maintain a constant extracellular fluid volume and composition. Postnatal renal tubular development was once thought to be due to an increase in the transporter abundance to meet the developmental increase in glomerular filtration rate. However, postnatal renal development of each nephron segment is quite complex. There are isoform changes of several transporters as well as developmental changes in signal transduction that affect the capacity of renal tubules to reabsorb solutes and water. This review will discuss neonatal tubular function with an emphasis on the differences that have been found between the neonate and adult. We will also discuss some of the factors that are responsible for the maturational changes in tubular transport that occur during postnatal renal development. PMID:24253590

Developmental changes in renal tubular transport-an overview.

PubMed

Gattineni, Jyothsna; Baum, Michel

2015-12-01

The adult kidney maintains a constant volume and composition of extracellular fluid despite changes in water and salt intake. The neonate is born with a kidney that has a small fraction of the glomerular filtration rate of the adult and immature tubules that function at a lower capacity than that of the mature animal. Nonetheless, the neonate is also able to maintain a constant extracellular fluid volume and composition. Postnatal renal tubular development was once thought to be due to an increase in the transporter abundance to meet the developmental increase in glomerular filtration rate. However, postnatal renal development of each nephron segment is quite complex. There are isoform changes of several transporters as well as developmental changes in signal transduction that affect the capacity of renal tubules to reabsorb solutes and water. This review will discuss neonatal tubular function with an emphasis on the differences that have been found between the neonate and adult. We will also discuss some of the factors that are responsible for the maturational changes in tubular transport that occur during postnatal renal development.

Kidney Response to the Spectrum of Diet-Induced Acid Stress.

PubMed

Goraya, Nimrit; Wesson, Donald E

2018-05-11

Chronic ingestion of the acid (H⁺)-producing diets that are typical of developed societies appears to pose a long-term threat to kidney health. Mechanisms employed by kidneys to excrete this high dietary H⁺ load appear to cause long-term kidney injury when deployed over many years. In addition, cumulative urine H⁺ excretion is less than the cumulative increment in dietary H⁺, consistent with H⁺ retention. This H⁺ retention associated with the described high dietary H⁺ worsens as the glomerular filtration rate (GFR) declines which further exacerbates kidney injury. Modest H⁺ retention does not measurably change plasma acid⁻base parameters but, nevertheless, causes kidney injury and might contribute to progressive nephropathy. Current clinical methods do not detect H⁺ retention in its early stages but the condition manifests as metabolic acidosis as it worsens, with progressive decline of the glomerular filtration rate. We discuss this spectrum of H⁺ injury, which we characterize as “H⁺ stress”, and the emerging evidence that high dietary H⁺ constitutes a threat to long-term kidney health.

Comparison of glomerular filtration rate between greyhounds and non-Greyhound dogs.

PubMed

Drost, Wm Tod; Couto, C Guillermo; Fischetti, Anthony J; Mattoon, John S; Iazbik, Cristina

2006-01-01

Greyhounds have significantly higher serum creatinine (SCr) concentration than do non-Greyhound dogs that may be attributable to differences in glomerular filtration rate (GFR). By means of plasma clearance of technetium Tc 99m diethylenetriaminepentaacetic acid, GFR was measured in 10 Greyhounds and 10 non-Greyhound dogs with normal findings of physical examination, CBC, serum biochemical analysis, and urinalysis. Dogs were fed the same diet for a minimum of 6 weeks before GFR data collection. Greyhounds had significantly higher mean +/- SD GFR (3.0 +/- 0.1 vs 2.5 +/- 0.2 ml/min/ kg; P = .01) and SCr concentration (1.8 +/- 0.1 vs 1.5 +/- 0.1 mg/dL; P = .03) than did non-Greyhound dogs, but the serum urea nitrogen (SUN) concentration was not significantly different (18 +/- 1 vs 18 +/- 2 mg/dL; P = .8). Therefore, the higher SCr concentration in Greyhounds is not attributable to decreased GFR, and may be associated with the high muscle mass in the breed. Healthy Greyhounds have higher GFR than do non-Greyhound dogs.

Insight into podocyte differentiation from the study of human genetic disease: nail-patella syndrome and transcriptional regulation in podocytes.

PubMed

Morello, Roy; Lee, Brendan

2002-05-01

In recent years, our understanding of the molecular basis of kidney development has benefited from the study of rare genetic diseases affecting renal function. This has especially been the case with the differentiation of the highly specialized podocyte in the pathogenesis of human disorders and mouse phenotypes affecting the renal filtration barrier. This filtration barrier represents the end product of a complex series of signaling events that produce a tripartite structure consisting of interdigitating podocyte foot processes with intervening slit diaphragms, the glomerular basement membrane, and the fenestrated endothelial cell. Dysregulation of unique cytoskeletal and extracellular matrix proteins in genetic forms of nephrotic syndrome has shown how specific structural proteins contribute to podocyte function and differentiation. However, much less is known about the transcriptional determinants that both specify and maintain this differentiated cell. Our studies of a skeletal malformation syndrome, nail-patella syndrome, have shown how the LIM homeodomain transcription factor, Lmx1b, contributes to transcriptional regulation of glomerular basement membrane collagen expression by podocytes. Moreover, they raise intriguing questions about more global transcriptional regulation of podocyte morphogenesis.

Hyperkalemia in young children: blood pressure checked?

PubMed

Hollander, Richard; Mortier, Geert; van Hoeck, Koen

2016-12-01

Hyperkalemia in young children is a rare phenomenon and in many cases caused by hemolysis in the specimen due to difficulties in obtaining a sample. However, hyperkalemia can also be a sign of a rare Mendelian syndrome known as familial hyperkalemic hypertension or pseudohypoaldosteronism type II. This disease is characterized by hyperkalemia, hypertension, and mild hyperchloremic metabolic acidosis (with normal anion gap) despite normal glomerular filtration. Full recovery of these abnormalities with thiazide diuretics is essential not to miss the diagnosis of this syndrome. We describe two young patients with hyperkalemia as an incidental finding who were subsequently diagnosed with this rare endocrine disorder. Genetic testing revealed mutations in two recently discovered genes, the study of which has helped to unravel the pathophysiologic pathways. In patients with hyperkalemia and a normal glomerular filtration rate, the clinician should actively search for abnormalities in blood pressure since recognizing this condition can lead to simple, cheap, and effective treatment. What is Known: • True Hyperkalemia is rare in pediatrics and can be a sign of FHHt. What is New: • KLHL3 & CUL3 are recently discovered genes helping unravel the pathophysiologic pathway of FHHt.

Results of the first-in-human clinical trial for MB-102, a novel fluorescent tracer agent for real-time measurement of glomerular filtration rate

NASA Astrophysics Data System (ADS)

Dorshow, Richard B.; Debreczeny, Martin P.; Dowling, Thomas C.

2015-03-01

The fluorescent tracer agent 2,5-bis[N-(1-carboxy-2-hydroxy)]carbamoyl-3,6-diaminopyrazine, designated MB-102, has been developed with properties and attributes necessary for use as a direct measure of glomerular filtration rate (GFR). Comparison to known standard exogenous GFR agents in animal models has demonstrated an excellent correlation. A clinical trial to demonstrate this same correlation in humans is in progress. This clinical trial is the first in a series of trials necessary to obtain regulatory clearance from the FDA. We report herein the comparison of plasma pharmacokinetics between MB-102 and the known standard exogenous GFR agent Iohexol in healthy subjects with normal renal function. Post simultaneous administration of both agents, blood samples over a period of 12 hours were collected from each subject to assess pharmacokinetic parameters including GFR. Urine samples were collected over this same period to assess percent injected dose recovered in the urine. Results indicate MB-102 is a GFR agent in humans from the comparison to the standard agent.

Fluorescence-enhanced europium complexes for the assessment of renal function

NASA Astrophysics Data System (ADS)

Chinen, Lori K.; Galen, Karen P.; Kuan, K. T.; Dyszlewski, Mary E.; Ozaki, Hiroaki; Sawai, Hiroaki; Pandurangi, Raghootama S.; Jacobs, Frederick G.; Dorshow, Richard B.; Rajagopalan, Raghavan

2008-02-01

Real-time, non-invasive assessment of glomerular filtration rate (GFR) is essential not only for monitoring critically ill patients at the bedside, but also for staging and monitoring patients with chronic kidney disease. In our pursuit to develop exogenous luminescent probes for dynamic optical monitoring of GFR, we have prepared and evaluated Eu 3+ complexes of several diethylenetriamine pentaacetate (DTPA)-monoamide ligands bearing molecular "antennae" to enhance metal fluorescence via the intramolecular ligand-metal fluorescence resonance energy transfer (FRET) process. The results show that Eu-DTPA-monoamide complex 13a, which contains a quinoxanlinyl antenna, exhibits large (c.a. 2700-fold) Eu 3+ fluorescence enhancement over Eu-DTPA (4c). Indeed, complex 13a exhibits the highest fluorescent enhancement observed thus far in the DTPA-type metal complexes. The renal clearance profile of the corresponding radioactive 111In complex 13c is similar to that of 111In-DTPA, albeit 13c clears slower than 111In-DTPA. The biodistribution data indicates that 13c, and, by inference, 13a clear via a complex mechanism that includes glomerular filtration.

