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Sample records for decreased kidney function

  1. 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.

  2. Blood Lead Levels and Decreased Kidney Function in a Population-Based Cohort.

    PubMed

    Harari, Florencia; Sallsten, Gerd; Christensson, Anders; Petkovic, Marinka; Hedblad, Bo; Forsgard, Niklas; Melander, Olle; Nilsson, Peter M; Borné, Yan; Engström, Gunnar; Barregard, Lars

    2018-04-23

    Environmental lead exposure has been associated with decreased kidney function, but evidence from large prospective cohort studies examining low exposure levels is scarce. We assessed the association of low levels of lead exposure with kidney function and kidney disease. Prospective population-based cohort. 4,341 individuals aged 46 to 67 years enrolled into the Malmö Diet and Cancer Study-Cardiovascular Cohort (1991-1994) and 2,567 individuals subsequently followed up (2007-2012). Blood lead concentrations in quartiles (Q1-Q4) at baseline. Change in estimated glomerular filtration rate (eGFR) between the baseline and follow-up visit based on serum creatinine level alone or in combination with cystatin C level. Chronic kidney disease (CKD) incidence (185 cases) through 2013 detected using a national registry. Multivariable-adjusted linear regression models to assess associations between lead levels and eGFRs at baseline and follow-up and change in eGFRs over time. Cox regression was used to examine associations between lead levels and CKD incidence. Validation of 100 randomly selected CKD cases showed very good agreement between registry data and medical records and laboratory data. At baseline, 60% of study participants were women, mean age was 57 years, and median lead level was 25 (range, 1.5-258) μg/L. After a mean of 16 years of follow-up, eGFR decreased on average by 6mL/min/1.73m 2 (based on creatinine) and 24mL/min/1.73m 2 (based on a combined creatinine and cystatin C equation). eGFR change was higher in Q3 and Q4 of blood lead levels compared with Q1 (P for trend = 0.001). The HR for incident CKD in Q4 was 1.49 (95% CI, 1.07-2.08) compared with Q1 to Q3 combined. Lead level measured only at baseline, moderate number of CKD cases, potential unmeasured confounding. Low-level lead exposure was associated with decreased kidney function and incident CKD. Our findings suggest lead nephrotoxicity even at low levels of exposure. Copyright © 2018 The Authors

  3. Conversion to everolimus in kidney transplant recipients with decreased renal function.

    PubMed

    Inza, A; Balda, S; Alvarez, E; Zárraga, S; Gaínza, F J; Lampreabe, I

    2009-01-01

    Whenever graft function is good and proteinuria is under control, many reports describe the efficacy and safety of the conversion to Everolimus (EVL) among stable kidney recepients, simultaneously withdrawing the calcineurin inhibitor (CNI). However, there are few publications that evaluate the role of EVL in patients with decreased renal function. We describe our experience with 22 stable renal transplant recipients whose serum creatinine concentrations were >2 mg/dL and proteinuria <1000 mg/24 h who underwent an abrupt switch from a CNI to EVL. Conversion was simple, well-tolerated, and safe using an initial dose of 1-3 mg/d that was sufficient to achieve the recommended levels of 3-8 ng/dL. The adverse events were expected; most of them were of medium intensity. Globally, over the 24 months follow-up, there was improved renal function despite the initial creatinine. The improvement was greater when the switch was performed during the first year after transplantation. Two patients lost their grafts after a dramatic evolution with development of nephrotic syndrome and increasing creatinine. In our experience, conversion to EVL is a safe alternative among patients with chronic allograft nephropathy or nephrotoxicity due to CNI, even in patients with significantly decreased renal function at the time of the switch.

