Genome-wide association study of kidney function decline in individuals of European descent.

PubMed

Gorski, Mathias; Tin, Adrienne; Garnaas, Maija; McMahon, Gearoid M; Chu, Audrey Y; Tayo, Bamidele O; Pattaro, Cristian; Teumer, Alexander; Chasman, Daniel I; Chalmers, John; Hamet, Pavel; Tremblay, Johanne; Woodward, Marc; Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur; Harris, Tamara B; Launer, Lenore J; Smith, Albert V; Mitchell, Braxton D; O'Connell, Jeffrey R; Shuldiner, Alan R; Coresh, Josef; Li, Man; Freudenberger, Paul; Hofer, Edith; Schmidt, Helena; Schmidt, Reinhold; Holliday, Elizabeth G; Mitchell, Paul; Wang, Jie Jin; de Boer, Ian H; Li, Guo; Siscovick, David S; Kutalik, Zoltan; Corre, Tanguy; Vollenweider, Peter; Waeber, Gérard; Gupta, Jayanta; Kanetsky, Peter A; Hwang, Shih-Jen; Olden, Matthias; Yang, Qiong; de Andrade, Mariza; Atkinson, Elizabeth J; Kardia, Sharon L R; Turner, Stephen T; Stafford, Jeanette M; Ding, Jingzhong; Liu, Yongmei; Barlassina, Cristina; Cusi, Daniele; Salvi, Erika; Staessen, Jan A; Ridker, Paul M; Grallert, Harald; Meisinger, Christa; Müller-Nurasyid, Martina; Krämer, Bernhard K; Kramer, Holly; Rosas, Sylvia E; Nolte, Ilja M; Penninx, Brenda W; Snieder, Harold; Fabiola Del Greco, M; Franke, Andre; Nöthlings, Ute; Lieb, Wolfgang; Bakker, Stephan J L; Gansevoort, Ron T; van der Harst, Pim; Dehghan, Abbas; Franco, Oscar H; Hofman, Albert; Rivadeneira, Fernando; Sedaghat, Sanaz; Uitterlinden, André G; Coassin, Stefan; Haun, Margot; Kollerits, Barbara; Kronenberg, Florian; Paulweber, Bernhard; Aumann, Nicole; Endlich, Karlhans; Pietzner, Mike; Völker, Uwe; Rettig, Rainer; Chouraki, Vincent; Helmer, Catherine; Lambert, Jean-Charles; Metzger, Marie; Stengel, Benedicte; Lehtimäki, Terho; Lyytikäinen, Leo-Pekka; Raitakari, Olli; Johnson, Andrew; Parsa, Afshin; Bochud, Murielle; Heid, Iris M; Goessling, Wolfram; Köttgen, Anna; Kao, W H Linda; Fox, Caroline S; Böger, Carsten A

2015-05-01

Genome-wide association studies (GWASs) have identified multiple loci associated with cross-sectional eGFR, but a systematic genetic analysis of kidney function decline over time is missing. Here we conducted a GWAS meta-analysis among 63,558 participants of European descent, initially from 16 cohorts with serial kidney function measurements within the CKDGen Consortium, followed by independent replication among additional participants from 13 cohorts. In stage 1 GWAS meta-analysis, single-nucleotide polymorphisms (SNPs) at MEOX2, GALNT11, IL1RAP, NPPA, HPCAL1, and CDH23 showed the strongest associations for at least one trait, in addition to the known UMOD locus, which showed genome-wide significance with an annual change in eGFR. In stage 2 meta-analysis, the significant association at UMOD was replicated. Associations at GALNT11 with Rapid Decline (annual eGFR decline of 3 ml/min per 1.73 m(2) or more), and CDH23 with eGFR change among those with CKD showed significant suggestive evidence of replication. Combined stage 1 and 2 meta-analyses showed significance for UMOD, GALNT11, and CDH23. Morpholino knockdowns of galnt11 and cdh23 in zebrafish embryos each had signs of severe edema 72 h after gentamicin treatment compared with controls, but no gross morphological renal abnormalities before gentamicin administration. Thus, our results suggest a role in the deterioration of kidney function for the loci GALNT11 and CDH23, and show that the UMOD locus is significantly associated with kidney function decline.

Arterial stiffness and decline of renal function in a primary care population.

PubMed

van Varik, Bernard J; Vossen, Liv M; Rennenberg, Roger J; Stoffers, Henri E; Kessels, Alfons G; de Leeuw, Peter W; Kroon, Abraham A

2017-01-01

Arterial stiffness is an important pathophysiological factor linking cardiovascular disease and kidney disease. Controversy exists as to whether arterial stiffness causes renal function decline, or kidney dysfunction leads to stiffening or whether the association is mutual. We aimed to investigate the longitudinal association between arterial stiffness and annual rate of renal function decline. We prospectively investigated in a primary care population whether carotid-femoral pulse wave velocity (PWV) was associated with estimated glomerular filtration rate (eGFR) and annual decline in eGFR in participants aged ⩾40 years without overt kidney disease. Baseline data on PWV and eGFR were available for 587 participants; follow-up measurements with a mean duration of 5.6 years were available for 222 patients. PWV, female gender and mean arterial pressure were independently associated with eGFR at baseline, although age confounded this association. More importantly, baseline PWV, age and eGFR were independent predictors of renal function decline. Stratification for age showed that the effect of PWV on rate of eGFR decline was amplified with advancing age. On the other hand, baseline eGFR did not determine annual change in PWV, suggesting a unidirectional association between arterial stiffness and eGFR. Arterial stiffness amplifies age-related renal function decline, suggesting that arterial stiffness plays a causal role in the development of renal damage, at least at later stages of age-related renal function decline, possibly through impaired renal autoregulation and increased arterial blood pressure pulsatility.

Effects of RAAS Inhibitors in Patients with Kidney Disease.

PubMed

Zhang, Fan; Liu, Hong; Liu, Di; Liu, Yexin; Li, Huiqiong; Tan, Xia; Liu, Fuyou; Peng, Youming; Zhang, Hongqing

2017-08-08

Proteinuria and decline of renal function are associated with progression of kidney disease. The Renin Angiotensin Aldosterone System (RAAS) plays an important role in blood pressure regulation, fluid volume, and sodium balance. Overactivity of RAAS contributes to the pathogenesis of a variety of clinical conditions including progress of chronic kidney disease (CKD). This review summarizes the use of RAAS inhibitors as dual therapy or monotherapy in different stages of kidney disease. Experimental and clinical studies have demonstrated RAAS inhibitors prevent proteinuria, kidney fibrosis and slow decline of renal function and thus play a protective role in both early and end stages of kidney disease. While combination use of RAAS inhibitors showed higher efficiency compared with monotherapy, it is also associated with higher incidence of adverse events. Besides ACEI/ARBs, more mechanism research of mineralocorticoid receptor antagonists in kidney disease should be performed.

Effects of uric acid on kidney function decline differ depending on baseline kidney function in type 2 diabetic patients.

PubMed

Hanai, Ko; Tauchi, Eriko; Nishiwaki, Yui; Mori, Tomomi; Yokoyama, Yoichi; Uchigata, Yasuko; Babazono, Tetsuya

2018-05-30

Most existing data regarding effects of uric acid (UA) on diabetic kidney disease have considered patients with preserved kidney function. We examined a hypothesis that there are differences in the effects of serum UA levels on the decline in kidney function depending on baseline kidney function in diabetic patients. In this historical cohort study, 7033 type 2 diabetic patients were analyzed and classified into two groups as follows: nonchronic kidney disease (non-CKD), with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 (n = 4994), and CKD, with an eGFR <60 mL/min/1.73 m2 (n = 2039). The composite endpoint was a ≥30% decrease in eGFR from baseline or the initiation of renal replacement therapy. The hazard ratio (HR) of serum UA levels at baseline was estimated using multivariate Cox proportional hazards models. There was a significant interaction between UA levels and baseline eGFR with respect to the endpoint (P < 0.001). The HRs of 1 mg/dL increase in UA levels were 1.13 [95% confidence interval (CI) 1.05-1.22, P = 0.002] and 0.93 (95% CI 0.88-0.99, P = 0.02) in the non-CKD and CKD groups, respectively. When patients were classified by quintile of UA levels, the HRs of those in the 5th quintile (versus 1st quintile) were 1.64 (95% CI 1.23-2.18, P < 0.001) and 0.76 (95% CI 0.58-0.99, P = 0.05) in the non-CKD and CKD groups, respectively. The effects of UA on kidney function decline might differ depending on baseline kidney function in type 2 diabetic patients. High UA levels are the prognostic factor only in patients with preserved kidney function.

Longitudinal Blood Pressure Changes and Kidney Function Decline in Persons Without Chronic Kidney Disease: Findings From the MESA Study.

PubMed

Judson, Gregory L; Rubinsky, Anna D; Shlipak, Michael G; Katz, Ronit; Kramer, Holly; Jacobs, David R; Odden, Michelle C; Peralta, Carmen A

2018-04-13

While changes in blood pressure (BP) are independently associated with cardiovascular events, less is known about the association between changes in BP and subsequent changes in renal function in adults with an estimated glomerular filtration rate (eGFR) of >60 ml/min/1.73 m2. The present study included 3,920 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) study who had ≥2 BP measurements during the first 5 years of MESA and had eGFR measurements at both year 5 and 10. Change in BP was estimated as the annualized slope of BP between year 0 and 5 based on linear mixed models (mean number of measurements = 4.0). Participants were then grouped into 1 of 3 categories based on the distribution of systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) change (top 20%, middle 21-79%, bottom 20%). We calculated eGFR from cystatin C (ml/min/1.73 m2), estimated annual change in eGFR (ml/min/1.73 m2/year), and defined rapid kidney function decline as a >30% decrease in eGFR from year 5 to 10. We used multivariable logistic regression adjusting for year 0 demographic and clinical characteristics, including eGFR and BP, to determine associations of BP change with rapid kidney function decline. Median age was 59 [interquartile range (IQR): 52, 67] and median eGFR at year 0 was 95.5 (IQR: 81.7, 105.9) ml/min/1.73 m2. Median SBP at year 0 was 111, 121, and 147 mm Hg for increasing, stable, and decreasing SBP change, respectively. Increasing SBP and widening PP change were each associated with higher odds of rapid kidney function decline compared with stable SBP and PP groups, respectively [odds ratio, OR 1.7 (95% confidence interval, CI 1.3, 2.4) for SBP; OR 1.4 (95% CI 1.1, 1.9) for PP]. Decreasing SBP was associated with rapid kidney function decline after adjusting for all covariates except for year 0 BP [OR 1.4 (95% CI 1.0, 1.8)], but this association was no longer statistically significant after adjustment for year 0 BP. There were no significant associations between DBP change and rapid decline in the fully adjusted models. Similar findings were seen with annual change in eGFR. Increasing SBP and widening PP over time were associated with greater risk for accelerated kidney function decline even at BP levels below established hypertension thresholds.

Genome-wide association study of kidney function decline in individuals of European descent

PubMed Central

Gorski, Mathias; Tin, Adrienne; Garnaas, Maija; McMahon, Gearoid M.; Chu, Audrey Y.; Tayo, Bamidele O.; Pattaro, Cristian; Teumer, Alexander; Chasman, Daniel I.; Chalmers, John; Hamet, Pavel; Tremblay, Johanne; Woodward, Marc; Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur; Harris, Tammara B.; Launer, Lenore J.; Smith, Albert V.; Mitchell, Braxton D.; O'Connell, Jeffrey R.; Shuldiner, Alan R.; Coresh, Josef; Li, Man; Freudenberger, Paul; Hofer, Edith; Schmidt, Helena; Schmidt, Reinhold; Holliday, Elizabeth G.; Mitchell, Paul; Wang, Jie Jin; de Boer, Ian H.; Li, Guo; Siscovick, David S.; Kutalik, Zoltan; Corre, Tanguy; Vollenweider, Peter; Waeber, Gérard; Gupta, Jayanta; Kanetsky, Peter A.; Hwang, Shih-Jen; Olden, Matthias; Yang, Qiong; de Andrade, Mariza; Atkinson, Elizabeth J.; Kardia, Sharon L.R.; Turner, Stephen T.; Stafford, Jeanette M.; Ding, Jingzhong; Liu, Yongmei; Barlassina, Cristina; Cusi, Daniele; Salvi, Erika; Staessen, Jan A; Ridker, Paul M; Grallert, Harald; Meisinger, Christa; Müller-Nurasyid, Martina; Krämer, Bernhard K.; Kramer, Holly; Rosas, Sylvia E.; Nolte, Ilja M.; Penninx, Brenda W.; Snieder, Harold; Del Greco, Fabiola; Franke, Andre; Nöthlings, Ute; Lieb, Wolfgang; Bakker, Stephan J.L.; Gansevoort, Ron T.; van der Harst, Pim; Dehghan, Abbas; Franco, Oscar H.; Hofman, Albert; Rivadeneira, Fernando; Sedaghat, Sanaz; Uitterlinden, André G.; Coassin, Stefan; Haun, Margot; Kollerits, Barbara; Kronenberg, Florian; Paulweber, Bernhard; Aumann, Nicole; Endlich, Karlhans; Pietzner, Mike; Völker, Uwe; Rettig, Rainer; Chouraki, Vincent; Helmer, Catherine; Lambert, Jean-Charles; Metzger, Marie; Stengel, Benedicte; Lehtimäki, Terho; Lyytikäinen, Leo-Pekka; Raitakari, Olli; Johnson, Andrew; Parsa, Afshin; Bochud, Murielle; Heid, Iris M.; Goessling, Wolfram; Köttgen, Anna; Kao, H. Linda; Fox, Caroline S.; Böger, Carsten A.

2014-01-01

Genome wide association studies (GWAS) have identified multiple loci associated with cross-sectional eGFR, but a systematic genetic analysis of kidney function decline over time is missing. Here we conducted a GWAS meta-analysis among 63,558 participants of European descent, initially from 16 cohorts with serial kidney function measurements within the CKDGen Consortium, followed by independent replication among additional participants from 13 cohorts. In stage 1 GWAS meta-analysis, SNPs at MEOX2, GALNT11, IL1RAP, NPPA, HPCAL1 and CDH23 showed the strongest associations for at least one trait, in addition to the known UMOD locus which showed genome-wide significance with an annual change in eGFR. In stage 2 meta-analysis, the significant association at UMOD was replicated. Associations at GALNT11 with Rapid Decline (annual eGFRdecline of 3ml/min/1.73m2 or more), and CDH23 with eGFR change among those with CKD showed significant suggestive evidence of replication. Combined stage 1 and 2 meta-analyses showed significance for UMOD, GALNT11 and CDH23. Morpholino knockdowns of galnt11 and cdh23 in zebrafish embryos each had signs of severe edema 72 hours after gentamicin treatment compared to controls, but no gross morphological renal abnormalities before gentamicin administration. Thus, our results suggest a role in the deterioration of kidney function for the loci GALNT11 and CDH23, and show that the UMOD locus is significantly associated with kidney function decline. PMID:25493955

Associations of Sugar and Artificially Sweetened Soda with Albuminuria and Kidney Function Decline in Women

PubMed Central

Curhan, Gary C.

2011-01-01

Summary Background and objectives Sugar-sweetened soda is reported to be associated with increased risk for diabetes and albuminuria, but there are currently limited data on how sugar or artificially sweetened soda may be related to kidney function decline. Design, setting, participants, & measurements This study identified 3318 women participating in the Nurses' Health Study with data on soda intake and albuminuria; of these, 3256 also had data on estimated GFR (eGFR) change between 1989 and 2000. Cumulative average beverage intake was derived from the 1984, 1986, 1990, 1994, and 1998 food frequency questionnaires. Serving categories included <1/mo (referent), 1 to 4/mo, 2 to 6/wk, 1 to 1.9/d, and ≥2/d. Microalbuminuria (MA) was considered a urinary albumin-to-creatinine ratio of 25 to 355 μg/mg. For kidney function change, the primary outcome was a ≥30% decline in eGFR over 11 years; rapid eGFR decline defined as ≥3 ml/min per 1.73 m2 per year was also examined. Results Consumption of ≥2 servings per day of artificially sweetened (diet) soda was independently associated with eGFR decline ≥30% (OR 2.02, 95% CI 1.36 to 3.01) and ≥3 ml/min per 1.73 m2 per year (OR 2.20, 95% CI 1.36 to 3.55). No increased risk for eGFR decline was observed for <2 servings per day of diet soda. No associations were noted between diet soda and MA or sugar soda and MA or eGFR decline. Conclusions Consumption of ≥2 servings per day of artificially sweetened soda is associated with a 2-fold increased odds for kidney function decline in women. PMID:20884773

Associations of sugar and artificially sweetened soda with albuminuria and kidney function decline in women.

PubMed

Lin, Julie; Curhan, Gary C

2011-01-01

Sugar-sweetened soda is reported to be associated with increased risk for diabetes and albuminuria, but there are currently limited data on how sugar or artificially sweetened soda may be related to kidney function decline. This study identified 3318 women participating in the Nurses' Health Study with data on soda intake and albuminuria; of these, 3256 also had data on estimated GFR (eGFR) change between 1989 and 2000. Cumulative average beverage intake was derived from the 1984, 1986, 1990, 1994, and 1998 food frequency questionnaires. Serving categories included <1/mo (referent), 1 to 4/mo, 2 to 6/wk, 1 to 1.9/d, and ≥ 2/d. Microalbuminuria (MA) was considered a urinary albumin-to-creatinine ratio of 25 to 355 μg/mg. For kidney function change, the primary outcome was a ≥ 30% decline in eGFR over 11 years; rapid eGFR decline defined as ≥ 3 ml/min per 1.73 m(2) per year was also examined. Consumption of ≥ 2 servings per day of artificially sweetened (diet) soda was independently associated with eGFR decline ≥ 30% (OR 2.02, 95% CI 1.36 to 3.01) and ≥ 3 ml/min per 1.73 m(2) per year (OR 2.20, 95% CI 1.36 to 3.55). No increased risk for eGFR decline was observed for <2 servings per day of diet soda. No associations were noted between diet soda and MA or sugar soda and MA or eGFR decline. Consumption of ≥ 2 servings per day of artificially sweetened soda is associated with a 2-fold increased odds for kidney function decline in women.

Exercise and CKD: Skeletal Muscle Dysfunction and Practical Application of Exercise to Prevent and Treat Physical Impairments in CKD.

PubMed

Roshanravan, Baback; Gamboa, Jorge; Wilund, Kenneth

2017-06-01

Patients with chronic kidney disease experience substantial loss of muscle mass, weakness, and poor physical performance. As kidney disease progresses, skeletal muscle dysfunction forms a common pathway for mobility limitation, loss of functional independence, and vulnerability to disease complications. Screening for those at high risk for mobility disability by self-reported and objective measures of function is an essential first step in developing an interdisciplinary approach to treatment that includes rehabilitative therapies and counseling on physical activity. Exercise has beneficial effects on systemic inflammation, muscle, and physical performance in chronic kidney disease. Kidney health providers need to identify patient and care delivery barriers to exercise in order to effectively counsel patients on physical activity. A thorough medical evaluation and assessment of baseline function using self-reported and objective function assessment is essential to guide an effective individualized exercise prescription to prevent function decline in persons with kidney disease. This review focuses on the impact of kidney disease on skeletal muscle dysfunction in the context of the disablement process and reviews screening and treatment strategies that kidney health professionals can use in clinical practice to prevent functional decline and disability. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

The Importance of Residual Kidney Function in Haemodialysis Patients.

PubMed

Kong, Jessica; Davies, Matthew; Mount, Peter

2018-06-19

In contrast to peritoneal dialysis, residual kidney function is commonly disregarded for haemodialysis patients, and not regularly monitored or taken into account in routine clinical care. This is despite evidence that higher levels of residual kidney function in haemodialysis patients associate with better outcomes including survival, total solute clearance, nutrition, inflammation, and fluid balance. This review aims to summarise the clinical effects of residual kidney function specifically in haemodialysis patients. Some level of residual kidney function is present in over 80% of patients at the time of dialysis initiation, and while this declines over time, up to 30% of patients on haemodialysis for 5 years still have a measurable level of native kidney function. There is little evidence on how best to preserve residual kidney function in haemodialysis patients, although it has been observed that intensive haemodialysis regimens in incident haemodialysis patients appear to accelerate residual kidney function decline. Residual kidney function is not commonly factored in to haemodialysis prescription and measures of adequacy, despite the fact that some guidelines such as KDOQI and European Best Practice Guidelines suggest that it is reasonable to do. This likely relates, at least in part, to perceived concerns regarding the inconvenience of timed urine collections, and to the complexity and lack of consensus regarding the methods for integrating the intermittent clearance of haemodialysis with the continuous clearance of native renal function. Further research is required into how best to maintain and maximise the benefits of residual kidney function in haemodialysis patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Relationship of fibroblast growth factor 21 with kidney function and albuminuria: multi-ethnic study of atherosclerosis.

PubMed

Anuwatmatee, Sahapab; Allison, Matthew A; Shlipak, Michael G; McClelland, Robyn L; Kramer, Holly; Tang, Shudi; Hou, Liming; Rye, Kerry-Anne; Ong, Kwok Leung

2018-05-15

Fibroblast growth factor 21 (FGF21) may play a role in the development of chronic kidney disease (CKD). We therefore investigated the relationship of plasma FGF21 levels with kidney function and albuminuria in the Multi-Ethnic Study of Atherosclerosis (MESA). The analysis included 5724 MESA participants ages 45-84 years between 2000 and 2002, free of clinically apparent cardiovascular disease (CVD). Participants were followed up in person at four additional clinic visits over 10 years. Plasma FGF21 levels were measured at baseline examination by enzyme-linked immunosorbent assay. Kidney function was assessed by estimated glomerular filtration rate (eGFR). Outcomes were urinary albumin:creatinine ratio (UACR) progression, incident CKD by eGFR (reaching eGFR <60 mL/min/1.73 m2 with eGFR loss rate ≥1 mL/min/1.73 m2 per year) and rapid kidney function decline (eGFR decline >5%/year). At baseline, higher FGF21 levels, assessed as both continuous and categorical quartile variables, were significantly associated with lower eGFR and higher UACR, after adjusting for demographic, socioeconomic and other confounding factors [adjusted mean differences of -2.63 mL/min/1.73 m2 in eGFR and 0.134 in log normally transformed UACR (mg/g) for the highest FGF21 quartile compared with the lowest quartile, all P < 0.001]. However, in longitudinal analyses, baseline FGF21 levels did not predict incident CKD by eGFR, rapid kidney function decline or UACR progression. No significant interaction with sex and race/ethnicity was found (all P > 0.05). Our study does not support a role of FGF21 as a biomarker for predicting kidney function decline or albuminuria in adults free of clinically apparent CVD at baseline.

Patterns of Kidney Function Decline in Autosomal Dominant Polycystic Kidney Disease: A Post Hoc Analysis From the HALT-PKD Trials.

PubMed

Brosnahan, Godela M; Abebe, Kaleab Z; Moore, Charity G; Rahbari-Oskoui, Frederic F; Bae, Kyongtae T; Grantham, Jared J; Schrier, Robert W; Braun, William E; Chapman, Arlene B; Flessner, Michael F; Harris, Peter C; Hogan, Marie C; Perrone, Ronald D; Miskulin, Dana C; Steinman, Theodore I; Torres, Vicente E

2018-05-01

Previous clinical studies of autosomal dominant polycystic kidney disease (ADPKD) reported that loss of kidney function usually follows a steep and relentless course. A detailed examination of individual patterns of decline in estimated glomerular filtration rate (eGFR) has not been performed. Longitudinal post hoc analysis of data collected during the Halt Progression of Polycystic Kidney Disease (HALT-PKD) trials. 494 HALT-PKD Study A participants (younger; preserved eGFR) and 435 Study B participants (older; reduced eGFR) who had more than 3 years of follow-up and 7 or more eGFR assessments. Longitudinal eGFR assessments using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation. Demographic, clinical, laboratory, and imaging features of participants. Probability of linear and nonlinear decline patterns or of stable eGFR calculated for each participant from a Bayesian model of individual eGFR trajectories. Most (62.5% in Study A and 81% in Study B) participants had a linear decline in eGFR during up to 8 years of follow-up. A proportion (22% in Study A and 13% in Study B) of progressors had a nonlinear pattern. 15.5% of participants in Study A and 6% in Study B had a prolonged (≥4.5 years) period of stable eGFRs. These individuals (Study A) had significantly smaller total kidney volumes, higher renal blood flows, lower urinary albumin excretion, and lower body mass index at baseline and study end. In Study B, participants with reduced but stable eGFRs were older than the progressors. Two-thirds of nonprogressors in both studies had PKD1 mutations, with enrichment for weak nontruncating mutations. Relatively short follow-up of a clinical trial population. Although many individuals with ADPKD have a linear decline in eGFR, prolonged intervals of stable GFRs occur in a substantial fraction. Lower body mass index was associated with more stable kidney function in early ADPKD. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Post Hoc Analyses of Randomized Clinical Trial for the Effect of Clopidogrel Added to Aspirin on Kidney Function.

PubMed

Ikeme, Jesse C; Pergola, Pablo E; Scherzer, Rebecca; Shlipak, Michael G; Benavente, Oscar R; Peralta, Carmen A

2017-07-07

Despite the high burden of CKD, few specific therapies are available that can halt disease progression. In animal models, clopidogrel has emerged as a potential therapy to preserve kidney function. The effect of clopidogrel on kidney function in humans has not been established. The Secondary Prevention of Small Subcortical Strokes Study randomized participants with prior lacunar stroke to treatment with aspirin or aspirin plus clopidogrel. We compared annual eGFR decline and incidence of rapid eGFR decline (≥30% from baseline) using generalized estimating equations and interval-censored proportional hazards regression, respectively. We also stratified our analyses by baseline eGFR, systolic BP target, and time after randomization. At randomization, median age was 62 (interquartile range, 55-71) years old; 36% had a history of diabetes, 90% had hypertension, and the median eGFR was 81 (interquartile range, 65-94) ml/min per 1 m 2 . Persons receiving aspirin plus clopidogrel had an average annual change in kidney function of -1.39 (95% confidence interval, -1.15 to -1.62) ml/min per 1.73 m 2 per year compared with -1.52 (95% confidence interval, -1.30 to -1.74) ml/min per 1.73 m 2 per year among persons receiving aspirin only ( P =0.42). Rapid kidney function decline occurred in 21% of participants receiving clopidogrel plus aspirin compared with 22% of participants receiving aspirin plus placebo (hazard ratio, 0.94; 95% confidence interval, 0.79 to 1.10; P =0.42). Findings did not vary by baseline eGFR, time after randomization, or systolic BP target (all P values for interaction were >0.3). We found no effect of clopidogrel added to aspirin compared with aspirin alone on kidney function decline among persons with prior lacunar stroke. Copyright © 2017 by the American Society of Nephrology.

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.

The natural history of renal function after surgical management of renal cell carcinoma: Results from the Canadian Kidney Cancer Information System.

PubMed

Mason, Ross; Kapoor, Anil; Liu, Zhihui; Saarela, Olli; Tanguay, Simon; Jewett, Michael; Finelli, Antonio; Lacombe, Louis; Kawakami, Jun; Moore, Ronald; Morash, Christopher; Black, Peter; Rendon, Ricardo A

2016-11-01

Patients who undergo surgical management of renal cell carcinoma (RCC) are at risk for chronic kidney disease and its sequelae. This study describes the natural history of renal function after radical and partial nephrectomy and explores factors associated with postoperative decline in renal function. This is a multi-institutional cohort study of patients in the Canadian Kidney Cancer Information System who underwent partial or radical nephrectomy for RCC. Estimated glomerular filtration rate (eGFR) and stage of chronic kidney disease were determined preoperatively and at 3, 12, and 24 months postoperatively. Linear regression was used to determine the association between postoperative eGFR and type of surgery (radical vs. partial), duration of ischemia, ischemia type (warm vs. cold), and tumor size. With a median follow-up of 26 months, 1,379 patients were identified from the Canadian Kidney Cancer Information System database including 665 and 714 who underwent partial and radical nephrectomy, respectively. Patients undergoing radical nephrectomy had a lower eGFR (mean = 19ml/min/1.73m 2 lower) at 3, 12, and 24 months postoperatively (P<0.001). Decline in renal function occurred early and remained stable throughout follow-up. A lower preoperative eGFR and increasing age were also associated with a lower postoperative eGFR (P<0.01). Ischemia type and duration were not predictive of postoperative decline in eGFR (P>0.05). Severe renal failure (eGFR<30ml/min/1.73m 2 ) developed postoperatively in 12.5% and 4.1% of radical and partial nephrectomy patients, respectively (P<0.001). After the initial postoperative decline, renal function remains stable in patients undergoing surgery for RCC. Patients undergoing radical nephrectomy have a greater long-term reduction in renal function compared with those undergoing partial nephrectomy. Ischemia duration and type are not predictive of postoperative renal function when adhering to generally short ischemia durations. Copyright © 2016 Elsevier Inc. All rights reserved.

Fibroblast Growth Factor 23 and Kidney Disease Progression in Autosomal Dominant Polycystic Kidney Disease.

PubMed

Chonchol, Michel; Gitomer, Berenice; Isakova, Tamara; Cai, Xuan; Salusky, Isidro; Pereira, Renata; Abebe, Kaleab; Torres, Vicente; Steinman, Theodor I; Grantham, Jared J; Chapman, Arlene B; Schrier, Robert W; Wolf, Myles

2017-09-07

Increases in fibroblast growth factor 23 precede kidney function decline in autosomal dominant polycystic kidney disease; however, the role of fibroblast growth factor 23 in autosomal dominant polycystic kidney disease has not been well characterized. We measured intact fibroblast growth factor 23 levels in baseline serum samples from 1002 participants in the HALT-PKD Study A ( n =540; mean eGFR =91±17 ml/min per 1.73 m 2 ) and B ( n =462; mean eGFR =48±12 ml/min per 1.73 m 2 ). We used linear mixed and Cox proportional hazards models to test associations between fibroblast growth factor 23 and eGFR decline, percentage change in height-adjusted total kidney volume, and composite of time to 50% reduction in eGFR, onset of ESRD, or death. Median (interquartile range) intact fibroblast growth factor 23 was 44 (33-56) pg/ml in HALT-PKD Study A and 69 (50-93) pg/ml in Study B. In adjusted models, annualized eGFR decline was significantly faster in the upper fibroblast growth factor 23 quartile (Study A: quartile 4, -3.62; 95% confidence interval, -4.12 to -3.12 versus quartile 1, -2.51; 95% confidence interval, -2.71 to -2.30 ml/min per 1.73 m 2 ; P for trend <0.001; Study B: quartile 4, -3.74; 95% confidence interval, -4.14 to -3.34 versus quartile 1, -2.78; 95% confidence interval, -2.92 to -2.63 ml/min per 1.73 m 2 ; P for trend <0.001). In Study A, higher fibroblast growth factor 23 quartiles were associated with greater longitudinal percentage increase in height-adjusted total kidney volume in adjusted models (quartile 4, 6.76; 95% confidence interval, 5.57 to 7.96 versus quartile 1, 6.04; 95% confidence interval, 5.55 to 6.54; P for trend =0.03). In Study B, compared with the lowest quartile, the highest fibroblast growth factor 23 quartile was associated with elevated risk for the composite outcome (hazard ratio, 3.11; 95% confidence interval, 1.84 to 5.25). Addition of fibroblast growth factor 23 to a model of annualized decline in eGFR≥3.0 ml/min per 1.73 m 2 did not improve risk prediction. Higher serum fibroblast growth factor 23 concentration was associated with kidney function decline, height-adjusted total kidney volume percentage increase, and death in patients with autosomal dominant polycystic kidney disease. However, fibroblast growth factor 23 did not substantially improve prediction of rapid kidney function decline. Copyright © 2017 by the American Society of Nephrology.

Reduced Renal Methylarginine Metabolism Protects against Progressive Kidney Damage

PubMed Central

Caplin, Ben; Boruc, Olga; Bruce-Cobbold, Claire; Cutillas, Pedro; Dormann, Dirk; Faull, Peter; Grossman, Rebecca C.; Khadayate, Sanjay; Mas, Valeria R.; Nitsch, Dorothea D.; Wang, Zhen; Norman, Jill T.; Wilcox, Christopher S.; Wheeler, David C.; Leiper, James

2015-01-01

Nitric oxide (NO) production is diminished in many patients with cardiovascular and renal disease. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthesis, and elevated plasma levels of ADMA are associated with poor outcomes. Dimethylarginine dimethylaminohydrolase-1 (DDAH1) is a methylarginine-metabolizing enzyme that reduces ADMA levels. We reported previously that a DDAH1 gene variant associated with increased renal DDAH1 mRNA transcription and lower plasma ADMA levels, but counterintuitively, a steeper rate of renal function decline. Here, we test the hypothesis that reduced renal-specific ADMA metabolism protects against progressive renal damage. Renal DDAH1 is expressed predominately within the proximal tubule. A novel proximal tubule–specific Ddah1 knockout (Ddah1PT−/−) mouse demonstrated tubular cell accumulation of ADMA and lower NO concentrations, but unaltered plasma ADMA concentrations. Ddah1PT−/− mice were protected from reduced kidney tissue mass, collagen deposition, and profibrotic cytokine expression in two independent renal injury models: folate nephropathy and unilateral ureteric obstruction. Furthermore, a study of two independent kidney transplant cohorts revealed higher levels of human renal allograft methylarginine-metabolizing enzyme gene expression associated with steeper function decline. We also report an association among DDAH1 expression, NO activity, and uromodulin expression supported by data from both animal and human studies, raising the possibility that kidney DDAH1 expression exacerbates renal injury through uromodulin-related mechanisms. Together, these data demonstrate that reduced renal tubular ADMA metabolism protects against progressive kidney function decline. Thus, circulating ADMA may be an imprecise marker of renal methylarginine metabolism, and therapeutic ADMA reduction may even be deleterious to kidney function. PMID:25855779

Post-discharge kidney function is associated with subsequent ten-year renal progression risk among survivors of acute kidney injury.

PubMed

Sawhney, Simon; Marks, Angharad; Fluck, Nick; Levin, Adeera; McLernon, David; Prescott, Gordon; Black, Corri

2017-08-01

The extent to which renal progression after acute kidney injury (AKI) arises from an initial step drop in kidney function (incomplete recovery), or from a long-term trajectory of subsequent decline, is unclear. This makes it challenging to plan or time post-discharge follow-up. This study of 14651 hospital survivors in 2003 (1966 with AKI, 12685 no AKI) separates incomplete recovery from subsequent renal decline by using the post-discharge estimated glomerular filtration rate (eGFR) rather than the pre-admission as a new reference point for determining subsequent renal outcomes. Outcomes were sustained 30% renal decline and de novo CKD stage 4, followed from 2003-2013. Death was a competing risk. Overall, death was more common than subsequent renal decline (37.5% vs 11.3%) and CKD stage 4 (4.5%). Overall, 25.7% of AKI patients had non-recovery. Subsequent renal decline was greater after AKI (vs no AKI) (14.8% vs 10.8%). Renal decline after AKI (vs no AKI) was greatest among those with higher post-discharge eGFRs with multivariable hazard ratios of 2.29 (1.88-2.78); 1.50 (1.13-2.00); 0.94 (0.68-1.32) and 0.95 (0.64-1.41) at eGFRs of 60 or more; 45-59; 30-44 and under 30, respectively. The excess risk after AKI persisted over ten years of study, irrespective of AKI severity, or post-episode proteinuria. Thus, even if post-discharge kidney function returns to normal, hospital admission with AKI is associated with increased renal progression that persists for up to ten years. Follow-up plans should avoid false reassurance when eGFR after AKI returns to normal. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Reduced Renal Methylarginine Metabolism Protects against Progressive Kidney Damage.

PubMed

Tomlinson, James A P; Caplin, Ben; Boruc, Olga; Bruce-Cobbold, Claire; Cutillas, Pedro; Dormann, Dirk; Faull, Peter; Grossman, Rebecca C; Khadayate, Sanjay; Mas, Valeria R; Nitsch, Dorothea D; Wang, Zhen; Norman, Jill T; Wilcox, Christopher S; Wheeler, David C; Leiper, James

2015-12-01

Nitric oxide (NO) production is diminished in many patients with cardiovascular and renal disease. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthesis, and elevated plasma levels of ADMA are associated with poor outcomes. Dimethylarginine dimethylaminohydrolase-1 (DDAH1) is a methylarginine-metabolizing enzyme that reduces ADMA levels. We reported previously that a DDAH1 gene variant associated with increased renal DDAH1 mRNA transcription and lower plasma ADMA levels, but counterintuitively, a steeper rate of renal function decline. Here, we test the hypothesis that reduced renal-specific ADMA metabolism protects against progressive renal damage. Renal DDAH1 is expressed predominately within the proximal tubule. A novel proximal tubule-specific Ddah1 knockout (Ddah1(PT-/-)) mouse demonstrated tubular cell accumulation of ADMA and lower NO concentrations, but unaltered plasma ADMA concentrations. Ddah1(PT-/-) mice were protected from reduced kidney tissue mass, collagen deposition, and profibrotic cytokine expression in two independent renal injury models: folate nephropathy and unilateral ureteric obstruction. Furthermore, a study of two independent kidney transplant cohorts revealed higher levels of human renal allograft methylarginine-metabolizing enzyme gene expression associated with steeper function decline. We also report an association among DDAH1 expression, NO activity, and uromodulin expression supported by data from both animal and human studies, raising the possibility that kidney DDAH1 expression exacerbates renal injury through uromodulin-related mechanisms. Together, these data demonstrate that reduced renal tubular ADMA metabolism protects against progressive kidney function decline. Thus, circulating ADMA may be an imprecise marker of renal methylarginine metabolism, and therapeutic ADMA reduction may even be deleterious to kidney function. Copyright © 2015 by the American Society of Nephrology.

Cognitive Decline and Its Risk Factors in Prevalent Hemodialysis Patients.

PubMed

Drew, David A; Weiner, Daniel E; Tighiouart, Hocine; Duncan, Sarah; Gupta, Aditi; Scott, Tammy; Sarnak, Mark J

2017-06-01

Cognitive impairment is common in patients treated with hemodialysis. The trajectory of cognitive function and risk factors for cognitive decline remain uncertain in this population. Longitudinal cohort. 314 prevalent hemodialysis patients. Age, sex, race, education level, hemodialysis vintage, cause of end-stage renal disease, and baseline history of cardiovascular disease. Cognitive function as determined by a comprehensive neurocognitive battery, administered at baseline and yearly when possible. Individual cognitive test results were reduced into 2 domain scores using principal components analysis, representing memory and executive function, which were used as our coprimary outcomes and by definition have a mean of zero and SD of 1. Mean age was 63 years; 54% were men, 22% were black, and 90% had at least a high school education. During a median follow-up of 2.1 (IQR, 0.9-4.2) years, 196 had at least 1 follow-up test, 156 died, and 43 received a kidney transplant. Linear mixed models and joint models, which accounted for competing risks from death, dropout, or kidney transplantation, showed nearly identical results. The joint model demonstrated a decline in executive function (-0.09 [95% CI, -0.13 to -0.05] SD per year), whereas memory improved slightly (0.05 [95% CI, 0.02 to 0.08] SD per year). A significant yearly decline was also seen in the Mini-Mental State Examination score (median change, -0.41; 95% CI, -0.57 to -0.25). Older age was the only significant risk factor for steeper executive function decline (-0.04 [95% CI, -0.06 to -0.02] SD steeper annual decline for each 10 years of age). Prevalent hemodialysis patients only, limited follow-up testing due to high mortality rate, and exclusion of participants with severe cognitive deficits or dementia. Prevalent hemodialysis patients demonstrate significant cognitive decline, particularly within tests of executive function. Older age was the only statistically significant risk factor for steeper cognitive decline, which may have important clinical consequences for patient management and education. Future studies should evaluate strategies to maintain or improve cognitive function. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Nocturnal Hypoxia and Loss of Kidney Function

PubMed Central

Ahmed, Sofia B.; Ronksley, Paul E.; Hemmelgarn, Brenda R.; Tsai, Willis H.; Manns, Braden J.; Tonelli, Marcello; Klarenbach, Scott W.; Chin, Rick; Clement, Fiona M.; Hanly, Patrick J.

2011-01-01

Background Although obstructive sleep apnea (OSA) is more common in patients with kidney disease, whether nocturnal hypoxia affects kidney function is unknown. Methods We studied all adult subjects referred for diagnostic testing of sleep apnea between July 2005 and December 31 2007 who had serial measurement of their kidney function. Nocturnal hypoxia was defined as oxygen saturation (SaO2) below 90% for ≥12% of the nocturnal monitoring time. The primary outcome, accelerated loss of kidney function, was defined as a decline in estimated glomerular filtration rate (eGFR) ≥4 ml/min/1.73 m2 per year. Results 858 participants were included and followed for a mean study period of 2.1 years. Overall 374 (44%) had nocturnal hypoxia, and 49 (5.7%) had accelerated loss of kidney function. Compared to controls without hypoxia, patients with nocturnal hypoxia had a significant increase in the adjusted risk of accelerated kidney function loss (odds ratio (OR) 2.89, 95% confidence interval [CI] 1.25, 6.67). Conclusion Nocturnal hypoxia was independently associated with an increased risk of accelerated kidney function loss. Further studies are required to determine whether treatment and correction of nocturnal hypoxia reduces loss of kidney function. PMID:21559506

Indication for Dialysis Initiation and Mortality in Patients With Chronic Kidney Failure: A Retrospective Cohort Study

PubMed Central

Rivara, Matthew B.; Chen, Chang Huei; Nair, Anupama; Cobb, Denise; Himmelfarb, Jonathan; Mehrotra, Rajnish

2016-01-01

Background Initiation of maintenance dialysis for patients with chronic kidney failure is a period of high risk for adverse patient outcomes. Whether indications for dialysis initiation are associated with mortality among this population is unknown. Study Design Retrospective cohort study. Setting & Participants 461 patients who initiated dialysis (hemodialysis, 437; peritoneal dialysis, 24) from January 1st, 2004 through December 31st, 2012 and were treated in facilities operated by a single dialysis organization. Follow-up for the primary outcome was through December 31st, 2013. Predictor Clinically documented primary indication for dialysis initiation, as categorized into four groups: laboratory evidence of kidney function decline (reference category), uremic symptoms, volume overload or hypertension, and other/unknown. Outcomes All-cause mortality Results Over a median follow-up of 2.4 years, 183 (40%) patients died. Crude mortality rates were 10.0 (95% CI, 6.8–14.7), 12.7 (95% CI, 10.2–15.7), 21.7 (95% CI, 16.4–28.6), and 12.2 (95% CI, 6.8–14.7) per 100 patient-years among patients initiating dialysis primarily for laboratory evidence of kidney function decline, uremic symptoms, volume overload or hypertension, and other/unknown reason, respectively. Following adjustment for demographic variables, coexisting illnesses, and estimated glomerular filtration rate, initiation of dialysis for uremic symptoms, volume overload or hypertension, or for other/unknown reasons were associated with 1.12 (95% CI, 0.72–1.77), 1.71 (95% CI, 1.03–2.84), and 1.28 (95% CI, 0.73–2.26) times higher risk, respectively, for subsequent mortality compared to initiation for laboratory evidence of kidney function decline. Limitations Possibility of residual confounding by unmeasured variables; reliance on clinical documentation to ascertain exposure Conclusions Patients initiating dialysis due to volume overload may have increased risk for mortality compared to patients initiating dialysis due to laboratory evidence of kidney function decline. Further studies are needed to identify and test interventions that might reduce this risk. PMID:27637132

Increasing Body Mass Index Predicts Rapid Decline in Renal Function: A 5 Year Retrospective Study.

PubMed

Ma, Xiaojing; Zhang, Chengyin; Su, Hong; Gong, Xiaojie; Kong, Xianglei

2018-05-02

While obesity is a recognized risk factor for chronic kidney disease, it remains unclear whether change in body mass index (ΔBMI ) is independently associated with decline in renal function (evaluated by the change in estimated glomerular filtration rate, ΔeGFR) over time. Accordingly, to help clarify this we conducted a retrospective study to measure the association of ΔBMI with decline in renal function in Chinese adult population. A total of 4007 adults (aged 45.3±13.7 years, 68.6% male) without chronic kidney disease at baseline were enrolled between 2008 and 2013. Logistic regression models were applied to explore the relationships between baseline BMI and ΔBMI, and rapid decline in renal function (defined as the lowest quartile of ΔeGFR ). During 5 years of follow-up, the ΔBMI and ΔeGFR were 0.47±1.6 (kg/m 2 ) and -3.0±8.8 (ml/min/1.73 m 2 ), respectively. After adjusted for potential confounders, ΔBMI (per 1 kg/m 2 increase) was independently associated with the rapid decline in renal function [with a fully adjusted OR of 1.12 (95% CI, 1.05 to 1.20). By contrast, the baseline BMI was not associated with rapid decline in renal function [OR=1.05 (95% CI, 0.98 to 1.13)]. The results were robust among 2948 hypertension-free and diabetes-free participants, the adjusted ORs of ΔBMI and baseline BMI were 1.14 (95% CI, 1.05 to 1.23) and 1.0 (95% CI, 0.96 to 1.04) for rapid decline in renal function, respectively. The study revealed that increasing ΔBMI predicts rapid decline in renal function. © Georg Thieme Verlag KG Stuttgart · New York.

Prospective safety study of bardoxolone methyl in patients with type 2 diabetes mellitus, end-stage renal disease and peritoneal dialysis.

PubMed

Warnock, David G; Hebbar, Sudarshan; Bargman, Joanne; Burkart, John; Davies, Simon; Finkelstein, Frederic O; Mehrotra, Rajnish; Ronco, Claudio; Teitelbaum, Isaac; Urakpo, Kingsley; Chertow, Glenn M

2012-01-01

Patients on peritoneal dialysis experience inflammation associated with advanced chronic kidney disease and the therapy itself. An important consequence of the inflammation may be acceleration of the rate of decline in residual renal function. The decline in residual renal function has been associated with an increased mortality for patients in this population. Bardoxolone methyl is a synthetic triterpenoid. To date, the effects of bardoxolone methyl on kidney function in humans have been studied in patients with type 2 diabetes mellitus. A large-scale event-driven study of bardoxolone methyl in patients with type 2 diabetes mellitus with stage 4 chronic kidney disease is underway. The safety of bardoxolone methyl has not been evaluated in patients with more advanced (stage 5) chronic kidney disease or patients on dialysis. This report describes a proposed double blind, prospective evaluation of bardoxolone methyl in patients with type 2 diabetes mellitus receiving peritoneal dialysis. In addition to assessing the safety of bardoxolone methyl in this population, the study will evaluate the effect of bardoxolone methyl on residual renal function over 6 months as compared to placebo. Copyright © 2012 S. Karger AG, Basel.

Comparison between Different Measures of Body Fat with Kidney Function Decline and Incident CKD.

PubMed

Madero, Magdalena; Katz, Ronit; Murphy, Rachel; Newman, Anne; Patel, Kushang; Ix, Joachim; Peralta, Carmen; Satterfield, Suzanne; Fried, Linda; Shlipak, Michael; Sarnak, Mark

2017-06-07

Although anthropometric measures of body fat are associated with development of CKD, they may not be able to distinguish between various forms of fat and therefore may be less accurate than computed tomography (CT) measures. We compared the association of CT and anthropometric measures of obesity with kidney outcomes in the Health Aging and Body Composition Study. Participants were recruited from March of 1997 through July of 1998. CT measures included visceral abdominal fat (VAT), subcutaneous adipose tissue (SAT), and intermuscular fat area (IMAT), whereas anthropometric measures included waist circumference (WC) and body mass index (BMI). Kidney outcomes included kidney function (KF) decline (30% decrease in eGFR cysC in follow-up at either year 3 or 10) or incident CKD (follow-up eGFR cysC ≤60 ml/min per 1.73 m 2 in individuals with baseline GFR>60 ml/min per 1.73 m 2 ). Multivariable logistic regression models and Poisson regression models were used to evaluate the association with decline in KF and incident kidney disease, respectively. We also assessed for the independent associations among the exposure measures by including them in the same model. Two-thousand four-hundred and eighty-nine individuals were included. Mean age was 74±3 years, 49% were men, 39% were black, 59% were hypertensive, and 15% were diabetic. KF decline occurred in 17% of the population, whereas incident CKD also occurred in 17% of those at risk. In continuous models, SAT, VAT, IMAT, BMI, and WC (per SD increase) were all significantly associated with KF decline. There was a significant interaction between VAT and CKD with regard to KF decline ( P =0.01). Only VAT, BMI, and WC were associated with incident CKD. Only VAT remained a significant risk factor for incident CKD when other exposure variables were included in the same model. There was no association between any measure of obesity and kidney outcomes when creatinine values at years 3 and 10 were used to estimate changes in eGFR. Anthropometric measures of body fat appear to provide as consistent estimates of KF decline risk as CT measures in elders. Copyright © 2017 by the American Society of Nephrology.

Continuous cognitive improvement 1 year following successful kidney transplant.

PubMed

Harciarek, Michał; Biedunkiewicz, Bogdan; Lichodziejewska-Niemierko, Monika; Dębska-Ślizień, Alicja; Rutkowski, Bolesław

2011-06-01

Successful kidney transplantation was recently shown to lead to improvement in the cognitive performance of patients on chronic dialysis. To examine whether the early cognitive benefits of transplantation continue to develop over time, along with the patients' ongoing recovery, we addressed these questions in a prospective controlled study of 27 dialyzed patients who subsequently received a kidney transplant, 18 dialyzed patients awaiting kidney transplant, and 30 matched controls without kidney disease. Overall, successful kidney transplant contributed to a statistically significant improvement in performance on tests of motor/psychomotor speed, visual planning, memory, and abstract reasoning tested 1 year later. We also studied whether the cognitive performance of patients maintained on dialysis is stable or declines over time and found that it actually declined over this time even in adequately dialyzed patients. Measures of memory functions were particularly affected. This study indicates that the early beneficial effects of transplantation are not transient and were still evident 1 year following transplantation.

The Kidney in Aging: Physiological Changes and Pathological Implications.

PubMed

Sobamowo, H; Prabhakar, S S

2017-01-01

Aging is associated with progressive decline in renal function along with concurrent morphological changes that ultimately lead to glomerulosclerosis. The mechanisms leading to such changes in the kidney with age as well as the basis of controversies that surround the physiological basis vs pathological nature of aging kidney are the focus of this in-depth review. In addition, the renal functional defects of acid-base homeostasis and electrolyte disturbances in elderly and the physiological basis of such disorders are also discussed. © 2017 Elsevier Inc. All rights reserved.

The association of periodontal disease with kidney function decline: a longitudinal retrospective analysis of the MrOS dental study.

PubMed

Grubbs, Vanessa; Vittinghoff, Eric; Taylor, George; Kritz-Silverstein, Donna; Powe, Neil; Bibbins-Domingo, Kirsten; Ishani, Areef; Cummings, Steven R

2016-03-01

Identifying modifiable risk factors for chronic kidney disease (CKD) is essential for reducing its burden. Periodontal disease is common, modifiable and has been implicated as a novel potential CKD risk factor, but evidence of its association with kidney function decline over time is limited. In a longitudinal retrospective cohort of 761 elderly men with preserved kidney function [estimated glomerular filtration rate > 60 mL/min/1.73 m(2) using a calibrated creatinine and cystatin C (eGFRcr-cys) equation] at baseline, we performed multivariable Poisson's regression to examine the association of severe periodontal disease with incident CKD, defined as incident eGFRcr-cys <60 mL/min/1.73 m(2) and rapid (>5% annualized) eGFRcr-cys decline. Severe periodontal disease was defined in two ways: (i) ≥5 mm proximal attachment loss in 30% of teeth examined (European Workshop in Periodontology Group C, European Workshop); and (ii) 2+ interproximal sites with attachment loss ≥6 mm and 1+ interproximal sites with probing depth ≥5 mm (Centers for Disease Control/American Academy of Periodontology, CDC/AAP). At baseline, the mean age was 73.4 (SD 4.8) years, the median eGFRcr-cys was 82.4 mL/min/1.73 m(2), and 35.5 and 25.4% of participants had severe periodontal disease by European Workshop and CDC/AAP criteria, respectively. After a mean follow-up of 4.9 years (SD 0.3), 56 (7.4%) participants had incident CKD. Severe periodontal disease was associated with a 2-fold greater rate of incident CKD [incidence rate ratio (IRR) 2.01 (1.21-3.44), P = 0.007] after adjusting for confounders compared with not severe periodontal disease by European Workshop criteria but did not reach statistical significance by CDC/AAP criteria [IRR 1.10 (0.63-1.91), P = 0.9]. Severe periodontal disease may be associated with incident clinically significant kidney function decline among a cohort of elderly men. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Racial Differences in Estimated GFR Decline, ESRD, and Mortality in an Integrated Health System

PubMed Central

Derose, Stephen F.; Rutkowski, Mark P.; Crooks, Peter W.; Shi, Jiaxiao M.; Wang, Jean; Kalantar-Zadeh, Kamyar; Kovesdy, Csaba P.; Levin, Nathan W.; Jacobsen, Steven J.

2013-01-01

Background Current evidence does not clearly identify the contribution of kidney function decline and mortality to racial disparities in ESRD incidence. We used observed eGFR to project the time of onset of kidney failure and examined mortality to better understand these racial disparities. Study Design Retrospective cohort. Setting & Participants Adult members of Kaiser Permanente Southern California from 2003–2009 with >2 serum creatinine tests and >180 days between tests: 526,498 whites, 350,919 Hispanics, 136,923 blacks, and 105,476 Asians. Predictor Race/ethnicity. Outcomes ESRD (dialysis, transplantation); mortality. Measurements eGFR decline was modeled using linear regression. Kidney failure was projected based on predicted eGFR <15 mL/min/1.73m2 at specified times. Racial differences in projected kidney failure and mortality among those with projected kidney failure were estimated with adjustment for age, sex, and entry eGFR. Results Blacks had more extreme rates of eGFR decline (1st percentile, −23.6 mL/min/1.73m2 per year), followed by Hispanics (−20.9 mL/min/1.73m2 per year), whites (−20.1 mL/min/1.73m2 per year), and Asians (−17.6 mL/min/1.73m2 per year; P<0.001). There were 25,065 white, 11,368 Hispanic, 6,785 black, and 3,176 Asians with projected kidney failure during the study period. The ORs for projected kidney failure vs. whites during CKD stages 3 and 4 were 1.54 (95% CI, 1.46–1.62) in blacks, 1.49 (95% CI, 1.42–1.56) in Hispanics, and 1.41 (95% CI, 1.32–1.51) in Asians. Among those with projected kidney failure, the HRs of death vs. whites during CKD stages 3 and 4 were 0.82 (95% CI, 0.77–0.88) in blacks, 0.67 (95% CI, 0.63–0.72) in Hispanics, and 0.58 (95% CI, 0.52–0.65) in Asians. Limitations Results may not generalize to the uninsured or subgroups within a race. Projected kidney failure was based on linear trends from clinically obtained eGFR. Conclusions We found more extreme rates of eGFR decline in blacks. Projected kidney failure during CKD stages 3 and 4 was high in blacks, Hispanics, and Asians relative to whites. Mortality among those with projected kidney failure was highest in whites. Differences in eGFR decline and mortality contributed to racial disparities in ESRD incidence. PMID:23499049

Kidney Function After a Hypertensive Disorder of Pregnancy: A Longitudinal Study.

PubMed

Paauw, Nina D; van der Graaf, Anne Marijn; Bozoglan, Rita; van der Ham, David P; Navis, Gerjan; Gansevoort, Ron T; Groen, Henk; Lely, A Titia

2018-05-01

Registry-based studies report an increased risk for end-stage kidney disease after hypertensive disorders of pregnancy (HDPs). It is unclear whether HDPs lead to an increased incidence of chronic kidney disease (CKD) and/or progression of kidney function decline. Subanalysis of the Prevention of Renal and Vascular Endstage Disease (PREVEND) Study, a Dutch population-based cohort with follow-up of 5 visits approximately 3 years apart. Women without and with patient-reported HDPs (non-HDP, n=1,805; HDP, n=977) were identified. Mean age was 50 years at baseline and median follow-up was 11 years. An HDP. (1) The incidence of CKD using Cox regression and (2) the course of kidney function (estimated glomerular filtration rate [eGFR] and 24-hour albuminuria) over 5 visits using generalized estimating equation analysis adjusted for age, mean arterial pressure, and renin-angiotensin system (RAS) blockade. CKD was defined as eGFR<60mL/min/1.73m 2 and/or 24-hour albuminuria with albumin excretion > 30mg, and end-stage kidney disease was defined as receiving dialysis or kidney transplantation. During follow-up, none of the women developed end-stage renal disease and the incidence of CKD during follow-up was similar across HDP groups (HR, 1.04; 95% CI, 0.79-1.37; P=0.8). Use of RAS blockade was higher after HDP at all visits. During a median of 11 years, we observed a decrease in eGFR in both groups, with a slightly steeper decline in the HDP group (98±15 to 88±16 vs 99±17 to 91±15mL/min/1.73m 2 ; P group <0.01, P group*visit <0.05). The group effect remained significant after adjusting for mean arterial pressure, but disappeared after adjusting for RAS blockade. The 24-hour albuminuria did not differ between groups. No obstetric records available. HDPs defined by patient report rather than health records. HDPs did not detectably increase the incidence of CKD. During follow-up, we observed no differences in albuminuria, but observed a marginally lower eGFR after HDP that was no longer statistically significant after adjusting for the use of RAS blockers. In this population, we were unable to identify a significant risk for kidney function decline after patient-reported HDP. Copyright © 2017. Published by Elsevier Inc.

Clinical Courses of Graft Failure Caused by Chronic Allograft Dysfunction in Kidney Transplantation.

PubMed

Fujiwara, T; Teruta, S; Tsudaka, S; Ota, K; Matsuda, H

Chronic allograft dysfunction (CAD) is a main cause of graft failure in kidney transplantation. We retrospectively analyzed 279 kidney transplant recipients who survived with a functioning graft for at least 2 years. CAD was defined as chronic graft deterioration, excluding other specific causes. We defined the pattern of decline in estimated glomerular filtration rate (eGFR), as follows: (1) "plateau" was defined as decline in eGFR ≤2 mL/min/1.73 m 2 /year; "long plateaus" were those lasting more than 5 years; (2) "rapid decline" was a decrease in eGFR ≥20 mL/min/1.73 m 2 /year. Patients diagnosed with CAD were categorized according to the occurrence of rapid decline and/or long plateau as follows: group 1, neither rapid decline nor long plateau; group 2, rapid decline only; group 3, long plateau only; and group 4, both rapid decline and long plateau. From a total of 81 graft losses, 51 (63%) failed because of CAD, with a median of 9.4 years. Sixteen patients belonged to group 1, 14 to group 2, 12 to group 3, and nine to group 4. Mean graft survival times in the four groups were 7.7 ± 1.1, 6.1 ± 3.1, 16.2 ± 2.5, and 10.8 ± 3.6 years, respectively (P < .001). There were significant differences among groups in donor age, year of transplantation, mean eGFR at baseline, and acute rejection rate after transplantation. The results indicate that this cohort of kidney transplant recipients who had CAD comprised subgroups with different clinical courses. Copyright © 2016 Elsevier Inc. All rights reserved.

Indoxyl Sulfate Induces Apoptosis and Hypertrophy in Human Kidney Proximal Tubular Cells.

PubMed

Ellis, Robert J; Small, David M; Ng, Keng Lim; Vesey, David A; Vitetta, Luis; Francis, Ross S; Gobe, Glenda C; Morais, Christudas

2018-06-01

Indoxyl sulfate (IS) is a protein-bound uremic toxin that accumulates in patients with declining kidney function. Although generally thought of as a consequence of declining kidney function, emerging evidence demonstrates direct cytotoxic role of IS on endothelial cells and cardiomyocytes, largely through the expression of pro-inflammatory and pro-fibrotic factors. The direct toxicity of IS on human kidney proximal tubular epithelial cells (PTECs) remains a matter of debate. The current study explored the effect of IS on primary cultures of human PTECs and HK-2, an immortalized human PTEC line. Pathologically relevant concentrations of IS induced apoptosis and increased the expression of the proapoptotic molecule Bax in both cell types. IS impaired mitochondrial metabolic activity and induced cellular hypertrophy. Furthermore, statistically significant upregulation of pro-fibrotic (transforming growth factor-β, fibronectin) and pro-inflammatory molecules (interleukin-6, interleukin-8, and tumor necrosis factor-α) in response to IS was observed. Albumin had no influence on the toxicity of IS. The results of this study suggest that IS directly induced a pro-inflammatory and pro-fibrotic phenotype in proximal tubular cells. In light of the associated apoptosis, hypertrophy, and metabolic dysfunction, this study demonstrates that IS may play a role in the progression of chronic kidney disease.

Intermediate Volume on Computed Tomography Imaging Defines a Fibrotic Compartment that Predicts Glomerular Filtration Rate Decline in Autosomal Dominant Polycystic Kidney Disease Patients

PubMed Central

Caroli, Anna; Antiga, Luca; Conti, Sara; Sonzogni, Aurelio; Fasolini, Giorgio; Ondei, Patrizia; Perico, Norberto; Remuzzi, Giuseppe; Remuzzi, Andrea

2011-01-01

Total kidney and cyst volumes have been used to quantify disease progression in autosomal dominant polycystic kidney disease (ADPKD), but a causal relationship with progression to renal failure has not been demonstrated. Advanced image processing recently allowed to quantify extracystic tissue, and to identify an additional tissue component named “intermediate,” appearing hypoenhanced on contrast-enhanced computed tomography (CT). The aim of this study is to provide a histological characterization of intermediate volume, investigate its relation with renal function, and provide preliminary evidence of its role in long-term prediction of functional loss. Three ADPKD patients underwent contrast-enhanced CT scans before nephrectomy. Histological samples of intermediate volume were drawn from the excised kidneys, and stained with hematoxylin and eosin and with saturated picrosirius solution for histological analysis. Intermediate volume showed major structural changes, characterized by tubular dilation and atrophy, microcysts, inflammatory cell infiltrate, vascular sclerosis, and extended peritubular interstitial fibrosis. A significant correlation (r = −0.69, P < 0.001) between relative intermediate volume and baseline renal function was found in 21 ADPKD patients. Long-term prediction of renal functional loss was investigated in an independent cohort of 13 ADPKD patients, followed for 3 to 8 years. Intermediate volume, but not total kidney or cyst volume, significantly correlated with glomerular filtration rate decline (r = −0.79, P < 0.005). These findings suggest that intermediate volume may represent a suitable surrogate marker of ADPKD progression and a novel therapeutic target. PMID:21683674

Thrombospondin-1 deficiency causes a shift from fibroproliferative to inflammatory kidney disease and delays onset of renal failure.

PubMed

Zeisberg, Michael; Tampe, Björn; LeBleu, Valerie; Tampe, Desiree; Zeisberg, Elisabeth M; Kalluri, Raghu

2014-10-01

Thrombospondin-1 (TSP1) is a multifunctional matricellular protein known to promote progression of chronic kidney disease. To gain insight into the underlying mechanisms through which TSP1 accelerates chronic kidney disease, we compared disease progression in Col4a3 knockout (KO) mice, which develop spontaneous kidney failure, with that of Col4a3;Tsp1 double-knockout (DKO) mice. Decline of excretory renal function was significantly delayed in the absence of TSP1. Although Col4a3;Tsp1 DKO mice did progress toward end-stage renal failure, their kidneys exhibited distinct histopathological lesions, compared with creatinine level-matched Col4a3 KO mice. Although kidneys of both Col4a3 KO and Col4a3;Tsp1 DKO mice exhibited a widened tubulointerstitium, predominant lesions in Col4a3 KO kidneys were collagen deposition and fibroblast accumulation, whereas in Col4a3;Tsp1 DKO kidney inflammation was predominant, with less collagen deposition. Altered disease progression correlated with impaired activation of transforming growth factor-β1 (TGF-β1) in vivo and in vitro in the absence of TSP1. In summary, our findings suggest that TSP1 contributes to progression of chronic kidney disease by catalyzing activation of latent TGF-β1, resulting in promotion of a fibroproliferative response over an inflammatory response. Furthermore, the findings suggest that fibroproliferative and inflammatory lesions are independent entities, both of which contribute to decline of renal function. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Unresolved subclinical hypothyroidism is independently associated with progression of chronic kidney disease.

PubMed

Kim, Eun Oh; Lee, Ihn Suk; Choi, Yoo A; Lee, Sang Ju; Chang, Yoon Kyung; Yoon, Hye Eun; Jang, Yi Sun; Lee, Jong Min; Kim, Hye Soo; Yang, Chul Woo; Kim, Suk Young; Hwang, Hyeon Seok

2014-01-01

Patients with chronic kidney disease (CKD) often have subclinical hypothyroidism. However, few reports have investigated changes in the status of subclinical hypothyroidism in CKD patients and its clinical significance in CKD progression. We included 168 patients with nondialysis-dependent CKD stages 2-4. The normalization of subclinical hypothyroidism during follow-up was assessed, and the association between transitions in subclinical hypothyroid status and the rate of decline of the estimated glomerular filtration rate (eGFR) was investigated. At baseline, 127 patients were euthyroid and 41 (24.4%) patients were diagnosed with subclinical hypothyroidism. Of these 41 patients, 21 (51.2%) spontaneously resolved to euthyroid during follow-up. The rate of eGFR decline of patients with resolved subclinical hypothyroidism was similar to that of euthyroid patients. The patients with unresolved subclinical hypothyroidism showed a steeper renal function decline than patients with euthyroidism or resolved subclinical hypothyroidism (all p < 0.05). The progression to end-stage renal disease was more frequent in those with unresolved subclinical hypothyroidism than in those who were euthyroid (p = 0.006). In multivariate linear regression for rate of eGFR decrease, unresolved subclinical hypothyroidism (β = -5.77, p = 0.001), baseline renal function (β = -0.12, p < 0.001) and level of proteinuria (β = -2.36, p = 0.015) were independently associated with the rate of renal function decline. Half of the CKD patients with subclinical hypothyroidism did not resolve to euthyroidism, and this lack of resolution was independently associated with rapid renal function decline.

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.

The potential role of perivascular lymphatic vessels in preservation of kidney allograft function.

PubMed

Tsuchimoto, Akihiro; Nakano, Toshiaki; Hasegawa, Shoko; Masutani, Kosuke; Matsukuma, Yuta; Eriguchi, Masahiro; Nagata, Masaharu; Nishiki, Takehiro; Kitada, Hidehisa; Tanaka, Masao; Kitazono, Takanari; Tsuruya, Kazuhiko

2017-08-01

Lymphangiogenesis occurs in diseased native kidneys and kidney allografts, and correlates with histological injury; however, the clinical significance of lymphatic vessels in kidney allografts is unclear. This study retrospectively reviewed 63 kidney transplant patients who underwent protocol biopsies. Lymphatic vessels were identified by immunohistochemical staining for podoplanin, and were classified according to their location as perivascular or interstitial lymphatic vessels. The associations between perivascular lymphatic density and kidney allograft function and pathological findings were analyzed. There were no significant differences in perivascular lymphatic densities in kidney allograft biopsy specimens obtained at 0 h, 3 months and 12 months. The groups with higher perivascular lymphatic density showed a lower proportion of progression of interstitial fibrosis/tubular atrophy grade from 3 to 12 months (P for trend = 0.039). Perivascular lymphatic density was significantly associated with annual decline of estimated glomerular filtration rate after 12 months (r = -0.31, P = 0.017), even after adjusting for multiple confounders (standardized β = -0.30, P = 0.019). High perivascular lymphatic density is associated with favourable kidney allograft function. The perivascular lymphatic network may be involved in inhibition of allograft fibrosis and stabilization of graft function.

Angiotensin converting enzyme inhibition and the kidney

NASA Technical Reports Server (NTRS)

Hollenberg, N. K.

1988-01-01

Angiotensin II (Ang II) induces a marked reduction in renal blood flow at doses well below those required to induce a pressor response, and as blood flow falls there is a decline in glomerular filtration rate and sodium excretion. This striking sensitivity of the renal blood supply led many workers to consider the possibility that angiotensin functions as a local renal hormone. As angiotensin converting enzyme (ACE) was found in particular abundance in the lung, it seemed reasonable to suspect that most of the conversion occurred there, and that the function of Ang II would be primarily systemic, rather than intrarenal. In this review, I will explore the evidence that has accumulated on these two possibilities, since they have important implications for our current understanding of normal kidney function and derangements of kidney function in disease.

NephroCheck data compared to serum creatinine in various clinical settings.

PubMed

Pajenda, Sahra; Ilhan-Mutlu, Aysegül; Preusser, Matthias; Roka, Sebastian; Druml, Wilfred; Wagner, Ludwig

2015-12-09

Acute kidney injury is frequently observed at the intensive care unit, after surgery, and after toxic drug administration. A rise in serum creatinine and a fall in urine output are consequences of much earlier injury to the most sensitive part of tubular cells located at the proximal tubule. The aim of the present study was to investigate the course of two cell-cycle arrest urinary biomarkers compared to serum creatinine in four clinical settings: ischemic reperfusion injury, cardiac failure, severe acute kidney injury, and chemotherapy-induced kidney injury. A recently developed bedside test known as NephroCheck measures two urinary parameters: insulin-like growth factor binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinase-2 (TIMP-2). The test is based on a sandwich immunoassay technique. The final test output, labeled AKIRisk, is shown as a numeric result. This report revealed that [IGFBP7] · [TIMP-2] in urine rise rapidly prior to any change in serum creatinine. A unique feature of all four clinical settings is that a rapid decline predicts the recovery of kidney function. Besides, a subclinical kidney injury might be detected by the test. This bedside test detects biomarkers of renal injury. A rapid decline in AKIRisk was associated with the restoration of kidney function, whereas a prolonged high AKIRisk score was associated with end-stage renal disease. However, the dynamics seem to differ, depending on the cause and the extent of injury. Further studies will be needed to clarify the issue.

The impact of pre-intervention rate of kidney function change on the assessment of CKD progression.

PubMed

Fassett, Robert G; Geraghty, Dominic P; Coombes, Jeff S

2014-10-01

Without a run-in phase, chronic kidney disease (CKD) patients enrolled in clinical trials may not be identified as having progressive disease. The aim of this analysis was to quantify the effects of a run-in phase on kidney function outcome in CKD patients enrolled in the Lipid Lowering and Onset of Renal Disease (LORD) trial. The LORD trial assessed the effects of atorvastatin on the rate of change in the estimated glomerular filtration rate (eGFR) and included patients with serum creatinine 120 μmol/l. In this post hoc analysis, we assessed eGFR change during the 12-month period prior to enrolment, the 3-month run-in phase and the first 12-month period of the trial. Eighty of the original 132 patients (where retrospective data were available) were included. The rate of eGFR change during each period was compared. Overall kidney function decreased during the 12 months prior to enrolment by (mean, SD) 0.39 ± 0.98 ml/min/1.73 m(2)/month, improved during the 3-month run-in phase by 0.48 ± 2.90 ml/min/1.73 m(2)/month and decreased during the first 12 months of the trial by 0.15 ± 0.57 ml/min/1.73 m(2)/month. However, only 39 % of patients had declining eGFR during the 12 months prior, 19 % in the 3-month run-in and 42 % during the first 12-month study phase. Most patients (>60 %) entering this clinical trial had stable or improving kidney function. Enrolment was associated with further improved kidney function, which may have been due to 'regression to the mean' or to the Hawthorne effect. Investigators should include a run-in period to establish the presence of eGFR decline to use as an inclusion criterion in clinical trials assessing this measure of CKD progression.

Uric acid lowering to prevent kidney function loss in diabetes: the preventing early renal function loss (PERL) allopurinol study.

PubMed

Maahs, David M; Caramori, Luiza; Cherney, David Z I; Galecki, Andrzej T; Gao, Chuanyun; Jalal, Diana; Perkins, Bruce A; Pop-Busui, Rodica; Rossing, Peter; Mauer, Michael; Doria, Alessandro

2013-08-01

Diabetic kidney disease causes significant morbidity and mortality among people with type 1 diabetes (T1D). Intensive glucose and blood pressure control have thus far failed to adequately curb this problem and therefore a major need for novel treatment approaches exists. Multiple observations link serum uric acid levels to kidney disease development and progression in diabetes and strongly argue that uric acid lowering should be tested as one such novel intervention. A pilot of such a trial, using allopurinol, is currently being conducted by the Preventing Early Renal Function Loss (PERL) Consortium. Although the PERL trial targets T1D individuals at highest risk of kidney function decline, the use of allopurinol as a renoprotective agent may also be relevant to a larger segment of the population with diabetes. As allopurinol is inexpensive and safe, it could be cost-effective even for relatively low-risk patients, pending the completion of appropriate trials at earlier stages.

Correlation between cognitive functions and syndromes of traditional Chinese medicine in amnestic mild cognitive impairment.

PubMed

Miao, Ying-chun; Tian, Jin-zhou; Shi, Jing; Mao, Min; Zhao, Xiao-dong; Fang, Li-yan; Zeng, Chui-you; Liu, Jian-ping; Wang, Zhi-liang; Li, Xiao-bin

2009-03-01

To explore the correlation between the cognitive functions and syndromes of traditional Chinese medicine (TCM) in amnestic mild cognitive impairment (aMCI), and to provide evidence for clinical syndrome differentiation treatment. Six hundred subjects from Dongzhimen Hospital and seven communities in Beijing, aged between 40 and 85 years, accepted neuropsychological assessments, imaging and biochemical examinations, and syndrome differentiation, from whom 159 aMCI patients, 213 normal control (NC) subjects and 171 Alzheimer's dementia (AD) patients were screened out. Correlation between the cognitive functions and TCM syndromes in aMCI patients was analyzed. Mini-Mental State Examination (MMSE) score in aMCI patients was closely correlated with kidney essence vacuity and deficiency of blood and qi (r = -0.11, r = -0.11; P = 0.003, P = 0.015). Delayed Word Recall (DWR) score was correlated with kidney essence vacuity (r = -0.20, P = 0.020). Instant Story Recall (ISR) and Delayed Story Recall (DSR) scores were respectively correlated with turbid phlegm blocking upper orifices (r = -0.11, r = -0.27; P = 0.021, P = 0.000). Language function was correlated with kidney essence vacuity and deficiency of blood and qi (r = -0.11, r = -0.13; P = 0.042, P = 0.007). Attention/calculation was also closely correlated with kidney essence vacuity and deficiency of blood and qi (r = -0.10, r = -0.21; P = 0.039, P = 0.010). Attention score of aMCI patients was correlated with excess of heat toxin syndrome (r = -0.29, P = 0.026). The memory decline of aMCI is correlated with kidney essence vacuity and turbid phlegm blocking upper orifices. Furthermore, turbid phlegm blocking upper orifices is correlated with episodic memory decline, which is closely related to AD. The aMCI patients with phlegm have the risk to progress into AD. Although other cognitive functions of aMCI remain relatively intact, the patients' language function, attention/calculation and the whole cognitive function may be worsen as the aggravation of kidney essence vacuity, deficiency of blood and qi, phlegm and heat toxin, and may eventually lead to multiple cognitive domains impairment, even dementia.

Pancreas Transplantation of US and Non-US Cases from 2005 to 2014 as Reported to the United Network for Organ Sharing (UNOS) and the International Pancreas Transplant Registry (IPTR)

PubMed Central

Gruessner, Angelika C.; Gruessner, Rainer W.G.

2016-01-01

This report is an update of pancreas and kidney transplant activities in the US and non-US region in two periods, 2005-2009 and 2010-2014. The aim of the report was to analyze transplant progress and success in the US compared to non-US countries, and to compare trends between the two periods. Between 2005-2009 and 2010-2014, the number of US pancreas transplants declined by over 20%, while the overall number of pancreas transplants performed outside the US has increased. The decline in US numbers is predominantly due to the decline in primary and secondary pancreas after kidney transplants (PAK). During the time period studied, the number of PAK transplants dropped by 50%. In contrast, the number of simultaneous pancreas/kidney transplants (SPK) declined by only 10%, and the number of pancreas transplants alone (PTA) by 20%. Over 90% of pancreas transplants worldwide were performed, with a simultaneous kidney transplant and excellent results. Transplant outcomes in SPK improved significantly because of a decrease in the rates of technical and immunologic graft loss. In 2010-2014 vs. 2005-2009, US SPK transplant patient survival at 1 year post-transplant increased from 95.7% to 97.4%, pancreas graft function from 88.3% to 91.3%, and kidney function from 93.6% to 95.5%. A significant improvement was also noted in PAK transplants. One-year patient survival increased from 96.4% to 97.9% and pancreas graft function from 81.0% to 86.0%. PTA 1-year patient survival remained constant at 97%, and pancreas 1-year graft survival improved from 81.0% to 85.7%. With the decline in the number of transplants, a change towards better pancreas donor selection was observed. In solitary transplants, the donors were primarily young trauma victims, and the pancreas preservation time was relatively short. A general tendency towards transplanting older recipients was noted. In 2010-2014 vs. 2005-2009, PTA recipients 50 years of age or older accounted for 32% vs. 22%, PAK for 28% vs. 22%, and SPK for 22% vs. 20%. This may be due to a relatively lower immunologic graft loss rate, especially in solitary transplants, which historically has been high in young recipients. The number of pancreas transplants in patients with type 2 diabetes and end-stage renal disease has increased, and accounted for 9% of all SPK recipients in 2010-2014. PMID:26982345

Estimated GFR and Subsequent Higher Left Ventricular Mass in Young and Middle-Aged Adults With Normal Kidney Function: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

PubMed

Bansal, Nisha; Lin, Feng; Vittinghoff, Eric; Peralta, Carmen; Lima, Joao; Kramer, Holly; Shlipak, Michael; Bibbins-Domingo, Kirsten

2016-02-01

Left ventricular hypertrophy is common and is associated with cardiovascular events and death among patients with known chronic kidney disease. However, the link between reduced glomerular filtration rate (GFR) and left ventricular mass index (LVMI) remains poorly explored among young and middle-aged adults with preserved kidney function. In this study, we examined the association of cystatin C-based estimated GFR (eGFRcys) and rapid decline in eGFR with subsequent LVMI. Observational study. We included 2,410 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort with eGFRcys > 60mL/min/1.73m(2) at year 15 and who had an echocardiogram obtained at year 25. eGFRcys at year 15 and rapid decline in eGFRcys (defined as >3% per year over 5 years from years 15 to 20). LVMI measured at year 25. We adjusted for age, sex, race, diabetes, body mass index, low- and high-density lipoprotein cholesterol levels, cumulative systolic blood pressure, and albuminuria. Mean age was 40±4 (SD) years, 58% were women, and 43% were black. After 10 years of follow-up, mean LVMI was 39.6±13.4g/m(2.7). Compared with eGFRcys > 90mL/min/1.73m(2) (n = 2,228), eGFRcys of 60 to 75mL/min/1.73m(2) (n = 29) was associated with 5.63 (95% CI, 0.90-10.36) g/m(2.7) greater LVMI (P = 0.02), but there was no association of eGFRcys of 76 to 90mL/min/1.73m(2) (n = 153) with LVMI after adjustment for confounders. Rapid decline in eGFRcys was associated with higher LVMI compared with participants without a rapid eGFRcys decline (β coefficient, 1.48; 95% CI, 0.11-2.83; P = 0.03) after adjustment for confounders. There were a limited number of participants with eGFRcys of 60 to 90mL/min/1.73m(2). Among young and middle-aged adults with preserved kidney function, eGFRcys of 60 to 75mL/min/1.73m(2) and rapid decline in eGFRcys were significantly associated with subsequently higher LVMI. Further studies are needed to understand the mechanisms that contribute to elevated LVMI in this range of eGFRcys. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Short communication: timeline of radiation-induced kidney function loss after stereotactic ablative body radiotherapy of renal cell carcinoma as evaluated by serial (99m)Tc-DMSA SPECT/CT.

PubMed

Jackson, Price; Foroudi, Farshad; Pham, Daniel; Hofman, Michael S; Hardcastle, Nicholas; Callahan, Jason; Kron, Tomas; Siva, Shankar

2014-11-26

Stereotactic ablative body radiotherapy (SABR) has been proposed as a definitive treatment for patients with inoperable primary renal cell carcinoma. However, there is little documentation detailing the radiobiological effects of hypofractionated radiation on healthy renal tissue. In this study we describe a methodology for assessment of regional change in renal function in response to single fraction SABR of 26 Gy. In a patient with a solitary kidney, detailed follow-up of kidney function post-treatment was determined through 3-dimensional SPECT/CT imaging and (51)Cr-EDTA measurements. Based on measurements of glomerular filtration rate, renal function declined rapidly by 34% at 3 months, plateaued at 43% loss at 12 months, with minimal further decrease to 49% of baseline by 18 months. The pattern of renal functional change in (99m)Tc-DMSA uptake on SPECT/CT imaging correlates with dose delivered. This study demonstrates a dose effect relationship of SABR with loss of kidney function.

Unresolved Subclinical Hypothyroidism is Independently Associated with Progression of Chronic Kidney Disease

PubMed Central

Kim, Eun Oh; Lee, Ihn Suk; Choi, Yoo A; Lee, Sang Ju; Chang, Yoon Kyung; Yoon, Hye Eun; Jang, Yi Sun; Lee, Jong Min; Kim, Hye Soo; Yang, Chul Woo; Kim, Suk Young; Hwang, Hyeon Seok

2014-01-01

Background and Aim: Patients with chronic kidney disease (CKD) often have subclinical hypothyroidism. However, few reports have investigated changes in the status of subclinical hypothyroidism in CKD patients and its clinical significance in CKD progression. Methods: We included 168 patients with nondialysis-dependent CKD stages 2-4. The normalization of subclinical hypothyroidism during follow-up was assessed, and the association between transitions in subclinical hypothyroid status and the rate of decline of the estimated glomerular filtration rate (eGFR) was investigated. Results: At baseline, 127 patients were euthyroid and 41 (24.4%) patients were diagnosed with subclinical hypothyroidism. Of these 41 patients, 21 (51.2%) spontaneously resolved to euthyroid during follow-up. The rate of eGFR decline of patients with resolved subclinical hypothyroidism was similar to that of euthyroid patients. The patients with unresolved subclinical hypothyroidism showed a steeper renal function decline than patients with euthyroidism or resolved subclinical hypothyroidism (all p < 0.05). The progression to end-stage renal disease was more frequent in those with unresolved subclinical hypothyroidism than in those who were euthyroid (p = 0.006). In multivariate linear regression for rate of eGFR decrease, unresolved subclinical hypothyroidism (β = -5.77, p = 0.001), baseline renal function (β = -0.12, p < 0.001) and level of proteinuria (β = -2.36, p = 0.015) were independently associated with the rate of renal function decline. Conclusions: Half of the CKD patients with subclinical hypothyroidism did not resolve to euthyroidism, and this lack of resolution was independently associated with rapid renal function decline. PMID:24396286

Impact of post-kidney transplant parathyroidectomy on allograft function

PubMed Central

Parikh, Samir; Nagaraja, Haikady; Agarwal, Anil; Samavedi, Srinivas; Von Visger, Jon; Nori, Uday; Andreoni, Kenneth; Pesavento, Todd; Singh, Neeraj

2013-01-01

Background The impact of parathyroidectomy on allograft function in kidney transplant patients is unclear. Methods We conducted a retrospective, observational study of all kidney transplant recipients from 1988 to 2008 who underwent parathyroidectomy for uncontrolled hyperparathyroidism (n = 32). Post-parathyroidectomy, changes in estimated glomerular filtration rate (eGFR) and graft loss were recorded. Cross-sectional associations at baseline between eGFR and serum calcium, phosphate, and parathyroid hormone (PTH), and associations between their changes within subjects during the first two months post-parathyroidectomy were assessed. Results Post-parathyroidectomy, the mean eGFR declined from 51.19 mL/min/1.73 m2 at parathyroidectomy to 44.78 mL/min/1.73 m2 at two months (p < 0.0001). Subsequently, graft function improved, and by 12 months, mean eGFR recovered to 49.76 mL/min/1.73 m2 (p = 0.035). Decrease in serum PTH was accompanied by a decrease in eGFR (p = 0.0127) in the first two months post-parathyroidectomy. Patients whose eGFR declined by ≥ 20% (group 1) in the first two months post-parathyroidectomy were distinguished from the patients whose eGFR declined by <20% (group 2). The two groups were similar except that group 1 had a higher baseline mean serum PTH compared with group 2, although not significant (1046.7 ± 1034.2 vs. 476.6 ± 444.9, p = 0.14). In group 1, eGFR declined at an average rate of 32% (p < 0.0001) during the first month post-parathyroidectomy compared with 7% (p = 0.1399) in group 2, and the difference between these two groups was significant (p = 0.0003). The graft function recovered in both groups by one yr. During median follow-up of 66.00 ± 49.45 months, 6 (18%) patients lost their graft with a mean time to graft loss from parathyroidectomy of 37.2 ± 21.6 months. The causes of graft loss were rejection (n = 2), pyelonephritis (n = 1) and chronic allograft nephropathy (n = 3). No graft loss occurred during the first-year post-surgery. Conclusion Parathyroidectomy may lead to transient kidney allograft dysfunction with eventual recovery of graft function by 12 months post-parathyroidectomy. Higher level of serum PTH pre-parathyoidectomy is associated with a more profound decrease in eGFR post-parathyroidectomy. PMID:23448282

Structural and Functional Changes in Human Kidneys with Healthy Aging.

PubMed

Hommos, Musab S; Glassock, Richard J; Rule, Andrew D

2017-10-01

Aging is associated with significant changes in structure and function of the kidney, even in the absence of age-related comorbidities. On the macrostructural level, kidney cortical volume decreases, surface roughness increases, and the number and size of simple renal cysts increase with age. On the microstructural level, the histologic signs of nephrosclerosis (arteriosclerosis/arteriolosclerosis, global glomerulosclerosis, interstitial fibrosis, and tubular atrophy) all increase with age. The decline of nephron number is accompanied by a comparable reduction in measured whole-kidney GFR. However, single-nephron GFR remains relatively constant with healthy aging as does glomerular volume. Only when glomerulosclerosis and arteriosclerosis exceed that expected for age is there an increase in single-nephron GFR. In the absence of albuminuria, age-related reduction in GFR with the corresponding increase in CKD (defined by an eGFR<60 ml/min per 1.73 m 2 ) has been shown to associate with a very modest to no increase in age-standardized mortality risk or ESRD. These findings raise the question of whether disease labeling of an age-related decline in GFR is appropriate. These findings also emphasize the need for a different management approach for many elderly individuals considered to have CKD by current criteria. Copyright © 2017 by the American Society of Nephrology.

Age and treatment of kidney failure.

PubMed

Elliott, Meghan J; Tam-Tham, Helen; Hemmelgarn, Brenda R

2013-05-01

This review discusses issues related to treatment of chronic kidney disease, and kidney failure in particular, among older adults. A substantial proportion of older adults have chronic kidney disease and progress to kidney failure. There is considerable variability in treatment practices for advanced kidney disease among older adults, and evidence that treatment decisions such as dialysis initiation may be made without adequate preparation. When initiated, survival among older adults on chronic dialysis remains poor, and is associated with a significant decline in functional status. There is also evidence to suggest that dialysis initiation may not reflect overall treatment goals of elderly patients, but rather a lack of clear communication between patients and health practitioners, and underdeveloped conservative care programs in many centers. Kidney failure is common among older adults. When considering treatment options for kidney failure, patient priorities, preferences, and symptoms should be taken into account, using a shared decision-making approach.

Atherosclerotic renovascular disease among hypertensive adults

PubMed Central

Davis, Ross P.; Pearce, Jeffrey D.; Craven, Timothy E.; Moore, Phillip S.; Edwards, Matthew S.; Godshall, Christopher J.; Hansen, Kimberley J.

2010-01-01

Purpose Ths report describes the change in atherosclerotic renovascular disease (AS-RVD) among hypertensive adults referred for renal duplex sonography (RDS) scan. Methods From Oct 1993 through July 2008, 20,994 patients had RDS at our center. A total of 434 hypertensive patients with two or more RDS exams without intervention comprised the study cohort. Patient demographics (blood pressures, medications, serum creatinine levels, and data from RDS) were collected. Analyses of longitudinal changes in Doppler scan parameters, blood pressures, and renal function were performed by fitting linear growth-curve models. After confirming the linearity of change in Doppler scan parameters among patients with variable number of studies, estimates of mean slopes were calculated using maximum likelihood techniques. For changes in renal function, quadratic growth curves were required to describe longitudinal change. Results A total of 434 subjects (212 men [49%] and 222 women [51%]; mean age, 64.6 ± 12.2 years) provided 1351 studies (mean, 3.2 ± 2.4; range, 2 to 18) for 863 kidneys over a mean follow-up of 34.4 ± 25.1 months. At baseline, 20.6% of kidneys demonstrated hemodynamically significant stenosis. On follow-up, 72 kidneys (9.1%) demonstrated anatomic progression of disease. A total of 54 kidneys (6.9%) progressed to significant stenosis and 18 (2.3%) progressed to occlusion. Controlling for progression of disease, baseline renal artery status demonstrated a strong association with baseline kidney length (P = .0006). Significant annualized change in renal length was observed (cm change/year ± standard error of the mean [SEM]: 0.042 ± 0.011; P = .0002) among both kidneys with and without critical disease at baseline, however, decline in length was significantly greater among kidneys exhibiting progression of renovascular disease (−0.152 ± 0.028 cm/year; comparison of slopes between groups P = .0005). In the absence of progression, the presence or absence of critical renal artery stenosis at baseline did not affect the rate of decline in renal length. Fitted models for the natural log transform of serum creatinine demonstrated a significant increase during follow-up (P < .0001). No association was observed between change in serum creatinine and baseline renovascular disease status, or its progression. Conclusion A total of 32% of hypertensive adults referred for RDS demonstrated hemodynamically significant renal artery stenosis. Regardless of the presence or absence of baseline disease, a small percentage of patients demonstrated anatomic progression of AS-RVD. A total of 9.1% demonstrated anatomic progression and 2.3% progressed to occlusion. Although anatomic progression of AS-RVD was associated with an increased rate of decline in renal length, progression did not predict a decline in excretory renal function. Intervention for AS-RVD should be selective and reserved for strict indications. PMID:19700093

Insights into cellular and molecular basis for urinary tract infection in autosomal-dominant polycystic kidney disease.

PubMed

Gao, Chao; Zhang, Long; Zhang, Ye; Wallace, Darren P; Lopez-Soler, Reynold I; Higgins, Paul J; Zhang, Wenzheng

2017-11-01

Urinary tract infection (UTI) is a broad term referring to an infection of the kidneys, ureters, bladder, and/or urethra. Because of its prevalence, frequent recurrence, and rising resistance to antibiotics, UTI has become a challenge in clinical practice. Autosomal-dominant polycystic kidney disease (ADPKD) is the most common monogenic disorder of the kidney and is characterized by the growth of fluid-filled cysts in both kidneys. Progressive cystic enlargement, inflammation, and interstitial fibrosis result in nephron loss with subsequent decline in kidney function. ADPKD patients frequently develop UTI; however, the cellular and molecular mechanisms responsible for the high UTI incidence in ADPKD patients remain virtually unaddressed. Emerging evidence suggests that α-intercalated cells (α-ICs) of the collecting ducts function in the innate immune defense against UTI. α-ICs inhibit bacterial growth by acidifying urine and secreting neutrophil gelatinase-associated lipocalin (NGAL) that chelates siderophore-containing iron. It is necessary to determine, therefore, if ADPKD patients with recurrent UTI have a reduced number and/or impaired function of α-ICs. Identification of the underlying cellular and molecular mechanisms may lead to the development of novel strategies to reduce UTI in ADPKD. Copyright © 2017 the American Physiological Society.

Association of Urinary Biomarkers of Inflammation, Injury, and Fibrosis with Renal Function Decline: The ACCORD Trial

PubMed Central

Nadkarni, Girish N.; Rao, Veena; Ismail-Beigi, Faramarz; Fonseca, Vivian A.; Shah, Sudhir V.; Simonson, Michael S.; Cantley, Lloyd; Devarajan, Prasad; Parikh, Chirag R.

2016-01-01

Background and objectives Current measures for predicting renal functional decline in patients with type 2 diabetes with preserved renal function are unsatisfactory, and multiple markers assessing various biologic axes may improve prediction. We examined the association of four biomarker-to-creatinine ratio levels (monocyte chemotactic protein-1, IL-18, kidney injury molecule-1, and YKL-40) with renal outcome. Design, setting, participants, & measurements We used a nested case-control design in the Action to Control Cardiovascular Disease Trial by matching 190 participants with ≥40% sustained eGFR decline over the 5-year follow-up period to 190 participants with ≤10% eGFR decline in a 1:1 fashion on key characteristics (age within 5 years, sex, race, baseline albumin-to-creatinine ratio within 20 μg/mg, and baseline eGFR within 10 ml/min per 1.73 m2), with ≤10% decline. We used a Mesoscale Multiplex Platform and measured biomarkers in baseline and 24-month specimens, and we examined biomarker associations with outcome using conditional logistic regression. Results Baseline and 24-month levels of monocyte chemotactic protein-1-to-creatinine ratio levels were higher for cases versus controls. The highest quartile of baseline monocyte chemotactic protein-1-to-creatinine ratio had fivefold greater odds, and each log increment had 2.27-fold higher odds for outcome (odds ratio, 5.27; 95% confidence interval, 2.19 to 12.71 and odds ratio, 2.27; 95% confidence interval, 1.44 to 3.58, respectively). IL-18-to-creatinine ratio, kidney injury molecule-1-to-creatinine ratio, and YKL-40-to-creatinine ratio were not consistently associated with outcome. C statistic for traditional predictors of eGFR decline was 0.70, which improved significantly to 0.74 with monocyte chemotactic protein-1-to-creatinine ratio. Conclusions Urinary monocyte chemotactic protein-1-to-creatinine ratio concentrations were strongly associated with sustained renal decline in patients with type 2 diabetes with preserved renal function. PMID:27189318

Association of Urinary Biomarkers of Inflammation, Injury, and Fibrosis with Renal Function Decline: The ACCORD Trial.