The Prediction of Key Cytoskeleton Components Involved in Glomerular Diseases Based on a Protein-Protein Interaction Network.

PubMed

Ding, Fangrui; Tan, Aidi; Ju, Wenjun; Li, Xuejuan; Li, Shao; Ding, Jie

2016-01-01

Maintenance of the physiological morphologies of different types of cells and tissues is essential for the normal functioning of each system in the human body. Dynamic variations in cell and tissue morphologies depend on accurate adjustments of the cytoskeletal system. The cytoskeletal system in the glomerulus plays a key role in the normal process of kidney filtration. To enhance the understanding of the possible roles of the cytoskeleton in glomerular diseases, we constructed the Glomerular Cytoskeleton Network (GCNet), which shows the protein-protein interaction network in the glomerulus, and identified several possible key cytoskeletal components involved in glomerular diseases. In this study, genes/proteins annotated to the cytoskeleton were detected by Gene Ontology analysis, and glomerulus-enriched genes were selected from nine available glomerular expression datasets. Then, the GCNet was generated by combining these two sets of information. To predict the possible key cytoskeleton components in glomerular diseases, we then examined the common regulation of the genes in GCNet in the context of five glomerular diseases based on their transcriptomic data. As a result, twenty-one cytoskeleton components as potential candidate were highlighted for consistently down- or up-regulating in all five glomerular diseases. And then, these candidates were examined in relation to existing known glomerular diseases and genes to determine their possible functions and interactions. In addition, the mRNA levels of these candidates were also validated in a puromycin aminonucleoside(PAN) induced rat nephropathy model and were also matched with existing Diabetic Nephropathy (DN) transcriptomic data. As a result, there are 15 of 21 candidates in PAN induced nephropathy model were consistent with our predication and also 12 of 21 candidates were matched with differentially expressed genes in the DN transcriptomic data. By providing a novel interaction network and prediction, GCNet contributes to improving the understanding of normal glomerular function and will be useful for detecting target cytoskeleton molecules of interest that may be involved in glomerular diseases in future studies.

The Prediction of Key Cytoskeleton Components Involved in Glomerular Diseases Based on a Protein-Protein Interaction Network

PubMed Central

Ju, Wenjun; Li, Xuejuan; Li, Shao; Ding, Jie

2016-01-01

Maintenance of the physiological morphologies of different types of cells and tissues is essential for the normal functioning of each system in the human body. Dynamic variations in cell and tissue morphologies depend on accurate adjustments of the cytoskeletal system. The cytoskeletal system in the glomerulus plays a key role in the normal process of kidney filtration. To enhance the understanding of the possible roles of the cytoskeleton in glomerular diseases, we constructed the Glomerular Cytoskeleton Network (GCNet), which shows the protein-protein interaction network in the glomerulus, and identified several possible key cytoskeletal components involved in glomerular diseases. In this study, genes/proteins annotated to the cytoskeleton were detected by Gene Ontology analysis, and glomerulus-enriched genes were selected from nine available glomerular expression datasets. Then, the GCNet was generated by combining these two sets of information. To predict the possible key cytoskeleton components in glomerular diseases, we then examined the common regulation of the genes in GCNet in the context of five glomerular diseases based on their transcriptomic data. As a result, twenty-one cytoskeleton components as potential candidate were highlighted for consistently down- or up-regulating in all five glomerular diseases. And then, these candidates were examined in relation to existing known glomerular diseases and genes to determine their possible functions and interactions. In addition, the mRNA levels of these candidates were also validated in a puromycin aminonucleoside(PAN) induced rat nephropathy model and were also matched with existing Diabetic Nephropathy (DN) transcriptomic data. As a result, there are 15 of 21 candidates in PAN induced nephropathy model were consistent with our predication and also 12 of 21 candidates were matched with differentially expressed genes in the DN transcriptomic data. By providing a novel interaction network and prediction, GCNet contributes to improving the understanding of normal glomerular function and will be useful for detecting target cytoskeleton molecules of interest that may be involved in glomerular diseases in future studies. PMID:27227331

Alport syndrome and Pierson syndrome: Diseases of the glomerular basement membrane.

PubMed

Funk, Steven D; Lin, Meei-Hua; Miner, Jeffrey H

2018-04-16

The glomerular basement membrane (GBM) is an important component of the kidney's glomerular filtration barrier. Like all basement membranes, the GBM contains type IV collagen, laminin, nidogen, and heparan sulfate proteoglycan. It is flanked by the podocytes and glomerular endothelial cells that both synthesize it and adhere to it. Mutations that affect the GBM's collagen α3α4α5(IV) components cause Alport syndrome (kidney disease with variable ear and eye defects) and its variants, including thin basement membrane nephropathy. Mutations in LAMB2 that impact the synthesis or function of laminin α5β2γ1 (LM-521) cause Pierson syndrome (congenital nephrotic syndrome with eye and neurological defects) and its less severe variants, including isolated congenital nephrotic syndrome. The very different types of kidney diseases that result from mutations in collagen IV vs. laminin are likely due to very different pathogenic mechanisms. A better understanding of these mechanisms should lead to targeted therapeutic approaches that can help people with these rare but important diseases. Copyright © 2017 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

Renin-angiotensin system within the diabetic podocyte.

PubMed

Márquez, Eva; Riera, Marta; Pascual, Julio; Soler, María José

2015-01-01

Diabetic kidney disease is the leading cause of end-stage renal disease. Podocytes are differentiated cells necessary for the development and maintenance of the glomerular basement membrane and the capillary tufts, as well as the function of the glomerular filtration barrier. The epithelial glomerular cells express a local renin-angiotensin system (RAS) that varies in different pathological situations such as hyperglycemia or mechanical stress. RAS components have been shown to be altered in diabetic podocytopathy, and their modulation may modify diabetic nephropathy progression. Podocytes are a direct target for angiotensin II-mediated injury by altered expression and distribution of podocyte proteins. Furthermore, angiotensin II promotes podocyte injury indirectly by inducing cellular hypertrophy, increased apoptosis, and changes in the anionic charge of the glomerular basement membrane, among other effects. RAS blockade has been shown to decrease the level of proteinuria and delay the progression of chronic kidney disease. This review summarizes the local intraglomerular RAS and its imbalance in diabetic podocytopathy. A better understanding of the intrapodocyte RAS might provide a new approach for diabetic kidney disease treatment. Copyright © 2015 the American Physiological Society.

Outcome of the acute glomerular injury in proliferative lupus nephritis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chagnac, A.; Kiberd, B.A.; Farinas, M.C.

1989-09-01

Treatment with total lymphoid irradiation (TLI) and corticosteroids markedly reduced activity of systemic lupus erythematosis in 10 patients with diffuse proliferative lupus nephritis (DPLN) complicated by a nephrotic syndrome. Physiologic and morphometric techniques were used serially before, and 12 and 36 mo post-TLI to characterize the course of glomerular injury. Judged by a progressive reduction in the density of glomerular cells and immune deposits, glomerular inflammation subsided. A sustained reduction in the fractional clearance of albumin, IgG and uncharged dextrans of radius greater than 50 A, pointed to a parallel improvement in glomerular barrier size-selectivity. Corresponding changes in GFR weremore » modest, however. A trend towards higher GFR at 12 mo was associated with a marked increase in the fraction of glomerular tuft area occupied by patent capillary loops as inflammatory changes receded. A late trend toward declining GFR beyond 12 mo was associated with progressive glomerulosclerosis, which affected 57% of all glomeruli globally by 36 mo post-TLI. Judged by a parallel increase in volume by 59%, remaining, patent glomeruli had undergone a process of adaptive enlargement. We propose that an increasing fraction of glomeruli continues to undergo progressive sclerosis after DPLN has become quiescent, and that the prevailing GFR depends on the extent to which hypertrophied remnant glomeruli can compensate for the ensuing loss of filtration surface area.« less

Gender differences in the progression of target organ damage in patients with increased insulin resistance: the LOD-DIABETES study.