  4. Dietary Approach to Recurrent or Chronic Hyperkalaemia in Patients with Decreased Kidney Function

    PubMed Central

    Cupisti, Adamasco; Kovesdy, Csaba P.; D’Alessandro, Claudia

    2018-01-01

    Whereas the adequate intake of potassium is relatively high in healthy adults, i.e., 4.7 g per day, a dietary potassium restriction of usually less than 3 g per day is recommended in the management of patients with reduced kidney function, especially those who tend to develop hyperkalaemia including patients who are treated with angiotensin pathway modulators. Most potassium-rich foods are considered heart-healthy nutrients with high fibre, high anti-oxidant vitamins and high alkali content such as fresh fruits and vegetables; hence, the main challenge of dietary potassium management is to maintain high fibre intake and a low net fixed-acid load, because constipation and metabolic acidosis are per se major risk factors for hyperkalaemia. To achieve a careful reduction of dietary potassium load without a decrease in alkali or fibre intake, we recommend the implementation of certain pragmatic dietary interventions as follows: Improving knowledge and education about the type of foods with excess potassium (per serving or per unit of weight); identifying foods that are needed for healthy nutrition in renal patients; classification of foods based on their potassium content normalized per unit of dietary fibre; education about the use of cooking procedures (such as boiling) in order to achieve effective potassium reduction before eating; and attention to hidden sources of potassium, in particular additives in preserved foods and low-sodium salt substitutes. The present paper aims to review dietary potassium handling and gives information about practical approaches to limit potassium load in chronic kidney disease patients at risk of hyperkalaemia. PMID:29495340

  5. 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, ...

  6. 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.

  7. [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.

  8. 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.

  9. Pre-transplant angiotensin II type 1receptor antibodies: a risk factor for decreased kidney graft function in the early post-transplant period?

    PubMed

    Hernández-Méndez, Erick Alejandro; Arreola-Guerra, José Manuel; Morales-Buenrostro, Luis E; Ramírez, Julia B; Calleja, Said; Castelán, Natalia; Salcedo, Isaac; Vilatobá, Mario; Contreras, Alan G; Gabilondo, Bernardo; Granados, Julio; Alberú, Josefina

    2014-01-01

    Angiotensin II type 1 receptor antibodies (AT1Rab) are associated to a significantly lower graft survival and a higher risk of acute rejection after kidney transplantation. This study aimed to evaluate graft function and BPAR during the 1st year post-transplant (PT) in adult kidney transplant recipients (KTR), between 03/2009 and 08/2012. Pre-KT sera were screened for AT1Rab (ELISA) and HLA-DSA (Luminex). Three groups were analyzed: AT1Rab only (n = 13); HLA-DSA only (n = 8); and no AT1Rab or HLA-DSA (n = 90). No differences were observed in clinical characteristics across groups. A higher percentage of BPAR was observed in the AT1Rab positive group, but this difference was not significant. KTR with AT1Rab had a lower mean eGFR (20 mL/min/1.73m2) when compared to KTR with no Abs at 12 months. The significant difference in eGFR was observed since the 1st month PT. Multivariate analysis showed 4 factors independently and significantly associated with eGFR at 12mos PT: BPAR (-18.7 95%, CI -28.2 to -9.26, p<0.001), AT1Rab (-10.51, CI -20.9 to -0.095, p = 0.048), donor age (-0.42, CI -0.75 to -0.103 p = 0.010), and recipient age (-0.36, CI -0.67 to -0.048, p = 0.024). In this study AT1Rab in pre-transplant sera from KTR, was an independent and significant risk factor contributing to a lower eGFR 12 months. PT. This finding deserves to be confirmed in a larger KTR population.

  10. Nitric Oxide Decreases Acute Kidney Injury and Stage 3 Chronic Kidney Disease after Cardiac Surgery.

    PubMed

    Lei, Chong; Berra, Lorenzo; Rezoagli, Emanuele; Yu, Binglan; Dong, Hailong; Yu, Shiqiang; Hou, Lihong; Chen, Min; Chen, Wensheng; Wang, Hongbing; Zheng, Qijun; Shen, Jie; Jin, Zhenxiao; Chen, Tao; Zhao, Rong; Christie, Emily; Sabbisetti, Venkata S; Nordio, Francesco; Bonventre, Joseph V; Xiong, Lize; Zapol, Warren M