PubMed

Nadkarni, Girish N; Rao, Veena; Ismail-Beigi, Faramarz; Fonseca, Vivian A; Shah, Sudhir V; Simonson, Michael S; Cantley, Lloyd; Devarajan, Prasad; Parikh, Chirag R; Coca, Steven G

2016-08-08

Current measures for predicting renal functional decline in patients with type 2 diabetes with preserved renal function are unsatisfactory, and multiple markers assessing various biologic axes may improve prediction. We examined the association of four biomarker-to-creatinine ratio levels (monocyte chemotactic protein-1, IL-18, kidney injury molecule-1, and YKL-40) with renal outcome. We used a nested case-control design in the Action to Control Cardiovascular Disease Trial by matching 190 participants with ≥40% sustained eGFR decline over the 5-year follow-up period to 190 participants with ≤10% eGFR decline in a 1:1 fashion on key characteristics (age within 5 years, sex, race, baseline albumin-to-creatinine ratio within 20 μg/mg, and baseline eGFR within 10 ml/min per 1.73 m(2)), with ≤10% decline. We used a Mesoscale Multiplex Platform and measured biomarkers in baseline and 24-month specimens, and we examined biomarker associations with outcome using conditional logistic regression. Baseline and 24-month levels of monocyte chemotactic protein-1-to-creatinine ratio levels were higher for cases versus controls. The highest quartile of baseline monocyte chemotactic protein-1-to-creatinine ratio had fivefold greater odds, and each log increment had 2.27-fold higher odds for outcome (odds ratio, 5.27; 95% confidence interval, 2.19 to 12.71 and odds ratio, 2.27; 95% confidence interval, 1.44 to 3.58, respectively). IL-18-to-creatinine ratio, kidney injury molecule-1-to-creatinine ratio, and YKL-40-to-creatinine ratio were not consistently associated with outcome. C statistic for traditional predictors of eGFR decline was 0.70, which improved significantly to 0.74 with monocyte chemotactic protein-1-to-creatinine ratio. Urinary monocyte chemotactic protein-1-to-creatinine ratio concentrations were strongly associated with sustained renal decline in patients with type 2 diabetes with preserved renal function. Copyright © 2016 by the American Society of Nephrology.

Renal cell carcinoma in a cat with polycystic kidney disease undergoing renal transplantation.

PubMed

Adams, Daniel J; Demchur, Jolie A; Aronson, Lillian R

2018-01-01

A 10-year-old spayed female American Shorthair cat underwent renal transplantation due to worsening chronic kidney disease secondary to polycystic kidney disease. During transplantation, the right kidney grossly appeared to be more diseased than the left and was firmly adhered to the surrounding tissues. An intraoperative fine-needle aspirate of the right native kidney revealed inflammatory cells but no evidence of neoplasia. To create space for the allograft, a right nephrectomy was performed. Following nephrectomy, the right native kidney was submitted for biopsy. Biopsy results revealed a renal cell carcinoma. Although the cat initially recovered well from surgery, delayed graft function was a concern in the early postoperative period. Significant azotemia persisted and the cat began to have diarrhea. Erythematous skin lesions developed in the perineal and inguinal regions, which were suspected to be secondary to thromboembolic disease based on histopathology. The cat's clinical status continued to decline with development of signs of sepsis, followed by marked obtundation with uncontrollable seizures. Given the postoperative diagnosis of renal cell carcinoma and the cat's progressively declining clinical status, humane euthanasia was elected. This case is the first to document renal cell carcinoma in a cat with polycystic kidney disease. An association of the two diseases has been reported in the human literature, but such a link has yet to be described in veterinary medicine. Given the association reported in the human literature, a plausible relationship between polycystic kidney disease and renal cell carcinoma in cats merits further investigation.

Hypertension in pediatric patients with chronic kidney disease: management challenges.

PubMed

Gallibois, Claire M; Jawa, Natasha A; Noone, Damien G

2017-01-01

In contrast to adults where hypertension is a leading cause of chronic kidney disease, in pediatrics, hypertension is predominantly a sequela, however, an important one that, like in adults, is likely associated with a more rapid decline in kidney function or progression of chronic kidney disease to end stage. There is a significant issue with unrecognized, or masked, hypertension in childhood chronic kidney disease. Recent evidence and, therefore, guidelines now suggest targeting a blood pressure of <50th percentile for age, sex, and height in children with proteinuria and chronic kidney disease. This often cannot be achieved by monotherapy and additional agents need to be added. Blockade of the renin angiotensin aldosterone system represents the mainstay of therapy, although often limited by the side effect of hyperkalemia. The addition of a diuretic, at least in the earlier stages of chronic kidney disease, might help mitigate this problem.

Sleep Characteristics in Early Stages of Chronic Kidney Disease in the HypnoLaus Cohort.

PubMed

Ogna, Adam; Forni Ogna, Valentina; Haba Rubio, José; Tobback, Nadia; Andries, Dana; Preisig, Martin; Tafti, Mehdi; Vollenweider, Peter; Waeber, Gerard; Marques-Vidal, Pedro; Heinzer, Raphaël

2016-04-01

To evaluate the association between early stages of chronic kidney disease (CKD) and sleep disordered breathing (SDB), restless legs syndrome (RLS), and subjective and objective sleep quality (SQ). Cross-sectional analysis of a general population-based cohort (HypnoLaus). 1,760 adults (862 men, 898 women; age 59.3 (± 11.4) y) underwent complete polysomnography at home. 8.2% of participants had mild CKD (stage 1-2, estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m(2) with albuminuria) and 7.8% moderate CKD (stage 3, eGFR 30-60 mL/min/1.73 m(2)). 37.3% of our sample had moderate-to-severe SDB (apnea-hypopnea index [AHI] ≥ 15/h) and 15.3% had severe SDB (AHI ≥ 30/h). SDB prevalence was positively associated with CKD stages and negatively with eGFR. In multivariate analysis, age, male sex, and body mass index were independently associated with SDB (all P < 0.001), but kidney function was not. The prevalence of RLS was 17.5%, without difference between CKD stages. Periodic leg movements index (PLMI) was independently associated with CKD stages. Subjective and objective SQ decreased and the use of sleep medication was more frequent with declining kidney function. Older age, female sex, and the severity of SDB were the strongest predictors of poor SQ in multivariate regression analysis but CKD stage was also independently associated with reduced objective SQ. Patients with early stages of CKD have impaired SQ, use more hypnotic drugs, and have an increased prevalence of SDB and PLM. After controlling for confounders, objective SQ and PLMI were still independently associated with declining kidney function. © 2016 Associated Professional Sleep Societies, LLC.

Uromodulin mRNA from Urinary Extracellular Vesicles Correlate to Kidney Function Decline in Type 2 Diabetes Mellitus.

PubMed

Yamamoto, Cindy M; Murakami, Taku; Oakes, Melanie L; Mitsuhashi, Masato; Kelly, Colleen; Henry, Robert R; Sharma, Kumar

2018-05-18

Extracellular vesicles (EVs) enclose mRNA derived from their cell of origin and are considered a source of potential biomarkers. We examined urinary EV mRNA from individuals with diabetic kidney disease (DKD), chronic kidney disease, type 2 diabetes (T2DM), and obese and healthy controls to determine if such biomarkers had the potential to classify kidney disease and predict patients at higher risk of renal function decline. A total of 242 participants enrolled in this study. Urinary EV mRNA from all subjects were isolated by a filter-based platform, and the expression of 8 target genes were determined by quantitative polymerase chain reaction (qPCR). Changes in estimated glomerular filtration rate (eGFR) in 161 T2DM patients were evaluated for 2 consecutive years and compared with EV RNA profiles at baseline. We observe that mild and severe DKD groups show a significant 3.2- and -4.4-fold increase in UMOD compared to healthy controls and expression increases linearly from healthy, diabetic, and DKD subjects. UMOD expression is significantly correlated to albumin creatinine ratio (ACR), eGFR, and HbA1c. Using linear discriminant analyses with mRNA from severe DKD and T2DM as training data, a multi-gene signature classified DKD and -non-DKD with a sensitivity of 93% and specificity of 73% with area under the receiver operating characteristic (ROC) curve (AUC) = 0.90. Although 6% of T2DM were determined to have a > 80% posterior probability of developing DKD based on this mRNA profile, eGFR changes observed within the 2-year follow-up did not reveal a decline in kidney function. Urinary EV UMOD mRNA levels are progressively elevated from T2DM to DKD groups and correlate with widely used eGFR and ACR diagnostic criteria. An EV mRNA signature could identify DKD with greater than 90% sensitivity and 70% specificity. © 2018 S. Karger AG, Basel.

Long-term Effects of Off-Pump Coronary Bypass Versus Conventional Coronary Bypass Grafting on Renal Function.

PubMed

Hynes, Conor F; Colo, Sanchez; Amdur, Richard L; Chawla, Lakhmir S; Greenberg, Michael D; Trachiotis, Gregory D

2016-01-01

This study aimed to evaluate the short- and long-term effects of conventional on-pump coronary bypass grafting (cCABG) compared with off-pump coronary artery bypass (OPCAB) on renal function. A retrospective review of patients undergoing coronary bypass grafting from 2004 through 2013 at a single center was conducted. Preoperative renal function, perioperative acute kidney injury, and long-term glomerular filtration were evaluated. Multivariable analyses were used to determine factors contributing to short- and long-term renal impairment. A total of 234 patients underwent cCABG, and 582 underwent OPCAB. Patients undergoing OPCAB were significantly older, had greater preoperative renal dysfunction, had greater functional dependence, and took more hypertension medications. Multivariable analyses found that 30-day acute kidney injury was an independent risk factor for a 10% decline in glomerular filtration rate at 1 and 5 years (P < 0.0001 and 0.002, respectively). However, the use of cardiopulmonary bypass was not found to influence long-term renal function (P = 0.78 at 1 year, P = 0.76 at 5 years). The percentage of patients experiencing a 10% drop in renal function from baseline at 1 year (33% OPCAB, 35% cCABG; P = 0.73) and 5 years (16% OPCAB, 16% cCABG; P = 0.93) were not significantly different. Independent predictors of acute kidney injury included baseline kidney function (P = 0.04) and age (P < 0.0001), whereas cardiopulmonary bypass did not affect the incidence (P = 0.17). A propensity-matched analysis confirmed these findings. Acute kidney injury is a risk factor for long-term renal dysfunction after either bypass method and was not greater after cCABG compared with OPCAB. Patients undergoing OPCAB did not experience greater decrease in long-term kidney function despite having worse baseline kidney function.

Incremental short daily home hemodialysis: a case series.

PubMed

Toth-Manikowski, Stephanie M; Mullangi, Surekha; Hwang, Seungyoung; Shafi, Tariq

2017-07-05

Patients starting dialysis often have substantial residual kidney function. Incremental hemodialysis provides a hemodialysis prescription that supplements patients' residual kidney function while maintaining total (residual + dialysis) urea clearance (standard Kt/Vurea) targets. We describe our experience with incremental hemodialysis in patients using NxStage System One for home hemodialysis. From 2011 to 2015, we initiated 5 incident hemodialysis patients on an incremental home hemodialysis regimen. The biochemical parameters of all patients remained stable on the incremental hemodialysis regimen and they consistently achieved standard Kt/Vurea targets. Of the two patients with follow-up >6 months, residual kidney function was preserved for ≥2 years. Importantly, the patients were able to transition to home hemodialysis without automatically requiring 5 sessions per week at the outset and gradually increased the number of treatments and/or dialysate volume as the residual kidney function declined. An incremental home hemodialysis regimen can be safely prescribed and may improve acceptability of home hemodialysis. Reducing hemodialysis frequency by even one treatment per week can reduce the number of fistula or graft cannulations or catheter connections by >100 per year, an important consideration for patient well-being, access longevity, and access-related infections. The incremental hemodialysis approach, supported by national guidelines, can be considered for all home hemodialysis patients with residual kidney function.

Effect of low-protein diet supplemented with keto acids on progression of chronic kidney disease.

PubMed

Garneata, Liliana; Mircescu, Gabriel

2013-05-01

Hypoproteic diets are most often discussed for patients with chronic kidney disease (CKD) who do not receive dialysis. A very low-protein diet supplemented with ketoanalogues of essential amino acids (keto-diet) proved effective in ameliorating metabolic disturbances of advanced CKD and delaying the initiation of dialysis without deleterious effects on nutritional status. Several recent studies report that the keto-diet could also slow down the rate of decline in renal function, with better outcomes after the initiation of dialysis. Results of a single-center randomized controlled trial addressing the rate of CKD progression revealed a 57% slower decline in renal function with the keto-diet compared with a conventional low-protein diet (LPD). The keto-diet allowed the safe management of selected patients with stage 4-5 CKD, delaying dialysis for almost 1 year, with a major impact on patient quality of life and health expenditures. Therefore, the keto-diet could be a link in the integrated care model. Careful selection of patients, nutritional monitoring, and dietary counseling are required. Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Role of oxidants/inflammation in declining renal function in chronic kidney disease and normal aging.

PubMed

Vlassara, Helen; Torreggiani, Massimo; Post, James B; Zheng, Feng; Uribarri, Jaime; Striker, Gary E

2009-12-01

Oxidant stress (OS) and inflammation increase in normal aging and in chronic kidney disease (CKD), as observed in human and animal studies. In cross-sectional studies of the US population, these changes are associated with a decrease in renal function, which is exhibited by a significant proportion of the population. However, since many normal adults have intact renal function, and longitudinal studies show that some persons maintain normal renal function with age, the link between OS, inflammation, and renal decline is not clear. In aging mice, greater oxidant intake is associated with increased age-related CKD and mortality, which suggests that interventions that reduce OS and inflammation may be beneficial for older individuals. Both OS and inflammation can be readily lowered in normal subjects and patients with CKD stage 3-4 by a simple dietary modification that lowers intake and results in reduced serum and tissue levels of advanced glycation end products. Diabetic patients, including those with microalbuminuria, have a decreased ability to metabolize and excrete oxidants prior to observable changes in serum creatinine. Thus, OS and inflammation may occur in the diabetic kidney at an early time. We review the evidence that oxidants in the diet directly lead to increased serum levels of OS and inflammatory mediators in normal aging and in CKD. We also discuss a simple dietary intervention that helps reduce OS and inflammation, an important and achievable therapeutic goal for patients with CKD and aging individuals with reduced renal function.

Coping with missing data in phase III pivotal registration trials: Tolvaptan in subjects with kidney disease, a case study.

PubMed

Ouyang, John; Carroll, Kevin J; Koch, Gary; Li, Junfang

2017-07-01

Missing data cause challenging issues, particularly in phase III registration trials, as highlighted by the European Medicines Agency (EMA) and the US National Research Council. We explore, as a case study, how the issues from missing data were tackled in a double-blind phase III trial in subjects with autosomal dominant polycystic kidney disease. A total of 1445 subjects were randomized in a 2:1 ratio to receive active treatment (tolvaptan), or placebo. The primary outcome, the rate of change in total kidney volume, favored tolvaptan (P < .0001). The key secondary efficacy endpoints of clinical progression of disease and rate of decline in kidney function also favored tolvaptan. However, as highlighted by Food and Drug Administration and EMA, the interpretation of results was hampered by a high number of unevenly distributed dropouts, particularly early dropouts. In this paper, we outline the analyses undertaken to address the issue of missing data thoroughly. "Tipping point analyses" were performed to explore how extreme and detrimental outcomes among subjects with missing data must be to overturn the positive treatment effect attained in those subjects who had complete data. Nonparametric rank-based analyses were also performed accounting for missing data. In conclusion, straightforward and transparent analyses directly taking into account missing data convincingly support the robustness of the preplanned analyses on the primary and secondary endpoints. Tolvaptan was confirmed to be effective in slowing total kidney volume growth, which is considered an efficacy endpoint by EMA, and in lessening the decline in renal function in patients with autosomal dominant polycystic kidney disease. Copyright © 2017 John Wiley & Sons, Ltd.

Deleterious effects of incense smoke exposure on kidney function and architecture in male albino rats.

PubMed

Hussain, Tajamul; Al-Attas, Omar S; Alrokayan, Salman A; Ahmed, Mukhtar; Al-Daghri, Nasser M; Al-Ameri, Salman; Pervez, Shamsh; Dewangan, Shippi; Mohammed, Arif; Gambhir, Dikshit; Sumague, Terrance S

2016-07-01

Previous studies, including ours, have shown adverse effects of incense smoke on human health. However, the effect of incense smoke on kidney function and structure remains unknown. To evaluate possible adverse effects of incense smoke on kidney function and architecture in albino rats after chronic exposure to Arabian incense. Emission characteristics including particle size distribution, volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs) were determined by gravimetric and GCMS analyses. Kidney functional markers, oxidative stress and inflammatory markers were measured by standard or ELISA based procedures. Ultrastructural changes in kidney were examined by transmission electron microscope (TEM) and the gene expression of xenobiotic metabolizing enzymes including cytochrome P-450-1A1 (CYP1A1) and CYP1A2 were studied by real time PCR. Rats exposed to incense smoke demonstrated a significant increase in serum creatinine, uric acid, blood urea nitrogen (BUN), tissue malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α) and interleukin-4 (IL-4) levels and a significant decline in tissue reduced glutathione (GSH) and catalase activity. Incense smoke exposed rats also displayed marked ultrastructural changes in kidney tissue. Further, a significant increase in tissue gene expression of both CYP1A1 and CYP1A2 was noted in exposed rats. Changes to kidney functional markers and architecture appear to be mediated through augmented oxidative stress and inflammation. Long-term exposure to incense smoke may have deleterious effects on kidney function and architecture. Though, inhalation is the rout of exposure, findings of this study underscore that incense smoke may also have an effect on non-pulmonary tissues.

Reversal deterioration of renal function accompanied with primary hypothyrodism.

PubMed

Dragović, Tamara

2012-02-01

Hypothyroidism is often accompanied with decline of kidney function, or inability to maintain electrolyte balance. These changes are usually overlooked in everyday practice. Early recognition of this association eliminates unnecessary diagnostic procedures that postpone the adequate treatment. Two patients with elevated serum creatinine levels due to primary autoimmune hypothyroidism, with complete recovery of creatinine clearance after thyroid hormone substitution therapy are presented. The first patient was a young male whose laboratory tests suggested acute renal failure, and the delicate clinical presentation of reduced thyroid function. The second patient was an elderly woman with a history of a long-term signs and symptoms attributed to ageing, including the deterioration of renal function, with consequently delayed diagnosis of hypothyroidism. Serum thyrotropin and thyroxin levels measurement should be done in all cases of renal failure with undefined renal desease, even if the typical clinical presentation of hypothyroidism is absent. Thyroid hormone assays sholud also be performed in all patients with chronic kidney disease whose kidney function is rapidly worsening.

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 Association between a Mediterranean-Style Diet and Kidney Function in the Northern Manhattan Study Cohort

PubMed Central

Moon, Yeseon P.; Scarmeas, Nikolaos; Gu, Yian; Gardener, Hannah; Cheung, Ken; Wright, Clinton B.; Sacco, Ralph L.; Nickolas, Thomas L.; Elkind, Mitchell S.V.

2014-01-01

Background and objectives Various dietary strategies have been investigated to slow kidney function decline. However, it is unknown whether a Mediterranean diet, which has been associated with improved cardiovascular risk, is associated with change in kidney function. Design, setting, participants, & measurements This study used the Northern Manhattan Study, a prospective, multiethnic, observational cohort of participants who were stroke free at baseline. Data were collected between 1993 and 2008. Serum creatinine measurements were taken a mean 6.9 years apart. A baseline dietary questionnaire was extrapolated into a previously used 9-point scoring system (MeDi). The primary outcome was incident eGFR<60 ml/min per 1.73 m2using the Modification of Diet in Renal Disease formula. A secondary outcome was the upper quartile of annualized eGFR decline (≥2.5 ml/min per 1.73 m2 per year). Conditional logistic regression models adjusted for demographics and baseline vascular risk factors. Results Mean baseline age was 64 years, with 59% women and 65% Hispanics (N=900); mean baseline eGFR was 83.1 ml/min per 1.73 m2. Incident eGFR<60 ml/min per 1.73 m2 developed in 14% . In adjusted models, every 1-point increase in the MeDi score, indicating increasing adherence to a Mediterranean diet, was associated with decreased odds of incident eGFR<60 ml/min per 1.73 m2 (odds ratio, 0.83; 95% confidence interval, 0.71 to 0.96) and decreased odds of being in the upper quartile of eGFR decline (odds ratio, 0.88; 95% confidence interval, 0.79 to 0.98). Conclusions A Mediterranean diet was associated with a reduced incidence of eGFR<60 ml/min per 1.73 m2 and upper quartile of eGFR decline in a multiethnic cohort. PMID:25359387

The association between a Mediterranean-style diet and kidney function in the Northern Manhattan Study cohort.

PubMed

Khatri, Minesh; Moon, Yeseon P; Scarmeas, Nikolaos; Gu, Yian; Gardener, Hannah; Cheung, Ken; Wright, Clinton B; Sacco, Ralph L; Nickolas, Thomas L; Elkind, Mitchell S V

2014-11-07

Various dietary strategies have been investigated to slow kidney function decline. However, it is unknown whether a Mediterranean diet, which has been associated with improved cardiovascular risk, is associated with change in kidney function. This study used the Northern Manhattan Study, a prospective, multiethnic, observational cohort of participants who were stroke free at baseline. Data were collected between 1993 and 2008. Serum creatinine measurements were taken a mean 6.9 years apart. A baseline dietary questionnaire was extrapolated into a previously used 9-point scoring system (MeDi). The primary outcome was incident eGFR<60 ml/min per 1.73 m(2)using the Modification of Diet in Renal Disease formula. A secondary outcome was the upper quartile of annualized eGFR decline (≥ 2.5 ml/min per 1.73 m(2) per year). Conditional logistic regression models adjusted for demographics and baseline vascular risk factors. Mean baseline age was 64 years, with 59% women and 65% Hispanics (N=900); mean baseline eGFR was 83.1 ml/min per 1.73 m(2). Incident eGFR<60 ml/min per 1.73 m(2) developed in 14% . In adjusted models, every 1-point increase in the MeDi score, indicating increasing adherence to a Mediterranean diet, was associated with decreased odds of incident eGFR<60 ml/min per 1.73 m(2) (odds ratio, 0.83; 95% confidence interval, 0.71 to 0.96) and decreased odds of being in the upper quartile of eGFR decline (odds ratio, 0.88; 95% confidence interval, 0.79 to 0.98). A Mediterranean diet was associated with a reduced incidence of eGFR<60 ml/min per 1.73 m(2) and upper quartile of eGFR decline in a multiethnic cohort. Copyright © 2014 by the American Society of Nephrology.

Effect of Coaching to Increase Water Intake on Kidney Function Decline in Adults With Chronic Kidney Disease: The CKD WIT Randomized Clinical Trial.

PubMed

Clark, William F; Sontrop, Jessica M; Huang, Shih-Han; Gallo, Kerri; Moist, Louise; House, Andrew A; Cuerden, Meaghan S; Weir, Matthew A; Bagga, Amit; Brimble, Scott; Burke, Andrew; Muirhead, Norman; Pandeya, Sanjay; Garg, Amit X

2018-05-08

In observational studies, increased water intake is associated with better kidney function. To determine the effect of coaching to increase water intake on kidney function in adults with chronic kidney disease. The CKD WIT (Chronic Kidney Disease Water Intake Trial) randomized clinical trial was conducted in 9 centers in Ontario, Canada, from 2013 until 2017 (last day of follow-up, May 25, 2017). Patients had stage 3 chronic kidney disease (estimated glomerular filtration rate [eGFR] 30-60 mL/min/1.73 m2 and microalbuminuria or macroalbuminuria) and a 24-hour urine volume of less than 3.0 L. Patients in the hydration group (n = 316) were coached to drink more water, and those in the control group (n = 315) were coached to maintain usual intake. The primary outcome was change in kidney function (eGFR from baseline to 12 months). Secondary outcomes included 1-year change in plasma copeptin concentration, creatinine clearance, 24-hour urine albumin, and patient-reported overall quality of health (0 [worst possible] to 10 [best possible]). Of 631 randomized patients (mean age, 65.0 years; men, 63.4%; mean eGFR, 43 mL/min/1.73 m2; median urine albumin, 123 mg/d), 12 died (hydration group [n = 5]; control group [n = 7]). Among 590 survivors with 1-year follow-up measurements (95% of 619), the mean change in 24-hour urine volume was 0.6 L per day higher in the hydration group (95% CI, 0.5 to 0.7; P < .001). The mean change in eGFR was -2.2 mL/min/1.73 m2 in the hydration group and -1.9 mL/min/1.73 m2 in the control group (adjusted between-group difference, -0.3 mL/min/1.73 m2 [95% CI, -1.8 to 1.2; P = .74]). The mean between-group differences (hydration vs control) in secondary outcomes were as follows: plasma copeptin, -2.2 pmol/L (95% CI, -3.9 to -0.5; P = .01); creatinine clearance, 3.6 mL/min/1.73 m2 (95% CI, 0.8 to 6.4; P = .01); urine albumin, 7 mg per day (95% CI, -4 to 51; P = .11); and quality of health, 0.2 points (95% CI, -0.3 to 0.3; P = .22). Among adults with chronic kidney disease, coaching to increase water intake compared with coaching to maintain the same water intake did not significantly slow the decline in kidney function after 1 year. However, the study may have been underpowered to detect a clinically important difference. clinicaltrials.gov Identifier: NCT01766687.

Estimated Kidney Function Based on Serum Cystatin C and Risk of Subsequent Coronary Artery Calcium in Young and Middle-aged Adults With Preserved Kidney Function: Results From the CARDIA Study

PubMed Central

Bansal, Nisha; Vittinghoff, Eric; Peralta, Carmen A.; Shlipak, Michael G.; Grubbs, Vanessa; Jacobs, David R.; Siscovick, David; Steffes, Michael; Carr, John Jeffrey; Bibbins-Domingo, Kirsten

2013-01-01

Whether kidney dysfunction is associated with coronary artery calcium (CAC) in young and middle-aged adults who have a cystatin C–derived estimated glomerular filtration rate (eGFRcys) greater than 60 mL/min/1.73 m2 is unknown. In the Coronary Artery Risk Development in Young Adults (CARDIA) cohort (recruited in 1985 and 1986 in Birmingham, Alabama; Chicago, Illinois; Minneapolis, Minnesota; and Oakland, California), we examined 1) the association of eGFRcys at years 10 and 15 and detectable CAC over the subsequent 5 years and 2) the association of change in eGFRcys and subsequent CAC, comparing those with stable eGFRcys to those whose eGFRcys increased (>3% annually over 5 years), declined moderately (3%–5%), or declined rapidly (>5%). Generalized estimating equation Poisson models were used, with adjustment for age, sex, race, educational level, income, family history of coronary artery disease, diabetes, body mass index, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and tobacco use. Among 3,070 participants (mean age 35.6 (standard deviation, 4.1) years and mean eGFRcys 106.7 (standard deviation, 18.5) mL/min/1.73 m2), 529 had detectable CAC. Baseline eGFRcys was not associated with CAC. Moderate eGFRcys decline was associated with a 33% greater relative risk of subsequent CAC (95% confidence interval: 5, 68; P = 0.02), whereas rapid decline was associated with a 51% higher relative risk (95% confidence interval: 10, 208; P = 0.01) in adjusted models. In conclusion, among young and middle-aged adults with eGFRcys greater than 60 mL/min/1.73 m2, annual decline in eGFRcys is an independent risk factor for subsequent CAC. PMID:23813702

Endoplasmic Reticulum Stress in Ischemic and Nephrotoxic Acute Kidney Injury.

PubMed

Yan, Mingjuan; Shu, Shaoqun; Guo, Chunyuan; Tang, Chengyuan; Dong, Zheng

2018-06-12

Acute kidney injury is a medical condition characterized by kidney damage with a rapid decline of renal function, which is associated with high mortality and morbidity. Recent research has further established an intimate relationship between acute kidney injury and chronic kidney disease. Perturbations of kidney cells in acute kidney injury result in the accumulation of unfolded and misfolded proteins in the endoplasmic reticulum, leading to unfolded protein response or endoplasmic reticulum stress. In this review, we analyze the role and regulation of endoplasmic reticulum stress in acute kidney injury triggered by renal ischemia-reperfusion and cisplatin nephrotoxicity. The balance between the two major components of unfolded protein response, the adaptive pathway and the apoptotic pathway, plays a critical role in determining the cell fate in endoplasmic reticulum stress. The adaptive pathway is evoked to attenuate translation, induce chaperones, maintain protein homeostasis, and promote cell survival. Prolonged endoplasmic reticulum stress activates the apoptotic pathway, resulting in the elimination of dysfunctional cells. Therefore, regulating ER stress in kidney cells may provide a therapeutic target in acute kidney injury.

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

Nutrition Interventions in Chronic Kidney Disease.

PubMed

Anderson, Cheryl A M; Nguyen, Hoang Anh; Rifkin, Dena E

2016-11-01

Dietary modification is recommended in the management of chronic kidney disease (CKD). Individuals with CKD often have multiple comorbidities, such as high blood pressure, diabetes, obesity, and cardiovascular disease, for which dietary modification is also recommended. As CKD progresses, nutrition plays an important role in mitigating risk for cardiovascular disease and decline in kidney function. The objectives of nutrition interventions in CKD include management of risk factors, ensuring optimal nutritional status throughout all stages of CKD, preventing buildup of toxic metabolic products, and avoiding complications of CKD. Recommended dietary changes should be feasible, sustainable, and suited for patients' food preferences and clinical needs. Copyright © 2016 Elsevier Inc. All rights reserved.

Estimated GFR and Subsequent Higher Left Ventricular Mass in Young and Middle-Aged Adults With Normal Kidney Function: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

PubMed Central

Bansal, Nisha; Lin, Feng; Vittinghoff, Eric; Peralta, Carmen; Lima, Joao; Kramer, Holly; Shlipak, Michael; Bibbins-Domingo, Kirsten

2015-01-01

Background Left ventricular hypertrophy (LVH) is common and is associated with cardiovascular events and death among patients with known chronic kidney disease (CKD). However, the link between reduced glomerular filtration rate (GFR) and left ventricular mass index (LVMI) remains poorly explored among young and middle-aged adults with preserved kidney function. In this study, we examined the association of cystatin C-based estimated GFR (eGFRcys) and rapid decline in eGFR with subsequent LVMI. Study Design Observational study Setting & Participants We included 2,410 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort with eGFRcys >60 ml/min/1.73 m2 at Year 15 and who had an echocardiogram performed at Year 25. Predictor eGFRcys at Year 15 and rapid decline of eGFRcys (defined as >3% per year over 5 years from Years 15 to 20) Outcome LVMI measured at Year 25 Measurements We adjusted for age, sex, race, diabetes, body mass index, LDL and HDL cholesterol, cumulative systolic blood pressure, and albuminuria. Results Mean age was 40 ±4 (SD) years, 58% were female and 43% were Black. After 10 years of follow-up, mean LVMI was 39.6 ±13.4 g/m2.7. Compared with eGFRcys >90 ml/min/1.73 m2 (n=2228), eGFRcys 60-75 ml/min/1.73 m2 (n=29) was associated with 5.63 (95% CI, 0.90-10.36) g/m2.7 greater LVMI (p=0.02), but there was no association of eGFR 76-90 ml/min/1.73 m2 (n=153) with LVMI after adjustment for confounders. Rapid decline in eGFRcys was associated with higher LVMI compared to participants without a rapid GFR decline (β-coefficient, 1.48; 95% CI, 0.11-2.83; p=0.03) after adjustment for confounders. Limitations There were a limited number of participants with eGFR 60-90 ml/min/1.73 m2. Conclusions Among young and middle-aged adults with preserved kidney function, eGFRcys 60-75 ml/min/1.73 m2 and rapid decline of eGFRcys were significantly associated with subsequently higher LVMI. Further studies are needed to understand the mechanisms that contribute to elevated LVMI in this range of eGFR. PMID:26253992

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.

A dual agonist of farnesoid X receptor (FXR) and the G protein-coupled receptor TGR5, INT-767, reverses age-related kidney disease in mice.

PubMed

Wang, Xiaoxin X; Luo, Yuhuan; Wang, Dong; Adorini, Luciano; Pruzanski, Mark; Dobrinskikh, Evgenia; Levi, Moshe

2017-07-21

Even in healthy individuals, renal function gradually declines during aging. However, an observed variation in the rate of this decline has raised the possibility of slowing or delaying age-related kidney disease. One of the most successful interventional measures that slows down and delays age-related kidney disease is caloric restriction. We undertook the present studies to search for potential factors that are regulated by caloric restriction and act as caloric restriction mimetics. Based on our prior studies with the bile acid-activated nuclear hormone receptor farnesoid X receptor (FXR) and G protein-coupled membrane receptor TGR5 that demonstrated beneficial effects of FXR and TGR5 activation in the kidney, we reasoned that FXR and TGR5 could be excellent candidates. We therefore determined the effects of aging and caloric restriction on the expression of FXR and TGR5 in the kidney. We found that FXR and TGR5 expression levels are decreased in the aging kidney and that caloric restriction prevents these age-related decreases. Interestingly, in long-lived Ames dwarf mice, renal FXR and TGR5 expression levels were also increased. A 2-month treatment of 22-month-old C57BL/6J mice with the FXR-TGR5 dual agonist INT-767 induced caloric restriction-like effects and reversed age-related increases in proteinuria, podocyte injury, fibronectin accumulation, TGF-β expression, and, most notably, age-related impairments in mitochondrial biogenesis and mitochondrial function. Furthermore, in podocytes cultured in serum obtained from old mice, INT-767 prevented the increases in the proinflammatory markers TNF-α, toll-like receptor 2 (TLR2), and TLR4. In summary, our results indicate that FXR and TGR5 may play an important role in modulation of age-related kidney disease. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Bariatric surgery is associated with improvement in kidney outcomes.

PubMed

Chang, Alex R; Chen, Yuan; Still, Christopher; Wood, G Craig; Kirchner, H Lester; Lewis, Meredith; Kramer, Holly; Hartle, James E; Carey, David; Appel, Lawrence J; Grams, Morgan E

2016-07-01

Severe obesity is associated with increased risk of kidney disease. Whether bariatric surgery reduces the risk of adverse kidney outcomes is uncertain. To resolve this we compared the risk of estimated glomerular filtration rate (eGFR) decline of ≥30% and doubling of serum creatinine or end-stage renal disease (ESRD) in 985 patients who underwent bariatric surgery with 985 patients who did not undergo such surgery. Patients were matched on demographics, baseline body mass index, eGFR, comorbidities, and previous nutrition clinic use. Mean age was 45 years, 97% were white, 80% were female, and 33% had baseline eGFR <90 ml/min per 1.73 m(2). Mean 1-year weight loss was 40.4 kg in the surgery group compared with 1.4 kg in the matched cohort. Over a median follow-up of 4.4 years, 85 surgery patients had an eGFR decline of ≥30% (22 had doubling of serum creatinine/ESRD). Over a median follow-up of 3.8 years, 177 patients in the matched cohort had an eGFR decline of ≥30% (50 had doubling of serum creatinine/ESRD). In adjusted analysis, bariatric surgery patients had a significant 58% lower risk for an eGFR decline of ≥30% (hazard ratio 0.42, 95% confidence interval 0.32-0.55) and 57% lower risk of doubling of serum creatinine or ESRD (hazard ratio 0.43, 95% confidence interval: 0.26-0.71) compared with the matched cohort. Results were generally consistent among subgroups of patients with and without eGFR <90 ml/min per 1.73 m(2), hypertension, and diabetes. Thus, bariatric surgery may be an option to prevent kidney function decline in severely obese individuals. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Common Elements in Rare Kidney Diseases: Conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

PubMed

Aymé, Ségolène; Bockenhauer, Detlef; Day, Simon; Devuyst, Olivier; Guay-Woodford, Lisa M; Ingelfinger, Julie R; Klein, Jon B; Knoers, Nine V A M; Perrone, Ronald D; Roberts, Julia; Schaefer, Franz; Torres, Vicente E; Cheung, Michael; Wheeler, David C; Winkelmayer, Wolfgang C

2017-10-01

Rare kidney diseases encompass at least 150 different conditions, most of which are inherited. Although individual rare kidney diseases raise specific issues, as a group these rare diseases can have overlapping challenges in diagnosis and treatment. These challenges include small numbers of affected patients, unidentified causes of disease, lack of biomarkers for monitoring disease progression, and need for complex care. To address common clinical and patient issues among rare kidney diseases, the KDIGO Controversies Conference entitled, Common Elements in Rare Kidney Diseases, brought together a panel of multidisciplinary clinical providers and patient advocates to address five central issues for rare kidney diseases. These issues encompassed diagnostic challenges, management of kidney functional decline and progression of chronic kidney disease, challenges in clinical study design, translation of advances in research to clinical care, and provision of practical and integrated patient support. Thus, by a process of consensus, guidance for addressing these challenges was developed and is presented here. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Regional cyst concentration as a prognostic biomarker for polycystic kidney disease

NASA Astrophysics Data System (ADS)

Warner, Joshua D.; Irazabal, Maria V.; Torres, Vicente E.; King, Bernard F.; Erickson, Bradley J.

2014-03-01

Polycystic kidney disease (PKD) is a major cause of renal failure. Despite recent advances in understanding the biochemistry and genetics of PKD, the functional mechanisms underpinning the declines in renal function observed in the disorder are not well established. No studies investigating the distribution of cysts within polycystic kidneys exist. This work introduces regional cyst concentration as a new biomarker for evaluation of patients suffering from PKD. We derive a method to define central and peripheral regions of the kidney, approximating the anatomical division between cortex and medulla, and apply it to two cohorts of ten patients with early/mild or late/severe disease. Our results from the late/severe cohort show peripheral cyst concentration correlates with the current standard PKD biomarker, total kidney volume (TKV), signi cantly better than central cyst concentration (p < 0.05). We also find that cyst concentration was globally increased in the late/severe cohort (p << 0.01) compared to the early/mild cohort, for both central and peripheral regions. These findings show cysts in PKD are not distributed homogeneously throughout the renal tissues.

Use of bortezomib in heavy-chain deposition disease: a report of 3 cases.

PubMed

Patel, Kinjal; Dillon, John J; Leung, Nelson; Bomback, Andrew S; Appel, Gerald B; D'Agati, Vivette; Canetta, Pietro A

2014-07-01

Heavy-chain deposition disease (HCDD) is a rare complication of plasma cell dyscrasia in which monoclonal heavy chains deposit in glomerular and tubular basement membranes of the kidney. Clinical and pathologic features of HCDD have been well described in case reports and series, but evidence supporting specific therapies is sparse. Historically, the disease has had a poor prognosis, intensifying the need to clarify optimal treatments. We describe 3 cases of HCDD with biopsy-proven glomerular involvement, severe nephrotic syndrome, and decline in kidney function that were treated successfully with bortezomib, a proteasome inhibitor. None of these patients had multiple myeloma. In all cases, bortezomib-based therapy resulted in sustained resolution of nephrotic syndrome and improvement in kidney function. All 3 patients developed peripheral neuropathy; otherwise, treatment was well tolerated. To our knowledge, this is the first description of the clinical effectiveness of bortezomib against HCDD. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Successful Dual Kidney Transplantation After Hypothermic Oxygenated Perfusion of Discarded Human Kidneys

PubMed Central

Ravaioli, Matteo; De Pace, Vanessa; Comai, Giorgia; Busutti, Marco; Gaudio, Massimo Del; Amaduzzi, Annalisa; Cucchetti, Alessandro; Siniscalchi, Antonio; La Manna, Gaetano; D’Errico, Antonietta A.D.; Pinna, Antonio Daniele

2017-01-01

Patient: Female, 58 Final Diagnosis: Nephroangiosclerosis Symptoms: Renal failure Medication: — Clinical Procedure: Resuscitation of grafts by hypothermic oxygenated perfusion Specialty: Transplantology Objective: Challenging differential diagnosis Background: The recovery of discarded human kidneys has increased in recent years and impels to use of unconventional organ preservation strategies that improve graft function. We report the first case of human kidneys histologically discarded and transplanted after hypothermic oxygenated perfusion (HOPE). Case Report: Marginal kidneys from a 78-year-old woman with brain death were declined by Italian transplant centers due to biopsy score (right kidney: 6; left kidney: 7). We recovered and preserved both kidneys through HOPE and we revaluated their use for transplantation by means of perfusion parameters. The right kidney was perfused for 1 h 20 min and the left kidney for 2 h 30 min. During organ perfusion, the renal flow increased progressively. We observed an increase of 34% for the left kidney (median flow 52 ml/min) and 50% for the right kidney (median flow 24 ml/min). Both kidneys had low perfusate’s lactate levels. We used perfusion parameters as important determinants of the organ discard. Based on our previous organ perfusion experience, the increase of renal flow and the low level of lactate following 1 h of HOPE lead us to declare both kidneys as appropriate for dual kidney transplantation (DKT). No complications were reported during the transplant and in the post-transplant hospital stay. The recipient had immediate graft function and serum creatinine value of 0.95 mg/dL at 3 months post-transplant. Conclusions: HOPE provides added information in the organ selection process and may improve graft quality of marginal kidneys. PMID:28928357

Aging and the Kidneys: Anatomy, Physiology and Consequences for Defining Chronic Kidney Disease.

PubMed

Glassock, Richard J; Rule, Andrew D

2016-01-01

The varied functions of the kidneys are influenced by the complex process of aging. The glomerular filtration rate (GFR) steadily declines with normal aging, and the progress of this process can be influenced by superimposed diseases. Microscopically, nephron numbers decrease as global glomerulosclerosis becomes more evident. The precise mechanisms underlying nephron loss with aging are not well understood, but derangements in podocyte biology appear to be involved. Classifications of chronic kidney disease (CKD) incorporate GFR values and attendant risk of adverse events. Arbitrary and fixed thresholds of GFR for defining CKD have led to an overdiagnosis of CKD in the elderly. An age-sensitive definition of CKD could offer a solution to this problem and more meaningfully capture the prognostic implications of CKD. © 2016 S. Karger AG, Basel.

Change in Estimated GFR Associates with Coronary Heart Disease and Mortality

PubMed Central

Matsushita, Kunihiro; Bash, Lori D.; Franceschini, Nora; Astor, Brad C.; Coresh, Josef

2009-01-01

Kidney function predicts cardiovascular and all-cause mortality, but little is known about the association of changes in estimated GFR (eGFR) with clinical outcomes. We investigated whether 3- and 9-yr changes in eGFR associated with risk for coronary heart disease (CHD) and all-cause mortality among 13,029 participants of the Atherosclerosis Risk in Communities (ARIC) Study. After adjustment for baseline covariates including eGFR in Cox proportional hazards models, the quartile of participants with the greatest annual decline (annual decline ≥5.65%) in eGFR were at significantly greater risk for CHD and all-cause mortality (hazard ratio 1.30 [95% confidence interval 1.11 to 1.52] and 1.22 [95% confidence interval 1.06 to 1.41], respectively) compared with the third quartile (annual decline between 0.33 and 0.47%). We observed similar results when we analyzed 9-yr changes in eGFR. Adjustment for covariates at the second eGFR used to estimate change reduced the association with CHD but not with mortality. Among participants with stage 3 chronic kidney disease, an increase in eGFR during the first 3 yr also associated with a higher risk for mortality, perhaps as a result of clinical instability. In conclusion, a steeper than average decline in eGFR associates with a higher risk for CHD and all-cause mortality. Increases in eGFR among participants with chronic kidney disease associate with similar increased risks. PMID:19892932

Type 2 Diabetes Mellitus and Impaired Renal Function Are Associated With Brain Alterations and Poststroke Cognitive Decline.

PubMed

Ben Assayag, Einor; Eldor, Roy; Korczyn, Amos D; Kliper, Efrat; Shenhar-Tsarfaty, Shani; Tene, Oren; Molad, Jeremy; Shapira, Itzhak; Berliner, Shlomo; Volfson, Viki; Shopin, Ludmila; Strauss, Yehuda; Hallevi, Hen; Bornstein, Natan M; Auriel, Eitan

2017-09-01

Type 2 diabetes mellitus (T2DM) is associated with diseases of the brain, kidney, and vasculature. However, the relationship between T2DM, chronic kidney disease, brain alterations, and cognitive function after stroke is unknown. We aimed to evaluate the inter-relationship between T2DM, impaired renal function, brain pathology on imaging, and cognitive decline in a longitudinal poststroke cohort. The TABASCO (Tel Aviv brain acute stroke cohort) is a prospective cohort of stroke/transient ischemic attack survivors. The volume and white matter integrity, ischemic lesions, and brain and hippocampal volumes were measured at baseline using 3-T MRI. Cognitive tests were performed on 507 patients, who were diagnosed as having mild cognitive impairment, dementia, or being cognitively intact after 24 months. At baseline, T2DM and impaired renal function (estimated creatinine clearance [eCCl] <60 mL/min) were associated with smaller brain and hippocampal volumes, reduced cortical thickness, and worse white matter microstructural integrity. Two years later, both T2DM and eCCl <60 mL/min were associated with poorer cognitive scores, and 19.7% of the participants developed cognitive decline (mild cognitive impairment or dementia). Multiple analysis, controlling for age, sex, education, and apolipoprotein E4, showed a significant association of both T2DM and eCCl <60 mL/min with cognitive decline. Having both conditions doubled the risk compared with patients with T2DM or eCCl <60 mL/min alone and almost quadrupled the risk compared with patients without either abnormality. T2DM and impaired renal function are independently associated with abnormal brain structure, as well as poorer performance in cognitive tests, 2 years after stroke. The presence of both conditions quadruples the risk for cognitive decline. T2DM and lower eCCl have an independent and additive effect on brain atrophy and the risk of cognitive decline. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01926691. © 2017 American Heart Association, Inc.

Iohexol clearance is superior to creatinine-based renal function estimating equations in detecting short-term renal function decline in chronic heart failure.

PubMed

Cvan Trobec, Katja; Kerec Kos, Mojca; von Haehling, Stephan; Anker, Stefan D; Macdougall, Iain C; Ponikowski, Piotr; Lainscak, Mitja

2015-12-01

To compare the performance of iohexol plasma clearance and creatinine-based renal function estimating equations in monitoring longitudinal renal function changes in chronic heart failure (CHF) patients, and to assess the effects of body composition on the equation performance. Iohexol plasma clearance was measured in 43 CHF patients at baseline and after at least 6 months. Simultaneously, renal function was estimated with five creatinine-based equations (four- and six-variable Modification of Diet in Renal Disease, Cockcroft-Gault, Cockcroft-Gault adjusted for lean body mass, Chronic Kidney Disease Epidemiology Collaboration equation) and body composition was assessed using bioimpedance and dual-energy x-ray absorptiometry. Over a median follow-up of 7.5 months (range 6-17 months), iohexol clearance significantly declined (52.8 vs 44.4 mL/[min ×1.73 m2], P=0.001). This decline was significantly higher in patients receiving mineralocorticoid receptor antagonists at baseline (mean decline -22% of baseline value vs -3%, P=0.037). Mean serum creatinine concentration did not change significantly during follow-up and no creatinine-based renal function estimating equation was able to detect the significant longitudinal decline of renal function determined by iohexol clearance. After accounting for body composition, the accuracy of the equations improved, but not their ability to detect renal function decline. Renal function measured with iohexol plasma clearance showed relevant decline in CHF patients, particularly in those treated with mineralocorticoid receptor antagonists. None of the equations for renal function estimation was able to detect these changes. ClinicalTrials.gov registration number: NCT01829880.

Urine Volume and Change in Estimated GFR in a Community-Based Cohort Study

PubMed Central

Sontrop, Jessica M.; Macnab, Jennifer J.; Suri, Rita S.; Moist, Louise; Salvadori, Marina; Garg, Amit X.

2011-01-01

Summary Background and objectives The effect of increased fluid intake on kidney function is unclear. This study evaluates the relationship between urine volume and renal decline over 6 years in a large community-based cohort. Design, setting, participants, & measurements This prospective cohort study was undertaken in Canada from 2002 to 2008. We obtained 24-hour urine samples from adult participants with an estimated GFR (eGFR) ≥60ml/min per 1.73 m2 at study entry. Percentage annual change in eGFR from baseline was categorized as average decline <1% per year, between 1% and 4.9% (mild-to-moderate decline) or ≥5% (rapid decline). Results 2148 participants provided valid 24-hour urine samples, grouped as <1 L/d (14.5%); 1 to 1.9 L/d (51.5%); 2 to 2.9 L/d (26.3%); and ≥3 L/d (7.7%). Baseline eGFR for each category of urine volume was 90, 88, 84, and 87 ml/min per 1.73 m2, respectively. Overall, eGFR declined by 1% per year, with 10% demonstrating rapid decline and 40% demonstrating mild-to-moderate decline. An inverse, graded relationship was evident between urine volume and eGFR decline: For each increasing category of 24-hour urine volume, percentage annual eGFR decline was progressively slower, from 1.3%, 1.0%, 0.8%, to 0.5%, respectively; P = 0.02. Compared with those with urine volume 1 to 1.9 L/d, those with urine volume ≥3 L/d were significantly less likely to demonstrate mild-to-moderate decline (adjusted odds ratio 0.66; 95% confidence interval 0.46 to 0.94) or rapid decline (adjusted odds ratio 0.46; 95% confidence interval 0.23 to 0.92); adjusted for age, gender, baseline eGFR, medication use for hypertension (including diuretics), proteinuria, diabetes, and cardiovascular disease. Conclusions In this community-based cohort, decline in kidney function was significantly slower in those with higher versus lower urine volume. PMID:21885793

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

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.

Hemoglobin Decline in Children with Chronic Kidney Disease: Baseline Results from the Chronic Kidney Disease in Children Prospective Cohort Study

PubMed Central

Fadrowski, Jeffrey J.; Pierce, Christopher B.; Cole, Stephen R.; Moxey-Mims, Marva; Warady, Bradley A.; Furth, Susan L.

2008-01-01

Background and objectives: The level of glomerular filtration rate at which hemoglobin declines in chronic kidney disease is poorly described in the pediatric population. Design, setting, participants, & measurements: This cross-sectional study of North American children with chronic kidney disease examined the association of glomerular filtration rate, determined by the plasma disappearance of iohexol, and hemoglobin concentration. Results: Of the 340 patients studied, the mean age was 11 ± 4 yr, the mean glomerular filtration rate was 42 ± 14 ml/min per 1.73 m2, and the mean hemoglobin was 12.5 ± 1.5. Below a glomerular filtration rate of 43, the hemoglobin declined by 0.3 g/dl (95% confidence interval −0.2 to −0.5) for every 5-ml/min per 1.73 m2 decrease in glomerular filtration rate. Above a glomerular filtration rate of 43 ml/min per 1.73 m2, the hemoglobin showed a nonsignificant decline of 0.1 g/dl for every 5-ml/min per 1.73 m2 decrease in glomerular filtration rate. Conclusions: In pediatric patients with chronic kidney disease, hemoglobin declines as an iohexol-determined glomerular filtration rate decreases below 43 ml/min per 1.73 m2. Because serum creatinine–based estimated glomerular filtration rates may overestimate measured glomerular filtration rate in this population, clinicians need to be mindful of the potential for hemoglobin decline and anemia even at early stages of chronic kidney disease, as determined by current Schwartz formula estimates. Future longitudinal analyses will further characterize the relationship between glomerular filtration rate and hemoglobin, including elucidation of reasons for the heterogeneity of this association among individuals. PMID:18235140

Sleep Characteristics in Early Stages of Chronic Kidney Disease in the HypnoLaus Cohort

PubMed Central

Ogna, Adam; Forni Ogna, Valentina; Haba Rubio, José; Tobback, Nadia; Andries, Dana; Preisig, Martin; Tafti, Mehdi; Vollenweider, Peter; Waeber, Gerard; Marques-Vidal, Pedro; Heinzer, Raphaël

2016-01-01

Study Objectives: To evaluate the association between early stages of chronic kidney disease (CKD) and sleep disordered breathing (SDB), restless legs syndrome (RLS), and subjective and objective sleep quality (SQ). Methods: Cross-sectional analysis of a general population-based cohort (HypnoLaus). 1,760 adults (862 men, 898 women; age 59.3 (± 11.4) y) underwent complete polysomnography at home. Results: 8.2% of participants had mild CKD (stage 1–2, estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m2 with albuminuria) and 7.8% moderate CKD (stage 3, eGFR 30–60 mL/min/1.73 m2). 37.3% of our sample had moderate-to-severe SDB (apnea-hypopnea index [AHI] ≥ 15/h) and 15.3% had severe SDB (AHI ≥ 30/h). SDB prevalence was positively associated with CKD stages and negatively with eGFR. In multivariate analysis, age, male sex, and body mass index were independently associated with SDB (all P < 0.001), but kidney function was not. The prevalence of RLS was 17.5%, without difference between CKD stages. Periodic leg movements index (PLMI) was independently associated with CKD stages. Subjective and objective SQ decreased and the use of sleep medication was more frequent with declining kidney function. Older age, female sex, and the severity of SDB were the strongest predictors of poor SQ in multivariate regression analysis but CKD stage was also independently associated with reduced objective SQ. Conclusions: Patients with early stages of CKD have impaired SQ, use more hypnotic drugs, and have an increased prevalence of SDB and PLM. After controlling for confounders, objective SQ and PLMI were still independently associated with declining kidney function. Citation: Ogna A, Forni Ogna V, Haba Rubio J, Tobback N, Andries D, Preisig M, Tafti M, Vollenweider P, Waeber G, Marques-Vidal P, Heinzer R. Sleep characteristics in early stages of chronic kidney disease in the HypnoLaus cohort. SLEEP 2016;39(4):945–953. PMID:26715230

Heart Failure Increases the Risk of Adverse Renal Outcomes in Patients With Normal Kidney Function.

PubMed

George, Lekha K; Koshy, Santhosh K G; Molnar, Miklos Z; Thomas, Fridtjof; Lu, Jun L; Kalantar-Zadeh, Kamyar; Kovesdy, Csaba P

2017-08-01

Heart failure (HF) is associated with poor cardiac outcomes and mortality. It is not known whether HF leads to poor renal outcomes in patients with normal kidney function. We hypothesized that HF is associated with worse long-term renal outcomes. Among 3 570 865 US veterans with estimated glomerular filtration rate (eGFR) ≥60 mL min -1 1.73 m -2 during October 1, 2004 to September 30, 2006, we identified 156 743 with an International Classification of Diseases , Ninth Revision , diagnosis of HF. We examined the association of HF with incident chronic kidney disease (CKD), the composite of incident CKD or mortality, and rapid rate of eGFR decline (slopes steeper than -5 mL min -1 1.73 m -2 y -1 ) using Cox proportional hazard analyses and logistic regression. Adjustments were made for various confounders. The mean±standard deviation baseline age and eGFR of HF patients were 68±11 years and 78±14 mL min -1 1.73 m -2 and in patients without HF were 59±14 years and 84±16 mL min -1 1.73 m -2 , respectively. HF patients had higher prevalence of hypertension, diabetes mellitus, cardiac, peripheral vascular and chronic lung diseases, stroke, and dementia. Incidence of CKD was 69.0/1000 patient-years in HF patients versus 14.5/1000 patient-years in patients without HF, and 22% of patients with HF had rapid decline in eGFR compared with 8.5% in patients without HF. HF patients had a 2.12-, 2.06-, and 2.13-fold higher multivariable-adjusted risk of incident CKD, composite of CKD or mortality, and rapid eGFR decline, respectively. HF is associated with significantly higher risk of incident CKD, incident CKD or mortality, and rapid eGFR decline. Early diagnosis and management of HF could help reduce the risk of long-term renal complications. © 2017 American Heart Association, Inc.

Iohexol clearance is superior to creatinine-based renal function estimating equations in detecting short-term renal function decline in chronic heart failure

PubMed Central

Cvan Trobec, Katja; Kerec Kos, Mojca; von Haehling, Stephan; Anker, Stefan D.; Macdougall, Iain C.; Ponikowski, Piotr; Lainscak, Mitja

2015-01-01

Aim To compare the performance of iohexol plasma clearance and creatinine-based renal function estimating equations in monitoring longitudinal renal function changes in chronic heart failure (CHF) patients, and to assess the effects of body composition on the equation performance. Methods Iohexol plasma clearance was measured in 43 CHF patients at baseline and after at least 6 months. Simultaneously, renal function was estimated with five creatinine-based equations (four- and six-variable Modification of Diet in Renal Disease, Cockcroft-Gault, Cockcroft-Gault adjusted for lean body mass, Chronic Kidney Disease Epidemiology Collaboration equation) and body composition was assessed using bioimpedance and dual-energy x-ray absorptiometry. Results Over a median follow-up of 7.5 months (range 6-17 months), iohexol clearance significantly declined (52.8 vs 44.4 mL/[min ×1.73 m2], P = 0.001). This decline was significantly higher in patients receiving mineralocorticoid receptor antagonists at baseline (mean decline -22% of baseline value vs -3%, P = 0.037). Mean serum creatinine concentration did not change significantly during follow-up and no creatinine-based renal function estimating equation was able to detect the significant longitudinal decline of renal function determined by iohexol clearance. After accounting for body composition, the accuracy of the equations improved, but not their ability to detect renal function decline. Conclusions Renal function measured with iohexol plasma clearance showed relevant decline in CHF patients, particularly in those treated with mineralocorticoid receptor antagonists. None of the equations for renal function estimation was able to detect these changes. ClinicalTrials.gov registration number NCT01829880 PMID:26718759

Change in kidney function after unilateral adrenalectomy in patients with primary aldosteronism: identification of risk factors for decreased kidney function.

PubMed

Kim, Il Young; Park, In Seong; Kim, Min Jeong; Han, Miyeun; Rhee, Harin; Seong, Eun Young; Lee, Dong Won; Lee, Soo Bong; Kwak, Ihm Soo; Song, Sang Heon; Chung, Hyun Chul

2018-05-19

Glomerular filtration rate (GFR) has been reported to decrease after unilateral adrenalectomy in patients with primary aldosteronism (PA). The aim of this study was to identify clinical predictors for decreased GFR after adrenalectomy in patients with PA. The records of 187 patients (98 patients with PA and 89 with non-PA adrenal disease) who were followed up for at least 6 months after unilateral adrenalectomy were retrospectively analyzed. Estimated GFR (eGFR) was investigated at 1, 3, and 6 months postoperatively. Preoperative risk factors for eGFR% decline at 1 month ([preoperative eGFR-eGFR at 1 month]/preoperative eGFR × 100) and postoperative CKD development were investigated. The eGFR decreased significantly at 1 month and remained stable in the PA group. However, there were no significant changes in eGFR in the non-PA group over the 6-month period. In the PA group, a high preoperative eGFR and high aldosterone to renin ratio (ARR) were independently associated with eGFR% decline at 1 month. In patients with PA but without preoperative CKD (n = 68), a low preoperative eGFR and high ARR were independent risk factors for developing postoperative CKD. The best preoperative cut-off values of eGFR and ARR for predicting the development of postoperative CKD were ≤ 102 ml/min/1.73 m 2 and ≥ 448 ng/dl:ng/ml/h, respectively. Renal function deteriorated significantly after unilateral adrenalectomy in patients with PA. Clinicians must pay attention to postoperative renal function in PA patients at elevated risk of developing decreased kidney function.

Longitudinal Assessment of Renal Perfusion and Oxygenation in Transplant Donor-Recipient Pairs Using Arterial Spin Labeling and Blood Oxygen Level-Dependent Magnetic Resonance Imaging.

PubMed

Niles, David J; Artz, Nathan S; Djamali, Arjang; Sadowski, Elizabeth A; Grist, Thomas M; Fain, Sean B

2016-02-01

The aims of this study were to assess renal function in kidney transplant recipients and their respective donors over 2 years using arterial spin labeling (ASL) and blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) and to prospectively evaluate the effect of losartan on functional MRI measures in recipients. The study included 15 matched pairs of renal transplant donors and recipients. Arterial spin labeling and BOLD MRI of the kidneys were performed on donors before transplant surgery (baseline) and on both donors and recipients at 3 months, 1 year, and 2 years after transplant. After 3 months, 7 of the 15 recipients were prescribed 25 to 50 mg/d losartan for the remainder of the study. A linear mixed-effects model was used to evaluate perfusion, R2*, estimated glomerular filtration rate, and fractional excretion of sodium for changes across time or associated with losartan treatment. In donors, cortical perfusion in the remaining kidney decreased by 50 ± 19 mL/min per 100 g (11.8%) between baseline and 2 years (P < 0.05), while cortical R2* declined modestly by 0.7 ± 0.3 s-1 (5.6%; P < 0.05). In transplanted kidneys, cortical perfusion decreased markedly by 141 ± 21 mL/min per 100 g (34.2%) between baseline and 2 years (P < 0.001), while medullary R2* declined by 1.5 ± 0.8 s-1 (8.3%; P = 0.06). Single-kidney estimated glomerular filtration rate increased between baseline and 2 years by 17.7 ± 2.7 mL/min per 1.73 m (40.3%; P < 0.0001) in donors and to 14.6 ± 4.3 mL/min per 1.73 m (33.3%; P < 0.01) in recipients. Cortical perfusion at 1 and 2 years in recipients receiving 25 to 50 mg/d losartan was 62 ± 24 mL/min per 100 g higher than recipients not receiving the drug (P < 0.05). No significant effects of losartan were observed for any other markers of renal function. The results suggest an important role for noninvasive functional monitoring with ASL and BOLD MRI in kidney transplant recipients and donors, and they indicate a potentially beneficial effect of losartan in recipients.

Utility of Urinary Biomarkers in Predicting Loss of Residual Renal Function: The balANZ Trial

PubMed Central

Cho, Yeoungjee; Johnson, David W.; Vesey, David A.; Hawley, Carmel M.; Clarke, Margaret; Topley, Nicholas

2015-01-01

♦ Background: The ability of urinary biomarkers to predict residual renal function (RRF) decline in peritoneal dialysis (PD) patients has not been defined. The present study aimed to explore the utility of established biomarkers from kidney injury models for predicting loss of RRF in incident PD patients, and to evaluate the impact on RRF of using neutral-pH PD solution low in glucose degradation products. ♦ Methods: The study included 50 randomly selected participants from the balANZ trial who had completed 24 months of follow-up. A change in glomerular filtration rate (GFR) was used as the primary clinical outcome measure. In a mixed-effects general linear model, baseline measurements of 18 novel urinary biomarkers and albumin were used to predict GFR change. The model was further used to evaluate the impact of biocompatible PD solution on RRF, adjusted for each biomarker. ♦ Results: Baseline albuminuria was not a useful predictor of change in RRF in PD patients (p = 0.84). Only clusterin was a significant predictor of GFR decline in the whole population (p = 0.04, adjusted for baseline GFR and albuminuria). However, the relationship was no longer apparent when albuminuria was removed from the model (p = 0.31). When the effect of the administered PD solutions was examined using a model adjusted for PD solution type, baseline albuminuria, and GFR, higher baseline urinary concentrations of trefoil factor 3 (TFF3, p = 0.02), kidney injury molecule 1 (KIM-1, p = 0.04), and interferon γ-induced protein 10 (IP-10, p = 0.03) were associated with more rapid decline of RRF in patients receiving conventional PD solution compared with biocompatible PD solution. ♦ Conclusions: Higher urinary levels of kidney injury biomarkers (TFF3, KIM-1, IP-10) at baseline predicted significantly slower RRF decline in patients receiving biocompatible PD solutions. Findings from the present investigation should help to guide future studies to validate the utility of urinary biomarkers as tools to predict RRF decline in PD patients. PMID:24711637

Serum Bicarbonate and Mortality in Stage 3 and Stage 4 Chronic Kidney Disease

PubMed Central

Schold, Jesse D.; Arrigain, Susana; Jolly, Stacey E.; Wehbe, Edgard; Raina, Rupesh; Simon, James F.; Srinivas, Titte R.; Jain, Anil; Schreiber, Martin J.; Nally, Joseph V.

2011-01-01

Summary Background and objectives The incidence and prevalence of metabolic acidosis increase with declining kidney function. We studied the associations of both low and high serum bicarbonate levels with all-cause mortality among stage 3 and 4 chronic kidney disease (CKD) patients. Design, setting, participants, & measurements We examined factors associated with low (<23 mmol/L) and high (>32 mmol/L) serum bicarbonate levels using logistic regression models and associations between bicarbonate and all-cause mortality using Cox-proportional hazard models, Kaplan–Meier survival curves, and time-dependent analysis. Results Out of 41,749 patients, 13.9% (n = 5796) had low and 1.6% (n = 652) had high serum bicarbonate levels. After adjusting for relevant covariates, there was a significant association between low serum bicarbonate and all-cause mortality (hazard ratio [HR] 1.23, 95% CI 1.16, 1.31). This association was not statistically significant among patients with stage 4 CKD and diabetes. The time-dependent analysis demonstrated a significant mortality risk associated with a decline from normal to low bicarbonate level (HR 1.59, 95% CI 1.49, 1.69). High serum bicarbonate levels were associated with death irrespective of the level of kidney function (HR 1.74, 95% CI 1.52, 2.00). When serum bicarbonate was examined as a continuous variable, a J-shaped relationship was noted between serum bicarbonate and mortality. Conclusions Low serum bicarbonate levels are associated with increased mortality among stage 3 CKD patients and patients without diabetes. High serum bicarbonate levels are associated with mortality in both stage 3 and stage 4 CKD patients. PMID:21885787

Allopurinol treatment and its effect on renal function in gout: a controlled study.

PubMed Central

Gibson, T; Rodgers, V; Potter, C; Simmonds, H A

1982-01-01

Fifty-nine patients with primary gout were treated with either a combination of colchicine and allopurinol or colchicine alone. Assessments of renal function over 2 years revealed a statistically significant fall of glomerular filtration rate an urine concentrating ability in those receiving only colchicine. The renal function of patients given allopurinol did not change. Treatment with allopurinol resulted ina significant reduction of ammonium excretion, a phenomenon which could not be readily explained. Urate clearance also declined during allopurinol treatment, and the impaired urate clearance associated with gout became more evident. The most important observation was that allopurinol retarded an apparent decline of renal function. Presumably this was achieved through its hypouricaemic effect and implies that the hyperuricaemia of gouty patients is deleterious to the kidneys. PMID:7039523

Cognitive function and advanced kidney disease: longitudinal trends and impact on decision-making.

PubMed

Iyasere, Osasuyi; Okai, David; Brown, Edwina

2017-02-01

Background: Cognitive impairment commonly affects renal patients. But little is known about the influence of dialysis modality on cognitive trends or the influence of cognitive impairment on decision-making in renal patients. This study evaluated cognitive trends amongst chronic kidney disease (CKD), haemodialysis (HD) and peritoneal dialysis (PD) patients. The relationship between cognitive impairment and decision-making capacity (DMC) was also assessed. Methods: Patients were recruited from three outpatient clinics. Cognitive function was assessed 4-monthly for up to 2 years, using the Montreal Cognitive Assessment (MoCA) tool. Cognitive trends were assessed using mixed model analysis. DMC was assessed using the Macarthur Competency Assessment tool (MacCAT-T). MacCAT-T scores were compared between patients with cognitive impairment (MoCA <26) and those without. Results: In total, 102 (41 HD, 25 PD and 36 CKD) patients were recruited into the prospective study. After multivariate analysis, the total MoCA scores declined faster in dialysis compared with CKD patients [coefficient = -0.03, 95% confidence interval (95% CI) = -0.056 to - 0.004; P = 0.025]. The MoCA executive scores declined faster in the HD compared with PD patients (coefficient = -0.12, 95% CI = -0.233 to - 0.007; P = 0.037). DMC was assessed in 10 patients. Those with cognitive impairment had lower MacCAT-T compared with those without [median (interquartile range) 19 (17.9-19.6) versus 17.4 (16.3-18.4); P = 0.049]. Conclusions: Cognition declines faster in dialysis patients compared with CKD patients and in HD patients compared with PD patients. Cognitive impairment affects DMC in patients with advanced kidney disease.

Is Fluid Overload More Important than Diabetes in Renal Progression in Late Chronic Kidney Disease?

PubMed Central

Tsai, Yi-Chun; Tsai, Jer-Chia; Chiu, Yi-Wen; Kuo, Hung-Tien; Chen, Szu-Chia; Hwang, Shang-Jyh; Chen, Tzu-Hui; Kuo, Mei-Chuan; Chen, Hung-Chun

2013-01-01

Fluid overload is one of the major presentations in patients with late stage chronic kidney disease (CKD). Diabetes is the leading cause of renal failure, and progression of diabetic nephropathy has been associated with changes in extracellular fluid volume. The aim of the study was to assess the association of fluid overload and diabetes in commencing dialysis and rapid renal function decline (the slope of estimated glomerular filtration rate (eGFR) less than -3 ml/min per 1.73 m2/y) in 472 patients with stages 4-5 CKD. Fluid status was determined by bioimpedance spectroscopy method, Body Composition Monitor. The study population was further classified into four groups according to the median of relative hydration status (△HS =fluid overload/extracellular water) and the presence or absence of diabetes. The median level of relative hydration status was 7%. Among all patients, 207(43.9 %) were diabetic. 71 (15.0%) subjects had commencing dialysis, and 187 (39.6%) subjects presented rapid renal function decline during a median 17.3-month follow-up. Patients with fluid overload had a significantly increased risk for commencing dialysis and renal function decline independent of the presence or absence of diabetes. No significantly increased risk for renal progression was found between diabetes and non-diabetes in late CKD without fluid overload. In conclusion, fluid overload has a higher predictive value of an elevated risk for renal progression than diabetes in late CKD. PMID:24349311

Successful transplantation of kidneys from elderly circulatory death donors by using microscopic and macroscopic characteristics to guide single or dual implantation.

PubMed

Mallon, D H; Riddiough, G E; Summers, D M; Butler, A J; Callaghan, C J; Bradbury, L L; Bardsley, V; Broecker, V; Saeb-Parsy, K; Torpey, N; Bradley, J A; Pettigrew, G J

2015-11-01

Most kidneys from potential elderly circulatory death (DCD) donors are declined. We report single center outcomes for kidneys transplanted from DCD donors over 70 years old, using preimplantation biopsy Remuzzi grading to inform implantation as single or dual transplants. Between 2009 and 2012, 43 single transplants and 12 dual transplants were performed from elderly DCD donors. Remuzzi scores were higher for dual than single implants (4.4 vs. 3.4, p < 0.001), indicating more severe baseline injury. Donor and recipient characteristics for both groups were otherwise similar. Early graft loss from renal vein thrombosis occurred in two singly implanted kidneys, and in one dual-implanted kidney; its pair continued to function satisfactorily. Death-censored graft survival at 3 years was comparable for the two groups (single 94%; dual 100%), as was 1 year eGFR. Delayed graft function occurred less frequently in the dual-implant group (25% vs. 65%, p = 0.010). Using this approach, we performed proportionally more kidney transplants from elderly DCD donors (23.4%) than the rest of the United Kingdom (7.3%, p < 0.001), with graft outcomes comparable to those achieved nationally for all deceased-donor kidney transplants. Preimplantation biopsy analysis is associated with acceptable transplant outcomes for elderly DCD kidneys and may increase transplant numbers from an underutilized donor pool. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Adiponectin is not associated with renal function decline in community-dwelling elderly adults.

PubMed

Kobayashi, Hiroki; Otsuka, Hiromasa; Yanai, Mitsuru; Haketa, Akira; Hara, Motohiko; Hishiki, Mikano; Abe, Masanori; Soma, Masayoshi

2018-05-01

Adiponectin secreted by adipocytes plays an important role in the regulation of glucose and fatty acid metabolism. Contrary to findings in patients with chronic kidney disease (CKD), no prospective data about the association of serum adiponectin with renal function decline in the general population have yet appeared. Our objective was to analyze the relationship of total and high molecular weight (HMW) adiponectin with renal function decline as measured by cystatin C in community-dwelling elderly adults without moderate or severe CKD.In a prospective observational analysis, a total of 216 healthy elderly volunteers with eGFRcys ≥60 mL/min/1.73 m underwent anthropometric and laboratory tests at baseline and at follow-up visits. A subgroup with serum samples collected 5 years apart was further analyzed.There were no differences in either total or HMW adiponectin level between subjects subsequently undergoing rapid renal function decline and subjects with normal physiologic renal function decline (P = .71, P = .81). On univariate linear regression, neither total nor HMW adiponectin were associated with annual renal function decline (β = -0.23; P = .71, β = -0.057; P = .90). Multivariate analysis did not show a significant contribution of either total or HMW adiponectin to annual renal function decline (β = -0.50; P = .46, β = 0.01; P = .98). In the logistic regression analysis, we did not observe any statistically significant association of serum adiponectin levels with rapid renal function decline or incidence of CKD.Contrary to findings in populations with CKD, neither total nor HMW adiponectin had a substantial association with renal function decline in an elderly population with eGFRcys ≥60 mL/min/1.73 m. Our results and conclusions should not be extrapolated to subjects with other characteristics.

Longitudinal changes in hematocrit in hypertensive chronic kidney disease: results from the African-American Study of Kidney Disease and Hypertension (AASK)

PubMed Central

Chen, Teresa K.; Estrella, Michelle M.; Astor, Brad C.; Greene, Tom; Wang, Xuelei; Grams, Morgan E.; Appel, Lawrence J.

2015-01-01

Background Anemia is common in chronic kidney disease (CKD) and associated with poor outcomes. In cross-sectional studies, lower estimated glomerular filtration rate (eGFR) has been associated with increased risk for anemia. The aim of this study was to determine how hematocrit changes as eGFR declines and what factors impact this longitudinal association. Methods We followed 1094 African-Americans with hypertensive nephropathy who participated in the African-American Study of Kidney Disease and Hypertension. Mixed effects models were used to determine longitudinal change in hematocrit as a function of eGFR. Interaction terms were used to assess for differential effects of age, gender, baseline eGFR, baseline proteinuria, malnutrition and inflammation on eGFR-associated declines in hematocrit. In sensitivity analyses, models were run using iGFR (by renal clearance of I125 iothalamate) in place of eGFR. Results At baseline, mean hematocrit was 39% and 441 (40%) individuals had anemia. The longitudinal relationship between eGFR and hematocrit differed by baseline eGFR and was steeper when baseline eGFR was <45 mL/min/1.73 m2. For example, the absolute decline in hematocrit per 10 mL/min/1.73 m2 decline in longitudinal eGFR was −3.7, −1.3 and −0.5% for baseline eGFR values of 20, 40 and 60 mL/min/1.73 m2, respectively (P < 0.001 comparing the longitudinal association between baseline eGFR = 40 or 60 versus baseline eGFR = 20 mL/min/1.73 m2). Similarly, male sex, younger age (<65 years) and higher baseline proteinuria (protein-to-creatinine ratio >0.22) were associated with greater hematocrit declines per unit decrease in longitudinal eGFR compared with female sex, older age and low baseline proteinuria, respectively (P-interaction <0.05 for each comparison). The longitudinal eGFR–hematocrit association did not differ by body mass index, serum albumin or C-reactive protein. Conclusions Men, younger individuals and those with low baseline eGFR (<45 mL/min/1.73 m2) or baseline proteinuria are particularly at risk for eGFR-related declines in hematocrit. PMID:25817226

Decrease in Urinary Creatinine Excretion in Early Stage Chronic Kidney Disease

PubMed Central

Tynkevich, Elena; Flamant, Martin; Haymann, Jean-Philippe; Metzger, Marie; Thervet, Eric; Boffa, Jean-Jacques; Vrtovsnik, François; Houillier, Pascal; Froissart, Marc; Stengel, Bénédicte

2014-01-01

Background Little is known about muscle mass loss in early stage chronic kidney disease (CKD). We used 24-hour urinary creatinine excretion rate to assess determinants of muscle mass and its evolution with kidney function decline. We also described the range of urinary creatinine concentration in this population. Methods We included 1072 men and 537 women with non-dialysis CKD stages 1 to 5, all of them with repeated measurements of glomerular filtration rate (mGFR) by 51Cr-EDTA renal clearance and several nutritional markers. In those with stage 1 to 4 at baseline, we used a mixed model to study factors associated with urinary creatinine excretion rate and its change over time. Results Baseline mean urinary creatinine excretion decreased from 15.3±3.1 to 12.1±3.3 mmol/24 h (0.20±0.03 to 0.15±0.04 mmol/kg/24 h) in men, with mGFR falling from ≥60 to <15 mL/min/1.73 m2, and from 9.6±1.9 to 7.6±2.5 (0.16±0.03 to 0.12±0.03) in women. In addition to mGFR, an older age, diabetes, and lower levels of body mass index, proteinuria, and protein intake assessed by urinary urea were associated with lower mean urinary creatinine excretion at baseline. Mean annual decline in mGFR was 1.53±0.12 mL/min/1.73 m2 per year and that of urinary creatinine excretion rate, 0.28±0.02 mmol/24 h per year. Patients with fast annual decline in mGFR of 5 mL/min/1.73 m2 had a decrease in urinary creatinine excretion more than twice as big as in those with stable mGFR, independent of changes in urinary urea as well as of other determinants of low muscle mass. Conclusions Decrease in 24-hour urinary creatinine excretion rate may appear early in CKD patients, and is greater the more mGFR declines independent of lowering protein intake assessed by 24-hour urinary urea. Normalizing urine analytes for creatininuria may overestimate their concentration in patients with reduced kidney function and low muscle mass. PMID:25401694

Does a patent foramen ovale influence cognitive function in dialysis patients?

PubMed

George, Sudhakar; Holt, Stephen; Medford, Nick; Hildick-Smith, David

2013-01-01

Patients with chronic kidney disease on dialysis treatment have poorer cognitive function than age- and sex-matched controls. One proposed mechanism is cerebral microembolisation due to material from the dialysis circuit crossing a patent foramen ovale (PFO). Cognitive testing was carried out in haemodialysis (HD) patients and peritoneal dialysis (PD) patients. Transthoracic echocardiography was used to identify PFO. Follow-up testing 1 year later enabled comparison of cognitive decline between patients with and without a PFO, and between those undergoing different dialysis modalities. 80 patients (aged 60.4 ± 15.0 years) were recruited (51 HD patients and 29 PD controls). A PFO was found in 21% of patients. 83% of dialysis patients suffered a decline in one or more cognitive function tests over 1 year. There was a significant difference in only one test between HD patients with or without a PFO. PD patients showed a more rapid cognitive decline than those on HD. Cognitive decline in dialysis patients is rapid and affects most patients. The presence of a PFO made only subtle differences to the rates of cognitive decline during 1 year of follow-up. Patients with a PFO should not be prevented from considering HD because of concerns of cerebral decline due to microembolisation. Copyright © 2013 S. Karger AG, Basel.

Is Kidney Transplantation a Better State of CKD? Impact on Diagnosis and Management.

PubMed

Parajuli, Sandesh; Clark, Dana F; Djamali, Arjang

2016-09-01

Patients with CKD are at increased risk for cardiovascular events, hospitalizations, and mortality. Kidney transplantation (KTx) is the preferred treatment for end-stage kidney disease. Although comorbidities including anemia and bone and mineral disease improve or are even halted after KTx, kidney transplant recipients carry higher cardiovascular mortality risk than the general population, as well as an increased risk of infections, malignancies, fractures, and obesity. When comparing CKD with CKD after transplantation (CKD-T), the rate of decline of estimated glomerular filtration rate (eGFR) is significantly lower in CKD-T. Higher rate of decline of eGFR has been associated with increased risk of mortality. However, due to the significant increased risk of mortality due to cardiovascular events, infections, and malignancies, many kidney transplant recipients may not benefit of decline in the rate of eGFR. Patients with CKD-T are a unique subset of patients with multiple traditional and transplant-specific risk factors. Proper management and appropriate preventive health measures may improve long-term patient and allograft survival in patients with CKD-T. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

[Vascular complications following kidney transplant: the role of color-Doppler imaging].

PubMed

Granata, Antonio; Floccari, Fulvio; Lentini, Paolo; Vittoria, Salvatore; Di Pietro, Fabio; Zamboli, Pasquale; Fiorini, Fulvio; Fatuzzo, Pasquale

2012-01-01

The progressive decline in the incidence of graft rejection has made urological, surgical, parenchymal and vascular complications of kidney transplant more frequent. The latter, although accounting for only 5-10% of all post-transplant complications, are a frequent cause of graft loss. Ultrasonography, both in B-mode and with Doppler ultrasound, is an important diagnostic tool in case of clinical conditions which might impair kidney function. Even though ultrasonography is considered fundamental in the diagnosis of parenchymal and surgical complications of the transplanted kidney, its role is not fully understood in case of vascular complications of the graft. The specificity of Doppler ultrasound is very important in case of stenosis of the transplanted renal artery, pseudoaneurysms, arteriovenous fistulas, and thrombosis with complete or partial artery or vein occlusion. Doppler and color determinations present high diagnostic accuracy, which is higher in case of successive measurements performed during the follow-up of the graft. Modern techniques including contrast-enhanced ultrasound increase the diagnostic power of ultrasonography in case of vascular complications of the transplanted kidney, planted kidney.

Heart failure in patients with kidney disease.

PubMed

Tuegel, Courtney; Bansal, Nisha

2017-12-01

Heart failure (HF) is a leading cause of morbidity and mortality in patients with chronic kidney disease (CKD), and the population of CKD patients with concurrent HF continues to grow. The accurate diagnosis of HF is challenging in patients with CKD in part due to a lack of validated imaging and biomarkers specifically in this population. The pathophysiology between the heart and the kidneys is complex and bidirectional. Patients with CKD have greater prevalence of traditional HF risk factors as well as unique kidney-specific risk factors including malnutrition, acid-base alterations, uraemic toxins, bone mineral changes, anemia and myocardial stunning. These risk factors also contribute to the decline of kidney function seen in patients with subclinical and clinical HF. More targeted HF therapies may improve outcomes in patients with kidney disease as current HF therapies are underutilised in this population. Further work is also needed to develop novel HF therapies for the CKD population. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Could occupational physical activity mitigate the link between moderate kidney dysfunction and coronary heart disease?

PubMed

Esquirol, Yolande; Tully, Mark; Ruidavets, Jean-Bernard; Fogarty, Damian; Ferrieres, Jean; Quinn, Michael; Hughes, Maria; Kee, Frank

2014-12-20

Chronic kidney disease is now regarded as a risk factor for cardiovascular disease. The impact of occupational or non-occupational physical activity (PA) on moderate decreases of renal function is uncertain. We aimed to identify the potential association of PA (occupational and leisure-time) on early decline of estimated glomerular filtration rate (eGFR) and to determine the potential mediating effect of PA on the relationship between eGFR and heart disease. From the PRIME study analyses were conducted in 1058 employed men. Energy expended during leisure, work and commuting was calculated. Linear regression analyses were used to determine the link between types of PA and moderate decrements of eGFR determined with the KDIGO guideline at the baseline assessment. Cox proportional hazards analyses were used to explore the potential effect of PA on the relationship between eGFR and heart disease, ascertained during follow-up over 10 years. For these employed men, and after adjustment for known confounders of GFR change, more time spent sitting at work was associated with increased risk of moderate decline in kidney function, while carrying objects or being active at work was associated with decreased risk. In contrast, no significant link with leisure PA was apparent. No potential mediating effect of occupational PA was found for the relationship between eGFR and coronary heart disease. Occupational PA (potential modifiable factors) could provide a dual role on early impairment of renal function, without influence on the relationship between early decrease of e-GFR and CHD risk. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Clinicopathological analysis of biopsy-proven diabetic nephropathy based on the Japanese classification of diabetic nephropathy.

PubMed

Furuichi, Kengo; Shimizu, Miho; Yuzawa, Yukio; Hara, Akinori; Toyama, Tadashi; Kitamura, Hiroshi; Suzuki, Yoshiki; Sato, Hiroshi; Uesugi, Noriko; Ubara, Yoshifumi; Hohino, Junichi; Hisano, Satoshi; Ueda, Yoshihiko; Nishi, Shinichi; Yokoyama, Hitoshi; Nishino, Tomoya; Kohagura, Kentaro; Ogawa, Daisuke; Mise, Koki; Shibagaki, Yugo; Makino, Hirofumi; Matsuo, Seiichi; Wada, Takashi

2018-06-01

The Japanese classification of diabetic nephropathy reflects the risks of mortality, cardiovascular events and kidney prognosis and is clinically useful. Furthermore, pathological findings of diabetic nephropathy are useful for predicting prognoses. In this study, we evaluated the characteristics of pathological findings in relation to the Japanese classification of diabetic nephropathy and their ability to predict prognosis. The clinical data of 600 biopsy-confirmed diabetic nephropathy patients were collected retrospectively from 13 centers across Japan. Composite kidney events, kidney death, cardiovascular events, all-cause mortality, and decreasing rate of estimated GFR (eGFR) were evaluated based on the Japanese classification of diabetic nephropathy. The median observation period was 70.4 (IQR 20.9-101.0) months. Each stage had specific characteristic pathological findings. Diffuse lesions, interstitial fibrosis and/or tubular atrophy (IFTA), interstitial cell infiltration, arteriolar hyalinosis, and intimal thickening were detected in more than half the cases, even in Stage 1. An analysis of the impacts on outcomes in all data showed that hazard ratios of diffuse lesions, widening of the subendothelial space, exudative lesions, mesangiolysis, IFTA, and interstitial cell infiltration were 2.7, 2.8, 2.7, 2.6, 3.5, and 3.7, respectively. Median declining speed of eGFR in all cases was 5.61 mL/min/1.73 m 2 /year, and the median rate of declining kidney function within 2 years after kidney biopsy was 24.0%. This study indicated that pathological findings could categorize the high-risk group as well as the Japanese classification of diabetic nephropathy. Further study using biopsy specimens is required to clarify the pathogenesis of diabetic kidney disease.

Changes of mitochondrial ultrastructure and function during ageing in mice and Drosophila.

PubMed

Brandt, Tobias; Mourier, Arnaud; Tain, Luke S; Partridge, Linda; Larsson, Nils-Göran; Kühlbrandt, Werner

2017-07-12

Ageing is a progressive decline of intrinsic physiological functions. We examined the impact of ageing on the ultrastructure and function of mitochondria in mouse and fruit flies ( Drosophila melanogaster ) by electron cryo-tomography and respirometry. We discovered distinct age-related changes in both model organisms. Mitochondrial function and ultrastructure are maintained in mouse heart, whereas subpopulations of mitochondria from mouse liver show age-related changes in membrane morphology. Subpopulations of mitochondria from young and old mouse kidney resemble those described for apoptosis. In aged flies, respiratory activity is compromised and the production of peroxide radicals is increased. In about 50% of mitochondria from old flies, the inner membrane organization breaks down. This establishes a clear link between inner membrane architecture and functional decline. Mitochondria were affected by ageing to very different extents, depending on the organism and possibly on the degree to which tissues within the same organism are protected against mitochondrial damage.

Rationale and Design of a Clinical Trial Investigating Tolvaptan Safety and Efficacy in Autosomal Dominant Polycystic Kidney Disease.

PubMed

Torres, Vicente E; Devuyst, Olivier; Chapman, Arlene B; Gansevoort, Ron T; Perrone, Ronald D; Ouyang, John; Blais, Jaime D; Czerwiec, Frank S; Sergeyeva, Olga

2017-01-01

In TEMPO 3:4, the vasopressin V2-receptor antagonist tolvaptan slowed kidney growth and function decline in autosomal dominant polycystic kidney disease (ADPKD) patients with relatively preserved kidney function. Prospective, phase 3b, multi-center, randomized-withdrawal, placebo-controlled, double-blind trial of tolvaptan in ADPKD patients with late stage 2 to early stage 4 chronic kidney disease (CKD). The primary endpoint was estimated glomerular filtration rate (eGFR) change from pre-treatment baseline to post-treatment follow-up. Secondary endpoints included annualized eGFR slope, incidence of ADPKD complications, and overall and hepatic safety profiles. Participants were 18-55 year-old ADPKD patients with baseline eGFR ≥25 and ≤65 mL/min/1.73 m2 or 56-65 year-old with eGFR ≥25 and ≤44 mL/min/1.73 m2 and evidence of eGFR decline >2.0 mL/min/1.73 m2 per year. Daily split doses of tolvaptan were titrated to tolerance (30/15, 45/15, 60/30, or 90/30 mg) and maintained for 12 months, after an 8-week pre-randomization period to screen out subjects unable to tolerate at least 60/30 mg for 3 weeks. Of 1,495 subjects who entered the tolvaptan titration period, 125 (8.4%) discontinued the study before randomization. One thousand three hundred seventy subjects (684 tolvaptan, 686 placebo) from 213 centers across 21 countries were randomized. Baseline demographics were well balanced across treatment arms. Information collected during the study included eGFR, survey scores (PKD history and outcome), adverse events, vital signs, hematology, urinalysis, and serum chemistry tests. Replicating Evidence of Preserved Renal Function: An Investigation of Tolvaptan Safety and Efficacy (REPRISE) determines whether tolvaptan administered over 1 year exhibits disease-modifying properties in ADPKD patients with late stage 2 to early stage 4 CKD, which provides an important therapeutic advancement for this difficult-to-treat disease. © 2017 S. Karger AG, Basel.

Dual Kidney Transplantation Offers a Valuable Source for Kidneys With Good Functional Outcome.

PubMed

Khalid, U; Asderakis, A; Rana, T; Szabo, L; Chavez, R; Ilham, M A; Ablorsu, E

2016-01-01

Reasons for declining kidney donors are older age, with or without, hypertension, kidney dysfunction, and diabetes. Implantation of both kidneys into a single recipient from such donors may improve their acceptability and outcome. Patients who underwent dual kidney transplantation (DKT) between June 2010 and May 2014 were identified from a prospectively maintained database. Single kidney transplantations (SKT) with matching donor criteria were also identified. Donors considered for DKT were the following: DBDs >70 years of age with diabetes and/or hypertension; DCDs >65 years of age with diabetes and/or hypertension; and DCDs >70 years of age. Over a 4-year period, 34 patients underwent adult DKT, and 51, with matching donor criteria, underwent SKT. The median estimated glomerular filtration rate (eGFR) at 12 and 36 months of DKT was 49 (range, 5-79) and 42 (range, 15-85) mL/min compared with SKT of 35 (range, 10-65) and 32 (range, 6-65), respectively. The 1-year graft survival for DKT and SKT was 88% and 96% (P = .52), and patient survival was 94% and 98%, respectively (P = .12). Median hospital stay, intensive care unit admission, and wound complications were more frequent in the DKT group. Graft function following DKT is significantly better compared with matched criteria SKT; graft and patient survival are similar. There is an increased rate of complications following DKT, with longer hospital stay and ICU admission. Copyright © 2016 Elsevier Inc. All rights reserved.

Forty-five year follow-up after uninephrectomy.

PubMed

Narkun-Burgess, D M; Nolan, C R; Norman, J E; Page, W F; Miller, P L; Meyer, T W

1993-05-01

This study examined the consequences of nephrectomy in United States Army personnel who lost a kidney due to trauma during World War II (WWII). Records of 62 servicemen who underwent nephrectomy at an average age of 25 years were obtained. Mortality was compared with that of WWII servicemen of the same age. Medical records of 28 deceased subjects were reviewed for evidence of kidney disease. Medical histories were obtained and blood pressure and kidney function were assessed in 28 living subjects. Two subjects could not be located, and four subjects declined to participate. Mortality at 45 years was not increased in nephrectomized subjects. Kidney disease present in six of 28 deceased subjects was attributable to causes other than prior nephrectomy. Glomerular sclerosis was not increased in 10 subjects who had autopsy examinations. The prevalence of hypertension was not increased in living subjects. Five of 28 living subjects had abnormal renal function manifested by proteinuria greater than 250 mg/day in four cases (range: 377 to 535 mg/day) and serum creatinine levels greater than 1.5 mg/dl in three cases (range: 1.7 to 1.9 mg/dl). Conditions other than nephrectomy could have contributed to impairment of renal function in each of these subjects. These findings suggest that uninephrectomy in young adults has few major adverse consequences over 45 years.

Preoperative Renal Volume: A Surrogate Measure for Radical Nephrectomy-Induced Chronic Kidney Disease.

PubMed

Wu, Fiona Mei Wen; Tay, Melissa Hui Wen; Tai, Bee Choo; Chen, Zhaojin; Tan, Lincoln; Goh, Benjamin Yen Seow; Raman, Lata; Tiong, Ho Yee

2015-12-01

Surgically induced chronic kidney disease (CKD) has been found to have less impact on survival as well as function when compared to medical causes for CKD. The aim of this study is to evaluate whether preoperative remaining kidney volume correlates with renal function after nephrectomy, which represents an individual's renal reserve before surgically induced CKD. A retrospective review of 75 consecutive patients (29.3% females) who underwent radical nephrectomy (RN) (2000-2010) was performed. Normal side kidney parenchyma, excluding renal vessels and central sinus fat, was manually outlined in each transverse slice of CT image and multiplied by slice thickness to calculate volume. Estimated glomerular filtration rate (eGFR) was determined using the Modification of Diet in Renal Disease equation. CKD is defined as eGFR < 60 mL/min/1.73 m(2). Mean preoperative normal kidney parenchymal volume (mean age 55 [SD 13] years) is 150.7 (SD 36.4) mL. Over median follow-up of 36 months postsurgery, progression to CKD occurred in 42.6% (n = 32) of patients. On multivariable analysis, preoperative eGFR and preoperative renal volume <144 mL are independent predictors for postoperative CKD. On Kaplan-Meier analysis, median time to reach CKD postnephrectomy is 12.7 (range 0.03-43.66) months for renal volume <144 mL but not achieved if renal volume is >144 mL. Normal kidney parenchymal volume and preoperative eGFR are independent predictive factors for postoperative CKD after RN and may represent renal reserve for both surgically and medically induced CKD, respectively. Preoperative remaining kidney volume may be an adjunct representation of renal reserve postsurgery and predict later renal function decline due to perioperative loss of nephrons.