PubMed

Gómez-Marcos, Manuel Ángel; Recio-Rodríguez, José Ignacio; Gómez-Sánchez, Leticia; Agudo-Conde, Cristina; Rodríguez-Sanchez, Emiliano; Maderuelo-Fernandez, JoseAngel; Gomez-Sanchez, Marta; García-Ortiz, Luís

2015-10-01

The purpose of this study was to analyze the evolution of vascular, cardiac and renal target organ damage (TOD) in patients with increased insulin resistance over a 3.5 year follow-up and to investigate gender difference and factors that influence its progression. We performed a prospective observational study involving 112 patients (71 men, 41 women) who were followed for 3.5 years. Measurements included blood pressure, blood glucose, lipids, smoking, body mass index (BMI) and HOMA-Ir Vascular TOD included carotid intima-media thickness (IMT), pulse wave velocity (PWV) and ankle/brachial index (ABI). Cardiac TOD included Cornell voltage-duration product and Sokolow. Renal TOD included creatinine, glomerular filtration and albumin/creatinine ratio. The IMT increased in both genders. Each year, the IMT increased 0.005 mm in men and 0.011 in women and the PWV 0.024 and 0.020 m/sec, respectively. The highest increase was in women with type 2 diabetes mellitus, who had an increase in TOD carotid (40%), PWV (24%) and renal TOD (20 %). Multiple regression analysis, after adjusting for age and gender, showed a negative association between duration since diabetes diagnosis and ABI (β = -0.006; p = 0.017) and between BMI and glomerular filtration (β = -0.813; p = 0.014). HbA1c was positively associated with PWV (β = 0.501; p = 0.014). This study showed that the progression of vascular and renal TOD differs by gender. The increase in vascular and renal TOD was higher in women, especially in diabetic women. The PWV increase showed a positive association with mean HbA1c levels during the follow-up. Glomerular filtration was associated with BMI and the ABI was associated with duration since type 2 diabetes mellitus diagnosis. Clinical Trials.gov Identifier NCT01065155.

Semaphorin3a Promotes Advanced Diabetic Nephropathy

PubMed Central

Aggarwal, Pardeep K.; Veron, Delma; Thomas, David B.; Siegel, Dionicio; Moeckel, Gilbert; Kashgarian, Michael

2015-01-01

The onset of diabetic nephropathy (DN) is highlighted by glomerular filtration barrier abnormalities. Identifying pathogenic factors and targetable pathways driving DN is crucial to developing novel therapies and improving the disease outcome. Semaphorin3a (sema3a) is a guidance protein secreted by podocytes. Excess sema3a disrupts the glomerular filtration barrier. Here, using immunohistochemistry, we show increased podocyte SEMA3A in renal biopsies from patients with advanced DN. Using inducible, podocyte-specific Sema3a gain-of-function (Sema3a+) mice made diabetic with streptozotocin, we demonstrate that sema3a is pathogenic in DN. Diabetic Sema3a+ mice develop massive proteinuria, renal insufficiency, and extensive nodular glomerulosclerosis, mimicking advanced DN in humans. In diabetic mice, Sema3a+ exacerbates laminin and collagen IV accumulation in Kimmelstiel-Wilson-like glomerular nodules and causes diffuse podocyte foot process effacement and F-actin collapse via nephrin, αvβ3 integrin, and MICAL1 interactions with plexinA1. MICAL1 knockdown and sema3a inhibition render podocytes not susceptible to sema3a-induced shape changes, indicating that MICAL1 mediates sema3a-induced podocyte F-actin collapse. Moreover, sema3a binding inhibition or podocyte-specific plexinA1 deletion markedly ameliorates albuminuria and abrogates renal insufficiency and the diabetic nodular glomerulosclerosis phenotype of diabetic Sema3a+ mice. Collectively, these findings indicate that excess sema3a promotes severe diabetic nephropathy and identifies novel potential therapeutic targets for DN. PMID:25475434

Antibody and complement reduce renal hemodynamic function in isolated perfused rat kidney.

PubMed

Jocks, T; Zahner, G; Helmchen, U; Kneissler, U; Stahl, R A

1996-01-01

To evaluate the effect of antibody and complement on renal hemodynamic changes, glomerular injury was induced in isolated perfused kidneys by an anti-thymocyte antibody (ATS) and rat serum (RS). Glomerular filtration rate (GFR), renal vascular resistance (RVR), and renal perfusate flow (RPF) were assessed over an 80-min period. The possible role of thromboxane (Tx) was tested by the application of the Tx synthesis inhibitor UK-38485 and the Tx receptor blocker daltroban. Perfusion of kidneys with ATS and RS significantly reduced GFR at 10 min (control, 501 +/- 111; ATS + RS, 138 +/- 86 ml.g kidney-1.min-1, significance of F = 0.000) after RS. Similarly, RPF (ml.g kidney-1.min-1) fell from 19.2 +/- 1.8 to 6.1 +/- 2.0 (significance of F = 0.000), whereas RVR (mmHg.ml-1.g.min) increased threefold from 5.2 +/- 0.4 to 17.9 +/- 5.0 at 10 min. These changes were ameliorated by the pretreatment of the rats with daltroban and UK-38485. Addition of erythrocytes to the perfusate increased RVR and GFR, whereas RPF decreased compared with cell-free perfused kidneys. ATS and RS in this preparation also decrease GFR and RPF. The hemodynamic alterations appeared without changes in filtration fraction. Compared with untreated, perfused control kidneys, glomerular Tx formation was significantly increased in ATS and RS perfused kidneys. These data demonstrate that antibody and RS induce impairment of renal hemodynamics, which are mediated by increased Tx formation.

Use of a Microsoft Excel based add-in program to calculate plasma sinistrin clearance by a two-compartment model analysis in dogs.

PubMed

Steinbach, Sarah M L; Sturgess, Christopher P; Dunning, Mark D; Neiger, Reto

2015-06-01

Assessment of renal function by means of plasma clearance of a suitable marker has become standard procedure for estimation of glomerular filtration rate (GFR). Sinistrin, a polyfructan solely cleared by the kidney, is often used for this purpose. Pharmacokinetic modeling using adequate software is necessary to calculate disappearance rate and half-life of sinistrin. The purpose of this study was to describe the use of a Microsoft excel based add-in program to calculate plasma sinistrin clearance, as well as additional pharmacokinetic parameters such as transfer rates (k), half-life (t1/2) and volume of distribution (Vss) for sinistrin in dogs with varying degrees of renal function. Copyright © 2015 Elsevier Ltd. All rights reserved.

Genome-Wide Association and Functional Follow-Up Reveals New Loci for Kidney Function

PubMed Central

Fuchsberger, Christian; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Taliun, Daniel; Li, Man; Gao, Xiaoyi; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C.; O'Seaghdha, Conall M.; Glazer, Nicole; Isaacs, Aaron; Liu, Ching-Ti; Smith, Albert V.; O'Connell, Jeffrey R.; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Johnson, Andrew D.; Gierman, Hinco J.; Feitosa, Mary; Hwang, Shih-Jen; Atkinson, Elizabeth J.; Lohman, Kurt; Cornelis, Marilyn C.; Johansson, Åsa; Tönjes, Anke; Dehghan, Abbas; Chouraki, Vincent; Holliday, Elizabeth G.; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y.; Murgia, Federico; Trompet, Stella; Imboden, Medea; Kollerits, Barbara; Pistis, Giorgio; Harris, Tamara B.; Launer, Lenore J.; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D.; Boerwinkle, Eric; Schmidt, Helena; Cavalieri, Margherita; Rao, Madhumathi; Hu, Frank B.; Demirkan, Ayse; Oostra, Ben A.; de Andrade, Mariza; Turner, Stephen T.; Ding, Jingzhong; Andrews, Jeanette S.; Freedman, Barry I.; Koenig, Wolfgang; Illig, Thomas; Döring, Angela; Wichmann, H.-Erich; Kolcic, Ivana; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E.; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H.; Wright, Alan F.; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Endlich, Karlhans; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K.; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G.; Rivadeneira, Fernando; Aulchenko, Yurii S.; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Ketkar, Shamika; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Giulianini, Franco; Krämer, Bernhard K.; Portas, Laura; Ford, Ian; Buckley, Brendan M.; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Metzger, Marie; Mitchell, Paul; Ciullo, Marina; Kim, Stuart K.; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J. Wouter; Probst-Hensch, Nicole M.; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R.; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; Siscovick, David S.; van Duijn, Cornelia M.; Borecki, Ingrid; Kardia, Sharon L. R.; Liu, Yongmei; Curhan, Gary C.; Rudan, Igor; Gyllensten, Ulf; Wilson, James F.; Franke, Andre; Pramstaller, Peter P.; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline C. M.; Hayward, Caroline; Ridker, Paul; Parsa, Afshin; Bochud, Murielle; Heid, Iris M.; Goessling, Wolfram; Chasman, Daniel I.; Kao, W. H. Linda; Fox, Caroline S.

2012-01-01

Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD. PMID:22479191

Genome-wide association and functional follow-up reveals new loci for kidney function.