    2018-06-22

    No medical intervention has been identified that decreases acute kidney injury and improves renal outcome at 1-year after cardiac surgery. To determine whether administration of nitric oxide reduces the incidence of post-operative acute kidney injury and improves long-term kidney outcomes after multiple cardiac valve replacement requiring prolonged cardiopulmonary bypass. 244 Patients undergoing elective, multiple valve replacement surgery mostly due to rheumatic fever were randomized to receive either nitric oxide (treatment) or nitrogen (control). Nitric oxide and nitrogen were administered via the gas exchanger during cardiopulmonary bypass and by inhalation for 24h post-operatively. Primary outcome: Oxidation of ferrous plasma oxyhemoglobin to ferric methemoglobin was associated to a reduced post-operative acute kidney injury from 64% (control group) to 50% (nitric oxide) (RR, 95% CI; 0.78, 0.62-0.97;P=0.014). At 90-days, transition to stage 3 chronic kidney disease was reduced from 33% in the controls to 21% in the treatment group (RR, 95%CI; 0.64, 0.41 - 0.99;P=0.024); and at 1-year, from 31% to 18% (RR, 95% CI; 0.59, 0.36 - 0.96;P=0.017). Nitric oxide treatment reduced the overall major adverse kidney events at 30-days (RR, 95% CI; 0.40, 0.18 - 0.92;P=0.016, 90-days (RR, 95% CI; 0.40, 0.17 - 0.92;P=0.015 and 1-year (RR, 95% CI; 0.47, 0.20-1.10;P=0.041). In patients undergoing multiple valve replacement and prolonged cardiopulmonary bypass, administration of nitric oxide decreased the incidence of acute kidney injury, transition to stage 3 chronic kidney disease and major adverse kidney events at 30-days, 90-days, and 1-year. Clinical trial registered with ClinicalTrials.gov (NCT01802619).

  11. Validity of estimated prevalence of decreased kidney function and renal replacement therapy from primary care electronic health records compared with national survey and registry data in the United Kingdom.

    PubMed

    Iwagami, Masao; Tomlinson, Laurie A; Mansfield, Kathryn E; Casula, Anna; Caskey, Fergus J; Aitken, Grant; Fraser, Simon D S; Roderick, Paul J; Nitsch, Dorothea

    2017-04-01

    Anonymous primary care records are an important resource for observational studies. However, their external validity is unknown in identifying the prevalence of decreased kidney function and renal replacement therapy (RRT). We thus compared the prevalence of decreased kidney function and RRT in the Clinical Practice Research Datalink (CPRD) with a nationally representative survey and national registry. Among all people ≥25 years of age registered in the CPRD for ≥1 year on 31 March 2014, we identified patients with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, according to their most recent serum creatinine in the past 5 years using the Chronic Kidney Disease Epidemiology Collaboration equation and patients with recorded diagnoses of RRT. Denominators were the entire population in each age-sex band irrespective of creatinine measurement. The prevalence of eGFR <60 mL/min/1.73 m2 was compared with that in the Health Survey for England (HSE) 2009/2010 and the prevalence of RRT was compared with that in the UK Renal Registry (UKRR) 2014. We analysed 2 761 755 people in CPRD [mean age 53 (SD 17) years, men 49%], of whom 189 581 (6.86%) had an eGFR <60 mL/min/1.73 m2 and 3293 (0.12%) were on RRT. The prevalence of eGFR <60 mL/min/1.73 m2 in CPRD was similar to that in the HSE and the prevalence of RRT was close to that in the UKRR across all age groups in men and women, although the small number of younger patients with an eGFR <60 mL/min/1.73 m2 in the HSE might have hampered precise comparison. UK primary care data have good external validity for the prevalence of decreased kidney function and RRT. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA.

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. Association of serum albumin levels with kidney function decline and incident chronic kidney disease in elders.