Chlorogenic acid protects D-galactose-induced liver and kidney injury via antioxidation and anti-inflammation effects in mice.

PubMed

Feng, Yan; Yu, Ying-Hua; Wang, Shu-Ting; Ren, Jing; Camer, Danielle; Hua, Yu-Zhou; Zhang, Qian; Huang, Jie; Xue, Dan-Lu; Zhang, Xiao-Fei; Huang, Xu-Feng; Liu, Yi

2016-01-01

Oxidative stress and inflammation are implicated in the aging process and its related hepatic and renal function decline. Chlorogenic acid (CGA) is one of the most abundant polyphenol compounds in the human diet. Recently, CGA has shown in vivo and in vitro antioxidant properties. The current study investigates the effects of protective effects of chlorogenic acid (CGA) on D-galactose-induced liver and kidney injury. Hepatic and renal injuries were induced in a mouse model by subcutaneously injection of D-galactose (D-gal; 100 mg/kg) once a day for 8 consecutive weeks and orally administered simultaneously with CGA included in the food (200 mg/kg of diet). The liver and renal functions were examined. Histological analyses of liver and kidney were done by haematoxylin and eosin staining. The oxidative stress markers and pro-inflammatory cytokines in the liver and the kidney were measured. Results CGA significantly reduced the serum aminotransferase, serum creatinine (SCr) and blood urea nitrogen (BUN) levels in D-gal mice (p <0.05). CGA also restored superoxide dismutase, catalase, and malondialdehyde levels and decreased glutathione content in the liver and kidney in D-gal mice (p <0.05). Improvements in liver and kidney were also noted in histopathological studies. CGA reduced tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) protein levels in the liver and kidney in D-gal mice (p <0.05). These findings suggest that CGA attenuates D-gal-induced chronic liver and kidney injury and that this protection may be due to its antioxidative and anti-inflammatory activities.

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

Living-Donor Kidney Transplantation: Reducing Financial Barriers to Live Kidney Donation--Recommendations from a Consensus Conference.

PubMed

Tushla, Lara; Rudow, Dianne LaPointe; Milton, Jennifer; Rodrigue, James R; Schold, Jesse D; Hays, Rebecca

2015-09-04

Live-donor kidney transplantation (LDKT) is the best treatment for eligible people with late-stage kidney disease. Despite this, living kidney donation rates have declined in the United States in recent years. A potential source of this decline is the financial impact on potential and actual living kidney donors (LKDs). Recent evidence indicates that the economic climate may be associated with the decline in LDKT and that there are nontrivial financial ramifications for some LKDs. In June 2014, the American Society of Transplantation's Live Donor Community of Practice convened a Consensus Conference on Best Practices in Live Kidney Donation. The conference included transplant professionals, patients, and other key stakeholders (with the financial support of 10 other organizations) and sought to identify best practices, knowledge gaps, and opportunities pertaining to living kidney donation. This workgroup was tasked with exploring systemic and financial barriers to living kidney donation. The workgroup reviewed literature that assessed the financial effect of living kidney donation, analyzed employment and insurance factors, discussed international models for addressing direct and indirect costs faced by LKDs, and summarized current available resources. The workgroup developed the following series of recommendations to reduce financial and systemic barriers and achieve financial neutrality for LKDs: (1) allocate resources for standardized reimbursement of LKDs' lost wages and incidental costs; (2) pass legislation to offer employment and insurability protections to LKDs; (3) create an LKD financial toolkit to provide standardized, vetted education to donors and providers about options to maximize donor coverage and minimize financial effect within the current climate; and (4) promote further research to identify systemic barriers to living donation and LDKT to ensure the creation of mitigation strategies. Copyright © 2015 by the American Society of Nephrology.

Living-Donor Kidney Transplantation: Reducing Financial Barriers to Live Kidney Donation—Recommendations from a Consensus Conference

PubMed Central

Rudow, Dianne LaPointe; Milton, Jennifer; Rodrigue, James R.; Schold, Jesse D.; Hays, Rebecca

2015-01-01

Live-donor kidney transplantation (LDKT) is the best treatment for eligible people with late-stage kidney disease. Despite this, living kidney donation rates have declined in the United States in recent years. A potential source of this decline is the financial impact on potential and actual living kidney donors (LKDs). Recent evidence indicates that the economic climate may be associated with the decline in LDKT and that there are nontrivial financial ramifications for some LKDs. In June 2014, the American Society of Transplantation’s Live Donor Community of Practice convened a Consensus Conference on Best Practices in Live Kidney Donation. The conference included transplant professionals, patients, and other key stakeholders (with the financial support of 10 other organizations) and sought to identify best practices, knowledge gaps, and opportunities pertaining to living kidney donation. This workgroup was tasked with exploring systemic and financial barriers to living kidney donation. The workgroup reviewed literature that assessed the financial effect of living kidney donation, analyzed employment and insurance factors, discussed international models for addressing direct and indirect costs faced by LKDs, and summarized current available resources. The workgroup developed the following series of recommendations to reduce financial and systemic barriers and achieve financial neutrality for LKDs: (1) allocate resources for standardized reimbursement of LKDs' lost wages and incidental costs; (2) pass legislation to offer employment and insurability protections to LKDs; (3) create an LKD financial toolkit to provide standardized, vetted education to donors and providers about options to maximize donor coverage and minimize financial effect within the current climate; and (4) promote further research to identify systemic barriers to living donation and LDKT to ensure the creation of mitigation strategies. PMID:26002904

Risk of Progression of Nonalbuminuric CKD to End-Stage Kidney Disease in People With Diabetes: The CRIC (Chronic Renal Insufficiency Cohort) Study.

PubMed

Koye, Digsu N; Magliano, Dianna J; Reid, Christopher M; Jepson, Christopher; Feldman, Harold I; Herman, William H; Shaw, Jonathan E

2018-05-18

Reduced glomerular filtration rate (GFR) in the absence of albuminuria is a common manifestation of chronic kidney disease (CKD) in diabetes. However, the frequency with which it progresses to end-stage kidney disease (ESKD) is unknown. Multicenter prospective cohort study. We included 1,908 participants with diabetes and reduced GFR enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study in the United States. Urinary albumin and protein excretion. Incident ESKD, CKD progression (ESKD or ≥50% reduction in estimated GFR [eGFR] from baseline), and annual rate of decline in kidney function. ESKD was ascertained by self-report and by linkage to the US Renal Data System. We used Cox proportional hazards modeling to estimate the association of albuminuria and proteinuria with incident ESKD or CKD progression and linear mixed-effects models to assess differences in eGFR slopes among those with and without albuminuria. Mean eGFR at baseline was 41.2mL/min/1.73m 2 . Normal or mildly increased 24-hour urinary albumin excretion (<30mg/d) at baseline was present in 28% of participants, but in only 5% of those progressing to ESKD. For those with baseline normal or mildly increased albuminuria, moderately increased albuminuria (albumin excretion, 30-299mg/d), and 2 levels of severely increased albuminuria (albumin excretion, 300-999 and ≥1,000mg/d): crude rates of ESKD were 7.4, 34.8, 78.7, and 178.7 per 1,000 person-years, respectively; CKD progression rates were 17.0, 61.4, 130.5, and 295.1 per 1,000 person-years, respectively; and annual rates of eGFR decline were -0.17, -1.35, -2.74, and -4.69mL/min/1.73m 2 , respectively. We were unable to compare the results with healthy controls. In people with diabetes with reduced eGFRs, the absence of albuminuria or proteinuria is common and carries a much lower risk for ESKD, CKD progression, or rapid decline in eGFR compared with those with albuminuria or proteinuria. The rate of eGFR decline in normoalbuminuric CKD was similar to that reported for the general diabetic population. Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

A critical assessment on kidney allocation systems.

PubMed

Formica, Richard N

2017-01-01

The kidney allocation system that took effect on December 4, 2014 represents a significant improvement over the prior approach. It seeks to improve outcomes by longevity matching - pairing kidneys expected to function the longest with recipients expected to live the longest. It addresses the biological barriers faced by highly sensitized patients in an evidence based fashion and it begins to introduce the concept of medical need into kidney allocation by crediting time from the starting dialysis to a patient's waiting time. Additionally, it adds a more granular and continuous approach to classifying deceased donor kidneys through the kidney donor profile index and moves away from the dichotomous and flawed, standard criteria/extended criteria approach to allocating kidneys. Despite these changes, access to kidney transplantation across the age spectrum has remained intact and equitable. However even with these numerous positive improvements the system is not without its flaws. The increased sharing and by extension shipping of kidneys have created logistical challenges for organ procurement organizations and transplant centers. Early results seem to indicate that there have been an increase in cold ischemic time, an increase in delayed graft function and an increase in organ discard rate. There is also a reduced offer rate for children and while not a statistically significant decline in the number of transplants, it is a trend that requires close monitoring. Finally, the new kidney allocation system has done nothing to address the glaring deficiencies in the multi-organ allocation practices, all of which include a kidney, in the United States. Therefore despite the improvements made in kidney allocation, there is work yet to be done to ensure that the allocation of life saving and life prolonging organs for transplantation is done in a fashion consistent with ethical principles, based on science and free from local self interest so that this national resource is used for the betterment of the population it is meant to serve. Copyright © 2016. Published by Elsevier Inc.

Prevalence of chronic kidney disease and its determinants in coronary heart disease patients in 24 European countries: Insights from the EUROASPIRE IV survey of the European Society of Cardiology.

PubMed

Wagner, Martin; Wanner, Christoph; Kotseva, Kornelia; Wood, David; De Bacquer, Dirk; Rydén, Lars; Störk, Stefan; Heuschmann, Peter U

2017-07-01

Aims Chronic kidney disease (CKD) is associated with the development and progression of coronary heart disease (CHD), in addition to classic cardiovascular risk factors. We analysed the prevalence of CKD in CHD patients from 24 European countries in the ambulatory setting and in a preceding hospital stay for CHD (index). Methods and results A total of 7998 EUROASPIRE IV participants (median 65 years of age, 76% male) attended a study visit 6-36 months after the index hospitalisation. CKD was classified according to stages of estimated glomerular filtration rate (eGFR) and albuminuria (urinary albumin/creatinine ratio). In stable CHD conditions (study visit), 17.3% had CKD (eGFR <60 mL/min/1.73 m 2 ) with variation among participating countries (range 13.1-26.4%). A further 12% presented with preserved eGFR but significant albuminuria. During the hospital stay due to a coronary event, impaired kidney function was observed in 17.6% (range 7.5-38.2%). Risk factors for impaired kidney function included older age, female gender, classic cardiovascular (CV) risk factors, details of CHD history and congestive heart failure (multivariate regression). Of all patients, 38.9% had declined, 31.3% were stable and 29.8% had improved kidney function between hospital discharge and the study visit, dependent on age, gender, CV risk factors, CHD history and cardiac dysfunction (multivariate regression). Conclusions Every fifth CHD patient had CKD, while every tenth exhibited albuminuria as the sole indicator of kidney damage. These subjects are at increased risk of progression of CKD and CHD complications. After hospital stays due to CHD, there is potential of recovery of kidney function, but our findings underline the importance of identifying patients who are at high risk of developing CKD in order to counteract disease progression.

Trends in serum creatinine testing in Oxfordshire, UK, 1993-2013: a population-based cohort study.

PubMed

Oke, Jason; Shine, Brian; McFadden, Emily; Stevens, Richard; Lasserson, Daniel; Perera, Rafael

2015-12-16

To determine how many kidney function tests are done, on whom, how frequently they are performed and how they have changed over time. Retrospective study of all serum creatinine, urine albumin and urine creatinine tests. Primary and secondary care in Oxfordshire from 1993 to 2013. Unselected population of 1,220,447 people. The total number of creatinine and urinary protein tests ordered from primary and secondary care and the number of tests per year stratified by categories of estimated glomerular filtration rate (eGFR). The frequency of testing in patients having their kidney function monitored. Creatinine requests from primary care increased steadily from 1997 and exceeded 220,000 requests in 2013. Tests corresponding to normal kidney function (eGFR >60/mL/min/1.73 m(2)) constituted 59% of all kidney function tests in 1993 and accounted for 83% of all tests in 2013. Test corresponding to chronic kidney disease (CKD) stages 3-5 declined after 2007. Reduced kidney function, albuminuria, male gender, diabetes and age were independently associated with more frequent monitoring. For a female patient between 61 and 80 years and with stage 3a CKD, the average number of serum creatinine tests (95% CI) was 3.23/year (3.19 to 3.26) and for a similar woman with diabetes, the average number of tests was 5.50 (5.44 to 5.56) tests per year. There has been a large increase in the number of kidney function tests over the past two decades. However, we found little evidence that this increase is detecting more CKD. Tests are becoming more frequent in people with and without evidence of renal impairment. Future work using a richer data source could help unravel the underlying reasons for the increased testing and determine how much is necessary and useful. 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/

Absence of Decline of Kidney Function in Human Immunodeficiency Virus-Infected Patients Under Routine Clinical Management.

PubMed

Boucquemont, Julie; Lawson-Ayayi, Sylvie; Rigothier, Claire; Bonnet, Fabrice; Proust-Lima, Cécile; Neau, Didier; Greib, Carine; Miremont-Salamé, Ghada; Dabis, François; Dupon, Michel; Dauchy, Frédéric-Antoine

2017-01-01

Since the introduction of antiretroviral therapy (ART), human immunodeficiency virus (HIV)-infected patients have a drastically improved prognosis but at the same time they are also more affected by non-HIV related complications, such as chronic kidney disease. The objective of our study was to investigate the effect of proteinuria and tenofovir (TDF)-containing ART regimens on the temporal evolution of estimated glomerular filtration rate (eGFR). Between April 2008 and October 2012, we enrolled 395 patients with a complete renal evaluation among patients from the ANRS C03 Aquitaine cohort, a prospective hospital-based cohort of HIV-1-infected patients under routine clinical management in southwestern France. eGFR was estimated at each patient follow-up visit. A linear mixed model was used to analyze eGFR dynamics, accounting for change in TDF by modeling eGFR trajectory according to treatment periods. At inclusion, 56.7% of patients were treated with TDF-containing ART regimens; prevalence of glomerular and tubular proteinuria was 7.9 and 10.8% respectively. A 1-year increase of cumulative exposure to TDF was significantly associated with a mean eGFR decrease of 1.27 mL/min/1.73 m2 (95% CI [-2.14 to -0.41]). Only a urine protein to creatinine ratio >100 mg/mmol and/or a urine albumin to creatinine ratio >70 mg/mmol were associated with eGFR trajectory (mean slope 6.18 mL/min/1.73 m2 per year; 95% CI [2.71 to 9.65]), whereas TDF use was not associated with such eGFR temporal evolution. Decline in kidney function is limited under routine clinical management with monitoring of renal function and interventions including decision to continue or discontinue TDF. © 2017 S. Karger AG, Basel.

Role of renin-angiotensin-aldosterone system gene polymorphisms and hypertension-induced end-stage renal disease in autosomal dominant polycystic kidney disease.

PubMed

Ramanathan, Gnanasambandan; Elumalai, Ramprasad; Periyasamy, Soundararajan; Lakkakula, Bhaskar

2014-07-01

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited disease of the kidneys and is marked by progressive cyst growth and decline in kidney function, resulting in end-stage renal disease (ESRD). Hypertension is thought to be a significant modifying factor in the progression of renal failure in ADPKD. A number of genetic variations involved in renin-angiotensin-aldosterone system (RAAS) pathway genes have clinical or physiological impacts on pathogenesis of hypertension-induced ESRD in ADPKD. Information on RAAS pathway gene polymorphisms and their association with ESRD and ADPKD, published till March 2013, was collected using MEDLINE search. The present review deals with RAAS gene polymorphisms focused on hypertension-induced ESRD in ADPKD in different populations. The results were inconclusive and limited by heterogeneity in the study designs and the population stratification. In lieu of applying next generation sequencing technologies to study complex diseases, it is also possible to apply the same to unravel the complexity of ESRD in ADPKD.

Bardoxolone Methyl Improves Kidney Function in Patients with Chronic Kidney Disease Stage 4 and Type 2 Diabetes: Post-Hoc Analyses from Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes Study

PubMed Central

Chin, Melanie P.; Bakris, George L.; Block, Geoffrey A.; Chertow, Glenn M.; Goldsberry, Angie; Inker, Lesley A.; Heerspink, Hiddo J.L.; O'Grady, Megan; Pergola, Pablo E.; Wanner, Christoph; Warnock, David G.; Meyer, Colin J.

2018-01-01

Background Increases in measured inulin clearance, measured creatinine clearance, and estimated glomerular filtration rate (eGFR) have been observed with bardoxolone methyl in 7 studies enrolling approximately 2,600 patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). The largest of these studies was Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), a multinational, randomized, double-blind, placebo-controlled phase 3 trial which enrolled patients with T2D and CKD stage 4. The BEACON trial was terminated after preliminary analyses showed that patients randomized to bardoxolone methyl experienced significantly higher rates of heart failure events. We performed post-hoc analyses to characterize changes in kidney function induced by bardoxolone methyl. Methods Patients in ­BEACON (n = 2,185) were randomized 1: 1 to receive once-daily bardoxolone methyl (20 mg) or placebo. We compared the effects of bardoxolone methyl and placebo on a post-hoc composite renal endpoint consisting of ≥30% decline from baseline in eGFR, eGFR <15 mL/min/1.73 m2, and end-stage renal disease (ESRD) events (provision of dialysis or kidney transplantation). Results Consistent with prior studies, patients randomized to bardoxolone methyl experienced mean increases in eGFR that were sustained through study week 48. Moreover, increases in eGFR from baseline were sustained 4 weeks after cessation of treatment. Patients randomized to bardoxolone methyl were significantly less likely to experience the composite renal endpoint (hazards ratio 0.48 [95% CI 0.36–0.64]; p < 0.0001). Conclusions Bardoxolone methyl preserves kidney function and may delay the onset of ESRD in patients with T2D and stage 4 CKD. PMID:29402767

Bardoxolone Methyl Improves Kidney Function in Patients with Chronic Kidney Disease Stage 4 and Type 2 Diabetes: Post-Hoc Analyses from Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes Study.

PubMed

Chin, Melanie P; Bakris, George L; Block, Geoffrey A; Chertow, Glenn M; Goldsberry, Angie; Inker, Lesley A; Heerspink, Hiddo J L; O'Grady, Megan; Pergola, Pablo E; Wanner, Christoph; Warnock, David G; Meyer, Colin J

2018-01-01

Increases in measured inulin clearance, measured creatinine clearance, and estimated glomerular filtration rate (eGFR) have been observed with bardoxolone methyl in 7 studies enrolling approximately 2,600 patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). The largest of these studies was Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), a multinational, randomized, double-blind, placebo-controlled phase 3 trial which enrolled patients with T2D and CKD stage 4. The BEACON trial was terminated after preliminary analyses showed that patients randomized to bardoxolone methyl experienced significantly higher rates of heart failure events. We performed post-hoc analyses to characterize changes in kidney function induced by bardoxolone methyl. Patients in -BEACON (n = 2,185) were randomized 1: 1 to receive once-daily bardoxolone methyl (20 mg) or placebo. We compared the effects of bardoxolone methyl and placebo on a post-hoc composite renal endpoint consisting of ≥30% decline from baseline in eGFR, eGFR <15 mL/min/1.73 m2, and end-stage renal disease (ESRD) events (provision of dialysis or kidney transplantation). Consistent with prior studies, patients randomized to bardoxolone methyl experienced mean increases in eGFR that were sustained through study week 48. Moreover, increases in eGFR from baseline were sustained 4 weeks after cessation of treatment. Patients randomized to bardoxolone methyl were significantly less likely to experience the composite renal endpoint (hazards ratio 0.48 [95% CI 0.36-0.64]; p < 0.0001). Bardoxolone methyl preserves kidney function and may delay the onset of ESRD in patients with T2D and stage 4 CKD. © 2018 The Author(s) Published by S. Karger AG, Basel.

18β-Glycyrrhetinic acid protects against methotrexate-induced kidney injury by up-regulating the Nrf2/ARE/HO-1 pathway and endogenous antioxidants.

PubMed

Abd El-Twab, Sanaa M; Hozayen, Walaa G; Hussein, Omnia E; Mahmoud, Ayman M

2016-10-01

18β-glycyrrhetinic acid (18β-GA) has multiple beneficial and therapeutic effects. However, its protective roles on methotrexate (MTX)-induced renal injury are not well defined. In the present study, we investigated the possible protective effects of 18β-GA against MTX-induced nephrotoxicity in rats. 18β-GA (50 and 100 mg/kg) was administered for 7 days either before or after MTX. The rats were decapitated and kidney and serum samples were collected. MTX-induced renal injury in rats was evidenced by the significant (p < 0.001) increase in circulating kidney function markers and tumor necrosis factor alpha (TNF-α), as well as the histopathological alterations. MTX-induced rats exhibited significantly increased lipid peroxidation (p < 0.05) and nitric oxide (p < 0.001) levels, with concomitant marked (p < 0.001) decline in the antioxidant defenses. 18β-GA, administered either before or after MTX, produced a significant amelioration of circulating kidney function markers, TNF-α, kidney lipid peroxidation, nitric oxide, and antioxidant defenses. In addition, 18β-GA supplementation significantly up-regulated the mRNA abundance of both nuclear factor-erythroid 2-related factor 2 (Nrf2) and hemoxygenase 1 (HO-1) in the kidney of MTX-induced rats. These results indicate that 18β-GA has a protective effect on MTX-induced nephrotoxicity with possible mechanisms of attenuating oxidative stress and inflammation through up-regulating the Nrf2/ARE signaling. These findings make 18β-GA candidate as a potent agent in preventing MTX-induced kidney injury.

Biomarkers of cardiovascular stress and incident chronic kidney disease.

PubMed

Ho, Jennifer E; Hwang, Shih-Jen; Wollert, Kai C; Larson, Martin G; Cheng, Susan; Kempf, Tibor; Vasan, Ramachandran S; Januzzi, James L; Wang, Thomas J; Fox, Caroline S

2013-11-01

Growth differentiation factor-15 (GDF-15), soluble ST2 (sST2), and high-sensitivity troponin I (hsTnI) are emerging predictors of adverse clinical outcomes. We examined whether circulating concentrations are related to the development of kidney disease in the community. Plasma GDF-15, sST2, and hsTnI concentrations were measured in 2614 Framingham Offspring cohort participants (mean age 57 years, 54% women) at the sixth examination cycle (1995-1998). Associations of biomarkers with incident chronic kidney disease [CKD, eGFR <60 mL · min(-1) · (1.73 m(2)) (-1), n = 276], microalbuminuria (urinary albumin to creatinine ratio ≥25 mg/g in women and 17 mg/g in men, n = 191), and rapid decline in renal function [decline in eGFR ≥3 mL · min(-1) · (1.73 m(2)) (-1) per year, n = 237], were evaluated using multivariable logistic regression; P < 0.006 was considered statistically significant in primary analyses. Participants were followed over a mean of 9.5 years. Higher plasma GDF-15 was associated with incident CKD [multivariable-adjusted odds ratio (OR) 1.9 per 1-U increase in log-GDF-15, 95% CI 1.6-2.3, P < 0.0001] and rapid decline in renal function (OR, 1.6; 95% CI, 1.3-1.8; P < 0.0001). GDF-15, sST2, and hsTnI had suggestive associations with incident microalbuminuria but did not meet the prespecified P-value threshold after multivariable adjustment. Adding plasma GDF-15 to clinical covariates improved risk prediction of incident CKD: the c-statistic increased from 0.826 to 0.845 (P = 0.0007), and categorical net reclassification was 6.3% (95% CI, 2.7-9.9%). Higher circulating GDF-15 is associated with incident renal outcomes and improves risk prediction of incident CKD. These findings may provide insights into the mechanisms of renal injury.

Decline in Kidney Function among Apparently Healthy Young Adults at Risk of Mesoamerican Nephropathy.

PubMed

Gonzalez-Quiroz, Marvin; Smpokou, Evangelia-Theano; Silverwood, Richard J; Camacho, Armando; Faber, Dorien; Garcia, Brenda La Rosa; Oomatia, Amin; Hill, Michael; Glaser, Jason; Le Blond, Jennifer; Wesseling, Catharina; Aragon, Aurora; Smeeth, Liam; Pearce, Neil; Nitsch, Dorothea; Caplin, Ben

2018-06-15

Background Epidemic levels of CKD of undetermined cause, termed Mesoamerican nephropathy in Central America, have been found in low- and middle-income countries. We investigated the natural history of, and factors associated with, loss of kidney function in a population at high risk for this disease. Methods We conducted a 2-year prospective, longitudinal study with follow-up every 6 months in nine rural communities in northwestern Nicaragua and included all men ( n =263) and a random sample of women ( n =87) ages 18-30 years old without self-reported CKD, diabetes, or hypertension. We used growth mixture modeling to identify subgroups of eGFR trajectory and weighted multinomial logistic regression to examine associations with proposed risk factors. Results Among men, we identified three subpopulations of eGFR trajectory (mean baseline eGFR; mean eGFR change over follow-up): 81% remained stable (116 ml/min per 1.73 m 2 ; -0.6 ml/min per 1.73 m 2 per year), 9.5% experienced rapid decline despite normal baseline function (112 ml/min per 1.73 m 2 ; -18.2 ml/min per 1.73 m 2 per year), and 9.5% had baseline dysfunction (58 ml/min per 1.73 m 2 ; -3.8 ml/min per 1.73 m 2 per year). Among women: 96.6% remained stable (121 ml/min per 1.73 m 2 ; -0.6 ml/min per 1.73 m 2 per year), and 3.4% experienced rapid decline (132 ml/min per 1.73 m 2 ; -14.6 ml/min per 1.73 m 2 per year; n =3 women). Among men, outdoor and agricultural work and lack of shade availability during work breaks, reported at baseline, were associated with rapid decline. Conclusions Although Mesoamerican nephropathy is associated with agricultural work, other factors may also contribute to this disease. Copyright © 2018 by the American Society of Nephrology.

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.

The impact of conversion from prograf to generic tacrolimus in liver and kidney transplant recipients with stable graft function.

PubMed

Momper, J D; Ridenour, T A; Schonder, K S; Shapiro, R; Humar, A; Venkataramanan, R

2011-09-01

Bioequivalence of the recently available generic tacrolimus formulation, manufactured by Sandoz, to the reference product (Prograf; Astellas Pharma, Tokyo, Japan) has been demonstrated in healthy subjects. However, the safety and efficacy of substitution with generic tacrolimus in transplant patients have not been evaluated. Tacrolimus trough concentrations and indices of liver and kidney function were recorded before and after generic substitution in 48 liver and 55 kidney transplant recipients. In liver transplant patients, the mean tacrolimus concentration/dose (C/D) ratio (± SD) was 184.1 (± 123.2) ([ng/mL]/[mg/kg/day]) for the reference product and 154.7 (± 87.8) ([ng/mL]/[mg/kg/day]) for the generic product (p < 0.05). The mean C/D-ratios in kidney transplant patients were 125.3 (± 92.7) and 110.4 (± 79.2) ([ng/mL]/[mg/kg/day]) for the reference and generic products, respectively (p < 0.05). Actual trough concentrations declined by an average of 1.98 ng/mL in liver and 0.87 ng/mL in kidney transplant patients following the switch, after accounting for all significant covariates. No change was observed in biochemical indices of liver or kidney function and no cases of acute rejection occurred following the substitution. These results suggest that transplant patients currently taking the reference tacrolimus formulation may be safely switched to the Sandoz-generic product provided trough concentrations are closely monitored following the substitution. © 2011 The Authors Journal compilation © 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.

Acute kidney injury in acute liver failure: a review.

PubMed

Moore, Joanna K; Love, Eleanor; Craig, Darren G; Hayes, Peter C; Simpson, Kenneth J

2013-11-01

Acute liver failure is a rare and often devastating condition consequent on massive liver cell necrosis that frequently affects young, previously healthy individuals resulting in altered cognitive function, coagulopathy and peripheral vasodilation. These patients frequently develop concurrent acute kidney injury (AKI). This abrupt and sustained decline in renal function, through a number of pathogenic mechanisms such as renal hypoperfusion, direct drug-induced nephrotoxicity or sepsis/systemic inflammatory response contributes to increased morbidity and is strongly associated with a worse prognosis. Improved understanding of the pathophysiology AKI in the context of acute liver failure may be beneficial in a number of areas; the development of new and sensitive biomarkers of renal dysfunction, refining prognosis and organ allocation, and ultimately leading to the development of novel treatment strategies, these issues are discussed in more detail in this expert review.

Cognitive dysfunction and depression in adult kidney transplant recipients: baseline findings from the FAVORIT Ancillary Cognitive Trial (FACT)

USDA-ARS?s Scientific Manuscript database

Hyperhomocysteinemia and B-vitamin deficiency may be treatable risk factors for cognitive impairment and decline. Hyperhomocysteinemia, cognitive impairment and depression all are common in individuals with kidney disease, including kidney transplant recipient. Accordingly, we assessed the prevalenc...

Peritransplant Soluble CD30 as a Risk Factor for Slow Kidney Allograft Function, Early Acute Rejection, Worse Long-Term Allograft Function, and Patients' Survival.

PubMed

Trailin, Andriy V; Ostapenko, Tetyana I; Nykonenko, Tamara N; Nesterenko, Svitlana N; Nykonenko, Olexandr S

2017-01-01

We aimed to determine whether serum soluble CD30 (sCD30) could identify recipients at high risk for unfavorable early and late kidney transplant outcomes. Serum sCD30 was measured on the day of kidney transplantation and on the 4th day posttransplant. We assessed the value of these measurements in predicting delayed graft function, slow graft function (SGF), acute rejection (AR), pyelonephritis, decline of allograft function after 6 months, and graft and patient survival during 5 years of follow-up in 45 recipients. We found the association between low pretransplant serum levels of sCD30 and SGF. The absence of significant decrease of sCD30 on the 4th day posttransplant was characteristic for SGF, early AR (the 8th day-6 months), late AR (>6 months), and early pyelonephritis (the 8th day-2 months). Lower pretransplant and posttransplant sCD30 predicted worse allograft function at 6 months and 2 years, respectively. Higher pretransplant sCD30 was associated with higher frequency of early AR, and worse patients' survival, but only in the recipients of deceased-donor graft. Pretransplant sCD30 also allowed to differentiate patients with early pyelonephritis and early AR. Peritransplant sCD30 is useful in identifying patients at risk for unfavorable early and late transplant outcomes.

[Ornithine decarboxylase in mammalian organs and tissues at hibernation and artificial hypobiosis].

PubMed

Logvinovich, O S; Aksenova, G E

2013-01-01

Ornithine decarboxylase (ODC, EC 4.1.1.17.) is a short-lived and dynamically regulated enzyme of polyamines biosynthesis. Regulation of functional, metabolic and proliferative state of organs and tissues involves the modifications of the ODC enzymatic activity. The organ-specific changes in ODC activity were revealed in organs and tissues (liver, spleen, bone marrow, kidney, and intestinal mucosa) of hibernating mammals - squirrels Spermophilus undulates - during the hibernating season. At that, a positive correlation was detected between the decline and recovery of the specialized functions of organs and tissues and the respective modifications of ODC activity during hibernation bouts. Investigation of changes in ODC activity in organs and tissues of non-hibernating mammals under artificial hypobiosis showed that in Wistar rats immediately after exposure to hypothermia-hypoxia-hypercapnia (hypobiosis) the level of ODC activity was low in thymus, spleen, small intestine mucosa, neocortex, and liver. The most marked reduction in enzyme activity was observed in actively proliferating tissues: thymus, spleen, small intestine mucosa. In bone marrow of squirrels, while in a state of torpor, as well as in thymus of rats after exposure to hypothermia-hypoxia-hypercapnia, changes in the ODC activity correlated with changes in the rate of cell proliferation (by the criterion of cells distribution over cell cycle). The results obtained, along with the critical analysis of published data, indicate that the ODC enzyme is involved in biochemical adaptation of mammals to natural and artificial hypobiosis. A decline in the ODC enzymatic activity indicates a decline in proliferative, functional, and metabolic activity of organs and tissues of mammals (bone marrow, mucosa of small intestine, thymus, spleen, neocortex, liver, kidneys) when entering the state of hypobiosis.

Kidney function changes with aging in adults: comparison between cross-sectional and longitudinal data analyses in renal function assessment.

PubMed

Chung, Sang M; Lee, David J; Hand, Austin; Young, Philip; Vaidyanathan, Jayabharathi; Sahajwalla, Chandrahas

2015-12-01

The study evaluated whether the renal function decline rate per year with age in adults varies based on two primary statistical analyses: cross-section (CS), using one observation per subject, and longitudinal (LT), using multiple observations per subject over time. A total of 16628 records (3946 subjects; age range 30-92 years) of creatinine clearance and relevant demographic data were used. On average, four samples per subject were collected for up to 2364 days (mean: 793 days). A simple linear regression and random coefficient models were selected for CS and LT analyses, respectively. The renal function decline rates per year were 1.33 and 0.95 ml/min/year for CS and LT analyses, respectively, and were slower when the repeated individual measurements were considered. The study confirms that rates are different based on statistical analyses, and that a statistically robust longitudinal model with a proper sampling design provides reliable individual as well as population estimates of the renal function decline rates per year with age in adults. In conclusion, our findings indicated that one should be cautious in interpreting the renal function decline rate with aging information because its estimation was highly dependent on the statistical analyses. From our analyses, a population longitudinal analysis (e.g. random coefficient model) is recommended if individualization is critical, such as a dose adjustment based on renal function during a chronic therapy. Copyright © 2015 John Wiley & Sons, Ltd.

Asymptomatic cerebral lacunae in patients with chronic kidney disease.

PubMed

Kobayashi, Shuzo; Ikeda, Toshio; Moriya, Hidekazu; Ohtake, Takayasu; Kumagai, Hiromichi

2004-07-01

It remains unknown whether the prevalence of silent lacunar infarcts increases as renal function declines or what factors known as atherosclerotic risk factors are related to the development of lacunar infarcts. Fifty-one patients with chronic kidney disease without diabetes mellitus and 80 patients with essential hypertension with normal renal function were included in the study. The existence of lacunar infarcts was evaluated on brain magnetic resonance imaging scans. We evaluated the severity of carotid atherosclerosis by means of intima-media thickness of 1.0 mm or greater height in bilateral carotid arteries and by affecting factors, including plasma homocysteine levels. Lacunae prevalence was 25% in patients with a creatinine clearance (Ccr) greater than 40 mL/min/1.73 m2, 85% in patients with a Ccr less than 40 mL/min/1.73 m2, and 29% in patients with essential hypertension with normal renal function. Patients with lacunae had significantly lower hematocrits associated with increased fibrinogen and lipoprotein(a) levels compared with those without lacunae. Plasma total homocysteine and insulin levels at 2 hours after a 75-g glucose tolerance test correlated significantly with lacunae. Ischemic heart changes shown by electrocardiogram and thickened carotid intima-media thickness were significantly more frequent in patients with lacunae. However, logistic regression analysis showed that the most strongly contributing factor for lacunar infarcts was decline in Ccr (confidence interval, 0.933 to 0.995; P < 0.05). Decreased renal function, even without diabetes mellitus, is a risk factor for silent lacunar infarcts.

[Effect of age, different light conditions, melatonin, and epitalon on lysosomal proteinase activity in the liver and kidneys of rats].

PubMed

Rendakov, N L; Tiutiunnik, N N; Vinogradova, I A

2006-01-01

Ageing, melatonin, epithalon (tetrapeptide Ala-Glu-Asp-Gly) and different light conditions effects on protein content and cathepsins B and D activities in rat liver and kidneys lysosomal fractions were studied. Ageing leads to decrease of cathepsins activity in rat liver lysosomal fractions. Constant light and darkness conditions result in earlier age decline of cathepsins activity. Absence of day and night succession in comparison with alternating light conditions causes decline of both general and specific cathepsin D activity. Melatonin and epithalon administration resulted in decrease of cathepsin D activity in liver only under control interchangeable light conditions. Cathepsin B activity in liver and kidneys lysosomal fractions declined in all experimental light conditions. Cathepsins activity decrease under the influence of epiphysial factors is evidently connected with their inhibitory effect on protein and general metabolism.

Robotic Partial Nephrectomy in Patients with Chronic Kidney Disease: Objective Measurement of Short- and Long-term Renal Functional Outcomes.

PubMed

Chalouhy, Charbel; Ruck, Jessica Moore; Zhou, Tian Cheng; Srivastava, Abhishek; Keehn, Aryeh; Watts, Kara L; Maria, Pedro; Ghavamian, Reza

2018-05-31

Minimal literature informs the use of robotic partial nephrectomy (RPN) in patients with chronic kidney disease (CKD). Therefore, we evaluated the renal functional outcomes in CKD patients undergoing RPN. We reviewed a prospective database of patients undergoing RPN 2010-2015 and identified 182 patients who had preoperative and postoperative nuclear renal scintigraphy (at 2 and 12 months postop). Pre-operative and 12-month post-operative eGFR (mL/min/1.73m2, by MDRD) were calculated. CKD was defined as eGFR <60mL/min/1.73m2 (CKD stages III&IV). Changes in creatinine, eGFR and split function on Mercaptuacetyltriglycine (MAG) 3 scan were compared by baseline CKD status. Correlations between pre- and post-operative eGFR were calculated. Of 182 patients, 30 (16.5%) had baseline CKD. Preoperative eGFR was 48.5 and 99.0 in CKD and non-CKD patients, respectively (p<0.001). From pre-operation to 12 months post-operation, eGFR decreased by 2.8 and 1.1 mL/min/1.73m2, respectively (p=0.6). On MAG-3 scan, the contribution of the surgical kidney to overall renal function decreased by 5.0% and 4.8% (p = 0.9) in the CKD and non-CKD cohorts, respectively. When comparing renal scans at 2 and 12 months post-operation, in both groups the surgical kidney significantly recovered (both p<0.001) and the patterns of kidney function recovery was similar in both groups (CKD +2.0%, non-CKD +1.4%, p=0.6). On long-term follow-up (>2years), eGFR did not change significantly in either the CKD or non-CKD group (-2.8 vs -1.1 mL/min/1.73m2, p=0.6). On pathology, tumors were more frequently malignant in CKD vs. non-CKD patients (93.3% vs 73.2%, p=0.02) and of higher Fuhrman Grade (grade >3: 49.7% vs 28.1%, p<0.001). RPN is a reasonable treatment option in patients with CKD, as it did not lead to a greater decline in renal function contributed by the surgical kidney. The patterns of kidney function recovery after surgery are similar between patients with and without CKD.

High Baseline Levels of Tumor Necrosis Factor Receptor 1 Are Associated With Progression of Kidney Disease in Indigenous Australians With Diabetes: The eGFR Follow-up Study.

PubMed

Barr, Elizabeth L M; Barzi, Federica; Hughes, Jaquelyne T; Jerums, George; Hoy, Wendy E; O'Dea, Kerin; Jones, Graham R D; Lawton, Paul D; Brown, Alex D H; Thomas, Mark; Ekinci, Elif I; Sinha, Ashim; Cass, Alan; MacIsaac, Richard J; Maple-Brown, Louise J

2018-04-01

To examine the association between soluble tumor necrosis factor receptor 1 (sTNFR1) levels and kidney disease progression in Indigenous Australians at high risk of kidney disease. This longitudinal observational study examined participants aged ≥18 years recruited from >20 sites across diabetes and/or kidney function strata. Baseline measures included sTNFR1, serum creatinine, urine albumin-to-creatinine ratio (uACR), HbA 1c , C-reactive protein (CRP), waist-to-hip ratio, systolic blood pressure, and medical history. Linear regression was used to estimate annual change in estimated glomerular filtration rate (eGFR) for increasing sTNFR1, and Cox proportional hazards were used to estimate the hazard ratio (HR) and 95% CI for developing a combined renal outcome (first of a ≥30% decline in eGFR with a follow-up eGFR <60 mL/min/1.73 m 2 , progression to renal replacement therapy, or renal death) for increasing sTNFR1. Over a median of 3 years, participants with diabetes ( n = 194) in the highest compared with the lowest quartile of sTNFR1 experienced significantly greater eGFR decline (-4.22 mL/min/1.73 m 2 /year [95% CI -7.06 to -1.38]; P = 0.004), independent of baseline age, sex, eGFR, and uACR. The adjusted HR (95% CI) for participants with diabetes per doubling of sTNFR1 for the combined renal outcome ( n = 32) was 3.8 (1.1-12.8; P = 0.03). No association between sTNFR1 and either renal outcome was observed for those without diabetes ( n = 259). sTNFR1 is associated with greater kidney disease progression independent of albuminuria and eGFR in Indigenous Australians with diabetes. Further research is required to assess whether TNFR1 operates independently of other metabolic factors associated with kidney disease progression. © 2018 by the American Diabetes Association.

Chronic Kidney Disease.

PubMed

Webster, Angela C; Nagler, Evi V; Morton, Rachael L; Masson, Philip

2017-03-25

The definition and classification of chronic kidney disease (CKD) have evolved over time, but current international guidelines define this condition as decreased kidney function shown by glomerular filtration rate (GFR) of less than 60 mL/min per 1·73 m 2 , or markers of kidney damage, or both, of at least 3 months duration, regardless of the underlying cause. Diabetes and hypertension are the main causes of CKD in all high-income and middle-income countries, and also in many low-income countries. Incidence, prevalence, and progression of CKD also vary within countries by ethnicity and social determinants of health, possibly through epigenetic influence. Many people are asymptomatic or have non-specific symptoms such as lethargy, itch, or loss of appetite. Diagnosis is commonly made after chance findings from screening tests (urinary dipstick or blood tests), or when symptoms become severe. The best available indicator of overall kidney function is GFR, which is measured either via exogenous markers (eg, DTPA, iohexol), or estimated using equations. Presence of proteinuria is associated with increased risk of progression of CKD and death. Kidney biopsy samples can show definitive evidence of CKD, through common changes such as glomerular sclerosis, tubular atrophy, and interstitial fibrosis. Complications include anaemia due to reduced production of erythropoietin by the kidney; reduced red blood cell survival and iron deficiency; and mineral bone disease caused by disturbed vitamin D, calcium, and phosphate metabolism. People with CKD are five to ten times more likely to die prematurely than they are to progress to end stage kidney disease. This increased risk of death rises exponentially as kidney function worsens and is largely attributable to death from cardiovascular disease, although cancer incidence and mortality are also increased. Health-related quality of life is substantially lower for people with CKD than for the general population, and falls as GFR declines. Interventions targeting specific symptoms, or aimed at supporting educational or lifestyle considerations, make a positive difference to people living with CKD. Inequity in access to services for this disease disproportionally affects disadvantaged populations, and health service provision to incentivise early intervention over provision of care only for advanced CKD is still evolving in many countries. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cognitive Performance Is Highly Stable over a 2-Year-Follow-Up in Chronic Kidney Disease Patients in a Dedicated Medical Environment.

PubMed

Gronewold, Janine; Todica, Olga; Seidel, Ulla K; Volsek, Michaela; Kribben, Andreas; Bruck, Heike; Hermann, Dirk M

2016-01-01

As kidney and brain functions decline with aging, chronic kidney disease (CKD) and dementia are becoming increasing health burdens worldwide. Among the risk factors for cognitive impairment, CKD is increasingly recognized. The precise impact of CKD on the development of cognitive impairment is poorly understood. In the New Tools for the Prevention of Cardiovascular Disease in Chronic Kidney Disease (NTCVD) cohort, which was recruited in a dedicated nephrology department, we examined the 2-year course of cognitive performance in 120 patients (73 patients with CKD stages 3-5D, 47 control patients without CKD with similar vascular risk profile) using a comprehensive battery of 10 neuropsychological tests. Kidney function, vascular risk factors and cognitive performance were highly stable both in CKD and control patients. The summary score of cognitive performance in CKD patients was very similar at baseline (z = -0.63±0.76) and follow-up (z = -0.54±0.79, p = 0.113), as was cognitive performance in control patients (z = -0.01±0.59 and 0.01±0.70, p = 0.862, at baseline and follow-up, respectively). Total serum cholesterol (199.6±36.0 and 186.0±32.9, p = 0.005 in controls; 194.4±46.1 and 181.2±41.2, p = 0.008 in CKD) and common carotid intima-media thickness (0.87±0.18 and 0.84±0.17, p = 0.351 in controls; 0.88±0.21 and 0.82±0.16, p = 0.002 in CKD) moderately but significantly decreased during the follow-up. In multivariable regression analyses, high age (β = -0.28, 95%CI = -0.48 to 0.08, p = 0.007) predicted decrease in cognitive performance. In this well-defined cohort receiving state-of-the-art therapy, cognitive performance did not decrease over 2 years. Our data emphasize the aspect of risk factor control, suggesting that dedicated medical care might prevent cognitive decline in CKD patients.

Iron-Hepcidin Dysmetabolism, Anemia and Renal Hypoxia, Inflammation and Fibrosis in the Remnant Kidney Rat Model

PubMed Central

Garrido, Patrícia; Ribeiro, Sandra; Fernandes, João; Vala, Helena; Bronze-da-Rocha, Elsa; Rocha-Pereira, Petronila; Belo, Luís; Costa, Elísio; Santos-Silva, Alice; Reis, Flávio

2015-01-01

Anemia is a common complication of chronic kidney disease (CKD) that develops early and its severity increases as renal function declines. It is mainly due to a reduced production of erythropoietin (EPO) by the kidneys; however, there are evidences that iron metabolism disturbances increase as CKD progresses. Our aim was to study the mechanisms underlying the development of anemia of CKD, as well as renal damage, in the remnant kidney rat model of CKD induced by 5/6 nephrectomy. This model of CKD presented a sustained degree of renal dysfunction, with mild and advanced glomerular and tubulointerstitial lesions. Anemia developed 3 weeks after nephrectomy and persisted throughout the protocol. The remnant kidney was still able to produce EPO and the liver showed an increased EPO gene expression. In spite of the increased EPO blood levels, anemia persisted and was linked to low serum iron and transferrin levels, while serum interleukin (IL)-6 and high sensitivity C-reactive protein (hs-CRP) levels showed the absence of systemic inflammation. The increased expression of duodenal ferroportin favours iron absorption; however, serum iron is reduced which might be due to iron leakage through advanced kidney lesions, as showed by tubular iron accumulation. Our data suggest that the persistence of anemia may result from disturbances in iron metabolism and by an altered activity/function of EPO as a result of kidney cell damage and a local inflammatory milieu, as showed by the increased gene expression of different inflammatory proteins in the remnant kidney. In addition, this anemia and the associated kidney hypoxia favour the development of fibrosis, angiogenesis and inflammation that may underlie a resistance to EPO stimuli and reduced iron availability. These findings might contribute to open new windows to identify putative therapeutic targets for this condition, as well as for recombinant human EPO (rHuEPO) resistance, which occurs in a considerable percentage of CKD patients. PMID:25867633

Riser pattern is a predictor of kidney mortality among patients with chronic kidney disease.

PubMed

Nakai, Kentaro; Fujii, Hideki; Watanabe, Kentaro; Watanabe, Shuhei; Awata, Rie; Kono, Keiji; Yonekura, Yuriko; Goto, Shunsuke; Nishi, Shinichi

Hypertension is a crucial risk factor for cardiovascular death and loss of residual kidney function. Absence of the nocturnal decline in blood pressure (BP) predicts cardiovascular events and poor prognosis. However, characteristics of hypertension in moderate-to-severe chronic kidney disease (CKD) have not been fully evaluated. We aimed to assess the circadian variation of BP and kidney survival in CKD patients. Patients who were examined by 24-h ambulatory BP monitoring (ABPM) and estimated glomerular filtration rate (eGFR), <45 ml/min/1.73 m(2), were enrolled in the study. The impacts of BP circadian rhythm and brain natriuretic peptide (BNP) on kidney survival were evaluated. A total of 124 patients were enrolled. The average age was 64 ± 14 years, 57% were male, and 43% had diabetes. Forty-five percent of patients had a non-dipper pattern, 35% had a riser pattern, 19% had a dipper pattern, and 1% had an extreme-dipper pattern. The prevalence of diabetes and plasma BNP levels was higher and eGFR was lower in the riser-pattern group than in the non-riser-pattern group. Kidney survival rates were significantly worse in the riser-pattern group than in the non-riser-pattern group (p < 0.05). Moreover, among riser and non-riser pattern groups divided by BNP levels, the riser group with higher BNP level showed the worst kidney survival (p < 0.05). The riser pattern is frequently associated with several conditions at higher risk for kidney survival. Patients with a rising pattern and higher BNP levels have a worse kidney prognosis.

Urinary Biomarkers at Early ADPKD Disease Stage

PubMed Central

Petzold, Katja; Poster, Diane; Krauer, Fabienne; Spanaus, Katharina; Andreisek, Gustav; Nguyen-Kim, Thi Dan Linh; Pavik, Ivana; Ho, Thien Anh; Serra, Andreas L.; Rotar, Laura

2015-01-01

Background Autosomal dominant polycystic kidney disease (ADPKD) is characterized by a decline in renal function at late disease stage when the majority of functional renal parenchyma is replaced by cystic tissue. Thus, kidney function, assessed by estimated glomerular filtration rate (eGFR) does not well represent disease burden in early disease. Here, we investigated various urinary markers for tubular injury and their association with disease burden in ADPKD patients at early disease course. Methods ADPKD patients between 18 and 40 years with an eGFR greater or equal to 70 ml per min per 1.73m2 were eligible for this cross-sectional study. Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL), Kidney Injury Molecule-1 (KIM-1), and Uromodulin (UMOD) were investigated by Enzyme-Linked Immunosorbent Assay. Clara Cell Protein 16 (CC16) was investigated by Latex Immuno Assay. Cryoscopy was performed to assess urine osmolality and Urinary Albumin-to-Creatinine Ratio (UACR) was calculated. The association and the predictive properties of the markers on eGFR and height adjusted total kidney volume (htTKV) was evaluated using multiple regression analysis, incorporating different control variables for adjustment. Internal bootstrapping validated the obtained results. Results In 139 ADPKD patients (age 31 ±7 years, mean eGFR of 93 ± 19 ml per min per 1.73 m2) the total kidney volume was negatively correlated with eGFR and UMOD and positive associated with age, UACR, KIM-1 and urine osmolality after adjustment for possible confounders. Urine osmolality and htTKV were also associated with eGFR, whereas no association of CC16, NGAL and UMOD with eGFR or htTKV was found. Conclusion UACR and urinary KIM-1 are independently associated with kidney size but not with renal function in our study population. Urine osmolality was associated with eGFR and kidney volume following adjustment for multiple confounders. Despite statistical significance, the clinical value of our results is not yet conceivable. Further studies are needed to evaluate the property of the aforementioned biomarkers to assess disease state at early ADPKD stage. PMID:25875363

Brachial-ankle pulse wave velocity predicts decline in renal function and cardiovascular events in early stages of chronic kidney disease.

PubMed

Yoon, Hye Eun; Shin, Dong Il; Kim, Sung Jun; Koh, Eun Sil; Hwang, Hyeon Seok; Chung, Sungjin; Shin, Seok Joon

2013-01-01

In this study, we investigated the predictive capacity of the brachial-ankle aortic pulse wave velocity (baPWV), a marker of arterial stiffness, for the decline in renal function and for cardiovascular events in the early stages of chronic kidney disease (CKD). Two hundred forty-one patients who underwent a comprehensive check-up were included and were divided into two groups according to their estimated glomerular filtration rates (eGFR): patients with CKD categories G2, G3a and G3b (30 ≤ eGFR < 90 ml/min/1.73m(2), eGFR < 90 group; n=117) and those with eGFR ≥ 90 ml/min/1.73 m(2) (eGFR ≥ 90 group; n=124). The change in renal function, the eGFR change, was determined by the slope of eGFR against time. We analysed whether baPWV was associated with eGFR change or predicted cardiovascular events. baPWV was independently associated with eGFR change in a multivariate analysis of the total patients (β=-0.011, p=0.011) and remained significantly associated with eGFR change in a subgroup analysis of the eGFR < 90 group (β=-0.015, p=0.035). baPWV was independently associated with cardiovascular events (odds ratio=1.002, p=0.048) in the eGFR < 90 group, but not in the eGFR ≥ 90 group. The receiver operative characteristic curve analysis showed that 1,568 cm/sec was the cut-off value of baPWV for predicting CV events in the eGFR < 90 group (area under curve=0.691, p=0.03) CONCLUSIONS: In patients with early stages of CKD, baPWV was independently associated with the decline in renal function and short-term cardiovascular events.

The directed differentiation of human iPS cells into kidney podocytes.

PubMed

Song, Bi; Smink, Alexandra M; Jones, Christina V; Callaghan, Judy M; Firth, Stephen D; Bernard, Claude A; Laslett, Andrew L; Kerr, Peter G; Ricardo, Sharon D

2012-01-01

The loss of glomerular podocytes is a key event in the progression of chronic kidney disease resulting in proteinuria and declining function. Podocytes are slow cycling cells that are considered terminally differentiated. Here we provide the first report of the directed differentiation of induced pluripotent stem (iPS) cells to generate kidney cells with podocyte features. The iPS-derived podocytes share a morphological phenotype analogous with cultured human podocytes. Following 10 days of directed differentiation, iPS podocytes had an up-regulated expression of mRNA and protein localization for podocyte markers including synaptopodin, nephrin and Wilm's tumour protein (WT1), combined with a down-regulation of the stem cell marker OCT3/4. In contrast to human podocytes that become quiescent in culture, iPS-derived cells maintain a proliferative capacity suggestive of a more immature phenotype. The transduction of iPS podocytes with fluorescent labeled-talin that were immunostained with podocin showed a cytoplasmic contractile response to angiotensin II (AII). A permeability assay provided functional evidence of albumin uptake in the cytoplasm of iPS podocytes comparable to human podocytes. Moreover, labeled iPS-derived podocytes were found to integrate into reaggregated metanephric kidney explants where they incorporated into developing glomeruli and co-expressed WT1. This study establishes the differentiation of iPS cells to kidney podocytes that will be useful for screening new treatments, understanding podocyte pathogenesis, and offering possibilities for regenerative medicine.

Risk Factors for Progression of Chronic Kidney Disease

PubMed Central

Staples, Amy; Wong, Craig

2010-01-01

Purpose of Review Provides an overview of the identified risk factors for chronic kidney disease (CKD) progression emphasizing the pediatric population. Recent findings Over the past ten years, there have been significant changes to our understanding and study of pre-terminal kidney failure. Recent refinements in the measurement of glomerular filtration rate (GFR) and GFR estimating equations are important tools for identification and association of risk factors for CKD progression in children. In pediatric CKD, lower level of kidney function at presentation, higher levels of proteinuria, and hypertension are known markers for a more rapid decline in GFR. Anemia and other reported risk factors from the pre-genomic era have need for further study and validation. Genome-wide association studies have identified genetic loci which have provided novel genetic risk factors for CKD progression. Summary With cohort studies of children with CKD becoming mature, they have started to yield important refinements to the assessment of CKD progression. While many of the traditional risk factors for renal progression will certainly be assessed, such cohorts will be important for evaluating novel risk factors identified by genome-wide studies. PMID:20090523

Peritransplant Soluble CD30 as a Risk Factor for Slow Kidney Allograft Function, Early Acute Rejection, Worse Long-Term Allograft Function, and Patients' Survival

PubMed Central

Ostapenko, Tetyana I.; Nykonenko, Tamara N.; Nesterenko, Svitlana N.; Nykonenko, Olexandr S.

2017-01-01

Background We aimed to determine whether serum soluble CD30 (sCD30) could identify recipients at high risk for unfavorable early and late kidney transplant outcomes. Methods Serum sCD30 was measured on the day of kidney transplantation and on the 4th day posttransplant. We assessed the value of these measurements in predicting delayed graft function, slow graft function (SGF), acute rejection (AR), pyelonephritis, decline of allograft function after 6 months, and graft and patient survival during 5 years of follow-up in 45 recipients. Results We found the association between low pretransplant serum levels of sCD30 and SGF. The absence of significant decrease of sCD30 on the 4th day posttransplant was characteristic for SGF, early AR (the 8th day–6 months), late AR (>6 months), and early pyelonephritis (the 8th day–2 months). Lower pretransplant and posttransplant sCD30 predicted worse allograft function at 6 months and 2 years, respectively. Higher pretransplant sCD30 was associated with higher frequency of early AR, and worse patients' survival, but only in the recipients of deceased-donor graft. Pretransplant sCD30 also allowed to differentiate patients with early pyelonephritis and early AR. Conclusions Peritransplant sCD30 is useful in identifying patients at risk for unfavorable early and late transplant outcomes. PMID:28694560

Renal Control of Calcium, Phosphate, and Magnesium Homeostasis

PubMed Central

Chonchol, Michel; Levi, Moshe

2015-01-01

Calcium, phosphate, and magnesium are multivalent cations that are important for many biologic and cellular functions. The kidneys play a central role in the homeostasis of these ions. Gastrointestinal absorption is balanced by renal excretion. When body stores of these ions decline significantly, gastrointestinal absorption, bone resorption, and renal tubular reabsorption increase to normalize their levels. Renal regulation of these ions occurs through glomerular filtration and tubular reabsorption and/or secretion and is therefore an important determinant of plasma ion concentration. Under physiologic conditions, the whole body balance of calcium, phosphate, and magnesium is maintained by fine adjustments of urinary excretion to equal the net intake. This review discusses how calcium, phosphate, and magnesium are handled by the kidneys. PMID:25287933

Cognitive Changes in Chronic Kidney Disease and After Transplantation.

PubMed

Van Sandwijk, Marit S; Ten Berge, Ineke J M; Majoie, Charles B L M; Caan, Matthan W A; De Sonneville, Leo M J; Van Gool, Willem A; Bemelman, Frederike J

2016-04-01

Cognitive impairment is very common in chronic kidney disease (CKD) and is strongly associated with increased mortality. This review article will discuss the pathophysiology of cognitive impairment in CKD, as well as the effect of dialysis and transplantation on cognitive function. In CKD, uremic toxins, hyperparathyroidism and Klotho deficiency lead to chronic inflammation, endothelial dysfunction and vascular calcifications. This results in an increased burden of cerebrovascular disease in CKD patients, who consistently have more white matter hyperintensities, microbleeds, microinfarctions and cerebral atrophy on magnetic resonance imaging scans. Hemodialysis, although beneficial in terms of uremic toxin clearance, also contributes to cognitive decline by causing rapid fluid and osmotic shifts. Decreasing the dialysate temperature and increasing total dialysis time limits these shifts and helps maintain cognitive function in hemodialysis patients. For many patients, kidney transplantation is the preferred treatment modality, because it reverses the underlying mechanisms causing cognitive impairment in CKD. These positive effects have to be balanced against the possible neurotoxicity of infections and immunosuppressive medications, especially glucocorticosteroids and calcineurin inhibitors. A limited number of studies have addressed the overall effect of transplantation on cognitive function. These have mostly found an improvement after transplantation, but have a limited applicability to daily practice because they have only included relatively young patients.

Greater Dietary Inflammatory Index score is associated with higher likelihood of chronic kidney disease.

PubMed

Mazidi, Mohsen; Shivappa, Nitin; Wirth, Michael D; Hebert, James R; Kengne, Andre P

2018-07-01

Chronic kidney disease (CKD) is described as a progressive alteration of kidney function, resulting from multiple factors, including behaviours. We investigated the association of the Dietary Inflammatory Index (DII®) with prevalent CKD in adult Americans. National Health and Nutrition Examination Survey participants with measured data on kidney function markers from 2005 to 2012 were included in this study. Prevalent CKD was based on an estimated glomerular filtration rate (eGFR) <60 ml/min per 1·73 m2 or urinary albumin/creatinine≥30 mg/g. Energy-adjusted DII (E-DIITM) scores were calculated from 24-h dietary recalls. Statistical analyses accounted for the survey design and sample weights. We included 21 649 participants, with 1634 (6·8 %) having prevalent CKD. Participants with high E-DII scores had greater BMI, fasting blood glucose and systolic blood pressure, and were more likely to be diabetic or hypertensive (all P<0·001) compared with those with lower E-DII scores. In regression models adjusted for age, sex, race, fasting blood glucose, blood pressure, BMI, hypertension and diabetes status, mean eGFR significantly decreased across increasing quartiles of E-DII, whereas serum uric acid level and log urinary albumin:creatinine ratio significantly increased (all P<0·001). Prevalent CKD increased from 5·3 % in the lowest to 9·3 % in the highest E-DII quartile (P=0·02). In multivariable-adjusted logistic regression models, the odds of prevalent CKD were 29 % higher in the highest compared with the lowest E-DII quartile. Pro-inflammatory diet is associated with declining kidney function and high prevalence of CKD. Dietary changes that reduce inflammation have a potential to prevent CKD.

Prolonged prenatal hypoxia selectively disrupts collecting duct patterning and postnatal function in male mouse offspring.

PubMed

Walton, Sarah L; Singh, Reetu R; Little, Melissa H; Bowles, Josephine; Li, Joan; Moritz, Karen M

2018-04-20

In this study we investigated whether hypoxia during late pregnancy impairs kidney development in mouse offspring, and also whether this has long-lasting consequences affecting kidney function in adulthood. Hypoxia disrupted growth of the kidney, particularly the collecting duct network, in juvenile male offspring. By mid-late adulthood, these mice developed early signs of kidney disease, notably a compromised response to water deprivation. Female offspring showed no obvious signs of impaired kidney development and did not develop kidney disease, suggesting a underlying protection mechanism from the hypoxia insult. These results help us better understand the long-lasting impact of gestational hypoxia on kidney development and the increased risk of chronic kidney disease. Prenatal hypoxia is a common perturbation to arise during pregnancy, and can lead to adverse health outcomes in later life. The long-lasting impact of prenatal hypoxia on postnatal kidney development and maturation of the renal tubules, particularly the collecting duct system, is relatively unknown. Here, we used a model of moderate chronic maternal hypoxia throughout late gestation (12% O 2 exposure from E14.5 until birth). Histological analyses revealed marked changes in the tubular architecture of male hypoxia-exposed neonates as early as postnatal day 7, with disrupted medullary development and altered expression of Ctnnb1, and Crabp2 (encoding a retinoic acid binding protein). Kidneys of RARElacZ line offspring exposed to hypoxia showed reduced β-galactosidase activity indicating reduced retinoic acid-directed transcriptional activation. Wildtype male mice exposed to hypoxia had an early decline in urine concentrating capacity, evident at 4 months of age. At 12 months of age, hypoxia-exposed male mice displayed a compromised response to a water deprivation challenge which was was correlated with altered cellular composition of the collecting duct and diminished expression of AQP2. There were no differences in the tubular structures or urine concentrating capacity between the control and hypoxia-exposed female offspring at any age. This study suggests that prenatal hypoxia selectively disrupts collecting duct patterning through altered Wnt/β-catenin and retinoic acid signaling and this results in impaired function in male mouse offspring in later life. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Betaine supplementation mitigates cisplatin-induced nephrotoxicity by abrogation of oxidative/nitrosative stress and suppression of inflammation and apoptosis in rats.

PubMed

Hagar, Hanan; Medany, Azza El; Salam, Reem; Medany, Gamila El; Nayal, Omina A

2015-02-01

Cisplatin is one of the most potent chemotherapeutic antitumor drugs used in the treatment of a wide range of solid tumors. Its primary dose-limiting side effect is nephrotoxicity. This study aims to investigate the effect of betaine supplementation on cisplatin-induced nephrotoxicity. A single intraperitoneal injection of cisplatin (5mg/kg) deteriorated the kidney functions as reflected by elevated blood urea nitrogen and serum creatinine levels. Oxidative/nitrosative stress was evident in cisplatin group by increased renal thiobarbituric acid-reactive substances (TBARS), an indicator of lipid peroxidation, reduced renal total antioxidant status and increased renal nitrite concentration. Cisplatin resulted in a decline in the concentrations of reduced glutathione, glutathione peroxidase, catalase, and superoxide dismutase in renal tissues. Renal tumor necrosis factor-α (TNF-α) was also elevated. Expressions of nuclear factor-kappa B (NF-κB) and caspase-3 were up-regulated in renal tissues as indicated by immunohistochemical analysis. Histopathological changes were observed in cisplatin group. Betaine supplementation (250 mg/kg/day) orally via gavage for 21 days prior to cisplatin injection was able to protect against deterioration in kidney function, abrogate the decline in antioxidants enzymes and suppressed the increase in TBARS, nitrite and TNF-α concentrations. Moreover, betaine inhibited NF-κB and caspase-3 activation and improved the histological changes induced by cisplatin. Thus, the present study demonstrated the renoprotective nature of betaine by attenuating the pro-inflammatory and apoptotic mediators and improving antioxidant competence in kidney tissues of cisplatin treated rats. Betaine could be a beneficial dietary supplement to attenuate cisplatin nephrotoxicity. Copyright © 2014 Elsevier GmbH. All rights reserved.

Predictors of insulin initiation in metformin and sulfonylurea users in primary care practices: the role of kidney function.

PubMed

Kostev, Karel; Dippel, Franz-Werner; Rathmann, Wolfgang

2014-09-01

The aims were to investigate predictors of insulin initiation in new users of metformin or sulfonylureas in primary care practices, in particular, its association with decreased renal function. Data from 9103 new metformin and 1120 sulfonylurea users with normal baseline glomerular filtration rate (eGFR) >90 ml/min/1.73 m(2) from 1072 practices were retrospectively analyzed (Disease Analyzer Germany: 01/2003-06/2012). Cox regression models and propensity score matching was used to adjust for confounders (age, sex, practice characteristics, comorbidity). Insulin treatment was started in 394 (4.3%) metformin and in 162 (14.5%) sulfonylurea users within 6 years (P < .001). Kaplan-Meier curves (propensity score matched patients) showed that the metformin group was at a lower risk of insulin initiation compared to sulfonylurea users throughout the study period. A substantial eGFR decline (category: 15-<30 ml/min/1.73 m(2)) was significantly associated with a higher likelihood to have insulin initiated (adjusted hazard ratio [HR]: 2.39; 95% CI: 1.09-5.23) in metformin but not in sulfonylurea (HR: 0.45; 95% CI: 0.16-1.30) users. New users of sulfonylurea monotherapy in primary care practices in Germany were about 3-fold more likely to start insulin therapy than those with metformin. Kidney function decline was associated with earlier insulin initiation in metformin but not in sulfonylurea users. © 2014 Diabetes Technology Society.

Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey.

PubMed

Coresh, Josef; Astor, Brad C; Greene, Tom; Eknoyan, Garabed; Levey, Andrew S

2003-01-01

Recently developed clinical practice guidelines and calibration of the Third National Health and Nutrition Examination Survey (NHANES III) serum creatinine assay provide a basis for estimating the prevalence and distribution of chronic kidney disease (CKD) in the United States using standardized criteria based on estimated glomerular filtration rate (GFR) and persistent albuminuria. A nationally representative sample of 15,625 noninstitutionalized adults aged 20 years and older from the NHANES III was analyzed. Kidney function (GFR), kidney damage (albuminuria), and stages of CKD (GFR and albuminuria) were estimated from calibrated serum creatinine level, spot urine albumin level, age, sex, and race. GFR was estimated using the simplified Modification of Diet in Renal Disease Study equation and compared with the Cockcroft-Gault equation for creatinine clearance (CCr). The prevalence of CKD in the US adult population was 11% (19.2 million). By stage, an estimated 5.9 million individuals (3.3%) had stage 1 (persistent albuminuria with a normal GFR), 5.3 million (3.0%) had stage 2 (persistent albuminuria with a GFR of 60 to 89 mL/min/1.73 m(2)), 7.6 million (4.3%) had stage 3 (GFR, 30 to 59 mL/min/1.73 m(2)), 400,000 individuals (0.2%) had stage 4 (GFR, 15 to 29 mL/min/1.73 m(2)), and 300,000 individuals (0.2%) had stage 5, or kidney failure. Aside from hypertension and diabetes, age is a key predictor of CKD, and 11% of individuals older than 65 years without hypertension or diabetes had stage 3 or worse CKD. Compared with GFR estimates, CCr estimates showed a steeper decline with age and were lower in non-Hispanic blacks. CKD is common and warrants improved detection and classification using standardized criteria to improve outcomes. Am J Kidney Dis 41:1-12. Copyright 2003 by the National Kidney Foundation, Inc.

An evaluation of longitudinal changes in serum uric acid levels and associated risk of cardio-metabolic events and renal function decline in gout.

PubMed

Desai, Rishi J; Franklin, Jessica M; Spoendlin-Allen, Julia; Solomon, Daniel H; Danaei, Goodarz; Kim, Seoyoung C

2018-01-01

Gout patients have a high burden of co-morbid conditions including diabetes mellitus (DM), chronic kidney disease (CKD), and cardiovascular disease (CVD). We sought to evaluate the association between changes in serum uric acid (SUA) levels over time and the risk of incident DM, CVD, and renal function decline in gout patients. An observational cohort study was conducted among enrollees of private health insurance programs in the US between 2004 and 2015. Gout patients were included on the index date of a SUA measurement ≥6.8 mg/dl. The exposure of interest was cumulative change in SUA levels from baseline. Hazard ratios (HR) and 95% confidence intervals (CI) for incident DM, incident CVD, and renal function decline (≥30% reduction in glomerular filtration rate) were derived using marginal structural models with stabilized inverse probability weights accounting for baseline confounders (age, gender, co-morbidities, co-medications) and time-varying confounders (serum creatinine, blood urea nitrogen, glycated hemoglobin). Among 26,341 patients with gout, the average age was 62, 75% were men, and the median baseline SUA was 8.6 mg/dl (interquartile range 7.7 to 9.5). The incidence rates/100 person-years (95% CI) were 1.63 (1.51-1.75) for DM, 0.77 (0.70-0.84) for CVD, and 4.32 (4.14-4.49) for renal function decline. The adjusted HR (95% CI) per 3 mg/dl reduction in SUA, corresponding on average to achieving the target level of <6 mg/dl in this population, was 1.04 (0.92-1.17) for DM, 1.07 (0.89-1.29) for CVD, and 0.85 (0.78-0.92) for renal function decline. Reduction in SUA in patients with gout may be associated with a reduced risk of renal function decline, but not with DM or CVD.

Living Donor Kidney Transplantation: Overcoming Disparities in Live Kidney Donation in the US—Recommendations from a Consensus Conference

PubMed Central

Rodrigue, James R.; Kazley, Abby Swanson; Mandelbrot, Didier A.; Hays, Rebecca; LaPointe Rudow, Dianne

2015-01-01

Despite its superior outcomes relative to chronic dialysis and deceased donor kidney transplantation, live donor kidney transplantation (LDKT) is less likely to occur in minorities, older adults, and poor patients than in those who are white, younger, and have higher household income. In addition, there is considerable geographic variability in LDKT rates. Concomitantly, in recent years, the rate of living kidney donation (LKD) has stopped increasing and is declining, after decades of consistent growth. Particularly noteworthy is the decline in LKD among black, younger, male, and lower-income adults. The Live Donor Community of Practice within the American Society of Transplantation, with financial support from 10 other organizations, held a Consensus Conference on Best Practices in Live Kidney Donation in June 2014. The purpose of this meeting was to identify LKD best practices and knowledge gaps that might influence LDKT, with a focus on patient and donor education, evaluation efficiencies, disparities, and systemic barriers to LKD. In this article, we discuss trends in LDKT/LKD and emerging novel strategies for attenuating disparities, and we offer specific recommendations for future clinical practice, education, research, and policy from the Consensus Conference Workgroup focused on disparities. PMID:25883072

Urbanization and kidney function decline in low and middle income countries.

PubMed

Jagannathan, Ram; Patzer, Rachel E

2017-08-29

Urbanization is expected to increase in low and middle-income countries (LMICs), and might contribute to the increased disease burden. The association between urbanization and CKD is incompletely understood among LMICs. Recently, Inoue et al., explored the association of urbanization on renal function from the China Health and Nutrition Survey. The study found that individuals living in an urban environment had a higher odds of reduced renal function independent of behavioral and cardiometabolic measures, and this effect increased in a dose dependent manner. In this commentary, we discuss the results of these findings and explain the need for more surveillance studies among LMICs.

Decline in measured glomerular filtration rate is associated with a decrease in endurance, strength, balance and fine motor skills.

PubMed

Hellberg, Matthias; Höglund, Peter; Svensson, Philippa; Abdulahi, Huda; Clyne, Naomi

2017-07-01

Physical performance in chronic kidney disease affects morbidity and mortality. The aim was to find out which measures of physical performance are important in chronic kidney disease (CKD) and if there are associations with declining measured glomerular filtration rate (GFR). Endurance was assessed by 6 min walk test (6-MWT) and stair climbing, muscular endurance by 30 s sit to stand, heel rises and toe lifts, strength by quadriceps- and handgrip-strength, balance by functional reach and Berg's balance scale, and fine motor skills by Moberg's picking-up test. GFR was measured by Iohexol clearance. The study comprised 101 patients with CKD 3b-5 not started dialysis, 40 women and 61 men, with a mean age of 67 ± 13 (range: 22 - 87) years. All measures of physical performance were impaired. A decrease in GFR of 10 mL/min per 1.73 m 2 corresponded to a 35 metre shorter walking distance in the 6-MWT. Multivariable linear regression analysis showed significant relationships between decline in GFR and the 6-MWT (P = 0.04), isometric quadriceps strength left (P = 0.04), balance measured as functional reach (P = 0.02) and fine motor skills in the left hand as measured by Moberg's picking-up test (P = 0.01), respectively, after sex, age, comorbidity and the interaction between sex and age had been taken into account. Endurance, muscular endurance, strength, balance and fine motor skills were impaired in patients with CKD 3b-5. Walking capacity, isometric quadriceps strength, balance, and fine motor skills were associated with declining GFR. The left extremities were more susceptible to GFR, ageing and comorbidities and seem thus to be more sensitive. © 2016 Asian Pacific Society of Nephrology.

Macrophage Phenotype Controls Long-Term AKI Outcomes—Kidney Regeneration versus Atrophy

PubMed Central

Gröbmayr, Regina; Ryu, Mi; Lorenz, Georg; Hartter, Ingo; Mulay, Shrikant R.; Susanti, Heni Eka; Kobayashi, Koichi S.; Flavell, Richard A.; Anders, Hans-Joachim

2014-01-01

The mechanisms that determine full recovery versus subsequent progressive CKD after AKI are largely unknown. Because macrophages regulate inflammation as well as epithelial recovery, we investigated whether macrophage activation influences AKI outcomes. IL-1 receptor–associated kinase-M (IRAK-M) is a macrophage-specific inhibitor of Toll-like receptor (TLR) and IL-1 receptor signaling that prevents polarization toward a proinflammatory phenotype. In postischemic kidneys of wild-type mice, IRAK-M expression increased for 3 weeks after AKI and declined thereafter. However, genetic depletion of IRAK-M did not affect immunopathology and renal dysfunction during early postischemic AKI. Regarding long-term outcomes, wild-type kidneys regenerated completely within 5 weeks after AKI. In contrast, IRAK-M−/− kidneys progressively lost up to two-thirds of their original mass due to tubule loss, leaving atubular glomeruli and interstitial scarring. Moreover, M1 macrophages accumulated in the renal interstitial compartment, coincident with increased expression of proinflammatory cytokines and chemokines. Injection of bacterial CpG DNA induced the same effects in wild-type mice, and TNF-α blockade with etanercept partially prevented renal atrophy in IRAK-M−/− mice. These results suggest that IRAK-M induction during the healing phase of AKI supports the resolution of M1 macrophage– and TNF-α–dependent renal inflammation, allowing structural regeneration and functional recovery of the injured kidney. Conversely, IRAK-M loss-of-function mutations or transient exposure to bacterial DNA may drive persistent inflammatory mononuclear phagocyte infiltrates, which impair kidney regeneration and promote CKD. Overall, these results support a novel role for IRAK-M in the regulation of wound healing and tissue regeneration. PMID:24309188

Inflammation and Atherosclerosis Are Associated With Hypertension in Kidney Transplant Recipients.

PubMed

Azancot, Maria A; Ramos, Natalia; Torres, Irina B; García-Carro, Clara; Romero, Katheryne; Espinel, Eugenia; Moreso, Francesc; Seron, Daniel

2015-12-01

The aim of the current study was to evaluate risk factors associated with hypertension in kidney transplant recipients. The authors recruited 92 consecutive kidney transplant recipients and 30 age-matched patients with chronic kidney disease without history of cardiovascular events. Twenty-four-hour ambulatory blood pressure monitoring, pulse wave velocity, and carotid ultrasound were performed. Serum levels of log-transformed interleukin 6 (Log IL-6), soluble tumor necrosis factor receptor 2, and intercellular adhesion molecule 1 were determined. Twenty-four-hour systolic blood pressure (SBP) (P=.0001), Log IL-6 (P=.011), and total number of carotid plaques (P=.013) were higher, while the percentage decline of SBP from day to night was lower in kidney transplant recipients (P=.003). Independent predictors of 24-hour SBP were urinary protein/creatinine ratio and circulating monocytes (P=.001), while Log IL-6, serum creatinine, and total number of carotid plaques (P=.0001) were independent predictors of percentage decline of SBP from day to night. These results suggest that subclinical atherosclerosis and systemic inflammation are associated with hypertension after transplantation. © 2015 Wiley Periodicals, Inc.

Plasma Biomarkers and Kidney Function Decline in Early and Established Diabetic Kidney Disease.

PubMed

Coca, Steven G; Nadkarni, Girish N; Huang, Yuan; Moledina, Dennis G; Rao, Veena; Zhang, Jane; Ferket, Bart; Crowley, Susan T; Fried, Linda F; Parikh, Chirag R

2017-09-01

Biomarkers of diverse pathophysiologic mechanisms may improve risk stratification for incident or progressive diabetic kidney disease (DKD) in persons with type 2 diabetes. To evaluate such biomarkers, we performed a nested case-control study ( n =190 cases of incident DKD and 190 matched controls) and a prospective cohort study ( n =1156) using banked baseline plasma samples from participants of randomized, controlled trials of early (ACCORD) and advanced (VA NEPHRON-D) DKD. We assessed the association and discrimination obtained with baseline levels of plasma TNF receptor-1 (TNFR-1), TNFR-2, and kidney injury molecule-1 (KIM-1) for the outcomes of incident DKD (ACCORD) and progressive DKD (VA-NEPHRON-D). At baseline, median concentrations of TNFR-1, TNFR-2, and KIM-1 were roughly two-fold higher in the advanced DKD population (NEPHRON-D) than in the early DKD population (ACCORD). In both cohorts, patients who reached the renal outcome had higher baseline levels than those who did not reach the outcome. Associations between doubling in TNFR-1, TNFR-2, and KIM-1 levels and risk of the renal outcomes were significant for both cohorts. Inclusion of these biomarkers in clinical models increased the area under the curve (SEM) for predicting the renal outcome from 0.68 (0.02) to 0.75 (0.02) in NEPHRON-D. Systematic review of the literature illustrated high consistency in the association between these biomarkers of inflammation and renal outcomes in DKD. In conclusion, TNFR-1, TNFR-2, and KIM-1 independently associated with higher risk of eGFR decline in persons with early or advanced DKD. Moreover, addition of these biomarkers to clinical prognostic models significantly improved discrimination for the renal outcome. Copyright © 2017 by the American Society of Nephrology.

Renal function changes after fenestrated endovascular aneurysm repair.

PubMed

Tran, Kenneth; Fajardo, Andres; Ullery, Brant W; Goltz, Christopher; Lee, Jason T

2016-08-01

Limited data exist regarding the effect of fenestrated endovascular aneurysm repair (fEVAR) on renal function. We performed a comprehensive analysis of acute and chronic renal function changes in patients after fEVAR. This study included patients undergoing fEVAR at two institutions between September 2012 and March 2015. Glomerular filtration rate was estimated using the Modification of Diet in Renal Disease formula with serum creatinine levels obtained during the study period. Acute and chronic renal dysfunction was assessed using the RIFLE (Risk, Injury, Failure, Loss, End-stage renal disease) criteria and the chronic kidney disease (CKD) staging system, respectively. fEVAR was performed in 110 patients for juxtarenal or paravisceral aortic aneurysms, with a mean follow-up of 11.7 months. A total of 206 renal stents were placed, with a mean aneurysm size of 62.9 mm (range, 45-105 mm) and a mean neck length of 4.1 mm. Primary renal stent patency was 97.1% at the latest follow-up. Moderate kidney disease (CKD stage ≥ 3) was present in 51% of patients at baseline, with a mean preoperative glomerular filtration rate of 60.0 ± 19.6 mL/min/1.73 m 2 . Acute kidney injury occurred in 25 patients (22.7%), although 15 of these (60%) were classified as having mild dysfunction. During follow-up, 59 patients (73.7%) were found to have no change or improved renal disease by CKD staging, and 19 (23.7%) had a CKD increase of one stage. Two patients were noted to have end-stage renal failure requiring hemodialysis. Clinically significant renal dysfunction was noted in 21 patients (26.2%) at the latest follow-up. Freedom from renal decline at 1 year was 76.1% (95% confidence interval, 63.2%-85.0%). Surrogate markers for higher operative complexity, including operating time (P = .001), fluoroscopy time (P < .001), contrast volume (P = .017), and blood loss (P = .002), served as dependent risk factors for acute kidney injury, although though no independent predictors were identified. Age (P = .008) was an independent risk factor for long-term decline, whereas paradoxically, baseline kidney disease (P = .032) and longer operative times (P = .014) were protective of future renal dysfunction. Acute and chronic renal dysfunction both occur in approximately one-quarter of patients after fEVAR; however, most of these cases are classified as mild according to consensus definitions of renal injury. The presence of mild or moderate baseline kidney disease should not preclude endovascular repair in the juxtarenal population. Routine biochemical analysis and branch vessel surveillance remain important aspects of clinical follow-up for patients undergoing fEVAR. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Heart failure and kidney dysfunction: epidemiology, mechanisms and management.

PubMed

Schefold, Joerg C; Filippatos, Gerasimos; Hasenfuss, Gerd; Anker, Stefan D; von Haehling, Stephan

2016-10-01

Heart failure (HF) is a major health-care problem and the prognosis of affected patients is poor. HF often coexists with a number of comorbidities of which declining renal function is of particular importance. A loss of glomerular filtration rate, as in acute kidney injury (AKI) or chronic kidney disease (CKD), independently predicts mortality and accelerates the overall progression of cardiovascular disease and HF. Importantly, cardiac and renal diseases interact in a complex bidirectional and interdependent manner in both acute and chronic settings. From a pathophysiological perspective, cardiac and renal diseases share a number of common pathways, including inflammatory and direct, cellular immune-mediated mechanisms; stress-mediated and (neuro)hormonal responses; metabolic and nutritional changes including bone and mineral disorder, altered haemodynamic and acid-base or fluid status; and the development of anaemia. In an effort to better understand the important crosstalk between the two organs, classifications such as the cardio-renal syndromes were developed. This classification might lead to a more precise understanding of the complex interdependent pathophysiology of cardiac and renal diseases. In light of exceptionally high mortality associated with coexisting HF and kidney disease, this Review describes important crosstalk between the heart and kidney, with a focus on HF and kidney disease in the acute and chronic settings. Underlying molecular and cellular pathomechanisms in HF, AKI and CKD are discussed in addition to current and future therapeutic approaches.

Tissue distribution of selenium and effect of season and age on selenium content in roe deer from northwestern Poland.

PubMed

Pilarczyk, Bogumiła; Tomza-Marciniak, Agnieszka; Pilarczyk, Renata; Hendzel, Diana; Błaszczyk, Barbara; Bąkowska, Małgorzata

2011-06-01

The aim of the study was to compare selenium concentrations in different organs of roe deer from northwestern Poland. Samples of liver, kidneys, heart and lungs, collected from 74 roe deer shot during the hunting seasons of 2008-2009 in northwestern Poland, were studied. Selenium concentration in the organs was determined spectrofluorimetrically. Mean selenium concentration was 0.06 µg/g w.w. in the liver, 0.41 µg/g w.w. in the kidneys and 0.05 µg/g w.w. in the heart and lungs. Season had a significant effect on selenium concentration in the liver, kidneys, lungs and heart. In all the organs, the highest selenium concentration was found in spring and the lowest in autumn and winter. All animals studied were deficient in selenium. The low selenium concentration in the liver or heart can disturb their function, and in the future, it may be a factor contributing to the population decline of roe deer in the northwestern part of Poland.

Management of diabetes mellitus in individuals with chronic kidney disease: therapeutic perspectives and glycemic control

PubMed Central

Betônico, Carolina C R; Titan, Silvia M O; Correa-Giannella, Maria Lúcia C; Nery, Márcia; Queiroz, Márcia

2016-01-01

The purpose of this study was to evaluate the therapeutic options for diabetes treatment and their potential side effects, in addition to analyzing the risks and benefits of tight glycemic control in patients with diabetic kidney disease. For this review, a search was performed using several pre-defined keyword combinations and their equivalents: “diabetes kidney disease” and “renal failure” in combination with “diabetes treatment” and “oral antidiabetic drugs” or “oral hypoglycemic agents.” The search was performed in PubMed, Endocrine Abstracts and the Cochrane Library from January 1980 up to January 2015. Diabetes treatment in patients with diabetic kidney disease is challenging, in part because of progression of renal failure-related changes in insulin signaling, glucose transport and metabolism, favoring both hyperglycemic peaks and hypoglycemia. Additionally, the decline in renal function impairs the clearance and metabolism of antidiabetic agents and insulin, frequently requiring reassessment of prescriptions. The management of hyperglycemia in patients with diabetic kidney disease is even more difficult, requiring adjustment of antidiabetic agents and insulin doses. The health team responsible for the follow-up of these patients should be vigilant and prepared to make such changes; however, unfortunately, there are few guidelines addressing the nuances of the management of this specific population. PMID:26872083

The effects of environmental chemicals on renal function.

PubMed

Kataria, Anglina; Trasande, Leonardo; Trachtman, Howard

2015-10-01

The global incidence of chronic kidney disease (CKD) is increasing among individuals of all ages. Despite advances in proteomics, genomics and metabolomics, there remains a lack of safe and effective drugs to reverse or stabilize renal function in patients with glomerular or tubulointerstitial causes of CKD. Consequently, modifiable risk factors that are associated with a progressive decline in kidney function need to be identified. Numerous reports have documented the adverse effects that occur in response to graded exposure to a wide range of environmental chemicals. This Review summarizes the effects of such chemicals on four aspects of cardiorenal function: albuminuria, glomerular filtration rate, blood pressure and serum uric acid concentration. We focus on compounds that individuals are likely to be exposed to as a consequence of normal consumer activities or medical treatment, namely phthalates, bisphenol A, polyfluorinated alkyl acids, dioxins and furans, polycyclic aromatic hydrocarbons and polychlorinated biphenyls. Environmental exposure to these chemicals during everyday life could have adverse consequences on renal function and might contribute to progressive cumulative renal injury over a lifetime. Regulatory efforts should be made to limit individual exposure to environmental chemicals in an attempt to reduce the incidence of cardiorenal disease.

The effects of environmental chemicals on renal function

PubMed Central

Kataria, Anglina; Trasande, Leonardo; Trachtman, Howard

2015-01-01

The global incidence of chronic kidney disease (CKD) is increasing among individuals of all ages. Despite advances in proteomics, genomics and metabolomics, there remains a lack of safe and effective drugs to reverse or stabilize renal function in patients with glomerular or tubulointerstitial causes of CKD. Consequently, modifiable risk factors that are associated with a progressive decline in kidney function need to be identified. Numerous reports have documented the adverse effects that occur in response to graded exposure to a wide range of environmental chemicals. This Review summarizes the effects of such chemicals on four aspects of cardiorenal function: albuminuria, glomerular filtration rate, blood pressure and serum uric acid concentration. We focus on compounds that individuals are likely to be exposed to as a consequence of normal consumer activities or medical treatment, namely phthalates, bisphenol A, polyfluorinated alkyl acids, dioxins and furans, polycyclic aromatic hydrocarbons and polychlorinated biphenyls. Environmental exposure to these chemicals during everyday life could have adverse consequences on renal function and might contribute to progressive cumulative renal injury over a lifetime. Regulatory efforts should be made to limit individual exposure to environmental chemicals in an attempt to reduce the incidence of cardiorenal disease. PMID:26100504

Progenitor-like cells derived from mouse kidney protect against renal fibrosis in a remnant kidney model via decreased endothelial mesenchymal transition.

PubMed

Chen, C L; Chou, K J; Fang, H C; Hsu, C Y; Huang, W C; Huang, C W; Huang, C K; Chen, H Y; Lee, P T

2015-12-02

Pathophysiological changes associated with chronic kidney disease impair angiogenic processes and increase renal fibrosis. Progenitor-like cells derived from adult kidney have been previously used to promote regeneration in acute kidney injury, even though it remained unclear whether the cells could be beneficial in chronic kidney disease (CKD). In this study, we established a CKD model by five-sixths nephrectomy and mouse kidney progenitor-like cells (MKPCs) were intravenously administered weekly for 5 weeks after establishing CKD. We examined the impact of MKPCs on the progression of renal fibrosis and the potential of MKPCs to preserve the angiogenic process and prevent endothelial mesenchymal transition in vivo and in vitro. Our results demonstrate that the MKPCs delayed interstitial fibrosis and the progression of glomerular sclerosis and ameliorated the decline of kidney function. At 17 weeks, the treated mice exhibited lower blood pressures, higher hematocrit levels, and larger kidney sizes than the control mice. In addition, the MKPC treatment prolonged the survival of the mice with chronic kidney injuries. We observed a decreased recruitment of macrophages and myofibroblasts in the interstitium and the increased tubular proliferation. Notably, MKPC both decreased the level of vascular rarefaction and prevented endothelial mesenchymal transition (EndoMT) in the remnant kidneys. Moreover, the conditioned medium from the MKPCs ameliorated endothelial cell death under hypoxic culture conditions and prevented TGF-β-induced EndoMT through downregulation of phosphorylated Smad 3 in vitro. MKPCs may be a beneficial treatment for kidney diseases characterized by progressive renal fibrosis. The enhanced preservation of angiogenic processes following MKPC injections may be associated with decreased fibrosis in the remnant kidney. These findings provide further understanding of the mechanisms involved in these processes and will help develop new cell-based therapeutic strategies for regenerative medicine in renal fibrosis.

Extreme hydronephrosis due to uretropelvic junction obstruction in infant (case report).

PubMed

Krzemień, Grażyna; Szmigielska, Agnieszka; Bombiński, Przemysław; Barczuk, Marzena; Biejat, Agnieszka; Warchoł, Stanisław; Dudek-Warchoł, Teresa

2016-01-01

Hydronephrosis is the one of the most common congenital abnormalities of urinary tract. The left kidney is more commonly affected than the right side and is more common in males. To determine the role of ultrasonography, renal dynamic scintigraphy and lowerdose computed tomography urography in preoperative diagnostic workup of infant with extreme hydronephrosis. We presented the boy with antenatally diagnosed hydronephrosis. In serial, postnatal ultrasonography, renal scintigraphy and computed tomography urography we observed slightly declining function in the dilated kidney and increasing pelvic dilatation. Pyeloplasty was performed at the age of four months with good result. Results of ultrasonography and renal dynamic scintigraphy in child with extreme hydronephrosis can be difficult to asses, therefore before the surgical procedure a lower-dose computed tomography urography should be performed.

Renal control of calcium, phosphate, and magnesium homeostasis.

PubMed

Blaine, Judith; Chonchol, Michel; Levi, Moshe

2015-07-07

Calcium, phosphate, and magnesium are multivalent cations that are important for many biologic and cellular functions. The kidneys play a central role in the homeostasis of these ions. Gastrointestinal absorption is balanced by renal excretion. When body stores of these ions decline significantly, gastrointestinal absorption, bone resorption, and renal tubular reabsorption increase to normalize their levels. Renal regulation of these ions occurs through glomerular filtration and tubular reabsorption and/or secretion and is therefore an important determinant of plasma ion concentration. Under physiologic conditions, the whole body balance of calcium, phosphate, and magnesium is maintained by fine adjustments of urinary excretion to equal the net intake. This review discusses how calcium, phosphate, and magnesium are handled by the kidneys. Copyright © 2015 by the American Society of Nephrology.

Copeptin Plasma Levels are Associated With Decline of Renal Function in Patients With Type 2 Diabetes Mellitus.

PubMed

Villela-Torres, Maria De La Luz; Higareda-Mendoza, Ana Edith; Gómez-García, Anel; Alvarez-Paredes, Alfonso Rafael; García-López, Elvia; Stenvikel, Peter; Gu, Harvest F; Rashid-Qureshi, Abbul; Lindholm, Bengt; Alvarez-Aguilar, Cleto

2018-04-14

Chronic kidney disease (CKD) is a leading complication of type 2 diabetes mellitus (T2DM) and is considered as a public health problem. Copeptin is a surrogate marker of arginine vasopressin (AVP) system and is proposed as a biomarker of decline renal function. Evaluate whether plasma copeptin levels may be used as a biomarker of decline renal function in patients with T2DM. A total of 480 patients with T2DM and different stages of CKD were included. Plasma levels of copeptin, cystatin-C, and other biochemical parameters were measured. The correlation between copeptin and glomerular filtration rate (GFR), estimated based on plasma cystatin-C levels, was investigated. Plasma copeptin levels were gradually increased from the stage 1-5 of CKD in the patients with T2DM. In univariate linear regression analysis, high plasma levels of copeptin were associated with lower GFR (Standardized β = -0.535, R 2  = 0.287, p <0.0001). This association remained significant even after being adjusted for glucose levels and years of T2DM diagnosis, mean blood pressure, pharmacological treatment, gender, and age. The results show that high plasma copeptin levels are associated with the decline of renal function in patients with T2DM and, therefore, copeptin may be considered as a biomarker of renal function. Further evaluation of plasma copeptin levels to predict morbidity and mortality of T2DM patients, with or without CKD, has been taken into our consideration. Copyright © 2018. Published by Elsevier Inc.