PubMed

Pattaro, Cristian; Köttgen, Anna; Teumer, Alexander; Garnaas, Maija; Böger, Carsten A; Fuchsberger, Christian; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Taliun, Daniel; Li, Man; Gao, Xiaoyi; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C; O'Seaghdha, Conall M; Glazer, Nicole; Isaacs, Aaron; Liu, Ching-Ti; Smith, Albert V; O'Connell, Jeffrey R; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Johnson, Andrew D; Gierman, Hinco J; Feitosa, Mary; Hwang, Shih-Jen; Atkinson, Elizabeth J; Lohman, Kurt; Cornelis, Marilyn C; Johansson, Åsa; Tönjes, Anke; Dehghan, Abbas; Chouraki, Vincent; Holliday, Elizabeth G; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y; Murgia, Federico; Trompet, Stella; Imboden, Medea; Kollerits, Barbara; Pistis, Giorgio; Harris, Tamara B; Launer, Lenore J; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D; Boerwinkle, Eric; Schmidt, Helena; Cavalieri, Margherita; Rao, Madhumathi; Hu, Frank B; Demirkan, Ayse; Oostra, Ben A; de Andrade, Mariza; Turner, Stephen T; Ding, Jingzhong; Andrews, Jeanette S; Freedman, Barry I; Koenig, Wolfgang; Illig, Thomas; Döring, Angela; Wichmann, H-Erich; Kolcic, Ivana; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H; Wright, Alan F; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Endlich, Karlhans; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G; Rivadeneira, Fernando; Aulchenko, Yurii S; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Ketkar, Shamika; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Giulianini, Franco; Krämer, Bernhard K; Portas, Laura; Ford, Ian; Buckley, Brendan M; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Metzger, Marie; Mitchell, Paul; Ciullo, Marina; Kim, Stuart K; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J Wouter; Probst-Hensch, Nicole M; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; Siscovick, David S; van Duijn, Cornelia M; Borecki, Ingrid; Kardia, Sharon L R; Liu, Yongmei; Curhan, Gary C; Rudan, Igor; Gyllensten, Ulf; Wilson, James F; Franke, Andre; Pramstaller, Peter P; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline C M; Hayward, Caroline; Ridker, Paul; Parsa, Afshin; Bochud, Murielle; Heid, Iris M; Goessling, Wolfram; Chasman, Daniel I; Kao, W H Linda; Fox, Caroline S

2012-01-01

Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.

Impacts of sodium-glucose co-transporter type 2 inhibitors on central blood pressure.

PubMed

Takenaka, Tsuneo; Ohno, Yoichi; Suzuki, Hiromichi

2018-03-01

To assess the effects of sodium-glucose co-transporter type 2 inhibitors on central blood pressure, an important determinant of cardiovascular events. Canagliflozin, Empagliflozin or Luseogliflozin was given for 102 type 2 diabetic patients with hypertension and nephropathy. Central blood pressure was evaluated by radial tonometry. Clinical parameters were followed for 6 months. Three differing sodium-glucose co-transporter type 2 inhibitors similarly reduced brachial and central blood pressures, casual blood sugar, haemoglobin A1c, estimated glomerular filtration rate and albuminuria without significant changes in pulse rate and lipid profiles. Central systolic blood pressure was associated with the decreases in albuminuria by sodium-glucose co-transporter type 2 inhibitors. Comparable influences of various sodium-glucose co-transporter type 2 inhibitors on central blood pressure suggest class effects.

Intravital Imaging Reveals Angiotensin II–Induced Transcytosis of Albumin by Podocytes

PubMed Central

Schießl, Ina Maria; Hammer, Anna; Kattler, Veronika; Gess, Bernhard; Theilig, Franziska; Witzgall, Ralph

2016-01-01

Albuminuria is a hallmark of kidney disease of various etiologies and usually caused by deterioration of glomerular filtration barrier integrity. We recently showed that angiotensin II (Ang II) acutely increases albumin filtration in the healthy kidney. Here, we used intravital microscopy to assess the effects of Ang II on podocyte function in rats. Acute infusion of 30, 60, or 80 ng/kg per minute Ang II enhanced the endocytosis of albumin by activation of the type 1 Ang II receptor and resulted in an average (±SEM) of 3.7±2.2, 72.3±18.6 (P<0.001), and 239.4±34.6 µm3 (P<0.001) albumin-containing vesicles per glomerulus, respectively, compared with none at baseline or 10 ng/kg per minute Ang II. Immunostaining of Ang II–infused kidneys confirmed the presence of albumin-containing vesicles, which colocalized with megalin, in podocin-positive cells. Furthermore, podocyte endocytosis of albumin was markedly reduced in the presence of gentamicin, a competitive inhibitor of megalin-dependent endocytosis. Ang II infusion increased the concentration of albumin in the subpodocyte space, a potential source for endocytic protein uptake, and gentamicin further increased this concentration. Some endocytic vesicles were acidified and colocalized with LysoTracker. Most vesicles migrated from the capillary to the apical aspect of the podocyte and were eventually released into the urinary space. This transcytosis accounted for approximately 10% of total albumin filtration. In summary, the transcellular transport of proteins across the podocyte constitutes a new pathway of glomerular protein filtration. Ang II enhances the endocytosis and transcytosis of plasma albumin by podocytes, which may eventually impair podocyte function. PMID:26116357

Measured glomerular filtration rate does not improve prediction of mortality by cystatin C and creatinine.

PubMed

Sundin, Per-Ola; Sjöström, Per; Jones, Ian; Olsson, Lovisa A; Udumyan, Ruzan; Grubb, Anders; Lindström, Veronica; Montgomery, Scott

2017-04-01

Cystatin C may add explanatory power for associations with mortality in combination with other filtration markers, possibly indicating pathways other than glomerular filtration rate (GFR). However, this has not been firmly established since interpretation of associations independent of measured GFR (mGFR) is limited by potential multicollinearity between markers of GFR. The primary aim of this study was to assess associations between cystatin C and mortality, independent of mGFR. A secondary aim was to evaluate the utility of combining cystatin C and creatinine to predict mortality risk. Cox regression was used to assess the associations of cystatin C and creatinine with mortality in 1157 individuals referred for assessment of plasma clearance of iohexol. Since cystatin C and creatinine are inversely related to mGFR, cystatin C - 1 and creatinine - 1 were used. After adjustment for mGFR, lower cystatin C - 1 (higher cystatin C concentration) and higher creatinine - 1 (lower creatinine concentration) were independently associated with increased mortality. When nested models were compared, avoiding the potential influence of multicollinearity, the independence of the associations was supported. Among models combining the markers of GFR, adjusted for demographic factors and comorbidity, cystatin C - 1 and creatinine - 1 combined explained the largest proportion of variance in associations with mortality risk ( R 2  = 0.61). Addition of mGFR did not improve the model. Our results suggest that both creatinine and cystatin C have independent associations with mortality not explained entirely by mGFR and that mGFR does not offer a more precise mortality risk assessment than these endogenous filtration markers combined. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Coexistent findings of renal glomerular disease with Hashimoto's thyroiditis.

PubMed

Koçak, Gülay; Huddam, Bülent; Azak, Alper; Ortabozkoyun, Levent; Duranay, Murat

2012-05-01

Hashimoto's thyroiditis (HT) is a common autoimmune thyroid disease with a female preponderance. Renal involvement in HT is not uncommon. In the present study, we aimed to define the frequency and characteristics of the glomerular diseases associated with HT and further the understanding of any common pathogenesis between HT and glomerular disease. We reviewed retrospectively 28 patients with HT who were referred to our Department because of unexplained haematuria, proteinuria or renal impairment from 2007 to 2011. Routine laboratory investigations including blood count, serum biochemistry, urinalysis and 24-h urinary protein excretion were performed on all patients. Renal biopsy was performed in 20 patients with HT, and the specimens were examined by light microscopy and immunofluorescence staining. We detected four cases of focal segmental glomerulosclerosis (FSGS), four membranous glomerulonephritis (MGN), two minimal-change disease (MCD), three immunoglobulin A nephritis (IgAN), three chronic glomerulonephritis (CGN) and one amyloidosis. In three patients, the renal biopsy findings were nonspecific. Daily urinary protein excretion and glomerular filtration rates were found to be independent of the level of thyroid hormone and thyroid-specific autoantibodies. Glomerular pathologies associated with HT are similar to those in the general population, the most common lesions being MGN, FSGS and IgA nephritis. © 2012 Blackwell Publishing Ltd.