    PubMed

    Lang, Joshua; Katz, Ronit; Ix, Joachim H; Gutierrez, Orlando M; Peralta, Carmen A; Parikh, Chirag R; Satterfield, Suzanne; Petrovic, Snezana; Devarajan, Prasad; Bennett, Michael; Fried, Linda F; Cummings, Steven R; Sarnak, Mark J; Shlipak, Michael G

    2018-06-01

    Previous studies in HIV-infected individuals have demonstrated serum albumin to be strongly associated with kidney function decline, independent of urine albumin and inflammatory markers. Lower serum albumin concentrations may be an under-appreciated risk factor for kidney function decline in elders. We performed a cohort analysis in the Health Aging and Body Composition Study, a cohort of well-functioning, bi-racial, community-dwelling elders between the age of 70 and 79 years. We examined the associations of serum albumin concentration with longitudinal kidney function decline by estimated glomerular filtration rate (eGFR). Outcomes included linear eGFR decline, rapid kidney function decline defined as >30% decrease in eGFR, defined as a final eGFR <60 mL/min/1.73 m2 in those with an eGFR >60 mL/min/1.73 m2 at baseline. Cystatin C-based eGFR was calculated at baseline, Year 3 and Year 10. Mean age was 74 years, and mean eGFR was 73 mL/min/1.73 m2 at baseline. The mean rate of eGFR change was 1.81 mL/min/1.73 m2 per year. After multivariate adjustment, lower serum albumin concentrations were strongly and independently associated with kidney function decline (-0.11 mL/min/1.73 m2 per year for each standard deviation decrease serum albumin; -0.01 to - 0.20) with no attenuation after adjustment for urine albumin and inflammatory markers (-0.12, -0.03 to - 0.22). When divided into quartiles, serum albumin levels ≤3.80 g/dL were associated with increased odds of rapid kidney function decline (odds ratio 1.59; 1.12-2.26) and increased risk of incident chronic kidney disease (incident rate ratio 1.29; 1.03-1.62) relative to levels >4.21g/dL. Urine albumin to creatinine ratio (ACR) was also significantly and independently associated with kidney function decline (-0.08 mL/min/1.73 m2 per year for urine ACR >30 mg/g; -0.82 to - 0.13). Lower serum albumin levels are strongly and independently associated with kidney function decline

  19. Kidney function estimating equations in patients with chronic kidney disease.

    PubMed

    Hojs, R; Bevc, S; Ekart, R; Gorenjak, M; Puklavec, L

    2011-04-01

    The current guidelines emphasise the need to assess kidney function using predictive equations rather than just serum creatinine. The present study compares serum cystatin C-based equations and serum creatinine-based equations in patients with chronic kidney disease (CKD). Seven hundred and sixty-four adult patients with CKD were enrolled. In each patient serum creatinine and serum cystatin C were determined. Their glomerular filtration rate (GFR) was estimated using three serum creatinine-based equations [Cockcroft-Gault (C&G), modification of diet in renal disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI)] and two serum cystatin C-based equations [our own cystatin C formula (GFR=90.63 × cystatin C(-1.192) ) and simple cystatin C formula (GFR=100/cystatin C)]. The GFR was measured using (51) CrEDTA clearance. Statistically significant correlation between (51) CrEDTA clearance with serum creatinine, serum cystatin C and all observed formulas was found. The receiver operating characteristic curve analysis (cut-off for GFR 60 ml/min/1.73m(2)) showed that serum cystatin C and both cystatin C formulas had a higher diagnostic accuracy than C&G formula. Bland and Altman analysis for the same cut-off value showed that all formulas except simple cystatin C formula underestimated measured GFR. The accuracy within 30% of estimated (51) CrEDTA clearance values differs according to stages of CKD. Analysis of ability to correctly predict patient's GFR below or above 60 ml/min/1.73m(2) showed statistically significant higher ability for both cystatin C formulas compared to MDRD formula. Our results indicate that serum cystatin C-based equations are reliable markers of GFR comparable with creatinine-based formulas. © 2011 Blackwell Publishing Ltd.