Renal function following xenon anesthesia for partial nephrectomy-An explorative analysis of a randomized controlled study.

PubMed

Stevanovic, Ana; Schaefer, Patrick; Coburn, Mark; Rossaint, Rolf; Stoppe, Christian; Boor, Peter; Pfister, David; Heidenreich, Axel; Christ, Hildegard; Hellmich, Martin; Fahlenkamp, Astrid V

2017-01-01

Perioperative preservation of renal function has a significant impact on morbidity and mortality in kidney surgery. Nephroprotective effects of the anesthetic xenon on ischemia-reperfusion injury were found in several experimental studies. We aimed to explore whether xenon anesthesia can reduce renal damage in humans undergoing partial nephrectomy and to gather pilot data of possible nephroprotection in these patients. A prospective randomized, single-blinded, controlled study. Single-center, University Hospital of Aachen, Germany between July 2013-October 2015. Forty-six patients with regular renal function undergoing partial nephrectomy. Patients were randomly assigned to receive xenon- (n = 23) or isoflurane (n = 23) anesthesia. Primary outcome was the maximum postoperative glomerular filtration rate (GFR) decline within seven days after surgery. Secondary outcomes included intraoperative and tumor-related data, assessment of further kidney injury markers, adverse events and optional determination of renal function after 3-6 months. Unexpected radical nephrectomy was performed in 5 patients, thus they were excluded from the per-protocol analysis, but included in the intention-to-treat analysis. The maximum postoperative GFR decline was attenuated by 45% in the xenon-group (10.9 ml min-1 1.73 cm-2 versus 19.7 ml min-1 1.73 cm-2 in the isoflurane group), but without significance (P = 0.084). Occurrence of adverse events was reduced (P = 0.003) in the xenon group. Renal function was similar among the groups after 3-6 months. Xenon anesthesia was feasible and safe in patients undergoing partial nephrectomy with regard to postoperative renal function. We found no significant effect on early renal function but less adverse events in the xenon group. Larger randomized controlled studies in more heterogeneous collectives are required, to confirm or refute the possible clinical benefit on renal function by xenon. ClinicalTrials.gov NCT01839084 and EudraCT 2012-005698-30.

Incidence of end-stage renal disease attributed to diabetes among persons with diagnosed diabetes --- United States and Puerto Rico, 1996-2007.

PubMed

2010-10-29

During 2007, approximately 110,000 persons in the United States and Puerto Rico began treatment for end-stage renal disease (ESRD) (i.e., kidney failure requiring dialysis or transplantation). Diabetes is the leading cause of ESRD in the United States, accounting for 44% of new cases in 2007. Although the number of persons initiating treatment for kidney failure each year who have diabetes listed as a primary cause (ESRD-D) has increased since 1996, ESRD-D incidence among persons with diagnosed diabetes has declined since 1996. To determine whether this decline occurred in every U.S. region and in every state, CDC analyzed 1996-2007 data from the U.S. Renal Data System (USRDS) and the Behavioral Risk Factor Surveillance System (BRFSS). During the period, the age-adjusted rate of ESRD-D among persons with diagnosed diabetes declined 35% overall, from 304.5 to 199.1 per 100,000 persons with diagnosed diabetes, and declined in all U.S. regions and in most states. No state showed a significant increase in the age-adjusted ESRD-D rate. Continued awareness of risk factors for kidney failure and interventions to improve diabetes care are needed to sustain and improve these trends.

The effect of the Syrian crisis on organ transplantation in Syria.

PubMed

Saeed, Bassam

2015-04-01

The war in Syria that started in March 2011 has destroyed much of the country's infrastructure including many hospitals. The total number of kidney transplants performed in Syria in 2010 was 385 transplants before the number gradually declined to 154 transplants in 2013, a decrease of 60%. In addition, the number of operational kidney transplant centers has decreased from 8 to 4 centers. Unrelated-donor kidney transplant decreased from 70% during the years that preceded the crisis to 47% in 2013. More than 50% of physicians and surgeons involved in kidney transplant are not practicing transplant currently in their centers. Difficulties in the provision of immunosuppressive drugs for all patients in all provinces constitute a major challenge for the health authorities and transplant patients, especially patients who cannot arrange an alternate source. The project to initiate liver transplant came to a halt because foreign trainers could not visit Syria. The autologous bone marrow transplant program continued to function, but in a smaller and irregular manner. The commitment of transplant teams despite the large challenges was, and still is, extraordinary. In conclusion, all aspects of organ transplant have been affected, paralyzing new projects and negatively affecting existing programs.

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

Is biological aging accelerated in drug addiction?

PubMed

Bachi, Keren; Sierra, Salvador; Volkow, Nora D; Goldstein, Rita Z; Alia-Klein, Nelly

2017-02-01

Drug-addiction may trigger early onset of age-related disease, due to drug-induced multi-system toxicity and perilous lifestyle, which remains mostly undetected and untreated. We present the literature on pathophysiological processes that may hasten aging and its relevance to addiction, including: oxidative stress and cellular aging, inflammation in periphery and brain, decline in brain volume and function, and early onset of cardiac, cerebrovascular, kidney, and liver disease. Timely detection of accelerated aging in addiction is crucial for the prevention of premature morbidity and mortality.

The Kidney Disease Screening and Awareness Program (KDSAP): A Novel Translatable Model for Increasing Interest in Nephrology Careers

PubMed Central

Wu, Jingshing; Yeh, Albert C.; Shieh, Eric C.; Cui, Cheryl; Polding, Laura C.; Ahmed, Rayhnuma; Lim, Kenneth; Lu, Tzong-Shi; Rhee, Connie M.; Bonventre, Joseph V.

2014-01-01

Despite the increasing prevalence of CKD in the United States, there is a declining interest among United States medical graduates in nephrology as a career choice. Effective programs are needed to generate interest at early educational stages when career choices can be influenced. The Kidney Disease Screening and Awareness Program (KDSAP) is a novel program initiated at Harvard College that increases student knowledge of and interest in kidney health and disease, interest in nephrology career paths, and participation in kidney disease research. This model, built on physician mentoring, kidney screening of underserved populations, direct interactions with kidney patients, and opportunities to participate in kidney research, can be reproduced and translated to other workforce-challenged subspecialties. PMID:24876120

Microvascular disease precedes the decline in renal function in the streptozotocin-induced diabetic rat

PubMed Central

Maric-Bilkan, Christine; Flynn, Elizabeth R.

2012-01-01

Diabetic nephropathy is a progressive and generalized vasculopathic condition associated with abnormal angiogenesis. We aim to determine whether changes in renal microvascular (MV) density correlate with and play a role in the progressive deterioration of renal function in diabetes. We hypothesize that MV changes represent the early steps of renal injury that worsen as diabetes progresses, initiating a vicious circle that leads to irreversible renal injury. Male nondiabetic (ND) or streptozotocin-induced diabetic (D) Sprague-Dawley rats were followed for 4 or 12 wk. Renal blood flow and glomerular filtration rate (GFR) were measured by PAH and 125I-[iothalamate], respectively. Renal MV density was quantified ex vivo using three-dimensional micro computed tomography and JG-12 immunoreactivity. Vascular endothelial growth factor (VEGF) levels (ELISA) and expression of VEGF receptors and factors involved in MV remodeling were quantified in renal tissue by Western blotting. Finally, renal morphology was investigated by histology. Four weeks of diabetes was associated with increased GFR, accompanied by a 34% reduction in renal MV density and augmented renal VEGF levels. However, at 12 wk, while GFR remained similarly elevated, reduction of MV density was more pronounced (75%) and associated with increased MV remodeling, renal fibrosis, but unchanged renal VEGF compared with ND at 12 wk. The damage, loss, and subsequent remodeling of the renal MV architecture in the diabetic kidney may represent the initiating events of progressive renal injury. This study suggests a novel concept of MV disease as an early instigator of diabetic kidney disease that may precede and likely promote the decline in renal function. PMID:22031855

Effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular disease, death and safety outcomes in type 2 diabetes - A systematic review.

PubMed

Rådholm, Karin; Wu, Jason Hy; Wong, Muh Geot; Foote, Celine; Fulcher, Gregory; Mahaffey, Kenneth W; Perkovic, Vlado; Neal, Bruce

2018-06-01

Sodium glucose co-transporter 2 (SGLT2) inhibitors appear to protect against increased risks of cardiovascular and kidney disease in patients with type 2 diabetes but also cause some harms. Whether effects are comparable across drug class or specific to individual compounds is unclear. This meta-analysis assessed the class and individual compound effects of SGLT2 inhibition versus control on cardiovascular events, death, kidney disease and safety outcomes in patients with type 2 diabetes. MEDLINE, EMBASE, the Cochrane Library and regulatory databases were systematically searched for data from randomized clinical trials that included reporting of cardiovascular events, deaths or safety outcomes. We used fixed effects models and inverse variance weighting to calculate relative risks with the 95% confidence intervals. The analyses included data from 82 trials, four overviews and six regulatory reports and there were 1,968 major cardiovascular events identified for analysis. Patients randomly assigned to SGLT2 had lower risks of major cardiovascular events (RR 0.85, 95%CI 0.77-0.93), heart failure (RR 0.67, 95%CI 0.55-0.80), all-cause death (RR 0.79, 95%CI 0.70-0.88) and serious decline in kidney function (RR 0.59, 0.49-0.71). Significant adverse effects were observed for genital infections (RR 3.06, 95%CI 2.73-4.43), volume depletion events (RR 1.24, 95%CI 1.07-1.43) and amputation (RR 1.44 95%CI 1.13-1.83). There was a high likelihood of differences in the associations of the individual compounds with cardiovascular death, hypoglycaemia and amputation (all I 2  > 80%) and a moderate likelihood of differences in the associations with non-fatal stroke, all-cause death, urinary tract infection and fracture (all I 2  > 30%). There are strong overall associations of SGLT2 inhibition with protection against major cardiovascular events, heart failure, serious decline in kidney function and all-cause death. SGLT2 inhibitors were also associated with infections, volume depletion effects and amputation. Some associations appear to differ between compounds. Copyright © 2018 Elsevier B.V. All rights reserved.

Characterization of kidney CD45intCD11bintF4/80+MHCII+CX3CR1+Ly6C- "intermediate mononuclear phagocytic cells".

PubMed

Lee, Sul A; Noel, Sanjeev; Sadasivam, Mohanraj; Allaf, Mohamad E; Pierorazio, Phillip M; Hamad, Abdel R A; Rabb, Hamid

2018-01-01

Kidney immune cells play important roles in pathogenesis of many diseases, including ischemia-reperfusion injury (IRI) and transplant rejection. While studying murine kidney T cells, we serendipitously identified a kidney mononuclear phagocytic cell (MPC) subset characterized by intermediate surface expression of CD45 and CD11b. These CD45intCD11bint MPCs were further identified as F4/80+MHCII+CX3CR1+Ly6C- cells, comprising ~17% of total CD45+ cells in normal mouse kidney (P < 0.01) and virtually absent from all other organs examined except the heart. Systemic clodronate treatment had more significant depletive effect on the CD45intCD11bint population (77.3%±5.9%, P = 0.03) than on CD45highCD11b+ population (14.8%±16.6%, P = 0.49). In addition, CD45intCD11bint MPCs had higher phagocytic function in the normal kidney (35.6%±3.3% vs. 24.1%±2.2%, P = 0.04), but lower phagocytic capacity in post-ischemic kidney (54.9%±1.0% vs. 67.8%±1.9%, P < 0.01) compared to the CD45highCD11b+ population. Moreover, the CD45intCD11bint population had higher intracellular production of the pro-inflammatory tumor necrosis factor (TNF)-α (58.4%±5.2% vs. 27.3%±0.9%, P < 0.001) after lipopolysaccharide (LPS) stimulation and lower production of the anti-inflammatory interleukin (IL)-10 (7.2%±1.3% vs. 14.9%±2.2%, P = 0.02) following kidney IRI, suggesting a functional role under inflammatory conditions. The CD45intCD11bint cells increased early after IRI, and then abruptly decreased 48h later, whereas CD45highCD11b+ cells steadily increased after IRI before declining at 72h (P = 0.03). We also identified the CD45intCD11bint MPC subtype in human kidney. We conclude that CD45intCD11bint F4/80+MHCII+CX3CR1+Ly6C-population represent a unique subset of MPCs found in both mouse and human kidneys. Future studies will further characterize their role in kidney health and disease.

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.

Renal arterial resistive index is associated with severe histological changes and poor renal outcome during chronic kidney disease

PubMed Central

2012-01-01

Background Chronic kidney disease (CKD) is a growing public health problem and end stage renal disease (ESRD) represents a large human and economic burden. It is important to identify patients at high risk of ESRD. In order to determine whether renal Doppler resistive index (RI) may discriminate those patients, we analyzed whether RI was associated with identified prognosis factors of CKD, in particular histological findings, and with renal outcome. Methods RI was measured in the 48 hours before renal biopsy in 58 CKD patients. Clinical and biological data were collected prospectively at inclusion. Arteriosclerosis, interstitial fibrosis and glomerulosclerosis were quantitatively assessed on renal biopsy in a blinded fashion. MDRD eGFR at 18 months was collected for 35 (60%) patients. Renal function decline was defined as a decrease in eGFR from baseline of at least 5 mL/min/ 1.73 m2/year or need for chronic renal replacement therapy. Pearson’s correlation, Mann–Whitney and Chi-square tests were used for analysis of quantitative and qualitative variables respectively. Kaplan Meier analysis was realized to determine renal survival according to RI value using the log-rank test. Multiple logistic regression was performed including variables with p < 0.20 in univariate analysis. Results Most patients had glomerulonephritis (82%). Median age was 46 years [21–87], eGFR 59 mL/min/ 1.73m2 [5–130], percentage of interstitial fibrosis 10% [0–90], glomerulosclerosis 13% [0–96] and RI 0.63 [0.31-1.00]. RI increased with age (r = 0.435, p = 0.0063), pulse pressure (r = 0.303, p = 0.022), renal atrophy (r = −0.275, p = 0.038) and renal dysfunction (r = −0.402, p = 0.0018). Patients with arterial intima/media ratio ≥ 1 (p = 0.032), interstitial fibrosis > 20% (p = 0.014) and renal function decline (p = 0.0023) had higher RI. Patients with baseline RI ≥ 0.65 had a poorer renal outcome than those with baseline RI < 0.65 (p = 0.0005). In multiple logistic regression, RI≥0.65 was associated with accelerated renal function decline independently of baseline eGFR and proteinuria/creatininuria ratio (OR=13.04 [1.984-85.727], p = 0.0075). Sensitivity, specificity, predictive positive and predictive negative values of RI ≥ 0.65 for renal function decline at 18 months were respectively 77%, 86%, 71% and 82%. Conclusions Our results suggest that RI ≥ 0.65 is associated with severe interstitial fibrosis and arteriosclerosis and renal function decline. Thus, RI may contribute to identify patients at high risk of ESRD who may benefit from nephroprotective treatments. PMID:23098365

Dietary salt restriction is beneficial to the management of autosomal dominant polycystic kidney disease.

PubMed

Torres, Vicente E; Abebe, Kaleab Z; Schrier, Robert W; Perrone, Ronald D; Chapman, Arlene B; Yu, Alan S; Braun, William E; Steinman, Theodore I; Brosnahan, Godela; Hogan, Marie C; Rahbari, Frederic F; Grantham, Jared J; Bae, Kyongtae T; Moore, Charity G; Flessner, Michael F

2017-02-01

The CRISP study of polycystic kidney disease (PKD) found that urinary sodium excretion associated with the rate of total kidney volume increase. Whether sodium restriction slows the progression of Autosomal Dominant PKD (ADPKD) is not known. To evaluate this we conducted a post hoc analysis of the HALT-PKD clinical trials of renin-angiotensin blockade in patients with ADPKD. Linear mixed models examined whether dietary sodium affected rates of total kidney volume or change in estimated glomerular filtration rate (eGFR) in patients with an eGFR over 60 ml/min/1.73 m 2 (Study A) or the risk for a composite endpoint of 50% reduction in eGFR, end-stage renal disease or death, or the rate of eGFR decline in patients with an eGFR 25-60 ml/min/1.73 m 2 (Study B) all in patients initiated on an under100 mEq sodium diet. During the trial urinary sodium excretion significantly declined by an average of 0.25 and 0.41 mEq/24 hour per month in studies A and B, respectively. In Study A, averaged and time varying urinary sodium excretions were significantly associated with kidney growth (0.43%/year and 0.09%/year, respectively, for each 18 mEq urinary sodium excretion). Averaged urinary sodium excretion was not significantly associated with faster eGFR decline (-0.07 ml/min/1.73m 2 /year for each 18 mEq urinary sodium excretion). In Study B, the averaged but not time-varying urinary sodium excretion significantly associated with increased risk for the composite endpoint (hazard ratio 1.08 for each 18 mEq urinary sodium excretion) and a significantly faster eGFR decline (-0.09 ml/min/1.73m 2 /year for each mEq 18 mEq urinary sodium excretion). Thus, sodium restriction is beneficial in the management of ADPKD. Copyright © 2016 International Society of Nephrology. All rights reserved.

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

Dubovsky, E.V.; Curtis, J.J.; Luke, R.G.

Impaired function of renal allografts caused by recurrent disease or rejection is often accompanied by hypertension. The etiology of persistent severe hypertension in recipients with good renal function is more difficult to explain. To study this problem, 33 patients with mean arterial pressure (MAP) > 105 mm Hg (at least one year after transplantation) were tested. When compared to a normotensive group, they were found to have increased renal vascular resistance, lower ERPF, and increased renin-angiotensin activity. The effect of Captopril, a converting enzyme inhibitor, was studied to evaluate the role of angiotension. The paper concludes that Captopril test maymore » permit differentiation between native kidney-dependent hypertension (increase in ERPF) and functionally active renal artery stenosis (decline in ERPF) in patients with persistent hypertension and good renal function.« less

Galectin-9 ameliorates anti-GBM glomerulonephritis by inhibiting Th1 and Th17 immune responses in mice.

PubMed

Zhang, Qian; Luan, Hong; Wang, Le; He, Fan; Zhou, Huan; Xu, Xiaoli; Li, Xingai; Xu, Qing; Niki, Toshiro; Hirashima, Mitsuomi; Xu, Gang; Lv, Yongman; Yuan, Jin

2014-04-15

Antiglomerular basement membrane glomerulonephritis (anti-GBM GN) is a Th1- and Th17-predominant autoimmune disease. Galectin-9 (Gal-9), identified as the ligand of Tim-3, functions in diverse biological processes and leads to the apoptosis of CD4(+)Tim-3(+) T cells. It is still unclear how Gal-9 regulates the functions of Th1 and Th17 cells and prevents renal injury in anti-GBM GN. In this study, Gal-9 was administered to anti-GBM GN mice for 7 days. We found that Gal-9 retarded the increase of Scr, ameliorated renal tubular injury, and reduced the formation of crescents. The infiltration of Th1 and Th17 cells into the spleen and kidneys significantly decreased in Gal-9-treated nephritic mice. The reduced infiltration of Th1 and Th17 cells might be associated with the downregulation of CCL-20, CXCL-9, and CXCL-10 mRNAs in the kidney. In parallel, the blood levels of IFN-γ and IL-17A declined in Gal-9-treated nephritic mice at days 21 and 28. In addition, an enhanced Th2 cell-mediated immune response was observed in the kidneys of nephritic mice after a 7-day injection of Gal-9. In conclusion, the protective role of Gal-9 in anti-GBM GN is associated with the inhibition of Th1 and Th17 cell-mediated immune responses and enhanced Th2 immunity in the kidney.

Hyperpolarized 13 C,15 N2 -Urea MRI for assessment of the urea gradient in the porcine kidney.

PubMed

Hansen, Esben S S; Stewart, Neil J; Wild, Jim M; Stødkilde-Jørgensen, Hans; Laustsen, Christoffer

2016-12-01

A decline in cortico-medullary osmolality gradient of the kidney may serve as an early indicator of pathological disruption of the tubular reabsorption process. The purpose of this study was to investigate the feasibility of hyperpolarized 13 C, 15 N 2 -urea MRI as a biomarker of renal function in healthy porcine kidneys resembling the human physiology. Five healthy female Danish domestic pigs (weight 30 kg) were scanned at 3 Tesla (T) using a 13 C 3D balanced steady-state MR pulse sequence following injection of hyperpolarized 13 C, 15 N 2 -urea via a femoral vein catheter. Images were acquired at different time points after urea injection, and following treatment with furosemide. A gradient in cortico-medullary urea was observed with an intramedullary accumulation 75 s after injection of hyperpolarized 13 C, 15 N 2 -urea, whereas images acquired at earlier time points postinjection were dominated by cortical perfusion. Furosemide treatment resulted in an increased urea accumulation in the cortical space, leading to a reduction of the medullary-to-cortical signal ratio of 49%. This study demonstrates that hyperpolarized 13 C, 15 N 2 -urea MRI is capable of identifying the intrarenal accumulation of urea and can differentiate acute renal functional states in multipapillary kidneys, highlighting the potential for human translation. Magn Reson Med 76:1895-1899, 2016. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Exercise training normalizes renal blood flow responses to acute hypoxia in experimental heart failure: role of the α1-adrenergic receptor.

PubMed

Pügge, Carolin; Mediratta, Jai; Marcus, Noah J; Schultz, Harold D; Schiller, Alicia M; Zucker, Irving H

2016-02-01

Recent data suggest that exercise training (ExT) is beneficial in chronic heart failure (CHF) because it improves autonomic and peripheral vascular function. In this study, we hypothesized that ExT in the CHF state ameliorates the renal vasoconstrictor responses to hypoxia and that this beneficial effect is mediated by changes in α1-adrenergic receptor activation. CHF was induced in rabbits. Renal blood flow (RBF) and renal vascular conductance (RVC) responses to 6 min of 5% isocapnic hypoxia were assessed in the conscious state in sedentary (SED) and ExT rabbits with CHF with and without α1-adrenergic blockade. α1-adrenergic receptor expression in the kidney cortex was also evaluated. A significant decline in baseline RBF and RVC and an exaggerated renal vasoconstriction during acute hypoxia occurred in CHF-SED rabbits compared with the prepaced state (P < 0.05). ExT diminished the decline in baseline RBF and RVC and restored changes during hypoxia to those of the prepaced state. α1-adrenergic blockade partially prevented the decline in RBF and RVC in CHF-SED rabbits and eliminated the differences in hypoxia responses between SED and ExT animals. Unilateral renal denervation (DnX) blocked the hypoxia-induced renal vasoconstriction in CHF-SED rabbits. α1-adrenergic protein in the renal cortex of animals with CHF was increased in SED animals and normalized after ExT. These data provide evidence that the acute decline in RBF during hypoxia is caused entirely by the renal nerves but is only partially mediated by α1-adrenergic receptors. Nonetheless, α1-adrenergic receptors play an important role in the beneficial effects of ExT in the kidney. Copyright © 2016 the American Physiological Society.

Corticosteroid for IgA Nephropathy: Are They Really Therapeutic?

PubMed

Lin, Yujia; Jia, Junya; Guo, Yipeng; He, Dandan; Zhang, Yaru; Wang, Fuzhen; Yan, Tiekun; Liu, Youxia; Lin, Shan

2018-06-06

IgA nephropathy (IgAN) is a common chronic glomerular disease that, in most patients, slowly progresses to end-stage kidney disease. The therapy with corticosteroid in IgAN is still a worldwide problem that is confusing the clinicians. MEDLINE, EMBASE, the Cochrane Library, and article reference lists were searched for randomized controlled trials (RCTs) that compared corticosteroids with placebo and any other non-immunosuppressive agents in treating IgAN. Twelve RCTs involving 1,057 patients were included. Overall, we found that steroids had statistically significant effects in preventing the decline in renal function (relative risk 0.42, 95% CI 0.25-0.71, p < 0.001) and reducing proteinuria (SMD: -0.58 g/day, 95% CI -0.80 to -0.36 g/day) in patients with IgAN. The association between glucocorticoid and risk of kidney outcome was not modified by steroids' type (prednisone or methylprednisone), dose (≤30 or > 30 mg/day), duration (≤8 or > 8 months), or serum creatinine (< 1.10 or ≥1.10 mg/dL). But steroids increased the risk of side effects such as gastrointestinal and endocrinium symptoms. This study provides the clear beneficial effects of the steroids therapy on the kidney function and proteinuria, although it should be used with caution. © 2018 S. Karger AG, Basel.

Effect of a Gonadotrophin-Releasing Hormone Analogue on Lung Function in Lymphangioleiomyomatosis

PubMed Central

Harari, Sergio; Cassandro, Roberto; Chiodini, Jacopo; Taveira-DaSilva, Angelo M.; Moss, Joel

2010-01-01

Background Lymphangioleiomyomatosis (LAM), a multisystem disease occurring primarily in women, is characterized by cystic lung destruction, and kidney and lymphatic tumors, caused by the proliferation of abnormal-appearing cells (ie, LAM cells) with a smooth muscle cell phenotype that express melanoma antigens and are capable of metastasizing. Estrogen receptors are present in LAM cells, and this finding, along with reports of disease progression during pregnancy or following exogenous estrogen administration, suggest the involvement of estrogens in the pathogenesis of LAM. Consequently, antiestrogen therapies have been employed in treatment. The goal of this prospective study was to evaluate the efficacy of triptorelin, a gonadotrophin-releasing hormone analogue, in 11 premenopausal women with LAM. Methods Patients were evaluated at baseline and every 3 to 6 months thereafter, for a total of 36 months. Hormonal assays, pulmonary function tests, 6-min walk tests, high-resolution CT scans of the chest, and bone mineral density studies were performed. Results Gonadal suppression was achieved in all patients. Overall, a significant decline in lung function was observed; two patients underwent lung transplantation 1 year after study enrollment, and another patient was lost to follow-up. Treatment with triptorelin was associated with a decline in bone mineral density. Conclusions Triptorelin appears not to prevent a decline in lung function in patients with LAM. Its use, however, may be associated with the loss of bone mineral density. PMID:18071009

Consensus Conference on Best Practices in Live Kidney Donation: Recommendations to Optimize Education, Access, and Care

PubMed Central

Rudow, Dianne LaPointe; Hays, Rebecca; Baliga, Prabhakar; Cohen, David J.; Cooper, Matthew; Danovitch, Gabriel M.; Dew, Mary Amanda; Gordon, Elisa J.; Mandelbrot, Didier A.; McGuire, Suzanne; Milton, Jennifer; Moore, Deonna R.; Morgieivich, Marie; Schold, Jesse D.; Segev, Dorry L.; Serur, David; Steiner, Robert W.; Tan, Jane C.; Waterman, Amy D.; Zavala, Edward Y.; Rodrigue, James R.

2015-01-01

Live donor kidney transplantation is the best treatment option for most patients with late-stage chronic kidney disease; however, the rate of living kidney donation has declined in the United States. A consensus conference was held June 5–6, 2014 to identify best practices and knowledge gaps pertaining to live donor kidney transplantation and living kidney donation. Transplant professionals, patients, and other key stakeholders discussed processes for educating transplant candidates and potential living donors about living kidney donation; efficiencies in the living donor evaluation process; disparities in living donation; and financial and systemic barriers to living donation. We summarize the consensus recommendations for best practices in these educational and clinical domains, future research priorities, and possible public policy initiatives to remove barriers to living kidney donation. PMID:25648884

Renal Atrophy Secondary to Chemoradiotherapy of Abdominal Malignancies

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

Yang, Gary Y., E-mail: Gary.Yang@RoswellPark.or; May, Kilian Salerno; Iyer, Renuka V.

2010-10-01

Purpose: To identify factors predictive of renal atrophy after chemoradiotherapy of gastrointestinal malignancies. Methods and Materials: Patients who received chemotherapy and abdominal radiotherapy (RT) between 2002 and 2008 were identified for this study evaluating change in kidney size and function after RT. Imaging and biochemical data were obtained before and after RT in 6-month intervals. Kidney size was defined by craniocaudal measurement on CT images. The primarily irradiated kidney (PK) was defined as the kidney that received the greater mean kidney dose. Receiver operating characteristic (ROC) curves were generated to predict risk for renal atrophy. Results: Of 130 patients, medianmore » age was 64 years, and 51.5% were male. Most primary disease sites were pancreas and periampullary tumors (77.7%). Median follow-up was 9.4 months. Creatinine clearance declined 20.89%, and size of the PK decreased 4.67% 1 year after completion of chemoradiation. Compensatory hypertrophy of the non-PK was not seen. Percentage volumes of the PK receiving {>=}10 Gy (V{sub 10}), 15 Gy (V{sub 15}), and 20 Gy (V{sub 20}) were significantly associated with renal atrophy 1 year after RT (p = 0.0030, 0.0029, and 0.0028, respectively). Areas under the ROC curves for V{sub 10}, V{sub 15}, and V{sub 20} to predict >5% decrease in PK size were 0.760, 0.760, and 0.762, respectively. Conclusions: Significant detriments in PK size and renal function were seen after abdominal RT. The V{sub 10}, V{sub 15}, and V{sub 20} were predictive of risk for PK atrophy 1 year after RT. Analyses suggest the association of lower-dose renal irradiation with subsequent development of renal atrophy.« less

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.

Serine proteases, inhibitors and receptors in renal fibrosis

PubMed Central

Eddy, Allison A.

2011-01-01

Summary Chronic kidney disease (CKD) is estimated to affect one in eight adults. Their kidney function progressively deteriorates as inflammatory and fibrotic processes damage nephrons. New therapies to prevent renal functional decline must build on basic research studies that identify critical cellular and molecular mediators. Plasminogen activator inhibitor-1 (PAI-1), a potent fibrosis-promoting glycoprotein, is one promising candidate. Absent from normal kidneys, PAI-1 is frequently expressed in injured kidneys. Studies in genetically engineered mice have demonstrated its potency as a pro-fibrotic molecule. Somewhat surprising, its ability to inhibit serine protease activity does not appear to be its primary pro-fibrotic effect in CKD. Both tissue-type plasminogen activator and plasminogen deficiency significantly reduced renal fibrosis severity after ureteral obstruction, while genetic urokinase (uPA) deficiency had no effect. PAI-1 expression is associated with enhanced recruitment of key cellular effectors of renal fibrosis – interstitial macrophages and myofibroblasts. The ability of PAI-1 to promote cell migration involves interactions with the low-density lipoprotein receptor-associate protein-1 and also complex interactions with uPA bound to its receptor (uPAR) and several leukocyte and matrix integrins that associate with uPAR as co-receptors. uPAR is expressed by several cell types in damaged kidneys, and studies in uPAR-deficient mice have shown that its serves a protective role. uPAR mediates additional anti-fibrotic effects - it interacts with specific co-receptors to degrade PAI-1 and extracellular collagens, and soluble uPAR has leukocyte chemoattractant properties. Molecular pathways activated by serine proteases and their inhibitor, PAI-1, are promising targets for future anti-fibrotic therapeutic agents. PMID:19350108

Sepsis and Acute Kidney Injury.

PubMed

Bilgili, Beliz; Haliloğlu, Murat; Cinel, İsmail

2014-12-01

Acute kindney injury (AKI) is a clinical syndrome which is generally defined as an abrupt decline in glomerular filtration rate, causing accumulation of nitrogenous products and rapid development of fluid, electrolyte and acid base disorders. In intensive care unit sepsis and septic shock are leading causes of AKI. Sepsis-induced AKI literally acts as a biologic indicator of clinical deterioration. AKI triggers variety of immune, inflammatory, metabolic and humoral patways; ultimately leading distant organ dysfunction and increases morbidity and mortality. Serial mesurements of creatinine and urine volume do not make it possible to diagnose AKI at early stages. Serum creatinine influenced by age, weight, hydration status and become apparent only when the kidneys have lost 50% of their function. For that reason we need new markers, and many biomarkers in the diagnosis of early AKI activity is assessed. Historically "Risk-Injury-Failure-Loss-Endstage" (RIFLE), "Acute Kidney Injury Netwok" (AKIN) and "The Kidney Disease/ Improving Global Outcomes" (KDIGO) classification systems are used for diagnosing easily in clinical practice and research and grading disease. Classifications including diagnostic criteria are formed for the identification of AKI. Neutrophil gelatinase associated lipocalin (NGAL), cystatin-C (Cys-C), kidney injury molecule-1 (KIM-1) and also "cell cycle arrest" molecules has been concerned for clinical use. In this review the pathophysiology of AKI, with the relationship of sepsis and the importance of early diagnosis of AKI is evaluated.

Vasopressin and Diabetic Kidney Disease.

PubMed

El Boustany, Ray

2018-01-01

Diabetic nephropathy has become the most common cause of chronic kidney disease (CKD). Despite the progress accomplished in therapy, the prevalence of renal disorders remains high. Some modifiable factors driving the increase in incidence of CKD, in diabetes and other settings, might have been overlooked. Consistent evidence supports a role for vasopressin, hydration state, and urine concentration in kidney health. Plasma vasopressin is elevated in diabetes, even if metabolic control is good. Several epidemiological studies have pointed to a positive association between markers of vasopressin secretion (24-h fluid intake, urine volume, plasma copeptin concentration) and renal function decline in both the community and populations at high risk of CKD, namely, diabetic patients. Research involving animal models also supports a critical causal role of the V2 receptor antidiuretic effects of vasopressin in the early signs of kidney disease associated with type 1 or type 2 diabetes. Key Messages: Data supporting the detrimental effects of chronic vasopressin action on the kidney is consistent in animal models and human observational studies. Since vasopressin secretion can be modulated by water intake, and its actions by selective receptor antagonists, the vasopressin-hydration system could be a potential therapeutic target for the prevention and treatment of diabetic nephropathy. Intervention studies are needed to examine the relevance of lifestyle or pharmacological interventions. © 2018 The Author(s) Published by S. Karger AG, Basel.

Alcohol and Exercise Affect Declining Kidney Function in Healthy Males Regardless of Obesity: A Prospective Cohort Study.

PubMed

Kanda, Eiichiro; Muneyuki, Toshitaka; Suwa, Kaname; Nakajima, Kei

2015-01-01

Although lifestyle is associated with metabolic syndrome and cardiovascular diseases, there has been no sufficient evidence of lifestyles on incident chronic kidney disease (CKD). The purpose of this prospective cohort study is to investigate the effects of lifestyles on kidney function in healthy people. A total of 7473 healthy people were enrolled in this Saitama Cardiometabolic Disease and Organ Impairment Study, Japan. Data on alcohol consumption, exercise frequency, and sleep duration were collected. The outcome event was incident CKD or decrease in estimated glomerular filtration rate (eGFR) by >25% in 3 years. Subjects were classified into four groups according to body mass index and gender. Mean ± standard deviation of age was 38.8±10.5 years; eGFR, 78.1±15.2 ml/min/1.73 m2. In the male groups, multivariate logistic regression models showed that the outcome events were associated with a small amount of alcohol consumed (20 to 140 g of alcohol/week) (ref. more than 140 g of alcohol/week); non-obese male, adjusted odds ratio 1.366 (95% confidence interval, 1.086, 1.718); obese male (body mass index ≥25), 1.634 (1.160, 2.302); and with frequent exercise (twice a week or more) (ref. no exercise); non-obese male, 1.417 (1.144, 1.754); obese male, 1.842 (1.317, 2.577). Sleep duration was not associated with the outcome events. These findings suggest that, regardless of obesity, a small amount of alcohol consumed and high exercise frequency were associated with the increased risk of loss of kidney function in the male groups.

Angiotensin II Type 1 Receptor-Associated Protein Regulates Kidney Aging and Lifespan Independent of Angiotensin.

PubMed

Uneda, Kazushi; Wakui, Hiromichi; Maeda, Akinobu; Azushima, Kengo; Kobayashi, Ryu; Haku, Sona; Ohki, Kohji; Haruhara, Kotaro; Kinguchi, Sho; Matsuda, Miyuki; Ohsawa, Masato; Minegishi, Shintaro; Ishigami, Tomoaki; Toya, Yoshiyuki; Atobe, Yoshitoshi; Yamashita, Akio; Umemura, Satoshi; Tamura, Kouichi

2017-07-27

The kidney is easily affected by aging-associated changes, including glomerulosclerosis, tubular atrophy, and interstitial fibrosis. Particularly, renal tubulointerstitial fibrosis is a final common pathway in most forms of progressive renal disease. Angiotensin II type 1 receptor (AT1R)-associated protein (ATRAP), which was originally identified as a molecule that binds to AT1R, is highly expressed in the kidney. Previously, we have shown that ATRAP suppresses hyperactivation of AT1R signaling, but does not affect physiological AT1R signaling. We hypothesized that ATRAP has a novel functional role in the physiological age-degenerative process, independent of modulation of AT1R signaling. ATRAP-knockout mice were used to study the functional involvement of ATRAP in the aging. ATRAP-knockout mice exhibit a normal age-associated appearance without any evident alterations in physiological parameters, including blood pressure and cardiovascular and metabolic phenotypes. However, in ATRAP-knockout mice compared with wild-type mice, the following takes place: (1) age-associated renal function decline and tubulointerstitial fibrosis are more enhanced; (2) renal tubular mitochondrial abnormalities and subsequent increases in the production of reactive oxygen species are more advanced; and (3) life span is 18.4% shorter (median life span, 100.4 versus 123.1 weeks). As a key mechanism, age-related pathological changes in the kidney of ATRAP-knockout mice correlated with decreased expression of the prosurvival gene, Sirtuin1 . On the other hand, chronic angiotensin II infusion did not affect renal sirtuin1 expression in wild-type mice. These results indicate that ATRAP plays an important role in inhibiting kidney aging, possibly through sirtuin1-mediated mechanism independent of blocking AT1R signaling, and further protecting normal life span. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

The association between elevated serum uric acid level and an increased risk of renal function decline in a health checkup cohort in China.

PubMed

Cao, Xia; Wu, Liuxin; Chen, Zhiheng

2018-03-01

To investigate whether an elevated serum uric acid (SUA) level is an independent risk factor for rapid decline in renal function or new-onset chronic kidney disease (CKD) in a Chinese health checkup population. A cohort study of 6495 Chinese individuals who underwent health checkups with normal estimated glomerular filtration rate (eGFR) at baseline was carried out from May 2011 to April 2016. Examinations included a questionnaire, physical measurements, and blood sampling. The gender-specific quartiles of blood uric acid were used to present baseline descriptive data. Rapid decline of renal function was defined as eGFR loss of > 3 mL/min/1.73 m 2 /year. New-onset CKD was defined as follow-up eGFR < 60 mL/min/1.73 m 2 or positive proteinuria. Multivariable logistic regression was used to assess the relationship between serum uric acid and the following outcomes: rapid decline of renal function, incident CKD, and combined renal outcomes. During mean follow-up of 52.8 months, 1608 (24.8%) individuals reached combined renal events. Rapid decline in renal function developed in 1506 (23.2%) individuals, and incident CKD was documented in 372 (5.7%) individuals. In a multivariate model adjusted for age, BMI, diabetes, hypertension, alcohol drinking, SBP, total cholesterol, and eGFR, the odds ratio for rapid decline of renal function increased across quartiles of serum uric acid level, reaching a 1.32 (95% CI 1.02-2.97) for the top quartile compared to the lowest quartile (P for trend < 0.001). Meanwhile, higher SUA was also associated with incident CKD in all models. Furthermore, an increased risk of reaching renal outcomes across increasing quartiles of SUA levels appeared to be similar among subgroups stratified according to age, eGFR, and SBP (P < 0.05 in all). These findings suggest that higher SUA may predict progressive renal damage and dysfunction in a health checkup population in China.

Elevated serum uric acid level predicts rapid decline in kidney function

PubMed Central

Kuwabara, Masanari; Bjornstad, Petter; Hisatome, Ichiro; Niwa, Koichiro; Roncal-Jimenez, Carlos A; Andres-Hernando, Ana; Jensen, Thomas; Milagres, Tamara; Sato, Yuka; Garcia, Gabriela; Ohno, Minoru; Lanaspa, Miguel A; Johnson, Richard J

2018-01-01

Background While elevated serum uric acid level (SUA) is a recognized risk factor for chronic kidney disease (CKD), it remains unclear whether change in SUA is independently associated with change in estimated glomerular filtration rate (eGFR) over time. Accordingly, we examined the longitudinal associations between change in SUA and change in eGFR over 5-years in a general Japanese population. Methods This was a large, single-center, retrospective 5-year cohort study at St. Luke's International Hospital, Tokyo, Japan, between 2004 and 2009. We included 13,070 subjects (30–85 years) in our analyses whose data were available at 2004 and 2009. Of those, we excluded 492 subjects with eGFR <60 mL/min/1.73m2 at baseline. In addition to examining the entire cohort (n=12,578), we stratified our analyses by baseline eGFR groups; 60–90 mL/min/1.73m2, 90–120 mL/min/1.73m2, and ≥120 mL/min/1.73m2. Linear and logistic regressions models were applied to examine the relationships between baseline and change in SUA, change in eGFR and rapid eGFR decline (defined as the highest quantile of change in eGFR), adjusted for age, sex, body mass index, abdominal circumference, hypertension, dyslipidemia, and diabetes mellitus. Results After multivariable adjustments including baseline eGFR, 1 mg/dL increase in baseline SUA was associated with greater odds of developing rapid eGFR decline (OR: 1.27, 95% CI: 1.17–1.38), and 1 mg/dL increase in SUA over 5-years was associated with 3.77-fold greater odds of rapid eGFR decline (OR: 3.77, 95% CI: 3.35–4.26). Conclusions Elevated baseline SUA and increasing SUA over time were independent risk factors for rapid eGFR decline over 5-years. PMID:28285309

Poorer Visual Acuity Is Associated with Declines in Cognitive Performance Across Multiple Cognitive Domains: The Maine-Syracuse Longitudinal Study.

PubMed

Dearborn, Peter J; Elias, Merrill F; Sullivan, Kevin J; Sullivan, Cara E; Robbins, Michael A

2018-06-21

Prior studies have found associations between visual acuity (VA) and cognitive function. However, these studies used a limited range of cognitive measures and did not control for cardiovascular disease risk factors (CVD-RFs) and baseline function. The primary objective of this study was to analyze the associations of VA and cognitive performance using a thorough neuropsychological test battery. This study used community-dwelling sample data across the sixth (2001-2006) and seventh (2006-2010) waves of the Maine-Syracuse Longitudinal Study (n=655). Wave 6 VA as measured by the Snellen Eye Test was the primary predictor of wave 6 and wave 7 Global cognitive performance, Visual-Spatial Organization and Memory, Verbal Episodic Memory, Working Memory, Scanning and Tracking, and Executive Function. Additionally, VA was used to predict longitudinal changes in wave 7 cognitive performance (wave 6 performance adjusted). We analyzed these relationships with multiple linear and logistic regression models adjusted for age, sex, education, ethnicity, depressive symptoms, physical function deficits in addition to CVD-RFs, chronic kidney disease, homocysteine, continuous systolic blood pressure, and hypertension status. Adjusted for demographic covariates and CVD-RFs, poorer VA was associated with concurrent and approximate 5-year declines in Global cognitive function, Visual-Spatial Organization and Memory, and Verbal Episodic Memory. VA may be used in combination with other screening measures to determine risk for cognitive decline. (JINS, 2018, 24, 1-9).

Iron deficiency anaemia in chronic kidney disease.

PubMed

Wittwer, Iain

2013-09-01

Iron Deficiency Anaemia (IDA) has been shown to be the most common cause of anaemia worldwide. It is accepted that people with chronic kidney disease (CKD) develop anaemia as their kidney function declines. To better understand IDA in CKD, it is necessary to appreciate the normal iron metabolism and utilisation of iron and how these processes can be disordered in patients with CKD. The problems related to infection / inflammation and oxidative stress are examined. Whilst National and international guidelines recommend specific tests for IDA, these and alternative tests are reviewed. Whilst iron supplementation is necessary for CKD patients with IDA, iron metabolism and utilisation can be affected by factors such as infection or inflammation. Iron is essential element for all life, it can be toxic to cells through the process of oxidative stress. The recommended tests for IDA may be affected by factors such as infection and inflammation. Alternative tests are available, which may be a more accurate indicator of IDA as they are not affected by external factors. © 2013 European Dialysis and Transplant Nurses Association/European Renal Care Association.

Evaluation of urine biomarkers of kidney injury in Polycystic Kidney Disease

PubMed Central

Parikh, Chirag R.; Dahl, Neera K.; Chapman, Arlene; Bost, James E.; Edelstein, Charles L.; Comer, Diane M.; Zeltner, Raoul; Tian, Xin; Grantham, Jared J.; Somlo, Stefan

2012-01-01

Progressive disruption of renal tubular integrity in the setting of increased cellular proliferation and apoptosis is a feature of ADPKD. Here we evaluated the effect of these processes on the expression of NGAL and IL-18, markers of tubular injury, in rodent models and in the cyst fluid and urine of patients with ADPKD. Two mouse models where Pkd2 was inactivated which resulted in early or adult onset cysts, were used to evaluate NGAL levels. Further, the Han:SPRD rat model of polycystic disease was used to study IL-18 levels. In four annual serial urine samples from 107 patients with ADPKD in the Consortium for Radiologic Imaging for the Study of Polycystic Kidney Disease (CRISP) study, NGAL and IL-18 excretion rates were determined in conjunction with measures of total kidney volume and estimated GFR (eGFR) by the MDRD equation. Kidneys from affected mice and rats showed prominent expression of NGAL and IL-18/IL-18R, respectively, in epithelial cells lining kidney cysts. In human ADPKD cyst fluid, both NGAL and IL-18 were elevated. In CRISP patients, the mean percentage increase in total kidney volume was 5.4 /year and the mean decline in eGFR 2.4 mL/min/year. The trend of increased mean urine NGAL and IL-18 over three years was statistically significant; however, there was no association of tertiles of IL-18 or quartiles of NGAL and the change in total kidney volume or eGFR over this period. Thus, urinary NGAL and IL-18 excretion are mildly and stably elevated in ADPKD, but do not correlate with changes in total kidney volume or kidney function. This may be due, in part, to the lack of communication between individual cysts and the urinary collecting system in this disorder. PMID:22258321

Low Ankle Brachial Index and the Development of Rapid Estimated GFR Decline and CKD

PubMed Central

Foster, Meredith C.; Ghuman, Nimrta; Hwang, Shih-Jen; Murabito, Joanne M.; Fox, Caroline S.

2012-01-01

Background Low ankle brachial index (ABI) is associated with increases in serum creatinine. Whether low ABI is associated with the development of rapid estimated glomerular filtration rate (eGFR) decline, stage 3 chronic kidney disease (CKD), or microalbuminuria is uncertain. Study Design Prospective cohort study. Setting & Participants Framingham Offspring cohort participants who attended the sixth (1995-98) and eighth (2005-08) exams. Predictor ABI, categorized as normal (>1.1 to <1.4), low-normal (>0.9 to 1.1), and low (≤0.9). Outcomes Rapid eGFR decline (eGFR decline ≥3mL/min/1.73m2 per year), incident stage 3 CKD (eGFR<60mL/min/1.73m2), incident microalbuminuria. Measurements GFR was estimated using the serum creatinine-based CKD-EPI (CKD Epidemiology Collaboration) equation. Urinary albumin-creatinine ratio (UACR) was determined based on spot urine samples. Results Over 9.5 years, 9.0% (232 of 2592) experienced rapid eGFR decline and 11.1% (270 of 2426) developed stage 3 CKD. Compared to a normal ABI, low ABI was associated with a 5.73-fold increased odds of rapid eGFR decline (95% CI, 2.77-11.85; p<0.001) after age, sex, and baseline eGFR adjustment; this persisted after multivariable adjustment for standard CKD risk factors (OR, 3.60; 95% CI, 1.65-7.87; p=0.001). After adjustment for age, sex, and baseline eGFR, low ABI was associated with a 2.51-fold increased odds of stage 3 CKD (OR, 2.51; 95% CI, 1.16-5.44; p=0.02), although this was attenuated after multivariable adjustment (OR, 1.68; 95% CI, 0.75-3.76; p=0.2). Among 1902 free of baseline microalbuminuria, low ABI was associated with an increased odds of microalbuminuria after adjustment for age, sex, and baseline UACR (OR, 2.81; 95% CI, 1.07-7.37; p=0.04), with attenuation upon further adjustment (OR, 1.88; p=0.1). Limitations Limited number of events with a low ABI. Outcomes based on single serum creatinine and UACR measurements at each exam. Conclusions Low ABI is associated with an increased risk of rapid eGFR decline, suggesting that systemic atherosclerosis predicts decline in kidney function. PMID:22901770

Assessment of cisplatin-induced kidney injury using an integrated rodent platform

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

Chen, Yafei; Brott, David; Luo, Wenli

Current diagnosis of drug-induced kidney injury (DIKI) primarily relies on detection of elevated plasma creatinine (Cr) or blood urea nitrogen (BUN) levels; however, both are indices of overall kidney function and changes are delayed with respect to onset of nephron injury. Our aim was to investigate whether early changes in new urinary DIKI biomarkers predict plasma Cr, BUN, renal hemodynamic and kidney morphological changes associated with kidney injury following a single dose of cisplatin (CDDP) using an integrated platform in rodent. Conscious surgically prepared male Han Wistar rats were given a single intraperitoneal dose of CDDP (15 mg/kg). Glomerular filtrationmore » rate (GFR), effective renal plasma flow (ERPF), urinalysis, DIKI biomarkers, CDDP pharmacokinetics, blood pressures, heart rate, body temperature and electroencephalogram (EEG) were measured in the same vehicle- or CDDP-treated animals over 72 h. Plasma chemistry (including Cr and BUN) and renal tissues were examined at study termination. Cisplatin caused progressive reductions of GFR, ERPF, heart rate and body temperature from day 1 (0–24 h). DIKI biomarkers including alpha-glutathione S-transferase (α-GST) significantly increased as early as 6 h post-dose, which preceded significant declines of GFR and ERPF (24 h), increased plasma Cr and BUN (72 h), and associated with renal acute tubular necrosis at 72 h post-dose. The present study adds to the current understanding of CDDP action by demonstrating that early increases in urinary excretion of α-GST predict DIKI risk following acute exposure to CDDP in rats, before changes in traditional DIKI markers are evident. - Highlights: ► CDDP causes direct damage to kidneys without affecting EEG or CVS function. ► α-GST and albumin detect DIKI earlier when compared with traditional indices. ► Integrated “cardiovascular-EEG-renal” model to better understand DIKI mechanisms ► Promotes 3R's principles in drug discovery and development.« less

[Advances in the research of effects of glutamine on immune function of burn patients].

PubMed

Liu, Y H; Guo, P F; Chen, G Y; Bo, Y C; Ma, Y; Cui, Z J

2018-04-20

Glutamine is the most abundant amino acid found in plasma and cells. It is the preferred fuel for enterocytes in the small intestine, macrophages, and lymphocytes. After serious burn, increased requirement of glutamine by the gastrointestinal tract, kidney and lymphocytes, and relatively insufficient self synthesis likely contribute to the rapid decline of glutamine in circulation and cells. Glutamine supplementation can not only protect intestinal mucosa, maintain normal intestinal barrier function, reduce bacterial translocation, and enhance the intestinal immune function, but also increase the number of lymphocytes, enhance the phagocytic function of macrophage, promote the synthesis of immunoglobulin, and reduce the body's inflammatory response, so as to enhance the immune function. Therefore, glutamine supplementation can improve and enhance the immune function, reduce complications and promote the prognosis of severely burned patients.

[Causes of decreased use of peritoneal dialysis as a kidney replacement therapy in the Netherlands].

PubMed

Hemke, Aline C; Dekker, Friedo W; Bos, Willem Jan W; Krediet, Raymond T; Heemskerk, Martin B A; Hoitsma, Andries J

2012-01-01

To study the extent and causes of the declining use of peritoneal dialysis (PD) as kidney replacement therapy in patients with end-stage renal disease in the Netherlands. Retrospective cohort study. The prevalence and incidence of various kidney replacement therapies in the Netherlands from 1995 to 2010 were analysed. Also the 5-year outflow of patients on PD or haemodialysis (HD) from 1995 to 2006 was analysed using the cumulative incidence competing risks method and Cox regression analysis. The absolute number of patients starting PD between 1995 and 2008 was stable at about 400 per year. There was a relative decline in the use of PD in the total dialysis population from 15% in 1995 to 8% in 2010. This decrease was seen in both large and small centres and was related to a relative increase in the numbers undergoing HD (67% before 2001, 74% in 2009), and kidney transplantation before dialysis (3% before 2002, 9% in 2009), as well as a decrease in change of therapy from HD to PD. The increased number starting on HD was associated with the growth of the incident patient group aged 65 years or older, most of whom (80-85%) underwent HD. Within the younger group (0-65 years) there was an increase in numbers on HD and in the number of pre-emptive transplantations. The decline in the prevalence of PD was partly explained by the relative increase in numbers starting HD, associated with an ageing patient population, fewer people changing from HD to PD therapy, and the increased number of kidney transplantations before dialysis in younger patients. The increasing prevalence of HD has been made possible by growth of the HD capacity.

Frequency of Acute Kidney Injury Caused by Tazobactam/Piperacillin in Patients with Pneumonia and Chronic Kidney Disease: A Retrospective Observational Study.

PubMed

Morimoto, Takeyori; Nagashima, Hiroki; Morimoto, Yasuko; Tokuyama, Shogo

2017-01-01

 Tazobactam/piperacillin (TAZ/PIPC) is a combination antibiotic frequently used to treat pneumonia. It has recently been reported that TAZ/PIPC worsens renal function in patients with existing renal impairment. Creatinine clearance is generally between 10 and 40 mL/min in Japanese patients, so TAZ/PIPC is given at a dose of 2.25 g three times daily or 4.5 g twice daily. If pneumonia is severe or intractable, the dose frequency may be increased to 2.25 g four times daily and 4.5 g three times daily. We examined the effect of these different dosing regimens on renal function. We studied a cohort of 57 patients with impaired renal function hospitalized with pneumonia and treated with TAZ/PIPC between January 2015 and November 2016. Patients were classified into four groups according to TAZ/PIPC dose: 2.25 g three times daily (Group A); 2.25 g four times daily (B); 4.5 g twice daily (C) and 4.5 g three times daily (D). We examined the frequency of acute kidney injury (AKI) and treatment effectiveness. In Groups A, B, C and D, AKI occurred in 5.6%, 0.0%, 25.0% and 38.5% of patient. In groups C and D, hydration and dose reduction were required to address early signs of impending AKI. Our findings suggest that the higher TAZ/PIPC dose of 4.5 g was responsible for the decline in renal function, even if the dose frequency was reduced.

Kidney function and cognitive decline in frail elderly: two faces of the same coin?

PubMed

Coppolino, Giuseppe; Bolignano, Davide; Gareri, Pietro; Ruberto, Carmen; Andreucci, Michele; Ruotolo, Giovanni; Rocca, Maurizio; Castagna, Alberto

2018-06-04

Cognitive and renal impairment are pervasive among elderly frails, a high-risk, geriatric sub-population with peculiar clinical characteristics. In a series of frail individuals with non-advanced chronic kidney disease (CKD), we aimed at assessing the entity of functional, general health and cognitive impairment and the possible relationship between these types of dysfunction and the severity of renal impairment. 2229 geriatric subjects were screened for frailty and CKD. Severity of CKD was assessed by eGFR (CKD-EPI formula). Frailty was established by the Fried Index. Functional, general health and cognitive status were assessed by validated score measures. Final analysis included 271 frail CKD subjects (162 women, 109 men). Mean eGFR was 64.25 ± 25.04 mL/min/1.73 m 2 . Prevalence of mild-to-moderate CKD (stage 3-4) was 44%. Twenty-six percent of patients had severe cognitive impairment, while mild and moderate impairment was found in 7 and 67% of individuals, respectively. All subjects had poor functional and general health status. Cognitive capacities significantly decreased across CKD stages (p for trend < 0.0001). In fully adjusted multivariate analyses, cognitive status remained an independent predictor of eGFR (β = 0.465; p < 0.0001). Mild-to-moderate CKD is highly pervasive among frail elderly individuals and the severity of renal dysfunction is independently correlated with that of cognitive impairment. Future studies are advocated to clarify whether the combination of kidney and mental dysfunction may portend a higher risk of worsen outcomes in this high-risk population.

Isozyme-specific comprehensive characterization of transglutaminase-crosslinked substrates in kidney fibrosis.

PubMed

Tatsukawa, Hideki; Otsu, Risa; Tani, Yuji; Wakita, Ryosuke; Hitomi, Kiyotaka

2018-05-09

Chronic kidney disease is characterized by prolonged decline in renal function, excessive accumulation of ECM, and progressive tissue fibrosis. Transglutaminase (TG) is a crosslinking enzyme that catalyzes the formation of covalent bonds between glutamine and lysine residues, and is involved in the induction of renal fibrosis via the stabilization of ECM and the activation of TGF-β1. Despite the accumulating evidences indicating that TG2 is a key enzyme in fibrosis, genetic knockout of TG2 reduced by only 50% the elevated protein crosslinking and fibrous protein in renal fibrosis model, whereas treatment with TG inhibitor almost completely reduced these levels. Here, we also clarified the distributions of TG isozymes and their in situ activities and identified the isozyme-specific crosslinked substrates for both TG1 and TG2 in fibrotic kidney. We found that TG1 activity was markedly enhanced in renal tubular epithelium and interstitial areas, whereas TG2 activity increased only in the extracellular space. In total, 47 and 67 possible candidates were identified as TG1 and TG2 substrates, respectively, only in fibrotic kidney. Among them, several possible substrates related to renal disease and fibrosis were identified. These findings provide novel insights into the mechanisms of renal fibrosis through the targeting of isozyme-specific TG substrates.

Effect of trichloroethylene (TCE) toxicity on the enzymes of carbohydrate metabolism, brush border membrane and oxidative stress in kidney and other rat tissues.

PubMed

Khan, Sheeba; Priyamvada, Shubha; Khan, Sara A; Khan, Wasim; Farooq, Neelam; Khan, Farah; Yusufi, A N K

2009-07-01

Trichloroethylene (TCE), an industrial solvent, is a major environmental contaminant. Histopathological examinations revealed that TCE caused liver and kidney toxicity and carcinogenicity. However, biochemical mechanism and tissue response to toxic insult are not completely elucidated. We hypothesized that TCE induces oxidative stress to various rat tissues and alters their metabolic functions. Male Wistar rats were given TCE (1000 mg/kg/day) in corn oil orally for 25 d. Blood and tissues were collected and analyzed for various biochemical and enzymatic parameters. TCE administration increased blood urea nitrogen, serum creatinine, cholesterol and alkaline phosphatase but decreased serum glucose, inorganic phosphate and phospholipids indicating kidney and liver toxicity. Activity of hexokinase, lactate dehydrogenase increased in the intestine and liver whereas decreased in renal tissues. Malate dehydrogenase and glucose-6-phosphatase and fructose-1, 6-bisphosphatase decreased in all tissues whereas increased in medulla. Glucose-6-phosphate dehydrogenase increased but NADP-malic enzyme decreased in all tissues except in medulla. The activity of BBM enzymes decreased but renal Na/Pi transport increased. Superoxide dismutase and catalase activities variably declined whereas lipid peroxidation significantly enhanced in all tissues. The present results indicate that TCE caused severe damage to kidney, intestine, liver and brain; altered carbohydrate metabolism and suppressed antioxidant defense system.

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.

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.

Oxidative stress responses in Wistar rats on subacute exposure to pharmaceutical wastewater.

PubMed

Sharif, Ali; Ashraf, Muhammad; Javeed, Aqeel; Anjum, Aftab Ahmed; Akhtar, Muhammad Furqan; Akhtar, Bushra; Saleem, Ammara

2016-12-01

Water pollution has been a major concern for agrarian societies like Pakistan. Pharmaceutical industries are amongst the foremost contributor to industrial waste. Present study addresses the generation of oxidative stress caused by 2 months exposure to pharmaceutical wastewater in rats and their response to oral treatment with vitamin E, a potent antioxidant. The rats were randomized into five groups (n = 5) named as negative control, pharmaceutical wastewater (PEW) 100 %, PEW 10 %, PEW 1 %, and PEW 100 % + vitamin E. Oxidative damage in rats was evaluated by estimation of the activities of total superoxide dismutase (T-SOD), catalase (CAT), and the concentration of hydrogen peroxide (H 2 O 2 ) in the liver, kidney, and blood/plasma. Exposure to pharmaceutical wastewater significantly decreased the activities of T-SOD and CAT and concentration of H 2 O 2 in the liver and kidney and blood/plasma. Exposure to 100 % pharmaceutical wastewater exhibited a maximum decline in T-SOD activity, and activity was reduced to only 63.57 U/mL, 32.65, and 43.57 U/mg of protein in the plasma, kidney, and liver, respectively. Exposure to wastewater minimized activity CAT to 89.25 U/g of hemoglobin, 54.36, and 62.95 U/mg of protein in the blood, kidney, and liver, respectively. Treatment with vitamin E significantly increased the activity of T-SOD and CAT. However, increase in concentration of H 2 O 2 was also observed in vitamin E exposed rats. Histopathology of the kidney revealed coagulative necrosis of renal epithelial cells and peritubular congestion. Endocardium showed infiltration of inflammatory cells and cellular breakdown in some areas. Lung sections exhibited atelectasis and emphysema of alveoli suggesting decline in lung function. The anatomy of the liver was also compromised due to severe degeneration and cellular swelling. The present study concluded that pharmaceutical wastewater induced severe oxidative stress in Wistar rats and ensued in histopathological lesions in several vital organs suggesting its high toxicity. Non-enzymatic antioxidant vitamin E may ameliorate oxidative stress induced by pharmaceutical wastewater.

Oxidized LDL accumulation in experimental renal ischemia reperfusion injury model.

PubMed

Kulah, Eyup; Tascilar, Oge; Acikgoz, Serefden; Tekin, Ishak Ozel; Karadeniz, Guldeniz; Can, Murat; Gun, Banu; Barut, Figen; Comert, Mustafa

2007-01-01

The aim of this study was to identify oxidative damage of kidney during ischemia reperfusion injury (IRI) by evaluating changes in lipid peroxidation markers in tissue and blood by an experimental model. Oxidized LDL (ox-LDL) was used as an oxidative stress biomarker, whereas paraoxonase (PON-1) activity was used as an antioxidative biomarker. Sixty-three male Wistar rats were randomly assigned into three groups: renal IRI, sham, and control. In the renal IRI group, the right kidney was removed and the artery and vein of the left kidney were clamped for 90 minutes. The presence of ox-LDL in the kidney tissue sections was determined by using an immunofluorescent staining method. The plasma ox-LDL levels did not increase significantly at the 24th hour following IRI, made a peak at the 48th hour, and declined at the 72nd hour. Accumulation of ox-LDL was detected in the kidney tissue on the 24th, 48th, and 72nd hours of the renal IRI. Serum PON-1 levels have peaked on the 24th hour and then declined. This study demonstrates the accumulation of ox-LDL molecules in the renal tissues of the IRI model. Future strategies aimed to reduce the lipid peroxidation during the initial hours of renal IRI may be useful to prevent complications of ischemia.

Effects of Coffee Intake on Incident Chronic Kidney Disease: Community-Based Prospective Cohort Study.

PubMed

Jhee, Jong Hyun; Nam, Ki Heon; An, Seong Yeong; Cha, Min-Uk; Lee, Misol; Park, Seohyun; Kim, Hyoungnae; Yun, Hae-Ryong; Kee, Youn Kyung; Park, Jung Tak; Chang, Tae-Ik; Kang, Ea Wha; Yoo, Tae-Hyun; Kang, Shin-Wook; Han, Seung Hyeok

2018-06-12

Drinking coffee can raise public health problems, but the association between coffee and kidney disease is unknown. We studied whether coffee intake can affect the development of chronic kidney disease in the general population. We analyzed 8717 subjects with normal renal function recruited from the KoGES cohort. Based on food frequency questionnaire, coffee consumption was categorized into five groups: 0/week, <1 cup/week, 1-6 cups/week, 1 cup/day, and ≥2 cups/day. The primary outcome was incident chronic kidney disease defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m 2 . The mean age of study subjects was 52.0 (8.8) years and 47.8% were male. Among the subjects, 52.8% were daily coffee consumers. During a mean follow-up of 11.3 [5.9-11.5] years, 9.5% of participants developed chronic kidney disease. The incident chronic kidney disease occurred less in daily coffee consumers. Unadjusted HRs was significantly lower in daily coffee consumers. In multivariable Cox model even after adjustment of blood pressure, hypertension, cardiovascular disease, diabetes, and amount of daily intake for caffeine-containing foods such as tea and chocolate, coffee consumers with 1 cup/day (HR, 0.76; 95% CI, 0.63-0.92) and ≥2 cups/day (HR, 0.80; 95% CI, 0.65-0.98) were associated with a lower risk of chronic kidney disease development than non-drinkers. Time-averaged and time-varying Cox models yielded similar results. The rates of decline in eGFR were lower in daily coffee consumers. Our findings suggest that daily coffee intake is associated with decreased risk of the development of CKD. Copyright © 2018. Published by Elsevier Inc.

Alkaline Diet and Metabolic Acidosis: Practical Approaches to the Nutritional Management of Chronic Kidney Disease.

PubMed

Rodrigues Neto Angéloco, Larissa; Arces de Souza, Gabriela Cristina; Almeida Romão, Elen; Garcia Chiarello, Paula

2018-05-01

The kidneys play an extremely important role in maintaining the body acid-base balance by excreting nonvolatile acids and regenerating and reabsorbing bicarbonate in the kidney tubules. As the individual loses their kidney function, renal excretion of nonvolatile acid produced by metabolism of the diet is impaired, resulting in low-grade metabolic acidosis. With this in mind, it is relevant to better understand the dietary aspects related to the acid-base balance in chronic kidney disease metabolic acidosis and try to provide possible strategies for the nutritional management of these cases. The type of diet can deeply affect the body by providing acid or base precursors. Generally speaking, foods such as meat, eggs, cheese, and grains increase the production of acid in the organism, whereas fruit and vegetables are alkalizing. On the other hand, milk is considered neutral as well as fats and sugars, which have a small effect on acid-base balance. The modern Western-type diet is deficient in fruits and vegetables and contains excessive animal products. Thus metabolic acidosis may be exacerbated by a contemporary Western diet, which delivers a high nonvolatile acid load. The remaining acid is neutralized or stored within the body. Bone and muscle are lost to neutralize the acid and serum bicarbonate falls. Early studies suggest that lowering the dietary acid load with a reduced protein content and vegetable proteins replacements, associated with an increase in fruits and vegetables intake can improve the metabolic parameters of acidosis, preserve bone and muscle, and slow the glomerular filtration rate decline. More studies focusing on the effects of controlled dietary interventions among chronic kidney disease patients are needed to determining the optimal target for nutritional therapy. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Progression of hypertension and kidney disease in aging fawn-hooded rats is mediated by enhanced influence of renin-angiotensin system and suppression of nitric oxide system and epoxyeicosanoids.

PubMed

Doleželová, Šárka; Jíchová, Šárka; Husková, Zuzana; Vojtíšková, Alžběta; Kujal, Petr; Hošková, Lenka; Kautzner, Josef; Sadowski, Janusz; Červenka, Luděk; Kopkan, Libor

The fawn-hooded hypertensive (FHH) rat serves as a genetic model of spontaneous hypertension associated with glomerular hyperfiltration and proteinuria. However, the knowledge of the natural course of hypertension and kidney disease in FHH rats remains fragmentary and the underlying pathophysiological mechanisms are unclear. In this study, over the animals' lifetime, we followed the survival rate, blood pressure (telemetry), indices of kidney damage, the activity of renin-angiotensin (RAS) and nitric oxide (NO) systems, and CYP450-epoxygenase products (EETs). Compared to normotensive controls, no elevation of plasma and renal RAS was observed in prehypertensive and hypertensive FHH rats; however, RAS inhibition significantly reduced systolic blood pressure (137 ± 9 to 116 ± 8, and 159 ± 8 to 126 ± 4 mmHg, respectively) and proteinuria (62 ± 2 to 37 ± 3, and 132 ± 8 to 87 ± 5 mg/day, respectively). Moreover, pharmacological RAS inhibition reduced angiotensin (ANG) II and increased ANG 1-7 in the kidney and thereby may have delayed the progression of kidney disease. Furthermore, renal NO and EETs declined in the aging FHH rats but not in the control strain. The present results, especially the demonstration of exaggerated vascular responsiveness to ANG II, indicate that RAS may contribute to the development of hypertension and kidney disease in FHH rats. The activity of factors opposing the development of hypertension and protecting the kidney declined with age in this model. Therefore, therapeutic enhancement of this activity besides RAS inhibition could be attempted in the therapy of human hypertension associated with kidney disease.

Removal of kidney stones by extracorporeal shock wave lithotripsy is associated with delayed progression of chronic kidney disease.

PubMed

Yoo, Dong Eun; Han, Seung Hyeok; Oh, Hyung Jung; Kim, Seung Jun; Shin, Dong Ho; Lee, Mi Jung; Yoo, Tae-Hyun; Kang, Shin-Wook; Choi, Kyu Hun

2012-07-01

This study aimed to elucidate whether stone removal by extracorporeal shock wave lithotripsy (ESWL) is associated with delayed chronic kidney disease (CKD) progression. We conducted a retrospective analysis of 131 nephrolithiasis patients with stage 3 and 4 CKD. We collected baseline clinical and laboratory data, kidney stone characteristics, and history of receiving ESWL. We classified study patients into two groups according to whether they underwent ESWL or not (Non-ESWL group vs. ESWL group). We initially compared annual estimated glomerular filtration rate (eGFR) changes of Non-ESWL group with those of ESWL group before undergoing ESWL. In the next step, we sought to compare annual eGFR changes in the same patients before and after ESWL. Finally, we compared annual eGFR changes between success and failure groups among patients undergoing ESWL. The mean age of the patients was 62 years and 72.5% were male. The mean observation period was 3.2 years. Non-ESWL group and ESWL group before undergoing ESWL showed similar annual eGFR changes (-1.75±6.5 vs. -1.63±7.2 mL/min/1.73 m²/year, p=0.425). However, eGFR declined slower after undergoing ESWL than before ESWL (annual eGFR changes, -0.29±6.1 vs. -1.63±7.2 mL/min/1.73 m²/year, p<0.05). In addition, among patients in ESWL group, eGFR declined faster in the failure group than in the success group (annual eGFR change, -1.01±4.7 vs. -0.05±5.2 mL/min/1.73 m²/year, p<0.05). Our results suggest that stone removal by ESWL is associated with delayed deterioration of renal function in CKD patients with nephrolithiasis.

DASH (Dietary Approaches to Stop Hypertension) Diet and Risk of Subsequent Kidney Disease.

PubMed

Rebholz, Casey M; Crews, Deidra C; Grams, Morgan E; Steffen, Lyn M; Levey, Andrew S; Miller, Edgar R; Appel, Lawrence J; Coresh, Josef

2016-12-01

There are established guidelines for recommended dietary intake for hypertension treatment and cardiovascular disease prevention. Evidence is lacking for effective dietary patterns for kidney disease prevention. Prospective cohort study. Atherosclerosis Risk in Communities (ARIC) Study participants with baseline estimated glomerular filtration rate (eGFR) ≥ 60mL/min/1.73m 2 (N=14,882). The Dietary Approaches to Stop Hypertension (DASH) diet score was calculated based on self-reported dietary intake of red and processed meat, sweetened beverages, sodium, fruits, vegetables, whole grains, nuts and legumes, and low-fat dairy products, averaged over 2 visits. Cases were ascertained based on the development of eGFRs<60mL/min/1.73m 2 accompanied by ≥25% eGFR decline from baseline, an International Classification of Diseases, Ninth/Tenth Revision code for a kidney disease-related hospitalization or death, or end-stage renal disease from baseline through 2012. 3,720 participants developed kidney disease during a median follow-up of 23 years. Participants with a DASH diet score in the lowest tertile were 16% more likely to develop kidney disease than those with the highest score tertile (HR, 1.16; 95% CI, 1.07-1.26; P for trend < 0.001), after adjusting for sociodemographics, smoking status, physical activity, total caloric intake, baseline eGFR, overweight/obese status, diabetes status, hypertension status, systolic blood pressure, and antihypertensive medication use. Of the individual components of the DASH diet score, high red and processed meat intake was adversely associated with kidney disease and high nuts, legumes, and low-fat dairy products intake was associated with reduced risk for kidney disease. Potential measurement error due to self-reported dietary intake and lack of data for albuminuria. Consuming a DASH-style diet was associated with lower risk for kidney disease independent of demographic characteristics, established kidney risk factors, and baseline kidney function. Healthful dietary patterns such as the DASH diet may be beneficial for kidney disease prevention. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Soy-based renoprotection

PubMed Central

McGraw, Nancy J; Krul, Elaine S; Grunz-Borgmann, Elizabeth; Parrish, Alan R

2016-01-01

Chronic kidney disease (CKD) is a significant public health problem as risk factors such as advanced age, obesity, hypertension and diabetes rise in the global population. Currently there are no effective pharmacologic treatments for this disease. The role of diet is important for slowing the progression of CKD and managing symptoms in later stages of renal insufficiency. While low protein diets are generally recommended, maintaining adequate levels of intake is critical for health. There is an increasing appreciation that the source of protein may also be important. Soybean protein has been the most extensively studied plant-based protein in subjects with kidney disease and has demonstrated renal protective properties in a number of clinical studies. Soy protein consumption has been shown to slow the decline in estimated glomerular filtration rate and significantly improve proteinuria in diabetic and non-diabetic patients with nephropathy. Soy’s beneficial effects on renal function may also result from its impact on certain physiological risk factors for CKD such as dyslipidemia, hypertension and hyperglycemia. Soy intake is also associated with improvements in antioxidant status and systemic inflammation in early and late stage CKD patients. Studies conducted in animal models have helped to identify the underlying molecular mechanisms that may play a role in the positive effects of soy protein on renal parameters in polycystic kidney disease, metabolically-induced kidney dysfunction and age-associated progressive nephropathy. Despite the established relationship between soy and renoprotection, further studies are needed for a clear understanding of the role of the cellular and molecular target(s) of soy protein in maintaining renal function. PMID:27152261

Urinary NGAL marks cystic disease in HIV-associated nephropathy.

PubMed

Paragas, Neal; Nickolas, Thomas L; Wyatt, Christina; Forster, Catherine S; Sise, Meghan; Morgello, Susan; Jagla, Bernd; Buchen, Charles; Stella, Peter; Sanna-Cherchi, Simone; Carnevali, Maria Luisa; Mattei, Silvia; Bovino, Achiropita; Argentiero, Lucia; Magnano, Andrea; Devarajan, Prasad; Schmidt-Ott, Kai M; Allegri, Landino; Klotman, Paul; D'Agati, Vivette; Gharavi, Ali G; Barasch, Jonathan

2009-08-01

Nephrosis and a rapid decline in kidney function characterize HIV-associated nephropathy (HIVAN). Histologically, HIVAN is a collapsing focal segmental glomerulosclerosis with prominent tubular damage. We explored the expression of neutrophil gelatinase-associated lipocalin (NGAL), a marker of tubular injury, to determine whether this protein has the potential to aid in the noninvasive diagnosis of HIVAN. We found that expression of urinary NGAL was much higher in patients with biopsy-proven HIVAN than in HIV-positive and HIV-negative patients with other forms of chronic kidney disease. In the HIV-transgenic mouse model of HIVAN, NGAL mRNA was abundant in dilated, microcystic segments of the nephron. In contrast, urinary NGAL did not correlate with proteinuria in human or in mouse models. These data show that marked upregulation of NGAL accompanies HIVAN and support further study of uNGAL levels in large cohorts to aid in the noninvasive diagnosis of HIVAN and screen for HIVAN-related tubular damage.

Selenium deficiency induced damages and altered expressions of metalloproteinases and their inhibitors (MMP1/3, TIMP1/3) in the kidneys of growing rats.

PubMed

Han, Jing; Liang, Hua; Yi, Jianhua; Tan, Wuhong; He, Shulan; Wu, Xiaofang; Shi, Xiaowei; Ma, Jing; Guo, Xiong

2016-03-01

Selenium is an essential trace element for the maintenance of structures and functions of kidney. To evaluate the effects of low selenium on the kidneys of growing rats, newborn rats were fed with selenium deficient and normal diets respectively for 109 days. As a result, rats fed with low selenium diets resulted in a decline in the body weight and the concentration of selenium in the kidney, especially the male rats from the low selenium groups. Moreover, the ultrastructure of glomerulus and tubules were damaged in low selenium group: the glomeruli were observed with hyperplasia of mesangial cells, fusion of podocyte foot processes and thickening of basement membrane; and the tubules were observed with vacuolar degenerated epithelial cells, increased edema fluid or protein solution between cells, microvilli edema, increased cell gaps and decreased cell links. Furthermore, the pathological changes in selenium deficient group included the increase of fibers around renal hilum aorta and in the renal collecting duct, and shed of cells in the proximal convoluted tubules. In addition, up-regulated expressions of matrix metalloproteinases (MMP1/3) and down-regulated expressions of their inhibitors (TIMP1/3) at the mRNA and protein levels were also appeared to be relevant to low selenium. The results suggested that low selenium in diet may cause low selenium concentration in the kidney of growing rat and lead to damages of the ultrastructure and extracellular matrix (ECM) of kidney. Copyright © 2015 Elsevier GmbH. All rights reserved.

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.

Prevention of cardiorenal syndromes.

PubMed

McCullough, Peter A

2010-01-01

The cardiorenal syndromes (CRS) are composed of five recently defined syndromes which represent common clinical scenarios in which both the heart and the kidney are involved in a bidirectional injury process leading to dysfunction of both organs. Common to each subtype are multiple complex pathogenic factors, a precipitous decline in function and a progressive course. Most pathways that lead to CRS involve acute injury to organs which manifest evidence of chronic disease, suggesting reduced ability to sustain damage, maintain vital functions, and facilitate recovery. Prevention of CRS is an ideal clinical goal, because once initiated, CRS cannot be readily aborted, are not completely reversible, and are associated with serious consequences including hospitalization, complicated procedures, need for renal replacement therapy, and death. Principles of prevention include identification and amelioration of precipitating factors, optimal management of both chronic heart and kidney diseases, and future use of multimodality therapies for end-organ protection at the time of systemic injury. This paper will review the core concepts of prevention of CRS with practical applications to be considered in today's practice. 2010 S. Karger AG, Basel.

Relationship between body mass index and renal function deterioration among the Taiwanese chronic kidney disease population.

PubMed

Chang, Tian-Jong; Zheng, Cai-Mei; Wu, Mei-Yi; Chen, Tzu-Ting; Wu, Yun-Chun; Wu, Yi-Lien; Lin, Hsin-Ting; Zheng, Jing-Quan; Chu, Nain-Feng; Lin, Yu-Me; Su, Sui-Lung; Lu, Kuo-Cheng; Chen, Jin-Shuen; Sung, Fung-Chang; Lee, Chien-Te; Yang, Yu; Hwang, Shang-Jyh; Wang, Ming-Cheng; Hsu, Yung-Ho; Chiou, Hung-Yi; Kao, Senyeong; Lin, Yuh-Feng

2018-05-02

This study investigated the characteristics of patients with different chronic kidney disease (CKD) stages according to various body mass index (BMI) categories and determined the influence of BMI in renal function deterioration. We conducted a multicenter, longitudinal cohort study based on the Epidemiology and Risk Factors Surveillance of CKD project (2008-2013) and National Health Insurance Research Database (2001-2013). A total of 7357 patients with CKD aged 20-85 years from 14 hospitals were included in the study. A higher male sex, diabetes mellitus (DM) and hypertension were noted among overweight and obese CKD patients, while more cancer prevalence was noted among underweight CKD patients. Charlson comorbidity index was significantly higher and correlated with BMI among late CKD patients. Patients with BMI < 18.5 kg/m 2 exhibited non-significantly higher events of eGFR decline events in both early and late CKD stages than other BMI groups. BMI alone is not a determinant of CKD progression among our Taiwanese CKD patients. Obesity should be re-defined and body weight manipulation should be individualized in CKD patients.

Population Income and Longitudinal Trends in Living Kidney Donation in the United States

PubMed Central

Dong, Jianghu; Gill, John

2015-01-01

Living kidney donation is declining in the United States. We examined longitudinal trends in living donation as a function of median household income and donor relation to assess the effect of financial barriers on donation in a changing economic environment. The zip code–level median household income of all 71,882 living donors was determined by linkage to the 2000 US Census. Longitudinal changes in the rate of donation were determined in income quintiles between 1999 and 2004, when donations were increasing, and between 2005 and 2010, when donations were declining. Rates were adjusted for population differences in age, sex, race, and ESRD rate using multilevel linear regression models. Between 1999 and 2004, the rate of growth in living donation per million population was directly related to income, increasing progressively from the lowest to highest income quintile, with annualized changes of 0.55 (95% confidence interval [95% CI], 0.14 to 1.05) for Q1 and 1.77 (95% CI, 0.66 to 2.77) for Q5 (P<0.05). Between 2005 and 2010, donation declined in Q1, Q2, and Q3; was stable in Q4; and continued to grow in Q5. Longitudinal changes varied by donor relationship, and the association of income with longitudinal changes also varied by donor relationship. In conclusion, changes in living donation in the past decade varied by median household income, resulting in increased disparities in donation between low- and high-income populations. These findings may inform public policies to support living donation during periods of economic volatility. PMID:25035519

1D.12: THE CONTRIBUTION OF INFLAMMATION AND ATHEROSCLEROSIS TO HYPERTENSION IN KIDNEY TRANSPLANTS.

PubMed

Rivero, M Azancot; Ramos, N; Torres, I; Moreso, F; Garcia, C; Romero, K; Espiinel, E; Seron, D

2015-06-01

Hypertension is more severe in kidney transplant patients than in patients with chronic kidney disease (CKD) and similar renal function. The aim is to study the contribution of subclinical atherosclerosis and low grade inflammation to hypertension in kidney transplants. Between June and September 2011, consecutive kidney transplants with an estimated glomerular filtration rate (e-GFR) <60 ml/min/1.73m2, and without previous history of cardiovascular events were included. At entry, 24 h ambulatory blood pressure monitoring (ABPM), pulse wave velocity (PWV) and carotid echography were performed. A serum sample to determinate interleukin 6 (IL-6), soluble tumor necrosis factor receptor 2 (sTNFR2) and intercellular adhesion molecule 1 (ICAM-1) levels was obtained. CKD patients with similar characteristics were recruited at the same time as a control group. A total of 92 transplants and 30 CKD patients were included. Awake systolic blood pressure (SBP) (135.6 ± 15.3 vs 123.8 ± 15.7 mmHg, p = 0.0001), sleep SBP (131.2 ± 16.2 vs. 113.6 ± 14.3 mmHg, p = 0.0001), Log IL-6 (0.89 ± 0.33 vs 0.71 ± 0.31, p = 0.011) and the total number of carotid plaques (1.17 ± 1.48 vs 0.53 ± 1.07, p = 0.013) were higher and the percentage decline of SBP from day to night was lower in kidney transplants (-3.05 ± 8.19 vs -8.13 ± 7.54, p = 0.003). Independent predictors of awake SBP were urinary protein/creatinine ratio and PWV (R2 = 0.170, p = 0.0001), of sleep SBP were log IL-6 and urinary protein/creatinine (R2 = 0.138, p = 0.001), of percentage decline of SBP from day to night were log IL-6 (figure 1), serum creatinine and total number of carotid plaques (R2 = 0.202, p = 0.0001) and of reverse dipper pattern were log IL6 and total number of carotid plaques.(Figure is included in full-text article.) : IL-6 and number of carotid plaques are increased in kidney transplants in comparison with CKD patients and are associated with higher sleep SBP and reverse dipper pattern in transplantation.

Impact of acute versus prolonged exercise and dehydration on kidney function and injury.

PubMed

Bongers, Coen C W G; Alsady, Mohammad; Nijenhuis, Tom; Tulp, Anouk D M; Eijsvogels, Thijs M H; Deen, Peter M T; Hopman, Maria T E

2018-06-01

Exercise and dehydration may be associated with a compromised kidney function and potential signs of kidney injury. However, the kidney responses to exercise of different durations and hypohydration levels are not yet known. Therefore, we aimed to compare the effects of acute versus prolonged exercise and dehydration on estimated glomerular filtration rate (eGFR) and kidney injury biomarkers in healthy male adults. A total of 35 subjects (23 ± 3 years) were included and invited for two study visits. Visit 1 consisted of a maximal cycling test. On Visit 2, subjects performed a submaximal exercise test at 80% of maximal heart rate until 3% hypohydration. Blood and urine samples were taken at baseline, after 30 min of exercise (acute effects; low level of hypohydration) and after 150 min of exercise or when 3% hypohydration was achieved (prolonged effects, high level of hypohydration). Urinary outcome parameters were corrected for urinary cystatin C, creatinine, and osmolality. Subjects dehydrated on average 0.6 ± 0.3% and 2.9 ± 0.7% after acute and prolonged exercise, respectively (P < 0.001). The eGFR cystatin C did not differ between baseline and acute exercise (118 ± 11 vs. 116 ± 12 mL/min/1.73 m 2 , P = 0.12), whereas eGFR cystatin C was significantly lower after prolonged exercise (103 ± 16 mL/min/1.73 m 2 , P < 0.001). We found no difference in osmolality corrected uKIM1 concentrations after acute and prolonged exercise (P > 0.05), and elevated osmolality corrected uNGAL concentrations after acute and prolonged exercise (all P-values < 0.05). In conclusion, acute exercise did barely impact on eGFR cystatin C and kidney injury biomarkers, whereas prolonged exercise is associated with a decline in eGFR cystatin C and increased biomarkers for kidney injury. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Chloroquine and inhibition of Toll-like receptor 9 protect from sepsis-induced acute kidney injury

PubMed Central

Yasuda, Hideo; Leelahavanichkul, Asada; Tsunoda, Shinichiro; Dear, James W.; Takahashi, Yoshiyuki; Ito, Shuichi; Hu, Xuzhen; Zhou, Hua; Doi, Kent; Childs, Richard; Klinman, Dennis M.; Yuen, Peter S.T.; Star, Robert A.

2008-01-01

Mortality from sepsis has remained high despite recent advances in supportive and targeted therapies. Toll-like receptors (TLRs) sense bacterial products and stimulate pathogenic innate immune responses. Mice deficient in the common adapter protein MyD88, downstream from most TLRs, have reduced mortality and acute kidney injury (AKI) from polymicrobial sepsis. However, the identity of the TLR(s) responsible for the host response to polymicrobial sepsis is unknown. Here, we show that chloroquine, an inhibitor of endocytic TLRs (TLR3, 7, 8, 9), improves sepsis-induced mortality and acute kidney injury in a clinically relevant polymicrobial sepsis mouse model, even when administered 6h after the septic insult. Chloroquine administration attenuated the decline in renal function, splenic apoptosis, serum markers of damage to other organs, and prototypical serum pro- and anti-inflammatory cytokines TNF-alpha and IL-10. An oligodeoxynucleotide inhibitor (H154) of TLR9 and TLR9-deficient mice mirror the actions of chloroquine in all functional parameters that we tested. In addition, chloroquine decreased TLR9 protein abundance in spleen, further suggesting that TLR9 signaling may be a major target for the protective actions of chloroquine. Our findings indicate that chloroquine improves survival by inhibiting multiple pathways leading to polymicrobial sepsis, and that chloroquine and TLR9 inhibitors represent viable broad-spectrum and targeted therapeutic strategies, respectively, that are promising candidates for further clinical development. PMID:18305095

Results from the Atherosclerosis Risk in Communities study suggest that low serum magnesium is associated with incident kidney disease.

PubMed

Tin, Adrienne; Grams, Morgan E; Maruthur, Nisa M; Astor, Brad C; Couper, David; Mosley, Thomas H; Selvin, Elizabeth; Coresh, Josef; Kao, Wen Hong Linda

2015-04-01

Low serum magnesium has been associated with kidney function decline in persons with diabetes as well as cardiovascular disease in the general population. As the association of serum magnesium with incident kidney disease in the general population is unknown, we assessed this in 13,226 participants (aged 45-65) in the Atherosclerosis Risk in Communities study with baseline estimated glomerular filtration rate of at least 60 ml/min per 1.73 m(2) in years 1987-89 and followed through 2010. The risks for incident chronic kidney disease (CKD) and end-stage renal disease (ESRD) associated with baseline total serum magnesium levels were evaluated using Cox regression. There were 1965 CKD and 208 ESRD events during a median follow-up of 21 years. In adjusted analysis, low serum magnesium levels (0.7 mmol/l or less) had significant associations with incident CKD and ESRD compared with the highest quartile with adjusted hazard ratio of 1.58 (95% CI: 1.35-1.87) for CKD and 2.39 (95% CI: 1.61-3.56) for ESRD. These associations remained significant after excluding users of diuretics and across subgroups stratified by hypertension, diabetes, and self-reported race. Thus, in a large sample of middle-aged adults, low total serum magnesium was independently associated with incident CKD and ESRD. Further studies are needed to determine whether modification of serum magnesium levels might alter subsequent incident kidney disease rates.

Results from the Atherosclerosis Risk in Communities study suggest that low serum magnesium is associated with incident kidney disease

PubMed Central

Tin, Adrienne; Grams, Morgan E.; Maruthur, Nisa M.; Astor, Brad C.; Couper, David; Mosley, Thomas H.; Selvin, Elizabeth; Coresh, Josef; Linda Kao, Wen Hong

2014-01-01

Low serum magnesium has been associated with kidney function decline in persons with diabetes as well as cardiovascular disease in the general population. Since the association of serum magnesium with incident kidney disease in the general population is unknown, we assessed this in 13,226 participants (aged 45 to 65) in the Atherosclerosis Risk in Communities study with baseline estimated glomerular filtration rate of at least 60 ml/min/1.73m2 in years 1987–89 and followed through 2010. The risks for incident chronic kidney disease (CKD) and end-stage renal disease (ESRD) associated with baseline total serum magnesium levels were evaluated using Cox regression. There were 1,965 CKD and 208 ESRD events during a median follow-up of 21 years. In adjusted analysis, low serum magnesium levels (0.7mmol/L or less) had significant associations with incident CKD and ESRD compared with the highest quartile with adjusted hazard ratio of 1.58 (95% CI: 1.35–1.87) for CKD and 2.39 (95% CI: 1.61–3.56) for ESRD. These associations remained significant after excluding users of diuretics and across subgroups stratified by hypertension, diabetes, and self-reported race. Thus, in a large sample of middle-aged adults, low total serum magnesium was independently associated with incident CKD and ESRD. Further studies are needed to determine whether modification of serum magnesium levels might alter subsequent incident kidney disease rates. PMID:25272232

DASH (Dietary Approaches to Stop Hypertension) Diet and Risk of Subsequent Kidney Disease

PubMed Central

Rebholz, Casey M.; Crews, Deidra C.; Grams, Morgan E.; Steffen, Lyn M.; Levey, Andrew S.; Miller, Edgar R.; Appel, Lawrence J.; Coresh, Josef

2016-01-01

Background There are established guidelines for recommended dietary intake for hypertension treatment and cardiovascular disease prevention. Evidence is lacking for effective dietary patterns for kidney disease prevention. Study Design Prospective cohort study Setting & Participants Atherosclerosis Risk in Communities (ARIC) study participants with baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 (N=14,882) Predictor The Dietary Approaches to Stop Hypertension (DASH) diet score was calculated based on self-reported dietary intake of red and processed meat, sweetened beverages, sodium, fruits, vegetables, whole grains, nuts and legumes, and low-fat dairy products, averaged over two visits. Outcomes Cases were ascertained based on development of eGFR <60 mL/min/1.73 m2 accompanied by ≥25% eGFR decline from baseline, an ICD-9/10 code for a kidney disease–related hospitalization or death, or end-stage renal disease from baseline through 2012. Results A total of 3,720 participants developed kidney disease during a median follow-up of 23 years. Participants with a DASH diet score in the lowest tertile were 16% more likely to develop kidney disease than those with the highest score tertile (HR, 1.16; 95% CI, 1.07-1.26; p for trend <0.001), after adjusting for socio-demographics, smoking status, physical activity, total caloric intake, baseline eGFR, overweight/obese status, diabetes status, hypertension status, systolic blood pressure, and anti-hypertensive medication use. Of the individual components of the DASH diet score, high intake of red and processed meat was adversely associated with kidney disease and high intake of nuts, legumes, and low-fat dairy products was associated with reduced risk of kidney disease. Limitations Potential measurement error due to self-reported dietary intake and lack of data on albuminuria Conclusions Consuming a DASH-style diet was associated with lower risk for kidney disease, independent of demographic characteristics, established kidney risk factors, and baseline kidney function. Healthful dietary patterns, such as the DASH diet, may be beneficial for kidney disease prevention. PMID:27519166

Factors Associated With Ischemic Stroke Survival and Recovery in Older Adults.