Podocyte-Specific VEGF-A Gain of Function Induces Nodular Glomerulosclerosis in eNOS Null Mice

PubMed Central

Veron, Delma; Aggarwal, Pardeep K.; Velazquez, Heino; Kashgarian, Michael; Moeckel, Gilbert

2014-01-01

VEGF-A and nitric oxide are essential for glomerular filtration barrier homeostasis and are dysregulated in diabetic nephropathy. Here, we examined the effect of excess podocyte VEGF-A on the renal phenotype of endothelial nitric oxide synthase (eNOS) knockout mice. Podocyte-specific VEGF164 gain of function in eNOS−/− mice resulted in nodular glomerulosclerosis, mesangiolysis, microaneurysms, and arteriolar hyalinosis associated with massive proteinuria and renal failure in the absence of diabetic milieu or hypertension. In contrast, podocyte-specific VEGF164 gain of function in wild-type mice resulted in less pronounced albuminuria and increased creatinine clearance. Transmission electron microscopy revealed glomerular basement membrane thickening and podocyte effacement in eNOS−/− mice with podocyte-specific VEGF164 gain of function. Furthermore, glomerular nodules overexpressed collagen IV and laminin extensively. Biotin-switch and proximity ligation assays demonstrated that podocyte-specific VEGF164 gain of function decreased glomerular S-nitrosylation of laminin in eNOS−/− mice. In addition, treatment with VEGF-A decreased S-nitrosylated laminin in cultured podocytes. Collectively, these data indicate that excess glomerular VEGF-A and eNOS deficiency is necessary and sufficient to induce Kimmelstiel-Wilson–like nodular glomerulosclerosis in mice through a process that involves deposition of laminin and collagen IV and de-nitrosylation of laminin. PMID:24578128

A Pharmacokinetics, Efficacy, and Safety Study of Gadoterate Meglumine in Pediatric Subjects Aged Younger Than 2 Years

PubMed Central

Scala, Mario; Koob, Meriam; de Buttet, Sophie; Bourrinet, Philippe; Felices, Mathieu; Jurkiewicz, Elzbieta

2018-01-01

Objectives The primary objective of this study was to investigate the pharmacokinetic profile of gadoterate meglumine in pediatric patients younger than 2 years; the secondary objectives were to document its efficacy and safety. Material and Methods This was a Phase IV open-label, prospective study conducted in 9 centers (4 countries). Forty-five patients younger than 2 years with normal estimated glomerular filtration rate and scheduled to undergo routine gadolinium-enhanced magnetic resonance imaging (MRI) of any organ were included and received a single intravenous injection of gadoterate meglumine (0.1 mmol/kg). To perform the population pharmacokinetics analysis, 3 blood samples per subject were drawn during 3 time windows at time points allocated by randomization. Results Gadoterate meglumine concentrations were best fitted using a 2-compartmental model with linear elimination from central compartment. The median total clearance adjusted to body weight was estimated at 0.06 L/h per kg and increased with estimated glomerular filtration rate according to a power model. The median volume of distribution at steady state (Vss) adjusted to body weight was estimated at 0.047 L/kg. Estimated median terminal half-life (t1/2β) was 1.35 h, and the median systemic exposure (area under the curve) was 1591 μmol h/L. Efficacy was assessed by comparing precontrast +postcontrast images to precontrast images in a subset of 28 subjects who underwent an MRI examination of brain, spine, and associated tissues. A total of 28 lesions were identified and analyzed in 15 subjects with precontrast images versus 30 lesions in 16 subjects with precontrast + postcontrast images. Lesion visualization was improved with a mean (SD) increase in scores at subject level of 0.7 (1.0) for lesion border delineation, 0.9 (1.6) for internal morphology, and 3.1 (3.2) for contrast enhancement. Twenty-six adverse events occurred postinjection in 13 subjects (28.9%), including 3 serious reported in 1 subject (2.2%). One subject (2.2%) experienced 1 rash of moderate intensity considered as related to gadoterate meglumine. Conclusions The pharmacokinetic profile of gadoterate meglumine after a single intravenous injection of 0.1 mmol/kg was appropriately described in newborns and infants younger than 2 years, for whom no dose adjustment is required. The improved efficacy of gadoterate meglumine for contrast-enhanced MRI examination of brain, spine, and associated tissues, as well as its good safety profile, was also demonstrated in this population. PMID:28906338

A Pharmacokinetics, Efficacy, and Safety Study of Gadoterate Meglumine in Pediatric Subjects Aged Younger Than 2 Years.

PubMed

Scala, Mario; Koob, Meriam; de Buttet, Sophie; Bourrinet, Philippe; Felices, Mathieu; Jurkiewicz, Elzbieta

2018-02-01

The primary objective of this study was to investigate the pharmacokinetic profile of gadoterate meglumine in pediatric patients younger than 2 years; the secondary objectives were to document its efficacy and safety. This was a Phase IV open-label, prospective study conducted in 9 centers (4 countries). Forty-five patients younger than 2 years with normal estimated glomerular filtration rate and scheduled to undergo routine gadolinium-enhanced magnetic resonance imaging (MRI) of any organ were included and received a single intravenous injection of gadoterate meglumine (0.1 mmol/kg). To perform the population pharmacokinetics analysis, 3 blood samples per subject were drawn during 3 time windows at time points allocated by randomization. Gadoterate meglumine concentrations were best fitted using a 2-compartmental model with linear elimination from central compartment. The median total clearance adjusted to body weight was estimated at 0.06 L/h per kg and increased with estimated glomerular filtration rate according to a power model. The median volume of distribution at steady state (Vss) adjusted to body weight was estimated at 0.047 L/kg. Estimated median terminal half-life (t1/2β) was 1.35 h, and the median systemic exposure (area under the curve) was 1591 μmol h/L. Efficacy was assessed by comparing precontrast +postcontrast images to precontrast images in a subset of 28 subjects who underwent an MRI examination of brain, spine, and associated tissues. A total of 28 lesions were identified and analyzed in 15 subjects with precontrast images versus 30 lesions in 16 subjects with precontrast + postcontrast images. Lesion visualization was improved with a mean (SD) increase in scores at subject level of 0.7 (1.0) for lesion border delineation, 0.9 (1.6) for internal morphology, and 3.1 (3.2) for contrast enhancement. Twenty-six adverse events occurred postinjection in 13 subjects (28.9%), including 3 serious reported in 1 subject (2.2%). One subject (2.2%) experienced 1 rash of moderate intensity considered as related to gadoterate meglumine. The pharmacokinetic profile of gadoterate meglumine after a single intravenous injection of 0.1 mmol/kg was appropriately described in newborns and infants younger than 2 years, for whom no dose adjustment is required. The improved efficacy of gadoterate meglumine for contrast-enhanced MRI examination of brain, spine, and associated tissues, as well as its good safety profile, was also demonstrated in this population.

Mechanisms responsible for decreased glomerular filtration in hibernation and hypothermia

NASA Technical Reports Server (NTRS)

Tempel, G. E.; Musacchia, X. J.; Jones, S. B.

1977-01-01

Measurements of blood pressure, heart rate, red blood cell and plasma volumes, and relative distribution of cardiac output were made on hibernating and hypothermic adult male and female golden hamsters weighing 120-140 g to study the mechanisms underlying the elimination or marked depression of renal function in hibernation and hypothermia. The results suggest that the elimination or marked depression in renal function reported in hibernation and hypothermia may partly be explained by alterations in cardiovascular system function. Renal perfusion pressure which decreases nearly 60% in both hibernation and hypothermia and a decrease in plasma volume of roughly 35% in the hypothermic animal might both be expected to markedly alter glomerular function.

Circulating Lipocalin 2 Levels Predict Fracture-Related Hospitalizations in Elderly Women: A Prospective Cohort Study.

PubMed

Lim, Wai H; Wong, Germaine; Lim, Ee M; Byrnes, Elizabeth; Zhu, Kun; Devine, Amanda; Pavlos, Nathan J; Prince, Richard L; Lewis, Joshua R

2015-11-01

Lipocalin 2 (LCN2) or neutrophil gelatinase-associated lipocalin (NGAL) is expressed in a wide range of cells and pathological states. Mounting evidence suggests lipocalin 2 may be an important regulator of bone homeostasis. Recently it has been suggested LCN2 is a novel mechanoresponsive gene central to the pathological response to low mechanical force. We undertook a prospective study of 1009 elderly women over 70 years of age to study the association between circulating LCN2 and potential associated variables, including estimated glomerular filtration rate, physical activity, and baseline measures of hip bone density and heel bone quality. Osteoporotic fractures requiring hospitalizations were identified from the Western Australian Data Linkage System. Over 14.5 years, 272 (27%) of women sustained an osteoporotic fracture-related hospitalization; of these, 101 were hip fractures. Circulating LCN2 levels were correlated with body mass index and estimated glomerular filtration rate (r = 0.249, p < 0.001 and r = -0.481, p < 0.001, respectively) that modified the association with hip and heel bone measures. Per standard deviation increase in LCN2, there was a 30% multivariable-adjusted increase in the risk of any osteoporotic fracture (hazard ratio [HR] = 1.30, 95% confidence interval [CI] 1.13-1.50, p < 0.001). In participants with elevated LCN2 levels above the median (76.6 ng/mL), there was an 80% to 81% increase in the risk of any osteoporotic or hip fracture (HR = 1.81, 95% CI 1.38-2.36, p < 0.001 and HR = 1.80, 95% CI 1.16-2.78, p = 0.008, respectively). These associations remained significant after adjustment for total hip bone mineral density (p < 0.05). In conclusion, we have demonstrated that circulating LCN2 levels predict future risk of osteoporotic fractures requiring hospitalization. Measurement of LCN2 levels may improve fracture prediction in addition to current fracture risk factors in the elderly, particularly in those with impaired renal function. © 2015 American Society for Bone and Mineral Research.

Antihyperglycemic Medication Use Among Medicare Beneficiaries With Heart Failure, Diabetes Mellitus, and Chronic Kidney Disease.