  20. Neurocognitive functions of pediatric kidney transplant recipients.

    PubMed

    Molnar-Varga, Marta; Novak, Marta; Szabo, Attila J; Kelen, Kata; Streja, Elani; Remport, Adam; Mucsi, Istvan; Molnar, Miklos Z; Reusz, Gyorgy

    2016-09-01

    End-stage renal disease (ESRD) in children is associated with impaired neurocognitive function and development. However, data on factors associated with neurocognitive dysfunctions in children with kidney transplants are limited. We conducted a cross-sectional analysis comparing cognitive functions (using the Woodcock-Johnson International Edition, WJIE) in 35 kidney transplant and 35 healthy control children. Data on laboratory measurements, comorbidities, and social characteristics were collected. Transplant children had significantly worse scores on the intelligence quotient (IQ) test compared with controls [Full Scale IQ score 85 (26) vs 107 (10), p <0.001]. Lower maternal education level was significantly associated with lower WJIE cognitive test scores; however, no association was found between laboratory values and WJIE scores. Among children with kidney transplants, those with medical comorbid conditions had significantly lower Verbal Ability and Full Scale IQ scores. Earlier age of dialysis onset and a longer total time on dialysis (>9 months) were associated with lower test scores. Age-standardized duration of hospitalization was inversely correlated with IQ (r = -0.46, p <0.01) and was an independent significant predictor (Beta = -0.38, p = 0.02) of IQ scores in transplanted children. Child kidney transplant recipients have neurocognitive function impairments that are associated with markers of socioeconomic status (SES) and factors related to disease severity.

  1. Renal transplantation induces mitochondrial uncoupling, increased kidney oxygen consumption, and decreased kidney oxygen tension.

    PubMed

    Papazova, Diana A; Friederich-Persson, Malou; Joles, Jaap A; Verhaar, Marianne C

    2015-01-01

    Hypoxia is an acknowledged pathway to renal injury and ischemia-reperfusion (I/R) and is known to reduce renal oxygen tension (Po2). We hypothesized that renal I/R increases oxidative damage and induces mitochondrial uncoupling, resulting in increased oxygen consumption and hence kidney hypoxia. Lewis rats underwent syngenic renal transplantation (TX) and contralateral nephrectomy. Controls were uninephrectomized (1K-CON) or left untreated (2K-CON). After 7 days, urinary excretion of protein and thiobarbituric acid-reactive substances were measured, and after 14 days glomerular filtration rate (GFR), renal blood flow, whole kidney Qo2, cortical Po2, kidney cortex mitochondrial uncoupling, renal oxidative damage, and tubulointerstitial injury were assessed. TX, compared with 1K-CON, resulted in mitochondrial uncoupling mediated via uncoupling protein-2 (16 ± 3.3 vs. 0.9 ± 0.4 pmol O2 · s(-1)· mg protein(-1), P < 0.05) and increased whole kidney Qo2 (55 ± 16 vs. 33 ± 10 μmol O2/min, P < 0.05). Corticomedullary Po2 was lower in TX compared with 1K-CON (30 ± 13 vs. 47 ± 4 μM, P < 0.05) whereas no significant difference was observed between 2K-CON and 1K-CON rats. Proteinuria, oxidative damage, and the tubulointerstitial injury score were not significantly different in 1K-CON and TX. Treatment of donors for 5 days with mito-TEMPO reduced mitochondrial uncoupling but did not affect renal hemodynamics, Qo2, Po2, or injury. Collectively, our results demonstrate increased mitochondrial uncoupling as an early event after experimental renal transplantation associated with increased oxygen consumption and kidney hypoxia in the absence of increases in markers of damage. Copyright © 2015 the American Physiological Society.