PubMed

Winovich, Divya Thekkethala; Longstreth, William T; Arnold, Alice M; Varadhan, Ravi; Zeki Al Hazzouri, Adina; Cushman, Mary; Newman, Anne B; Odden, Michelle C

2017-07-01

Little is known about factors that predispose older adults to poor recovery after a stroke. In this study, we sought to evaluate prestroke measures of frailty and related factors as markers of vulnerability to poor outcomes after ischemic stroke. In participants aged 65 to 99 years with incident ischemic strokes from the Cardiovascular Health Study, we evaluated the association of several risk factors (frailty, frailty components, C-reactive protein, interleukin-6, and cystatin C) assessed before stroke with stroke outcomes of survival, cognitive decline (≥5 points on Modified Mini-Mental State Examination), and activities of daily living decline (increase in limitations). Among 717 participants with incident ischemic stroke with survival data, slow walking speed, low grip strength, and cystatin C were independently associated with shorter survival. Among participants <80 years of age, frailty and interleukin-6 were also associated with shorter survival. Among 509 participants with recovery data, slow walking speed, and low grip strength were associated with both cognitive and activities of daily living decline poststroke. C-reactive protein and interleukin-6 were associated with poststroke cognitive decline among men only. Frailty status was associated with activities of daily living decline among women only. Markers of physical function-walking speed and grip strength-were consistently associated with survival and recovery after ischemic stroke. Inflammation, kidney function, and frailty also seemed to be determinants of survival and recovery after an ischemic stroke. These markers of vulnerability may identify targets for differing pre and poststroke medical management and rehabilitation among older adults at risk of poor stroke outcomes. © 2017 American Heart Association, Inc.

Management of protein-energy wasting in non-dialysis-dependent chronic kidney disease: reconciling low protein intake with nutritional therapy1234

PubMed Central

Kovesdy, Csaba P; Kopple, Joel D; Kalantar-Zadeh, Kamyar

2013-01-01

Protein-energy wasting (PEW), characterized by a decline in body protein mass and energy reserves, including muscle and fat wasting and visceral protein pool contraction, is an underappreciated condition in early to moderate stages of chronic kidney disease (CKD) and a strong predictor of adverse outcomes. The prevalence of PEW in early to moderate CKD is ≥20–25% and increases as CKD progresses, in part because of activation of proinflammatory cytokines combined with superimposed hypercatabolic states and declines in appetite. This anorexia leads to inadequate protein and energy intake, which may be reinforced by prescribed dietary restrictions and inadequate monitoring of the patient's nutritional status. Worsening uremia also renders CKD patients vulnerable to potentially deleterious effects of uncontrolled diets, including higher phosphorus and potassium burden. Uremic metabolites, some of which are anorexigenic and many of which are products of protein metabolism, can exert harmful effects, ranging from oxidative stress to endothelial dysfunction, nitric oxide disarrays, renal interstitial fibrosis, sarcopenia, and worsening proteinuria and kidney function. Given such complex pathways, nutritional interventions in CKD, when applied in concert with nonnutritional therapeutic approaches, encompass an array of strategies (such as dietary restrictions and supplementations) aimed at optimizing both patients’ biochemical variables and their clinical outcomes. The applicability of many nutritional interventions and their effects on outcomes in patients with CKD with PEW has not been well studied. This article reviews the definitions and pathophysiology of PEW in patients with non-dialysis-dependent CKD, examines the current indications for various dietary modification strategies in patients with CKD (eg, manufactured protein-based supplements, amino acids and their keto acid or hydroxyacid analogues), discusses the rationale behind their potential use in patients with PEW, and highlights areas in need of further research. PMID:23636234

Long-term kidney outcomes among users of proton pump inhibitors without intervening acute kidney injury.

PubMed

Xie, Yan; Bowe, Benjamin; Li, Tingting; Xian, Hong; Yan, Yan; Al-Aly, Ziyad

2017-06-01

Proton pump inhibitor (PPI) use is associated with an increased risk of acute kidney injury (AKI), incident chronic kidney disease (CKD), and progression to end-stage renal disease (ESRD). PPI-associated CKD is presumed to be mediated by intervening AKI. However, whether PPI use is associated with an increased risk of chronic renal outcomes in the absence of intervening AKI is unknown. To evaluate this we used the Department of Veterans Affairs national databases to build a cohort of 144,032 incident users of acid suppression therapy that included 125,596 PPI and 18,436 Histamine H2 receptor antagonist (H2 blockers) consumers. Over 5 years of follow-up in survival models, cohort participants were censored at the time of AKI occurrence. Compared with incident users of H2 blockers, incident users of PPIs had an increased risk of an estimated glomerular filtration rate (eGFR) under 60 ml/min/1.73m 2 (hazard ratio 1.19; 95% confidence interval 1.15-1.24), incident CKD (1.26; 1.20-1.33), eGFR decline over 30% (1.22; 1.16-1.28), and ESRD or eGFR decline over 50% (1.30; 1.15-1.48). Results were consistent in models that excluded participants with AKI either before chronic renal outcomes, during the time in the cohort, or before cohort entry. The proportion of PPI effect mediated by AKI was 44.7%, 45.47%, 46.00%, and 46.72% for incident eGFR under 60 ml/min/1.73m 2 , incident CKD, eGFR decline over 30%, and ESRD or over 50% decline in eGFR, respectively. Thus, PPI use is associated with increased risk of chronic renal outcomes in the absence of intervening AKI. Hence, reliance on antecedent AKI as warning sign to guard against the risk of CKD among PPI users is not sufficient as a sole mitigation strategy. Published by Elsevier Inc.

Influence of CT-based depth correction of renal scintigraphy in evaluation of living kidney donors on side selection and postoperative renal function: is it necessary to know the relative renal function?

PubMed

Weinberger, Sarah; Klarholz-Pevere, Carola; Liefeldt, Lutz; Baeder, Michael; Steckhan, Nico; Friedersdorff, Frank

2018-03-22

To analyse the influence of CT-based depth correction in the assessment of split renal function in potential living kidney donors. In 116 consecutive living kidney donors preoperative split renal function was assessed using the CT-based depth correction. Influence on donor side selection and postoperative renal function of the living kidney donors were analyzed. Linear regression analysis was performed to identify predictors of postoperative renal function. A left versus right kidney depth variation of more than 1 cm was found in 40/114 donors (35%). 11 patients (10%) had a difference of more than 5% in relative renal function after depth correction. Kidney depth variation and changes in relative renal function after depth correction would have had influence on side selection in 30 of 114 living kidney donors. CT depth correction did not improve the predictability of postoperative renal function of the living kidney donor. In general, it was not possible to predict the postoperative renal function from preoperative total and relative renal function. In multivariate linear regression analysis, age and BMI were identified as most important predictors for postoperative renal function of the living kidney donors. Our results clearly indicate that concerning the postoperative renal function of living kidney donors, the relative renal function of the donated kidney seems to be less important than other factors. A multimodal assessment with consideration of all available results including kidney size, location of the kidney and split renal function remains necessary.

Nephrectomy (Kidney Removal)

MedlinePlus

... nephrectomy is needed because of other kidney diseases. Kidney function Most people have two kidneys — fist-sized ... and the disease that prompted the surgery? Monitoring kidney function Most people can function well with only ...

Selective Arterial Clamping Versus Hilar Clamping for Minimally Invasive Partial Nephrectomy.

PubMed

Yezdani, Mona; Yu, Sue-Jean; Lee, David I

2016-05-01

Partial nephrectomy has become an accepted treatment of cT1 renal masses as it provides improved long-term renal function compared to radical nephrectomy (Campbell et al. J Urol. 182:1271-9, 2009). Hilar clamping is utilized to help reduce bleeding and improve visibility during tumor resection. However, concern over risk of kidney injury with hilar clamping has led to new techniques to reduce length of warm ischemia time (WIT) during partial nephrectomy. These techniques have progressed over the years starting with early hilar unclamping, controlled hypotension during tumor resection, selective arterial clamping, minimal margin techniques, and off-clamp procedures. Selective arterial clamping has progressed significantly over the years. The main question is what are the exact short- and long-term renal effects from increasing clamp time. Moreover, does it make sense to perform these more time-consuming or more complex procedures if there is no long-term preservation of kidney function? More recent studies have shown no difference in renal function 6 months from surgery when selective arterial clamping or even hilar clamping is employed, although there is short-term improved decline in estimated glomerular filtration rate (eGFR) with selective clamping and off-clamp techniques (Komninos et al. BJU Int. 115:921-8, 2015; Shah et al. 117:293-9, 2015; Kallingal et al. BJU Int. doi: 10.1111/bju.13192, 2015). This paper reviews the progression of total hilar clamping to selective arterial clamping (SAC) and the possible difference its use makes on long-term renal function. SAC may be attempted based on surgeon's decision-making, but may be best used for more complex, larger, more central or hilar tumors and in patients who have renal insufficiency at baseline or a solitary kidney.

Epoetin beta pegol alleviates oxidative stress and exacerbation of renal damage from iron deposition, thereby delaying CKD progression in progressive glomerulonephritis rats.

PubMed

Hirata, Michinori; Tashiro, Yoshihito; Aizawa, Ken; Kawasaki, Ryohei; Shimonaka, Yasushi; Endo, Koichi

2015-12-01

The increased deposition of iron in the kidneys that occurs with glomerulopathy hinders the functional and structural recovery of the tubules and promotes progression of chronic kidney disease (CKD). Here, we evaluated whether epoetin beta pegol (continuous erythropoietin receptor activator: CERA), which has a long half-life in blood and strongly suppresses hepcidin-25, exerts renoprotection in a rat model of chronic progressive glomerulonephritis (cGN). cGN rats showed elevated urinary total protein excretion (uTP) and plasma urea nitrogen (UN) from day 14 after the induction of kidney disease (day 0) and finally declined into end-stage kidney disease (ESKD), showing reduced creatinine clearance with glomerulosclerosis, tubular dilation, and tubulointerstitial fibrosis. A single dose of CERA given on day 1, but not on day 16, alleviated increasing uTP and UN, thereby delaying ESKD. In the initial disease phase, CERA significantly suppressed urinary 8-OHdG and liver-type fatty acid-binding protein (L-FABP), a tubular damage marker. CERA also inhibited elevated plasma hepcidin-25 levels and alleviated subsequent iron accumulation in kidneys in association with elevated urinary iron excretion and resulted in alleviation of growth of Ki67-positive tubular and glomerular cells. In addition, at day 28 when the exacerbation of uTP occurs, a significant correlation was observed between iron deposition in the kidney and urinary L-FABP. In our study, CERA mitigated increasing kidney damage, thereby delaying CKD progression in this glomerulonephritis rat model. Alleviation by CERA of the exacerbation of kidney damage could be attributable to mitigation of tubular damage that might occur with lowered iron deposition in tubules. © 2015 Chugai Pharmaceutical Co., Ltd. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Cystatin C and Cardiac Measures in Children and Adolescents With CKD.

PubMed

Brady, Tammy M; Townsend, Kelly; Schneider, Michael F; Cox, Christopher; Kimball, Thomas; Madueme, Peace; Warady, Bradley; Furth, Susan; Mitsnefes, Mark

2017-02-01

Cardiovascular disease (CVD) is highly prevalent among children with chronic kidney disease (CKD). Cystatin C is an established marker of kidney function and an emerging biomarker for CVD events. We quantified the relationship between cystatin C level and cardiac structure and function over time among children with CKD and assessed whether cystatin C level and diastolic function retained an association after accounting for kidney function. Prospective cohort study. 678 children and adolescents with mild to moderate CKD enrolled in the CKD in Children (CKiD) Study with 1,228 echocardiographically obtained cardiac structure and function measurements. Serum cystatin C (mg/L) measured annually. Cardiac structure (left ventricular mass index [g/m 2.7 ]) and cardiac function (shortening fraction; E/A, E'/A', E/E' ratios) measured every other year. Demographics and anthropometrics, measured glomerular filtration rate (mGFR), heart rate, blood pressure, hemoglobin z score, serum albumin level, and calcium-phosphorus product. Independent of time, each 1-mg/L increase in cystatin C level was independently associated with a concurrent 7.7% (95% CI, 5.3%-10.0%) increase in left ventricular mass index, a -4.7% (95% CI, -7.0% to -2.4%) change in E/A ratio, a -6.6% (95% CI, -9.0% to -4.2%) change in E'/A' ratio, and a 2.5% (95% CI, 0.3%-4.7%) increase in E/E' ratio. mGFR was also independently associated with E'/A' ratio. When cystatin C level and mGFR were included in the same model, cystatin C level remained independently associated with E'/A' ratio, whereas mGFR was not. 24% of the cohort was missing data for outcomes of interest or measurements; study population includes only children and adolescents with mild to moderate CKD. In this study of children and adolescents with mild to moderate CKD, cystatin C level was independently associated with cardiac structure and diastolic function. Cystatin C level remained able to predict diastolic function decline via E'/A' ratio even after adjusting for mGFR, suggesting that cystatin C level may have an independent role in CVD risk stratification among children and adolescents with CKD. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Parental health literacy and progression of chronic kidney disease in children.

PubMed

Ricardo, Ana C; Pereira, Lynn N; Betoko, Aisha; Goh, Vivien; Amarah, Amatur; Warady, Bradley A; Moxey-Mims, Marva; Furth, Susan; Lash, James P

2018-06-14

Limited health literacy has been associated with adverse outcomes in children. We evaluated this association in the setting of chronic kidney disease (CKD). We assessed the parental health literacy of 367 children enrolled in the Chronic Kidney Disease in Children (CKiD) Study, using the Short Test of Functional Health Literacy (STOFHLA). We evaluated the association between parental health literacy and CKD progression, defined as time to the composite event of renal replacement therapy (RRT, dialysis, or kidney transplant) or 50% decline in estimated glomerular filtration rate (eGFR). Median CKiD participant age was 9.5 years, 63% were male, and 59% non-Hispanic white. Median eGFR at baseline was 63 ml/min/1.73 m 2 , and median urine protein-to-creatinine ratio was 0.22. The median STOFHLA score was 98. Over a median follow-up of 3.7 years, the overall CKD progression rate was 2.8 per 100 person-years. After adjustment for demographic and clinical factors, the relative time to CKD progression was 28% longer per 1 SD increase in STOFHLA score (relative time, 95% CI, 1.28, 1.06-1.53). In this cohort of children with CKD, higher parental health literacy was associated with a nearly 30% longer time to the composite CKD progression outcome.

Momordica charantia polysaccharides mitigate the progression of STZ induced diabetic nephropathy in rats.

PubMed

Raish, Mohammad; Ahmad, Ajaz; Jan, Basit L; Alkharfy, Khalid M; Ansari, Mushtaq Ahmad; Mohsin, Kazi; Jenoobi, Fahad Al; Al-Mohizea, Abdullah

2016-10-01

Diabetic nephropathy (DN) has become a primary cause of end-stage kidney disease. Several complex dynamics converge together to accelerate the advancement of DN. The present investigation was postulated to explore the mechanism of reno-protective nature of Momordica Charantia polysaccharides (MCP) by evaluating the anti-hyperglycemic, anti-lipidemic as well as markers for oxidative stress and antioxidant proficiency in streptozotocin (STZ)-induced diabetic rats. The oral administration of MCP showed a significant normalization in the levels of kidney function test in the STZ-induced diabetic rats. The levels of blood urea nitrogen (BUN), urea protein and creatinine increased by 316.58%, 195.14% and 800.97% respectively, in STZ-induced diabetic rats when compared with normal rats. MCP treatment also illustrated a significant improvement in glutathione peroxidase, superoxide dismutase and catalase levels, with a significant decline in MDA in diabetic kidneys. Immunoblots of heme-oxygenase 1 (HO-1) and Nrf2 of MCP treated diabetic rats showed a significant up-regulation of HO-1 and Nrf2 protein. Histological and ultra-structural observations also reveal that MCP efficiently protects the kidneys from hyperglycemia-mediated oxidative damage. These findings illustrate that the reno-protective nature of MCP mitigates the progression of STZ induced DN in rats by suppression of oxidative stress and amelioration of the HO-1/Nrf2 pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

Hyaluronan and Stone Disease

NASA Astrophysics Data System (ADS)

Asselman, Marino

2008-09-01

Kidney stones cannot be formed as long as crystals are passed in the urine. However, when crystals are retained it becomes possible for them to aggregate and form a stone. Crystals are expected to be formed not earlier than the distal tubules and collecting ducts. Studies both in vitro and in vivo demonstrate that calcium oxalate monohydrate crystals do not adhere to intact distal epithelium, but only when the epithelium is proliferating or regenerating, so that it possesses dedifferentiated cells expressing hyaluronan, osteopontin (OPN) and their mutual receptor CD44 at the apical cell membrane. The polysaccharide hyaluronan is an excellent crystal binding molecule because of its negative ionic charge. We hypothesized that the risk for crystal retention in the human kidney would be increased when tubular cells express hyaluronan at their apical cell membrane. Two different patient categories in which nephrocalcinosis frequently occurs were studied to test this hypothesis (preterm neonates and kidney transplant patients). Hyaluronan (and OPN) expression at the luminal membrane of tubular cells indeed was observed, which preceded subsequent retention of crystals in the distal tubules. Tubular nephrocalcinosis has been reported to be associated with decline of renal function and thus further studies to extend our knowledge of the mechanisms of retention and accumulation of crystals in the kidney are warranted. Ultimately, this may allow the design of new strategies for the prevention and treatment of both nephrocalcinosis and nephrolithiasis in patients.

Immunogenicity of the meningococcal polysaccharide conjugate vaccine in pediatric kidney transplant patients.

PubMed

Nelson, Delphine R; Fadrowski, Jeffrey; Neu, Alicia

2018-06-01

Immunosuppressed kidney transplant patients may have suboptimal response to vaccinations. The aim of this study was to determine antibody response to a quadrivalent meningococcal conjugate vaccine (MenACWY-D) in adolescents with a kidney transplant. This was a prospective, single-center, cohort study. Adolescent patients (11-22 years old) with a functioning kidney transplant for at least 3 months and no previous meningococcal vaccination were eligible for enrollment. Antibody levels to all serogroups were measured before vaccination (baseline) and at 4 weeks and 1, 2 and 3 years after vaccination. Seropositivity was defined as a titer ≥ 1:8 at baseline, and seroconversion as a fourfold or greater increase in antibody titer from baseline at 4 weeks post-vaccination. Geometric mean titers (GMTs) were calculated at each time point and compared to published GMTs from vaccinated healthy adolescents. Nineteen patients were enrolled. No patient had seroprotective titers against all four serogroups at baseline. At 4 weeks post-vaccination 41% of patients seroconverted to all four serogroups, with seroconversion rates of 88, 53, 71 and 94% for serogroups A, C, W and Y, respectively. GMTs were significantly lower in adolescents with a kidney transplant than in healthy adolescents at 1 month (p = 0.02) and 3 years (p = 0.04) post-vaccination. There were no significant adverse events, episodes of rejection or death in any patient. Adolescents with a kidney transplant may not respond adequately to MenACWY-D and may experience more rapid declines in antibody titers than healthy adolescents. Further study is needed to determine if alternative dosing schedules can improve antibody response in this population.

Simultaneous Risk Factor Control Using Telehealth to slOw Progression of Diabetic Kidney Disease (STOP-DKD) study: Protocol and baseline characteristics of a randomized controlled trial.

PubMed

Diamantidis, Clarissa J; Bosworth, Hayden B; Oakes, Megan M; Davenport, Clemontina A; Pendergast, Jane F; Patel, Sejal; Moaddeb, Jivan; Barnhart, Huiman X; Merrill, Peter D; Baloch, Khaula; Crowley, Matthew J; Patel, Uptal D

2018-06-01

Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease (ESKD) in the United States. Multiple risk factors contribute to DKD development, yet few interventions target more than a single DKD risk factor at a time. This manuscript describes the study protocol, recruitment, and baseline participant characteristics for the Simultaneous Risk Factor Control Using Telehealth to slOw Progression of Diabetic Kidney Disease (STOP-DKD) study. The STOP-DKD study is a randomized controlled trial designed to evaluate the effectiveness of a multifactorial behavioral and medication management intervention to mitigate kidney function decline at 3 years compared to usual care. The intervention consists of up to 36 monthly educational modules delivered via telephone by a study pharmacist, home blood pressure monitoring, and medication management recommendations delivered electronically to primary care physicians. Patients seen at seven primary care clinics in North Carolina, with diabetes and [1] uncontrolled hypertension and [2] evidence of kidney dysfunction (albuminuria or reduced estimated glomerular filtration rate [eGFR]) were eligible to participate. Study recruitment completed in December 2014. Of the 281 participants randomized, mean age at baseline was 61.9; 52% were male, 56% were Black, and most were high school graduates (89%). Baseline co-morbidity was high- mean blood pressure was 134/76 mmHg, mean body mass index was 35.7 kg/m 2 , mean eGFR was 80.7 ml/min/1.73 m 2 , and mean glycated hemoglobin was 8.0%. Experiences of recruiting and implementing a comprehensive DKD program to individuals at high risk seen in the primary care setting are provided. NCT01829256. Copyright © 2018 Elsevier Inc. All rights reserved.

Fascin-1 is released from proximal tubular cells in response to calcineurin inhibitors (CNIs) and correlates with isometric vacuolization in kidney transplanted patients

PubMed Central

Jacobs-Cachá, Conxita; Torres, Irina B; López-Hellín, Joan; Cantarell, Carme; Azancot, María A; Román, Antonio; Moreso, Francesc; Serón, Daniel; Meseguer, Anna; Sarró, Eduard

2017-01-01

Immunosuppression based on calcineurin inhibitors (CNIs) has greatly improved organ transplantation, although subsequent nephrotoxicity significantly hinders treatment success. There are no currently available specific soluble biomarkers for CNI-induced nephrotoxicity and diagnosis relies on renal biopsy, which is costly, invasive and may cause complications. Accordingly, identification of non-invasive biomarkers distinguishing CNI-induced kidney tubular damage from that of other etiologies would greatly improve diagnosis and enable more precise dosage adjustment. For this purpose, HK-2 cells, widely used to model human proximal tubule, were treated with CNIs cyclosporine-A and FK506, or staurosporine as a calcineurin-independent toxic compound, and secretomes of each treatment were analyzed by proteomic means. Among the differentially secreted proteins identified, only fascin-1 was specifically released by both CNIs but not by staurosporine. To validate fascin-1 as a biomarker of CNI-induced tubular toxicity, fascin-1 levels were analyzed in serum and urine from kidney-transplanted patients under CNIs treatment presenting or not isometric vacuolization (IV), which nowadays represents the main histological hallmark of CNI-induced tubular damage. Patients with chronic kidney disease (CKD) and healthy volunteers were used as controls. Our results show that urinary fascin-1 was only significantly elevated in the subset of CNI-treated patients presenting IV. Moreover, fascin-1 anticipated the rise of sCr levels in serially collected urine samples from CNI-treated pulmonary-transplanted patients, where a decline in kidney function and serum creatinine (sCr) elevation was mainly attributed to CNIs treatment. In conclusion, our results point towards fascin-1 as a putative soluble biomarker of CNI-induced damage in the kidney tubular compartment. PMID:28979691

Fascin-1 is released from proximal tubular cells in response to calcineurin inhibitors (CNIs) and correlates with isometric vacuolization in kidney transplanted patients.

PubMed

Jacobs-Cachá, Conxita; Torres, Irina B; López-Hellín, Joan; Cantarell, Carme; Azancot, María A; Román, Antonio; Moreso, Francesc; Serón, Daniel; Meseguer, Anna; Sarró, Eduard

2017-01-01

Immunosuppression based on calcineurin inhibitors (CNIs) has greatly improved organ transplantation, although subsequent nephrotoxicity significantly hinders treatment success. There are no currently available specific soluble biomarkers for CNI-induced nephrotoxicity and diagnosis relies on renal biopsy, which is costly, invasive and may cause complications. Accordingly, identification of non-invasive biomarkers distinguishing CNI-induced kidney tubular damage from that of other etiologies would greatly improve diagnosis and enable more precise dosage adjustment. For this purpose, HK-2 cells, widely used to model human proximal tubule, were treated with CNIs cyclosporine-A and FK506, or staurosporine as a calcineurin-independent toxic compound, and secretomes of each treatment were analyzed by proteomic means. Among the differentially secreted proteins identified, only fascin-1 was specifically released by both CNIs but not by staurosporine. To validate fascin-1 as a biomarker of CNI-induced tubular toxicity, fascin-1 levels were analyzed in serum and urine from kidney-transplanted patients under CNIs treatment presenting or not isometric vacuolization (IV), which nowadays represents the main histological hallmark of CNI-induced tubular damage. Patients with chronic kidney disease (CKD) and healthy volunteers were used as controls. Our results show that urinary fascin-1 was only significantly elevated in the subset of CNI-treated patients presenting IV. Moreover, fascin-1 anticipated the rise of sCr levels in serially collected urine samples from CNI-treated pulmonary-transplanted patients, where a decline in kidney function and serum creatinine (sCr) elevation was mainly attributed to CNIs treatment. In conclusion, our results point towards fascin-1 as a putative soluble biomarker of CNI-induced damage in the kidney tubular compartment.

Pancreas Transplantation for Patients with Type 1 and Type 2 Diabetes Mellitus in the United States: A Registry Report.

PubMed

Gruessner, Angelika C; Gruessner, Rainer W G

2018-06-01

Successful pancreas transplantation is still the only method to restore short-term and long-term insulin independence and good metabolic control for patients with diabetes. Since the first transplant in 1966, tremendous progress in outcome was made; however, transplant numbers have declined since 2004. This article describes the development and risk factors of pancreas transplantation with or without a kidney graft between 2001 and 2016. Patient survival and graft function improved significantly owing to careful recipient and donor selection, which reduced technical failure and immunologic graft loss rates. Published by Elsevier Inc.

Englerin A Delivers One-Two Punch to Kidney Cancer Cells | Center for Cancer Research

Cancer.gov

While overall cancer death rates continue to decline in the U.S., mortality rates for certain cancer sites, including the kidney, are on the rise. New treatments are needed to reverse this trend and one potentially rich source is natural products, compounds derived from living organisms. John Beutler, Ph.D., and his colleagues, in CCR’s Molecular Targets Laboratory located at

Febuxostat Prevents Renal Interstitial Fibrosis by the Activation of BMP-7 Signaling and Inhibition of USAG-1 Expression in Rats.

PubMed

Cao, Jing; Li, Yong; Peng, Yingxian; Zhang, Yaqian; Li, Huanhuan; Li, Ran; Xia, Anzhou

2015-01-01

Renal interstitial fibrosis (RIF) is a common pathology associated with end-stage renal diseases. The activation of bone morphogenetic protein-7 (BMP-7)-Smad1/5/8 pathway seems to alleviate RIF. Uterine sensitization-associated gene-1 (USAG-1), a kidney-specific BMPs antagonist, is associated with the development and prognosis of several renal diseases. Febuxostat is a xanthine oxidase inhibitor that can attenuate the renal dysfunction of patients. The purpose of this study was to investigate the effects of febuxostat on renal fibrosis and to clarify the mechanisms underlying these effects. Rats were randomly divided into 6 groups termed a sham-operated group, a unilateral ureteral obstruction (UUO) group, 3 doses of febuxostat groups (low, intermediate and high doses) and a sham group treated with high-dose febuxostat. After 14 days, renal function, relative kidney weight, accumulation of glycogen and collagens were examined by different methods. Expression of α-SMA, transforming growth factor-β1 (TGF-β1), BMP-7 and USAG-1 was detected by western blotting and RT-PCR, respectively. The phosphorylation level of Smad1/5/8 was also quantified by western blotting. The renal function was declined, and large amounts of glycogen and collagens were deposited in the kidneys of UUO rats compared with the rats in the sham group. Besides, expression of α-SMA and USAG-1 in these kidneys was elevated, and the TGF-β1 was also activated, while the BMP-7-Smad1/5/8 pathway was inhibited. Febuxostat reversed the changes stated earlier, exhibiting protective effects on RIF induced by UUO. Febuxostat was able to attenuate RIF caused by UUO, which was associated with the activation of BMP-7-Smad1/5/8 pathway and the inhibition of USAG-1 expression in the kidneys of UUO rats. © 2015 S. Karger AG, Basel.

Impact of Obesity on Modality Longevity, Residual Kidney Function, Peritonitis, and Survival Among Incident Peritoneal Dialysis Patients.

PubMed

Obi, Yoshitsugu; Streja, Elani; Mehrotra, Rajnish; Rivara, Matthew B; Rhee, Connie M; Soohoo, Melissa; Gillen, Daniel L; Lau, Wei-Ling; Kovesdy, Csaba P; Kalantar-Zadeh, Kamyar

2018-06-01

The prevalence of severe obesity, often considered a contraindication to peritoneal dialysis (PD), has increased over time. However, mortality has decreased more rapidly in the PD population than the hemodialysis (HD) population in the United States. The association between obesity and clinical outcomes among patients with end-stage kidney disease remains unclear in the current era. Historical cohort study. 15,573 incident PD patients from a large US dialysis organization (2007-2011). Body mass index (BMI). Modality longevity, residual renal creatinine clearance, peritonitis, and survival. Higher BMI was significantly associated with shorter time to transfer to HD therapy (P for trend < 0.001), longer time to kidney transplantation (P for trend < 0.001), and, with borderline significance, more frequent peritonitis-related hospitalization (P for trend = 0.05). Compared with lean patients, obese patients had faster declines in residual kidney function (P for trend < 0.001) and consistently achieved lower total Kt/V over time (P for trend < 0.001) despite greater increases in dialysis Kt/V (P for trend < 0.001). There was a U-shaped association between BMI and mortality, with the greatest survival associated with the BMI range of 30 to < 35kg/m 2 in the case-mix adjusted model. Compared with matched HD patients, PD patients had lower mortality in the BMI categories of < 25 and 25 to < 35kg/m 2 and had equivalent survival in the BMI category ≥ 35kg/m 2 (P for interaction = 0.001 [vs < 25 kg/m 2 ]). This attenuation in survival difference among patients with severe obesity was observed only in patients with diabetes, but not those without diabetes. Inability to evaluate causal associations. Potential indication bias. Whereas obese PD patients had higher risk for complications than nonobese PD patients, their survival was no worse than matched HD patients. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Outcome Measures Used to Report Kidney Function in Studies Investigating Surgical Management of Kidney Tumours: A Systematic Review.

PubMed

Ellis, Robert J; Cho, Yeoungjee; Del Vecchio, Sharon J; McStea, Megan; Morais, Christudas; Coombes, Jeff S; Wood, Simon T; Gobe, Glenda C; Francis, Ross S

2018-05-01

Most practice decisions relevant to preserving kidney function in patients managed surgically for kidney tumours are driven by observational studies. A wide range of outcome measures are used in these studies, which reduces comparability and increases the risk of reporting bias. To comprehensively and succinctly describe the outcomes used to evaluate kidney function in studies evaluating surgical management of kidney tumours. Electronic search of the PubMed database was conducted to identify studies with at least one measure of kidney function in patients managed surgically for kidney tumours, published between January 2000 and September 2017. Abstracts were initially screened for eligibility. Full texts of articles were then evaluated in more detail for inclusion. A narrative synthesis of the evidence was conducted. A total of 312 studies, involving 127905 participants, were included in this review. Most were retrospective (n=274) studies and conducted in a single centre (n=264). Overall, 78 unique outcome measures were identified, which were grouped into six outcome categories. Absolute postoperative kidney function (n=187), relative kidney function (n=181), and postoperative chronic kidney disease (n=131) were most frequently reported. Kidney function was predominantly quantified using estimated glomerular filtration rate or creatinine clearance (n=255), most using the modification of diet in renal disease equation (n=182). Only 70 studies provided rationale for specific outcome measures used. There is significant variability in the reporting and quantification of kidney function in studies evaluating patients managed surgically for kidney tumours. A standardised approach to measuring and reporting kidney function will increase the effectiveness of outcomes reported and improve relevance of research findings within a clinical context. Although we know that the removal of a kidney can reduce kidney function, clinical significance of various approaches is a matter of debate. This article demonstrates significant variability in the way kidney function was reported across all studies of patients with kidney cancer undergoing surgery, indicating a need for standardisation. Copyright © 2018 European Association of Urology. All rights reserved.

Plasma Klotho and Cognitive Decline in Older Adults: Findings From the InCHIANTI Study

PubMed Central

Semba, Richard D.; Rosano, Caterina; Kalyani, Rita R.; Bandinelli, Stefania; Chia, Chee W.; Ferrucci, Luigi

2016-01-01

Background. The hormone klotho, encoded by the gene klotho, is primarily expressed in the kidney and choroid plexus of the brain. Higher klotho concentrations and certain genetic variants of klotho have been linked to better cognition; however, it is unknown whether klotho relates prospectively to slower cognitive decline in older adults. Methods: Plasma klotho was measured in 833 participants aged 55 or older without dementia enrolled in InCHIANTI, a prospective cohort study comprising Italian adults. Cognition was measured by Mini-Mental State Examination (MMSE) and Trail-Making Tests A and B (Trails A and Trails B) at enrollment and at 3 and 6 years after enrollment. We assessed whether klotho concentrations measured at the 3-year visit related to cognition and cognitive decline. Results: Each additional natural logarithm of klotho (pg/mL) was associated with 35% lower risk of meaningful decline in MMSE, defined as decline exceeding three points (relative risk = 0.65; 95% confidence interval 0.45, 0.95; p value = .02), and 0.75-point smaller average 3-year decline (baseline to 3-year visit) in MMSE (95% confidence interval 0.02, 1.48; p value = .04). No statistically significant associations were found between klotho and declining Trails A (relative risk = 0.99; 95% confidence interval 0.75, 1.32; p value = .97) and B (relative risk = 1.02; 95% confidence interval 0.84, 1.24; p value = .82). Conclusions: Higher plasma klotho concentrations were associated with lower risk of meaningful decline and smaller average decline in MMSE. We did not observe such findings with Trails A and B, perhaps because they test executive function and motor skills, whereas MMSE measures global cognition. Future studies should investigate mechanisms through which klotho may affect domain-specific cognitive changes. PMID:26297657

Hyperhomocysteinaemia as a potential marker of early renal function decline in middle-aged Asian people without chronic kidney disease.

PubMed

Tak, Young Jin; Jeong, Dong Wook; Kim, Yun Jin; Lee, Sang Yeoup; Lee, Jeong Gyu; Song, Sang Heon; Cha, Kwang Soo; Kang, Yang Ho

2016-02-01

High levels of serum total homocysteine (tHcy), often observed in chronic kidney disease (CKD) patients, are a risk factor for cardiovascular disease. However, little is known about the relationship between tHcy and renal function in healthy individuals. We examined whether tHcy levels are related to renal function in Asian individuals without CKD. This cross-sectional study examined 2032 subjects, aged 40-64 years. Individuals with kidney diseases or other conditions that could affect tHcy were excluded. Renal function was determined by estimated glomerular filtration rate (eGFR) from levels of serum creatinine (sCr) and cystatin C. Age, tHcy, sCr, and cystatin C of the subjects were 54.1 ± 6.0 years, 9.5 (8.0-11.4) μmol/L, 0.81 ± 0.1 mg/dL, and 0.82 ± 0.1 mg/L, respectively. In a multiple linear regression analysis, tHcy was a significant independent determinant of sCr and cystatin C in men (β = 0.206 and β = 0.282, respectively) and women (β = 0.247 and β = 0.229, respectively). Highest tHcy levels were independently associated with increased cystatin C (>s1.10 mg/L) with an odds ratio (OR) of 5.00 [95% confidence interval (CI) 2.81-8.09] and decreased eGFR (<90 mL/min/1.73 m(2)) with an OR of 1.69 (95% CI 1.36-2.11) compared to tHcy levels in the 1st-3rd quartiles. Higher levels of tHcy are independently associated with sCr and cystatin C elevation. Our study suggests that tHcy levels may be influenced by renal function in Asian populations without CKD. Future studies are needed to define the role of tHcy in renal function.

Urine peptidome analysis predicts risk of end-stage renal disease and reveals proteolytic pathways involved in autosomal dominant polycystic kidney disease progression.

PubMed

Pejchinovski, Martin; Siwy, Justyna; Metzger, Jochen; Dakna, Mohammed; Mischak, Harald; Klein, Julie; Jankowski, Vera; Bae, Kyongtae T; Chapman, Arlene B; Kistler, Andreas D

2017-03-01

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by slowly progressive bilateral renal cyst growth ultimately resulting in loss of kidney function and end-stage renal disease (ESRD). Disease progression rate and age at ESRD are highly variable. Therapeutic interventions therefore require early risk stratification of patients and monitoring of disease progression in response to treatment. We used a urine peptidomic approach based on capillary electrophoresis-mass-spectrometry (CE-MS) to identify potential biomarkers reflecting the risk for early progression to ESRD in the Consortium of Radiologic Imaging in Polycystic Kidney Disease (CRISP) cohort. A biomarker-based classifier consisting of 20 urinary peptides allowed the prediction of ESRD within 10-13 years of follow-up in patients 24-46 years of age at baseline. The performance of the biomarker score approached that of height-adjusted total kidney volume (htTKV) and the combination of the biomarker panel with htTKV improved prediction over either one alone. In young patients (<24 years at baseline), the same biomarker model predicted a 30 mL/min/1.73 m 2 glomerular filtration rate decline over 8 years. Sequence analysis of the altered urinary peptides and the prediction of the involved proteases by in silico analysis revealed alterations in distinct proteolytic pathways, in particular matrix metalloproteinases and cathepsins. We developed a urinary test that accurately predicts relevant clinical outcomes in ADPKD patients and suggests altered proteolytic pathways involved in disease progression. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Histopathologic Findings of Potential Kidney Donors With Asymptomatic Microscopic Hematuria: Impact on Donation.

PubMed

Hassan, E A; Ali, T Z; Abdulbaki, A; Ibrahim, I A; Almanae, H M; Aleid, H A

2017-10-01

Isolated microscopic hematuria (IMH) is not uncommon in potential kidney donors. The aim was to study the kidney biopsy findings of potential kidney donors with IMH and the impact of the histopathologic diagnoses on the decision to accept or decline such donors from kidney donation. In this retrospective study, all the potential kidney donors with IMH were identified from the medical records of patients who underwent kidney biopsies between January 2010 and December 2016. Forty-five such individuals were identified. The mean age of these potential donors was 32.6 years and 76% were male. All of them had normal blood pressure and no significant proteinuria. Seventeen (38%) biopsies showed histopathologic abnormalities; thin basement membrane disease (n = 13; 28%) was the most common cause followed by immunoglobulin (Ig)A nephropathy (n = 4; 9%). Donors with abnormal biopsy findings were excluded from donation. However, 62% of the potential donors had normal kidney biopsy findings and were accepted for kidney donation. IMH justifies extensive work-up including kidney biopsy to identify donors who may have underlying significant glomerular pathology excluding them from kidney donation. On the other hand, kidney biopsy also helps in accepting the donors if it does not show significant abnormality. Copyright © 2017 Elsevier Inc. All rights reserved.

Chronic Kidney Disease, Fluid Overload and Diuretics: A Complicated Triangle.

PubMed

Khan, Yusra Habib; Sarriff, Azmi; Adnan, Azreen Syazril; Khan, Amer Hayat; Mallhi, Tauqeer Hussain

2016-01-01

Despite promising role of diuretics to manage fluid overload among chronic kidney disease (CKD) patients, their use is associated with adverse renal outcomes. Current study aimed to determine the extent of renal deterioration with diuretic therapy. A total 312 non-dialysis dependent CKD (NDD-CKD) patients were prospectively followed-up for one year. Fluid overload was assessed via bioimpedance spectroscopy. Estimated GFR (eGFR) was calculated from serum creatinine values by using Chronic Kidney Disease- Epidemiology Collaboration (CKD-EPI) equation. Out of 312 patients, 64 (20.5%) were hypovolemic while euvolemia and hypervolemia were observed in 113 (36.1%) and 135 (43.4%) patients. Overall 144 patients were using diuretics among which 98 (72.6%) were hypervolemic, 35 (30.9%) euvolemic and 11 (17.2%) were hypovolemic. The mean decline in estimated GFR of entire cohort was -2.5 ± 1.4 ml/min/1.73m2 at the end of follow up. The use of diuretics was significantly associated with decline in eGFR. A total of 36 (11.5%) patients initiated renal replacement therapy (RRT) and need of RRT was more profound among diuretic users. The use of diuretics was associated with adverse renal outcomes indicated by decline in eGFR and increasing risk of RRT initiation in our cohort of NDD-CKD patients. Therefore, it is cautiously suggested to carefully prescribe diuretics by keeping in view benefit versus harm for each patient.

Managing type 1 diabetes mellitus in pregnancy--from planning to breastfeeding.

PubMed

Ringholm, Lene; Mathiesen, Elisabeth R; Kelstrup, Louise; Damm, Peter

2012-11-01

Type 1 diabetes mellitus in pregnant women increases the risk of adverse outcomes for mother and offspring. Careful preconception counselling and screening is important, with particular focus on glycaemic control, indications for antihypertensive therapy, screening for diabetic nephropathy, diabetic retinopathy and thyroid dysfunction, as well as review of other medications. Supplementation with folic acid should be initiated before conception in order to minimize the risk of fetal malformations. Obtaining and maintaining tight control of blood glucose and blood pressure before and during pregnancy is crucial for optimizing outcomes; however, the risk of severe hypoglycaemia during pregnancy is a major obstacle. Although pregnancy does not result in deterioration of kidney function in women with diabetic nephropathy and normal serum creatinine levels, pregnancy complications such as pre-eclampsia and preterm delivery are more frequent in these women than in women with T1DM and normal kidney function. Rapid-acting insulin analogues are considered safe to use in pregnancy and studies on long-acting insulin analogues have provided reassuring results. Immediately after delivery the insulin requirement declines to approximately 60% of the prepregnancy dose, and remains 10% lower than before pregnancy during breastfeeding.

Mediterranean diet as the diet of choice for patients with chronic kidney disease.

PubMed

Chauveau, Philippe; Aparicio, Michel; Bellizzi, Vincenzo; Campbell, Katrina; Hong, Xu; Johansson, Lina; Kolko, Anne; Molina, Pablo; Sezer, Siren; Wanner, Christoph; Ter Wee, Pieter M; Teta, Daniel; Fouque, Denis; Carrero, Juan J

2018-05-01

Traditional dietary management of chronic kidney disease (CKD) focuses on the quantity within the diet of energy and protein, and the restriction of single micronutrients, with little mention of dietary quality. Dietary patterns that are more plant-based, lower in meat (including processed meat), sodium and refined sugar, and have a higher content of grains and fibres are now included in multiple clinical guidelines for chronic disease prevention. The Mediterranean diet (MD) has been associated with reduced cardiovascular disease incidence in both observational and interventional studies. A wealth of evidence links MD with other beneficial effects on chronic diseases such as diabetes, obesity or cognitive health. This review examines each constituent of the classical MD and evaluates their suitability for the management of patients with CKD. We also evaluate the potential hyperkalaemia risk of increasing fruit and vegetable intake. Overall, a decrease in net endogenous acid production and increase in fibre may lead to a better control of metabolic acidosis. This, together with other putative favourable effects of MD on endothelial function, inflammation, lipid profile and blood pressure, provide mechanistic pathways to explain the observed reduced renal function decline and improved survival in CKD patients adhering to an MD.

Diuretic renography in hydronephrosis: renal tissue tracer transit predicts functional course and thereby need for surgery.

PubMed

Schlotmann, Andreas; Clorius, John H; Clorius, Sandra N

2009-10-01

The recognition of those hydronephrotic kidneys which require therapy to preserve renal function remains difficult. We retrospectively compared the 'tissue tracer transit' (TTT) of (99m)Tc-mercaptoacetyltriglycine ((99m)Tc-MAG(3)) with 'response to furosemide stimulation' (RFS) and with 'single kidney function < 40%' (SKF < 40%) to predict functional course and thereby need for surgery. Fifty patients with suspected unilateral obstruction and normal contralateral kidney had 115 paired (baseline/follow-up) (99m)Tc-MAG(3) scintirenographies. Three predictions of the functional development were derived from each baseline examination: the first based on TTT (visually assessed), the second on RFS and the third on SKF < 40%. Each prediction also considered whether the patient had surgery. Possible predictions were 'better', 'worse' or 'stable' function. A comparison of SKF at baseline and follow-up verified the predictions. The frequency of correct predictions for functional improvement following surgery was 8 of 10 kidneys with delayed TTT, 9 of 22 kidneys with obstructive RFS and 9 of 21 kidneys with SKF < 40%; for functional deterioration without surgery it was 2 of 3 kidneys with delayed TTT, 3 of 20 kidneys with obstructive RFS and 3 of 23 kidneys with SKF < 40%. Without surgery 67 of 70 kidneys with timely TTT maintained function. Without surgery 0 of 9 kidneys with timely TTT but obstructive RFS and only 1 of 16 kidneys with timely TTT but SKF < 40% lost function. Delayed TTT appears to identify the need for therapy to preserve function of hydronephrotic kidneys, while timely TTT may exclude risk even in the presence of an obstructive RFS or SKF < 40%.

Metabolically Healthy Obesity and Risk of Kidney Function Decline.

PubMed

Chang, Alex R; Surapaneni, Aditya; Kirchner, H Lester; Young, Amanda; Kramer, Holly J; Carey, David J; Appel, Lawrence J; Grams, Morgan E

2018-04-01

The aim of this study was to examine the association between BMI categories, stratified by metabolic health status, and the risk of kidney function decline (KFD). In this study, 42,128 adult patients with a stable BMI were classified over a 3-year baseline window by BMI and metabolic health status (assessed by Adult Treatment Panel-III criteria). KFD was defined as an estimated glomerular filtration rate (eGFR) decline ≥ 30%, eGFR < 15 mL/min/1.73 m 2 , or receipt of dialysis and/or transplant. Over a median of 5.1 years (interquartile range 2.1-8.9), 6,533 (15.5%) individuals developed KFD. Compared with the normal weight, metabolically healthy category, metabolically healthy obesity was associated with a higher risk of KFD (adjusted hazard ratio [aHR] 1.52; 95% CI: 1.22-1.89). aHRs for KFD were 1.17 (95% CI: 0.89-1.53), 2.21 (95% CI: 1.59-3.08), and 2.20 (95% CI: 1.55-3.11) for metabolically healthy obesity with BMI 30 to 34.9, BMI 35 to 39.9, and BMI ≥ 40 kg/m 2 . These associations were consistent among men and women, patients with eGFR ≥ or < 90 mL/min/1.73 m 2 , and age ≥ or < 55 years. The risk of KFD was highest among metabolically unhealthy individuals with BMI ≥ 40 (aHR 4.02; 95% CI: 3.40-4.75 vs. metabolically healthy individuals with normal weight). Obesity, whether in the presence or absence of metabolic health, is a risk factor for KFD. © 2018 The Obesity Society.

Predictive factors for renal failure and a control and treatment algorithm

PubMed Central

Cerqueira, Denise de Paula; Tavares, José Roberto; Machado, Regimar Carla

2014-01-01

Objectives to evaluate the renal function of patients in an intensive care unit, to identify the predisposing factors for the development of renal failure, and to develop an algorithm to help in the control of the disease. Method exploratory, descriptive, prospective study with a quantitative approach. Results a total of 30 patients (75.0%) were diagnosed with kidney failure and the main factors associated with this disease were: advanced age, systemic arterial hypertension, diabetes mellitus, lung diseases, and antibiotic use. Of these, 23 patients (76.6%) showed a reduction in creatinine clearance in the first 24 hours of hospitalization. Conclusion a decline in renal function was observed in a significant number of subjects, therefore, an algorithm was developed with the aim of helping in the control of renal failure in a practical and functional way. PMID:26107827

The assessment of cognitive function in older adult patients with chronic kidney disease: an integrative review.

PubMed

Hannan, Mary; Steffen, Alana; Quinn, Lauretta; Collins, Eileen G; Phillips, Shane A; Bronas, Ulf G

2018-05-25

Chronic kidney disease (CKD) is a common chronic condition in older adults that is associated with cognitive decline. However, the exact prevalence of cognitive impairment in older adults with CKD is unclear likely due to the variety of methods utilized to assess cognitive function. The purpose of this integrative review is to determine how cognitive function is most frequently assessed in older adult patients with CKD. Five electronic databases were searched to explore relevant literature related to cognitive function assessment in older adult patients with CKD. Inclusion and exclusion criteria were created to focus the search to the assessment of cognitive function with standardized cognitive tests in older adults with CKD, not on renal replacement therapy. Through the search methods, 36 articles were found that fulfilled the purpose of the review. There were 36 different types of cognitive tests utilized in the included articles, with each study utilizing between one and 12 tests. The most commonly utilized cognitive test was the Mini Mental State Exam (MMSE), followed by tests of digit symbol substitution and verbal fluency. The most commonly assessed aspect of cognitive function was global cognition. The assessment of cognitive function in older adults with CKD with standardized tests is completed in various ways. Unfortunately, the common methods of assessment of cognitive function may not be fully examining the domains of impairment commonly found in older adults with CKD. Further research is needed to identify the ideal cognitive test to best assess older adults with CKD for cognitive impairment.

Urinary NGAL Marks Cystic Disease in HIV-Associated Nephropathy

PubMed Central

Paragas, Neal; Nickolas, Thomas L.; Wyatt, Christina; Forster, Catherine S.; Sise, Meghan; Morgello, Susan; Jagla, Bernd; Buchen, Charles; Stella, Peter; Sanna-Cherchi, Simone; Carnevali, Maria Luisa; Mattei, Silvia; Bovino, Achiropita; Argentiero, Lucia; Magnano, Andrea; Devarajan, Prasad; Schmidt-Ott, Kai M.; Allegri, Landino; Klotman, Paul; D'Agati, Vivette; Gharavi, Ali G.

2009-01-01

Nephrosis and a rapid decline in kidney function characterize HIV-associated nephropathy (HIVAN). Histologically, HIVAN is a collapsing focal segmental glomerulosclerosis with prominent tubular damage. We explored the expression of neutrophil gelatinase-associated lipocalin (NGAL), a marker of tubular injury, to determine whether this protein has the potential to aid in the noninvasive diagnosis of HIVAN. We found that expression of urinary NGAL was much higher in patients with biopsy-proven HIVAN than in HIV-positive and HIV-negative patients with other forms of chronic kidney disease. In the HIV-transgenic mouse model of HIVAN, NGAL mRNA was abundant in dilated, microcystic segments of the nephron. In contrast, urinary NGAL did not correlate with proteinuria in human or in mouse models. These data show that marked upregulation of NGAL accompanies HIVAN and support further study of uNGAL levels in large cohorts to aid in the noninvasive diagnosis of HIVAN and screen for HIVAN-related tubular damage. PMID:19628667

A prospective cohort study of acute kidney injury in multi-stage ultramarathon runners: the Biochemistry in Endurance Runner Study (BIERS).

PubMed

Lipman, Grant S; Krabak, Brian J; Waite, Brandee L; Logan, Sarah B; Menon, Anil; Chan, Garrett K

2014-01-01

The purpose of the study was to evaluate the prevalence of acute kidney injury (AKI) during a multi-stage ultramarathon foot race. A prospective observational study was taken during the Gobi 2008; Sahara 2008; and Namibia 2009 RacingThePlanet 7-day, 6-stage, 150-mile foot ultramarathons. Blood was analyzed before, and immediately after stage 1 (25 miles), 3 (75 miles), and 5 (140 miles). Creatinine (Cr), glomerular filtration rate (GFR), and incidence of AKI were calculated and defined by RIFLE criteria. Thirty participants (76% male, mean age 40 + 11 years) were enrolled. There were significant declines in GFR after each stage compared with the pre-race baseline (p < 0.001), with the majority of participants (55-80%) incurring AKI. The majority of study participants encountered significant renal impairment; however, no apparent cumulative effect was observed, with resolution of renal function to near baseline levels between stages.

Effects of TORC1 Inhibition during the Early and Established Phases of Polycystic Kidney Disease

PubMed Central

Ta, Michelle H. T.; Schwensen, Kristina G.; Foster, Sheryl; Korgaonkar, Mayuresh; Ozimek-Kulik, Justyna E.; Phillips, Jacqueline K.; Peduto, Anthony; Rangan, Gopala K.

2016-01-01

The disease-modifying effects of target of rapamycin complex 1 (TORC1) inhibitors during different stages of polycystic kidney disease (PKD) are not well defined. In this study, male Lewis Polycystic Kidney Disease (LPK) rats (a genetic ortholog of human NPHP9, phenotypically characterised by diffuse distal nephron cystic growth) and Lewis controls received either vehicle (V) or sirolimus (S, 0.2 mg/kg by intraperitoneal injection 5 days per week) during the early (postnatal weeks 3 to 10) or late stages of disease (weeks 10 to 20). In early-stage disease, sirolimus reduced kidney enlargement (by 63%), slowed the rate of increase in total kidney volume (TKV) in serial MRI by 78.2% (LPK+V: 132.3±59.7 vs. LPK+S: 28.8±12.0% per week) but only partly reduced the percentage renal cyst area (by 19%) and did not affect the decline in endogenous creatinine clearance (CrCl) in LPK rats. In late-stage disease, sirolimus reduced kidney enlargement (by 22%) and the rate of increase in TKV by 71.8% (LPK+V: 13.1±6.6 vs. LPK+S: 3.7±3.7% per week) but the percentage renal cyst area was unaltered, and the CrCl only marginally better. Sirolimus reduced renal TORC1 activation but not TORC2, NF-κB DNA binding activity, CCL2 or TNFα expression, and abnormalities in cilia ultrastructure, hypertension and cardiac disease were also not improved. Thus, the relative treatment efficacy of TORC1 inhibition on kidney enlargement was consistent at all disease stages, but the absolute effect was determined by the timing of drug initiation. Furthermore, cystic microarchitecture, renal function and cardiac disease remain abnormal with TORC1 inhibition, indicating that additional approaches to normalise cellular dedifferentiation, inflammation and hypertension are required to completely arrest the progression of PKDs. PMID:27723777

Impact of early graft function on 10-year graft survival in recipients of kidneys from standard- or expanded-criteria donors.

PubMed

Smail, Nassima; Tchervenkov, Jean; Paraskevas, Steven; Baran, Dana; Mucsi, Istvan; Hassanain, Mazen; Chaudhury, Prosanto; Cantarovich, Marcelo

2013-07-27

The use of kidneys from expanded-criteria donors (ECD) is regarded with caution. We compared 279 kidney transplant recipients (KTxR) from standard-criteria donors (SCD) and 237 from ECD, transplanted between January 1990 and December 2006. We evaluated the impact of immediate graft function (IGF), slow graft function (SGF), and delayed graft function (DGF) and the drop in estimated glomerular filtration rate (ΔeGFR) ≤ 30% or > 30% during the first year after transplantation on long-term patient and death-censored graft survival (DCGS). Ten-year patient survival was similar in SCD- or ECD-KTxR (P = 0.38). DCGS was better in SCD-KTxR versus ECD-KTxR (77.3% vs. 67.3%; P = 0.01). DCGS did not differ in either group experiencing IGF (P = 0.17) or DGF (P = 0.12). However, DCGS was worse in ECD-KTxR experiencing SGF (84.9% vs. 73.7%; P = 0.04). Predictors of DCGS were 1-year serum creatinine (hazard ratio, 1.03; P < 0.0001) and ΔeGFR > 30% between 1 and 12 months (Δ1-12eGFR) after transplantation (hazard ratio, 2.2; P = 0.02). In ECD-KTxR with IGF and more than 1-year follow-up, 10-year DCGS was better in those with Δ1-12eGFR ≤ 30% versus those with Δ1-12eGFR > 30% (83.8% vs. 53.6%; P = 0.01). Recipients of SCD or ECD kidneys with IGF or DGF had similar 10-year patient survival and DCGS. SGF had a worse impact on DCGS in ECD-KTxR. In addition to 1-year serum creatinine, Δ1-12eGFR > 30% is a negative predictor of DCGS. Larger studies should confirm if increasing the use of ECD, avoiding factors that contribute to SGF or DGF, and/or a decline in eGFR during the first year after transplantation may expand the donor pool and result in acceptable long-term outcomes.

Application of prescribing recommendations in older people with reduced kidney function: a cross-sectional study in general practice.

PubMed

Wood, Su; Petty, Duncan; Glidewell, Liz; Raynor, Dk Theo

2018-05-01

Kidney function reduces with age, increasing the risk of harm from increased blood levels of many medicines. Although estimated glomerular filtration rate (eGFR) is reported for prescribing decisions in those aged ≥65 years, creatinine clearance (Cockcroft-Gault) gives a more accurate estimate of kidney function. To explore the extent of prescribing outside recommendations for people aged ≥65 years with reduced kidney function in primary care and to assess the impact of using eGFR instead of creatinine clearance to calculate kidney function. A cross-sectional survey of anonymised prescribing data in people aged ≥65 years from all 80 general practices (70 900 patients) in a north of England former primary care trust. The prevalence of prescribing outside recommendations was analysed for eight exemplar drugs. Data were collected for age, sex, actual weight, serum creatinine, and eGFR. Kidney function as creatinine clearance (Cockcroft-Gault) was calculated using actual body weight and estimated ideal body weight. Kidney function was too low for recommended prescribing in 4-40% of people aged ≥65 years, and in 24-80% of people aged ≥85 years despite more than 90% of patients having recent recorded kidney function results. Using eGFR overestimated kidney function for 3-28% of those aged ≥65 years, and for 13-58% of those aged ≥85 years. Increased age predicted higher odds of having a kidney function estimate too low for recommended prescribing of the study drugs. Prescribing recommendations when kidney function is reduced are not applied for many people aged ≥65 years in primary care. Using eGFR considerably overestimates kidney function for prescribing and, therefore, creatinine clearance (Cockcroft-Gault) should be assessed when prescribing for these people. Interventions are needed to aid prescribers when kidney function is reduced. © British Journal of General Practice 2018.

CT volumetry is superior to nuclear renography for prediction of residual kidney function in living donors.

PubMed

Barbas, Andrew S; Li, Yanhong; Zair, Murtuza; Van, Julie A; Famure, Olusegun; Dib, Martin J; Laurence, Jerome M; Kim, S Joseph; Ghanekar, Anand

2016-09-01

Living kidney donor evaluation commonly includes nuclear renography to assess split kidney function and computed tomography (CT) scan to evaluate anatomy. To streamline donor workup and minimize exposure to radioisotopes, we sought to assess the feasibility of using proportional kidney volume from CT volumetry in lieu of nuclear renography. We examined the correlation between techniques and assessed their ability to predict residual postoperative kidney function following live donor nephrectomy. In a cohort of 224 live kidney donors, we compared proportional kidney volume derived by CT volumetry with split kidney function derived from nuclear renography and found only modest correlation (left kidney R(2) =26.2%, right kidney R(2) =26.7%). In a subset of 88 live kidney donors with serum creatinine measured 6 months postoperatively, we compared observed estimated glomerular filtration rate (eGFR) at 6 months with predicted eGFR from preoperative imaging. Compared to nuclear renography, CT volumetry more closely approximated actual observed postoperative eGFR for Chronic Kidney Disease Epidemiology Collaboration (J-test: P=.02, Cox-Pesaran test: P=.01) and Mayo formulas (J-test: P=.004, Cox-Pesaran test: P<.001). These observations support the use of CT volumetry for estimation of split kidney function in healthy individuals with normal kidney function and morphology. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Change in Living Kidney Donation in Women and Men in the United States (2005-2015): A Population-Based Analysis.

PubMed

Gill, Jagbir; Joffres, Yayuk; Rose, Caren; Lesage, Julie; Landsberg, David; Kadatz, Matthew; Gill, John

2018-04-01

The factors underlying the decline in living kidney donation in the United States since 2005 must be understood to inform strategies to ensure access to this option for future patients. Population-based estimates provide a better assessment of donation activity than do trends in the number of living donor transplants. Using data from the Scientific Registry of Transplant Recipients and the United States Census, we determined longitudinal changes in living kidney donation between 2005 and 2015, focusing on the effect of sex and income. We used multilevel Poisson models to adjust for differences in age, race, the incidence of ESRD, and geographic factors (including population density, urbanization, and daily commuting). During the study period, the unadjusted rate of donation was 30.1 and 19.3 per million population in women and men, respectively, and the adjusted incidence of donation was 44% higher in women (incidence rate ratio [IRR], 1.44; 95% confidence interval [95% CI], 1.39 to 1.49). The incidence of donation was stable in women (IRR, 0.95; 95% CI, 0.84 to 1.07) but declined in men (IRR, 0.75; 95% CI, 0.68 to 0.83). Income was associated with longitudinal changes in donation in both sexes, yet donation was stable in the highest two population income quartiles in women but only in the highest income quartile in men. In both sexes, living related donations declined, irrespective of income. In conclusion, living donation declined in men but remained stable in women between 2005 and 2015, and income appeared to have a greater effect on living donation in men. Copyright © 2018 by the American Society of Nephrology.

The science of Stewardship: due diligence for kidney donors and kidney function in living kidney donation--evaluation, determinants, and implications for outcomes.

PubMed

Poggio, Emilio D; Braun, William E; Davis, Connie

2009-10-01

Living kidney donor transplantation is now a common treatment for ESRD because it provides excellent outcomes to transplant recipients and is considered a safe procedure for prospective donors. The short- and long-term safety of prospective donors is paramount to the continued success of this procedure. Whereas the initial experiences with living kidney donors mostly included the healthiest, the increase in the need for organs and the changing demographic characteristics of the general population have subtly reshaped the suitability for donation. Kidney function assessment is a critical component of the evaluation of prospective donors; therefore, special emphasis is usually placed on this aspect of the evaluation. At the same time, consideration of kidney function after donation is important because it assists with the determination of renal health in donors. This review summarizes the process of predonation kidney function assessment, determinants of pre- and postdonation renal function, and, importantly, the potential implications of kidney function to the long-term outcomes of kidney donors.

Mild cognitive impairment in older adults with pre-dialysis patients with chronic kidney disease: Prevalence and association with physical function.

PubMed

Otobe, Yuhei; Hiraki, Koji; Hotta, Chiharu; Nishizawa, Hajime; Izawa, Kazuhiro P; Taki, Yasuhiro; Imai, Naohiko; Sakurada, Tsutomu; Shibagaki, Yugo

2017-09-26

Chronic kidney disease (CKD) is a risk factor for declining cognitive and physical function. However, the prevalence of mild cognitive impairment (MCI) and its relationship with physical function is not clear. Therefore, our aim was to evaluate the prevalence of MCI and the relationship between MCI and physical function among older adults with pre-dialysis CKD. We conducted a cross-sectional study of 120 patients, aged ≥ 65 years (mean age, 77.3 years), with pre-dialysis CKD but without probable dementia (Mini Mental State Examination < 24). MCI was evaluated using the Japanese version of the Montreal Cognitive Assessment (MoCA-J). For analysis, patients were classified into two cognitive function groups: normal (MoCA-J ≥26) and MCI (MoCA-J <26). Physical, clinical, and biochemical parameters were compared between the groups. Logistic and linear regression analyses were used to evaluate the specific association between cognitive and physical function. Seventy-five patients (62.5%) patients belonged to the MCI group. Significant differences between the two groups were identified for gait speed, balance, age, and haemoglobin concentration. After adjustment for covariates, only gait speed was significantly associated with MCI (odds ratio, 0.06; 95% confidence interval, 0.009-0,411). The prevalence of MCI among older adults with pre-dialysis CKD was as high as 62.5%. The association between MCI and reduced gait speed supports the possible interaction between physical and cognitive functions and the need for early screening. This article is protected by copyright. All rights reserved.

The Renin-Aldosterone axis in kidney transplant recipients and its association with allograft function and structure

PubMed Central

Issa, Naim; Ortiz, Fernando; Reule, Scott; Kukla, Aleksandra; Kasiske, Bertram; Mauer, Michael; Jackson, Scott; Matas, Arthur J.; Ibrahim, Hassan N.

2013-01-01

The level of the renin-angiotensin-aldosterone system (RAAS) activity in kidney transplant recipients has not been extensively studied or serially profiled. To describe this axis and to determine its association with GFR change, interstitial expansion and end-stage renal disease (ESRD) we measured plasma renin activity (PRA) and plasma aldosterone levels annually for 5 years in 153 kidney transplant recipients randomly assigned to losartan or placebo. PRA and plasma aldosterone levels were in the normal range at all times and did not vary by immunosuppression regimen. Those on losartan exhibited higher PRA but similar plasma aldosterone levels. Neither baseline nor serial PRA or plasma aldosterone levels were associated with GFR decline, proteinuria or interstitial expansion. Losartan use, [HR 0.48 (95% CI 0.21–1.0), insignificant], and Caucasian donor, [HR 0.18 (95% CI 0.07–0.4), significant] were associated with less doubling of serum creatinine, death or ESRD. Hypertension, less than 3 HLA-matches, the combination of tacrolimus-rapamycin and acute rejection were associated with more events. Neither PRA nor plasma aldosterone levels were independently associated with this outcome. Higher serial plasma aldosterone levels were associated, however, with a significantly higher risk of ESRD, [HR 1.01 (95% CI 1.00–1.02)]. Thus, systemic RAAS is not overly activated in kidney transplant recipients but this may not reflect the intrarenal system. Importantly, plasma aldosterone levels may be associated with more ESRD. PMID:23965522

Kidney function after off-pump or on-pump coronary artery bypass graft surgery: a randomized clinical trial.

PubMed

Garg, Amit X; Devereaux, P J; Yusuf, Salim; Cuerden, Meaghan S; Parikh, Chirag R; Coca, Steven G; Walsh, Michael; Novick, Richard; Cook, Richard J; Jain, Anil R; Pan, Xiangbin; Noiseux, Nicolas; Vik, Karel; Stolf, Noedir A; Ritchie, Andrew; Favaloro, Roberto R; Parvathaneni, Sirish; Whitlock, Richard P; Ou, Yongning; Lawrence, Mitzi; Lamy, Andre

2014-06-04

Most acute kidney injury observed in the hospital is defined by sudden mild or moderate increases in the serum creatinine concentration, which may persist for several days. Such acute kidney injury is associated with lower long-term kidney function. However, it has not been demonstrated that an intervention that reduces the risk of such acute kidney injury better preserves long-term kidney function. To characterize the risk of acute kidney injury with an intervention in a randomized clinical trial and to determine if there is a difference between the 2 treatment groups in kidney function 1 year later. The Coronary Artery Bypass Grafting Surgery Off- or On-pump Revascularisation Study (CORONARY) enrolled 4752 patients undergoing first isolated coronary artery bypass graft (CABG) surgery at 79 sites in 19 countries. Patients were randomized to receive CABG surgery either with a beating-heart technique (off-pump) or with cardiopulmonary bypass (on-pump). From January 2010 to November 2011, 2932 patients (from 63 sites in 16 countries) from CORONARY were enrolled into a kidney function substudy to record serum creatinine concentrations during the postoperative period and at 1 year. The last 1-year serum creatinine concentration was recorded on January 18, 2013. Acute kidney injury within 30 days of surgery (≥50% increase in serum creatinine concentration from prerandomization concentration) and loss of kidney function at 1 year (≥20% loss in estimated glomerular filtration rate from prerandomization level). Off-pump (n = 1472) vs on-pump (n = 1460) CABG surgery reduced the risk of acute kidney injury (17.5% vs 20.8%, respectively; relative risk, 0.83 [95% CI, 0.72-0.97], P = .01); however, there was no significant difference between the 2 groups in the loss of kidney function at 1 year (17.1% vs 15.3%, respectively; relative risk, 1.10 [95% CI, 0.95-1.29], P = .23). Results were consistent with multiple alternate continuous and categorical definitions of acute kidney injury or kidney function loss, and in the subgroup with baseline chronic kidney disease. Use of off-pump compared with on-pump CABG surgery reduced the risk of postoperative acute kidney injury, without evidence of better preserved kidney function with off-pump CABG surgery at 1 year. In this setting, an intervention that reduced the risk of mild to moderate acute kidney injury did not alter longer-term kidney function. clinicaltrials.gov Identifier: NCT00463294.

The impact of slow graft function on graft outcome is comparable to delayed graft function in deceased donor kidney transplantation.

PubMed

Shin, Jung-Ho; Koo, Eun Hee; Ha, Sung Hae; Park, Ji Hyeon; Jang, Hye Ryoun; Lee, Jung Eun; Park, Jae-Berm; Kim, Sung Joo; Jung, Sin-Ho; Kim, Yoon-Goo; Kim, Dae Joong; Oh, Ha Young; Huh, Wooseong

2016-03-01

Slow graft function (SGF) can influence overall prognosis in patients receiving deceased donor kidney transplantation (DKT). However, the impact of SGF on renal function remains uncertain. We investigated retrospectively renal function in cases with SGF compared with early graft function (EGF) and delayed graft function (DGF). Renal function after transplantation was analyzed in 199 patients who underwent DKT. Patients were classified into 130 (65.3 %) cases with EGF, 27 (13.6 %) cases with SGF, 6 (3.0 %) cases with DGF and one dialysis (DGF1), and 36 (18.1 %) cases with DGF and two or more dialyses (DGF2). The 1-year estimated glomerular filtration rate (eGFR) in the SGF group was lower than that in the EGF group (P = 0.027), but the rate of eGFR decline did not differ between the groups. The risk factors for renal function were evaluated using the area under the eGFR curve over 3 years (AUCeGFR). Donor age was negatively, and recipient age and the number of HLA matches were positively correlated with the AUCeGFR (all P < 0.05). A multivariate analysis revealed that the AUCeGFR was lower in cases of younger recipient age, older donor age, and acute rejection (all P < 0.05). The AUCeGFR was significantly lower in the SGF and DGF2 groups compared with the EGF group (P = 0.031 and 0.006, respectively). SGF may be an independent risk factor for poor renal function after DKT. Moreover, it was comparable to DGF. Efforts should be dedicated to minimizing the development of SGF and DGF.

Principlism and communitarianism

PubMed Central

Callahan, D

2003-01-01

The decline in the interest in ethical theory is first outlined, as a background to the author's discussion of principlism. The author's own stance, that of a communitarian philosopher, is then described, before the subject of principlism itself is addressed. Two problems stand in the way of the author's embracing principlism: its individualistic bias and its capacity to block substantive ethical inquiry. The more serious problem the author finds to be its blocking function. Discussing the four scenarios the author finds that the utility of principlism is shown in the two scenarios about Jehovah's Witnesses but that when it comes to selling kidneys for transplantation and germline enhancement, principlism is of little help. PMID:14519838

Principlism and communitarianism.

PubMed

Callahan, D

2003-10-01

The decline in the interest in ethical theory is first outlined, as a background to the author's discussion of principlism. The author's own stance, that of a communitarian philosopher, is then described, before the subject of principlism itself is addressed. Two problems stand in the way of the author's embracing principlism: its individualistic bias and its capacity to block substantive ethical inquiry. The more serious problem the author finds to be its blocking function. Discussing the four scenarios the author finds that the utility of principlism is shown in the two scenarios about Jehovah's Witnesses but that when it comes to selling kidneys for transplantation and germline enhancement, principlism is of little help.

Relationships between appetite and quality of life in hemodialysis patients.

PubMed

Zabel, Rachel; Ash, Susan; King, Neil; Juffs, Philip; Bauer, Judith

2012-08-01

The aim of this paper was to investigate the association between appetite and kidney-disease specific quality of life in maintenance hemodialysis patients. Quality of life (QoL) was measured using the kidney disease quality of life survey. Appetite was measured using self-reported categories and a visual analog scale. Other nutritional parameters included Patient-Generated Subjective Global Assessment (PGSGA), dietary intake, body mass index and biochemical markers C-reactive protein and albumin. Even in this well nourished sample (n=62) of hemodialysis patients, PGSGA score (r=-0.629), subjective hunger sensations (r=0.420) and body mass index (r=-0.409) were all significantly associated with the physical health domain of QoL. As self-reported appetite declined, QoL was significantly lower in nine domains which were mostly in the SF36 component and covered social functioning and physical domains. Appetite and other nutritional parameters were not as strongly associated with the Mental Health domain and Kidney Disease Component Summary Domains. Nutritional parameters, especially PGSGA score and appetite, appear to be important components of the physical health domain of QoL. As even small reductions in nutritional status were associated with significantly lower QoL scores, monitoring appetite and nutritional status is an important component of care for hemodialysis patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

Bone metabolism dynamics in the early post-transplant period following kidney and liver transplantation.

PubMed

Schreiber, Peter W; Bischoff-Ferrari, Heike A; Boggian, Katia; Bonani, Marco; van Delden, Christian; Enriquez, Natalia; Fehr, Thomas; Garzoni, Christian; Hirsch, Hans H; Hirzel, Cédric; Manuel, Oriol; Meylan, Pascal; Saleh, Lanja; Weisser, Maja; Mueller, Nicolas J

2018-01-01

Bone disease contributes to relevant morbidity after solid organ transplantation. Vitamin D has a crucial role for bone metabolism. Activation of vitamin D depends on the endocrine function of both, liver and kidney. Our study assessed key markers of bone metabolism at time of transplantation and 6 months after transplantation among 70 kidney and 70 liver recipients. In 70 kidney recipients 25-OH vitamin D levels did not differ significantly between peri-transplant (median 32.5nmol/l) and 6 months post-transplant (median 41.9nmol/l; P = 0.272). Six months post-transplant median 1, 25-(OH)2 vitamin D levels increased by >300% (from 9.1 to 36.5ng/l; P<0.001) and median intact parathyroid hormone levels decreased by 68.4% (from 208.7 to 66.0 ng/l; P<0.001). Median β-Crosslaps (CTx) and total procollagen type 1 amino-terminal propeptide (P1NP) decreased by 65.1% (from 1.32 to 0.46ng/ml; P<0.001) and 60.6% (from 158.2 to 62.3ng/ml; P<0.001), respectively. Kidney recipients with incident fractures had significantly lower levels of 1, 25-(OH)2 vitamin D at time of transplantation and of intact parathyroid hormone 6 months post-transplant. Among 70 liver recipients, 25-OH vitamin D, 1, 25-(OH)2 vitamin D and intact parathyroid hormone levels were not significantly altered between peri-transplant and 6 months post-transplant. Contrary to kidney recipients, median CTx increased by 60.0% (from 0.45 to 0.72 ng/ml; P = 0.002) and P1NP by 49.3% (from 84.0 to 125.4ng/ml; P = 0.001) in the longitudinal course. Assessed biomarkers didn't differ between liver recipients with and without fractures. To conclude, the assessed panel of biomarkers proved highly dynamic after liver as well as kidney transplantation in the early post-transplant period. After kidney transplantation a significant gain in 1, 25-(OH)2 vitamin D combined with a decline in iPTH, CTx and P1NP, whereas after liver transplantation an increase in CTx and P1NP were characteristic.

Association of Proteinuria with Race, Cause of Chronic Kidney Disease, and Glomerular Filtration Rate in the Chronic Kidney Disease in Children Study

PubMed Central

Wong, Craig S.; Pierce, Christopher B.; Cole, Stephen R.; Warady, Bradley A.; Mak, Robert H.K.; Benador, Nadine M.; Kaskel, Fredrick; Furth, Susan L.; Schwartz, George J.

2009-01-01

Background and objectives: Proteinuria is associated with chronic kidney disease (CKD), and heavy proteinuria predicts a rapid decline in kidney function. However, the epidemiologic distribution of this important biomarker study is not well described in the pediatric CKD population. Design, setting, participants & measurements: This cross-sectional study of North American children with CKD examined the association of proteinuria among the baseline clinical variables in the cohort. Urinary protein-to-creatinine ratios (Up/c) were used to measure level of proteinuria. Results: Of the 419 subjects studied, the median GFR as measured by iohexol disappearance (iGFR) was 42 ml/min per 1.73 m2, median duration of CKD was six yr, and glomerular diseases accounted for 22% of the CKD diagnoses. Twenty-four percent of children had normal range (Up/c <0.2), 62% had significant, and 14% had nephrotic-range proteinuria (Up/c >2.0). A decrease in iGFR was associated with an increase in Up/c. At any level of GFR, a higher Up/c was associated with a glomerular cause of CKD and non-Caucasian race. Among subjects with a glomerular cause of CKD, Up/c was lower in subjects reporting utilization of renin-angiotensin system (RAS) antagonists (median Up/c = 0.93) compared with those who did not (median Up/c = 3.78). Conclusions: Proteinuria is associated with level of iGFR, cause of CKD, and race. The longitudinal study design of Chronic Kidney Disease in Children (CKiD) cohort study and the large number of subjects being studied has created an opportunity to better define the association between proteinuria and CKD progression. PMID:19297612

A prospective 10-year study of individualized, intensified enzyme replacement therapy in advanced Fabry disease.

PubMed

Schiffmann, Raphael; Swift, Caren; Wang, Xuan; Blankenship, Derek; Ries, Markus

2015-11-01

To test the hypothesis that more frequent enzyme replacement therapy (ERT) slows the decline in kidney function in adult patients with Fabry disease. A single center open label 10-year prospective clinical trial of 12 patients with advanced Fabry disease who, after having experienced an ongoing decline in renal function after 2-4 years of receiving ERT at the approved dose of 0.2 mg/kg agalsidase alfa every other week (EOW), were switched to weekly (EW) ERT at the same dose. We used linear regression to fit each individual patient's longitudinal estimated glomerular filtration rate (eGFR) record in order to compare the deterioration rates between EOW and EW ERT. For the entire group, mean slope on agalsidase alfa every 2 weeks was -7.92 ± 2.88 ml/min/1.73 m(2)/year and 3.84 ± 4.08 ml/min/1.73 m(2)/year on weekly enzyme infusions (p = 0.01, two-tailed paired t test). Three patients (25 %) completed the entire study with relatively preserved renal function while 50 % of patients reached end-stage renal disease (ESRD) during the 10 years of this study. The estimated average delay to ESRD was 13.8 years [n = 11; 95 % CI 0.66, 27]. One patient had a positive eGFR slope on weekly infusions while the patient with the highest antibody titer had a steeper slope after switching. Mean globotriaosylceramide concentrations in urine and plasma as well as urine protein excretion remained unchanged. Weekly enzyme infusions slow the decline of renal function in a subgroup of more severe patients thus showing that existing ERT can be further optimized.

Creatinine clearance test

MedlinePlus

Serum creatinine clearance; Kidney function - creatinine clearance; Renal function - creatinine clearance ... the body entirely by the kidneys. If kidney function is abnormal, creatinine level increases in the blood ...

Incidence of End-Stage Renal Disease Attributed to Diabetes Among Persons with Diagnosed Diabetes - United States and Puerto Rico, 2000-2014.

PubMed

Burrows, Nilka Rios; Hora, Israel; Geiss, Linda S; Gregg, Edward W; Albright, Ann

2017-11-03

During 2014, 120,000 persons in the United States and Puerto Rico began treatment for end-stage renal disease (ESRD) (i.e., kidney failure requiring dialysis or transplantation) (1). Among these persons, 44% (approximately 53,000 persons) had diabetes listed as the primary cause of ESRD (ESRD-D) (1). Although the number of persons initiating ESRD-D treatment each year has increased since 1980 (1,2), the ESRD-D incidence rate among persons with diagnosed diabetes has declined since the mid-1990s (2,3). To determine whether ESRD-D incidence has continued to decline in the United States overall and in each state, the District of Columbia (DC), and Puerto Rico, CDC analyzed 2000-2014 data from the U.S. Renal Data System and the Behavioral Risk Factor Surveillance System. During that period, the age-standardized ESRD-D incidence among persons with diagnosed diabetes declined from 260.2 to 173.9 per 100,000 diabetic population (33%), and declined significantly in most states, DC, and Puerto Rico. No state experienced an increase in ESRD-D incidence rates. Continued awareness of risk factors for kidney failure and interventions to improve diabetes care might sustain and improve these trends.

Transport of organic anions and cations in murine embryonic kidney development and in serially-reaggregated engineered kidneys

PubMed Central

Lawrence, Melanie L.; Chang, C-Hong; Davies, Jamie A.

2015-01-01

Recent advances in renal tissue engineering have shown that dissociated, early renogenic tissue from the developing embryo can self-assemble into morphologically accurate kidney-like organs arranged around a central collecting duct tree. In order for such self-assembled kidneys to be useful therapeutically or as models for drug screening, it is necessary to demonstrate that they are functional. One of the main functional characteristics of mature kidneys is transport of organic anions and cations into and out of the proximal tubule. Here, we show that the transport function of embryonic kidneys allowed to develop in culture follows a developmental time-course that is comparable to embryonic kidney development in vivo. We also demonstrate that serially-reaggregated engineered kidneys can transport organic anions and cations through specific uptake and efflux channels. These results support the physiological relevance of kidneys grown in culture, a commonly used model for kidney development and research, and suggest that serially-reaggregated kidneys self-assembled from separated cells have some functional characteristics of intact kidneys. PMID:25766625

Chronic kidney disease-mineral and bone disorder: Guidelines for diagnosis, treatment, and management.

PubMed

Moschella, Carla

2016-07-01

Chronic kidney disease affects 23 million Americans and is associated with many complications, one of the most complex of which is mineral and bone disorder. Pathophysiologic mechanisms begin to occur early in CKD but when the glomerular filtration rate declines to <50% of normal, biochemical and bone matrix abnormalities, which vary and are multifactorial, begin to be clinically apparent. Mainstays of treatment remain management of hyperphosphatemia and prevention or treatment of secondary hyperparathyroidism.

Chronic Kidney Disease, Fluid Overload and Diuretics: A Complicated Triangle

PubMed Central

Khan, Yusra Habib; Sarriff, Azmi; Adnan, Azreen Syazril; Khan, Amer Hayat; Mallhi, Tauqeer Hussain

2016-01-01

Background Despite promising role of diuretics to manage fluid overload among chronic kidney disease (CKD) patients, their use is associated with adverse renal outcomes. Current study aimed to determine the extent of renal deterioration with diuretic therapy. Methods A total 312 non-dialysis dependent CKD (NDD-CKD) patients were prospectively followed-up for one year. Fluid overload was assessed via bioimpedance spectroscopy. Estimated GFR (eGFR) was calculated from serum creatinine values by using Chronic Kidney Disease- Epidemiology Collaboration (CKD-EPI) equation. Results Out of 312 patients, 64 (20.5%) were hypovolemic while euvolemia and hypervolemia were observed in 113 (36.1%) and 135 (43.4%) patients. Overall 144 patients were using diuretics among which 98 (72.6%) were hypervolemic, 35 (30.9%) euvolemic and 11 (17.2%) were hypovolemic. The mean decline in estimated GFR of entire cohort was -2.5 ± 1.4 ml/min/1.73m2 at the end of follow up. The use of diuretics was significantly associated with decline in eGFR. A total of 36 (11.5%) patients initiated renal replacement therapy (RRT) and need of RRT was more profound among diuretic users. Conclusions The use of diuretics was associated with adverse renal outcomes indicated by decline in eGFR and increasing risk of RRT initiation in our cohort of NDD-CKD patients. Therefore, it is cautiously suggested to carefully prescribe diuretics by keeping in view benefit versus harm for each patient. PMID:27442587

Metabolic syndrome but not obesity measures are risk factors for accelerated age-related glomerular filtration rate decline in the general population.

PubMed

Stefansson, Vidar T N; Schei, Jørgen; Solbu, Marit D; Jenssen, Trond G; Melsom, Toralf; Eriksen, Bjørn O

2018-05-01

Rapid age-related glomerular filtration rate (GFR) decline increases the risk of end-stage renal disease, and a low GFR increases the risk of mortality and cardiovascular disease. High body mass index and the metabolic syndrome are well-known risk factors for patients with advanced chronic kidney disease, but their role in accelerating age-related GFR decline independent of cardiovascular disease, hypertension and diabetes is not adequately understood. We studied body mass index, waist circumference, waist-hip ratio and metabolic syndrome as risk factors for accelerated GFR decline in 1261 middle-aged people representative of the general population without diabetes, cardiovascular disease or kidney disease. GFR was measured as iohexol clearance at baseline and repeated after a median of 5.6 years. Metabolic syndrome was defined as fulfilling three out of five criteria, based on waist circumference, blood pressure, glucose, high-density lipoprotein cholesterol and triglycerides. The mean GFR decline rate was 0.95 ml/min/year. Neither the body mass index, waist circumference nor waist-hip ratio predicted statistically significant changes in age-related GFR decline, but individuals with baseline metabolic syndrome had a significant mean of 0.30 ml/min/year faster decline than individuals without metabolic syndrome in a multivariable adjusted linear regression model. This association was mainly driven by the triglyceride criterion of metabolic syndrome, which was associated with a significant 0.36 ml/min/year faster decline when analyzed separately. Results differed significantly when GFR was estimated using creatinine and/or cystatin C. Thus, metabolic syndrome, but not the body mass index, waist circumference or waist-hip ratio, is an independent risk factor for accelerated age-related GFR decline in the general population. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

[Methodological aspects related to the determination of the relative renal function using 99mTC MAG3].

PubMed

Ladrón De Guevara Hernández, D; Ham, H; Franken, P; Piepsz, A; Lobo Sotomayor, G

2002-01-01

The aim of the study was to evaluate three different methods for calculating the split renal function in patients with only one functioning kidney, keeping in mind that the split function should be zero on the side of the non-functioning kidney. We retrospectively selected 28 99mTc MAG3 renograms performed in children, 12 with unilateral nephrectomy, 4 with unilateral agenesis and 12 with a non-functioning kidney. A renal and perirenal region of interest (ROI) were delineated around the functioning kidney. The ROIs around the empty kidney were drawn symmetrically to the contralateral side. The split renal function was calculated using three different methods, the integral method, the slope method and the Patlak-Rutland algorithm. For the whole group of 28 kidneys as well as for the three categories of patients, the three methods provided a split function on the side of the non-functioning kidney close to the zero value, regardless of whether the empty kidney was the left or the right one. We recommend the use of the integral method for the whole range of split renal function with 99mTc MAG3. No significant improvement was obtained by means of the more sophisticated Patlak-Rutland method.

[Decline in renal function in old age : Part of physiological aging versus age-related disease].

PubMed

Braun, F; Brinkkötter, P T

2016-08-01

The incidence and prevalence of chronic renal disease (CKD) in elderly patients are continuously increasing worldwide. Loss of renal function is not only considered to be part of the aging process itself but also reflects the multimorbidity of many geriatric patients. Calculating the glomerular filtration rate using specific algorithms validated for the elderly population and measuring the amount of proteinuria allow an estimation of renal function in elderly patients with high accuracy. Chronic renal failure has many clinical consequences and not only results in a delayed excretion of toxins cleared by the kidneys but also affects hematogenesis, water and electrolyte balance as well as mineral bone metabolism. Furthermore, CKD directly leads to and aggravates geriatric syndromes and in particular the onset of frailty. Therapeutic strategies to halt progression of CKD not only comprise treatment of the underlying disease but also efficient blood pressure and diabetic control and the avoidance of nephrotoxic medications.

Emergence of an Israel faith-based community organization facilitating live donor kidney transplantation.

PubMed

Wasser, Walter G; Boner, Geoffrey; Koslowsky, Meni; Lazar, Adi

2018-06-07

The 2014 Consensus Conference on Best Practices in Living Kidney Donations recognized live donor kidney transplantation as the best treatment for late-stage kidney disease, yielding superior graft and patient survival, improved quality of life, fewer requirements for dialysis and increased cost-effectiveness compared to deceased donor kidney transplantation. Yet in spite of the excellent results of living kidney donation, the annual number of living kidney donors is declining in many countries, including the United States. In Israel, a non-profit organization, Matnat Chaim ("Gift of Life" in Hebrew), a faith-based initiative, has emerged as a major force for arranging living donor kidney transplantation mainly by facilitating altruistic living unrelated donor transplantation. A retrospective review of the records of live kidney donations facilitated by the Matnat Chaim organization and referred to Israel transplant centers, since the organization's inception in 2009, was performed and compared to published data from the Israel Ministry of Health. Matnat Chaim has facilitated 494 live kidney donations since its founding in February 2009 until the end of 2017. Of the 124 live kidney transplants performed in 2016, 111 (90%) were shown to be altruistic and unrelated. This large number of donations was associated with a doubling of the total number of kidney transplantations, performed in Israel (data published by the Israel Ministry of Health). The success of an Israel community organization in the promotion of kidney transplantation may serve as a model for other religious and non-religious communities worldwide.

Kidney function monitoring and nonvitamin K oral anticoagulant dosage in atrial fibrillation.

PubMed

Andreu Cayuelas, Jose Manuel; Caro Martínez, Cesar; Flores Blanco, Pedro Jose; Elvira Ruiz, Gines; Albendin Iglesias, Helena; Cerezo Manchado, Juan Jose; Bailen Lorenzo, Jose Luis; Januzzi, James L; García Alberola, Arcadio; Manzano-Fernández, Sergio

2018-06-01

Clinical practice guidelines recommend regular kidney function monitoring in atrial fibrillation patients on nonvitamin K oral anticoagulants (NOAC); however, information regarding compliance with these recommendations in daily life conditions is scarce. We sought to determine the compliance with kidney function monitoring recommendations in nonvalvular atrial fibrillation (NVAF) patients starting NOAC and its implication on the appropriateness of NOAC dosage. This study involves the retrospective analysis of a multicentre registry including consecutive NVAF patients who started NOAC (n = 692). Drug dosage changes and serum creatinine determinations were recorded during 1-year follow-up. European Heart Rhythm Association criteria were used to define the appropriateness of kidney function monitoring as well as adequate NOAC dosage. During the follow-up (334 ± 89 days), the compliance with kidney function monitoring recommendations was 61% (n = 425). After multivariate adjustment, age (OR × year: 0.92 (CI 95%: 0.89-0.95) P < .001), creatinine clearance (OR × mL/min: 1.02 (CI 95%: 1.01-1.03) P < .001) and adequate NOAC dosage at baseline (OR: 1.54 (CI 95%: 1.06-2.23), P = .024) were independent predictors of appropriate kidney function monitoring. Compliance with kidney function monitoring recommendations was independently associated with change to appropriate NOAC dose after 1 year (OR: 2.80 (CI 95%: 1.01-7.80), P = .049). Noncompliance with kidney function monitoring recommendations is common in NVAF patients starting NOAC, especially in elderly patients with kidney dysfunction. Compliance with kidney function monitoring recommendations was associated with adequate NOAC dosage at 1-year follow-up. Further studies are warranted to evaluate the implication of kidney function monitoring on prognosis. © 2018 Stichting European Society for Clinical Investigation Journal Foundation.

Aging is Associated with Impaired Renal Function, INF-gamma Induced Inflammation and with Alterations in Iron Regulatory Proteins Gene Expression.

PubMed

Costa, Elísio; Fernandes, João; Ribeiro, Sandra; Sereno, José; Garrido, Patrícia; Rocha-Pereira, Petronila; Coimbra, Susana; Catarino, Cristina; Belo, Luís; Bronze-da-Rocha, Elsa; Vala, Helena; Alves, Rui; Reis, Flávio; Santos-Silva, Alice

2014-12-01

Our aim was to contribute to a better understanding of the pathophysiology of anemia in elderly, by studying how aging affects renal function, iron metabolism, erythropoiesis and the inflammatory response, using an experimental animal model. The study was performed in male Wistar, a group of young rats with 2 months age and an old one with 18 months age. Old rats presented a significant higher urea, creatinine, interferon (INF)-gamma, ferritin and soluble transferrin receptor serum levels, as well as increased counts of reticulocytes and RDW. In addition, these rats showed significant lower erythropoietin (EPO) and iron serum levels. Concerning gene expression of iron regulatory proteins, old rats presented significantly higher mRNA levels of hepcidin (Hamp), transferrin (TF), transferrin receptor 2 (TfR2) and hemojuvelin (HJV); divalent metal transporter 1 (DMT1) mRNA levels were significantly higher in duodenal tissue; EPO gene expression was significantly higher in liver and lower in kidney, and the expression of the EPOR was significantly higher in both liver and kidney. Our results showed that aging is associated with impaired renal function, which could be in turn related with the inflammatory process and with a decline in EPO renal production. Moreover, we also propose that aging may be associated with INF-gamma-induced inflammation and with alterations upon iron regulatory proteins gene expression.

Current anti-myeloma therapies in renal manifestations of monoclonal light chain-associated Fanconi syndrome: a retrospective series of 49 patients.

PubMed

Vignon, M; Javaugue, V; Alexander, M P; El-Karoui, K; Karras, A; Roos-Weil, D; Royer, B; Asli, B; Knebelmann, B; Touchard, G; Jaccard, A; Arnulf, B; Bridoux, F; Leung, N; Fermand, J P

2017-01-01

We retrospectively reviewed 49 patients with light chain (LC) Fanconi syndrome (FS). Patients presented with chronic kidney disease (median estimated glomerular filtration rate (eGFR) of 33 ml/min/1.73 m 2 ) and tubular proteinuria. All patients tested had elevated fractional excretion of phosphate, uric acid, generalized aminoaciduria and/or normoglycemic glycosuria. Thirty-eight patients had monoclonal gammopathy of renal significance and eleven patients had an overt hematological malignancy. The monoclonal LC isotype was kappa in 46/49 cases. Kidney biopsy in 39 patients showed various proximal tubular lesions and characteristic LC intracytoplasmic crystalline inclusions in 24 patients. Forty-two patients received chemotherapy. Patients with plasma cell proliferation (n=38) received bortezomib-based regimens (n=11), immunomodulatory agents (n=7) or alkylating agents (n=6). High-dose melphalan (HDM) followed by autologous stem cell transplantation was performed in 14 patients. Hematological response was obtained in 90% of evaluable patients, assessed on serum free light chains (FLC). GFR remained stable as long as hematological response was maintained and declined when serum FLC level rebounded. Improvement in proximal tubule function occurred in 13 patients. In patients with LC-associated FS, chemotherapy using HDM and/or new generation anti-myeloma agents can stabilize renal function and improve proximal tubule function. Serum FLC should be used to assess the hematological response, related to renal outcome.

High Dietary Acid Load Predicts ESRD among Adults with CKD

PubMed Central

Crews, Deidra C.; Wesson, Donald E.; Tilea, Anca M.; Saran, Rajiv; Ríos-Burrows, Nilka; Williams, Desmond E.; Powe, Neil R.