PubMed

Patel, Priyesh A; Liang, Li; Khazanie, Prateeti; Hammill, Bradley G; Fonarow, Gregg C; Yancy, Clyde W; Bhatt, Deepak L; Curtis, Lesley H; Hernandez, Adrian F

2016-07-01

Diabetes mellitus, heart failure (HF), and chronic kidney disease are common comorbidities, but overall use and safety of antihyperglycemic medications (AHMs) among patients with these comorbidities are poorly understood. Using Get With the Guidelines-Heart Failure and linked Medicare Part D data, we assessed AHM use within 90 days of hospital discharge among HF patients with diabetes mellitus discharged from Get With the Guidelines-Heart Failure hospitals between January 1, 2006, and October 1, 2011. We further summarized use by renal function and assessed renal contraindicated AHM use for patients with estimated glomerular filtration rate <30 mL/min/1.73m(2). Among 8791 patients meeting inclusion criteria, the median age was 77 (interquartile range 71-83), 62.3% were female, median body mass index was 29.7 (interquartile range 25.5-35.3), median hemoglobin A1c was 6.8 (interquartile range 6.2-7.8), and 34% had ejection fraction <40%. 74.9% of patients filled a prescription for an AHM, with insulin (39.5%), sulfonylureas (32.4%), and metformin (17%) being the most commonly used AHMs. Insulin use was higher and sulfonylurea/metformin use was lower among patients with lower renal function classes. Among 1512 patients with estimated glomerular filtration rate <30 mL/min/1.73m(2), 35.4% filled prescriptions for renal contraindicated AHMs per prescribing information, though there was a trend toward lower renal contraindicated AHM use over time (Cochran-Mantel-Haenszel row-mean score test P=0.048). Although use of other AHMs was low overall, thiazolidinediones were used in 6.6% of HF patients, and dipeptidyl peptidase-4 inhibitors were used in 5.1%, with trends for decreasing thiazolidinedione use and increased dipeptidyl peptidase-4 inhibitor use over time (P<0.001). Treatment of diabetes mellitus in patients with HF and chronic kidney disease is complex, and these patients are commonly treated with renal contraindicated AHMs, including over 6% receiving a thiazolidinedione, despite known concerns regarding HF. More research regarding safety and efficacy of various AHMs among HF patients is needed. © 2016 American Heart Association, Inc.

Worsening Renal Function during Management for Chronic Heart Failure with Reduced Ejection Fraction: Results From the Pro-BNP Outpatient Tailored Chronic Heart Failure Therapy (PROTECT) Study.

PubMed

Ibrahim, Nasrien E; Gaggin, Hanna K; Rabideau, Dustin J; Gandhi, Parul U; Mallick, Aditi; Januzzi, James L

2017-02-01

To assess prognostic meaning of worsening renal failure (WRF) occurring during management of chronic heart failure (HF) with reduced ejection fraction. When WRF develops during titration of HF medical therapy, it commonly leads to less aggressive care. A total of 151 patients enrolled in a prospective, randomized study of standard of care (SOC) HF therapy versus SOC plus a goal N-terminal pro-B type natriuretic peptide (NT-proBNP) < 1000 pg/mL were examined. Cardiovascular (CV) event (defined as worsening HF, hospitalization for HF, significant ventricular arrhythmia, acute coronary or cerebral ischemia, or CV death) at 1 year relative to WRF (defined as any reduction in estimated glomerular filtration rate) 90 days postenrollment were tabulated. Those developing WRF by 3 months had an average 14% reduction in estimated glomerular filtration rate. There was no difference in incidence of WRF between study arms (43% in SOC, 57% in NT-proBNP, P = .29). During the first 3 months of therapy titration, incident WRF was associated with numerically fewer CV events at 1 year compared with those without WRF (mean 0.81 vs 1.16 events, P = .21). WRF was associated trend toward fewer CV events in the SOC arm (hazard ratio 0.45, 95% confidence interval 0.16-1.24, P = .12); the NT-proBNP-guided arm had numerically lower CV event rates regardless of WRF. Subjects with NT-proBNP <1000 pg/mL and WRF received higher doses of guideline directed medical therapies, lower doses of loop diuretics, and had significantly lower CV event rates (P < .001). Modest degrees of WRF are common during aggressive HF with reduced ejection fraction management, but we found no significant association with CV outcomes. HF care guided by NT-proBNP was not associated with more WRF compared with SOC, and led to benefit regardless of final renal function. Copyright © 2016 Elsevier Inc. All rights reserved.

Serum Fractalkine (CX3CL1) and Cardiovascular Outcomes and Diabetes: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

PubMed

Shah, Rachana; Matthews, Gregory J; Shah, Rhia Y; McLaughlin, Catherine; Chen, Jing; Wolman, Melanie; Master, Stephen R; Chai, Boyang; Xie, Dawei; Rader, Daniel J; Raj, Dominic S; Mehta, Nehal N; Budoff, Matthew; Fischer, Michael J; Go, Alan S; Townsend, Raymond R; He, Jiang; Kusek, John W; Feldman, Harold I; Foulkes, Andrea S; Reilly, Muredach P

2015-08-01

Cardiometabolic disease is a major cause of morbidity and mortality in persons with chronic kidney disease (CKD). Fractalkine (CX3CL1) is a potential mediator of both atherosclerosis and metabolic disease. Studies of the relationship of CX3CL1 with risk of cardiovascular disease (CVD) events and metabolic traits are lacking, particularly in the high-risk setting of CKD. Cross-sectional and longitudinal observational analysis. Adults with CKD from 7 US sites participating in the Chronic Renal Insufficiency Cohort (CRIC) Study. Quartiles of plasma CX3CL1 levels at baseline. Baseline estimated glomerular filtration rate from a creatinine and cystatin C-based equation, prevalent and incident CVD, diabetes, metabolic syndrome and its criteria, homeostatic model assessment of insulin resistance, hemoglobin A1c level, myocardial infarction, all-cause mortality, and the composite outcome of myocardial infarction/all-cause mortality. Among 3,687 participants, baseline CX3CL1 levels were associated positively with several CVD risk factors and metabolic traits, lower estimated glomerular filtration rate, and higher levels of inflammatory cytokines, as well as prevalent CVD (OR, 1.09; 95% CI, 1.01-1.19; P=0.03). Higher CX3CL1 level also was associated with prevalent diabetes (OR, 1.26; 95% CI, 1.16-1.38; P<0.001) in adjusted models. During a mean follow-up of 6 years, there were 352 deaths, 176 myocardial infarctions, and 484 composite outcomes. In fully adjusted models, 1-SD higher CX3CL1 level increased the hazard for all-cause mortality (1.11; 95% CI, 1.00-1.22; P=0.02) and the composite outcome (1.09; 95% CI, 1.00-1.19; P=0.04). Study design did not allow evaluation of changes over time, correlation with progression of phenotypes, or determination of causality of effect. Circulating CX3CL1 level may contribute to both atherosclerotic CVD and diabetes in a CKD cohort. Further studies are required to establish mechanisms through which CX3CL1 affects the pathogenesis of atherosclerosis and diabetes. Copyright © 2015 National Kidney Foundation, Inc. All rights reserved.

Telehealth by an Interprofessional Team in Patients With CKD: A Randomized Controlled Trial.

PubMed

Ishani, Areef; Christopher, Juleen; Palmer, Deirdre; Otterness, Sara; Clothier, Barbara; Nugent, Sean; Nelson, David; Rosenberg, Mark E

2016-07-01

Telehealth and interprofessional case management are newer strategies of care within chronic disease management. We investigated whether an interprofessional team using telehealth was a feasible care delivery strategy and whether this strategy could affect health outcomes in patients with chronic kidney disease (CKD). Randomized clinical trial. Minneapolis Veterans Affairs Health Care System (VAHCS), St. Cloud VAHCS, and affiliated clinics March 2012 to November 2013 in patients with CKD (estimated glomerular filtration rate < 60mL/min/1.73m(2)). Patients were randomly assigned to receive an intervention (n=451) consisting of care by an interprofessional team (nephrologist, nurse practitioner, nurses, clinical pharmacy specialist, psychologist, social worker, and dietician) using a telehealth device (touch screen computer with peripherals) or to usual care (n=150). The primary end point was a composite of death, hospitalization, emergency department visits, or admission to skilled nursing facilities, compared to usual care. Baseline characteristics of the overall study group: mean age, 75.1±8.1 (SD) years; men, 98.5%; white, 97.3%; and mean estimated glomerular filtration rate, 37±9mL/min/1.73m(2). Telehealth and interprofessional care were successfully implemented with meaningful engagement with the care system. One year after randomization, 208 (46.2%) patients in the intervention group versus 70 (46.7%) in the usual-care group had the primary composite outcome (HR, 0.98; 95% CI, 0.75-1.29; P=0.9). There was no difference between groups for any component of the primary outcome: all-cause mortality (HR, 1.46; 95% CI, 0.42-5.11), hospitalization (HR, 1.15; 95% CI, 0.80-1.63), emergency department visits (HR, 0.92; 95% CI, 0.68-1.24), or nursing home admission (HR, 3.07; 95% CI, 0.71-13.24). Older population, mostly men, potentially underpowered/wide CIs. Telehealth by an interprofessional team is a feasible care delivery strategy in patients with CKD. There was no statistically significant evidence of superiority of this intervention on health outcomes compared to usual care. Published by Elsevier Inc.