  2. Baseline kidney function as predictor of mortality and kidney disease progression in HIV-positive patients.

    PubMed

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

    2012-10-01

    Chronic kidney disease (CKD) is associated with increased all-cause mortality and kidney disease progression. Decreased kidney function at baseline may identify human immunodeficiency virus (HIV)-positive patients at increased risk of death and kidney disease progression. Observational cohort study. 7 large HIV cohorts in the United Kingdom with kidney function data available for 20,132 patients. Baseline estimated glomerular filtration rate (eGFR). Death and progression to stages 4-5 CKD (eGFR <30 mL/min/1.73 m(2) for >3 months) in Cox proportional hazards and competing-risk regression models. Median age at baseline was 34 (25th-75th percentile, 30-40) years, median CD4 cell count was 350 (25th-75th percentile, 208-520) cells/μL, and median eGFR was 100 (25th-75th percentile, 87-112) mL/min/1.73 m(2). Patients were followed up for a median of 5.3 (25th-75th percentile, 2.0-8.9) years, during which 1,820 died and 56 progressed to stages 4-5 CKD. A U-shaped relationship between baseline eGFR and mortality was observed. After adjustment for potential confounders, eGFRs <45 and >105 mL/min/1.73 m(2) remained associated significantly with increased risk of death. Baseline eGFR <90 mL/min/1.73 m(2) was associated with increased risk of kidney disease progression, with the highest incidence rates of stages 4-5 CKD (>3 events/100 person-years) observed in black patients with eGFR of 30-59 mL/min/1.73 m(2) and those of white/other ethnicity with eGFR of 30-44 mL/min/1.73 m(2). The relatively small numbers of patients with decreased eGFR at baseline and low rates of progression to stages 4-5 CKD and lack of data for diabetes, hypertension, and proteinuria. Although stages 4-5 CKD were uncommon in this cohort, baseline eGFR allowed the identification of patients at increased risk of death and at greatest risk of kidney disease progression. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  3. A patient with heart failure and worsening kidney function.

    PubMed

    Sarnak, Mark J

    2014-10-07

    There is high prevalence of CKD, defined by reduced GFR, in patients with heart failure. Reduced kidney function is associated with increased morbidity and mortality in this patient population. The cardiorenal syndrome (CRS) involves a bidirectional relationship between the heart and kidneys whereby dysfunction in either may exacerbate the function of the other, but this syndrome has been difficult to precisely define because it has many complex physiologic, biochemical, and hormonal abnormalities. The pathophysiology of CRS is not completely understood, but potential mechanisms include reduced kidney perfusion due to decreased forward flow, increased right ventricular and venous pressure, and neurohormonal adaptations. Treatment options include inotropic medications; diuretics; ultrafiltration; and medications, such as β-blockers, inhibitors of the renin-angiotensin-aldosterone system, and more novel treatments that focus on unique aspects of the pathophysiology. Recent observational studies suggest that treatments that result in a decrease in venous pressure and lead to hemoconcentration may be associated with improved outcomes. Patients with CRS that is not responsive to medical interventions should be considered for ventricular assist devices, heart transplantation, or combined heart and kidney transplantation. Copyright © 2014 by the American Society of Nephrology.

  4. Prenatal lead exposure and childhood blood pressure and kidney function.

    PubMed

    Skröder, Helena; Hawkesworth, Sophie; Moore, Sophie E; Wagatsuma, Yukiko; Kippler, Maria; Vahter, Marie