2015-01-01

Small clinical trials have shown that a reduction in dietary acid load (DAL) improves kidney injury and slows kidney function decline; however, the relationship between DAL and risk of ESRD in a population-based cohort with CKD remains unexamined. We examined the association between DAL, quantified by net acid excretion (NAEes), and progression to ESRD in a nationally representative sample of adults in the United States. Among 1486 adults with CKD age≥20 years enrolled in the National Health and Nutrition Examination Survey III, DAL was determined by 24-h dietary recall questionnaire. The development of ESRD was ascertained over a median 14.2 years of follow-up through linkage with the Medicare ESRD Registry. We used the Fine–Gray competing risks method to estimate the association of high, medium, and low DAL with ESRD after adjusting for demographics, nutritional factors, clinical factors, and kidney function/damage markers and accounting for intervening mortality events. In total, 311 (20.9%) participants developed ESRD. Higher levels of DAL were associated with increased risk of ESRD; relative hazards (95% confidence interval) were 3.04 (1.58 to 5.86) for the highest tertile and 1.81 (0.89 to 3.68) for the middle tertile compared with the lowest tertile in the fully adjusted model. The risk of ESRD associated with DAL tertiles increased as eGFR decreased (P trend=0.001). Among participants with albuminuria, high DAL was strongly associated with ESRD risk (P trend=0.03). In conclusion, high DAL in persons with CKD is independently associated with increased risk of ESRD in a nationally representative population. PMID:25677388

Advanced Glycation End Products Predict Loss of Renal Function and Correlate With Lesions of Diabetic Kidney Disease in American Indians With Type 2 Diabetes.

PubMed

Saulnier, Pierre-Jean; Wheelock, Kevin M; Howell, Scott; Weil, E Jennifer; Tanamas, Stephanie K; Knowler, William C; Lemley, Kevin V; Mauer, Michael; Yee, Berne; Nelson, Robert G; Beisswenger, Paul J

2016-12-01

We examined associations of advanced glycation end products (AGEs) with renal function loss (RFL) and its structural determinants in American Indians with type 2 diabetes. Data were from a 6-year clinical trial that assessed renoprotective efficacy of losartan. Participants remained under observation after the trial concluded. Glomerular filtration rate (GFR) was measured annually. Kidney biopsies were performed at the end of the trial. Five AGEs were measured in serum collected at enrollment and at kidney biopsy. RFL was defined as ≥40% decline of measured GFR from baseline. Of 168 participants (mean baseline age 41 years, HbA 1c 9.2%, GFR 164 mL/min, and albumin-to-creatinine ratio 31 mg/g), 104 reached the RFL end point during median follow-up of 8.0 years. After multivariable adjustment, each doubling of carboxyethyl lysine (hazard ratio [HR] 1.60 [95% CI 1.08-2.37]) or methylglyoxal hydroimidazolone (HR 1.30 [95% CI 1.02-1.65]) concentration was associated with RFL. Carboxyethyl lysine, carboxymethyl lysine, and methylglyoxal hydroimidazolone correlated positively with cortical interstitial fractional volume (partial r = 0.23, P = 0.03; partial r = 0.25, P = 0.02; and partial r = 0.31, P = 0.003, respectively). Glyoxyl hydroimidazolone and methylglyoxal hydroimidazolone correlated negatively with total filtration surface per glomerulus (partial r = -0.26, P = 0.01; and partial r = -0.21, P = 0.046, respectively). AGEs improve prediction of RFL and its major structural correlates. © 2016 by the American Diabetes Association.

Advanced Glycation End Products Predict Loss of Renal Function and Correlate With Lesions of Diabetic Kidney Disease in American Indians With Type 2 Diabetes

PubMed Central

Saulnier, Pierre-Jean; Wheelock, Kevin M.; Howell, Scott; Weil, E. Jennifer; Tanamas, Stephanie K.; Knowler, William C.; Lemley, Kevin V.; Mauer, Michael; Yee, Berne; Beisswenger, Paul J.

2016-01-01

We examined associations of advanced glycation end products (AGEs) with renal function loss (RFL) and its structural determinants in American Indians with type 2 diabetes. Data were from a 6-year clinical trial that assessed renoprotective efficacy of losartan. Participants remained under observation after the trial concluded. Glomerular filtration rate (GFR) was measured annually. Kidney biopsies were performed at the end of the trial. Five AGEs were measured in serum collected at enrollment and at kidney biopsy. RFL was defined as ≥40% decline of measured GFR from baseline. Of 168 participants (mean baseline age 41 years, HbA1c 9.2%, GFR 164 mL/min, and albumin-to-creatinine ratio 31 mg/g), 104 reached the RFL end point during median follow-up of 8.0 years. After multivariable adjustment, each doubling of carboxyethyl lysine (hazard ratio [HR] 1.60 [95% CI 1.08–2.37]) or methylglyoxal hydroimidazolone (HR 1.30 [95% CI 1.02–1.65]) concentration was associated with RFL. Carboxyethyl lysine, carboxymethyl lysine, and methylglyoxal hydroimidazolone correlated positively with cortical interstitial fractional volume (partial r = 0.23, P = 0.03; partial r = 0.25, P = 0.02; and partial r = 0.31, P = 0.003, respectively). Glyoxyl hydroimidazolone and methylglyoxal hydroimidazolone correlated negatively with total filtration surface per glomerulus (partial r = −0.26, P = 0.01; and partial r = −0.21, P = 0.046, respectively). AGEs improve prediction of RFL and its major structural correlates. PMID:27609106

zVAD-fmk prevents cisplatin-induced cleavage of autophagy proteins but impairs autophagic flux and worsens renal function

PubMed Central

Herzog, Christian; Yang, Cheng; Holmes, Alexandrea

2012-01-01

Cisplatin injury to renal tubular epithelial cells (RTEC) is accompanied by autophagy and caspase activation. However, autophagy gradually decreases during the course of cisplatin injury. The role of autophagy and the mechanism of its decrease during cisplatin injury are not well understood. This study demonstrated that autophagy proteins beclin-1, Atg5, and Atg12 were cleaved and degraded during the course of cisplatin injury in RTEC and the kidney. zVAD-fmk, a widely used pancaspase inhibitor, blocked cleavage of autophagy proteins suggesting that zVAD-fmk would promote the autophagy pathway. Unexpectedly, zVAD-fmk blocked clearance of the autophagosomal cargo, indicating lysosomal dysfunction. zVAD-fmk markedly inhibited cisplatin-induced lysosomal cathepsin B and calpain activities and therefore impaired autophagic flux. In a mouse model of cisplatin nephrotoxicity, zVAD-fmk impaired autophagic flux by blocking autophagosomal clearance as revealed by accumulation of key autophagic substrates p62 and LC3-II. Furthermore, zVAD-fmk worsened cisplatin-induced renal dysfunction. Chloroquine, a lysomotropic agent that is known to impair autophagic flux, also exacerbated cisplatin-induced decline in renal function. These findings demonstrate that impaired autophagic flux induced by zVAD-fmk or a lysomotropic agent worsened renal function in cisplatin acute kidney injury (AKI) and support a protective role of autophagy in AKI. These studies also highlight that the widely used antiapoptotic agent zVAD-fmk may be contraindicated as a therapeutic agent for preserving renal function in AKI. PMID:22896037

Long-term effects of moderate protein diet on renal function and low-grade inflammation in older adults with type 2 diabetes and chronic kidney disease.

PubMed

Giordano, Mauro; Ciarambino, Tiziana; Castellino, Pietro; Cataliotti, Alessandro; Malatino, Lorenzo; Ferrara, Nicola; Politi, Cecilia; Paolisso, Giuseppe

2014-09-01

The aim of this study was to determine the long-term effects of a moderate protein diet (MPD) on renal function, low-grade inflammation, and oxidative stress in older adults with type 2 diabetes, which to date are unclear. Seventy-four older adults with type 2 diabetes and chronic kidney disease (stage G3b-G4) were enrolled in the study. During the 4-wk baseline period (T0), all patients were asked to follow a normal protein diet regimen, providing 1.1 g/kg daily. Successively, all patients were asked to follow an MPD, for 36 mo, providing 0.7 g/kg daily, for only 6 d/wk. Patients who refused to follow an MPD treatment were included in the control (NPD [normal protein diet] group). During the 36 mo of the study, creatinine clearance, blood urea nitrogen, proteinuria, blood pressure, glycated hemoglobin (Hb)A1c, fat-free mass, low-grade inflammation (interleukin-6 and C-reactive protein) were evaluated monthly and oxidative stress (urinary 8-epiprostaglandin [Epi-PG]F2α) was evaluated every 3 mo. During T0, mean creatinine clearance, proteinuria, blood urea nitrogen, blood pressure, HbA1c, fat free mass, low-grade inflammation, and oxidative stress were similar in both groups. After 36 mo, a significant reduction in decline of renal function was observed in the MPD group but not in controls (2.4 ± 0.2 versus 5.7 ± 0.5 mL·min·y, respectively; P < 0.05 versus control). Similarly, a significant reduction in proteinuria, serum interleukin-6, serum C-reactive protein, and urinary 8-Epi-PGF2α excretion, was observed in the MPD group (P < 0.05 versus NPD). In older adults with type 2 diabetes, long-term effects of an MPD regimen are associated with a significant decline of renal function, proteinuria, low-grade inflammation, and oxidative stress without a change in fat-free mass. Copyright © 2014 Elsevier Inc. All rights reserved.

Long-term Effects of Renin-Angiotensin System–Blocking Therapy and a Low Blood Pressure Goal on Progression of Hypertensive Chronic Kidney Disease in African Americans

PubMed Central

Appel, Lawrence J.; Wright, Jackson T.; Greene, Tom; Kusek, John W.; Lewis, Julia B.; Wang, Xuelei; Lipkowitz, Michael S.; Norris, Keith C.; Bakris, George L.; Rahman, Mahboob; Contreras, Gabriel; Rostand, Stephen G.; Kopple, Joel D.; Gabbai, Francis B.; Schulman, Gerald I.; Gassman, Jennifer J.; Charleston, Jeanne; Agodoa, Lawrence Y.

2013-01-01

Background Antihypertensive drugs that block the renin-angiotensin system (angiotensin-converting enzyme inhibitors [ACEIs] or angiotensin receptor blockers) are recommended for patients with chronic kidney disease (CKD). A low blood pressure (BP) goal (BP, <130/80 mm Hg) is also recommended. The objective of this study was to determine the long-term effects of currently recommended BP therapy in 1094 African Americans with hypertensive CKD. Methods Multicenter cohort study following a randomized trial. Participants were 1094 African Americans with hypertensive renal disease (glomerular filtration rate, 20–65 mL/min/1.73 m2). Following a 3×2-factorial trial (1995–2001) that tested 3 drugs used as initial antihypertensive therapy (ACEIs, calcium channel blockers, and β-blockers) and 2 levels of BP control (usual and low), we conducted a cohort study (2002–2007) in which participants were treated with ACEIs to a BP lower than 130/80 mm Hg. The outcome measures were a composite of doubling of the serum creatinine level, end-stage renal disease, or death. Results During each year of the cohort study, the annual use of an ACEI or an angiotensin receptor blocker ranged from 83.7% to 89.0% (vs 38.5% to 49.8% during the trial). The mean BP in the cohort study was 133/78 mm Hg (vs 136/82 mm Hg in the trial). Overall, 567 participants experienced the primary outcome; the 10-year cumulative incidence rate was 53.9%. Of 576 participants with at least 7 years of follow-up, 33.5% experienced a slow decline in kidney function (mean annual decline in the estimated glomerular filtration rate, <1 mL/min/1.73 m2). Conclusion Despite the benefits of renin-angiotensin system–blocking therapy on CKD progression, most African Americans with hypertensive CKD who are treated with currently recommended BP therapy continue to progress during the long term. PMID:18443258

Effect of paricalcitol on mineral bone metabolism in kidney transplant recipients with secondary hyperparathyroidism.

PubMed

Borrego Utiel, Francisco José; Bravo Soto, Juan Antonio; Merino Pérez, María José; González Carmelo, Isabel; López Jiménez, Verónica; García Álvarez, Teresa; Acosta Martínez, Yelenei; Mazuecos Blanca, María Auxiliadora

2015-01-01

Secondary hyperparathyroidism is highly prevalent in kidney transplant recipients, and commonly results in hypercalcaemia; an association to osteopenia and bone fractures has also been observed. Paricalcitol has proved effective to control secondary hyperparathyroidism in chronic kidney disease in both dialysed and non-dialysed patients, with a low hypercalcaemia incidence. Currently available experience on paricalcitol use in kidney transplant recipients is scarce. Our main aim was to show the effect of paricalcitol on mineral bone metabolism in kidney transplant recipients with secondary hyperparathyroidism. A retrospective multicentre study in kidney transplant recipients aged>18 years with a 12-month or longer post-transplantation course, stable renal function, having received paricalcitol for more than 12 months, with available clinical follow-up for a 24-month period. A total of 69 patients with a 120 ± 92-month post-transplantation course were included. Baseline creatinine was 2.2 ± 0.9 mg/dl y GFR-MDRD was 36 ± 20 ml/min/1.73 m(2). Paricalcitol doses were gradually increased during the study: baseline 3.8 ± 1.9 μg/week, 12 months 5.2 ± 2.4 μg/week; 24 months 6.0 ± 2.9 μg/week (P<.001). Serum PTH levels showed a significant fast decline: baseline 288 ± 152 pg/ml; 6 months 226 ± 184 pg/ml; 12 months 207 ± 120; 24 months 193 ± 119 pg/ml (P<.001). Reduction from baseline PTH was ≥30% in 42.4% of patients at 12 months y in 65.2% of patients at 24 months. Alkaline phosphatase showed a significant decrease in first 6 months followed by a plateau: baseline 92 ± 50 IU/l; 6 months 85 ± 36 IU/l, 12 months 81 ± 39 IU/l (P<.001). Overall, no changes were observed in serum calcium and phosphorus, and in urine calcium excretion. PTH decline was larger in patients with higher baseline levels. Patients with lower baseline calcium levels showed significantly increased levels (mean increase was 0.5-0.6 mg/dl) but still within normal range, whereas patients with baseline calcium>10mg/dl showed gradually decreasing levels. Fifteen (21.7%) patients had received prior calcitriol therapy. When shifted to paricalcitol, such patients required paricalcitol doses significantly larger than those not having received calcitriol. Paricalcitol was used concomitantly to cinacalcet in 11 patients with significant PTH reductions being achieved; clinical course was similar to other patients and paricalcitol doses were also similar. Paricalcitol is an effective therapy for secondary hyperparathyroidism in kidney transplant recipients. Overall, no significant changes were observed in calcium and phosphorus levels or urinary excretion. Patients having previously received calcitriol required higher paricalcitol doses. When used in patients receiving cinacalcet, paricalcitol results in a significant PTH fall, with paricalcitol doses being similar to those used in patients not receiving cinacalcet. Copyright © 2015 The Authors. Published by Elsevier España, S.L.U. All rights reserved.

Stochastic Petri Net Modeling of Hypoxia Pathway Predicts a Novel Incoherent Feed-Forward Loop Controlling SDF-1 Expression in Acute Kidney Injury.

PubMed

Heidary, Zarifeh; Ghaisari, Jafar; Moein, Shiva; Naderi, Mahmood; Gheisari, Yousof

2016-01-01

Homing of stem cells to the sites of injury is crucial for tissue regeneration. Stromal derived factor 1 (SDF-1) is among the most important chemokines recruiting these cells. Unexpectedly, our previous experimental data on mouse models of acute kidney injury showed that SDF-1 has a declining trend following ischemic kidney insult. To describe this unforeseen observation, a stochastic Petri net model of SDF-1 regulation in the hypoxia pathway was constructed based on main related components extracted from literature. Using this strategy, predictions regarding the underlying mechanisms of SDF-1 kinetics are generated and a novel incoherent feed forward loop regulating SDF-1 expression is proposed. The computational approach suggested here can be exploited to propose novel therapies for debilitating disorders such as kidney injury.

[Effects of a resistance training program in patients with chronic kidney disease on hemodialysis].

PubMed

Cigarroa, Igor; Barriga, Rodrigo; Michéas, Camila; Zapata-Lamana, Rafael; Soto, Claudio; Manukian, Tomas

2016-07-01

Exercise may be a therapeutic tool for improving the functional capacity in patients with chronic kidney disease (CKD) who are on hemodialysis (HD). To determine the effects on muscle strength (MS), functional capacity (FC) and quality of life related to health (QOLRH) of a resistance training program in patients with CKD on HD. Thirteen CKD patients aged 38.8 ± 3 years, (7 men) on HD for more than one year participated in an exercise program twice a week during 8 weeks. At the beginning and at the end of the program, MS using a knee extension isometric strength test, FC using the six minutes walking test (6MWT) and QOLRH using the KDQOL CV-36 questionnaire were evaluated. Heart and respiratory rates, blood pressure, oxygen saturation and modified Borg scale were measured as control variables. After training, there were significant improvements in MS in both legs; in the distance travelled during 6MWT and in the physical component summary score of the KDQOL-36. Furthermore, a significant decline in diastolic blood pressure was observed. All other control variables did not change significantly. Exercise training during eight weeks in CKD patients in HD resulted in significant improvements in muscle strength, walking capacity and in the physical component of a quality of life score for patients with CKD.

Urinary MicroRNA as Biomarker in Renal Transplantation.

PubMed

van de Vrie, M; Deegens, J K; Eikmans, M; van der Vlag, J; Hilbrands, L B

2017-05-01

Urine represents a noninvasive source in which proteins and nucleic acids can be assessed. Such analytes may function as biomarkers to monitor kidney graft pathology at every desired frequency, thereby providing a time window to prevent graft damage by therapeutic intervention. Recently, several proteins have been measured in urine as markers of graft injury. However, the specificity is limited, and measuring urinary proteins generally lacks the potential to predict early kidney graft damage. Currently, urinary mRNA and microRNA are being investigated to evaluate the prognostic value of changes in gene expression during the initial stages of graft damage. At such time point, a change in treatment regimen and dosage is expected to have maximum potency to minimize future decline in graft function. Both mRNA and microRNAs have shown promising results in both detection and prediction of graft injury. An advantage of microRNAs compared to mRNA molecules is their stability, a characteristic that is beneficial when working with urine samples. In this review, we provide the current state of urinary biomarkers in renal transplantation, with a focus on urinary microRNA. In addition, we discuss the methods used to study urinary microRNA expression. © 2016 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of American Society of Transplant Surgeons.

Pharmacokinetics, Pharmacodynamics and Clinical Use of SGLT2 Inhibitors in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease.

PubMed

Scheen, André J

2015-07-01

Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) are proposed as a novel approach for the management of type 2 diabetes mellitus. SGLT2 cotransporters are responsible for reabsorption of 90 % of the glucose filtered by the kidney. The glucuretic effect resulting from SGLT2 inhibition contributes to reduce hyperglycaemia and also assists weight loss and blood pressure reduction. Several SGLT2 inhibitors are already available in many countries (dapagliflozin, canagliflozin, empagliflozin) and in Japan (ipragliflozin, tofogliflozin). These SGLT2 inhibitors share similar pharmacokinetic characteristics with a rapid oral absorption, a long elimination half-life allowing once-daily administration, an extensive hepatic metabolism mainly via glucuronidation to inactive metabolites and a low renal elimination as a parent drug. Pharmacokinetic parameters are slightly altered in the case of chronic kidney disease (CKD). While no dose adjustment is required in the case of mild CKD, SGLT2 inhibitors may not be used or only at a lower daily dose in patients with moderate CKD. Furthermore, the pharmacodynamic response to SGLT2 inhibitors as assessed by urinary glucose excretion declines with increasing severity of renal impairment as assessed by a reduction in the estimated glomerular filtration rate. Nevertheless, the glucose-lowering efficacy and safety of SGLT2 inhibitors are almost comparable in patients with mild CKD as in patients with normal kidney function. In patients with moderate CKD, the efficacy tends to be dampened and safety concerns may occur. In patients with severe CKD, the use of SGLT2 inhibitors is contraindicated. Thus, prescribing information should be consulted regarding dosage adjustments or restrictions in the case of renal dysfunction for each SGLT2 inhibitor. The clinical impact of SGLT2 inhibitors on renal function and their potential to influence the course of diabetic nephropathy deserve attention because of preliminary favourable results in animal models.

Kidney function tests

MedlinePlus

Kidney function tests are common lab tests used to evaluate how well the kidneys are working. Such tests include: ... Oh MS, Briefel G. Evaluation of renal function, water, electrolytes ... and Management by Laboratory Methods . 23rd ed. Philadelphia, ...

Imaging regional renal function parameters using radionuclide tracers

NASA Astrophysics Data System (ADS)

Qiao, Yi

A compartmental model is given for evaluating kidney function accurately and noninvasively. This model is cast into a parallel multi-compartment structure and each pixel region (picture element) of kidneys is considered as a single kidney compartment. The loss of radionuclide tracers from the blood to the kidney and from the kidney to the bladder are modelled in great detail. Both the uptake function and the excretion function of the kidneys can be evaluated pixel by pixel, and regional diagnostic information on renal function is obtained. Gamma Camera image data are required by this model and a screening test based renal function measurement is provided. The regional blood background is subtracted from the kidney region of interest (ROI) and the kidney regional rate constants are estimated analytically using the Kuhn-Pucker multiplier method in convex programming by considering the input/output behavior of the kidney compartments. The detailed physiological model of the peripheral compartments of the system, which is not available for most radionuclide tracers, is not required in the determination of the kidney regional rate constants and the regional blood background factors within the kidney ROI. Moreover, the statistical significance of measurements is considered to assure the improved statistical properties of the estimated kidney rate constants. The relations between various renal function parameters and the kidney rate constants are established. Multiple renal function measurements can be found from the renal compartmental model. The blood radioactivity curve and the regional (or total) radiorenogram determining the regional (or total) summed behavior of the kidneys are obtained analytically with the consideration of the statistical significance of measurements using convex programming methods for a single peripheral compartment system. In addition, a new technique for the determination of 'initial conditions' in both the blood compartment and the kidney compartment is presented. The blood curve and the radiorenogram are analyzed in great detail and a physiological analysis from the radiorenogram is given. Applications of Kuhn-Tucker multiplier methods are illustrated for the renal compartmental model in the field of nuclear medicine. Conventional kinetic data analysis methods, the maximum likehood method, and the weighted integration method are investigated and used for comparisons. Moreover, the effect of the blood background subtraction is shown by using the gamma camera images in man. Several functional images are calculated and the functional imaging technique is applied for evaluating renal function in man quantitatively and visually and compared with comments from a physician.

Increasing access to kidney transplantation in countries with limited resources: the Indian experience with kidney paired donation.

PubMed

Kute, Vivek B; Vanikar, Aruna V; Shah, Pankaj R; Gumber, Manoj R; Patel, Himanshu V; Engineer, Divyesh P; Modi, Pranjal R; Shah, Veena R; Trivedi, Hargovind L

2014-10-01

According to the Indian chronic kidney disease registry, in 2010 only 2% of end stage kidney disease patients were managed with kidney transplantation, 37% were managed with dialysis and 61% were treated conservatively without renal replacement therapy. In countries like India, where a well-organized deceased donor kidney transplantation program is not available, living donor kidney transplantation is the major source of organs for kidney transplantation. The most common reason to decline a donor for directed living donation is ABO incompatibility, which eliminates up to one third of the potential living donor pool. Because access to transplantation with human leukocyte antigen (HLA)-desensitization protocols and ABO incompatible transplantation is very limited due to high costs and increased risk of infections from more intense immunosuppression, kidney paired donation (KPD) promises hope to a growing number of end stage kidney disease patients. KPD is a rapidly growing and cost-effective living donor kidney transplantation strategy for patients who are incompatible with their healthy, willing living donor. In principle, KPD is feasible for any centre that performs living donor kidney transplantation. In transplant centres with a large living donor kidney transplantation program KPD does not require extra infrastructure, decreases waiting time, avoids transplant tourism and prevents commercial trafficking. Although KPD is still underutilized in India, it has been performed more frequently in recent times. To substantially increase donor pool and transplant rates, transplant centres should work together towards a national KPD program and frame a uniform acceptable allocation policy. © 2014 Asian Pacific Society of Nephrology.

The construction of a panel of serum amino acids for the identification of early chronic kidney disease patients.

PubMed

Li, Rui; Dai, Jinna; Kang, Hui

2018-03-01

Serum creatinine, urea, and cystatin-c are standardly used for the evaluation of renal function in the clinic. However, some patients have chronic kidney disease but still retain kidney function; a conventional serum index in these patients can be completely normal. Serum amino acid levels can reflect subtle changes in metabolism and are closely related to renal function. Here, we investigated how amino acids change as renal impairment increases. Subjects were divided into three groups by renal function glomerular filtration rate: healthy controls, patients with chronic kidney disease with normal kidney function, and patients with chronic kidney disease with decreased kidney function group. We identified 11 amino acids of interest using LC-MS/MS on MRM (+) mode. Statistical analysis indicated that alanine (ALA), valine (VAL), and tyrosine (TYR) decrease with renal function impairment, whereas phenylalanine (PHE) and citrulline (CIT) increase. We tried to construct a diagnostic model utilizing a combination of amino acids capable of identifying early chronic kidney disease patients. The accuracy, specificity, and sensitivity of the combining predictors were 86.9%, 84.6%, and 90.9%, respectively, which is superior to the reported values for serum creatinine, urea, and cystatin-c. Our data suggest that serum amino acid levels may supply important information for the early detection of chronic kidney disease. We are the first to establish a diagnostic model utilizing serum levels of multiple amino acids for the diagnosis of patients with early-stage chronic kidney disease. © 2017 Wiley Periodicals, Inc.

Effects of co-exposure to imidacloprid and gibberellic acid on redox status, kidney variables and histopathology in adult rats.

PubMed

Lafi, Bornia; Chaâbane, Mariem; Elwej, Awatef; Grati, Malek; Jamoussi, Kamel; Mnif, Hela; Boudawara, Tahia; Ketata Bouaziz, Hanen; Zeghal, Najiba

2018-05-01

Data on the individual nephrotoxic effects of imidacloprid (IMI) and gibberellic acid (GA 3 ) are scarce. Moreover, there is a lack of information about their combined effects on the renal tissue. Our study investigated the effects of IMI and GA 3 separately or together on rats kidney. IMI (64 mg/kg bw) was given for 3 weeks by gavage either individually or in combination with GA 3 (200 mg/L) via drinking water. IMI associated or no with GA 3 increased the levels of kidney malondialdehyde, advanced oxidation protein products, protein carbonyls and metallothionein, plasma creatinine, urea, blood urea nitrogen and lactate dehydrogenase activity. A decline of kidney uric acid level and antioxidant status was also observed. All these changes were supported by histopathological observations. Our results highlighted the role of IMI and/or GA 3 -induced nephrotoxicity. Co-exposure to IMI and GA 3 exhibited synergism in biochemical kidney variables and histopathology and antagonism in physical and morphological parameters.

N-Acetyl-Seryl-Aspartyl-Lysyl-Proline: mechanisms of renal protection in mouse model of systemic lupus erythematosus

PubMed Central

Liao, Tang-Dong; Nakagawa, Pablo; Janic, Branislava; D'Ambrosio, Martin; Worou, Morel E.; Peterson, Edward L.; Rhaleb, Nour-Eddine; Yang, Xiao-Ping

2015-01-01

Systemic lupus erythematosus is an autoimmune disease characterized by the development of auto antibodies against a variety of self-antigens and deposition of immune complexes that lead to inflammation, fibrosis, and end-organ damage. Up to 60% of lupus patients develop nephritis and renal dysfunction leading to kidney failure. N-acetyl-seryl-aspartyl-lysyl-proline, i.e., Ac-SDKP, is a natural tetrapeptide that in hypertension prevents inflammation and fibrosis in heart, kidney, and vasculature. In experimental autoimmune myocarditis, Ac-SDKP prevents cardiac dysfunction by decreasing innate and adaptive immunity. It has also been reported that Ac-SDKP ameliorates lupus nephritis in mice. We hypothesize that Ac-SDKP prevents lupus nephritis in mice by decreasing complement C5-9, proinflammatory cytokines, and immune cell infiltration. Lupus mice treated with Ac-SDKP for 20 wk had significantly lower renal levels of macrophage and T cell infiltration and proinflammatory chemokine/cytokines. In addition, our data demonstrate for the first time that in lupus mouse Ac-SDKP prevented the increase in complement C5-9, RANTES, MCP-5, and ICAM-1 kidney expression and it prevented the decline of glomerular filtration rate. Ac-SDKP-treated lupus mice had a significant improvement in renal function and lower levels of glomerular damage. Ac-SDKP had no effect on the production of autoantibodies. The protective Ac-SDKP effect is most likely achieved by targeting the expression of proinflammatory chemokines/cytokines, ICAM-1, and immune cell infiltration in the kidney, either directly or via C5-9 proinflammatory arm of complement system. PMID:25740596

Elevated bilirubin levels are associated with a better renal prognosis and ameliorate kidney fibrosis.

PubMed

Park, Sehoon; Kim, Do Hyoung; Hwang, Jin Ho; Kim, Yong-Chul; Kim, Jin Hyuk; Lim, Chun Soo; Kim, Yon Su; Yang, Seung Hee; Lee, Jung Pyo

2017-01-01

Bilirubin has been reported to protect against kidney injury. However, further studies highlighting the beneficial effects of bilirubin on renal fibrosis and chronic renal function decline are necessary. We assessed a prospective cohort with a reference range of total bilirubin levels. The primary outcome was a 30% reduction in the estimated glomerular filtration rate (eGFR) from baseline, and the secondary outcome was a doubling of the serum creatinine levels, halving of the eGFR and the initiation of dialysis. In addition, experiments with tubular epithelial cells and C57BL/6 mice were performed to investigate the protective effects of bilirubin on kidney fibrosis. As a result, 1,080 patients were included in the study cohort. The study group with relative hyperbilirubinemia (total bilirubin 0.8-1.2 mg/dL) showed a better prognosis in terms of the primary outcome (adjusted hazard ratio (HR) 0.33, 95% confidence interval (CI) 0.19-0.59, P < 0.001) and the secondary outcome (adjusted HR 0.20, 95% CI 0.05 to 0.71, P = 0.01) than that of the control group. Moreover, the bilirubin-treated mice showed less fibrosis in the unilateral ureteral obstruction (UUO) model (P < 0.05). In addition, bilirubin treatment decreased fibronectin expression in tubular epithelial cells in a dose-dependent manner (P < 0.05). Mildly elevated serum bilirubin levels were associated with better renal prognosis, and bilirubin treatment induced a beneficial effect on renal fibrosis. Therefore, bilirubin could be a potential therapeutic target to delay fibrosis-related kidney disease progression.

Elevated bilirubin levels are associated with a better renal prognosis and ameliorate kidney fibrosis

PubMed Central

Hwang, Jin Ho; Kim, Yong-Chul; Kim, Jin Hyuk; Lim, Chun Soo; Kim, Yon Su; Yang, Seung Hee; Lee, Jung Pyo

2017-01-01

Background Bilirubin has been reported to protect against kidney injury. However, further studies highlighting the beneficial effects of bilirubin on renal fibrosis and chronic renal function decline are necessary. Methods We assessed a prospective cohort with a reference range of total bilirubin levels. The primary outcome was a 30% reduction in the estimated glomerular filtration rate (eGFR) from baseline, and the secondary outcome was a doubling of the serum creatinine levels, halving of the eGFR and the initiation of dialysis. In addition, experiments with tubular epithelial cells and C57BL/6 mice were performed to investigate the protective effects of bilirubin on kidney fibrosis. Results As a result, 1,080 patients were included in the study cohort. The study group with relative hyperbilirubinemia (total bilirubin 0.8–1.2 mg/dL) showed a better prognosis in terms of the primary outcome (adjusted hazard ratio (HR) 0.33, 95% confidence interval (CI) 0.19–0.59, P < 0.001) and the secondary outcome (adjusted HR 0.20, 95% CI 0.05 to 0.71, P = 0.01) than that of the control group. Moreover, the bilirubin-treated mice showed less fibrosis in the unilateral ureteral obstruction (UUO) model (P < 0.05). In addition, bilirubin treatment decreased fibronectin expression in tubular epithelial cells in a dose-dependent manner (P < 0.05). Conclusions Mildly elevated serum bilirubin levels were associated with better renal prognosis, and bilirubin treatment induced a beneficial effect on renal fibrosis. Therefore, bilirubin could be a potential therapeutic target to delay fibrosis-related kidney disease progression. PMID:28225832

Sequential kidney/islet transplantation using prednisone-free immunosuppression.

PubMed

Kaufman, Dixon B; Baker, Marshall S; Chen, Xiaojuan; Leventhal, Joseph R; Stuart, Frank P

2002-08-01

Islet transplantation is becoming established as a treatment option for type I diabetes in select patients. Individuals with type I diabetes who have previously received a successful kidney allograft may be good candidates for islet transplantation. They have already assumed the risks of chronic immunosuppression, so the added procedural risk of a subsequent islet transplant would be minimal. Furthermore, because of the preimmunosuppressed state it is possible that islet-after-kidney transplantation may result in a more efficient early islet engraftment. Consequently, insulin independence might be achieved with significantly fewer islets than the approximately 8-10,000 islet equivalents/kg/b.w. currently required. A mass that usually demands two or more cadaveric donors. A case of successful islet-after-kidney transplantation is described using the steroid-free Edmonton immunosuppression protocol. Characteristics of the final islet product are: a) islet equivalents: 265,888 (4100 islet equivalents/kg/b.w.); b) islet purity: 75-80%; c) viability: >95% (trypan blue exclusion); and d) mean islet potency (static low-high glucose challenge): 4.16 +/- 1.91-fold increase. Post-transplant the patient's hypoglycemic episodes abated. Exogenous insulin requirements were eliminated at week 12 post-transplant as basal and Ensure (Abbott Laboratories, Abbott Park, IL, USA) oral glucose stimulated C-peptide levels peaked and stabilized. Twenty-four-hour continuous glucose monitoring confirmed moment-to-moment glycemic control, and periodic nonfasting finger stick glucose determinations over the next month confirmed glycemia was controlled. Hemoglobin A1c levels declined from a pretransplant level of 6.9% to 5.3%. Renal allograft function remained changed.

Protocatechuic Aldehyde Attenuates Cisplatin-Induced Acute Kidney Injury by Suppressing Nox-Mediated Oxidative Stress and Renal Inflammation

PubMed Central

Gao, Li; Wu, Wei-Feng; Dong, Lei; Ren, Gui-Ling; Li, Hai-Di; Yang, Qin; Li, Xiao-Feng; Xu, Tao; Li, Zeng; Wu, Bao-Ming; Ma, Tao-Tao; Huang, Cheng; Huang, Yan; Zhang, Lei; Lv, Xiongwen; Li, Jun; Meng, Xiao-Ming

2016-01-01

Cisplatin is a classic chemotherapeutic agent widely used to treat different types of cancers including ovarian, head and neck, testicular and uterine cervical carcinomas. However, cisplatin induces acute kidney injury by directly triggering an excessive inflammatory response, oxidative stress, and programmed cell death of renal tubular epithelial cells, all of which lead to high mortality rates in patients. In this study, we examined the protective effect of protocatechuic aldehyde (PA) in vitro in cisplatin-treated tubular epithelial cells and in vivo in cisplatin nephropathy. PA is a monomer of Traditional Chinese Medicine isolated from the root of S. miltiorrhiza (Lamiaceae). Results show that PA prevented cisplatin-induced decline of renal function and histological damage, which was confirmed by attenuation of KIM1 in both mRNA and protein levels. Moreover, PA reduced renal inflammation by suppressing oxidative stress and programmed cell death in response to cisplatin, which was further evidenced by in vitro data. Of note, PA suppressed NAPDH oxidases, including Nox2 and Nox4, in a dosage-dependent manner. Moreover, silencing Nox4, but not Nox2, removed the inhibitory effect of PA on cisplatin-induced renal injury, indicating that Nox4 may play a pivotal role in mediating the protective effect of PA in cisplatin-induced acute kidney injury. Collectively, our data indicate that PA blocks cisplatin-induced acute kidney injury by suppressing Nox-mediated oxidative stress and renal inflammation without compromising anti-tumor activity of cisplatin. These findings suggest that PA and its derivatives may serve as potential protective agents for cancer patients receiving cisplatin treatment. PMID:27999546

Dietary Approaches in the Management of Diabetic Patients with Kidney Disease

PubMed Central

Ko, Gang Jee; Goldstein-Fuchs, Jordi; Rhee, Connie M.

2017-01-01

Chronic kidney disease (CKD) is one of the most prevalent complications of diabetes, and patients with diabetic kidney disease (DKD) have a substantially higher risk of cardiovascular disease and death compared to their non-diabetic CKD counterparts. In addition to pharmacologic management strategies, nutritional and dietary interventions in DKD are an essential aspect of management with the potential for ameliorating kidney function decline and preventing the development of other end-organ complications. Among DKD patients with non-dialysis dependent CKD, expert panels recommend lower dietary protein intake of 0.8 g/kg of body weight/day, while higher dietary protein intake (>1.2 g/kg of body weight/day) is advised among diabetic end-stage renal disease patients receiving maintenance dialysis to counteract protein catabolism, dialysate amino acid and protein losses, and protein-energy wasting. Carbohydrates from sugars should be limited to less than 10% of energy intake, and it is also suggested that higher polyunsaturated and monounsaturated fat consumption in lieu of saturated fatty acids, trans-fat, and cholesterol are associated with more favorable outcomes. While guidelines recommend dietary sodium restriction to less than 1.5–2.3 g/day, excessively low sodium intake may be associated with hyponatremia as well as impaired glucose metabolism and insulin sensitivity. As patients with advanced DKD progressing to end-stage renal disease may be prone to the “burnt-out diabetes” phenomenon (i.e., spontaneous resolution of hypoglycemia and frequent hypoglycemic episodes), further studies in this population are particularly needed to determine the safety and efficacy of dietary restrictions in this population. PMID:28758978

Perceived Barriers and Support Strategies for Reducing Sodium Intake in Patients with Chronic Kidney Disease: a Qualitative Study.

PubMed

Meuleman, Yvette; Ten Brinke, Lucia; Kwakernaak, Arjan J; Vogt, Liffert; Rotmans, Joris I; Bos, Willem Jan W; van der Boog, Paul J M; Navis, Gerjan; van Montfrans, Gert A; Hoekstra, Tiny; Dekker, Friedo W; van Dijk, Sandra

2015-08-01

Reducing sodium intake can prevent cardiovascular complications and further decline of kidney function in patients with chronic kidney disease. However, the vast majority of patients fail to reach an adequate sodium intake, and little is known about why they do not succeed. This study aims to identify perceived barriers and support strategies for reducing sodium intake among both patients with chronic kidney disease and health-care professionals. A purposive sample of 25 patients and 23 health-care professionals from 4 Dutch medical centers attended 8 focus groups. Transcripts were analyzed thematically and afterwards organized according to the phases of behavior change of self-regulation theory. Multiple themes emerged across different phases of behavior change, including the patients' lack of practical knowledge and intrinsic motivation, the maladaptive illness perceptions and refusal skills, the lack of social support and feedback regarding disease progression and sodium intake, and the availability of low-sodium foods. The results indicate the need for the implementation of support strategies that target specific needs of patients across the whole process of changing and maintaining a low-sodium diet. Special attention should be paid to supporting patients to set sodium-related goals, strengthening intrinsic motivation, providing comprehensive and practical information (e.g., about hidden salt in products), increasing social support, stimulating the self-monitoring of sodium intake and disease progression, and building a supportive patient-professional relationship that encompasses shared decision making and coaching. Moreover, global programs should be implemented to reduce sodium levels in processed foods, introduce sodium-related product labels, and increase consumer awareness.

Cigarette smoking causes epigenetic changes associated with cardiorenal fibrosis

PubMed Central

Haller, Steven T.; Fan, Xiaoming; Xie, Jeffrey X.; Kennedy, David J.; Liu, Jiang; Yan, Yanling; Hernandez, Dawn-Alita; Mathew, Denzil P.; Cooper, Christopher J.; Shapiro, Joseph I.; Tian, Jiang

2016-01-01

Clinical studies indicate that smoking combustible cigarettes promotes progression of renal and cardiac injury, leading to functional decline in the setting of chronic kidney disease (CKD). However, basic studies using in vivo small animal models that mimic clinical pathology of CKD are lacking. To address this issue, we evaluated renal and cardiac injury progression and functional changes induced by 4 wk of daily combustible cigarette smoke exposure in the 5/6th partial nephrectomy (PNx) CKD model. Molecular evaluations revealed that cigarette smoke significantly (P < 0.05) decreased renal and cardiac expression of the antifibrotic microRNA miR-29b-3 and increased expression of molecular fibrosis markers. In terms of cardiac and renal organ structure and function, exposure to cigarette smoke led to significantly increased systolic blood pressure, cardiac hypertrophy, cardiac and renal fibrosis, and decreased renal function. These data indicate that decreased expression of miR-29b-3p is a novel mechanism wherein cigarette smoke promotes accelerated cardiac and renal tissue injury in CKD. (155 words) PMID:27789733

Enteric hyperoxaluria in chronic pancreatitis.

PubMed

Demoulin, Nathalie; Issa, Zaina; Crott, Ralph; Morelle, Johann; Danse, Etienne; Wallemacq, Pierre; Jadoul, Michel; Deprez, Pierre H

2017-05-01

Chronic pancreatitis may lead to steatorrhea, enteric hyperoxaluria, and kidney damage. However, the prevalence and determinants of hyperoxaluria in chronic pancreatitis patients as well as its association with renal function decline have not been investigated.We performed an observational study. Urine oxalate to creatinine ratio was assessed on 2 independent random urine samples in consecutive adult patients with chronic pancreatitis followed at the outpatient clinic from March 1 to October 31, 2012. Baseline characteristics and annual estimated glomerular filtration rate (eGFR) change during follow-up were compared between patients with hyper- and normo-oxaluria.A total of 48 patients with chronic pancreatitis were included. The etiology of the disease was toxic (52%), idiopathic (27%), obstructive (11%), autoimmune (6%), or genetic (4%). Hyperoxaluria (defined as urine oxalate to creatinine ratio >32 mg/g) was found in 23% of patients. Multivariate regression analysis identified clinical steatorrhea, high fecal acid steatocrit, and pancreatic atrophy as independent predictors of hyperoxaluria. Taken together, a combination of clinical steatorrhea, steatocrit level >31%, and pancreatic atrophy was associated with a positive predictive value of 100% for hyperoxaluria. On the contrary, none of the patients with a fecal elastase-1 level >100 μg/g had hyperoxaluria. Longitudinal evolution of eGFR was available in 71% of the patients, with a mean follow-up of 904 days. After adjustment for established determinants of renal function decline (gender, diabetes, bicarbonate level, baseline eGFR, and proteinuria), a urine oxalate to creatinine ratio >32 mg/g was associated with a higher risk of eGFR decline.Hyperoxaluria is highly prevalent in patients with chronic pancreatitis and associated with faster decline in renal function. A high urine oxalate to creatinine ratio in patients with chronic pancreatitis is best predicted by clinical steatorrhea, a high acid steatocrit, and pancreatic atrophy. Further studies will need to investigate the mechanisms of renal damage in chronic pancreatitis and the potential benefits of therapies reducing oxaluria.

Asymptomatic proteinuria. Clinical significance.

PubMed

Papper, S

1977-09-01

Patients with asymptomatic proteinuria have varied reasons for the proteinuria and travel diverse courses. In the individual with normal renal function and no systemic cause, ie, idiopathic asymptomatic proteinuria, the outlook is generally favorable. Microscopic hematuria probably raises some degree of question about prognosis. The kidney shows normal glomeruli, subtle changes, or an identifiable lesion. The initial approach includes a clinical and laboratory search for systemic disease, repeated urinalyses, quantitative measurements of proteinuria, determination of creatinine clearance, protein electrophoresis where indicated, and intravenous pyelography. The need for regularly scheduled follow-up evaluation is emphasized. Although the initial approach need not include renal biopsy, a decline in creatinine clearance, an increase in proteinuria, or both are indications for biopsy and consideration of drug therapy.

Thyroid function, reduced kidney function and incident chronic kidney disease in a community-based population: the Atherosclerosis Risk in Communities study.

PubMed

Schultheiss, Ulla T; Daya, Natalie; Grams, Morgan E; Seufert, Jochen; Steffes, Michael; Coresh, Josef; Selvin, Elizabeth; Köttgen, Anna

2017-11-01

Reduced kidney function is a common public health problem that increases risk for a wide variety of adverse outcomes, making the identification of potentially modifiable factors associated with the development of incident chronic kidney disease (CKD) important. Alterations in the hypothalamic-pituitary-thyroid axis have been linked to reduced kidney function, but the association of thyroid function with the development of incident CKD is largely uncharacterized. Concentrations of thyroid stimulating hormone (TSH), free thyroxine (FT4), triiodothyronine (T3) and thyroid peroxidase antibody (TPOAb) were quantified in 12 785 black and white participants of the ongoing community-based prospective Atherosclerosis Risk in Communities study. Thyroid markers and clinical categories of thyroid dysfunction (euthyroidism, combined subclinical and overt hypothyroidism, combined subclinical and overt hyperthyroidism) were also evaluated for their association with reduced kidney function (estimated glomerular filtration rate <60 mL/min/1.73 m2) at study baseline and with incident CKD over a median follow-up time of 19.6 years. Higher TSH and FT4 as well as lower T3 concentrations were strongly and independently associated with reduced kidney function at study baseline. The clinical entities hypothyroidism and hyperthyroidism were also associated with higher odds of baseline reduced kidney function, but this was not significant. However, none of the markers of thyroid function nor different clinical categories of thyroid dysfunction (hypothyroidism, hyperthyroidism or TPOAb positivity) were associated with incident CKD in adjusted analyses. Elevated TSH, FT4 and reduced T3 concentrations were associated with reduced kidney function cross-sectionally. The lack of association with the development of incident CKD suggests that altered thyroid function in the general population is not causally related to CKD development, but screening for thyroidal status may be especially relevant in persons with reduced kidney function. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

[Banff score changes in kidneys from marginal donors].

PubMed

Borda, Bernadett; Szederkényi, Edit; Ottlakán, Aurél; Kemény, Éva; Szabó, Viktor; Hódi, Zoltán; Lázár, György

2016-02-21

Despite an increase in the number of cadaver donors and the number of overall organ transplantations, the dramatic increase in the waiting list makes it necessary to reconsider donor criteria. The authors examined whether differences could exist in the function and/or morphology of transplanted kidneys originated from marginal and ideal donors one and five years after transplantation. Kidney function and histopathologic findings were analysed and compared one and 5 years after transplantation in 97 patients having marginal donor kidneys and 178 patients who received ideal donor kidneys. Serum creatinine level was significantly higher (p = 0.0001) and estimated glomerular filtration rate was significantly lower (p = 0.003) in patients having marginal donor kidneys as compared to those with ideal donor kidneys 5 years after transplantation. Morphological changes in the transplanted kidneys such as tubulitis (p = 0.014) and interstitial inflammation (p = 0.025) were significantly more frequently present in patients with marginal donor kidneys than in those with ideal donor kidneys one year after transplantation. Despite an absence of differences in kidney function one year after kidney transplantation between patients having marginal and ideal donor kidneys, morphologic differences in the transplanted kidneys can be detected between the two groups of patients.

Telomere attrition, kidney function, and prevalent chronic kidney disease in the United States.

PubMed

Mazidi, Moshen; Rezaie, Peyman; Covic, Adriac; Malyszko, Jolanta; Rysz, Jacek; Kengne, Andre Pascal; Banach, Maciej

2017-10-06

Telomere length is an emerging novel biomarker of biologic age, cardiovascular risk and chronic medical conditions. Few studies have focused on the association between telomere length (TL) and kidney function. We investigated the association between TL and kidney function/prevalent chronic kidney disease (CKD) in US adults. The National Health and Nutrition Examination Survey (NHANES) participants with measured data on kidney function and TL from 1999 to 2002 were included. Estimated glomerular filtration rate (eGFR) was based on CKD Epidemiology Collaboration (CKD-EPI) equation. Urinary albumin excretion was assessed using urinary albumin-creatinine ratio (ACR). We used multivariable adjusted linear and logistic regression models, accounting for the survey design and sample weights. Of the 10568 eligible participants, 48.0% ( n =5020) were men. Their mean age was 44.1 years. eGFR significantly decreased and ACR significantly increased across increasing quarters of TL (all p <0.001). The association between TL and kidney function remained robust even after adjusting for potential confounding factors, but the association between TL and ACR was only borderline significant (β-coefficient= -0.012, p =0.056). The association of kidney function with a marker of cellular senescence suggests an underlying mechanism influencing the progression of nephropathy.

What Is Atherosclerosis?

MedlinePlus

... builds up in the renal arteries. These arteries supply oxygen-rich blood to your kidneys. Over time, chronic kidney disease causes a slow loss of kidney function. The main function of the kidneys is to remove waste and extra water from the body. Overview The cause of atherosclerosis ...

(Re)Building a Kidney

PubMed Central

Carroll, Thomas J.; Cleaver, Ondine; Gossett, Daniel R.; Hoshizaki, Deborah K.; Hubbell, Jeffrey A.; Humphreys, Benjamin D.; Jain, Sanjay; Jensen, Jan; Kaplan, David L.; Kesselman, Carl; Ketchum, Christian J.; Little, Melissa H.; McMahon, Andrew P.; Shankland, Stuart J.; Spence, Jason R.; Valerius, M. Todd; Wertheim, Jason A.; Wessely, Oliver; Zheng, Ying; Drummond, Iain A.

2017-01-01

(Re)Building a Kidney is a National Institute of Diabetes and Digestive and Kidney Diseases-led consortium to optimize approaches for the isolation, expansion, and differentiation of appropriate kidney cell types and the integration of these cells into complex structures that replicate human kidney function. The ultimate goals of the consortium are two-fold: to develop and implement strategies for in vitro engineering of replacement kidney tissue, and to devise strategies to stimulate regeneration of nephrons in situ to restore failing kidney function. Projects within the consortium will answer fundamental questions regarding human gene expression in the developing kidney, essential signaling crosstalk between distinct cell types of the developing kidney, how to derive the many cell types of the kidney through directed differentiation of human pluripotent stem cells, which bioengineering or scaffolding strategies have the most potential for kidney tissue formation, and basic parameters of the regenerative response to injury. As these projects progress, the consortium will incorporate systematic investigations in physiologic function of in vitro and in vivo differentiated kidney tissue, strategies for engraftment in experimental animals, and development of therapeutic approaches to activate innate reparative responses. PMID:28096308

Poverty and racial disparities in kidney disease: the REGARDS study.

PubMed

McClellan, William M; Newsome, Britt B; McClure, Leslie A; Howard, George; Volkova, Nataliya; Audhya, Paul; Warnock, David G

2010-01-01

There are pronounced disparities among black compared to white Americans for risk of end-stage renal disease. This study examines whether similar relationships exist between poverty and racial disparities in chronic kidney disease (CKD) prevalence. We studied 22,538 participants in the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort study. We defined individual poverty as family income below USD 15,000 and a neighborhood as poor if 25% or more of the households were below the federal poverty level. As the estimated glomerular filtration rate (GFR) declined from 50-59 to 10-19 ml/min/ 1.73 m2, the black:white odds ratio (OR) for impaired kidney function increased from 0.74 (95% CI 0.66, 0.84) to 2.96 (95% CI 1.96, 5.57). Controlling for individual income below poverty, community poverty, demographic and comorbid characteristics attenuated the black:white prevalence to an OR of 0.65 (95% CI 0.57, 0.74) among individuals with a GFR of 59-50 ml/min/1.73 m2 and an OR of 2.21 (95% CI 1.25, 3.93) among individuals with a GFR between 10 and 19 ml/min/ 1.73 m2. Household, but not community poverty, was independently associated with CKD and attenuated but did not fully account for differences in CKD prevalence between whites and blacks. Copyright 2010 S. Karger AG, Basel.

MASTERPLAN: study of the role of nurse practitioners in a multifactorial intervention to reduce cardiovascular risk in chronic kidney disease patients.

PubMed

Van Zuilen, Arjan D; Wetzels, Jack F M; Bots, Michiel L; Van Blankestijn, Peter J

2008-01-01

Moderate to severe chronic kidney disease (CKD) is associated with increased cardiovascular risk. Usually nephrologists are primarily responsible for the care of CKD patients. However, in many cases treatment goals, as formulated in guidelines, are not met. The addition of a nurse practitioner might improve the quality of care. The Multifactorial Approach and Superior Treatment Efficacy in Renal Patients with the Aid of Nurse Practitioners (MASTERPLAN) study is a randomized controlled multicenter trial, aimed at investigating whether a multifactorial approach in patients with moderate to severe CKD (stage 3 and 4) to achieving treatment goals using both a polydrug strategy and lifestyle treatment either with or without the addition of a nurse practitioner will reduce cardiovascular risk and slow the decline of kidney function. Patients (n=793) have been randomized to nurse care or physician care. In the nurse-care arm of the study, nurse practitioners use flowcharts to address risk factors requiring drug and/or lifestyle modification. They have been trained to coach patients by motivational interviewing with the aim of improving patient self-management. At baseline, both treatment groups show equal distributions with regard to key variables in the study. Moreover, in only 1 patient were all risk factors within the limits as defined in various guidelines, which underscores the relevance of our initiative.

MRI tools for assessment of microstructure and nephron function of the kidney.

PubMed

Xie, Luke; Bennett, Kevin M; Liu, Chunlei; Johnson, G Allan; Zhang, Jeff Lei; Lee, Vivian S

2016-12-01

MRI can provide excellent detail of renal structure and function. Recently, novel MR contrast mechanisms and imaging tools have been developed to evaluate microscopic kidney structures including the tubules and glomeruli. Quantitative MRI can assess local tubular function and is able to determine the concentrating mechanism of the kidney noninvasively in real time. Measuring single nephron function is now a near possibility. In parallel to advancing imaging techniques for kidney microstructure is a need to carefully understand the relationship between the local source of MRI contrast and the underlying physiological change. The development of these imaging markers can impact the accurate diagnosis and treatment of kidney disease. This study reviews the novel tools to examine kidney microstructure and local function and demonstrates the application of these methods in renal pathophysiology. Copyright © 2016 the American Physiological Society.

Effect of blood pressure lowering on markers of kidney disease progression.

PubMed

Udani, Suneel M; Koyner, Jay L

2009-10-01

Hypertension remains a common comorbidity and cause of chronic kidney disease (CKD). As the number of patients with CKD grows, so does the need to identify modifiable risk factors for CKD progression. Data on slowing progression of CKD or preventing end-stage renal disease with aggressive blood pressure control have not yielded definitive conclusions regarding ideal blood pressure targets. Shifting the focus of antihypertensive therapy to alternative markers of end-organ damage, specifically proteinuria, has yielded some promise in preventing the progression of CKD. Nevertheless, proteinuria and decline in estimated GFR may represent an irreversible degree of injury to the kidney that limits the impact of any therapy. The identification and use of novel markers of kidney injury to assess the impact of antihyper-tensive therapy may yield clearer direction with regard to optimal management of hypertension in the setting of CKD.

Adaptive functional change of the contralateral kidney after partial nephrectomy.

PubMed

Choi, Se Young; Yoo, Sangjun; You, Dalsan; Jeong, In Gab; Song, Cheryn; Hong, Bumsik; Hong, Jun Hyuk; Ahn, Hanjong; Kim, Choung-Soo

2017-08-01

Partial nephrectomy aims to maintain renal function by nephron sparing; however, functional changes in the contralateral kidney remain unknown. We evaluate the functional change in the contralateral kidney using a diethylene triamine penta-acetic acid (DTPA) renal scan and determine factors predicting contralateral kidney function after partial nephrectomy. A total of 699 patients underwent partial nephrectomy, with a DTPA scan before and after surgery to assess the separate function of each kidney. Patients were divided into three groups according to initial contralateral glomerular filtration rate (GFR; group 1 : <30 ml·min -1 ·1.73 m -2 , group 2 : 30-45 ml·min -1 ·1.73 m -2 , and group 3 : ≥45 ml·min -1 ·1.73 m -2 ). Multiple-regression analysis was used to identify the factors associated with increased GFR of the contralateral kidney over a 4-yr postoperative period. Patients in group 1 had a higher mean age and hypertension history, worse American Society of Anesthesiologists score, and larger tumor size than in the other two groups. The ipsilateral GFR changes at 4 yr after partial nephrectomy were -18.9, -3.6, and 3.9% in groups 1 , 2 , and 3 , respectively, whereas the contralateral GFR changes were 10.8, 25.7, and 38.8%. Age [β: -0.105, 95% confidence interval (CI): -0.213; -0.011, P < 0.05] and preoperative contralateral GFR (β: -0.256, 95% CI: -0.332; -0.050, P < 0.01) were significant predictive factors for increased GFR of the contralateral kidney after 4 yr. The contralateral kidney compensated for the functional loss of the ipsilateral kidney. The increase of GFR in contralateral kidney is more prominent in younger patients with decreased contralateral renal function. Copyright © 2017 the American Physiological Society.

Postoperative elevation in creatine kinase and its impact on renal function in patients undergoing complex partial nephrectomy.

PubMed

Sidana, Abhinav; Walton-Diaz, Annerleim; Truong, Hong; Siddiqui, M Minhaj; Miao, Ning; Shih, Johanna; Mannes, Andrew; Bratslavsky, Gennady; Linehan, W Marston; Metwalli, Adam R

2016-07-01

To identify the risk factors associated with development of postoperative elevation of creatine kinase (CK) and study its effect on renal function in patients who underwent complex multifocal partial nephrectomy (PN). Patients who underwent PN at National Cancer Institute between January 2007 and December 2012 were included in the study. Elevated serum CK was defined as >2000 U/L. Kidney function was assessed using serum creatinine and estimated glomerular filtration rate (eGFR). Changes were reported as percent change from preoperative values and compared using the Wilcoxon test. Regression analysis was performed to identify the predictors of elevation in CK and decline in eGFR. From 407 total cases, 207 had adequate CK data for analysis. Median number of tumors removed was 3 (1-70). Median peak CK was 1458 (82-36,788). Forty-two percent developed CK elevation >2000 U/L. Factors associated with postoperative elevation of CK > 2000 were young age (p = 0.009), high BMI (p = 0.003) and operating room time (p < 0.001). Although CK > 2000 was associated with significantly greater decline in eGFR (37.4 vs. 20.3 %, p < 0.001) in immediate postoperative period, this change largely resolved to a much less clinically relevant (9.2 vs 3.3 %, p = 0.040) change after 3 months. On multivariate analysis, postoperative elevation in CK was not found to be an independent factor determining renal function at 3 months. In our cohort, a significant proportion of patients developed CK elevations >2000 U/L. While patients with elevated CK had more decline in eGFR in immediate postoperative period, postoperative elevations of CK did not appear to impact overall long-term renal function in patients undergoing PN.

Preoperative hydronephrosis is associated with less decline in renal function after radical nephroureterectomy for upper tract urothelial carcinoma.

PubMed

Singla, Nirmish; Hutchinson, Ryan; Haddad, Ahmed; Sagalowsky, Arthur; Lotan, Yair; Margulis, Vitaly

2016-08-01

To compare renal function changes after radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC) based on the presence of preoperative hydronephrosis. Clinicopathologic data of 208 patients with UTUC treated surgically from 1998 to 2013 were compiled. Patients with bilateral disease, less than 1 month follow up, missing hydronephrosis data, or who underwent nephron-sparing approaches were excluded. Estimated glomerular filtration rate (eGFR) was calculated preoperatively, at first follow up (within 3 months) and at last follow up using the Modification of Diet in Renal Disease equation. Events were defined as new-onset stage III chronic kidney disease (CKD) or worsening of CKD stage in preexisting CKD. Kaplan-Meier event-free survival was assessed. Cox regression was performed to identify predictors of events. A total of 132 patients were analyzed, including 62 (47.0%) with hydronephrosis. Median follow up was 28.6 months. Patients with hydronephrosis had larger tumors (p = 0.045) and higher pathologic stage (p = 0.010) than those without hydronephrosis. Baseline eGFR was comparable between groups (p = 0.088). Patients without hydronephrosis experienced greater declines in eGFR following surgery (p < 0.001) and higher event rates at first (42.8% versus 24.2%, p = 0.028) and last (54.2% versus 30.6%, p = 0.008) follow up. On Cox regression, hydronephrosis predicted lower event likelihood in the long term (univariate HR 0.54, p = 0.033), while ureteral tumor location predicted lower event likelihood in the short term (HR 0.52, p = 0.030). Patients with hydronephrosis undergoing RNU for UTUC experience less decline in renal function than those without hydronephrosis. Given the prevalence of renal dysfunction in patients with UTUC, our results may help inform preoperative counseling.

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.

Periodontitis associated with Chronic Kidney Disease among Mexican Americans

PubMed Central

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

2012-01-01

Objective In comparison to non-Hispanic whites, a number of healthcare 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 to Mexican Americans with normal kidney function, and that the level of kidney function would be inversely related to the prevalence of periodontal disease. Method We examined this hypothesis using the National Health and Nutrition Examination Survey 1988–1994 (NHANES III) dataset. We followed the American Academy of Periodontology (AAP)/Center for Disease Control and Prevention (CDC) case definition for periodontitis. Glomerular filtration rate was estimated using the CKD-Epidemiology (EPI) equation for Hispanic populations. The classification to CKD stages was based on the National Kidney Foundation Kidney Disease Outcomes Quality Initiative. Results 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 2-fold more likely to have periodontitis compared to 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 eGFR reduction from the mean. Conclusion This is the first report, to the best our knowledge, that showed an increase of periodontitis prevalence with decreased kidney function in this population. PMID:22775287

Is there a difference in progression of renal disease between South Asian and white European diabetic adults with moderately reduced kidney function?

PubMed

Pallayova, Maria; Rayner, Hugh; Taheri, Shahrad; Dasgupta, Indranil

2015-08-01

We examined potential ethnicity-related differences in progression of chronic kidney disease (CKD) between South Asian and white European diabetic adults with CKD stage 3 over a 5-year period. We analysed data collected from diabetic adults of white European and South Asian ethnicity who had attended diabetes and diabetes-renal outpatient clinics with baseline estimated glomerular filtration rate (eGFR) values ≥30 and <60 ml/min/1.73 m(2) over 5 years (2005-2010); 891 (76%) were white Europeans, 282 (24%) were South Asians. Despite similar baseline eGFR (P=0.103), South Asians were younger [median (interquartile range) 68 (63-73) vs. 70 (64-77) years; P<0.001] and had worse baseline glycated haemoglobin than white Europeans [8.0 (7.0-9.1) vs. 7.6 (6.8-8.7)%; P=0.004]. The 5-year follow-up eGFR and the decline in eGFR did not differ between the two groups. Thirty-five (12.4%) South Asians and 82 (9.2%) white Europeans progressed to stages 4-5 CKD (P=0.112). There was a trend towards higher follow-up glycated haemoglobin levels in South Asians (P=0.064). Despite worse glycaemic control, South Asian diabetic adults with CKD stage 3 did not show any difference in 5-year decline in eGFR compared with white Europeans. These data do not support ethnic differences in progression of CKD between the South Asian and white European patient populations. Copyright © 2015 Elsevier Inc. All rights reserved.

Trends in Acute Nonvariceal Upper Gastrointestinal Bleeding in Dialysis Patients

PubMed Central

Yang, Ju-Yeh; Lee, Tsung-Chun; Montez-Rath, Maria E.; Paik, Jane; Chertow, Glenn M.; Desai, Manisha

2012-01-01

Impaired kidney function is a risk factor for upper gastrointestinal (GI) bleeding, an event associated with poor outcomes. The burden of upper GI bleeding and its effect on patients with ESRD are not well described. Using data from the US Renal Data System, we quantified the rates of occurrence of and associated 30-day mortality from acute, nonvariceal upper GI bleeding in patients undergoing dialysis; we used medical claims and previously validated algorithms where available. Overall, 948,345 patients contributed 2,296,323 patient-years for study. The occurrence rates for upper GI bleeding were 57 and 328 episodes per 1000 person-years according to stringent and lenient definitions of acute, nonvariceal upper GI bleeding, respectively. Unadjusted occurrence rates remained flat (stringent) or increased (lenient) from 1997 to 2008; after adjustment for sociodemographic characteristics and comorbid conditions, however, we found a significant decline for both definitions (linear approximation, 2.7% and 1.5% per year, respectively; P<0.001). In more recent years, patients had higher hematocrit levels before upper GI bleeding episodes and were more likely to receive blood transfusions during an episode. Overall 30-day mortality was 11.8%, which declined significantly over time (relative declines of 2.3% or 2.8% per year for the stringent and lenient definitions, respectively). In summary, despite declining trends worldwide, crude rates of acute, nonvariceal upper GI bleeding among patients undergoing dialysis have not decreased in the past 10 years. Although 30-day mortality related to upper GI bleeding declined, perhaps reflecting improvements in medical care, the burden on the ESRD population remains substantial. PMID:22266666

Englerin A Delivers One-Two Punch to Kidney Cancer Cells | Center for Cancer Research

Cancer.gov

While overall cancer death rates continue to decline in the U.S., mortality rates for certain cancer sites, including the kidney, are on the rise. New treatments are needed to reverse this trend and one potentially rich source is natural products, compounds derived from living organisms. John Beutler, Ph.D., and his colleagues, in CCR’s Molecular Targets Laboratory located at the NCI campus in Frederick, Maryland, identified englerin A from an extract of the African plant Phyllanthus engleri that was particularly toxic to kidney cancer cells. To further investigate the activity of englerin A, the Beutler group teamed up with researchers led by Marston Linehan, M.D., and Len Neckers, Ph.D., in CCR’s Urologic Oncology Branch.

Predicting kidney disease progression in patients with acute kidney injury after cardiac surgery.

PubMed

Mizuguchi, K Annette; Huang, Chuan-Chin; Shempp, Ian; Wang, Justin; Shekar, Prem; Frendl, Gyorgy

2018-06-01

The study objective was to identify patients who are likely to develop progressive kidney dysfunction (acute kidney disease) before their hospital discharge after cardiac surgery, allowing targeted monitoring of kidney function in this at-risk group with periodic serum creatinine measurements. Risks of progression to acute kidney disease (a state in between acute kidney injury and chronic kidney disease) were modeled from acute kidney injury stages (Kidney Disease: Improving Global Outcomes) in patients undergoing cardiac surgery. A modified Poisson regression with robust error variance was used to evaluate the association between acute kidney injury stages and the development of acute kidney disease (defined as doubling of creatinine 2-4 weeks after surgery) in this observational study. Acute kidney disease occurred in 4.4% of patients with no preexisting kidney disease and 4.8% of patients with preexisting chronic kidney disease. Acute kidney injury predicted development of acute kidney disease in a graded manner in which higher stages of acute kidney injury predicted higher relative risk of progressive kidney disease (area under the receiver operator characteristic curve = 0.82). This correlation persisted regardless of baseline kidney function (P < .001). Of note, development of acute kidney disease was associated with higher mortality and need for renal replacement therapy. The degree of acute kidney injury can identify patients who will have a higher risk of progression to acute kidney disease. These patients may benefit from close follow-up of renal function because they are at risk of progressing to chronic kidney disease or end-stage renal disease. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Changes in glomerular kidney function among HIV-1-uninfected men and women receiving emtricitabine-tenofovir disoproxil fumarate preexposure prophylaxis: a randomized clinical trial.

PubMed

Mugwanya, Kenneth K; Wyatt, Christina; Celum, Connie; Donnell, Deborah; Mugo, Nelly R; Tappero, Jordan; Kiarie, James; Ronald, Allan; Baeten, Jared M

2015-02-01

Tenofovir disoproxil fumarate (TDF) use has been associated with declines in the estimated glomerular filtration rate (eGFR) when used as part of antiretroviral treatment by persons with human immunodeficiency virus (HIV) type 1, but limited data are available for risk when used as preexposure prophylaxis (PrEP) for HIV-1 prevention. To determine whether TDF-based PrEP causes eGFR decline in HIV-1-uninfected adults. A per-protocol safety analysis of changes in eGFR in the Partners PrEP Study, a randomized, placebo-controlled trial of daily oral TDF and emtricitabine (FTC)-TDF PrEP among heterosexual HIV-1-uninfected members of serodiscordant couples in Kenya and Uganda. The trial was conducted from 2008 to 2012. Predefined outcomes of this analysis were mean eGFR change and a 25% or greater eGFR decline from baseline. The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Of 4640 participants in the once-daily TDF (n = 1548), FTC-TDF (n = 1545), or placebo (n = 1547) groups, 63% were men. At enrollment, median age was 35 years (range, 18-64 years), and mean eGFR was 130 mL/min/1.73 m². During a median follow-up of 18 months (interquartile range 12-27 months), mean within-group eGFR change from baseline was +0.14 mL/min/1.73 m² for TDF, -0.22 mL/min/1.73 m² for FTC-TDF, and +1.37 mL/min/1.73 m² for placebo, translating into average declines in eGFR attributable to PrEP vs placebo of -1.23 mL/min/1.73 m² (95% CI, -2.06 to -0.40; P = .004) for TDF and -1.59 mL/min/1.73 m² (95% CI, -2.44 to -0.74; P < .001) for FTC-TDF. The difference in mean eGFR between PrEP and placebo appeared by 1 month after randomization, was stable through 12 months, and then appeared to wane thereafter. The respective proportions of persons who developed a confirmed 25% or greater eGFR decline from baseline by 12 and 24 months was 1.3% and 1.8% for TDF and 1.2% and 2.5% for FTC-TDF, and these frequencies were not statistically different from the confirmed decline in the placebo group (0.9% and 1.3% by 12 and 24 months, respectively). In this large randomized, placebo-controlled trial among heterosexual persons, with median follow-up of 18 months and maximum follow-up of 36 months, daily oral TDF-based PrEP resulted in a small but nonprogressive decline in eGFR that was not accompanied by a substantial increase in the risk of clinically relevant (≥25%) eGFR decline. clinicaltrials.gov Identifier: NCT00557245.

Interleukin-2-dependent mechanisms are involved in the development of glomerulosclerosis after partial renal ablation in rats.

PubMed

Hamar, P; Peti-Peterdi, J; Szabó, A; Becker, G; Flach, R; Rosivall, L; Heemann, U

2001-01-01

Glomerulosclerosis is a common feature of many end-stage renal diseases. The contribution of cellular immune mechanisms has been implicated in the development of glomerulosclerosis. We investigated whether the inhibition of lymphocyte activation influences this process in an established rat model of renal hyperfiltration. After removal of two-thirds of their respective kidney mass, rats were treated with either tacrolimus (0.08 mg/kg/day) or vehicle until the end of the study (n = 10/group). The rats were pair-fed and proteinuria was assessed regularly. Twenty weeks after nephrectomy, creatinine clearance and systemic blood pressure were determined, and kidneys were harvested for morphological, immunohistological and PCR analysis. In control animals, renal function started to decline from week 12, as indicated by an elevated proteinuria. Interleukin (IL)-2 and IL-2 receptor synthesis was upregulated in control animals and inhibited by tacrolimus treatment. Transforming growth factor-beta (TGF-beta(1)), platelet-derived growth factor-AA (PDGF-AA) and macrophage chemoattractant protein-1 (MCP-1) mRNA levels were upregulated in control animals, but were significantly lower in immunosuppressed hosts. Additionally, tacrolimus treatment resulted in a significant reduction of proteinuria. Morphological analysis supported these functional results; glomerular sclerosis, tubular atrophy and intimal proliferation were more pronounced in controls than in the tacrolimus group. These morphological parameters were accompanied by reduced infiltration of CD5+ (rat T-cell marker) T cells, ED1+ (rat macrophage marker) macrophages, and less intense staining for laminin and fibronectin. A continuous treatment with tacrolimus - an inhibitor of lymphocyte proliferation - reduced the pace of glomerulosclerosis in the remnant kidney. Copyright 2001 S. Karger AG, Basel

Comparison of the morphometric features of the left and right horse kidneys: a stereological approach.

PubMed

Bolat, D; Bahar, S; Tipirdamaz, S; Selcuk, M L

2013-12-01

The aims of this study were to determine the total volume of the horse kidney and volume fractions of its functional subcomponents (cortex, medulla, renal pelvis) using stereological methods and investigate any possible difference in the functional subcomponents of the right and left kidneys that may arise from differences in shape. The study was carried out on the kidneys of 5 horses of different breed and sex. The weight of the kidneys was measured by a digital scale, and kidney volume was calculated by Archimedes' principle. Total kidney volume and volume fractions of subcomponents of the right and left kidneys were estimated by the Cavalieri's principle. The weights of the right and left kidneys were 550 ± 25 g and 585 ± 23 g, respectively. The volumes of the right and left kidneys estimated using the Cavalieri method were 542 ± 46 ml and 581 ± 29 ml. The relative organ weight of the kidneys was calculated as 1:330. The densities of the right and left kidneys were determined to be 1.01 and 1.00, respectively. The mean volume fractions of the cortex, medulla and renal pelvis were determined as 55.6, 42.7 and 1.7 in both kidneys. No statistically significant difference existed between morphometric data pertaining to the right and left kidneys (P > 0.05). To determine precisely whether differences in shape cause any difference in the functional subcomponents of the right and left kidneys requires further investigation of differences in the number of microscopically functional unit of the kidney such as renal glomeruli and nephrons. © 2013 Blackwell Verlag GmbH.

Influence of thyroid function on glomerular filtration rate and other estimates of kidney function in two pediatric patients.

PubMed

Uemura, Osamu; Iwata, Naoyuki; Nagai, Takuhito; Yamakawa, Satoshi; Hibino, Satoshi; Yamamoto, Masaki; Nakano, Masaru; Tanaka, Kazuki

2018-05-01

To determine the optimal method of evaluating kidney function in patients with thyroid dysfunction, this study compared the estimated glomerular filtration rate derived from serum creatinine, cystatin C, or β2-microglobulin with inulin or creatinine clearance in two pediatric patients, one with hypothyroidism and the other with hyperthyroidism. It was observed that the kidney function decreased in a hypothyroid child and enhanced in a hyperthyroid child, with their kidney function becoming normalized by treatment with drugs, which normalized their thyroid function. Kidney function cannot be accurately evaluated using cystatin C-based or β2-microglobulin-based estimated glomerular filtration rate in patients with thyroid dysfunction, as these tests overestimated glomerular filtration rate in a patient with hypothyroidism and underestimated glomerular filtration rate in a patient with hyperthyroidism, perhaps through a metabolic rate-mediated mechanism. In both our patients, 24-h urinary creatinine secretion was identical before and after treatment, suggesting that creatinine production is not altered in patients with thyroid dysfunction. Therefore, kidney function in patients with thyroid dysfunction should be evaluated using creatinine-based estimated glomerular filtration rate.

A Decline in Intraoperative Renal Near-Infrared Spectroscopy Is Associated With Adverse Outcomes in Children Following Cardiac Surgery.

PubMed

Gist, Katja M; Kaufman, Jonathan; da Cruz, Eduardo M; Friesen, Robert H; Crumback, Sheri L; Linders, Megan; Edelstein, Charles; Altmann, Christopher; Palmer, Claire; Jalal, Diana; Faubel, Sarah

2016-04-01

Renal near-infrared spectroscopy is known to be predictive of acute kidney injury in children following cardiac surgery using a series of complex equations and area under the curve. This study was performed to determine if a greater than or equal to 20% reduction in renal near-infrared spectroscopy for 20 consecutive minutes intraoperatively or within the first 24 postoperative hours is associated with 1) acute kidney injury, 2) increased acute kidney injury biomarkers, or 3) other adverse clinical outcomes in children following cardiac surgery. Prospective single center observational study. Pediatric cardiac ICU. Children less than or equal to age 4 years who underwent cardiac surgery with the use of cardiopulmonary bypass during the study period (June 2011-July 2012). None. A reduction in near-infrared spectroscopy was not associated with acute kidney injury. Nine of 12 patients (75%) with a reduction in renal near-infrared spectroscopy did not develop acute kidney injury. The remaining three patients had mild acute kidney injury (pediatric Risk, Injury, Failure, Loss, End stage-Risk). A reduction in renal near-infrared spectroscopy was associated with the following adverse clinical outcomes: 1) a longer duration of mechanical ventilation (p = 0.05), 2) longer intensive care length of stay (p = 0.05), and 3) longer hospital length of stay (p < 0.01). A decline in renal near-infrared spectroscopy in combination with an increase in serum interleukin-6 and serum interleukin-8 was associated with a longer intensive care length of stay, and the addition of urine interleukin-18 to this was associated with a longer hospital length of stay. In this cohort, the rate of acute kidney injury was much lower than anticipated thereby limiting the evaluation of a reduction in renal near-infrared spectroscopy as a predictor of acute kidney injury. A greater than or equal to 20% reduction in renal near-infrared spectroscopy was significantly associated with adverse outcomes in children following cardiac surgery. The addition of specific biomarkers to the model was predictive of worse outcomes in these patients. Thus, real-time evaluation of renal near-infrared spectroscopy using the specific levels of change of a 20% reduction for 20 minutes may be useful in predicting prolonged mechanical ventilation and other adverse outcomes in children undergoing cardiac surgery.

A scheme based on ICD-10 diagnoses and drug prescriptions to stage chronic kidney disease severity in healthcare administrative records.

PubMed

Friberg, Leif; Gasparini, Alessandro; Carrero, Juan Jesus

2018-04-01

Information about renal function is important for drug safety studies using administrative health databases. However, serum creatinine values are seldom available in these registries. Our aim was to develop and test a simple scheme for stratification of renal function without access to laboratory test results. Our scheme uses registry data about diagnoses, contacts, dialysis and drug use. We validated the scheme in the Stockholm CREAtinine Measurements (SCREAM) project using information on approximately 1.1 million individuals residing in the Stockholm County who underwent calibrated creatinine testing during 2006-11, linked with data about health care contacts and filled drug prescriptions. Estimated glomerular filtration rate (eGFR) was calculated with the CKD-EPI formula and used as the gold standard for validation of the scheme. When the scheme classified patients as having eGFR <30 mL/min/1.73 m 2 , it was correct in 93.5% of cases. The specificity of the scheme was close to 100% in all age groups. The sensitivity was poor, ranging from 68.2% in the youngest age quartile, down to 10.7% in the oldest age quartile. Age-related decline in renal function makes a large proportion of elderly patients fall into the chronic kidney disease (CKD) range without receiving CKD diagnoses, as this often is seen as part of normal ageing. In the absence of renal function tests, our scheme may be of value for identifying patients with moderate and severe CKD on the basis of diagnostic and prescription data for use in studies of large healthcare databases.

Bone metabolism dynamics in the early post-transplant period following kidney and liver transplantation

PubMed Central

Schreiber, Peter W.; Bischoff-Ferrari, Heike A.; Boggian, Katia; Bonani, Marco; van Delden, Christian; Enriquez, Natalia; Fehr, Thomas; Garzoni, Christian; Hirsch, Hans H.; Hirzel, Cédric; Manuel, Oriol; Meylan, Pascal; Saleh, Lanja; Weisser, Maja

2018-01-01

Bone disease contributes to relevant morbidity after solid organ transplantation. Vitamin D has a crucial role for bone metabolism. Activation of vitamin D depends on the endocrine function of both, liver and kidney. Our study assessed key markers of bone metabolism at time of transplantation and 6 months after transplantation among 70 kidney and 70 liver recipients. In 70 kidney recipients 25-OH vitamin D levels did not differ significantly between peri-transplant (median 32.5nmol/l) and 6 months post-transplant (median 41.9nmol/l; P = 0.272). Six months post-transplant median 1, 25-(OH)2 vitamin D levels increased by >300% (from 9.1 to 36.5ng/l; P<0.001) and median intact parathyroid hormone levels decreased by 68.4% (from 208.7 to 66.0 ng/l; P<0.001). Median β-Crosslaps (CTx) and total procollagen type 1 amino-terminal propeptide (P1NP) decreased by 65.1% (from 1.32 to 0.46ng/ml; P<0.001) and 60.6% (from 158.2 to 62.3ng/ml; P<0.001), respectively. Kidney recipients with incident fractures had significantly lower levels of 1, 25-(OH)2 vitamin D at time of transplantation and of intact parathyroid hormone 6 months post-transplant. Among 70 liver recipients, 25-OH vitamin D, 1, 25-(OH)2 vitamin D and intact parathyroid hormone levels were not significantly altered between peri-transplant and 6 months post-transplant. Contrary to kidney recipients, median CTx increased by 60.0% (from 0.45 to 0.72 ng/ml; P = 0.002) and P1NP by 49.3% (from 84.0 to 125.4ng/ml; P = 0.001) in the longitudinal course. Assessed biomarkers didn’t differ between liver recipients with and without fractures. To conclude, the assessed panel of biomarkers proved highly dynamic after liver as well as kidney transplantation in the early post-transplant period. After kidney transplantation a significant gain in 1, 25-(OH)2 vitamin D combined with a decline in iPTH, CTx and P1NP, whereas after liver transplantation an increase in CTx and P1NP were characteristic. PMID:29338022

Kidney growth and renal functions under the growth hormone replacement therapy in children.

PubMed

Ece, Aydın; Çetinkaya, Semra; Ekşioğlu, Seçil; Şenel, Saliha; Özkasap, Serdar; Giniş, Tayfur; Sen, Velat; Şahin, Cahit

2014-05-01

The aim of this study was to investigate the kidney growth and renal functions in children receiving recombinant human growth hormone (rhGH) treatment. A total of 37 children who received rhGH for 1.5 years before the study was started and 48 healthy controls were included at first evaluation. Hormone levels were determined and kidney sizes were measured by ultrasound. Kidney functions were assessed by serum creatinine and estimated glomerular filtration rate (eGFR). After 3 years of first evaluation, 23 patients were re-assessed. Kidney sizes were found to be lower in rhGH received children compared with controls at first evaluation (p<0.05). Significant positive correlations were found between anthropometric measurements and kidney length and kidney volume (p<0.05). Height was the most significant predictor of kidney volume in rhGH received children (p<0.001). After 3-years of follow-up significantly increases were found in kidney length and volume compared with the first measurements (p<0.05). Increase percentage of body height was similar to increasing percent of kidney length and liver long axis (14.2%, 11.7.1% and 7.7%, respectively, p>0.05). Although no abnormal renal function test results were found at first and second evaluations; rhGH received children had significantly lower eGFR, at first evaluation, compared with controls; however, renal functions significantly increased after 3 years of follow-up (p<0.05). In conclusion, effect rhGH treatment on kidney growth is parallel to growth in body height and other visceral organs. A 3-years rhGH treatment resulted in significant increases in renal functions.

Preeclampsia and Long-term Renal Function in Women Who Underwent Kidney Transplantation.

PubMed

Vannevel, Valerie; Claes, Kathleen; Baud, David; Vial, Yvan; Golshayan, Delaviz; Yoon, Eugene W; Hodges, Ryan; Le Nepveu, Anne; Kerr, Peter G; Kennedy, Claire; Higgins, Mary; Resch, Elisabeth; Klaritsch, Philipp; Van Mieghem, Tim

2018-01-01

Preeclampsia often complicates pregnancies after maternal kidney transplantation. We aimed to assess whether preeclampsia is associated with kidney function decline either during the pregnancy or in the long term. We performed an international multicenter retrospective cohort study. Renal function at conception, pregnancy outcomes, and short- and long-term graft outcomes were collected for women who were pregnant after renal transplantation and had transplant and obstetric care at the participating centers. In women who had multiple pregnancies during the study period, only the last pregnancy was included. Univariate and multivariable analyses were performed. We retrieved pregnancy outcomes and long-term renal outcomes for 52 women. Chronic hypertension was present at baseline in 27%. Mean estimated glomerular filtration rate (GFR) at start of pregnancy was 52.4±17.5 mL/min/1.73 m. Mean estimated GFR at delivery was 47.6±21.6 mL/min/1.73 m, which was significantly lower than at conception (P=.03). Twenty women (38%) developed preeclampsia. In multivariable analysis, women who developed preeclampsia had a 10.7-mL/min/1.73 m higher drop in estimated GFR between conception and delivery than women who did not develop preeclampsia (P=.02). Long-term estimated GFR follow-up was obtained at a median of 5.8 years (range 1.3-27.5 years). Mean estimated GFR at last follow-up was 38±23 mL/kg/1.73 m. Seventeen women (33%) experienced graft loss over the follow-up period. Incidence of graft loss was similar in women with and without preeclampsia in their last pregnancy (30% and 34%, respectively; P=.99). In multivariable analysis, the decrease in estimated GFR between conception and last follow-up was similar in women who experienced preeclampsia during pregnancy and those who did not (difference -2.69 mL/min/1.73 m, P=.65). Preeclampsia commonly complicates pregnancies after renal transplantation but is not associated with long-term renal dysfunction or graft loss.

Acute and chronic effects of SGLT2 blockade on glomerular and tubular function in the early diabetic rat

PubMed Central

Rieg, Timo; Miracle, Cynthia; Mansoury, Hadi; Whaley, Jean; Vallon, Volker; Singh, Prabhleen

2012-01-01

Tubuloglomerular feedback (TGF) stabilizes nephron function from minute to minute and adapts to different steady-state inputs to maintain this capability. Such adaptation inherently renders TGF less efficient at buffering long-term disturbances, but the magnitude of loss is unknown. We undertook the present study to measure the compromise between TGF and TGF adaptation in transition from acute to chronic decline in proximal reabsorption (Jprox). As a tool, we blocked proximal tubule sodium-glucose cotransport with the SGLT2 blocker dapagliflozin in hyperglycemic rats with early streptozotocin diabetes, a condition in which a large fraction of proximal fluid reabsorption owes to SGLT2. Dapagliflozin acutely reduced proximal reabsorption leading to a 70% increase in early distal chloride, a saturated TGF response, and a major reduction in single nephron glomerular filtration rate (SNGFR). Acute and chronic effects on Jprox were indistinguishable. Adaptations to 10–12 days of dapagiflozin included increased reabsorption by Henle's loop, which caused a partial relaxation in the increased tone exerted by TGF that could be explained without desensitization of TGF. In summary, TGF contributes to long-term fluid and salt balance by mediating a persistent decline in SNGFR as the kidney adapts to a sustained decrease in Jprox. PMID:21940401

Renal Failure in Mice with Gsα Deletion in Juxtaglomerular Cells

PubMed Central

Chen, Limeng; Faulhaber-Walter, Robert; Wen, Yubing; Huang, Yuning; Mizel, Diane; Chen, Min; Sequeira Lopez, Maria Luisa; Weinstein, Lee S.; Gomez, R. Ariel; Briggs, Josephine P.; Schnermann, Jurgen

2010-01-01

Background Mice with deletion of Gsα in renin-producing cells (RC/FF mice) have been shown to have greatly reduced renin production and lack of responsiveness of renin secretion to acute stimuli. In addition, young RC/FF mice are hypotensive and have a vasopressin-resistant concentrating defect. In the present study we have determined the long-term effect on renal function, blood pressure, and renal pathology in this low renin and diuretic mouse model. Methods and Results Urine osmolarity of RC/FF mice was decreased in all age groups. GFR measured at 7, 14 and 20 weeks of age declined progressively. Single nephron GFR similarly declined while fractional proximal fluid absorption was maintained. Expression levels of extracellular matrix proteins (collagen I, IV and fibronectin) and α-smooth muscle actin were increased in kidneys of RC/FF mice at 20 weeks, and this was accompanied by focal segmental glomerulosclerosis and periglomerular interstitial fibrosis. RC/FF mice showed a progressive reduction of body weight, an increase in urine albumin excretion, and an increase of blood pressure with aging. Conclusion A chronic reduction of renin production in mice may be a risk factor in its own right, and does not protect renal function against the profibrotic influence of a chronically elevated urine flow. PMID:20551626

Functional principal component analysis of glomerular filtration rate curves after kidney transplant.

PubMed

Dong, Jianghu J; Wang, Liangliang; Gill, Jagbir; Cao, Jiguo

2017-01-01

This article is motivated by some longitudinal clinical data of kidney transplant recipients, where kidney function progression is recorded as the estimated glomerular filtration rates at multiple time points post kidney transplantation. We propose to use the functional principal component analysis method to explore the major source of variations of glomerular filtration rate curves. We find that the estimated functional principal component scores can be used to cluster glomerular filtration rate curves. Ordering functional principal component scores can detect abnormal glomerular filtration rate curves. Finally, functional principal component analysis can effectively estimate missing glomerular filtration rate values and predict future glomerular filtration rate values.

The State of the Human Proteome in 2013 as viewed through PeptideAtlas: Comparing the Kidney, Urine, and Plasma Proteomes for the Biology and Disease-driven Human Proteome Project

PubMed Central

Farrah, Terry; Deutsch, Eric W.; Omenn, Gilbert S.; Sun, Zhi; Watts, Julian D.; Yamamoto, Tadashi; Shteynberg, David; Harris, Micheleen M.; Moritz, Robert L.

2014-01-01

The kidney, urine, and plasma proteomes are intimately related: proteins and metabolic waste products are filtered from the plasma by the kidney and excreted via the urine, while kidney proteins may be secreted into the circulation or released into the urine. Shotgun proteomics datasets derived from human kidney, urine, and plasma samples were collated and processed using a uniform software pipeline, and relative protein abundances were estimated by spectral counting. The resulting PeptideAtlas builds yielded 4005, 2491, and 3553 nonredundant proteins at 1% FDR for the kidney, urine, and plasma proteomes, respectively—for kidney and plasma, the largest high-confidence protein sets to date. The same pipeline applied to all available human data yielded a 2013 Human PeptideAtlas build containing 12,644 nonredundant proteins and at least one peptide for each of ~14,000 Swiss-Prot entries, an increase over 2012 of ~7.5% of the predicted human proteome. We demonstrate that abundances are correlated between plasma and urine, examine the most abundant urine proteins not derived from either plasma or kidney, and consider the biomarker potential of proteins associated with renal decline. This analysis forms part of the Biology and Disease-driven Human Proteome Project (B/D-HPP) and a contribution to the Chromosome-centric Human Proteome Project (C-HPP) special issue. PMID:24261998

Diabetes induced renal urea transport alterations assessed with 3D hyperpolarized 13 C,15 N-Urea.

PubMed

Bertelsen, Lotte B; Nielsen, Per M; Qi, Haiyun; Nørlinger, Thomas S; Zhang, Xiaolu; Stødkilde-Jørgensen, Hans; Laustsen, Christoffer

2017-04-01

In the current study, we investigated hyperpolarized urea as a possible imaging biomarker of the renal function by means of the intrarenal osmolality gradient. Hyperpolarized three-dimensional balanced steady state 13 C MRI experiments alongside kidney function parameters and quantitative polymerase chain reaction measurements was performed on two groups of rats, a streptozotocin type 1 diabetic group and a healthy control group. A significant decline in intrarenal steepness of the urea gradient was found after 4 weeks of untreated insulinopenic diabetes in agreement with an increased urea transport transcription. MRI and hyperpolarized [ 13 C, 15 N]urea can monitor the changes in the corticomedullary urea concentration gradients in diabetic and healthy control rats. Magn Reson Med 77:1650-1655, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Effects of feline hyperthyroidism on kidney function: a review.

PubMed

Vaske, Heather H; Schermerhorn, Thomas; Grauer, Gregory F

2016-02-01

Chronic kidney disease and hyperthyroidism are two commonly diagnosed conditions in the geriatric feline population, and are often seen concurrently. Management of both diseases is recommended; however, the physiologic implications of both diseases must be understood to ensure the most favorable outcome for each patient. This report reviews the complex interplay between hyperthyroidism and kidney function, as well as the effects of hyperthyroid therapy on kidney function. © ISFM and AAFP 2015.

Restoration of parathyroid function after change of phosphate binder from calcium carbonate to lanthanum carbonate in hemodialysis patients with suppressed serum parathyroid hormone.

PubMed

Inaba, Masaaki; Okuno, Senji; Nagayama, Harumi; Yamada, Shinsuke; Ishimura, Eiji; Imanishi, Yasuo; Shoji, Shigeichi

2015-03-01

Control of phosphate is the most critical in the treatment of chronic kidney disease with mineral and bone disorder (CKD-MBD). Because calcium-containing phosphate binder to CKD patients is known to induce adynamic bone disease with ectopic calcification by increasing calcium load, we examined the effect of lanthanum carbonate (LaC), a non-calcium containing phosphate binder, to restore bone turnover in 27 hemodialysis patients with suppressed parathyroid function (serum intact parathyroid hormone [iPTH] ≦ 150 pg/mL). At the initiation of LaC administration, the dose of calcium-containing phosphate binder calcium carbonate (CaC) was withdrawn or reduced based on serum phosphate. After initiation of LaC administration, serum calcium and phosphate decreased significantly by 4 weeks, whereas whole PTH and iPTH increased. A significant and positive correlation between decreases of serum calcium, but not phosphate, with increases of whole PTH and iPTH, suggested that the decline in serum calcium with reduction of calcium load by LaC might increase parathyroid function. Serum bone resorption markers, such as serum tartrate-resistant acid phosphatase 5b, and N-telopeptide of type I collagen increased significantly by 4 weeks after LaC administration, which was followed by increases of serum bone formation markers including serum bone alkaline phosphatase, intact procollagen N-propeptide, and osteocalcin. Therefore, it was suggested that LaC attenuated CaC-induced suppression of parathyroid function and bone turnover by decreasing calcium load. In conclusion, replacement of CaC with LaC, either partially or totally, could increase parathyroid function and resultant bone turnover in hemodialysis patients with serum iPTH ≦ 150 pg/mL. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Delayed Graft Function in Living-Donor Kidney Transplant: A Middle Eastern Perspective.