Trajectory of Estimated Glomerular Filtration Rate Predicts Renal Injury in Children with Multicystic Dysplastic Kidney.

PubMed

Matsumura, Kazuya; Sugii, Kyoko; Awazu, Midori

2018-06-07

Children with a solitary functioning kidney have a risk of renal injury caused by hyperfiltration. Timely intervention with renin-angiotensin inhibitors may be beneficial. We examined whether trajectory of estimated glomerular filtration rate (eGFR) would predict renal injury, defined as microalbuminuria/proteinuria, hypertension, and/or a decline in eGFR. Seventeen patients (male 7, female 10) with multicystic dysplastic kidney (MCDK; median age 13 years, range 6-19 years) followed in our clinic were examined retrospectively. An eGFR decline was defined as a fall to < 90 mL/min/1.73 m2 or a decline of > 5 mL/min/1.73 m2/year for those with baseline eGFR of ≥90 or < 90 mL/min/1.73 m2 respectively. Nine patients had renal injury at the time of investigation. Compared with 8 patients without renal injury, those with renal injury tended to be older (14.7 ± 4.2 vs. 11.4 ± 4.6 years) and the birth weight was smaller (2,538 ± 281 vs. 2,966 ± 361 g, p < 0.05). The frequency of contralateral congenital anomaly of kidney and urinary tract (cyst, hydronephrosis, or vesicoureteral reflux) were not different. The trajectory of eGFR in those without renal injury was either an increase (n = 3) or unidentifiable (n = 5), whereas that in the renal injury group was exclusively an increase followed by decline (p < 0.05). The average age of the onset of eGFR decline was 9.4 ± 4.2 years and that of the start of renal injury (albuminuria/proteinuria 5, eGFR decline 4, hypertension 1) was 12.5 ± 4.2 years. All the children with MCDK who developed renal injury had eGFR trajectory of increase followed by decline. Renal injury followed the peak eGFR by 3 years on average. This observation is in agreement with the hyperfiltration theory and underscores the importance of following eGFR trajectory closely. © 2018 S. Karger AG, Basel.

The Effect of IV Amino Acid Supplementation on Mortality in ICU Patients May Be Dependent on Kidney Function: Post Hoc Subgroup Analyses of a Multicenter Randomized Trial.

PubMed

Zhu, Ran; Allingstrup, Matilde J; Perner, Anders; Doig, Gordon S

2018-05-15

We investigated whether preexisting kidney function determines if ICU patients may benefit from increased (2.0 g/kg/d) protein intake. Post hoc, hypothesis-generating, subgroup analysis of a multicenter, phase 2, randomized clinical trial. All analyses were conducted by intention to treat and maintained group allocation. Ninety-day mortality was the primary outcome. ICUs of 16 hospitals throughout Australia and New Zealand. Adult critically ill patients expected to remain in the study ICU for longer than 2 days. Random allocation to receive a daily supplement of up to 100 g of IV amino acids to achieve a total protein intake of 2.0 g/kg/d or standard nutrition care. A total of 474 patients were randomized: 235 to standard care and 239 to IV amino acid supplementation. There was a statistically significant interaction between baseline kidney function and supplementation with study amino acids (p value for interaction = 0.026). Within the subgroup of patients with normal kidney function at randomization, patients who were allocated to receive the study amino acid supplement were less likely to die before study day 90 (covariate-adjusted risk difference, -7.9%; 95% CI, -15.1 to -0.7; p = 0.034). Furthermore, amino acid supplementation significantly increased estimated glomerular filtration rate in these patients (repeated-measures treatment × time interaction p = 0.009). Within the subgroup of patients with baseline kidney dysfunction and/or risk of progression of acute kidney injury, a significant effect of the study intervention on mortality was not found (covariate-adjusted risk difference, -0.6%; 95% CI, -16.2 to 15.2; p = 0.95). In this post hoc, hypothesis-generating, subgroup analysis, we observed reduced mortality and improved estimated glomerular filtration rate in ICU patients with normal kidney function who were randomly allocated to receive increased protein intake (up to 2.0 g/kg/d). We strongly recommend confirmation of these results in trials with low risk of bias before this treatment is recommended for routine care.

The Relationship Between Pulse Pressure, the Estimated Glomerular Filtration Rate, and Urine Microalbumin/Creatinine Ratio in Korean Adults.

PubMed

Seong, Jeong Min; Park, Chang Eun; Gi, Mi Young; Sun, Kwang Soon; Kim, Yu Jeong; Yoon, Hyun

2017-01-01

Pulse pressure (PP) is a predictor of adverse outcomes in patients on haemodialysis. Thus, the present study was conducted to assess the relationship between PP, estimated glomerular filtration rate (eGFR), and urine microalbumin/creatinine ratio (uACR) in Korean adults. Data of 9,409 adults (4,206 men and 5,203 women) aged ≥ 20 years from the Sixth Korean National Health and Nutrition Examination Survey (2013-2014) were analyzed. A multivariate analysis revealed that systolic blood pressure (SBP) (β = -0.170, 95% confidence interval [CI], -0.216 to -0.159), diastolic blood pressure (DBP) (β = 0.088, 95% CI 0.108-0.200; p < 0.001), and PP (β = -0.134, 95% CI -0.215 to -0.157) were significant factors determining eGFR. In contrast, SBP (β = 0.152, 95% CI, 0.985-1.456; p < 0.001), DBP (β = -0.062, 95% CI -1.141 to -0.442; p < 0.001), and PP (β = 0.118, 95% CI 0.965-1.436; p < 0.001) were the significant factors determining uACR. The odds ratios (ORs) of a high PP (PP ≥ 60 mmHg) with a normal group [eGFR ≥ 60 ml/min/1.73 m2 and uACR < 30 mg/g] as a reference were significant for decreased eGFR [eGFR < 60 ml/min/1.73 m2, 1.484 (95% CI, 1.003-2.196)], elevated uACR [uACR ≥ 30 mg/g, 2.592 (95% CI, 2.085-3.223)], and decreased eGFR plus elevated uACR [eGFR < 60 ml/min/1.73 m2 and uACR ≥ 30 mg/g, 3.889 (95% CI, 2.519-6.004)]. Enhanced PP was associated with a decreased eGFR and an increase in uACR in Korean adults. In addition, the PP increased greatly when a decrease in eGFR and an increase in uACR appeared simultaneously. © 2017 The Author(s). Published by S. Karger AG, Basel.

Pancreatic Cysts in Autosomal Dominant Polycystic Kidney Disease: Prevalence and Association with PKD2 Gene Mutations.

PubMed

Kim, Jin Ah; Blumenfeld, Jon D; Chhabra, Shalini; Dutruel, Silvina P; Thimmappa, Nanda Deepa; Bobb, Warren O; Donahue, Stephanie; Rennert, Hanna E; Tan, Adrian Y; Giambrone, Ashley E; Prince, Martin R

2016-09-01

Purpose To define the magnetic resonance (MR) imaging prevalence of pancreatic cysts in a cohort of patients with autosomal dominant polycystic kidney disease (ADPKD) compared with a control group without ADPKD that was matched for age, sex, and renal function. Materials and Methods In this HIPAA-compliant, institutional review board-approved study, all patients with ADPKD provided informed consent; for control subjects, informed consent was waived. Patients with ADPKD (n = 110) with mutations identified in PKD1 or PKD2 and control subjects without ADPKD or known pancreatic disease (n = 110) who were matched for age, sex, estimated glomerular filtration rate, and date of MR imaging examination were evaluated for pancreatic cysts by using axial and coronal single-shot fast spin-echo T2-weighted images obtained at 1.5 T. Total kidney volume and liver volume were measured. Univariate and multivariable logistic regression analyses were conducted to evaluate potential associations between collected variables and presence of pancreatic cysts among patients with ADPKD. The number, size, location, and imaging characteristics of the cysts were recorded. Results Patients with ADPKD were significantly more likely than control subjects to have at least one pancreatic cyst (40 of 110 patients [36%] vs 25 of 110 control subjects [23%]; P = .027). In a univariate analysis, pancreatic cysts were more prevalent in patients with ADPKD with mutations in PKD2 than in PKD1 (21 of 34 patients [62%] vs 19 of 76 patients [25%]; P = .0002). In a multivariable logistic regression model, PKD2 mutation locus was significantly associated with the presence of pancreatic cysts (P = .0004) and with liver volume (P = .038). Patients with ADPKD and a pancreatic cyst were 5.9 times more likely to have a PKD2 mutation than a PKD1 mutation after adjusting for age, race, sex, estimated glomerular filtration rate, liver volume, and total kidney volume. Conclusion Pancreatic cysts were more prevalent in patients with ADPKD with PKD2 mutation than in control subjects or patients with PKD1 mutation. (©) RSNA, 2016 Online supplemental material is available for this article.