    2016-11-01

    Exposure to lead, a common environmental pollutant, is known to cause cardiovascular and nephrotoxic effects in adults. Potential effects of early-life lead exposure on these functions are, however, less well characterized. To assess blood pressure and kidney function in preschool-aged children in relation to prenatal lead exposure. This prospective study in rural Bangladesh measured children's systolic and diastolic blood pressure in triplicate at the follow-up at 4.5±0.11 years. Their kidney function was assessed by the estimated glomerular filtration rate (eGFR), calculated based on serum cystatin C concentrations, and by kidney volume, measured by sonography. Exposure to lead was assessed by concentrations in the mothers' blood (erythrocyte fraction; Ery-Pb) in gestational weeks (GW) 14 and 30, the effects of which were evaluated separately in multivariable-adjusted linear regression analyses. We found no associations between maternal exposure to lead [n~1500 for GW14 and 700 for GW30] and children's blood pressure or eGFR. However, we found an inverse association between late gestation lead and kidney volume, although the sample size was limited (n=117), but not with early gestation lead (n=573). An increase of 85µg/kg in Ery-Pb (median concentration at GW30) was associated with a 6.0cm 3 /m 2 decrease in kidney volume (=0.4SD; p=0.041). After stratifying on gender, there seemed to be a somewhat stronger association in girls. Prenatal lead exposure may cause long-lasting effects on the kidney. This warrants follow-up studies in older children, as well as additional studies in other populations. Copyright © 2016. Published by Elsevier Inc.

  5. 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.

  6. 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.

  7. Baseline Kidney Function as Predictor of Mortality and Kidney Disease Progression in HIV-Positive Patients

    PubMed Central

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

    2012-01-01

    Background Chronic kidney disease (CKD) is associated with increased all-cause mortality and kidney disease progression. Decreased kidney function at baseline may identify human immunodeficiency virus (HIV)-positive patients at increased risk of death and kidney disease progression. Study Design Observational cohort study. Setting & Participants 7 large HIV cohorts in the United Kingdom with kidney function data available for 20,132 patients. Predictor Baseline estimated glomerular filtration rate (eGFR). Outcomes Death and progression to stages 4-5 CKD (eGFR <30 mL/min/1.73 m2 for >3 months) in Cox proportional hazards and competing-risk regression models. Results Median age at baseline was 34 (25th-75th percentile, 30-40) years, median CD4 cell count was 350 (25th-75th percentile, 208-520) cells/μL, and median eGFR was 100 (25th-75th percentile, 87-112) mL/min/1.73 m2. Patients were followed up for a median of 5.3 (25th-75th percentile, 2.0-8.9) years, during which 1,820 died and 56 progressed to stages 4-5 CKD. A U-shaped relationship between baseline eGFR and mortality was observed. After adjustment for potential confounders, eGFRs <45 and >105 mL/min/1.73 m2 remained associated significantly with increased risk of death. Baseline eGFR <90 mL/min/1.73 m2 was associated with increased risk of kidney disease progression, with the highest incidence rates of stages 4-5 CKD (>3 events/100 person-years) observed in black patients with eGFR of 30-59 mL/min/1.73 m2 and those of white/other ethnicity with eGFR of 30-44 mL/min/1.73 m2. Limitations The relatively small numbers of patients with decreased eGFR at baseline and low rates of progression to stages 4-5 CKD and lack of data for diabetes, hypertension, and proteinuria. Conclusions Although stages 4-5 CKD were uncommon in this cohort, baseline eGFR allowed the identification of patients at increased risk of death and at greatest risk of kidney disease progression. PMID:22521282

  8. 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

  9. Kidney stones and kidney function loss: a cohort study.

    PubMed

    Alexander, R Todd; Hemmelgarn, Brenda R; Wiebe, Natasha; Bello, Aminu; Morgan, Catherine; Samuel, Susan; Klarenbach, Scott W; Curhan, Gary C; Tonelli, Marcello