PubMed

Al Otaibi, Torki; Ahmadpoor, Pedram; Allawi, Ali Abdulmajid Dyab; Habhab, Wael Taher; Khatami, Mohammad Reza; Nafar, Mohsen; Glotz, Denis

2016-02-01

With an increased incidence of living-donor kidney transplants, in response to increasing unmet needs for renal transplant, a clear understanding of determinants of posttransplant outcomes is essential. The importance of delayed graft function in deceased-donor kidney transplant is now part of conventional medical wisdom, due to the large amount of evidence focused on this aspect. However, the same is not true for living-donor kidney transplant, partly due to lack of evidence on this crucial clinical question and partly due to lack of awareness about this issue. The current review aims to highlight the importance of delayed graft function as a crucial determinant of outcomes in living-donor kidney transplant. An exhaustive search of online medical databases was performed with appropriate search criteria to collect evidence about delayed graft function after living-donor kidney transplant, with a special focus on studies from the Middle East. Data on incidence, impact, risk factors, and possible prevention modalities of delayed graft function in patients undergoing living-donor kidney transplant are presented. A key finding of this review is that contemporary incidence rates reported from the Middle East are comparatively higher than those reported from outside the region. Although in absolute terms the incidence is lower than deceased donor kidney transplant, the effects of delayed graft function on graft rejection and graft and patient survival are sufficiently large to warrant the formulation of specific treatment protocols. Key to formulating prevention and treatment strategies is identifying discrete risk factors for delayed graft function. Although this evidence is scant, an overview has been provided. Further studies examining different aspects of delayed graft function incidence after living-donor kidney transplant are urgently needed to address a so far little known clinical question.

Influence of low-level laser radiation on kidney functions

NASA Astrophysics Data System (ADS)

Koultchavenia, Ekaterina V.

1998-12-01

Most of all renal diseases are accompanied by lowering of kidney functions. That makes the quality of the treatment worse. On an example 69 patients receiving Low-Level Laser Therapy (LLLT), the influence of the laser radiation on a contracting system of blood, on current of an active and inactive tubercular inflammation and on partial functions of kidneys were investigated. Is established, that LLLT does not render influence to a contracting system; promotes stopping of unspecific and moderate peaking of a specific inflammation of kidneys. Is proved, that after a rate of laserotherapy the improving of a blood micricirculation in kidney occurs in 57.9% of patients; a secretion - in 63.1% of the patients; a stimulation of urodynamic is fixed in 79% of cases. Magnification of diuresis, improving filtration and concentration functions of kidneys also is marked.

Serum bicarbonate concentrations and kidney disease progression in community-living elders: the Health, Aging, and Body Composition (Health ABC) Study.

PubMed

Goldenstein, Leonard; Driver, Todd H; Fried, Linda F; Rifkin, Dena E; Patel, Kushang V; Yenchek, Robert H; Harris, Tamara B; Kritchevsky, Stephen B; Newman, Anne B; Sarnak, Mark J; Shlipak, Michael G; Ix, Joachim H

2014-10-01

In populations with prevalent chronic kidney disease (CKD), lower serum bicarbonate levels are associated with more rapid CKD progression, but whether lower bicarbonate levels also are associated with risk of incident estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2) and CKD progression among community-living persons with predominantly preserved kidney function is unknown. Longitudinal observational cohort study. Well-functioning community-living elders aged 70-79 years at inception. Serum bicarbonate level measured at the time of collection by arterialized venous blood sample using an arterial blood gas analyzer. Change in eGFR over 7 years, and new eGFR < 60 mL/min/1.73 m(2) with a rate of loss of at least 1 mL/min/1.73 m(2) per year. Linear and logistic regressions were used to evaluate associations of baseline serum bicarbonate level with change in eGFR and incident eGFR < 60 mL/min/1.73 m(2). At baseline, mean eGFR was 84 ± 16 (SD)mL/min/1.73 m(2), and serum bicarbonate level was 25.2 ± 1.9 mmol/L. Compared with participants with higher bicarbonate concentrations (23.0-28.0 mmol/L), those with bicarbonate concentrations < 23 mmol/L (n = 85 [8%]) lost eGFR0.55 (95% CI, 0.13-0.97) mL/min/1.73 m(2) per year faster in models adjusted for demographics, CKD risk factors, baseline eGFR, and urine albumin-creatinine ratio. Among the 989 (92%) participants with baseline eGFRs > 60 mL/min/1.73 m(2), 252 (25%) developed incident eGFRs < 60 mL/min/1.73 m(2) at follow-up. Adjusting for the same covariates, participants with bicarbonate concentrations < 23 mmol/L had nearly 2-fold greater odds of incident eGFRs < 60 mL/min/1.73 m(2) (OR, 1.72; 95% CI, 0.97-3.07) compared with those with higher bicarbonate concentrations. Only 2 measurements of kidney function separated by 7 years and loss to follow-up due to intervening mortality in this elderly population. Lower serum bicarbonate concentrations are associated independently with decline in eGFR and incident eGFR < 60 mL/min/1.73 m(2) in community-living older persons. If confirmed, serum bicarbonate levels may give insight into kidney tubule health in persons with preserved eGFRs and suggest a possible new target for intervention to prevent CKD development. Published by Elsevier Inc.

Serum Bicarbonate Concentrations and Kidney Disease Progression in Community-Living Elders: The Health, Aging, and Body Composition (Health ABC) Study

PubMed Central

Goldenstein, Leonard; Driver, Todd H.; Fried, Linda; Rifkin, Dena E.; Patel, Kushang V.; Yenchek, Robert H.; Harris, Tamara B.; Kritchevsky, Stephen B.; Newman, Anne B.; Sarnak, Mark J.; Shlipak, Michael G.; Ix, Joachim H.

2014-01-01

Background In populations with prevalent chronic kidney disease (CKD), lower serum bicarbonate is associated with more rapid CKD progression, but whether lower bicarbonate is also associated with risk of incident estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 and progression among community-living persons with predominantly preserved kidney function is unknown. Study Design Longitudinal observational cohort study. Setting & Participants Well functioning community living elders aged 70–79 years at inception. Predictor Serum bicarbonate measured at the time of collection by arterialized venous blood sample using an arterial blood gas analyzer. Outcomes Change in eGFR, and new eGFR < 60 ml/min/1.73m2 and loss of ≥1 ml/min/1.73m2 per year at follow-up. Measurements Linear and logistic regressions were used to evaluate associations of baseline serum bicarbonate with change in eGFR and incident eGFR <60 mL/min/1.73m2. Results At baseline, mean eGFR was 84±16 (SD) mL/min/1.73m2, and serum bicarbonate was 25.2±1.9 mmol/L. Compared to participants with higher bicarbonate concentrations (23.0–28.0 mmol/L), those with bicarbonate concentrations < 23 mmol/L (n=85 [8%]) lost eGFR 0.55 (95%CI, 0.13–0.97) mL/min/1.73m2 per year faster in models adjusted for demographics, CKD risk factors, baseline eGFR, and urine albumin-creatinine ratio. Among the 989 (92%) participants with baseline eGFR>60 mL/min/1.73m2, 252 (25%) developed incident eGFR <60 mL/min/1.73m2 at follow-up. Adjusting for the same covariates, participants with bicarbonate concentrations < 23 mmol/L had nearly 2-fold greater odds of incident eGFR <60 mL/min/1.73m2 (OR, 1.72; 95% CI, 0.97–3.07) compared to those with higher bicarbonate concentrations. Limitations Only two measurements of kidney function separated by seven years and loss to follow up due to intervening mortality in this elderly population. Conclusions Lower serum bicarbonate concentrations are independently associated with decline in eGFR and incident eGFR <60 mL/min/1.73m2 in community-living older persons. If confirmed, serum bicarbonate levels may give insights into kidney tubule health among persons with preserved eGFR and suggest a possible new target for intervention to prevent CKD development. PMID:24953890

Liver fatty-acid-binding protein in heart and kidney allograft recipients in relation to kidney function.

PubMed

Przybylowski, P; Koc-Zorawska, E; Malyszko, J S; Kozlowska, S; Mysliwiec, M; Malyszko, J

2011-10-01

Mammalian intracellular fatty-acid-binding proteins (FABPs), a large multigene family, encode 14-kD proteins that are members of a superfamily of lipid-binding proteins. FABPs are tissue specific. Liver-type FABP (L-FABP) can be filtered through the glomerulus owing to its small molecular size, similar to cystatin C, but it is reabsorbed by proximal tubule epithelial cells like other small proteins. In the human kidney, L-FABP is expressed predominantly in proximal tubules. It had been suggested that the presence of L-FABP in urine reflects hypoxic conditions resulting from decreased peritubular capillary flow, serving as a marker of acute kidney injury. The aim of this study was to assess urinary L-FABP in 111 heart and 76 kidney transplant recipients in relation to kidney function. Complete blood count, urea, fasting glucose, creatinine, and the N-terminal fragment of brain natriuretic protein were studied by standard laboratory methods; L-FABP and cystatin C, by ELISA using commercially available kits. Kidney transplant recipients displayed significantly higher L-FABP than heart recipients. Upon univariate analysis, urinary L-FABP correlated, with serum creatinine, cystatin C and estimated glomerular filtration ratio (eGFR) in kidney allograft recipients. However, in heart transplant recipients it was not related to kidney function, as reflected by creatinine or eGFR; was strongly related to cystatin C (r=0.34; P<.001) and urinary creatinine (r=-0.29; P<.01), and NGAL (r=0.29; P<.01). Upon multiple regression analysis, the best predictor of urinary L-FABP in kidney allograft recipients, was eGFR whereas in heart recipients, no parameter independently predicted L-FABP. Successful heart transplantation is associated with kidney injury as reflected by a reduced eGFR; however, in this population, L-FABP did not serve as a marker of kidney function. In contrast, in kidney allograft recipients, L-FABP may be a potential early marker for impaired kidney function/injury. Copyright © 2011 Elsevier Inc. All rights reserved.

Kidney Cancer Incidence and Mortality Among American Indians and Alaska Natives in the United States, 1990–2009

PubMed Central

Weir, Hannah K.; Jim, Melissa A.; King, Sallyann M.; Wilson, Reda; Master, Viraj A.

2014-01-01

Objectives. We describe rates and trends in kidney cancer incidence and mortality and identify disparities between American Indian/Alaska Native (AI/AN) and White populations. Methods. To improve identification of AI/AN race, incidence and mortality data were linked with Indian Health Service (IHS) patient records. Analysis focused on residents of IHS Contract Health Service Delivery Area counties; Hispanics were excluded. We calculated age-adjusted kidney cancer incidence (2001–2009) and death rates (1990–2009) by sex, age, and IHS region. Results. AI/AN persons have a 1.6 times higher kidney cancer incidence and a 1.9 times higher kidney cancer death rate than Whites. Despite a significant decline in kidney cancer death rates for Whites (annual percentage change [APC] = −0.3; 95% confidence interval [CI] = −0.5, 0.0), death rates for AI/AN persons remained stable (APC = 0.4; 95% CI = −0.7, 1.5). Kidney cancer incidence rates rose more rapidly for AI/AN persons (APC = 3.5; 95% CI = 1.2, 5.8) than for Whites (APC = 2.1; 95% CI = 1.4, 2.8). Conclusions. AI/AN individuals have greater risk of developing and dying of kidney cancers. Incidence rates have increased faster in AI/AN populations than in Whites. Death rates have decreased slightly in Whites but remained stable in AI/AN populations. Racial disparities in kidney cancer are widening. PMID:24754655

Probiotic Dahi containing Lactobacillus acidophilus and Bifidobacterium bifidum alleviates age-inflicted oxidative stress and improves expression of biomarkers of ageing in mice.

PubMed

Kaushal, Deepti; Kansal, Vinod K

2012-02-01

The potential benefiting effects of probiotic Dahi on age-inflicted accumulation of oxidation products, antioxidant enzymes and expression of biomarkers of ageing were evaluated in mice. Probiotic Dahi were prepared by co-culturing in buffalo milk (3% fat) Dahi bacteria (Lactococcus lactis ssp. cremoris NCDC-86 and Lactococcus lactis ssp. lactis biovar diacetylactis NCDC-60) along with selected strain of Lactobacillus acidophilus LaVK2 (La-Dahi) or combined L. acidophilus and Bifidobacterium bifidum BbVK3 (LaBb-Dahi). Four groups of 12 months old mice (6 each) were fed for 4 months supplements (5 g/day) of buffalo milk (3% fat), Dahi, La-Dahi and LaBb-Dahi, respectively, with basal diet. The activities of catalase (CAT) and glutathione peroxidase (GPx) declined and the contents of oxidation products, thiobarbituric acid reactive substances (TBARS) and protein carbonyls, increased in red blood corpuscles (RBCs), liver, kidney and heart tissues and superoxide dismutase (SOD) activity increased in RBCs and hepatic tissues during ageing of mice. Feeding ageing mice with La-Dahi or LaBb-Dahi increased CAT activity in all the four tissues, and GPx activity in RBCs and hepatic tissue, and a significant decline in TBARS in plasma, kidney and hepatic tissues and protein carbonyls in plasma. Feeding mice with probiotic Dahi also reversed age related decline in expression of biomarkers of ageing, peroxisome proliferators activated receptor-α, senescence marker protein-30 (SMP-30) and klotho in hepatic and kidney tissues. The present study suggests that probiotic Dahi containing selected strains of bacteria can be used as a potential nutraceutical intervention to combat oxidative stress and molecular alterations associated with ageing.

Tempol effect on epithelial-mesenchymal transition induced by hyperglycemia

PubMed Central

Jafari, Mohammad; Dadras, Farahnaz; Ghadimipour, Hamid Reza; Seif Rabiei, Mohamad Ali; Khoshjou, Farhad

2017-01-01

Background One of common mechanisms in pathophysiology of chronic kidney diseases is epithelial-mesenchymal transition (EMT). On the other hand oxidative stress has been known to participate in kidney damage of diabetic nephropathy (DN). Objectives We studied if tempol, a well-known antioxidant agent, can ameliorate EMT in DN induced in male rats. Materials and Methods Twenty-seven male rats were equally divided in to 4 groups. Group I (control or C), group II (diabetic or D), group III (T) rats which was given tempol (100 mg/kg/day) by gavages for 28 days and group IV (D&T) was diabetic rats that also received same dose of tempol. After treatment, their kidneys were studied by immunohistochemicalstaining. Results Pathological changes in the kidney were detected concurrently with increasing kidney weight and urinary albumin excretion. In addition, EMT indices, i.e. decline of E-cadherin and increase of α SMA staining were significantly emerged in the renal tubular cells of diabetic group and were partially modified in diabetic group which were simultaneously treated by tempol. Conclusions Tempol can modify, but not significantly, EMT induced by DN. PMID:28042546

An overview of experimental and early investigational therapies for the treatment of polycystic kidney disease.

PubMed

Santoro, Domenico; Pellicanò, Vincenzo; Visconti, Luca; Trifirò, Gianluca; Buemi, Michele; Cernaro, Valeria

2015-01-01

At present, treatment of autosomal dominant polycystic kidney disease (ADPKD) is essentially supportive as there is still no specific therapy. However, recent advances with ADPKD pathophysiology have stimulated research for new therapeutic strategies. The aim of this systematic review is to analyze the experimental and early investigational therapies currently under evaluation in this field. Data from completed clinical trials were retrieved from the currently available scientific literature and from the ClinicalTrials.gov website. Among the drugs currently being explored, mammalian target of rapamycin inhibitors reduce kidney volume enlargement but their role remains uncertain. The most promising drug is the V2 receptor antagonist tolvaptan, which reduces the increased rate of total kidney volume and slows down glomerular filtration rate decline. The main candidates for the treatment of cysts growth, both in the kidney and in the liver whenever present, are the somatostatin analogues, such as lanreotide and octreotide and more recently pasireotide. As for other therapies, some favorable results have been achieved but data are still not sufficient to establish if these approaches may be beneficial in slowing ADPKD progression in the future.

Curcumin reduces the risk of chronic kidney damage in mice with nonalcoholic steatohepatitis by modulating endoplasmic reticulum stress and MAPK signaling.

PubMed

Afrin, Mst Rejina; Arumugam, Somasundaram; Rahman, Md Azizur; Karuppagounder, Vengadeshprabhu; Harima, Meilei; Suzuki, Hiroshi; Miyashita, Shizuka; Suzuki, Kenji; Ueno, Kazuyuki; Yoneyama, Hiroyuki; Watanabe, Kenichi

2017-08-01

Developing confirmation recommends that in patients with dynamic type of NAFLD, particularly nonalcoholic steatohepatitis (NASH) may have the pathogenic parts in the advancement of kidney damage. In this study we have examined the impact of curcumin on NASH instigated chronic kidney damage (CKD) and the putative mechanisms. To prepare this NASH model, neonatal C57BL/6J male mice were exposed to low-dose streptozotocin (STZ) and were fed high-fat diet (HFD) at the age of 4weeks and continued up to 14weeks, curcumin was given at 100mg/kg dose by oral gavage daily after 10weeks of STZ injection and continued for 4weeks along with HFD feeding. NASH incited mice demonstrated nephrotoxicity as proved by declining renal capacity, which was evaluated by measuring blood urea nitrogen and creatinine in serum and histopathological variations from the norm. These progressions were switched by curcumin treatment, which brought about huge change in renal capacity. Furthermore, curcumin markedly decreased NAD(P)H oxidase subunits (p67phox, p47phox, p22phox), nitrotyrosine and CYP2E1 renal protein expression as well as reduced pro-inflammatory cytokine expression (TNFα, IL-1β, IFNγ). Renal protein expression of mitogen activated protein kinases (MAPKs) (p-JNK, p-ERK1/2) and glucose regulated protein 78, CHOP were increased in NASH induced mice and curcumin treatment attenuated these increased expressions. In addition, curcumin treatment also decreased the apoptosis signaling proteins (cleaved caspase-3, cleaved caspase-12) in the NASH kidney. Taken together, our results suggest that curcumin preserves the renal function, probably by attenuating the ER stress mediated MAPK signaling. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

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.

Urea, a true uremic toxin: the empire strikes back.

PubMed

Lau, Wei Ling; Vaziri, Nosratola D

2017-01-01

Blood levels of urea rise with progressive decline in kidney function. Older studies examining acute urea infusion suggested that urea was well-tolerated at levels 8-10× above normal values. More recent in vitro and in vivo work argue the opposite and demonstrate both direct and indirect toxicities of urea, which probably promote the premature aging phenotype that is pervasive in chronic kidney disease (CKD). Elevated urea at concentrations typically encountered in uremic patients induces disintegration of the gut epithelial barrier, leading to translocation of bacterial toxins into the bloodstream and systemic inflammation. Urea induces apoptosis of vascular smooth muscle cells as well as endothelial dysfunction, thus directly promoting cardiovascular disease. Further, urea stimulates oxidative stress and dysfunction in adipocytes, leading to insulin resistance. Finally, there are widespread indirect effects of elevated urea as a result of the carbamylation reaction, where isocyanic acid (a product of urea catabolism) alters the structure and function of proteins in the body. Carbamylation has been linked with renal fibrosis, atherosclerosis and anaemia. In summary, urea is a re-emerging Dark Force in CKD pathophysiology. Trials examining low protein diet to minimize accumulation of urea and other toxins suggest a clinical benefit in terms of slowing progression of CKD. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

[Risk factors for postoperative acute kidney injury in a cohort of 2378 patients from 59 hospitals].

PubMed

Sabaté, S; Gomar, C; Canet, J; Sierra, P; Castillo, J

2011-11-01

To assess risk factors for postoperative acute kidney injury (AKI) in adults with normal renal function hospitalized for major surgery. To analyze mortality and length of hospital stay in patients who develop postoperative AKI. Data for analysis were drawn from the 2006 ARISCAT study. The dependent variable was postoperative AKI defined as a decline in renal function demonstrated by a rise in plasma creatinine level to twice the baseline measurement or a 50% reduction in the glomerular filtration rate. Bivariate and multivariate analyses were used to identify preoperative and intraoperative risk factors. We analyzed 2378 of the ARISCAT cases, which had been enrolled from 59 participating hospitals; 25 patients (1.1%) developed AKI. Analysis identified 5 risk factors: age, peripheral arterial disease, type of surgical incision, blood loss, and infusion of colloids. The area under the receiver operating characteristic curve was 0.88% (95% confidence interval, 0.79%-0.69%). Duration of hospital stay was longer for patients with postoperative AKI (21.8 days, vs 5.5 days for other patients; P=.007). Mortality was higher in patients with AKI at 30 days (36% vs 0.9%) and at 3 months (48% vs 1.7%). The incidence of postoperative AKI was slightly over 1%. Knowledge of postoperative AKI risk factors can facilitate the planning of surgical interventions and anesthesia to reduce subsequent morbidity and mortality and length of hospital stay.

A new approach to define acute kidney injury in term newborns with hypoxic ischemic encephalopathy

PubMed Central

Gupta, Charu; Massaro, An N.

2016-01-01

Background Current definitions of acute kidney injury (AKI) are not sufficiently sensitive to identify all newborns with AKI during the first week of life. Methods To determine whether the rate of decline of serum creatinine (SCr) during the first week of life can be used to identify newborns with AKI, we reviewed the medical records of 106 term neonates at risk of AKI who were treated with hypothermia for hypoxic ischemic encephalopathy (HIE). Results Of the newborns enrolled in the study, 69 % showed a normal rate of decline of SCr to ≥50 % and/or reached SCr levels of ≤0.6 mg/dl before the 7th day of life, and therefore had an excellent clinical outcome (control group). Thirteen newborns with HIE (12 %) developed AKI according to an established neonatal definition (AKI–KIDGO group), and an additional 20 newborns (19 %) showed a rate of decline of SCr of <33, <40, and <46 % from birth to days 3, 5, or 7 of life, respectively (delayed rise in estimated SCr clearance group). Compared to the control group, newborns in the other two groups required more days of mechanical ventilation and vasopressor drugs and had higher gentamicin levels, more fluid overload, lower urinary epidermal growth factor levels, and a prolonged length of stay. Conclusions The rate of decline of SCr provides a sensitive approach to identify term newborns with AKI during the first week of life. PMID:26857710

A new approach to define acute kidney injury in term newborns with hypoxic ischemic encephalopathy.

PubMed

Gupta, Charu; Massaro, An N; Ray, Patricio E

2016-07-01

Current definitions of acute kidney injury (AKI) are not sufficiently sensitive to identify all newborns with AKI during the first week of life. To determine whether the rate of decline of serum creatinine (SCr) during the first week of life can be used to identify newborns with AKI, we reviewed the medical records of 106 term neonates at risk of AKI who were treated with hypothermia for hypoxic ischemic encephalopathy (HIE). Of the newborns enrolled in the study, 69 % showed a normal rate of decline of SCr to ≥50 % and/or reached SCr levels of ≤0.6 mg/dl before the 7th day of life, and therefore had an excellent clinical outcome (control group). Thirteen newborns with HIE (12 %) developed AKI according to an established neonatal definition (AKI-KIDGO group), and an additional 20 newborns (19 %) showed a rate of decline of SCr of <33, <40, and <46 % from birth to days 3, 5, or 7 of life, respectively (delayed rise in estimated SCr clearance group). Compared to the control group, newborns in the other two groups required more days of mechanical ventilation and vasopressor drugs and had higher gentamicin levels, more fluid overload, lower urinary epidermal growth factor levels, and a prolonged length of stay. The rate of decline of SCr provides a sensitive approach to identify term newborns with AKI during the first week of life.

Race, APOL1 Risk, and eGFR Decline in the General Population

PubMed Central

Rebholz, Casey M.; Chen, Yuan; Rawlings, Andreea M.; Estrella, Michelle M.; Selvin, Elizabeth; Appel, Lawrence J.; Tin, Adrienne; Coresh, Josef

2016-01-01

The APOL1 high-risk genotype, present in approximately 13% of blacks in the United States, is a risk factor for kidney function decline in populations with CKD. It is unknown whether genetic screening is indicated in the general population. We evaluated the prognosis of APOL1 high-risk status in participants in the population-based Atherosclerosis Risk in Communities (ARIC) study, including associations with eGFR decline, variability in eGFR decline, and related adverse health events (AKI, ESRD, hypertension, diabetes, cardiovascular disease, pre-ESRD and total hospitalization rate, and mortality). Among 15,140 ARIC participants followed from 1987–1989 (baseline) to 2011–2013, 75.3% were white, 21.5% were black/APOL1 low-risk, and 3.2% were black/APOL1 high-risk. In a demographic-adjusted analysis, blacks had a higher risk for all assessed adverse health events; however, in analyses adjusted for comorbid conditions and socioeconomic status, blacks had a higher risk for hypertension, diabetes, and ESRD only. Among blacks, the APOL1 high-risk genotype associated only with higher risk of ESRD in a fully adjusted analysis. Black race and APOL1 high-risk status were associated with faster eGFR decline (P<0.001 for each). However, we detected substantial overlap among the groups: median (10th–90th percentile) unadjusted eGFR decline was 1.5 (1.0–2.2) ml/min per 1.73 m2 per year for whites, 2.1 (1.4–3.1) ml/min per 1.73 m2 per year for blacks with APOL1 low-risk status, and 2.3 (1.5–3.5) ml/min per 1.73 m2 per year for blacks with APOL1 high-risk status. The high variability in eGFR decline among blacks with and without the APOL1 high-risk genotype suggests that population-based screening is not yet justified. PMID:26966015

Race, APOL1 Risk, and eGFR Decline in the General Population.

PubMed

Grams, Morgan E; Rebholz, Casey M; Chen, Yuan; Rawlings, Andreea M; Estrella, Michelle M; Selvin, Elizabeth; Appel, Lawrence J; Tin, Adrienne; Coresh, Josef

2016-09-01

The APOL1 high-risk genotype, present in approximately 13% of blacks in the United States, is a risk factor for kidney function decline in populations with CKD. It is unknown whether genetic screening is indicated in the general population. We evaluated the prognosis of APOL1 high-risk status in participants in the population-based Atherosclerosis Risk in Communities (ARIC) study, including associations with eGFR decline, variability in eGFR decline, and related adverse health events (AKI, ESRD, hypertension, diabetes, cardiovascular disease, pre-ESRD and total hospitalization rate, and mortality). Among 15,140 ARIC participants followed from 1987-1989 (baseline) to 2011-2013, 75.3% were white, 21.5% were black/APOL1 low-risk, and 3.2% were black/APOL1 high-risk. In a demographic-adjusted analysis, blacks had a higher risk for all assessed adverse health events; however, in analyses adjusted for comorbid conditions and socioeconomic status, blacks had a higher risk for hypertension, diabetes, and ESRD only. Among blacks, the APOL1 high-risk genotype associated only with higher risk of ESRD in a fully adjusted analysis. Black race and APOL1 high-risk status were associated with faster eGFR decline (P<0.001 for each). However, we detected substantial overlap among the groups: median (10th-90th percentile) unadjusted eGFR decline was 1.5 (1.0-2.2) ml/min per 1.73 m(2) per year for whites, 2.1 (1.4-3.1) ml/min per 1.73 m(2) per year for blacks with APOL1 low-risk status, and 2.3 (1.5-3.5) ml/min per 1.73 m(2) per year for blacks with APOL1 high-risk status. The high variability in eGFR decline among blacks with and without the APOL1 high-risk genotype suggests that population-based screening is not yet justified. Copyright © 2016 by the American Society of Nephrology.

Disruption of Hox9,10,11 function results in cellular level lineage infidelity in the kidney.

PubMed

Drake, Keri A; Adam, Mike; Mahoney, Robert; Potter, S Steven

2018-04-20

Hox genes are important regulators of development. The 39 mammalian Hox genes have considerable functional overlap, greatly confounding their study. In this report, we generated mice with multiple combinations of paralogous and flanking Abd-B Hox gene mutations to investigate functional redundancies in kidney development. The resulting mice developed a number of kidney abnormalities, including hypoplasia, agenesis, and severe cysts, with distinct Hox functions observed in early metanephric kidney formation and nephron progenitor maintenance. Most surprising, however, was that extensive removal of Hox shared function in these kidneys resulted in cellular level lineage infidelity. Strikingly, mutant nephron tubules consisted of intermixed cells with proximal tubule, loop of Henle, and collecting duct identities, with some single cells expressing markers associated with more than one nephron segment. These results indicate that Hox genes are required for proper lineage selection/maintenance and full repression of genes involved in cell fate restriction in the developing kidney.

Age at Immigration and Kidney Function among Self-Identified Healthy Africans in the United States.

PubMed

Ali, Mana; Mwendwa, Denée T; Sims, Regina; Ricks, Madia; Sumner, Anne E

2016-02-01

Kidney disease disparately affects those of African descent. Age trends have generally been established for kidney function in the overall US population, but the contribution of age at the time of immigration for African immigrants is unknown. To examine the independent and joint effects of age and age at the time of immigration, and kidney function. Estimated glomerular filtration rate (eGFR) was calculated for 93 African immigrants (60 % male; mean age = 33.5). Hierarchical regression and post hoc analyses revealed a significant age × age at the time of immigration interaction after accounting for traditional risk factors among those who immigrated at age ≤21. Younger age at the time of immigration to the US may exacerbate an inverse relationship between age and kidney function in a self-identified healthy African immigrant sample. Investigation of biopsychosocial factors associated with kidney health among African immigrants is warranted.

Using optical coherence tomography (OCT) to evaluate the status of human donor kidneys (Conference Presentation)

NASA Astrophysics Data System (ADS)

Andrews, Peter M.; Konkel, Brandon; Anderson, Erik; Stein, Matthew; Cooper, Matthew; Verbesey, Jennifer E.; Ghasemian, Seyed; Chen, Yu

2016-02-01

The main cause of delayed renal function following the transplant of donor kidneys is ischemic induced acute tubular necrosis (ATN). The ability to determine the degree of ATN suffered by donor kidneys prior to their transplant would enable transplant surgeons to use kidneys that might otherwise be discarded and better predict post-transplant renal function. Currently, there are no reliable tests to determine the extent of ATN of donor kidneys prior to their transplant. In ongoing clinical trials, we have been using optical coherence tomography (OCT) to non-invasively image the superficial proximal tubules of human donor kidneys prior to and following transplant, and correlate these observations with post-transplant renal function. Thus far we have studied over 40 living donor kidneys and 10 cadaver donor kidneys, and demonstrated that this imaging can be performed in a sterile and expeditious fashion in the operating room (OR). Because of many variables associated with a diverse population of donors/recipients and transplant operation parameters, more transplant data must be collected prior to drawing definite conclusions. Nevertheless, our observations have thus far mirrored our previously published laboratory results indicating that damage to the kidney proximal tubules as indicated by tubule swelling is a good measure of post-transplant ATN and delayed graft function. We conclude that OCT is a useful procedure for analyzing human donor kidneys.

Cold preservation with hyperbranched polyglycerol-based solution improves kidney functional recovery with less injury at reperfusion in rats

PubMed Central

Li, Shadan; Liu, Bin; Guan, Qiunong; Chafeeva, Irina; Brooks, Donald E; Nguan, Christopher YC; Kizhakkedathu, Jayachandran N; Du, Caigan

2017-01-01

Minimizing donor organ injury during cold preservation (including cold perfusion and storage) is the first step to prevent transplant failure. We recently reported the advantages of hyperbranched polyglycerol (HPG) as a novel substitute for hydroxyethyl starch in UW solution for both cold heart preservation and cold kidney perfusion. This study evaluated the functional recovery of the kidney at reperfusion after cold preservation with HPG solution. The impact of HPG solution compared to conventional UW and HTK solutions on tissue weight and cell survival at 4°C was examined using rat kidney tissues and cultured human umbilical vein endothelial cells (HUVECs), respectively. The kidney protection by HPG solution was tested in a rat model of cold kidney ischemia-reperfusion injury, and was evaluated by histology and kidney function. Here, we showed that preservation with HPG solution prevented cell death in cultured HUVECs and edema formation in kidney tissues at 4°C similar to UW solution, whereas HTK solution was less effective. In rat model of cold ischemia-reperfusion injury, the kidneys perfused and subsequently stored 1-hour with cold HPG solution showed less leukocyte infiltration, less tubular damage and better kidney function (lower levels of serum creatinine and blood urea nitrogen) at 48 h of reperfusion than those treated with UW or HTK solution. In conclusion, our data show the superiority of HPG solution to UW or HTK solution in the cold perfusion and storage of rat kidneys, suggesting that the HPG solution may be a promising candidate for improved donor kidney preservation prior to transplantation. PMID:28337272

Awareness level of kidney functions and diseases among adults in a Nigerian population

PubMed Central

Okwuonu, C. G.; Chukwuonye, I. I.; Ogah, S. O.; Abali, C.; Adejumo, O. A.; Oviasu, E.

2015-01-01

The prevalence of kidney diseases is on the increase in Nigeria. The cost of its management is far beyond the reach of an average patient. Prevention is thus of paramount importance and awareness of kidney diseases will help in its prevention. The aim of this study is to assess the level of awareness of kidney functions and diseases among adults in a Nigerian population. A semi-structured, researcher – administered questionnaire was the tool for data collection. Four hundred and thirty-five questionnaires were analyzed. There were 160 males (36.8%) and 275 females (63.2%). The mean age was 42.8 ± 14 years with a range of 18–78 years. Among these, 82.1% were aware of the kidneys' involvement in waste removal from the body through urine while 36% and 29% were aware of kidneys' role in blood pressure regulation and blood production, respectively. Only 26.6% correctly identified at least two basic functions of the kidneys. Also, 32.6% of the respondents were aware of at least three common causes of kidney diseases in our environment. Majority of the respondents (70.7%) did not know that kidney diseases could be inherited. Furthermore, belief in alternative therapy for kidney disease was documented in 83.2%, while unawareness of dialysis as a treatment modality was recorded in 68% of the respondents. The awareness of kidney functions and diseases among the population is poor. Measures are needed to improve this to stem the rising prevalence of chronic kidney disease in Nigeria. PMID:26060365

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.

Association between physical activity and kidney function: National Health and Nutrition Examination Survey.

PubMed

Hawkins, Marquis S; Sevick, Mary Ann; Richardson, Caroline R; Fried, Linda F; Arena, Vincent C; Kriska, Andrea M

2011-08-01

Chronic kidney disease is a condition characterized by the deterioration of the kidney's ability to remove waste products from the body. Although treatments to slow the progression of the disease are available, chronic kidney disease may eventually lead to a complete loss of kidney function. Previous studies have shown that physical activities of moderate intensity may have renal benefits. Few studies have examined the effects of total movement on kidney function. The purpose of this study was to determine the association between time spent at all levels of physical activity intensity and sedentary behavior and kidney function. Data were obtained from the 2003-2004 and 2005-2006 National Health and Nutrition Examination Survey, a cross-sectional study of a complex, multistage probability sample of the US population. Physical activity was assessed using an accelerometer and questionnaire. Glomerular filtration rate (eGFR) was estimated using the Modification of Diet in Renal Disease study formula. To assess linear associations between levels of physical activity and sedentary behavior with log-transformed estimated GFR (eGFR), linear regression was used. In general, physical activity (light and total) was related to log eGFR in females and males. For females, the association between light and total physical activity with log eGFR was consistent regardless of diabetes status. For males, the association between light and total physical activity and log eGFR was only significant in males without diabetes. When examining the association between physical activity, measured objectively with an accelerometer, and kidney function, total and light physical activities were found to be positively associated with kidney function.

Pathogenesis of renal failure in multiple myeloma: any role of contrast media?

PubMed

Mussap, Michele; Merlini, Giampaolo

2014-01-01

The spectrum of kidney disease-associated monoclonal immunoglobulin and plasma cell malignancies is remarkably broad and encompasses nearly all nephropathologic entities. Multiple myeloma with kidney impairment at presentation is a medical emergency since the recovery of kidney function is associated with survival benefits. In most cases, kidney impairment may be the first clinical manifestation of malignant plasma cell dyscrasias like multiple myeloma and light chain amyloidosis. Multiple myeloma per se cannot be considered a main risk factor for developing acute kidney injury following intravascular administration of iodinated contrast media. The risk is increased by comorbidities such as chronic kidney disease, diabetes, hypercalcemia, dehydration, and use of nephrotoxic drugs. Before the administration of contrast media, the current recommended laboratory tests for assessing kidney function are serum creatinine measurement and the estimation of glomerular filtration rate by using the CKD-EPI equation. The assessment of Bence Jones proteinuria is unnecessary for evaluating the risk of kidney failure in patients with multiple myeloma, since this test cannot be considered a surrogate biomarker of kidney function.

Pathogenesis of Renal Failure in Multiple Myeloma: Any Role of Contrast Media?

PubMed Central

Mussap, Michele; Merlini, Giampaolo

2014-01-01

The spectrum of kidney disease-associated monoclonal immunoglobulin and plasma cell malignancies is remarkably broad and encompasses nearly all nephropathologic entities. Multiple myeloma with kidney impairment at presentation is a medical emergency since the recovery of kidney function is associated with survival benefits. In most cases, kidney impairment may be the first clinical manifestation of malignant plasma cell dyscrasias like multiple myeloma and light chain amyloidosis. Multiple myeloma per se cannot be considered a main risk factor for developing acute kidney injury following intravascular administration of iodinated contrast media. The risk is increased by comorbidities such as chronic kidney disease, diabetes, hypercalcemia, dehydration, and use of nephrotoxic drugs. Before the administration of contrast media, the current recommended laboratory tests for assessing kidney function are serum creatinine measurement and the estimation of glomerular filtration rate by using the CKD-EPI equation. The assessment of Bence Jones proteinuria is unnecessary for evaluating the risk of kidney failure in patients with multiple myeloma, since this test cannot be considered a surrogate biomarker of kidney function. PMID:24877060

Cardio-renal syndromes: a systematic approach for consensus definition and classification.

PubMed

Ronco, Claudio; Ronco, Federico

2012-03-01

The "Cardio-Renal Syndrome" (CRS) is a disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. The general definition has been expanded to five subtypes reflecting the primacy of organ dysfunction and the time-frame of the syndrome: CRS type I: acute worsening of heart function (AHF-ACS) leading to kidney injury and/or dysfunction. CRS type II: chronic abnormalities in heart function (CHF-CHD) leading to kidney injury or dysfunction. CRS type III: acute worsening of kidney function (AKI) leading to heart injury and/or dysfunction. CRS type IV: chronic kidney disease (CKD) leading to heart injury, disease and/or dysfunction. CRS type V: systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney. Different pathophysiological mechanisms are involved in the combined dysfunction of heart and kidney in these five types of the syndrome.

Kidneys: Key Modulators of HDL Levels and Function

PubMed Central

Yang, Haichun; Fogo, Agnes B.; Kon, Valentina

2016-01-01

Purpose of review This review will examine advances in our understanding of the role kidneys play in HDL metabolism and the effect on levels, composition, and function of HDL particles. Recent findings Components of the HDL particles can cross the glomerular filtration barrier. Some of these components, including apolipoproteins and enzymes involved in lipid metabolism, are taken up by the proximal tubule and degraded, modified, salvaged/returned to the circulation, or lost in the urine. Injury of the glomerular capillaries or tubules can affect these intrarenal processes and modify HDL. Changes in the plasma and urine levels of HDL may be novel markers of kidney damage and/or mechanism(s) of kidney disease. Summary The kidneys have a significant role in metabolism of individual HDL components, which in turn modulate HDL levels, composition and functionality of HDL particles. These intrarenal effects may be useful markers of kidney damage and have consequences on kidney-related perturbations in HDL. PMID:27008596

Cardiorenal syndrome: new developments in the understanding and pharmacologic management.

PubMed

House, Andrew A

2013-10-01

Cardiorenal syndromes (CRSs) with bidirectional heart-kidney signaling are increasingly being recognized for their association with increased morbidity and mortality. In acute CRS, recognition of the importance of worsening kidney function complicating management of acute decompensated heart failure has led to the examination of this specific outcome in the context of acute heart failure clinical trials. In particular, the role of fluid overload and venous congestion has focused interest in the most effective use of diuretic therapy to relieve symptoms of heart failure while at the same time preserving kidney function. Additionally, many novel vasoactive therapies have been studied in recent years with the hopes of augmenting cardiac function, improving symptoms and patient outcomes, while maintaining or improving kidney function. Similarly, recent advances in our understanding of the pathophysiology of chronic CRS have led to reanalysis of kidney outcomes in pivotal trials in chronic congestive heart failure, and newer trials are including changes in kidney function as well as kidney injury biomarkers as prospectively monitored and adjudicated outcomes. This paper provides an overview of some new developments in the pharmacologic management of acute and chronic CRS, examines several reports that illustrate a key management principle for each subtype, and discusses opportunities for future research.

Computed Tomography Volumetry in Preoperative Living Kidney Donor Assessment for Prediction of Split Renal Function.

PubMed

Wahba, Roger; Franke, Mareike; Hellmich, Martin; Kleinert, Robert; Cingöz, Tülay; Schmidt, Matthias C; Stippel, Dirk L; Bangard, Christopher

2016-06-01

Transplant centers commonly evaluate split renal function (SRF) with Tc-99m-mercapto-acetyltriglycin (MAG3) scintigraphy in living kidney donation. Alternatively, the kidney volume can be measured based on predonation CT scans. The aim of this study was to identify the most accurate CT volumetry technique for SRF and the prediction of postdonation kidney function (PDKF). Three CT volumetry techniques (modified ellipsoid volume [MELV], smart region of interest [ROI] volume, renal cortex volume [RCV]) were performed in 101 living kidney donors. Preoperation CT volumetric SRF was determined and compared with MAG3-SRF, postoperation donor kidney function, and graft function. The correlation between donors predonation total kidney volume and predonation kidney function was the highest for RCV (0.58 with creatine clearance, 0.54 with estimated glomerular filtration rate-Cockcroft-Gault). The predonation volume of the preserved kidney was (ROI, MELV, RCV) 148.0 ± 29.1 cm, 151.2 ± 35.4 and 93.9 ± 25.2 (P < 0.005 MELV vs RCV and ROI vs RCV). Bland-Altman analysis showed agreement between CT volumetry SRF and MAG3-SRF (bias, 95% limits of agreement: ROI vs MAG3 0.4%, -7.7% to 8.6%; MELV vs MAG3 0.4%, -8.9% to 9.7%; RCV vs MAG3 0.8%, -9.1% to 10.7%). The correlation between predonation CT volumetric SRF of the preserved kidney and PDKF at day 3 was r = 0.85 to 0.88, between MAG3-SRF and PDKF (r = 0.84). The difference of predonation SRF between preserved and donated kidney was the lowest for ROI and RCV (median, 3% and 4%; 95th percentile, 9% and 13%). Overall renal cortex volumetry seems to be the most accurate technique for the evaluation of predonation SRF and allows a reliable prediction of donor's PDKF.

Information overload; a response to "Turn down for what? Patient outcomes associated with declining increased infectious risk kidneys."

PubMed

Singh, Pooja; Yadav, Anju; Shah, Ashesh P; Frank, Adam M

2018-04-30

"Donors are heroes" is a transplant axiom. Unfortunately, many history elements that go into labeling a donor public health service-high risk (PHS-HR), i.e. increased risk for transmitting HIV, Hepatitis C (HCV) and Hepatitis B (HBV), chip away at this dictum due to associated stigma. We read the article by Bowring et al 1 and applaud their work that showed accepting PHS-HR kidneys conferred substantial survival advantage. This article is protected by copyright. All rights reserved. This article is protected by copyright. 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.

When Your Child Needs a Kidney Transplant

MedlinePlus

... Search English Español When Your Child Needs a Kidney Transplant KidsHealth / For Parents / When Your Child Needs ... to monitor their new kidney function. About the Kidneys Kidneys are bean-shaped organs located near the ...

Pathophysiology of Acute Kidney Injury

PubMed Central

Basile, David P.; Anderson, Melissa D.; Sutton, Timothy A.

2014-01-01

Acute kidney injury (AKI) is the leading cause of nephrology consultation and is associated with high mortality rates. The primary causes of AKI include ischemia, hypoxia or nephrotoxicity. An underlying feature is a rapid decline in GFR usually associated with decreases in renal blood flow. Inflammation represents an important additional component of AKI leading to the extension phase of injury, which may be associated with insensitivity to vasodilator therapy. It is suggested that targeting the extension phase represents an area potential of treatment with the greatest possible impact. The underlying basis of renal injury appears to be impaired energetics of the highly metabolically active nephron segments (i.e., proximal tubules and thick ascending limb) in the renal outer medulla, which can trigger conversion from transient hypoxia to intrinsic renal failure. Injury to kidney cells can be lethal or sublethal. Sublethal injury represents an important component in AKI, as it may profoundly influence GFR and renal blood flow. The nature of the recovery response is mediated by the degree to which sublethal cells can restore normal function and promote regeneration. The successful recovery from AKI depends on the degree to which these repair processes ensue and these may be compromised in elderly or CKD patients. Recent data suggest that AKI represents a potential link to CKD in surviving patients. Finally, earlier diagnosis of AKI represents an important area in treating patients with AKI that has spawned increased awareness of the potential that biomarkers of AKI may play in the future. PMID:23798302

Outcomes at 7 years post-transplant in black vs nonblack kidney transplant recipients administered belatacept or cyclosporine in BENEFIT and BENEFIT-EXT.

PubMed

Florman, Sander; Vincenti, Flavio; Durrbach, Antoine; Abouljoud, Marwan; Bresnahan, Barbara; Garcia, Valter Duro; Mulloy, Laura; Rice, Kim; Rostaing, Lionel; Zayas, Carlos; Calderon, Kellie; Meier-Kriesche, Ulf; Polinsky, Martin; Yang, Lingfeng; Medina Pestana, Jose; Larsen, Christian P

2018-04-01

Clinical outcomes are generally worse for black vs nonblack renal allograft recipients. In BENEFIT and BENEFIT-EXT, recipients were randomized to belatacept more intense-based, belatacept less intense-based, or cyclosporine-based immunosuppression. At year 7, belatacept was associated with superior graft survival vs cyclosporine in BENEFIT (recipients of living or standard criteria deceased donor kidneys); belatacept was associated with similar graft survival vs cyclosporine in BENEFIT-EXT (recipients of extended criteria donor kidneys). In both studies, renal function was superior for belatacept-treated vs cyclosporine-treated patients. Seven-year outcomes were examined by race post hoc in each study. The effect of race and treatment on time to death or graft loss was compared using Cox regression. The interaction between treatment and race was also considered. Glomerular filtration rate (GFR) was estimated from months 1 to 84 using a repeated-measures model. In total, 8.3% (55/666) and 13.1% (71/543) of patients in BENEFIT and BENEFIT-EXT, respectively, were black. Time to death or graft loss was similar in blacks and nonblacks. For both subgroups, estimated mean GFR increased over 7 years for belatacept, but declined for cyclosporine. Outcomes were similar in belatacept-treated black and nonblack patients. Due to the small number of black patients, these results must be interpreted with caution. © 2018 The Authors. Clinical Transplantation Published by John Wiley & Sons Ltd.

Incidence and Progression of Chronic Kidney Disease in Black and White Individuals with Type 2 Diabetes.

PubMed

Gerber, Claire; Cai, Xuan; Lee, Jungwha; Craven, Timothy; Scialla, Julia; Souma, Nao; Srivastava, Anand; Mehta, Rupal; Paluch, Amanda; Hodakowski, Alexander; Frazier, Rebecca; Carnethon, Mercedes R; Wolf, Myles Selig; Isakova, Tamara

2018-06-07

Type 2 diabetes and associated CKD disproportionately affect blacks. It is uncertain if racial disparities in type 2 diabetes-associated CKD are driven by biologic factors that influence propensity to CKD or by differences in type 2 diabetes care. We conducted a post hoc analysis of 1937 black and 6372 white participants of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial to examine associations of black race with change in eGFR and risks of developing microalbuminuria, macroalbuminuria, incident CKD (eGFR<60 ml/min per 1.73m 2 , ≥25% decrease from baseline eGFR, and eGFR slope <-1.6 ml/min per 1.73 m 2 per year), and kidney failure or serum creatinine >3.3 mg/dl. During a median follow-up that ranged between 4.4 and 4.7 years, 278 black participants (58 per 1000 person-years) and 981 white participants (55 per 1000 person-years) developed microalbuminuria, 122 black participants (16 per 1000 person-years) and 374 white participants (14 per 1000 person-years) developed macroalbuminuria, 111 black participants (21 per 1000 person-years) and 499 white participants (28 per 1000 person-years) developed incident CKD, and 59 black participants (seven per 1000 person-years) and 178 white participants (six per 1000 person-years) developed kidney failure or serum creatinine >3.3 mg/dl. Compared with white participants, black participants had lower risks of incident CKD (hazard ratio, 0.73; 95% confidence intervals, 0.57 to 0.92). There were no significant differences by race in eGFR decline or in risks of microalbuminuria, macroalbuminuria, and kidney failure or of serum creatinine >3.3 mg/dl. Black participants enrolled in a randomized controlled trial had lower rates of incident CKD compared with white participants. Rates of eGFR decline, microalbuminuria, macroalbuminuria, and kidney failure did not vary by race. Copyright © 2018 by the American Society of Nephrology.

Comparative in vivo assessment of the subacute toxicity of gold and silver nanoparticles

NASA Astrophysics Data System (ADS)

Rathore, Mansee; Mohanty, Ipseeta Ray; Maheswari, Ujjwala; Dayal, Navami; Suman, Rajesh; Joshi, D. S.

2014-04-01

In spite of the projected therapeutic potentials of gold nanoparticles (GNP) and silver nanoparticles (SNP), very limited data are available on the interaction of nanoparticles with the biological systems. The present investigation was designed to evaluate as well as compare the subacute toxicity of GNP and SNP. Stable suspensions of GNP and SNP with mean particle diameter 10 and 25 nm, respectively, were prepared. Wistar rats were orally fed SNP (3 mg/kg) or GNP (20 μg/kg), once a day for 21 days. Biochemical indices (creatinine phosphokinase-MB, urea, blood urea nitrogen, aspartate transaminase, alkaline alanine transferase) and histopathological features of the liver, heart, brain, lungs, and kidney were evaluated for signs of toxicity. A significant decline in hepatic and renal function in the GNP treated group was observed as compared to SNP. GNP was found to be relatively more toxic on the lungs and SNP on the myocardial tissue as compared to SNP and GNP treatments, respectively. Interestingly, neither SNP nor GNP adversely affected the basal architecture of the brain as compared to sham. The present study demonstrated that GNP was significantly more noxious on the liver and kidney as compared with SNP.

Simultaneous evaluation of renal morphology and function in live kidney donors using dynamic magnetic resonance imaging.

PubMed

Artunc, F; Yildiz, S; Rossi, C; Boss, A; Dittmann, H; Schlemmer, H P; Risler, T; Heyne, N

2010-06-01

Evaluation of potential kidney donors requires the assessment of both kidney anatomy and function. In this prospective study, we sought to expand the diagnostic yield of magnetic resonance (MR) by adding functional measurements of glomerular filtration rate (GFR) and split renal function. Between 2007 and 2009, all potential kidney donors presenting to our facility underwent a comprehensive single-stop MR study that included an assessment of anatomy, angiography and functional measurements. 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. Split renal function was calculated from the increase of signal intensity over the renal cortex. Values were compared to renal scintigraphy with (99m)Tc-DTPA from the same day. The MR investigation was successfully performed in 21 participants. The GFR derived from MR (MR-GFR) correlated well (r = 0.84) with the GFR derived from scintigraphy (DTPA-GFR). The mean value of the paired differences was 4 +/- 13 [SD] ml/min/1.73 m(2) and was not significantly different from zero. The ratio between right and left kidney function was similar with both techniques (1.01 +/- 0.17 with MR and 1.06 +/- 0.12 with scintigraphy, P = 0.20). We demonstrate an MR-based approach to comprehensively evaluate both kidney anatomy and function in a single investigation, thereby facilitating the evaluation of potential kidney donors.

Genome-Wide Association of CKD Progression: The Chronic Renal Insufficiency Cohort Study.

PubMed

Parsa, Afshin; Kanetsky, Peter A; Xiao, Rui; Gupta, Jayanta; Mitra, Nandita; Limou, Sophie; Xie, Dawei; Xu, Huichun; Anderson, Amanda Hyre; Ojo, Akinlolu; Kusek, John W; Lora, Claudia M; Hamm, L Lee; He, Jiang; Sandholm, Niina; Jeff, Janina; Raj, Dominic E; Böger, Carsten A; Bottinger, Erwin; Salimi, Shabnam; Parekh, Rulan S; Adler, Sharon G; Langefeld, Carl D; Bowden, Donald W; Groop, Per-Henrik; Forsblom, Carol; Freedman, Barry I; Lipkowitz, Michael; Fox, Caroline S; Winkler, Cheryl A; Feldman, Harold I

2017-03-01

The rate of decline of renal function varies significantly among individuals with CKD. To understand better the contribution of genetics to CKD progression, we performed a genome-wide association study among participants in the Chronic Renal Insufficiency Cohort Study. Our outcome of interest was CKD progression measured as change in eGFR over time among 1331 blacks and 1476 whites with CKD. We stratified all analyses by race and subsequently, diabetes status. Single-nucleotide polymorphisms (SNPs) that surpassed a significance threshold of P <1×10 -6 for association with eGFR slope were selected as candidates for follow-up and secondarily tested for association with proteinuria and time to ESRD. We identified 12 such SNPs among black patients and six such SNPs among white patients. We were able to conduct follow-up analyses of three candidate SNPs in similar (replication) cohorts and eight candidate SNPs in phenotype-related (validation) cohorts. Among blacks without diabetes, rs653747 in LINC00923 replicated in the African American Study of Kidney Disease and Hypertension cohort (discovery P =5.42×10 -7 ; replication P =0.039; combined P =7.42×10 -9 ). This SNP also associated with ESRD (hazard ratio, 2.0 (95% confidence interval, 1.5 to 2.7); P =4.90×10 -6 ). Similarly, rs931891 in LINC00923 associated with eGFR decline ( P =1.44×10 -4 ) in white patients without diabetes. In summary, SNPs in LINC00923 , an RNA gene expressed in the kidney, significantly associated with CKD progression in individuals with nondiabetic CKD. However, the lack of equivalent cohorts hampered replication for most discovery loci. Further replication of our findings in comparable study populations is warranted. Copyright © 2017 by the American Society of Nephrology.

Validation of Surrogates of Urine Osmolality in Population Studies.

PubMed

Youhanna, Sonia; Bankir, Lise; Jungers, Paul; Porteous, David; Polasek, Ozren; Bochud, Murielle; Hayward, Caroline; Devuyst, Olivier

2017-01-01

The importance of vasopressin and/or urine concentration in various kidney, cardiovascular, and metabolic diseases has been emphasized recently. Due to technical constraints, urine osmolality (Uosm), a direct reflect of urinary concentrating activity, is rarely measured in epidemiologic studies. We analyzed 2 possible surrogates of Uosm in 4 large population-based cohorts (total n = 4,247) and in patients with chronic kidney disease (CKD, n = 146). An estimated Uosm (eUosm) based on the concentrations of sodium, potassium, and urea, and a urine concentrating index (UCI) based on the ratio of creatinine concentrations in urine and plasma were compared to the measured Uosm (mUosm). eUosm is an excellent surrogate of mUosm, with a highly significant linear relationship and values within 5% of mUosm (r = 0.99 or 0.98 in each population cohort). Bland-Altman plots show a good agreement between eUosm and mUosm with mean differences between the 2 variables within ±24 mmol/L. This was verified in men and women, in day and night urine samples, and in CKD patients. The relationship of UCI with mUosm is also significant but is not linear and exhibits more dispersed values. Moreover, the latter index is no longer representative of mUosm in patients with CKD as it declines much more quickly with declining glomerular filtration rate than mUosm. The eUosm is a valid marker of urine concentration in population-based and CKD cohorts. The UCI can provide an estimate of urine concentration when no other measurement is available, but should be used only in subjects with normal renal function. © 2017 S. Karger AG, Basel.

Commercial kidney transplantation: trends, outcomes and challenges-a single-centre experience.

PubMed

Adamu, Bappa; Ahmed, Mustafa; Mushtaq, Raees F; Alshaebi, Fuad

2012-01-01

Many experts believe that commercial organ transplants continue unabated despite international efforts to curb them. The aim was to determine the trends, outcomes and challenges of commercial living unrelated renal transplants (LURT) as seen in our institution. A retrospective study of LURT patients on follow-up at our institution. The list of all LURT patients was obtained from our renal registry. Inclusion criteria for the study were 1) Presentation to our hospital within the first month post transplant; 2) Completion of one-year follow-up OR patient or allograft losses prior to completing one-year follow-up. SPSS 17.0 was used for data analysis. Forty-five patients satisfied the entry criteria; 33 males and 12 females with age range 13-68 years, and mean ± SD of 40 + 15 years. The majority (28) of the transplants were carried out in Pakistan, the remaining in Egypt, Philippines, and China. There has been a steady decline in the number of new patients with commercial transplants over a four-year period. Complications encountered included infections in 19 (42.2%) patients, biopsy-proven acute rejections in nine patients (20%), surgical complications in 10 patients (22.2%), post-transplant diabetes in seven (15.6%), delayed graft function in one (2.2%), and chronic allograft nephropathy in one (2.2%) patient. Patient survival at one year was 97.8% and allograft survival was 88.9%. Commercial kidney transplant is on the decline as seen in our center, likely as a result of international efforts to curb it, as well as due to a parallel increase in renal transplants in the country. One-year patient and allograft survivals are good but there is a relatively high rate of infections.

Association of Kidney Function and Albuminuria With Prevalent and Incident Hypertension: The Atherosclerosis Risk in Communities (ARIC) Study

PubMed Central

Huang, Minxuan; Matsushita, Kunihiro; Sang, Yingying; Ballew, Shoshana H.; Astor, Brad C.; Coresh, Josef

2014-01-01

Background Decreased kidney function and kidney damage may predate hypertension, but only a few studies have investigated both types of markers simultaneously, and these studies have obtained conflicting results. Study Design Cross-sectional for prevalent and prospective observational study for incident hypertension. Setting & Participants 9,593 participants from the Atherosclerosis Risk in Communities (ARIC) Study, aged 53-75 years during 1996-1998. Predictors Several markers of kidney function (estimated glomerular filtration rate [eGFR] using serum creatinine and/or cystatin C and two novel markers [β-trace protein and β2-microglobulin]) and one marker of kidney damage (urinary albumin-creatinine ratio [ACR]). Every kidney marker was categorized by its quintiles (top quintile as a reference for eGFRs and bottom quintile for the rest). Outcomes Prevalent and incident hypertension. Measurements Prevalence and HRs of hypertension based on modified Poisson regression and Cox proportional hazards models, respectively. Results There were 4,378 participants (45.6%) with prevalent hypertension at baseline and 2,175 incident hypertension cases during a median follow-up of 9.8 years. While all five kidney function markers were significantly associated with prevalent hypertension, prevalent hypertension was most notably associated with higher ACR (adjusted prevalence ratio, 1.60 [95% CI, 1.50-1.71] for the highest vs lowest ACR quintile). Similarly, ACR was consistently associated with incident hypertension in all models tested (adjusted HR, 1.28 [95% CI, 1.10-1.49] for top quintile), while kidney function markers demonstrated significant associations in some, but not all, models. Even mildly increased ACR (9.14-14.0 mg/g) was significantly associated with incident hypertension. Limitations Self-reported use of antihypertensive medication for defining incident hypertension, single assessment of kidney markers, and relatively narrow age range. Conclusions Although all kidney markers were associated with prevalent hypertension, only elevated albuminuria was consistently associated with incident hypertension, suggesting that kidney damage is more closely related to hypertension than moderate reduction in overall kidney function. PMID:25151408

Supplementary Administration of Everolimus Reduces Cardiac Systolic Function in Kidney Transplant Recipients.

PubMed

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

2017-05-26

BACKGROUND The effect of everolimus, one of the mammalian targets of rapamycin inhibitors, on cardiac function was evaluated in kidney transplant recipients. MATERIAL AND METHODS Seventy-six participants who underwent kidney transplant between March 2009 and May 2016 were retrospectively reviewed. To standardize everolimus administration, the following criteria were used: (1) the recipient did not have a donor-specific antigen before kidney transplantation; (2) the recipient did not have proteinuria and uncontrollable hyperlipidemia after kidney transplantation; and (3) acute rejection was not observed on protocol biopsy 3 months after kidney transplantation. According to these criteria, everolimus administration for maintenance immunosuppression after kidney transplantation was included. Cardiac function was compared between the treatment group (n=30) and non-treatment group (n=46). RESULTS The mean observation periods of the treatment and non-treatment groups were 41.3±12.6 and 43.9±19.8 months, respectively (p=0.573). The mean ejection fraction and fractional shortening of the treatment and non-treatment groups after kidney transplant were 66.5±7.9% vs. 69.6±5.5% (p=0.024) and 37.1±6.2% vs. 39.3±4.7% (p=0.045), respectively. In the treatment group, the mean ejection fraction and fractional shortening before and after kidney transplantation did not differ significantly (p=0.604 and 0.606, respectively). In the non-treatment group, the mean ejection fraction and fractional shortening before and after kidney transplantation differed significantly (p=0.004 and 0.006, respectively). CONCLUSIONS Supplementary administration of everolimus after kidney transplantation can reduce cardiac systolic function.

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.

Association of mGFR of the Remaining Kidney Divided by Its Volume before Donation with Functional Gain in mGFR among Living Kidney Donors.

PubMed

Courbebaisse, Marie; Gaillard, François; Tissier, Anne-Marie; Fournier, Catherine; Le Nestour, Alexis; Corréas, Jean-Michel; Slimani-Thevenet, Hind; Martinez, Frank; Léon, Carine; Eladari, Dominique; Timsit, Marc-Olivier; Otal, Philippe; Hignette, Chantal; Friedlander, Gérard; Méjean, Arnaud; Houillier, Pascal; Kamar, Nassim; Legendre, Christophe

2016-08-08

The predictors of long-term renal function in living kidney donors are currently discussed. Our objectives were to describe the predictors of functional gain of the remaining kidney after kidney donation. We hypothesized that GFR of the remaining kidney divided by volume of this kidney (rk-GFR/vol) would reflect the density of functional nephrons and be inversely associated with functional gain of the remaining kidney. We conducted a prospective monocentric study including 63 living donors (26 men; 50.3±11.8 years old) who had been evaluated for (51)Cr-EDTA and measured GFR, split renal function by scintigraphy before donation (between 2004 and 2009), and measured GFR at 5.7±0.5 years after donation. For 52 donors, volume of the remaining kidney (measured and estimated with the ellipsoid formula using renal computed tomography scannography) was determined before donation. We tested our hypothesis in an external validation cohort of 39 living donors (13 men; 51.0±9.4 years old) from another single center during the same time period. For the main cohort, the mean measured GFR was 97.6±13.0 ml/min per 1.73 m(2) before donation and 63.8±9.4 ml/min per 1.73 m(2) at 5 years. Functional gain averaged 16.2±7.2 ml/min per 1.73 m(2) (+35.3%±16.7%). Multivariate analysis showed that age, body mass index, and rk-GFR/vol at donation were negatively correlated with functional gain and had strong predictive power of the 5-year functional gain (adjusted 5-year functional gain for age: -0.4 [95% confidence interval (95% CI), -0.5 to -0.1]; body mass index: -0.3 [95% CI, -0.6 to -0.1]; rk-GFR/vol: -55.1 [95% CI, -92.3 to -17.9]). We tested this model in the external validation cohort (adjusted 5-year functional gain for age: -0.1 [95% CI, -0.5 to 0.3]; body mass index: -0.9 [95% CI, -1.8 to -0.1]; rk-GFR/vol: -97.6 [95% CI, -137.5 to -57.6]) and confirmed that rk-GFR/vol was inversely associated with 5-year functional gain. For given age and body mass index, the long-term functional gain of the remaining kidney is inversely associated with the new variable rk-GFR/vol at donation. Copyright © 2016 by the American Society of Nephrology.

Assay development of inducible human renal phosphate transporter Npt2A (SLC34A1) in Flp-In-Trex-HEK293 cells.

PubMed

Wu, Hongzhong; Mao, Chonghong; Duenstl, Georg; Su, Wan; Qian, Su

2013-12-05

Hyperphosphatemia is associated with severe decline of renal function in chronic kidney disease and elevates cardiovascular mortality. Type II sodium dependent phosphate transporter 2A (Npt2A) plays a major role in renal phosphate reabsorption and could be explored as a target for anti-hyperphosphatemia therapy. Human Npt2A transporter activity was examined upon transfection into CHO, MDCK, HEK293, Flp-In-CHO and Flp-In-HEK293 cells. Only kidney-derived cells expressed functional Npt2A. HEK293 and Flp-In-HEK293 cell lines stably transfected with hNpt2A could be selected, but these cells were inactive in phosphate transport. This suggests that high-level, constitutive Npt2A expression has deleterious effects on the cell. By using the conditional promoter in the Flp-In-Trex vector, functional expression of Npt2A was achieved by doxycycline induction in HEK293 cells. The EGFP tagged and non-tagged, inducible stable hNpt2A-HEK293 cell lines afforded development of a robust phosphate uptake assay mediated by hNpt2A, which can be used to screen hNpt2A inhibitors and inducers of hNpt2A expression. Using this assay, the small molecule LC-1 was identified as a potent inhibitor of hNpt2A, suggesting that it is feasible to develop potent specific hNpt2A inhibitors to control phosphate overloading for hyperphosphatemia therapy. © 2013 Elsevier B.V. All rights reserved.

Potential Use of Autologous Renal Cells from Diseased Kidneys for the Treatment of Renal Failure.

PubMed

George, Sunil K; Abolbashari, Mehran; Jackson, John D; Aboushwareb, Tamer; Atala, Anthony; Yoo, James J

2016-01-01

Chronic kidney disease (CKD) occurs when certain conditions cause the kidneys to gradually lose function. For patients with CKD, renal transplantation is the only treatment option that restores kidney function. In this study, we evaluated primary renal cells obtained from diseased kidneys to determine whether their normal phenotypic and functional characteristics are retained, and could be used for cell therapy. Primary renal cells isolated from both normal kidneys (NK) and diseased kidneys (CKD) showed similar phenotypic characteristics and growth kinetics. The expression levels of renal tubular cell markers, Aquaporin-1 and E-Cadherin, and podocyte-specific markers, WT-1 and Nephrin, were similar in both NK and CKD kidney derived cells. Using fluorescence- activated cell sorting (FACS), specific renal cell populations were identified and included proximal tubular cells (83.1% from NK and 80.3% from CKD kidneys); distal tubular cells (11.03% from NK and 10.9% from CKD kidneys); and podocytes (1.91% from NK and 1.78% from CKD kidneys). Ultra-structural analysis using scanning electron microscopy (SEM) revealed microvilli on the apical surface of cultured cells from NK and CKD samples. Moreover, transmission electron microscopy (TEM) analysis showed a similar organization of tight junctions, desmosomes, and other intracellular structures. The Na+ uptake characteristics of NK and CKD derived renal cells were also similar (24.4 mmol/L and 25 mmol/L, respectively) and no significant differences were observed in the protein uptake and transport characteristics of these two cell isolates. These results show that primary renal cells derived from diseased kidneys such as CKD have similar structural and functional characteristics to their counterparts from a normal healthy kidney (NK) when grown in vitro. This study suggests that cells derived from diseased kidney may be used as an autologous cell source for renal cell therapy, particularly in patients with CKD or end-stage renal disease (ESRD).

Concentrations of heavy metals in American woodcock harvested in Connecticut.

PubMed

Hiller, Brian J; Barclay, John S

2011-01-01

The American woodcock is an important migratory species to both consumptive and nonconsumptive users throughout the species range. Woodcock populations have been declining steadily since surveys began in 1968. Laboratory and field studies have demonstrated several adverse effects associated with metals in other species, which has led to their inclusion as potential contributing factors to the woodcock population decline. We investigated the concentrations of arsenic (As), cadmium (Cd), chromium (Cr), mercury (Hg), lead (Pb), and selenium (Se) in pectoral muscle (n = 100), livers (n = 108), and kidneys (n = 104) and Pb in wing bones (n = 53) from woodcock harvested in Connecticut. Cd concentrations were elevated in 99% of woodcock livers and kidneys; 30% of kidneys were above 100 μg/g dry weight, a Cd level of reported adverse tissue and reproductive effects in other species. Hg and Cr concentrations were below current biologically significant thresholds. Asc, Pb, and Se in soft tissues were associated with lead shot use in collection. Se in 24% of livers was above 10 μg/g dry weight, the reported threshold for avian health. Wing-bone Pb was elevated above 20 μg/g in 61% of adults and 23% of juveniles examined. Our findings indicate that woodcock are being exposed to potentially damaging levels of at least two metals with known effects in other species.

Long-term prognosis after acute kidney injury (AKI): what is the role of baseline kidney function and recovery? A systematic review.

PubMed

Sawhney, Simon; Mitchell, Mhairi; Marks, Angharad; Fluck, Nick; Black, Corrinda

2015-01-06

To summarise the evidence from studies of acute kidney injury (AKI) with regard to the effect of pre-AKI renal function and post-AKI renal function recovery on long-term mortality and renal outcomes, and to assess whether these factors should be taken into account in future prognostic studies. A systematic review of observational studies listed in Medline and EMBASE from 1990 to October 2012. All AKI studies in adults with data on baseline kidney function to identify AKI; with outcomes either stratified by pre-AKI and/or post-AKI kidney function, or described by the timing of the outcomes. Long-term mortality and worsening chronic kidney disease (CKD). Of 7385 citations, few studies met inclusion criteria, reported baseline kidney function and stratified by pre-AKI or post-AKI function. For mortality outcomes, three studies compared patients by pre-AKI renal function and six by post-AKI function. For CKD outcomes, two studies compared patients by pre-AKI function and two by post-AKI function. The presence of CKD pre-AKI (compared with AKI alone) was associated with doubling of mortality and a fourfold to fivefold increase in CKD outcomes. Non-recovery of kidney function was associated with greater mortality and CKD outcomes in some studies, but findings were inconsistent varying with study design. Two studies also reported that risk of poor outcome reduced over time post-AKI. Meta-analysis was precluded by variations in definitions for AKI, CKD and recovery. The long-term prognosis after AKI varies depending on cause and clinical setting, but it may also, in part, be explained by underlying pre-AKI and post-AKI renal function rather than the AKI episode itself. While carefully considered in clinical practice, few studies address these factors and with inconsistent study design. Future AKI studies should report pre-AKI and post-AKI function consistently as additional factors that may modify AKI prognosis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Systematic review of kidney transplantation functional predictors.

PubMed

Miret Alomar, E; Trilla Herrera, E; Lorente Garcia, D; Regis Placido, L; López Del Campo, R; Cuadras Solé, M; Pont Castellana, T; Moreso Mateos, F; Serón Micas, D; Morote Robles, J

2018-05-01

Kidney transplantation from donors with expanded criteria has increased the pool of kidneys at the cost of a higher risk of short and long-term graft dysfunction. The main issue lies in determining which kidneys will offer acceptable function and survival compared with the risk represented by surgery and subsequent immunosuppression. The objective of our article is to review the current evidence on the tools for predicting the functionality of kidney transplantation from cadaveric donors with expanded criteria and determining the validity for their use in standard practice. We conducted a systematic literature review according to the PRISM criteria, through Medline (http://www.ncbi.nlm.nih.gov) and using the keywords (in isolation or in conjunction) "cadaveric renal transplantation; kidney graft function appraisal, graft function predictors". We selected prospective and retrospective series and review articles. A total of 375 articles were analysed, 39 of which were ultimately selected for review. The predictors of functionality include the following: The donor risk indices; the calculation of the renal functional weight or the assessment of the nephronic mass; the measurement of vascular resistances during perfusion in hypothermia; the measurement of the donor's biomarkers in urine and in the perfusion liquid; the measurement of functional and reperfusion parameters in normothermia; and the measurement of morphological parameters (microscopic and macroscopic) of the target organ. In this article, we present an explanatory summary of each of these parameters, as well as their most recent evidence on this issue. None of the reviewed parameters in isolation could reliably predict renal function and graft survival. There is a significant void in terms of the macroscopic assessment of kidney transplantation. We need to continue developing predictors of renal functionality to accurately define the distribution of each currently available donor kidney. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Urinary cadmium in the 1999–2008 U.S. National Health and Nutrition Examination Survey (NHANES)

EPA Science Inventory

Chronic low-level cadmium (Cd) exposure is linked to kidney and cardiovascular disease, fractures, and cancer. Diet and smoking are primary sources of exposure in the general population. We analyzed urinary Cd in NHANES 1999-2008 to determine whether levels declined significantly...

Vitamin status and needs for people with stages 3-5 chronic kidney disease.

PubMed

Steiber, Alison L; Kopple, Joel D

2011-09-01

Patients with chronic kidney disease (CKD) often experience a decline in their nutrient intake starting at early stages of CKD. This reduction in intake can affect both energy-producing nutrients, such as carbohydrates, proteins, and fats, as well as vitamins, minerals, and trace elements. Knowledge of the burden and bioactivity of vitamins and their effect on the health of the patients with CKD is very incomplete. However, without sufficient data, the use of nutritional supplements to prevent inadequate intake may result in either excessive or insufficient intake of micronutrients for people with CKD. The purpose of this article is to briefly summarize the current knowledge regarding vitamin requirements for people with stages 3, 4, or 5 CKD who are not receiving dialysis. Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Hydration Status, Kidney Function, and Kidney Injury in Florida Agricultural Workers.

PubMed

Mix, Jacqueline; Elon, Lisa; Vi Thien Mac, Valerie; Flocks, Joan; Economos, Eugenia; Tovar-Aguilar, Antonio J; Stover Hertzberg, Vicki; McCauley, Linda A

2018-05-01

Recent findings suggest that laboring in hot occupational environments is related to kidney damage in agricultural workers. We examined hydration status and kidney function in 192 Florida agricultural workers. Blood and urine samples were collected over 555 workdays during the summers of 2015 and 2016. Urine-specific gravity (USG), serum creatinine, and other kidney function markers were examined pre- and post-shift on each workday. Multivariable mixed modeling was used to examine the association of risk factors with hydration status and acute kidney injury (AKI). Approximately 53% of workers were dehydrated (USG ≥1.020) pre-shift and 81% post-shift; 33% of participants had AKI on at least one workday. The odds of AKI increased 47% for each 5-degree (°F) increase in heat index. A strikingly high prevalence of dehydration and AKI exists in Florida agricultural workers.

Intermittent hypoxia causes histological kidney damage and increases growth factor expression in a mouse model of obstructive sleep apnea

PubMed Central

Ayas, Najib T.

2018-01-01

Epidemiological studies demonstrate an association between obstructive sleep apnea (OSA) and accelerated loss of kidney function. It is unclear whether the decline in function is due to OSA per se or to other confounding factors such as obesity. In addition, the structural kidney abnormalities associated with OSA are unclear. The objective of this study was to determine whether intermittent hypoxia (IH), a key pathological feature of OSA, induces renal histopathological damage using a mouse model. Ten 8-week old wild-type male CB57BL/6 mice were randomly assigned to receive either IH or intermittent air (IA) for 60 days. After euthanasia, one kidney per animal was paraformaldehyde-fixed and then sectioned for histopathological and immunohistochemical analysis. Measurements of glomerular hypertrophy and mesangial matrix expansion were made in periodic acid–Schiff stained kidney sections, while glomerular transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF) and vascular endothelial growth factor-A (VEGF-A) proteins were semi-quantified by immunohistochemistry. The antigen-antibody reaction was detected by 3,3′-diaminobenzidine chromogen where the color intensity semi-quantified glomerular protein expression. To enhance the accuracy of protein semi-quantification, the percentage of only highly-positive staining was used for analysis. Levels of TGF-β, CTGF and VEGF-A proteins in the kidney cortex were further quantified by western blotting. Cellular apoptosis was also investigated by measuring cortical antiapoptotic B-cell lymphoma 2 (Bcl-2) and apoptotic Bcl-2-associated X (Bax) proteins by western blotting. Further investigation of cellular apoptosis was carried out by fluorometric terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) staining. Finally, the levels of serum creatinine and 24-hour urinary albumin were measured as a general index of renal function. Our results indicate that mice exposed to IH have an increased glomerular area (by 1.13 fold, p< 0.001) and expansion of mesangial matrix (by 1.8 fold, p< 0.01). Moreover, the glomerular expressions of TGF-β1, CTGF and VEGF-A proteins were 2.7, 2.2 and 3.8-fold higher in mice exposed to IH (p< 0.05 for all). Furthermore, western blotting protein analysis demonstrates that IH-exposed mice express higher levels of TGF-β1, CTGF and VEGF-A proteins by 1.9, 4.0 and 1.6-fold (p< 0.05 for all) respectively. Renal cellular apoptosis was greater in the IH group as shown by an increased cortical Bax/Bcl-2 protein ratio (p< 0.01) and higher fluorometric TUNEL staining (p< 0.001). Finally, 24-hr urinary albumin levels were higher in mice exposed to IH (43.4 μg vs 9.7 μg, p< 0.01), while there were no differences in serum creatinine levels between the two groups. We conclude that IH causes kidney injury that is accompanied by glomerular hypertrophy, mesangial matrix expansion, increased expression of glomerular growth factors and an increased cellular apoptosis. PMID:29389945

Impaired Kidney Function and Associated Factors Among Rural Adults With Disabilities in Taiwan.

PubMed

Chen, Chu-Yeh; Chiu, Wen-Nan; Lin, Yu-Chen; Jane, Sui-Hwi; Chiang, Hsin-Hung; Chen, Mei-Yen

2017-04-01

The results of numerous studies indicate that people with disabilities seek more healthcare than those who are not disabled, particularly for conditions such as chronic kidney disease, cardiovascular disease, and obesity. However, little is known about the incidence of impaired kidney function and its associated factors among adults with disabilities in Taiwan. The aim of this study was to explore the prevalence and factors associated with impaired kidney function among adults with disabilities. This descriptive study was nurse led and was conducted as part of a health promotion program for disadvantaged rural adults with disabilities in Chiayi County, Taiwan. Health screening and a health needs survey were conducted between July and December 2013. Kidney function, physiological biomarkers, health-related behaviors, and demographic characteristics were examined. Eight hundred ten rural adults with disabilities were enrolled. The most common disabilities included physical-related disability (33.1%), intellectual-related disability (26.7%), and hearing and vision impairment (18.6%). The prevalence of impaired kidney function in this population was 85%. According to classification for chronic kidney disease, 68.6% were in Stages 1-2, and 16.8% were in Stages 3-4. Univariate analysis showed that impaired kidney function was significantly associated with lower educational level (p < .001), hearing or vision impairment (p < .001), being overweight or obese (p < .05), high systolic blood pressure (p < .01), fasting blood glucose (p < .001), total cholesterol (p < .001), total triglyceride (p < .05), older age (p < .001), smoking (p < .05), chewing betel nuts (p = .001), and low levels of participation in social activities (p < .05). The final logistic regression model showed that residents with disabilities who were older or had less education, high fasting blood glucose, and high total cholesterol tended to have impaired kidney function after adjustment for other potential confounding variables. Most participants showed impaired kidney function. The factors that were found to relate significantly to this impairment include being overweight, having hyperlipidemia, having hypertension, having high fasting blood glucose, and having an unhealthy lifestyle. Because of the lack of symptoms during the early stages of chronic kidney disease, a community-based health promotion program for these factors is an important element in health advocacy for this vulnerable population.

A best-practice position statement on pregnancy after kidney transplantation: focusing on the unsolved questions. The Kidney and Pregnancy Study Group of the Italian Society of Nephrology.

PubMed

Gianfranca, Cabiddu; Donatella, Spotti; Giuseppe, Gernone; Domenico, Santoro; Gabriella, Moroni; Gina, Gregorini; Franca, Giacchino; Rossella, Attini; Monica, Limardo; Linda, Gammaro; Tullia, Todros; Piccoli, Giorgina Barbara

2018-06-14

Kidney transplantation (KT) is often considered to be the method best able to restore fertility in a woman with chronic kidney disease (CKD). However, pregnancies in KT are not devoid of risks (in particular prematurity, small for gestational age babies, and the hypertensive disorders of pregnancy). An ideal profile of the potential KT mother includes "normal" or "good" kidney function (usually defined as glomerular filtration rate, GFR ≥ 60 ml/min), scant or no proteinuria (usually defined as below 500 mg/dl), normal or well controlled blood pressure (one drug only and no sign of end-organ damage), no recent acute rejection, good compliance and low-dose immunosuppression, without the use of potentially teratogen drugs (mycophenolic acid and m-Tor inhibitors) and an interval of at least 1-2 years after transplantation. In this setting, there is little if any risk of worsening of the kidney function. Less is known about how to manage "non-ideal" situations, such as a pregnancy a short time after KT, or one in the context of hypertension or a failing kidney. The aim of this position statement by the Kidney and Pregnancy Group of the Italian Society of Nephrology is to review the literature and discuss what is known about the clinical management of CKD after KT, with particular attention to women who start a pregnancy in non-ideal conditions. While the experience in such cases is limited, the risks of worsening the renal function are probably higher in cases with markedly reduced kidney function, and in the presence of proteinuria. Well-controlled hypertension alone seems less relevant for outcomes, even if its effect is probably multiplicative if combined with low GFR and proteinuria. As in other settings of kidney disease, superimposed preeclampsia (PE) is differently defined and this impairs calculating its real incidence. No specific difference between non-teratogen immunosuppressive drugs has been shown, but calcineurin inhibitors have been associated with foetal growth restriction and low birth weight. The clinical choices in cases at high risk for malformations or kidney function impairment (pregnancies under mycophenolic acid or with severe kidney-function impairment) require merging clinical and ethical approaches in which, beside the mother and child dyad, the grafted kidney is a crucial "third element".

Cardiorenal Syndrome: New Developments in the Understanding and Pharmacologic Management

PubMed Central

2013-01-01

Summary Cardiorenal syndromes (CRSs) with bidirectional heart-kidney signaling are increasingly being recognized for their association with increased morbidity and mortality. In acute CRS, recognition of the importance of worsening kidney function complicating management of acute decompensated heart failure has led to the examination of this specific outcome in the context of acute heart failure clinical trials. In particular, the role of fluid overload and venous congestion has focused interest in the most effective use of diuretic therapy to relieve symptoms of heart failure while at the same time preserving kidney function. Additionally, many novel vasoactive therapies have been studied in recent years with the hopes of augmenting cardiac function, improving symptoms and patient outcomes, while maintaining or improving kidney function. Similarly, recent advances in our understanding of the pathophysiology of chronic CRS have led to reanalysis of kidney outcomes in pivotal trials in chronic congestive heart failure, and newer trials are including changes in kidney function as well as kidney injury biomarkers as prospectively monitored and adjudicated outcomes. This paper provides an overview of some new developments in the pharmacologic management of acute and chronic CRS, examines several reports that illustrate a key management principle for each subtype, and discusses opportunities for future research. PMID:23929925

Comparison of Recipient Outcomes After Kidney Transplantation: In-House Versus Imported Deceased Donors.

PubMed

Lim, S Y; Gwon, J G; Kim, M G; Jung, C W

2018-05-01

Increased cold ischemia time in cadaveric kidney transplants has been associated with a high rate of delayed graft function (DGF), and even with graft survival. Kidney transplantation using in-house donors reduces cold preservation time. The purpose of this study was to compare the clinical outcomes after transplantation in house and externally. We retrospectively reviewed the medical records of donors and recipients of 135 deceased-donor kidney transplantations performed in our center from March 2009 to March 2016. Among the 135 deceased donors, 88 (65.2%) received the kidneys from in-house donors. Median cold ischemia time of transplantation from in-house donors was shorter than for imported donors (180.00 vs 300.00 min; P < .001). The risks of DGF and slow graft function were increased among the imported versus in-house donors. Imported kidney was independently associated with greater odds of DGF in multivariate regression analysis (odds ratio, 4.165; P = .038). However, the renal function of recipients at 1, 3, 5, and 7 years after transplantation was not significantly different between the 2 groups. Transplantation with in-house donor kidneys was significantly associated with a decreased incidence of DGF, but long-term graft function and survival were similar compared with imported donor kidneys. Copyright © 2018 Elsevier Inc. All rights reserved.

Red Kidney: Kidney Transplant From a Deceased Donor Who Received Massive Blood Transfusion During Cardiopulmonary Bypass.

PubMed

Bell, Richard; Hanif, Faisal; Prasad, Padmini; Ahmad, Niaz

2016-06-01

Here, we present a case of a deceased-donor kidney transplant. The brain-dead donor had received a massive blood transfusion during cardiopulmonary bypass, which lead to hemolysis, hemoglobinuria, acute kidney injury, and renal replacement therapy. The kidney appeared red after in situ flush. Postoperatively, the recipient developed delayed graft function. Protocol biopsy during the postoperative period revealed the widespread deposition of heme pigment in the renal tubules. Massive blood transfusion and cardiopulmonary bypass surgery are associated with hemolysis and heme pigment deposition in the renal tubules, which subsequently lead to acute kidney injury. Kidneys from such donors appear red and, while this does not preclude transplant, are likely to develop delayed graft function.

Stem cells in kidney regeneration.

PubMed

Yokote, Shinya; Yokoo, Takashi

2012-01-01

Currently many efforts are being made to apply regenerative medicine to kidney diseases using several types of stem/progenitor cells, such as mesenchymal stem cells, renal stem/progenitor cells, embryonic stem cells and induced pluripotent stem cells. Stem cells have the ability to repair injured organs and ameliorate damaged function. The strategy for kidney tissue repair is the recruitment of stem cells and soluble reparative factors to the kidney to elicit tissue repair and the induction of dedifferentiation of resident renal cells. On the other hand, where renal structure is totally disrupted, absolute kidney organ regeneration is needed to rebuild a whole functional kidney. In this review, we describe current advances in stem cell research for kidney tissue repair and de novo organ regeneration.

Efficacy and safety of losartan in treatment of hyperuricemia and posttransplantation erythrocytosis: results of a prospective, open, randomized, case-control study.

PubMed

Zhu, X; Chen, J; Han, F; Cheng, M; Xu, L; Zhang, L; Ding, X; Le, Y

2009-11-01

Hyperuricemia and posttransplantation erythrocytosis (PTE) are frequent complications after kidney transplantation and are important risk factors for cardiovascular events. Losartan decreases serum uric acid and hemoglobin (Hb) concentrations and may be a useful agent for treatment of hyperuricemia and PTE. To evaluate the influence of losartan on serum creatinine (SCr), serum uric acid, and hemoglobin (Hb) concentrations in patients after kidney transplantation and to evaluate the safety profile of losartan in these patients. Sixty-six Han Chinese patients (43 men and 23 women; mean [SD] age, 40.45 [11.50] years) were enrolled in the study. All patients had undergone a first cadaveric donor kidney transplantation at least 3 months previously and had stable graft function with SCr concentration less than 176.8 micromol/L and Hb concentration greater than 110 g/L. The patients were divided into 2 groups (losartan group, n = 34; and control group, n = 32) according to the odevity of patient identification number. Patients in the losartan group received losartan, 50 mg/d; patients in the control group did not receive losartan. Each patient was followed up for 6 months. Nine patients in the losartan group and 5 patients in the control group dropped out because of acute renal insufficiency, anemia, acute rejection, or poor compliance. The serum uric acid concentration in the losartan group continuously decreased at months 1, 2, 3, and 6 (P = .12, P = .01, P = .04, and P = .005 compared with baseline, and P = .02, P = .003, P = .02, and P = .006 compared with control), especially in the patients with hyperuricemia (P = .02, P < .001, P = .003, and P < .001 compared with baseline, and P = .02, P = .002, P = .02, and P = .002 compared with control). The Hb level in the losartan group decreased significantly at months 1, 2, 3, and 6 (P = .003, P < .001, P = .004, and P = 0.02 compared with baseline, and P = .001, P < .001, P = .001, and P = .005 compared with control), especially in patients with PTE. In patients without PTE, there was no significant decline in Hb concentration in the losartan group compared with baseline. There was no significant decline in estimated glomerular filtration rate in the losartan group. Losartan may be an effective agent for treatment of hyperuricemia and PTE in Han Chinese patients after kidney transplantation. However, in some patients, losartan may not be safe.

Association of Proteinuria and Incident Atrial Fibrillation in Patients With Intact and Reduced Kidney Function.

PubMed

Molnar, Amber O; Eddeen, Anan Bader; Ducharme, Robin; Garg, Amit X; Harel, Ziv; McCallum, Megan K; Perl, Jeffrey; Wald, Ron; Zimmerman, Deborah; Sood, Manish M

2017-07-06

Early evidence suggests proteinuria is independently associated with incident atrial fibrillation (AF). We sought to investigate whether the association of proteinuria with incident AF is altered by kidney function. Retrospective cohort study using administrative healthcare databases in Ontario, Canada (2002-2015). A total of 736 666 patients aged ≥40 years not receiving dialysis and with no previous history of AF were included. Proteinuria was defined using the urine albumin-to-creatinine ratio (ACR) and kidney function by the estimated glomerular filtration rate (eGFR). The primary outcome was time to AF. Cox proportional models were used to determine the hazard ratio for AF censored for death, dialysis, kidney transplant, or end of follow-up. Fine and Grey models were used to determine the subdistribution hazard ratio for AF, with death as a competing event. Median follow-up was 6 years and 44 809 patients developed AF. In adjusted models, ACR and eGFR were associated with AF ( P <0.0001). The association of proteinuria with AF differed based on kidney function (ACR × eGFR interaction, P <0.0001). Overt proteinuria (ACR, 120 mg/mmol) was associated with greater AF risk in patients with intact (eGFR, 120) versus reduced (eGFR, 30) kidney function (adjusted hazard ratios, 4.5 [95% CI, 4.0-5.1] and 2.6 [95% CI, 2.4-2.8], respectively; referent ACR 0 and eGFR 120). Results were similar in competing risk analyses. Proteinuria increases the risk of incident AF markedly in patients with intact kidney function compared with those with decreased kidney function. Screening and preventative strategies should consider proteinuria as an independent risk factor for AF. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Incorporating Geriatric Assessment into a Nephrology Clinic: Preliminary Data from Two Models of Care.

PubMed

Hall, Rasheeda K; Haines, Carol; Gorbatkin, Steven M; Schlanger, Lynn; Shaban, Hesham; Schell, Jane O; Gurley, Susan B; Colón-Emeric, Cathleen S; Bowling, C Barrett

2016-10-01

Older adults with advanced chronic kidney disease (CKD) experience functional impairment that can complicate CKD management. Failure to recognize functional impairment may put these individuals at risk of further functional decline, nursing home placement, and missed opportunities for timely goals-of-care conversations. Routine geriatric assessment could be a useful tool for identifying older adults with CKD who are at risk of functional decline and provide contextual information to guide clinical decision-making. Two innovative programs were implemented in the Veterans Health Administration that incorporate geriatric assessment into a nephrology visit. In one program, a geriatrician embedded in a nephrology clinic used standardized geriatric assessment tools with individuals with CKD aged 70 and older (Comprehensive Geriatric Assessment for CKD) (CGA-4-CKD). In the second program, a nephrology clinic used comprehensive appointments for individuals aged 75 and older to conduct geriatric assessments and CKD care (Renal Silver). Data on 68 veterans who had geriatric assessments through these programs between November 2013 and May 2015 are reported. In CGA-4-CKD, difficulty with one or more activities of daily living (ADLs), history of falls, and cognitive impairment were each found in 27.3% of participants. ADL difficulty was found in 65.7%, falls in 28.6%, and cognitive impairment in 51.6% of participants in Renal Silver. Geriatric assessment guided care processes in 45.4% (n = 15) of veterans in the CGA-4-CKD program and 37.1% (n = 13) of those in Renal Silver. Findings suggest there is a significant burden of functional impairment in older adults with CKD. Knowledge of this impairment is applicable to CKD management. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

Differences in GFR and Tissue Oxygenation, and Interactions between Stenotic and Contralateral Kidneys in Unilateral Atherosclerotic Renovascular Disease.

PubMed

Herrmann, Sandra M S; Saad, Ahmed; Eirin, Alfonso; Woollard, John; Tang, Hui; McKusick, Michael A; Misra, Sanjay; Glockner, James F; Lerman, Lilach O; Textor, Stephen C

2016-03-07

Atherosclerotic renal artery stenosis (ARAS) can reduce renal blood flow, tissue oxygenation, and GFR. In this study, we sought to examine associations between renal hemodynamics and tissue oxygenation with single-kidney function, pressor hormones, and inflammatory biomarkers in patients with unilateral ARAS undergoing medical therapy alone or stent revascularization. Nonrandomized inpatient studies were performed in patients with unilateral ARAS (>60% occlusion) before and 3 months after revascularization (n=10) or medical therapy (n=20) or patients with essential hypertension (n=32) under identical conditions. The primary study outcome was change in single-kidney GFR. Individual kidney hemodynamics and volume were measured using multidetector computed tomography. Tissue oxygenation (using R(2)* as a measure of deoxyhemoglobin) was determined by blood oxygen level-dependent magnetic resonance imaging at 3 T. Renal vein neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemoattractant protein-1 (MCP-1), and plasma renin activity were measured. Total GFR did not change over 3 months in either group, but the stenotic kidney (STK) GFR rose over time in the stent compared with the medical group (+2.2[-1.8 to 10.5] versus -5.3[-7.3 to -0.3] ml/min; P=0.03). Contralateral kidney (CLK) GFR declined in the stent group (43.6±19.7 to 36.6±19.5 ml/min; P=0.03). Fractional tissue hypoxia fell in the STK (fraction R(2)* >30/s: 22.1%±20% versus 14.9%±18.3%; P<0.01) after stenting. Renal vein biomarkers correlated with the degree of hypoxia in the STK: NGAL(r=0.3; P=0.01) and MCP-1(r=0.3; P=0.02; more so after stenting). Renal vein NGAL was inversely related to renal blood flow in the STK (r=-0.65; P<0.001). Biomarkers were highly correlated between STK and CLK, NGAL (r=0.94; P<0.001), and MCP-1 (r=0.96; P<0.001). These results showed changes over time in single-kidney GFR that were not evident in parameters of total GFR. Furthermore, they delineate the relationship of measurable tissue hypoxia within the STK and markers of inflammation in human ARAS. Renal vein NGAL and MCP-1 indicated persistent interactions between the ischemic kidney and both CLK and systemic levels of inflammatory cytokines. Copyright © 2016 by the American Society of Nephrology.