Detection of relationships between SUDOSCAN with estimated glomerular filtration rate (eGFR) in Chinese patients with type 2 diabetes.

PubMed

Mao, Fei; Zhu, Xiaoming; Lu, Bin; Li, Yiming

2018-04-01

SUDOSCAN (Impeto Medical, Paris, France) has been proved to be a new and non-invasive method in detecting renal dysfunction in type 2 diabetes mellitus (T2DM) patients. In this study, we sought to compare the result of diabetic kidney dysfunction score (DKD-score) of SUDOSCAN with estimated glomerular filtration rate (eGFR) by using quantile regression analysis, which was completely different from previous studies. A total number of 223 Chinese T2DM patients were enrolled in the study. SUDOSCAN, renal function test (including blood urea nitrogen, creatinine and uric acid) and 99 mTc-diethylenetriamine pentaacetic acid ( 99 mTc-DTPA) renal dynamic imaging were performed in all T2DM patients. DKD-score of SUDOSCAN was compared with eGFR detected by 99 mTc-DTPA renal dynamic imaging through quantile regression analysis. Its validation and utility was further determined through bias and precision test. The quantile regression analysis demonstrated the relationship with eGFR was inverse and significant for almost all percentiles of DKD-score. The coefficients decreased as the percentile of DKD-score increased. And in validation data set, both the bias and precision were increased with the eGFR (median difference, -21.2 ml/min/1.73 m 2 for all individuals vs. -4.6 ml/min/1.73 m 2 for eGFR between 0 and 59 ml/min/1.73 m 2 ; interquartile range [IQR] for the difference, -25.4 ml/min/1.73 m 2 vs. -14.7 ml/min/1.73 m 2 ). The eGFR category misclassification rate were 10% in eGFR 0-59 ml/min/1.73 m 2 group, 57.3% in 60-90 group, and 87.2% in eGFR > 90 ml/min/1.73 m 2 group. DKD-score of SUDOSCAN could be used to detect renal dysfunction in T2DM patients. A higher prognostic value of DKD-score was detected when eGFR level was lower. Copyright © 2018 Elsevier B.V. All rights reserved.

Hepatic steatosis and non-alcoholic fatty liver disease are not associated with decline in renal function in people with Type 2 diabetes.

PubMed

Jenks, S J; Conway, B R; Hor, T J; Williamson, R M; McLachlan, S; Robertson, C; Morling, J R; Strachan, M W J; Price, J F

2014-09-01

We aimed to determine whether the presence of hepatic steatosis and/or non-alcoholic fatty liver disease was associated with decline in renal function or onset of microalbuminuria in a cohort of people with Type 2 diabetes, including those managed in both primary and secondary care. Nine hundred and thirty-three patients from the Edinburgh Type 2 Diabetes Study, a cohort of Scottish men and women aged 60-74 years with Type 2 diabetes, underwent assessment for hepatic steatosis by liver ultrasonography 1 year after recruitment. Non-alcoholic fatty liver disease was defined as the presence of steatosis following exclusion of secondary causes of liver disease. Patients were followed for 4 years and decline in renal function was assessed by the change in estimated glomerular filtration rate over time. Of the 933 subjects, 530 had hepatic steatosis and, of those with hepatic steatosis, 388 had non-alcoholic fatty liver disease. Neither hepatic steatosis nor non-alcoholic fatty liver disease were significantly associated with rate of decline in renal function, with the mean rate of decline in estimated glomerular filtration rate being -1.55 ml min(-1) 1.73 m(-2) per year for participants with hepatic steatosis compared with -1.84 ml min(-1) 1.73 m(-2) for those without steatosis (P = 0.19). Similar results were obtained when the analysis was restricted to participants with and without non-alcoholic fatty liver disease (-1.44 vs. -1.64 ml min(-1) 1.73 m(-2) per year, respectively; P = 0.44). Additionally, neither hepatic steatosis nor non-alcoholic fatty liver disease were associated with the onset or regression of albuminuria during follow-up (all P ≥ 0.05). The presence of hepatic steatosis/non-alcoholic fatty liver disease was not associated with decline in renal function during a 4-year follow-up in our cohort of older people with Type 2 diabetes. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

Autosomal Dominant Tubulointerstitial Kidney Disease: Clinical Presentation of Patients With ADTKD-UMOD and ADTKD-MUC1.

PubMed

Ayasreh, Nadia; Bullich, Gemma; Miquel, Rosa; Furlano, Mónica; Ruiz, Patricia; Lorente, Laura; Valero, Oliver; García-González, Miguel Angel; Arhda, Nisrine; Garin, Intza; Martínez, Víctor; Pérez-Gómez, Vanessa; Fulladosa, Xavier; Arroyo, David; Martínez-Vea, Alberto; Espinosa, Mario; Ballarín, Jose; Ars, Elisabet; Torra, Roser

2018-05-18

Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare underdiagnosed cause of end-stage renal disease (ESRD). ADTKD is caused by mutations in at least 4 different genes: MUC1, UMOD, HNF1B, and REN. Retrospective cohort study. 56 families (131 affected individuals) with ADTKD referred from different Spanish hospitals. Clinical, laboratory, radiologic, and pathologic data were collected, and genetic testing for UMOD, MUC1, REN, and HNF1B was performed. Hyperuricemia, ultrasound findings, renal histology, genetic mutations. Age at ESRD, rate of decline in estimated glomerular filtration rate. ADTKD was diagnosed in 25 families (45%), 9 carried UMOD pathogenic variants (41 affected members), and 16 carried the MUC1 pathogenic mutation c.(428)dupC (90 affected members). No pathogenic variants were identified in REN or HNF1B. Among the 77 individuals who developed ESRD, median age at onset of ESRD was 51 years for those with ADTKD-MUC1 versus 56 years (P=0.1) for those with ADTKD-UMOD. Individuals with the MUC1 duplication presented higher risk for developing ESRD (HR, 2.24; P=0.03). The slope of decline in estimated glomerular filtration rate showed no significant difference between groups (-3.0mL/min/1.73m 2 per year in the ADTKD-UMOD group versus -3.9mL/min/1.73m 2 per year in the ADTKD-MUC1 group; P=0.2). The prevalence of hyperuricemia was significantly higher in individuals with ADTKD-UMOD (87% vs 54%; P=0.006). Although gout occurred more frequently in this group, the difference was not statistically significant (24% vs 7%; P=0.07). Relatively small Spanish cohort. MUC1 analysis limited to cytosine duplication. The main genetic cause of ADTKD in our Spanish cohort is the MUC1 pathogenic mutation c.(428)dupC. Renal survival may be worse in individuals with the MUC1 mutation than in those with UMOD mutations. Clinical presentation does not permit distinguishing between these variants. However, hyperuricemia and gout are more frequent in individuals with ADTKD-UMOD. Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Meta-analysis of safety and efficacy for direct oral anticoagulation treatment of non-valvular atrial fibrillation in relation to renal function.

PubMed

Zou, Rongjun; Tao, Jun; Shi, Wanting; Yang, Minglei; Li, Hongmu; Lin, Xifeng; Yang, Songran; Hua, Ping

2017-12-01

We performed a meta-analysis of the safety and efficacy of anticoagulation treatment for atrial fibrillation (AF) in relation to renal function. We also examined the change in estimated glomerular filtration rate (eGFR) from baseline and compared the outcomes for patients with stable and worsening renal function. We selected studies that used randomized controlled trials in which outcomes for direct oral anticoagulants (DOACs) (dabigatran, rivaroxaban, apixaban, or edoxaban) were compared with those for warfarin in AF patients with normal, mild or moderate renal function, except the severe one (creatinine clearance<30). We assessed five clinical trials, involving 72,608 patients. Pooled analysis indicated that the risk of stroke was lower for DOACs than for warfarin among patients with mild renal impairment (Risk ratio, 0.79; 95% confidence interval, 0.68-0.91) and moderate renal impairment (0.80, 0.69-0.92). No major differences were found in patients with normal renal function. Additionally, DOACs were associated with fewer major bleeds among patients with normal (0.77, 0.70-0.84), mild (0.86, 0.77-0.95), and moderate renal impairment (0.73, 0.65-0.82). Among those treated with DOACs, a lower dosage was associated with lower risk of major bleeding (0.75, 0.68-0.83) and higher risk of stroke or systemic embolism (1.28, 1.12-1.47). Further, DOACs tended to be associated with a lower estimated glomerular filtration rate (eGFR) than warfarin even after 30months. Finally, we found significant differences in the risk of stroke (2.09, 1.64-2.68) and major bleeding (2.01, 1.66-2.42) between patients with stable and worsening renal function. DOACs have a greater clinical benefit than warfarin with respect to renal function. They are associated with a comparatively lower risk of stroke and major bleeding, as well lower eGFR. This suggests these agents are a better choice in patients with renal disease. Copyright © 2017. Published by Elsevier Ltd.