An unusual case of acute kidney injury due to vancomycin lessons learnt from reliance on eGFR.

PubMed

Barraclough, Katherine; Harris, Marianne; Montessori, Val; Levin, Adeera

2007-08-01

We present a case of renal impairment in an emaciated HIV-infected male that initially went unrecognized because of reliance on serum creatinine and estimated glomerular filtration rate (eGFR). Inaccurate vancomycin dosing led to toxic drug levels (66 mg/l), associated with acute and severe worsening of kidney function. This occurred in the context of escalating doses of vancomycin given in the presence of changing kidney function, albeit kidney function that always remained well within the normal range (serum creatinine 29 - 42 mumol/l). In the absence of other plausible explanations, a presumptive diagnosis of vancomycin nephrotoxicity was made. Given the rarity of this diagnosis in the current era, we discuss the pathophysiology of vancomycin nephrotoxicity. We also explore the potential reasons for inaccuracy of GFR prediction equations in the HIV population, and discuss the potential pitfalls associated with application of eGFR or even serum creatinine without appropriate understanding of their limitations. We believe our case highlights a number of important teaching points: Vancomycin nephrotoxitiy is rare but can occur in the setting of kidney dysfunction. Current assessment of kidney function using creatinine and eGFR requires awareness of the clinical caveats in which these measures may be misleading. Acute changes in kidney function, irrespective of the test used, should be contextualized to the individual situation. Persons with HIV and low muscle mass constitute a specific subgroup in whom assessment of kidney function may be problematic using creatinine. We support ongoing efforts to develop or refine equations for specific unique and easily identifiable populations.

The Impact of the Nitric Oxide (NO)/Soluble Guanylyl Cyclase (sGC) Signaling Cascade on Kidney Health and Disease: A Preclinical Perspective.

PubMed

Krishnan, Shalini M; Kraehling, Jan R; Eitner, Frank; Bénardeau, Agnès; Sandner, Peter

2018-06-09

Chronic Kidney Disease (CKD) is a highly prevalent disease with a substantial medical need for new and more efficacious treatments. The Nitric Oxide (NO), soluble guanylyl cyclase (sGC), cyclic guanosine monophosphate (cGMP) signaling cascade regulates various kidney functions. cGMP directly influences renal blood flow, renin secretion, glomerular function, and tubular exchange processes. Downregulation of NO/sGC/cGMP signaling results in severe kidney pathologies such as CKD. Therefore, treatment strategies aiming to maintain or increase cGMP might have beneficial effects for the treatment of progressive kidney diseases. Within this article, we review the NO/sGC/cGMP signaling cascade and its major pharmacological intervention sites. We specifically focus on the currently known effects of cGMP on kidney function parameters. Finally, we summarize the preclinical evidence for kidney protective effects of NO-donors, PDE inhibitors, sGC stimulators, and sGC activators.

Impact of the Triglycerides to High-Density Lipoprotein Cholesterol Ratio on the Incidence and Progression of CKD: A Longitudinal Study in a Large Japanese Population.

PubMed

Tsuruya, Kazuhiko; Yoshida, Hisako; Nagata, Masaharu; Kitazono, Takanari; Iseki, Kunitoshi; Iseki, Chiho; Fujimoto, Shouichi; Konta, Tsuneo; Moriyama, Toshiki; Yamagata, Kunihiro; Narita, Ichiei; Kimura, Kenjiro; Kondo, Masahide; Asahi, Koichi; Kurahashi, Issei; Ohashi, Yasuo; Watanabe, Tsuyoshi

2015-12-01

The impact of the triglycerides to high-density lipoprotein cholesterol (TG:HDL-C) ratio on chronic kidney disease (CKD) is unclear. Longitudinal cohort study. 124,700 participants aged 39 to 74 years in the Japanese Specific Health Check and Guidance System, including 50,392 men, 74,308 women, 102,900 without CKD, and 21,800 with CKD. Quartiles of TG:HDL-C ratio. Changes in estimated glomerular filtration rate (eGFR) and urinary protein excretion during the 2-year study period. Incident CKD in participants without CKD, and progression of CKD in participants with CKD. In the entire study population, higher quartile of TG:HDL-C ratio at baseline was significantly associated with greater decline in eGFR and increase in urinary protein excretion during the 2-year study period, even after adjustment for confounding factors. A higher ratio was associated with higher risk of incident CKD in participants without CKD and higher risk of rapid decline in eGFR and increase in urinary protein excretion in participants with CKD. Higher TG:HDL-C ratio was more strongly associated with decline in eGFR (P for interaction = 0.002) and with incident CKD (P for interaction = 0.05) in participants with diabetes than without diabetes. Short observation period and single measurement of all variables. A higher TG:HDL-C ratio affects the decline in eGFR and incidence and progression of CKD in the Japanese population. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

[Kidney function and liver transplantation].

PubMed

Gámán, György; Gelley, Fanni; Gerlei, Zsuzsa; Dabasi, Eszter; Görög, Dénes; Fehérvári, Imre; Kóbori, László; Lengyel, Gabriella; Zádori, Gergely; Fazakas, János; Doros, Attila; Sárváry, Enikő; Nemes, Balázs

2013-06-30

In liver cirrhosis renal function decreases as well. Hepatorenal syndrome is the most frequent cause of the decrease, but primary kidney failure, diabetes mellitus and some diseases underlying endstage liver failure (such as hepatitis C virus infection) can also play an important role. In liver transplantation several further factors (total cross-clamping of vena cava inferior, polytransfusion, immunosuppression) impair the renal function, too. The aim of this study was to analyse the changes in kidney function during the first postoperative year after liver transplantation. Retrospective data analysis was performed after primary liver transplantations (n = 319). impaired preoperative renal function increased the devepolment of postoperative complications and the first year cumulative patient survival was significantly worse (91,7% vs 69,9%; p<0,001) in this group. If renal function of the patients increased above 60 ml/min/1,73 m2 after the first year, patient survival was better. Independently of the preoperative kidney function, 76% of the patients had impaired kidney function at the first postoperative year. In this group, de novo diabetes mellitus was more frequently diagnosed (22,5% vs 9,5%; p = 0,023). Selection of personalized immunosuppressive medication has a positive effect on renal function.

Does size matter? Kidney transplant donor size determines kidney function among living donors

PubMed Central

Narasimhamurthy, Meenakshi; Smith, Lachlan M.; Machan, Jason T.; Reinert, Steven E.; Gohh, Reginald Y.; Dworkin, Lance D.; Merhi, Basma; Patel, Nikunjkumar; Beland, Michael D.

2017-01-01

Background Kidney donor outcomes are gaining attention, particularly as donor eligibility criteria continue to expand. Kidney size, a useful predictor of recipient kidney function, also likely correlates with donor outcomes. Although donor evaluation includes donor kidney size measurements, the association between kidney size and outcomes are poorly defined. Methods We examined the relationship between kidney size (body surface area-adjusted total volume, cortical volume and length) and renal outcomes (post-operative recovery and longer-term kidney function) among 85 kidney donors using general linear models and time-to-chronic kidney disease data. Results Donors with the largest adjusted cortical volume were more likely to achieve an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 over a median 24-month follow-up than those with smaller cortical volumes (P <0.001), had a shorter duration of renal recovery (1.3–2.2 versus 32.5 days) and started with a higher eGFR at pre-donation (107–110 versus 91 mL/min/1.73 m2) and immediately post-nephrectomy (∼63 versus 50–51 mL/min/1.73 m2). Similar findings were seen with adjusted total volume and length. Conclusions Larger kidney donors were more likely to achieve an eGFR ≥60 mL/min/1.73 m2 with renal recovery over a shorter duration due to higher pre-donation and initial post-nephrectomy eGFRs. PMID:28638611

Secreted Klotho and FGF23 in chronic kidney disease Stage 1 to 5: a sequence suggested from a cross-sectional study.

PubMed

Pavik, Ivana; Jaeger, Philippe; Ebner, Lena; Wagner, Carsten A; Petzold, Katja; Spichtig, Daniela; Poster, Diane; Wüthrich, Rudolf P; Russmann, Stefan; Serra, Andreas L

2013-02-01

Klotho and fibroblast growth factor 23 (FGF23) are key regulators of mineral metabolism in renal insufficiency. FGF23 levels have been shown to increase early in chronic kidney disease (CKD); however, the corresponding soluble Klotho levels at the different CKD stages are not known. Soluble Klotho, FGF23, parathyroid hormone (PTH), 1,25-dihydroxy vitamin D(3) (1,25D) and other parameters of mineral metabolism were measured in an observational cross-sectional study in 87 patients. Locally weighted scatter plot smoothing function of these parameters were plotted versus estimated glomerular filtration rate (eGFR) to illustrate the pattern of the relationship. Linear and non-linear regression analyses were performed to estimate changes in mineral metabolism parameters per 1mL/min/1.73 m(2) decline. In CKD 1-5, Klotho and 1,25D linearly decreased, whereas both FGF23 and PTH showed a baseline at early CKD stages and then a curvilinear increase. Crude mean Klotho level declined by 4.8 pg/mL (95% CI 3.5-6.2 pg/mL, P < 0.0001) and 1,25D levels by 0.30 ng/L (95% CI 0.18-0.41 ng/L, P < 0.0001) as GFR declined by 1 mL/min/1.73 m(2). After adjustment for age, gender, serum 25-hydroxyvitamin D levels and concomitant medications (calcium, supplemental vitamin D and calcitriol), we estimated that the mean Klotho change was 3.2 pg/mL (95% CI 1.2-5.2 pg/mL, P = 0.0019) for each 1 mL/min/1.73 m(2) GFR change. FGF23 departed from the baseline at an eGFR of 47 mL/min/1.73 m(2) (95% CI 39-56 mL/min/1.73 m(2)), whereas PTH departed at an eGFR of 34 mL/min/1.73 m(2) (95% CI 19-50 mL/min/1.73 m(2)). Soluble Klotho and 1,25D levels decrease and FGF23 levels increase at early CKD stages, whereas PTH levels increase at more advanced CKD stages.

Chronic Kidney Disease Epidemiology Collaboration versus Modification of Diet in Renal Disease equations for renal function evaluation in patients undergoing partial nephrectomy.

PubMed

Shikanov, Sergey; Clark, Melanie A; Raman, Jay D; Smith, Benjamin; Kaag, Matthew; Russo, Paul; Wheat, Jeffrey C; Wolf, J Stuart; Huang, William C; Shalhav, Arieh L; Eggener, Scott E

2010-11-01

A novel equation, the Chronic Kidney Disease Epidemiology Collaboration, has been proposed to replace the Modification of Diet in Renal Disease for estimated glomerular filtration rate due to higher accuracy, particularly in the setting of normal renal function. We compared these equations in patients with 2 functioning kidneys undergoing partial nephrectomy. We assembled a cohort of 1,158 patients from 5 institutions who underwent partial nephrectomy between 1991 and 2009. Only subjects with 2 functioning kidneys were included in the study. The end points were baseline estimated glomerular filtration rate, last followup estimated glomerular filtration rate (3 to 18 months), absolute and percent change estimated glomerular filtration rate ([absolute change/baseline] × 100%), and proportion of newly developed chronic kidney disease stage III. The agreement between the equations was evaluated using Bland-Altman plots and the McNemar test for paired observations. Mean baseline estimated glomerular filtration rate derived from the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration equations were 73 and 77 ml/minute/1.73 m(2), respectively, and following surgery were 63 and 67 ml/minute/1.73 m(2), respectively. Mean percent change estimated glomerular filtration rate was -12% for both equations (p = 0.2). The proportion of patients with newly developed chronic kidney disease stage III following surgery was 32% and 25%, according to the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration equations, respectively (p = 0.001). For patients with 2 functioning kidneys undergoing partial nephrectomy the Chronic Kidney Disease Epidemiology Collaboration equation provides slightly higher glomerular filtration rate estimates compared to the Modification of Diet in Renal Disease equation, with 7% fewer patients categorized as having chronic kidney disease stage III or worse. Copyright © 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Interactive effects of diabetes and impaired kidney function on cognitive performance in old age: a population-based study.

PubMed

Yin, Zhaoxue; Yan, Zhongrui; Liang, Yajun; Jiang, Hui; Cai, Chuanzhu; Song, Aiqin; Feng, Lei; Qiu, Chengxuan

2016-01-12

The interactive effect between diabetes and impaired kidney function on cognitive impairment in older adults has not yet been reported. The aim of this study was to investigate the association of diabetes and impaired kidney function with cognitive impairment among Chinese older people living in a rural area. This cross-sectional study included 1,358 participants (age ≥60 years; 60.5% women) in the population-based Confucius Hometown Aging Project in Shandong, China. Data on demographics, lifestyle factors, health history, use of medications, global cognitive function, and kidney function were collected through structured interviews, clinical examinations, and blood tests. We defined diabetes as a fasting plasma glucose level ≥7.0 mmol/l or use of hypoglycemic agents, impaired kidney function as glomerular filtration rate estimated from cystatin C (eGFRcys) <60 ml/min/1.73 m(2). Cognitive impairment was defined using the education-based cut-off scores of Mini-Mental State Examination (MMSE). Data were analyzed using multiple general linear and logistic regression models. Cognitive impairment was defined in 197 (14.5%) persons. The multi-adjusted β coefficient of MMSE score associated with diabetes was -0.06 (95% confidence interval [CI], -0.16, 0.03); the corresponding figures associated with eGFRcys <60, 60-89.9, and ≥90 ml/min/1.73 m(2) were -0.15 (-0.28, -0.02), -0.01 (-0.10, 0.08), and 0 (reference) (Ptrend = 0.046), respectively. Diabetes and impaired kidney function showed an interactive effect on cognitive impairment ( interaction = 0.02). Compared with individuals having neither diabetes nor impaired kidney function, those with both conditions had a multi-adjusted odds ratio of 4.23 (95% CI, 2.10-8.49) for cognitive impairment. The relative excess risk due to interaction was 2.74. This study suggests that concurrent presence of diabetes and impaired kidney function is associated with a substantial likelihood for cognitive impairment in older adults.

Effects of continuous and pulsatile flows generated by ventricular assist devices on renal function and pathology.

PubMed

Miyamoto, Takuma; Karimov, Jamshid H; Fukamachi, Kiyotaka

2018-03-01

Continuous-flow (CF) left ventricular assist devices (LVADs) are widely used to treat end-stage heart failure. Despite substantial improvement in clinical results, numerous complications remain associated with this technology. Worsening renal function is one, associated with morbidity and mortality in patients supported by CF LVADs. The effects of CF LVAD support on renal function have been investigated since the mid-1990s by many research groups. Area covered: We review the current status of LVAD therapy, experimental results regarding the effects of types of flow generated by LVADs on renal function and pathology, changes in renal function after LVAD implant, the influence of renal function on outcomes, and risk factors for renal dysfunction post implant. This information was obtained through online databases and direct extraction of single studies. Expert commentary: Immediately after CF LVAD implantation, renal function improves temporarily as patients recover from the kidneys' previously low perfusion and congestive state. However, many studies have shown that this initially recovered renal function gradually declines during long-term CF LVAD support. Although it is known that CF LVAD support adversely affects renal function over the long term, just how it does has not yet been clearly defined in terms of clinical symptoms or signs.

Kidney function endpoints in kidney transplant trials: a struggle for power.

PubMed

Ibrahim, A; Garg, A X; Knoll, G A; Akbari, A; White, C A

2013-03-01

Kidney function endpoints are commonly used in randomized controlled trials (RCTs) in kidney transplantation (KTx). We conducted this study to estimate the proportion of ongoing RCTs with kidney function endpoints in KTx where the proposed sample size is large enough to detect meaningful differences in glomerular filtration rate (GFR) with adequate statistical power. RCTs were retrieved using the key word "kidney transplantation" from the National Institute of Health online clinical trial registry. Included trials had at least one measure of kidney function tracked for at least 1 month after transplant. We determined the proportion of two-arm parallel trials that had sufficient sample sizes to detect a minimum 5, 7.5 and 10 mL/min difference in GFR between arms. Fifty RCTs met inclusion criteria. Only 7% of the trials were above a sample size of 562, the number needed to detect a minimum 5 mL/min difference between the groups should one exist (assumptions: α = 0.05; power = 80%, 10% loss to follow-up, common standard deviation of 20 mL/min). The result increased modestly to 36% of trials when a minimum 10 mL/min difference was considered. Only a minority of ongoing trials have adequate statistical power to detect between-group differences in kidney function using conventional sample size estimating parameters. For this reason, some potentially effective interventions which ultimately could benefit patients may be abandoned from future assessment. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

Outcome of organs procured from donors on extracorporeal membrane oxygenation support: an analysis of kidney and liver allograft data.

PubMed

Carter, Timothy; Bodzin, Adam S; Hirose, Hitoshi; West, Sharon; Hasz, Richard; Maley, Warren R; Cavarocchi, Nicholas C

2014-07-01

Extracorporeal membrane oxygenation has become rescue therapy for adults with overwhelming cardiac and/or respiratory failure. Not all patients are saved, creating a new cohort of potential organ donors. This study examines the outcomes of liver and kidney allografts procured from donors on extracorporeal membrane oxygenation (ECMO). A retrospective review was conducted through the local organ procurement organization. Donors on ECMO prior to notification were classified into donation after brain death (DBD) and donation after cardiac death (DCD). We compared short-term outcome data against published standards. Between 1995 and 2012, 97 organs were procured from 41 donors supported on ECMO. There were 68 kidneys donated, 51 were transplanted and 17 discarded. Excluding extended criteria donors, 29 DBD and 13 DCD kidneys were transplanted from donors supported on ECMO. Delayed graft function occurred in 34% of DBD kidneys and 38% of DCD kidneys. Kidney allograft survival at one yr was 93%. Twenty-four livers were procured, nine discarded, and 15 transplanted. Ninety-three percent of liver transplant recipients were alive with graft function at one yr. Donation after brain death kidneys procured from donors on ECMO perform similarly to non-ECMO organs with regard to delayed graft function (DGF), one-yr graft survival and function. Livers from ECMO donors have a higher discard rate than non-ECMO donors, but function similarly at six months and one yr. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model

PubMed Central

Wang, Xuexiang; Johnson, Ashley C.; Williams, Jan M.; White, Tiffani; Chade, Alejandro R.; Zhang, Jie; Liu, Ruisheng; Roman, Richard J.; Lee, Jonathan W.; Kyle, Patrick B.; Solberg-Woods, Leah

2015-01-01

Some studies have reported up to 40% of patients born with a single kidney develop hypertension, proteinuria, and in some cases renal failure. The increased susceptibility to renal injury may be due, in part, to reduced nephron numbers. Notably, children who undergo nephrectomy or adults who serve as kidney donors exhibit little difference in renal function compared with persons who have two kidneys. However, the difference in risk between being born with a single kidney versus being born with two kidneys and then undergoing nephrectomy are unclear. Animal models used previously to investigate this question are not ideal because they require invasive methods to model congenital solitary kidney. In this study, we describe a new genetic animal model, the heterogeneous stock-derived model of unilateral renal agenesis (HSRA) rat, which demonstrates 50%–75% spontaneous incidence of a single kidney. The HSRA model is characterized by reduced nephron number (more than would be expected by loss of one kidney), early kidney/glomerular hypertrophy, and progressive renal injury, which culminates in reduced renal function. Long-term studies of temporal relationships among BP, renal hemodynamics, and renal function demonstrate that spontaneous single-kidney HSRA rats are more likely than uninephrectomized normal littermates to exhibit renal impairment because of the combination of reduced nephron numbers and prolonged exposure to renal compensatory mechanisms (i.e., hyperfiltration). Future studies with this novel animal model may provide additional insight into the genetic contributions to kidney development and agenesis and the factors influencing susceptibility to renal injury in individuals with congenital solitary kidney. PMID:25349207

Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model.

PubMed

Wang, Xuexiang; Johnson, Ashley C; Williams, Jan M; White, Tiffani; Chade, Alejandro R; Zhang, Jie; Liu, Ruisheng; Roman, Richard J; Lee, Jonathan W; Kyle, Patrick B; Solberg-Woods, Leah; Garrett, Michael R

2015-07-01

Some studies have reported up to 40% of patients born with a single kidney develop hypertension, proteinuria, and in some cases renal failure. The increased susceptibility to renal injury may be due, in part, to reduced nephron numbers. Notably, children who undergo nephrectomy or adults who serve as kidney donors exhibit little difference in renal function compared with persons who have two kidneys. However, the difference in risk between being born with a single kidney versus being born with two kidneys and then undergoing nephrectomy are unclear. Animal models used previously to investigate this question are not ideal because they require invasive methods to model congenital solitary kidney. In this study, we describe a new genetic animal model, the heterogeneous stock-derived model of unilateral renal agenesis (HSRA) rat, which demonstrates 50%-75% spontaneous incidence of a single kidney. The HSRA model is characterized by reduced nephron number (more than would be expected by loss of one kidney), early kidney/glomerular hypertrophy, and progressive renal injury, which culminates in reduced renal function. Long-term studies of temporal relationships among BP, renal hemodynamics, and renal function demonstrate that spontaneous single-kidney HSRA rats are more likely than uninephrectomized normal littermates to exhibit renal impairment because of the combination of reduced nephron numbers and prolonged exposure to renal compensatory mechanisms (i.e., hyperfiltration). Future studies with this novel animal model may provide additional insight into the genetic contributions to kidney development and agenesis and the factors influencing susceptibility to renal injury in individuals with congenital solitary kidney. Copyright © 2015 by the American Society of Nephrology.

Silent ureteral stones: impact on kidney function--can treatment of silent ureteral stones preserve kidney function?

PubMed

Marchini, Giovanni S; Vicentini, Fabio C; Mazzucchi, Eduardo; Brito, Arthur; Ebaid, Gustavo; Srougi, Miguel

2012-02-01

To report our experience with silent ureteral stones and expose their true influence on renal function. We analyzed 506 patients who had undergone ureterolithotripsy from January 2005 to May 2010. Silent ureteral stones were calculi found in the absence of any specific or subjective ureteral stone-related symptoms. Of the 506 patients, 27 (5.3%) met these criteria (global cohort). All patients were assessed postoperatively with dimercaptosuccinic acid scintigraphy (DMSA). A difference in relative kidney function of >10% was considered abnormal. Pre- and postoperative comparative DMSA analyses were electively obtained for 9 patients (kidney function cohort). A t test was used to assess the numeric variables, and the chi-square test or Fisher's exact test was used for categorical variables. Two-tailed P<.05 was considered statistically significant. Stones were diagnosed by radiologic abdominal evaluation for nonurologic diseases in 40% and after previous nephrolithiasis treatment in 33%. The primary therapy was ureterolithotripsy in 88%. The mean follow-up time was 23 months. The overall ureteral stone-free rate after 1 and 2 procedures was 96% and 100%, respectively. In the global cohort, the mean pre- and postoperative serum creatinine levels were similar (P=.39), and the mean postoperative function on DMSA was 31%. In the kidney function cohort, no difference was found between the pre- and postoperative DMSA findings (22%±12.1% vs 20%±11.8%; P=.83) and serum creatinine (0.8±0.13 mg/dL vs 1.0±0.21 mg/dL; P=.45). Silent ureteral stones are associated with decreased kidney function present at the diagnosis. Hydronephrosis tends to diminish after stone removal, and kidney function remains unaltered. Copyright © 2012 Elsevier Inc. All rights reserved.

Assessing Intrarenal Non-perfusion and Vascular Leakage in Acute Kidney Injury withzz 19F MRI and Perfluorocarbon Nanoparticles

PubMed Central

Hu, Lingzhi; Chen, Junjie; Yang, Xiaoxia; Senpan, Angana; Allen, John S.; Yanaba, Noriko; Caruthers, Shelton D.; Lanza, Gregory M.; Hammerman, Marc R.; Wickline, Samuel A.

2014-01-01

Purpose We sought to develop a unique sensor-reporter approach for functional kidney imaging that employs circulating perfluorocarbon nanoparticles (PFC NPs) and 19F MRI. Methods Because the detected 19F signal intensity directly reflects local blood volume, and the 19F R1 is linearly proportional to local blood oxygen content (pO2), 19F spin density weighted and T1 weighted images were utilized to generate quantitative functional mapping in both healthy and ischemia-reperfusion (acute kidney injury, AKI) injured mouse kidneys. 1H Blood-Oxygenation-Level-Dependant (BOLD) MRI was also employed as a supplementary approach to facilitate the compressive analysis of renal circulation and its pathological changes in AKI. Results Heterogeneous blood volume distribution and intrarenal oxygenation gradient were confirmed in healthy kidneys by 19F MRI. In a mouse model of AKI, 19F MRI, in conjunction with BOLR MRI, sensitively delineated renal vascular damage and recovery. In the cortico-medullary (CM) junction region, we observed 25% lower 19F signal (p<0.05) and 70% longer 1H T2* (p<0.01) in injured kidneys compared to contralateral kidneys at 24 hours after initial ischemia-reperfusion injury. We also detected 71% higher 19F signal (p<0.01) and 40% lower 1H T2* (p<0.05) in the renal medulla region of injured kidneys compared to contralateral kidneys. Conclusion With demonstrated superior diagnostic capability, functional kidney 19F MRI using PFC NPs could serve as a new diagnostic measures for comprehensive evaluation of renal function and pathology. PMID:23929727

Regulation of mTOR Activity in Snell Dwarf and GH Receptor Gene-Disrupted Mice

PubMed Central

Dominick, Graham; Berryman, Darlene E.; List, Edward O.; Kopchick, John J.; Li, Xinna; Miller, Richard A.

2015-01-01

The involvement of mammalian target of rapamycin (mTOR) in lifespan control in invertebrates, calorie-restricted rodents, and extension of mouse lifespan by rapamycin have prompted speculation that diminished mTOR function may contribute to mammalian longevity in several settings. We show here that mTOR complex-1 (mTORC1) activity is indeed lower in liver, muscle, heart, and kidney tissue of Snell dwarf and global GH receptor (GHR) gene-disrupted mice (GHR−/−), consistent with previous studies. Surprisingly, activity of mTORC2 is higher in fasted Snell and GHR−/− than in littermate controls in all 4 tissues tested. Resupply of food enhanced mTORC1 activity in both controls and long-lived mutant mice but diminished mTORC2 activity only in the long-lived mice. Mice in which GHR has been disrupted only in the liver do not show extended lifespan and also fail to show the decline in mTORC1 and increase in mTORC2 seen in mice with global loss of GHR. The data suggest that the antiaging effects in the Snell dwarf and GHR−/− mice are accompanied by both a decline in mTORC1 in multiple organs and an increase in fasting levels of mTORC2. Neither the lifespan nor mTOR effects appear to be mediated by direct GH effects on liver or by the decline in plasma IGF-I, a shared trait in both global and liver-specific GHR−/− mice. Our data suggest that a more complex pattern of hormonal effects and intertissue interactions may be responsible for regulating both lifespan and mTORC2 function in these mouse models of delayed aging. PMID:25456069

Impact of a quality improvement project on deceased organ donor management

PubMed Central

Olmos, Andrea; Feiner, John; Hirose, Ryutaro; Swain, Sharon; Blasi, Annabel; Roberts, John P.; Niemann, Claus U.

2017-01-01

Context Donors showed poor glucose control in the period between declaration of brain death and organ recovery. The level of hyperglycemia in the donors was associated with a decline in terminal renal function. Objective To determine whether implementation of a quality improvement project improved glucose control and preserved renal function in deceased organ donors. Methods Data collected retrospectively included demographics, medical history, mechanism of death, laboratory values, and data from the United Network for Organ Sharing. Results After implementation of the quality improvement project, deceased donors had significantly lower mean glucose concentrations (mean [SD], 162 [44] vs 212 [42] mg/dL; P < .001) and prerecovery glucose concentration (143 [66] vs 241 [69] mg/dL; P < .001). When the donor cohorts from before and after the quality improvement project were analyzed together, mean glucose concentration remained a significant predictor of terminal creatinine level (P < .001). Multivariate analysis of delayed graft function in kidney recipients matched to donors indicated that higher terminal creatinine level was associated with delayed graft function in recipients (P < .001). Conclusion The quality improvement project improved donor glucose homeostasis, and the data confirm that poor glucose homeostasis is associated with worsening terminal renal function. PMID:26645930

Kidney transplantation: a systematic review of interventional and observational studies of physical activity on intermediate outcomes.

PubMed

Macdonald, Jamie Hugo; Kirkman, Danielle; Jibani, Mahdi

2009-11-01

Kidney transplant patients have decreased quality and longevity of life. Whether exercise can positively affect associated outcomes such as physical functioning, metabolic syndrome, kidney function, and immune function, has only been addressed in relatively small studies. Thus the aim of this systematic review was to determine effects of physical activity level on these intermediate outcomes in kidney transplant patients. We electronically and hand searched to identify 21 studies (6 retrospective assessments of habitual physical activity and 15 intervention studies including 6 controlled trials). After study quality assessment, intermediate outcomes associated with quality and longevity of life were expressed as correlations or percentage changes in addition to effect sizes. Habitual physical activity level was positively associated with quality of life and aerobic fitness and negatively associated with body fat (medium to large effect sizes). Exercise interventions also showed medium to large positive effects on aerobic capacity (10%-114% increase) and muscle strength (10%-22% increase). However, exercise programs had minimal or contradictory effects on metabolic syndrome and immune and kidney function. In kidney transplant patients, physical activity intervention is warranted to enhance physical functioning. Whether exercise impacts on outcomes associated with longevity of life requires further study.

Genomic integration of ERRγ-HNF1β regulates renal bioenergetics and prevents chronic kidney disease.

PubMed

Zhao, Juanjuan; Lupino, Katherine; Wilkins, Benjamin J; Qiu, Chengxiang; Liu, Jian; Omura, Yasuhiro; Allred, Amanda L; McDonald, Caitlin; Susztak, Katalin; Barish, Grant D; Pei, Liming

2018-05-22

Mitochondrial dysfunction is increasingly recognized as a critical determinant of both hereditary and acquired kidney diseases. However, it remains poorly understood how mitochondrial metabolism is regulated to support normal kidney function and how its dysregulation contributes to kidney disease. Here, we show that the nuclear receptor estrogen-related receptor gamma (ERRγ) and hepatocyte nuclear factor 1 beta (HNF1β) link renal mitochondrial and reabsorptive functions through coordinated epigenomic programs. ERRγ directly regulates mitochondrial metabolism but cooperatively controls renal reabsorption via convergent binding with HNF1β. Deletion of ERRγ in renal epithelial cells (RECs), in which it is highly and specifically expressed, results in severe renal energetic and reabsorptive dysfunction and progressive renal failure that recapitulates phenotypes of animals and patients with HNF1β loss-of-function gene mutations. Moreover, ERRγ expression positively correlates with renal function and is decreased in patients with chronic kidney disease (CKD). REC-ERRγ KO mice share highly overlapping renal transcriptional signatures with human patients with CKD. Together these findings reveal a role for ERRγ in directing independent and HNF1β-integrated programs for energy production and use essential for normal renal function and the prevention of kidney disease.

Renal volume assessed by magnetic resonance imaging volumetry correlates with renal function in living kidney donors pre- and postdonation: a retrospective cohort study.

PubMed

Lange, Daniel; Helck, Andreas; Rominger, Axel; Crispin, Alexander; Meiser, Bruno; Werner, Jens; Fischereder, Michael; Stangl, Manfred; Habicht, Antje

2018-07-01

Renal function of potential living kidney donors is routinely assessed with scintigraphy. Kidney anatomy is evaluated by imaging techniques such as magnetic resonance imaging (MRI). We evaluated if a MRI-based renal volumetry is a good predictor of kidney function pre- and postdonation. We retrospectively analyzed the renal volume (RV) in a MRI of 100 living kidney donors. RV was correlated with the tubular excretion rate (TER) of MAG3-scintigraphy, a measured creatinine clearance (CrCl), and the estimated glomerular filtration rate (eGFR) by Cockcroft-Gault (CG), CKD-EPI, and modification of diet in renal disease (MDRD) formula pre- and postdonation during a follow-up of 3 years. RV correlated significantly with the TER (total: r = 0.6735, P < 0.0001). Correlation between RV and renal function was the highest for eGFR by CG (r = 0.5595, P < 0.0001), in comparison with CrCl, MDRD-GFR, and CKD-EPI-GFR predonation. RV significantly correlated with CG-GFR postdonation and predicted CG-GFR until 3 years after donation. MRI renal volumetry might be an alternative technique for the evaluation of split renal function and prediction of renal function postdonation in living kidney donors. © 2018 Steunstichting ESOT.

Association of mGFR of the Remaining Kidney Divided by Its Volume before Donation with Functional Gain in mGFR among Living Kidney Donors

PubMed Central

Gaillard, François; Tissier, Anne-Marie; Fournier, Catherine; Le Nestour, Alexis; Corréas, Jean-Michel; Slimani-Thevenet, Hind; Martinez, Frank; Léon, Carine; Eladari, Dominique; Timsit, Marc-Olivier; Otal, Philippe; Hignette, Chantal; Friedlander, Gérard; Méjean, Arnaud; Houillier, Pascal; Kamar, Nassim; Legendre, Christophe

2016-01-01

Background and objectives The predictors of long–term renal function in living kidney donors are currently discussed. Our objectives were to describe the predictors of functional gain of the remaining kidney after kidney donation. We hypothesized that GFR of the remaining kidney divided by volume of this kidney (rk-GFR/vol) would reflect the density of functional nephrons and be inversely associated with functional gain of the remaining kidney. Design, setting, participants, & measurements We conducted a prospective monocentric study including 63 living donors (26 men; 50.3±11.8 years old) who had been evaluated for 51Cr-EDTA and measured GFR, split renal function by scintigraphy before donation (between 2004 and 2009), and measured GFR at 5.7±0.5 years after donation. For 52 donors, volume of the remaining kidney (measured and estimated with the ellipsoid formula using renal computed tomography scannography) was determined before donation. We tested our hypothesis in an external validation cohort of 39 living donors (13 men; 51.0±9.4 years old) from another single center during the same time period. Results For the main cohort, the mean measured GFR was 97.6±13.0 ml/min per 1.73 m2 before donation and 63.8±9.4 ml/min per 1.73 m2 at 5 years. Functional gain averaged 16.2±7.2 ml/min per 1.73 m2 (+35.3%±16.7%). Multivariate analysis showed that age, body mass index, and rk-GFR/vol at donation were negatively correlated with functional gain and had strong predictive power of the 5-year functional gain (adjusted 5-year functional gain for age: −0.4 [95% confidence interval (95% CI), −0.5 to −0.1]; body mass index: −0.3 [95% CI, −0.6 to −0.1]; rk-GFR/vol: −55.1 [95% CI, −92.3 to −17.9]). We tested this model in the external validation cohort (adjusted 5-year functional gain for age: −0.1 [95% CI, −0.5 to 0.3]; body mass index: −0.9 [95% CI, −1.8 to −0.1]; rk-GFR/vol: −97.6 [95% CI, −137.5 to −57.6]) and confirmed that rk-GFR/vol was inversely associated with 5-year functional gain. Conclusions For given age and body mass index, the long–term functional gain of the remaining kidney is inversely associated with the new variable rk-GFR/vol at donation. PMID:27189317

Cardiovascular risk factors among patients with chronic kidney disease attending a tertiary hospital in Uganda.

PubMed

Babua, Christopher; Kalyesubula, Robert; Okello, Emmy; Kakande, Barbara; Sebatta, Elias; Mungoma, Michael; Mondo, Charles Kiiza

2015-01-01

Chronic kidney disease (CKD) is a risk factor for the development of cardiovascular disease, which is the primary cause of morbidity and mortality in patients with CKD. Local data about cardiovascular risk factors among CKD patients is generally scanty. To determine the prevalence of the common cardiovascular risk factors among patients with CKD attending the nephrology out-patient clinic in Mulago national referral hospital in Uganda. This was a cross-sectional study in which 217 patients with a mean age of 43 years were recruited over a period of nine months. Data on demographic characteristics, risk factors for cardiovascular disease, complete blood count, renal function tests/electrolytes, and lipid profiles were collected using a standardised questionnaire. One hundred and eleven (51.2%) of the participants were male. Hypertension was reported in 90% of participants while cigarette smoking was present in 11.5%. Twenty-two participants (10.2%) were obese and 16.1% were diabetic. A total of 71.9% had a haemoglobin concentration < 11 g/dl, with the prevalence of anaemia increasing with advancing renal failure (p < 0.001); 44.7% were hypocalcaemic and 39.2% had hyperphosphataemia. The prevalence of abnormal calcium and phosphate levels was found to increase with declining renal function (p = 0.004 for calcium and p < 0.001 for phosphate). This study demonstrated that both traditional and non-traditional cardiovascular risk factors occurred frequently in patients with CKD attending the nephrology out-patient clinic at Mulago Hospital.

Evolutionary Nephrology.

PubMed

Chevalier, Robert L

2017-05-01

Progressive kidney disease follows nephron loss, hyperfiltration, and incomplete repair, a process described as "maladaptive." In the past 20 years, a new discipline has emerged that expands research horizons: evolutionary medicine. In contrast to physiologic (homeostatic) adaptation, evolutionary adaptation is the result of reproductive success that reflects natural selection. Evolutionary explanations for physiologically maladaptive responses can emerge from mismatch of the phenotype with environment or evolutionary tradeoffs. Evolutionary adaptation to a terrestrial environment resulted in a vulnerable energy-consuming renal tubule and a hypoxic, hyperosmolar microenvironment. Natural selection favors successful energy investment strategy: energy is allocated to maintenance of nephron integrity through reproductive years, but this declines with increasing senescence after ~40 years of age. Risk factors for chronic kidney disease include restricted fetal growth or preterm birth (life history tradeoff resulting in fewer nephrons), evolutionary selection for APOL1 mutations (that provide resistance to trypanosome infection, a tradeoff), and modern life experience (Western diet mismatch leading to diabetes and hypertension). Current advances in genomics, epigenetics, and developmental biology have revealed proximate causes of kidney disease, but attempts to slow kidney disease remain elusive. Evolutionary medicine provides a complementary approach by addressing ultimate causes of kidney disease. Marked variation in nephron number at birth, nephron heterogeneity, and changing susceptibility to kidney injury throughout life history are the result of evolutionary processes. Combined application of molecular genetics, evolutionary developmental biology (evo-devo), developmental programming and life history theory may yield new strategies for prevention and treatment of chronic kidney disease.

MECHANISMS IN ENDOCRINOLOGY: Kidney involvement in patients with primary hyperparathyroidism: an update on clinical and molecular aspects.

PubMed

Verdelli, C; Corbetta, S

2017-01-01

Primary hyperparathyroidism (PHPT) is the third most common endocrine disease. Kidney is a target of both chronic elevated PTH and calcium in PHPT. The classic PHPT complications of symptomatic kidney stones and nephrocalcinosis have become rare and the PHPT current presentation is asymptomatic with uncertain and long-lasting progression. Nonetheless, the routine use of imaging and of biochemical determinations have revealed the frequent occurrence of asymptomatic kidney stones, hypercalciuria and reduced kidney function in asymptomatic PHPT patients. Though the pathogenesis is far from being elucidated, PHPT is associated with reduced renal function, in terms of estimated glomerular filtration rate, and related increased morbidity and mortality. In the last decade, the effort of the Kidney Disease: Improving Global Outcomes (KDIGO) panel of experts highlighted that even mild reduction of kidney function is associated with increased risk of cardiovascular disease. These considerations provided the basis for the Fourth Workshop recommendations of a more extensive diagnostic workout about kidney features and of wider criteria for parathyroid surgery including asymptomatic kidney disease. Moreover, kidney involvement in PHPT is likely to be affected by variants of genes coding the key molecules regulating the calcium and ions renal handling; these features might have clinical relevance and should be considered both during diagnostic workout and follow-up. Finally, the effects of parathyroid surgery and of medical treatment on kidney involvement of PHPT are reviewed. © 2017 European Society of Endocrinology.

The Interaction Between Thyroid and Kidney Disease: An Overview of the Evidence

PubMed Central

Rhee, Connie M.

2016-01-01

Purpose of Review Hypothyroidism is highly prevalent in chronic kidney disease (CKD) patients, including those receiving dialysis. This review examines potential mechanistic links between thyroid and kidney disease; current evidence for hypothyroidism as a risk factor for de novo CKD and CKD progression; and studies of thyroid functional disorders, cardiovascular disease, and death in the CKD population. Recent Findings Epidemiologic data have demonstrated an incrementally higher prevalence of hypothyroidism with increasing severity of kidney dysfunction. Various thyroid functional test abnormalities are also commonly observed in CKD, due to alterations in thyroid hormone synthesis, metabolism, and regulation. While the mechanistic link between thyroid and kidney disease remains unclear, observational studies suggest hypothyroidism is associated with abnormal kidney structure and function. Previously thought to be a physiologic adaptation, recent studies show that hypothyroidism is associated with higher risk of cardiovascular disease and death in CKD. Summary A growing body of evidence suggests that hypothyroidism is a risk factor for incident CKD, CKD progression, and higher death risk in kidney disease patients. Rigorous studies are needed to determine impact of thyroid hormone replacement upon kidney disease progression, cardiovascular disease, and mortality, which may shed light into the causal implications of hypothyroidism in CKD. PMID:27428519

Role of AMP-activated protein kinase in kidney tubular transport, metabolism, and disease.

PubMed

Rajani, Roshan; Pastor-Soler, Nuria M; Hallows, Kenneth R

2017-09-01

AMP-activated protein kinase (AMPK) is a metabolic sensor that regulates cellular energy balance, transport, growth, inflammation, and survival functions. This review explores recent work in defining the effects of AMPK on various renal tubular epithelial ion transport proteins as well as its role in kidney injury and repair in normal and disease states. Recently, several groups have uncovered additional functions of AMPK in the regulation of kidney and transport proteins. These new studies have focused on the role of AMPK in the kidney in the setting of various diseases such as diabetes, which include evaluation of the effects of the hyperglycemic state on podocyte and tubular cell function. Other recent studies have investigated how reduced kidney mass, polycystic kidney disease (PKD), and fibrosis affect AMPK activation status. A general theme of several conditions that lead to chronic kidney disease (CKD) is that AMPK activity is abnormally suppressed relative to that in normal kidneys. Thus, the idea that AMPK activation may be a therapeutic strategy to slow down the progression of CKD has emerged. In addition to drugs such as metformin and 5-aminoimidazole-4-carboxamide ribonucleotide that are classically used as AMPK activators, recent studies have identified the therapeutic potential of other compounds that function at least partly as AMPK activators, such as salicylates, statins, berberine, and resveratrol, in preventing the progression of CKD. AMPK in the kidney plays a unique role at the crossroads of energy metabolism, ion and water transport, inflammation, and stress. Its potential role in modulating recovery from vs. progression of acute and chronic kidney injury has been the topic of recent research findings. The continued study of AMPK in kidney physiology and disease has improved our understanding of these physiological and pathological processes and offers great hope for therapeutic avenues for the increasing population at risk to develop kidney failure.

Erythropoiesis-stimulating agent use among non-dialysis-dependent CKD patients before and after the trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT) using a large US health plan database.

PubMed

Thamer, Mae; Zhang, Yi; Kshirsagar, Onkar; Cotter, Dennis J; Kaufman, James S

2014-11-01

In a landmark study, TREAT (Trial to Reduce Cardiovascular Events With Aranesp Therapy) examined the use of erythropoiesis-stimulating agent (ESA) therapy to treat anemia among patients with chronic kidney disease (CKD) and found no benefit compared to placebo. A retrospective observational design was used to determine the impact of TREAT on clinical practice. A large US health plan database with more than 1.2 million claims for patients with non-dialysis-dependent CKD stages 3 and 4. ESA prescribing 2 years before and after publication of TREAT. Rate of ESA prescribing for ESA-naive and -prevalent cohorts. (1) Monthly ESA prescribing in the 2 years before and after publication of TREAT (ordinary least squares regression), (2) adjusted likelihood of prescribing ESA after TREAT (clustered logistic regression), and (3) probability of receiving ESA therapy based on anemia status (χ(2) test). For patients with CKD stage 3, the proportion prescribed ESA therapy declined from 17% pre-TREAT to 11% post-TREAT (a 38% decline), and for those with CKD stage 4, from 34% to 27% (a 22% decline). Prescribing of ESA therapy was declining even before TREAT, but the decline accelerated in the post-TREAT period (stage 3: change of slope, -0.08 [P<0.001]; stage 4: change of slope, -0.16 [P<0.001]). ESA prescribing declined after TREAT regardless of anemia status; among patients with hemoglobin levels <10g/dL, only 25% of patients with CKD stage 3 and 33% of patients with stage 4 were prescribed ESAs 2 years after TREAT, a notable 50% decline. After adjusting for all covariates, the probability of prescribing ESAs was 35% lower during the 2-year period after versus before publication of TREAT (OR, 0.65; 95% CI, 0.63-0.67). The cumulative effect of adverse safety concerns in the period before TREAT also influenced physician prescribing of ESA therapy and could not be separated from the influence of TREAT. TREAT appears to be a watershed study that was followed by a marked decline in ESA prescribing for patients with CKD. Copyright © 2014 National Kidney Foundation, Inc. All rights reserved.

The Kidney Research Predicament

PubMed Central

Bryan, Lisa; Ibrahim, Tod; Fischer, Michael J.

2014-01-01

Research funding from public and private sources has reached an all-time low. Economic conditions, sequestration, and a trend of low award success rates have created an imbalance between the supply of highly qualified research investigators and the availability of critically necessary research dollars. This grim environment continues to hinder the success of established investigators and deter potential investigators from joining the research workforce. Without action and support of innovative science, the future of the US health care system is in jeopardy, and its leadership role in medical research will decrease. This work discusses the effects of the decline in research funding, the plight of kidney research, and the impact of the American Society of Nephrology Grants Program on scientists. The ASN also calls on the entire nephrology community to rejuvenate the research environment, improve the lives of millions of people with kidney disease, and ultimately, find a cure. PMID:24652790

Indian chronic kidney disease study: Design and methods.

PubMed

Kumar, Vivek; Yadav, Ashok Kumar; Gang, Sishir; John, Oommen; Modi, Gopesh K; Ojha, Jai Prakash; Pandey, Rajendra; Parameswaran, Sreejith; Prasad, Narayan; Sahay, Manisha; Varughese, Santosh; Baid-Agarwal, Seema; Jha, Vivekanand

2017-04-01

The rate and factors that influence progression of chronic kidney disease (CKD) in developing countries like India are unknown. A pan-country prospective, observational cohort study is needed to address these knowledge gaps. The Indian Chronic Kidney Disease (ICKD) study will be a cohort study of approximately 5000 patients with mild to moderate CKD presenting to centres that represent different geographical regions in India. Time to 50% decline in baseline estimated glomerular filtration rate, need of renal replacement therapy or any new cardiovascular disease (CVD) event or death from CVD are the primary end points. This study will provide the opportunity to determine risk factors for CKD progression and development of CVD in Indian subjects and perform international comparisons to determine ethnic and geographical differences. A bio-repository will provide a chance to discover biomarkers and explore genetic risk factors. © 2016 Asian Pacific Society of Nephrology.

Measuring and Assessing Kidney Function.

PubMed

Vart, Priya; Grams, Morgan E

2016-07-01

Assessment of kidney function is important for the detection and management of chronic kidney disease. The glomerular filtration rate (GFR) and level of albuminuria are two frequently used indices of kidney function assessment. Administration of an exogenous filtration marker to measure GFR and collection of urine for 24 hours to measure albumin excretion generally are considered the gold standard for GFR and albuminuria, respectively, but they are time consuming and onerous for the patient. Thus, in routine clinical practice, other methods are used more frequently to assess GFR and albuminuria. In this review, we discuss the role of GFR and albuminuria in staging of chronic kidney disease as well as the pros and cons and prognostic implications of various methods of assessment of GFR and albuminuria. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of computer tomographic volumetry versus nuclear split renal function to determine residual renal function after living kidney donation.

PubMed

Patankar, Khalil; Low, Ronny Su-Tong; Blakeway, Darryn; Ferrari, Paolo

2014-07-01

Living-donor kidney transplantation is an established practice. Traditionally a combination of renal scintigram and computed tomography (CT) is used to select the kidney that is to be harvested in each donor. To evaluate the ability of split renal volume (SRV) calculated from volumetric examination of CT images compared to nuclear split renal function (nSRF) derived from gamma camera scintigram to predict donor residual single kidney function after donor nephrectomy. This pilot study comprised a retrospective analysis of CT images and renal scintigrams from 12 subsequent live kidney donors who had at least 12 months post-donation renal function follow-up. nSRF derived from the renal scintigram, expressed as the right kidney's function in percent of the total, was 50.2 ± 3.3 (range, 44.1-54.0%) and SRV estimated following analysis of CT imaging was 49.0 ± 2.9 (range, 46.4-52.3%). Although the correlation between nSRF and SRV was moderate (R = 0.46), there was 92% agreement on the dominant kidney if a difference of <2% in nSRF versus SRV was considered. Post-donation glomerular filtration rate (GFR) by CKD-EPI formula was 92 ± 10 mL/min/1.73m2 at 1 year and the correlation between estimated GFR (eGFR) at 1 year and extrapolated single kidney eGFR adjusted by nSRF (R(2 )= 0.69, P = 0.0007) or SRV (R(2 )= 0.74, P = 0.0003) was similar. Calculation of SRV from pre-donation CT examination is a valid method to estimate nSRF with good concordance with nSRF determined by renal scintigram and could replace the latter in the assessment of potential kidney donors. © The Foundation Acta Radiologica 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Structural Predictors of Loss of Renal Function in American Indians with Type 2 Diabetes.

PubMed

Fufaa, Gudeta D; Weil, E Jennifer; Lemley, Kevin V; Knowler, William C; Brosius, Frank C; Yee, Berne; Mauer, Michael; Nelson, Robert G

2016-02-05

Diabetes is the leading cause of kidney failure in the United States, but early structural determinants of renal function loss in type 2 diabetes are poorly defined. We examined the association between morphometrically determined renal structural variables and loss of renal function in 111 American Indians with type 2 diabetes who volunteered for a research kidney biopsy at the end of a 6-year clinical trial designed to test the renoprotective efficacy of losartan versus placebo. Participants were subsequently followed in an observational study, in which annual measurements of GFR (iothalamate) initiated during the clinical trial were continued. Renal function loss was defined as ≥40% loss of GFR from the research examination performed at the time of kidney biopsy. Associations with renal function loss were evaluated by Cox proportional hazards regression. Hazard ratios (HRs) were reported per 1-SD increment for each morphometric variable. Of 111 participants (82% women; baseline mean [±SD] age, 46 years old [±10]; diabetes duration, 16 years [±6]; hemoglobin A1c =9.4% [±2.2]; GFR=147 ml/min [±56]; median albumin-to-creatinine ratio, 41 mg/g [interquartile range, 13-158]), 51 (46%) developed renal function loss during a median follow-up of 6.6 years (interquartile range, 3.1-9.0). Fourteen had baseline GFR <90 ml/min, and three had baseline GFR <60 ml/min. Higher mesangial fractional volume (HR, 2.27; 95% confidence interval [95% CI], 1.58 to 3.26), percentage of global glomerular sclerosis (HR, 1.63; 95% CI, 1.21 to 2.21), nonpodocyte cell number per glomerulus (HR, 1.50; 95% CI, 1.10 to 2.05), glomerular basement membrane width (HR, 1.48; 95% CI, 1.05 to 2.08), mean glomerular volume (HR, 1.42; 95% CI, 1.02 to 1.96), and podocyte foot process width (HR, 1.28; 95% CI, 1.03 to 1.60); lower glomerular filtration surface density (HR, 0.62; 95% CI, 0.41 to 0.94); and fewer endothelial fenestrations (HR, 0.68; 95% CI, 0.48 to 0.95) were each associated with GFR decline after adjustment for baseline age, sex, duration of diabetes, hemoglobin A1c, GFR, and treatment assignment during the clinical trial. Quantitative measures of glomerular structure predict loss of renal function in type 2 diabetes. Copyright © 2016 by the American Society of Nephrology.

Creatinine blood test

MedlinePlus

Serum creatinine; Kidney function - creatinine; Renal function - creatinine ... kidney damage or failure, infection, or reduced blood flow Loss of ... medicine overdose. Your provider will tell you more, if needed.

Incidence and predictors of sarcopenia onset in community-dwelling elderly Japanese women: 4-year follow-up study.

PubMed

Kim, Hunkyung; Suzuki, Takao; Kim, Miji; Kojima, Narumi; Yoshida, Yuko; Hirano, Hirohiko; Saito, Kyoko; Iwasa, Hajime; Shimada, Hiroyuki; Hosoi, Erika; Yoshida, Hideyo

2015-01-01

Several studies have explored the prevalence and risk factors of sarcopenia, but they have been based on cross-sectional data. The objective of this study was to determine the incidence and predictors of the onset of sarcopenia over 4 years in community-dwelling elderly women. Four-year longitudinal follow-up study. Urban community in Tokyo, Japan. A total of 538 nonsarcopenic women older than 75 years. Body composition was determined by bioelectrical impedance analysis. Functional fitness measurements, including grip strength, usual walking speed, timed up and go (TUG), and interview surveys were conducted at baseline and 4-year follow-up. Blood samples were obtained to analyze serum albumin and hemoglobin A1c, and kidney function was analyzed using serum creatinine and cystatin C. Sarcopenia was defined based on the criteria suggested by the European Working Group on Sarcopenia in Older People, and the development of all stages, that is, presarcopenia, sarcopenia, and severe sarcopenia as well as the components of sarcopenia skeletal muscle index (SMI), grip strength, and walking speed, were analyzed. The incidence of total sarcopenia was 39.6% (presarcopenia 23.8%, sarcopenia 11.2%, severe sarcopenia 4.6%). Older age was significantly predictive of the development of presarcopenia and severe sarcopenia. Body mass index (BMI) lower than 21.0 kg/m(2) was significantly predictive of the development of all stages of sarcopenia, as well as declines in SMI, grip strength, and walking speed. Slow TUG was a predictor of the development of presarcopenia and severe sarcopenia. Increased calf circumference showed protective effects from the development of all stages of sarcopenia. Greater albumin levels also showed lower risk of declines in SMI, walking speed, and development of presarcopenia. Cystatin C was positively associated with the development of severe sarcopenia (odds ratio 1.83, 95% confidence interval 1.08-3.12). Heart disease and hyperlipidemia history were associated with presarcopenia and sarcopenia, respectively. Age, BMI, calf circumference, and TUG were consistent predictors of the various stages and components of sarcopenia. The data also suggest that cystatin C was associated with higher odds of incident severe sarcopenia, and further study into kidney function and onset of sarcopenia in large populations is needed. Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

THE KNOCKED-OUT UNILATERAL KIDNEY! CAUSES AND PRESENTATION.

PubMed

Bangash, Kashif; Alam, Asaf; Amin, Mohammed; Anwar, Khursheed

2015-01-01

Due to lack of awareness and non-availability of proper medical facilities in Pakistan, patients with kidney problems tend to seek urological consultation very late when their kidney has already knocked-out. The aim of the study was to find the various presenting complaints of patients having unilateral loss of kidney function and their aetiologies. The study also targeted the patient's awareness regarding their disease. This descriptive case-series of 103 consecutive patients who were diagnosed as having less than 20% of function on DTPA Renal Scan were evaluated. The aetiology of the non-functioning kidney (NFK) was made on either imaging findings or during the exploration, and/or on histopathology if necessary. The results were analysed using SPSS 16.0. Results: The aetiology of the unilateral renal failure included those that were secondary to nephro-pelvic stones in 39.8% and ureteric stones in 14.6%. Of the other aetiologies culminating in a unilateral NFK, 7.8% of the patients had chronic pyelonephritis, 20.4% had PUJO and 5.8% were Genito-urinary Tuberculosis; 3.9% had VUR and were found incidentally, 3.9% developed non-functioning kidney iatrogenically. About 39.8% of the patients knew about their primary disease causing destruction of renal function since long. The remaining 60.2% were unaware that they had developed NFK already when they presented. Proper education through awareness program both for the public and general practitioners can detect early threats to the kidney and hence decrease the loss of a kidney. This will also decrease the number of nephrectomies carried out for the benign condition.

Diabetic kidney disease.

PubMed

Thomas, Merlin C; Brownlee, Michael; Susztak, Katalin; Sharma, Kumar; Jandeleit-Dahm, Karin A M; Zoungas, Sophia; Rossing, Peter; Groop, Per-Henrik; Cooper, Mark E

2015-07-30

The kidney is arguably the most important target of microvascular damage in diabetes. A substantial proportion of individuals with diabetes will develop kidney disease owing to their disease and/or other co-morbidity, including hypertension and ageing-related nephron loss. The presence and severity of chronic kidney disease (CKD) identify individuals who are at increased risk of adverse health outcomes and premature mortality. Consequently, preventing and managing CKD in patients with diabetes is now a key aim of their overall management. Intensive management of patients with diabetes includes controlling blood glucose levels and blood pressure as well as blockade of the renin-angiotensin-aldosterone system; these approaches will reduce the incidence of diabetic kidney disease and slow its progression. Indeed, the major decline in the incidence of diabetic kidney disease (DKD) over the past 30 years and improved patient prognosis are largely attributable to improved diabetes care. However, there remains an unmet need for innovative treatment strategies to prevent, arrest, treat and reverse DKD. In this Primer, we summarize what is now known about the molecular pathogenesis of CKD in patients with diabetes and the key pathways and targets implicated in its progression. In addition, we discuss the current evidence for the prevention and management of DKD as well as the many controversies. Finally, we explore the opportunities to develop new interventions through urgently needed investment in dedicated and focused research. For an illustrated summary of this Primer, visit: http://go.nature.com/NKHDzg.

2,4-Dichlorophenoxyacetic acid effects on nephrotoxicity in rats during late pregnancy and early postnatal periods.

PubMed

Troudi, Afef; Soudani, Nejla; Mahjoubi Samet, Amira; Ben Amara, Ibtissem; Zeghal, Najiba

2011-11-01

2,4-Dichlorophenoxyacetic acid (2,4-D) is largely used as a selective herbicide in Tunisia. The purpose of this study was to investigate the effects of 2,4-D on the kidneys of adult rats and their suckling pups. Female Wistar rats were divided into two groups: the controls and the treated rats that received 600 mg/L of 2,4-D in their drinking water from the 14th day of pregnancy until day 14 after delivery. Exposure to 2,4-D induced nephrotoxicity as evidenced by an increase in thiobarbituric acid reactive substances and protein carbonyl levels and a decrease in antioxidant enzyme activities such as catalase, superoxide dismutase, glutathione peroxidase in the kidneys of suckling pups and their mothers. In addition, a significant decline in kidney glutathione, non-protein thiol and vitamin C levels was also observed. Histological changes, seen in the kidney of mothers and their pups treated with 2,4-D are characterized by a narrowed Bowman's space, tubular epithelial cells degeneration, widened tubular lumen and vascular congestion. Copyright © 2011 Elsevier Inc. All rights reserved.

77 FR 6130 - National Institute of Diabetes and Digestive and Kidney Diseases Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-07

... Diabetes and Digestive and Kidney Diseases Notice of Closed Meeting Pursuant to section 10(d) of the... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; Cellular Biology of Kidney Function and... Research; 93.849, Kidney Diseases, Urology and Hematology Research, National Institutes of Health, HHS...

Notes on the Problems of the Transplantation of Kidneys in Dogs

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

Puza, A.; Drahovsky, V.; Neubauer, E.

1963-01-01

In a group of 29 mongrel dogs kidney homotransplantation was performed. In five dogs an autograft was performed to check the suitability of the surgical technique. In the remaining 24 dogs kidney homografts were carried out, Five dogs served as controls; in these animals the functioning of the homografted kidney stopped after 8 days on the average, In 12 animals an attempt at the induction of immunological tolerance by exsanguinotransfusion, whole-body irradiation and 6-MP-administration was made. Induction of immunological tolerance by total exsanguinotransfusion immediately after birth may render possible a successful homograft even in adult life. The transplanted organ thenmore » exhibits a permanent take and takes over the function of the recipient's removed kidneys. One dog is alive with its single kidney homograft after almost two years. 6-MP administration may lead to such a degree of induced tolerance that the function of a kidney homograft is prolonged by a factor of two to three. Whole-body irradiation within a range of 400 rad (Co 60 source) does not significantly prolong homograft survival.« less

Cerebral Small Vessel Disease and Chronic Kidney Disease

PubMed Central

2015-01-01

Chronic kidney disease, defined by a decreased glomerular filtration rate or albuminuria, is recognized as a major global health burden, mainly because it is an established risk factor for cardiovascular and cerebrovascular diseases. The magnitude of the effect of chronic kidney disease on incident stroke seems to be higher in persons of Asian ethnicity. Since the kidney and brain share unique susceptibilities to vascular injury due to similar anatomical and functional features of small artery diseases, kidney impairment can be predictive of the presence and severity of cerebral small vessel diseases. Chronic kidney disease has been reported to be associated with silent brain infarcts, cerebral white matter lesions, and cerebral microbleeds, independently of vascular risk factors. In addition, chronic kidney disease affects cognitive function, partly via the high prevalence of cerebral small vessel diseases. Retinal artery disease also has an independent relationship with chronic kidney disease and cognitive impairment. Stroke experts are no longer allowed to be ignorant of chronic kidney disease. Close liaison between neurologists and nephrologists can improve the management of cerebral small vessel diseases in kidney patients. PMID:25692105

Renal Function Can Improve at Any Stage of Chronic Kidney Disease

PubMed Central

Weis, Lise; Metzger, Marie; Haymann, Jean-Philippe; Thervet, Eric; Flamant, Martin; Vrtovsnik, François; Gauci, Cédric; Houillier, Pascal; Froissart, Marc; Letavernier, Emmanuel; Stengel, Bénédicte; Boffa, Jean-Jacques

2013-01-01

Introduction Even though renal function decline is considered relentless in chronic kidney disease (CKD), improvement has been shown in patients with hypertensive nephropathy. Whether this can occur in any type of nephropathy and at any stage is unknown as are the features of patients who improve. Methods We identified 406 patients in the NephroTest cohort with glomerular filtration rates (mGFR) measured by 51Cr-EDTA clearance at least 3 times during at least 2 years of follow-up. Individual examination of mGFR trajectories by 4 independent nephrologists classified patients as improvers, defined as those showing a sustained mGFR increase, or nonimprovers. Twelve patients with erratic trajectories were excluded. Baseline data were compared between improvers and nonimprovers, as was the number of recommended therapeutic targets achieved over time (specifically, for systolic and diastolic blood pressure, proteinuria, and use of renin angiotensin system blockers). Results Measured GFR improved over time in 62 patients (15.3%). Their median mGFR slope was +1.88[IQR 1.38, 3.55] ml/min/year; it was −2.23[−3.9, −0.91] for the 332 nonimprovers. Improvers had various nephropathies, but not diabetic glomerulopathy or polycystic kidney disease. They did not differ from nonimprovers for age, sex, cardiovascular history, or CKD stage, but their urinary albumin excretion rate was lower. Improvers achieved significantly more recommended therapeutic targets (2.74±0.87) than nonimprovers (2.44±0.80, p<0.01). They also had fewer CKD-related metabolic complications and a lower prevalence of 25OH-vitamin-D deficiency. Conclusion GFR improvement is possible in CKD patients at any CKD stage through stage 4–5. It is noteworthy that this GFR improvement is associated with a decrease in the number of metabolic complications over time. PMID:24349134

Single Daily Icodextrin Exchange as Initial and Solitary Therapy.

PubMed

Agar, Baris U; Sloand, James A

2018-01-01

Incremental dialysis utilizes gradually increasing dialysis doses in response to declines in residual kidney function, and it is the preferred renal replacement therapy for patients who have just transitioned to end-stage renal disease (ESRD). Incremental peritoneal dialysis (PD) may impose fewer restrictions on patients' lifestyle, help attenuate lifetime peritoneal and systemic exposure to glucose and its degradation products, and minimize connections that could compromise the sterile fluid path. In this study, we utilized a 3-pore kinetic model to assess fluid and solute removal during single daily icodextrin treatments for patients with varying glomerular filtration rates (GFR). Single icodextrin exchanges of 8 to 16 hours using 2- and 2.5-L bag volumes were simulated for different patient transport types (i.e., high to low) to predict daily peritoneal ultrafiltration (UF), daily peritoneal sodium removal, and weekly total (peritoneal + residual kidney) Kt/V (Kt/V Total ) for patients with residual renal GFRs ranging from 0 to 15 mL/min/1.73 m 2 . Daily peritoneal UF varied from 359 to 607 mL, and daily peritoneal Na removal varied from 52 to 87 mEq depending on length of icodextrin exchange and bag volume. Both were effectively independent of patient transport type. All but very large patients (total body water [TBW] > 60 L) were predicted to achieve adequate dialysis (Kt/V Total ≥ 1.7) with a GFR of 10 mL/min/1.73 m 2 , and small patients (TBW: 30 L) were predicted to achieve adequate dialysis with a GFR of 6 mL/min/1.73 m 2 . A single daily icodextrin exchange can be tailored to augment urea, UF, and Na removal in patients with sufficient residual kidney function (RKF). A solitary icodextrin exchange may therefore be reasonable initial therapy for some incident ESRD patients. Copyright © 2018 International Society for Peritoneal Dialysis.

Changes in glomerular parietal epithelial cells in mouse kidneys with advanced age

PubMed Central

Roeder, Sebastian S.; Stefanska, Ania; Eng, Diana G.; Kaverina, Natalya; Sunseri, Maria W.; McNicholas, Bairbre A.; Rabinovitch, Peter; Engel, Felix B.; Daniel, Christoph; Amann, Kerstin; Lichtnekert, Julia; Pippin, Jeffrey W.

2015-01-01

Kidney aging is accompanied by characteristic changes in the glomerulus, but little is known about the effect of aging on glomerular parietal epithelial cells (PECs), nor if the characteristic glomerular changes in humans and rats also occur in very old mice. Accordingly, a descriptive analysis was undertaken in 27-mo-old C57B6 mice, considered advanced age. PEC density was significantly lower in older mice compared with young mice (aged 3 mo), and the decrease was more pronounced in juxtamedullary glomeruli compared with outer cortical glomeruli. In addition to segmental and global glomerulosclerosis in older mice, staining for matrix proteins collagen type IV and heparan sulfate proteoglycan were markedly increased in Bowman's capsules of older mouse glomeruli, consistent with increased extracellular matrix production by PECs. De novo staining for CD44, a marker of activated and profibrotic PECs, was significantly increased in aged glomeruli. CD44 staining was more pronounced in the juxtamedullary region and colocalized with phosphorylated ERK. Additionally, a subset of aged PECs de novo expressed the epithelial-to-mesenchymal transition markers α-smooth muscle and vimentin, with no changes in epithelial-to-mesenchymal transition markers E-cadherin and β-catenin. The mural cell markers neural/glial antigen 2, PDGF receptor-β, and CD146 as well as Notch 3 were also substantially increased in aged PECs. These data show that mice can be used to better understand the aging kidney and that PECs undergo substantial changes, especially in juxtamedullary glomeruli, that may participate in the overall decline in glomerular structure and function with advancing age. PMID:26017974

[Kidney allotransplantation from the AB0-incompatible donors].

PubMed

Goriaĭnov, V A; Kaabak, M M; Babenko, N N; Shishlo, L A; Morozova, M M; Ragimov, A A; Dazhkova, N G; Salimov, E L

2013-01-01

The experience of 28 kidney allotransplantations from the AB0-incompatible donors was analyzed. The comparative group consisted of 38 patients, who received the AB0-compatible organ. The results were assessed using the following parameters: renal function, morphology of the biopsy samples of the transplanted kidney and actuary survival of the recipients with functioning transplants in both groups. The comparative analysis showed no significant difference between the two groups, giving the right to consider the kidney allotransplantation from the AB0-incompatible donors safe and effective.

Prognosis and treatment of diabetic nephropathy: Recent advances and perspectives.

PubMed

Rossing, Peter; Persson, Frederik; Frimodt-Møller, Marie

2018-04-01

Approximately 20 to 40% of patients with type 1 or type 2 diabetes develop diabetic kidney disease. It is a clinical syndrome characterized by persistent albuminuria (>300mg/24h, or 300mg/g creatinine), a relentless decline in glomerular filtration rate, raised arterial blood pressure and enhanced cardiovascular morbidity and mortality. The natural course of classical diabetic nephropathy is initially microalbuminuria or moderately increased urine albumin excretion (30-300mg/g creatinine). Untreated microalbuminuria may then rise gradually, reaching severely increased albuminuric (macroalbuminuria) over 5 to 15 years. Glomerular filtration rate then begins to decline and end-stage renal failure is reached without treatment in 5 to 7 years. Regular, systematic screening for diabetic kidney disease is needed to identify patients at risk for, or with presymptomatic stages of diabetic kidney disease. Multifactorial intervention targeting glucose, lipids and blood pressure including blockade of renin angiotensin system and lifestyle, has improved renal and cardiovascular prognosis and reduced mortality with 50%. Recent data suggest beneficial pleiotropic effects on renal endpoint with new glucose lowering agents. It is also being investigated if blocking aldosterone could be an option as a potential new treatment. Thus, although diabetic nephropathy remains a major burden, prognosis has improved and new options for further improvements are currently tested in phase 3 clinical renal outcome studies. Copyright © 2018 Association Société de néphrologie. Published by Elsevier Masson SAS. All rights reserved.

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

Outcomes after Angiography with Sodium Bicarbonate and Acetylcysteine.

PubMed

Weisbord, Steven D; Gallagher, Martin; Jneid, Hani; Garcia, Santiago; Cass, Alan; Thwin, Soe-Soe; Conner, Todd A; Chertow, Glenn M; Bhatt, Deepak L; Shunk, Kendrick; Parikh, Chirag R; McFalls, Edward O; Brophy, Mary; Ferguson, Ryan; Wu, Hongsheng; Androsenko, Maria; Myles, John; Kaufman, James; Palevsky, Paul M

2018-02-15

Intravenous sodium bicarbonate and oral acetylcysteine are widely used to prevent acute kidney injury and associated adverse outcomes after angiography without definitive evidence of their efficacy. Using a 2-by-2 factorial design, we randomly assigned 5177 patients at high risk for renal complications who were scheduled for angiography to receive intravenous 1.26% sodium bicarbonate or intravenous 0.9% sodium chloride and 5 days of oral acetylcysteine or oral placebo; of these patients, 4993 were included in the modified intention-to-treat analysis. The primary end point was a composite of death, the need for dialysis, or a persistent increase of at least 50% from baseline in the serum creatinine level at 90 days. Contrast-associated acute kidney injury was a secondary end point. The sponsor stopped the trial after a prespecified interim analysis. There was no interaction between sodium bicarbonate and acetylcysteine with respect to the primary end point (P=0.33). The primary end point occurred in 110 of 2511 patients (4.4%) in the sodium bicarbonate group as compared with 116 of 2482 (4.7%) in the sodium chloride group (odds ratio, 0.93; 95% confidence interval [CI], 0.72 to 1.22; P=0.62) and in 114 of 2495 patients (4.6%) in the acetylcysteine group as compared with 112 of 2498 (4.5%) in the placebo group (odds ratio, 1.02; 95% CI, 0.78 to 1.33; P=0.88). There were no significant between-group differences in the rates of contrast-associated acute kidney injury. Among patients at high risk for renal complications who were undergoing angiography, there was no benefit of intravenous sodium bicarbonate over intravenous sodium chloride or of oral acetylcysteine over placebo for the prevention of death, need for dialysis, or persistent decline in kidney function at 90 days or for the prevention of contrast-associated acute kidney injury. (Funded by the U.S. Department of Veterans Affairs Office of Research and Development and the National Health and Medical Research Council of Australia; PRESERVE ClinicalTrials.gov number, NCT01467466 .).

The renin-angiotensin-aldosterone system blockade in patients with advanced diabetic kidney disease.

PubMed

Bermejo, Sheila; García, Carles Oriol; Rodríguez, Eva; Barrios, Clara; Otero, Sol; Mojal, Sergi; Pascual, Julio; Soler, María José

Diabetic kidney disease is the leading cause of end-stage chronic kidney disease. The renin-angiotensin-aldosterone system (RAAS) blockade has been shown to slow the progression of diabetic kidney disease. Our objectives were: to study the percentage of patients with diabetic kidney disease treated with RAAS blockade, to determine its renal function, safety profile and assess whether its administration is associated with increased progression of CKD after 3 years of follow-up. Retrospective study. 197 diabetic kidney disease patients were included and divided into three groups according to the treatment: patients who had never received RAAS blockade (non-RAAS blockade), patients who at some point had received RAAS blockade (inconstant-RAAS blockade) and patients who received RAAS blockade (constant-RAAS blockade). Clinical characteristics and analytical variables such as renal function, electrolytes, glycosylated haemoglobin and glomerular filtration rate according to chronic kidney disease -EPI and MDRD formulas were assessed. We also studied their clinical course (baseline, 1 and 3 years follow-up) in terms of treatment group, survival, risk factors and renal prognosis. Non-RAAS blockade patients had worse renal function and older age (p<0.05) at baseline compared to RAAS blockade patients. Patients who received RAAS blockade were not found to have greater toxicity or chronic kidney disease progression and no differences in renal prognosis were identified. Mortality was higher in non-RAAS blockade patients, older patients and patients with worse renal function (p<0.05). In the multivariate analysis, older age and worse renal function were risk factors for mortality. Treatment with RAAS blockade is more common in diabetic kidney disease patients with eGFR≥30ml/min/1.73m 2 . In our study, there were no differences in the evolution of renal function between the three groups. Older age and worse renal function were associated with higher mortality in patients who did not receive RAAS blockade. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Serum Bicarbonate and Kidney Disease Progression and Cardiovascular Outcome in Patients With Diabetic Nephropathy: A Post Hoc Analysis of the RENAAL (Reduction of End Points in Non-Insulin-Dependent Diabetes With the Angiotensin II Antagonist Losartan) Study and IDNT (Irbesartan Diabetic Nephropathy Trial).

PubMed

Schutte, Elise; Lambers Heerspink, Hiddo J; Lutgers, Helen L; Bakker, Stephan J L; Vart, Priya; Wolffenbuttel, Bruce H R; Umanath, Kausik; Lewis, Julia B; de Zeeuw, Dick; Gansevoort, Ron T

2015-09-01

Low serum bicarbonate level has been reported to be an independent predictor of kidney function decline and mortality in patients with chronic kidney disease. Mechanisms underlying low serum bicarbonate levels may differ in patients with and without diabetes. We aimed to specifically investigate the association of serum bicarbonate level with kidney disease progression and cardiovascular outcome in a cohort of patients with type 2 diabetes and nephropathy. Post hoc analysis of 2 multicenter randomized controlled trials. 2,628 adults with type 2 diabetes and nephropathy. Serum bicarbonate level. Incidence of: (1) end-stage renal disease (ESRD), (2) ESRD or doubling of serum creatinine level, (3) all-cause mortality, (4) cardiovascular events (fatal/nonfatal stroke/myocardial infarction), and (5) heart failure. Serum bicarbonate was measured at baseline as total carbon dioxide. Associations of baseline serum bicarbonate level with end points were investigated using Cox regression models. Serum bicarbonate levels were studied as a continuous variable and stratified in quartiles. Follow-up was 2.8±1.0 (SD) years. Cox regression analyses showed that serum bicarbonate level had inverse associations with incident ESRD (HR, 0.91; 95% CI, 0.89-0.93; P<0.001) and incidence of the combined end point of ESRD or serum creatinine doubling (HR, 0.94; 95% CI, 0.92-0.96; P<0.001). These associations were independent of age, sex, and cardiovascular risk factors, but disappeared after adjustment for baseline estimated glomerular filtration rate (all P>0.05). Analysis of bicarbonate quartiles showed similar results for the quartile with the lowest bicarbonate (≤21 mEq/L) versus the quartile with normal bicarbonate levels (24-26 mEq/L). There was no association of bicarbonate level with cardiovascular events and heart failure. Post hoc analysis and single measurement of serum bicarbonate. In this cohort of patients with type 2 diabetes with nephropathy, serum bicarbonate level associations with kidney disease end points were not retained after adjustment for estimated glomerular filtration rate, which is in contrast to results of earlier studies in nondiabetic populations. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Cardio-renal syndromes: from foggy bottoms to sunny hills.

PubMed

Ronco, Claudio

2011-11-01

"Cardio-renal syndromes" (CRS) are disorders of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. The current definition has been expanded into five subtypes whose etymology reflects the primary and secondary pathology, the time-frame and simultaneous cardiac and renal co-dysfunction secondary to systemic disease: CRS type I: acute worsening of heart function (AHF-ACS) leading to kidney injury and/or dysfunction. CRS type II: chronic abnormalities in heart function (CHF-CHD) leading to kidney injury or dysfunction. CRS type III: acute worsening of kidney function (AKI) leading to heart injury and/or dysfunction. CRS type IV: chronic kidney disease (CKD) leading to heart injury, disease and/or dysfunction. CRS type V: systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney. These different subtypes may have a different pathophysiological mechanism and they may represent separate entities in terms of prevention and therapy.

Soy Protein Alleviates Hypertension and Fish Oil Improves Diastolic Heart Function in the Han:SPRD-Cy Rat Model of Cystic Kidney Disease.

PubMed

Ibrahim, Naser H M; Thandapilly, Sijo J; Jia, Yong; Netticadan, Thomas; Aukema, Harold

2016-05-01

Abnormalities in cardiac structure and function are very common among people with chronic kidney disease, in whom cardiovascular disease is the major cause of death. Dietary soy protein and fish oil reduce kidney disease progression in the Han:SPRD-Cy model of cystic renal disease. However, the effects of these dietary interventions in preventing alterations in cardiac structure and function due to kidney disease (reno-cardiac syndrome) in a cystic kidney disease model are not known. Therefore, weanling Han:SPRD-Cy diseased (Cy/+) and normal (+/+) rats were given diets containing either casein or soy protein, and either soy or fish oil in a three-way design for 8 weeks. Diseased rats had larger hearts, augmented left ventricular mass, and higher systolic and mean arterial blood pressure compared to the normal rats. Assessment of cardiac function using two-dimensional guided M-mode and pulse-wave Doppler echocardiography revealed that isovolumic relaxation time was prolonged in the diseased compared to normal rats, reflecting a diastolic heart dysfunction, and fish oil prevented this elevation. Soy protein resulted in a small improvement in systolic and mean arterial pressure but did not improve diastolic heart function, while fish oil prevented diastolic heart dysfunction in this model of cystic kidney disease.

The effect of prolonged of warm ischaemic injury on renal function in an experimental ex vivo normothermic perfusion system.

PubMed

Hosgood, Sarah A; Shah, K; Patel, M; Nicholson, M L

2015-06-30

Donation after circulatory death (DCD) kidney transplants inevitably sustain a degree of warm ischaemic injury, which is manifested clinically as delayed graft function. The aim of this study was to define the effects of prolonged periods of warm ischaemic injury on renal function in a normothermic haemoperfused kidney model. Porcine kidneys were subjected to 15, 60, 90 (n = 6 per group) and 120 min (n = 4) of in situ warm ischaemia (WI) and then retrieved, flushed with cold preservation fluid and stored in ice for 2 h. Kidneys then underwent 3 h of normothermic reperfusion with a whole blood-based perfusate using an ex vivo circuit developed from clinical grade cardiopulmonary bypass technology. Creatinine clearance, urine output and fractional excretion of sodium deteriorated sequentially with increasing warm time. Renal function was severely compromised after 90 or 120 min of WI but haemodynamic, metabolic and histological parameters demonstrated the viability of kidneys subjected to prolonged warm ischaemia. Isolated kidney perfusion using a warm, oxygenated, red cell-based perfusate allows an accurate ex vivo assessment of the potential for recovery from warm ischaemic injury. Prolonged renal warm ischaemic injury caused a severe decrement in renal function but was not associated with tissue necrosis.

Increased primary non-function in transplanted deceased-donor kidneys flushed with histidine-tryptophan-ketoglutarate solution.

PubMed

Stevens, R B; Skorupa, J Y; Rigley, T H; Yannam, G R; Nielsen, K J; Schriner, M E; Skorupa, A J; Murante, A; Holdaway, E; Wrenshall, L E

2009-05-01

Histidine-Tryptophan-Ketoglutarate (HTK) solution is increasingly used to flush and preserve organ donor kidneys, with efficacy claimed equivalent to University of Wisconsin (UW) solution. We observed and reported increased graft pancreatitis in pancreata flushed with HTK solution, which prompted this review of transplanting HTK-flushed kidneys. We analyzed outcomes of deceased-donor kidneys flushed with HTK and UW solutions with a minimum of 12 months follow-up, excluding pediatric and multi-organ recipients. We evaluated patient and graft survival and rejection rates, variables that might constitute hazards to graft survival and renal function. Two-year patient survival, rejection, renal function and graft survival were not different, but early graft loss (<6 months) was worse in HTK-flushed kidneys (p < 0.03). A Cox analysis of donor grade, cold ischemic time, panel reactive antibodies (PRA), donor race, first vs. repeat transplant, rejection and flush solution showed that only HTK use predicted early graft loss (p < 0.04; relative risk = 3.24), almost exclusively attributable to primary non-function (HTK, n = 5 (6.30%); UW, n = 1 (0.65%); p = 0.02). Delayed graft function and early graft loss with HTK occurred only in lesser grade kidneys, suggesting it should be used with caution in marginal donors.

Suramin protects from cisplatin-induced acute kidney injury

PubMed Central

Dupre, Tess V.; Doll, Mark A.; Shah, Parag P.; Sharp, Cierra N.; Kiefer, Alex; Scherzer, Michael T.; Saurabh, Kumar; Saforo, Doug; Siow, Deanna; Casson, Lavona; Arteel, Gavin E.; Jenson, Alfred Bennett; Megyesi, Judit; Schnellmann, Rick G.; Beverly, Levi J.

2015-01-01

Cisplatin, a commonly used cancer chemotherapeutic, has a dose-limiting side effect of nephrotoxicity. Approximately 30% of patients administered cisplatin suffer from kidney injury, and there are limited treatment options for the treatment of cisplatin-induced kidney injury. Suramin, which is Federal Drug Administration-approved for the treatment of trypanosomiasis, improves kidney function after various forms of kidney injury in rodent models. We hypothesized that suramin would attenuate cisplatin-induced kidney injury. Suramin treatment before cisplatin administration reduced cisplatin-induced decreases in kidney function and injury. Furthermore, suramin attenuated cisplatin-induced expression of inflammatory cytokines and chemokines, endoplasmic reticulum stress, and apoptosis in the kidney cortex. Treatment of mice with suramin 24 h after cisplatin also improved kidney function, suggesting that the mechanism of protection is not by inhibition of tubular cisplatin uptake or its metabolism to nephrotoxic species. If suramin is to be used in the context of cancer, then it cannot prevent cisplatin-induced cytotoxicity of cancer cells. Suramin did not alter the dose-response curve of cisplatin in lung adenocarcinoma cells in vitro. In addition, suramin pretreatment of mice harboring lung adenocarcinomas did not alter the initial cytotoxic effects of cisplatin (DNA damage and apoptosis) on tumor cells. These results provide evidence that suramin has potential as a renoprotective agent for the treatment/prevention of cisplatin-induced acute kidney injury and justify future long-term preclinical studies using cotreatment of suramin and cisplatin in mouse models of cancer. PMID:26661653

Kidney function and plasma copeptin levels in healthy kidney donors and autosomal dominant polycystic kidney disease patients.

PubMed

Zittema, Debbie; van den Berg, Else; Meijer, Esther; Boertien, Wendy E; Muller Kobold, Anneke C; Franssen, Casper F M; de Jong, Paul E; Bakker, Stephan J L; Navis, Gerjan; Gansevoort, Ron T

2014-09-05

Plasma copeptin, a marker of arginine vasopressin, is elevated in patients with autosomal dominant polycystic kidney disease and predicts disease progression. It is unknown whether elevated copeptin levels result from decreased kidney clearance or as compensation for impaired concentrating capacity. Data from patients with autosomal dominant polycystic kidney disease and healthy kidney donors before and after donation were used, because after donation, overall GFR decreases with a functionally normal kidney. Data were obtained between October of 2008 and January of 2012 from healthy kidney donors who visited the institution for routine measurements predonation and postdonation and patients with autosomal dominant polycystic kidney disease who visited the institution for kidney function measurement. Plasma copeptin levels were measured using a sandwich immunoassay, GFR was measured as (125)I-iothalamate clearance, and urine concentrating capacity was measured as urine-to-plasma ratio of urea. In patients with autosomal dominant polycystic kidney disease, total kidney volume was measured with magnetic resonance imaging. Patients with autosomal dominant polycystic kidney disease (n=122, age=40 years, men=56%) had significantly higher copeptin levels (median=6.8 pmol/L; interquartile range=3.4-15.7 pmol/L) compared with donors (n=134, age=52 years, men=49%) both predonation and postdonation (median=3.8 pmol/L; interquartile range=2.8-6.3 pmol/L; P<0.001; median=4.4 pmol/L; interquartile range=3.6-6.1 pmol/L; P<0.001). In donors, copeptin levels did not change after donation, despite a significant fall in GFR (from 105 ± 17 to 66 ± 10; P<0.001). Copeptin and GFR were significantly associated in patients with autosomal dominant polycystic kidney disease (β=-0.45, P<0.001) but not in donors. In patients with autosomal dominant polycystic kidney disease, GFR and total kidney volume were both associated significantly with urine-to-plasma ratio of urea (β=0.84, P<0.001; β=-0.51, P<0.001, respectively). On the basis of the finding in donors that kidney clearance is not a main determinant of plasma copeptin levels, it was hypothesized that, in patients with autosomal dominant polycystic kidney disease, kidney damage and associated impaired urine concentration capacity determine copeptin levels. Copyright © 2014 by the American Society of Nephrology.

Adverse effects of meglumine diatrizoate on renal function in the early post-transplant period.

PubMed

Light, J A; Perloff, L J; Etheredge, E E; Hill, G; Spees, E K

1975-11-01

Thirty-four renal transplant recipients received drip infusion urograms from 2-24 days post-transplantation. Twenty-two patients exhibited changes in renal function within 1-4 days of the urogram that were indistinguishable from allograft rejection: a tender, swollen kidney, elevation of serum creatinine, oliguria, decreased urine sodium concentration, weight gain, and hypertension. Two patients developed acute tubular necrosis and required hemodialysis, but renal function in the remaining 20 patients improved after therapy for "graft rejection" with i.v. methyprednisolone sodium succinnate. Kidneys from older-age donors that were functioning suboptimally and kidneys which exhibited subsequent clinical allograft rejection were more at risk for contrast media toxicity. This suggests that occult vascular lesions may have been present in the allograft which were exacerbated when exposed to the irritant vascular effects of contrast media, producing a mild, reversible toxic nephritis. However, several kidneys with normal function and several kidneys which never exhibited rejection activity were also adversely affected by exposure to contrast media. It appears these agents should be used cautiously, if at all, in the early post-transplant period.

Novel in vivo techniques to visualize kidney anatomy and function.

PubMed

Peti-Peterdi, János; Kidokoro, Kengo; Riquier-Brison, Anne

2015-07-01

Intravital imaging using multiphoton microscopy (MPM) has become an increasingly popular and widely used experimental technique in kidney research over the past few years. MPM allows deep optical sectioning of the intact, living kidney tissue with submicron resolution, which is unparalleled among intravital imaging approaches. MPM has solved a long-standing critical technical barrier in renal research to study several complex and inaccessible cell types and anatomical structures in vivo in their native environment. Comprehensive and quantitative kidney structure and function MPM studies helped our better understanding of the cellular and molecular mechanisms of the healthy and diseased kidney. This review summarizes recent in vivo MPM studies with a focus on the glomerulus and the filtration barrier, although select, glomerulus-related renal vascular and tubular functions are also mentioned. The latest applications of serial MPM of the same glomerulus in vivo, in the intact kidney over several days, during the progression of glomerular disease are discussed. This visual approach, in combination with genetically encoded fluorescent markers of cell lineage, has helped track the fate and function (e.g., cell calcium changes) of single podocytes during the development of glomerular pathologies, and provided visual proof for the highly dynamic, rather than static, nature of the glomerular environment. Future intravital imaging applications have the promise to further push the limits of optical microscopy, and to advance our understanding of the mechanisms of kidney injury. Also, MPM will help to study new mechanisms of tissue repair and regeneration, a cutting-edge area of kidney research.

Patient selection and volume in the era surrounding implementation of Medicare conditions of participation for transplant programs.

PubMed

White, Sarah L; Zinsser, Dawn M; Paul, Matthew; Levine, Gregory N; Shearon, Tempie; Ashby, Valarie B; Magee, John C; Li, Yi; Leichtman, Alan B

2015-04-01

To evaluate evidence of practice changes affecting kidney transplant program volumes, and donor, recipient and candidate selection in the era surrounding the introduction of Centers for Medicare and Medicaid Services (CMS) conditions of participation (CoPs) for organ transplant programs. Scientific Registry of Transplant Recipients; CMS ESRD and Medicare claims databases. Retrospective analysis of national registry data. A Cox proportional hazards model of 1-year graft survival was used to derive risks associated with deceased-donor kidney transplants performed from 2001 to 2010. Among programs with ongoing noncompliance with the CoPs, kidney transplant volumes declined by 38 percent (n = 766) from 2006 to 2011, including a 55 percent drop in expanded criteria donor transplants. Volume increased by 6 percent (n = 638) among programs remaining in compliance. Aggregate risk of 1-year graft failure increased over time due to increasing recipient age and obesity, and longer ESRD duration. Although trends in aggregate risk of 1-year kidney graft loss do not indicate that the introduction of the CoPs has systematically reduced opportunities for marginal candidates or that there has been a systematic shift away from utilization of higher risk deceased donor kidneys, total volume and expanded criteria donor utilization decreased overall among programs with ongoing noncompliance. © Health Research and Educational Trust.

Attenuation of CCl4-Induced Oxidative Stress and Hepatonephrotoxicity by Saudi Sidr Honey in Rats.

PubMed

Al-Yahya, Mohammed; Mothana, Ramzi; Al-Said, Mansour; Al-Dosari, Mohammed; Al-Musayeib, Nawal; Al-Sohaibani, Mohammed; Parvez, Mohammad Khalid; Rafatullah, Syed

2013-01-01

The present study was undertaken to investigate the possible protective effect of Saudi Sidr honey (SSH) on carbon tetrachloride (CCl4) induced oxidative stress and liver and kidney damage in rat. Moreover, the antioxidant activity and the phenolic and flavonoidal contents were determined. The hepatorenal protective activity of the SSH was determined by assessing biochemical, hematological, and histological parameters. Serum transaminases, ALP, GGT, creatinine, bilirubin urea, uric acid, and MDA level in liver and kidney tissues were significantly elevated, and the antioxidant status of nonprotein sulfhydryls, albumin, and total protein levels in liver and kidney were declined significantly in CCl4 alone treated animals. Pretreatment with SSH and silymarin prior to the administration of CCl4 significantly prevented the increase of the serum levels of enzyme markers and reduced oxidative stress. SSH also exhibited a significant lipid-lowering effect and caused an HDL-C enhanced level in serum. The histopathological evaluation of the liver and kidney also revealed that honey protected incidence of both liver and kidney lesions. Moreover, SSH showed a strong antioxidant activity in DPPH and β -carotene-linoleic acid assays. SSH was found to contain phenolic compounds. Additionally, the SSH supplementation restored the hepatocytes viability against 2',7'-dichlorofluorescein (DCF) toxicity in ex vivo test.

Attenuation of CCl4-Induced Oxidative Stress and Hepatonephrotoxicity by Saudi Sidr Honey in Rats

PubMed Central

Al-Yahya, Mohammed; Mothana, Ramzi; Al-Said, Mansour; Al-Dosari, Mohammed; Al-Musayeib, Nawal; Al-Sohaibani, Mohammed; Parvez, Mohammad Khalid; Rafatullah, Syed

2013-01-01

The present study was undertaken to investigate the possible protective effect of Saudi Sidr honey (SSH) on carbon tetrachloride (CCl4) induced oxidative stress and liver and kidney damage in rat. Moreover, the antioxidant activity and the phenolic and flavonoidal contents were determined. The hepatorenal protective activity of the SSH was determined by assessing biochemical, hematological, and histological parameters. Serum transaminases, ALP, GGT, creatinine, bilirubin urea, uric acid, and MDA level in liver and kidney tissues were significantly elevated, and the antioxidant status of nonprotein sulfhydryls, albumin, and total protein levels in liver and kidney were declined significantly in CCl4 alone treated animals. Pretreatment with SSH and silymarin prior to the administration of CCl4 significantly prevented the increase of the serum levels of enzyme markers and reduced oxidative stress. SSH also exhibited a significant lipid-lowering effect and caused an HDL-C enhanced level in serum. The histopathological evaluation of the liver and kidney also revealed that honey protected incidence of both liver and kidney lesions. Moreover, SSH showed a strong antioxidant activity in DPPH and β-carotene-linoleic acid assays. SSH was found to contain phenolic compounds. Additionally, the SSH supplementation restored the hepatocytes viability against 2′,7′-dichlorofluorescein (DCF) toxicity in ex vivo test. PMID:23533498