    2012-08-29

    To investigate whether the presence of kidney stones increase the risk of end stage renal disease (ESRD) or other adverse renal outcomes. A registry cohort study using validated algorithms based on claims and facility utilisation data. Median follow-up of 11 years. Alberta, Canada, between 1997 and 2009. 3,089,194 adult patients without ESRD at baseline or a history of pyelonephritis. Of these, 1,954,836 had outpatient serum creatinine measurements and were included in analyses of chronic kidney disease and doubling of serum creatinine level. One or more kidney stones during follow-up. Incident ESRD, development of stage 3b-5 chronic kidney disease (estimated glomerular filtration rate <45 mL/min/1.73 m(2)), and sustained doubling of serum creatinine concentration from baseline. 23,706 (0.8%) patients had at least one kidney stone, 5333 (0.2%) developed ESRD, 68,525 (4%) developed stage 3b-5 chronic kidney disease, and 6581 (0.3%) experienced sustained doubling of serum creatinine. Overall, one or more stone episodes during follow-up was associated with increased risk of ESRD (adjusted hazard ratio 2.16 (95% CI 1.79 to 2.62)), new stage 3b-5 chronic kidney disease (hazard ratio 1.74 (1.61 to 1.88)), and doubling of serum creatinine (hazard ratio 1.94 (1.56 to 2.43)), all compared with those without kidney stones during follow-up. The excess risk of adverse outcomes associated with at least one episode of stones seemed greater in women than in men, and in people aged <50 years than in those aged ≥ 50. However, the risks of all three adverse outcomes in those with at least one episode of stones were significantly higher than in those without stones in both sexes and age strata. The absolute increase in the rate of adverse renal outcomes associated with stones was small: the unadjusted rate of ESRD was 2.48 per million person days in people with one or more episodes of stones versus 0.52 per million person days in people without stones. Even a single kidney stone

  10. Left ventricular function before and after kidney transplantation.

    PubMed

    Omran, Mohammad T; Khakpour, Somayeh; Oliaie, Farshid

    2009-06-01

    To evaluate left ventricular function by echocardiography before and after kidney transplantation (KT). This analytical study included 50 patients that had successful KT in Shahid Beheshti Hospital, Babol, Iran from October 2005 to December 2007. The echocardiography study was performed by one cardiologist before and at least 3 months after KT. Data were analyzed by SPSS, and a p<0.05 was considered statistically significant. The mean age of patients was 33.94 +/- 11.66 years, 66% were male and 56% less than 45 years old. The ejection fraction and stroke volume after KT increased, however, the left ventricular end diastolic volume, left ventricular end systolic volume, left ventricular end systolic dimension, and left ventricular end diastolic diameter decreased. In patients with end stage renal disease, successful kidney transplantation could improve the function of the left ventricle.

  11. Resveratrol Rescues Kidney Mitochondrial Function Following Hemorrhagic Shock

    PubMed Central

    Wang, Hao; Guan, Yuxia; Karamercan, Mehmet Akif; Ye, Lan; Bhatti, Tricia; Becker, Lance B.; Baur, Joseph A.; Sims, Carrie A.

    2015-01-01

    Objective Hemorrhagic shock may contribute to acute kidney injury by profoundly altering renal mitochondrial function. Resveratrol (RSV), a naturally occurring sirtuin-1 (SIRT1) activator, has been shown to promote mitochondrial function and reduce oxidative damage in a variety of aging-related disease states. We hypothesized that RSV treatment during resuscitation would ameliorate kidney mitochondrial dysfunction and decrease oxidative damage following hemorrhagic shock. Method Using a decompensated hemorrhagic shock model, male Long-Evans rats (n=6 per group) were sacrificed prior to hemorrhage (Sham), at severe shock, and following either lactated Ringer’s (LR) Resuscitation or LR+RSV Resuscitation (RSV: 30mg/kg). At each time point, blood samples were assayed for arterial blood gases, lactate, blood urea nitrogen (BUN) and serum creatinine. Mitochondria were also isolated from kidney samples in order to assess individual electron transport complexes (CI, CII, and CIV) using high-resolution respirometry. Total mitochondria reactive oxygen species (ROS) were measured using fluorometry and lipid peroxidation was assessed by measuring 4-hydroxynonenal by Western blot. qPCR was used quantify mRNA from PGC1-α, SIRT1, and proteins known to mitigate oxidative damage and promote mitochondrial biogenesis. Results RSV supplementation during resuscitation restored mitochondrial respiratory capacity, decreased mitochondrial ROS and lipid peroxidation. Compared to standard LR resuscitation, RSV treatment significantly increased SIRT1 and PGC1-α expression and significantly increased both SOD2 and catalase expression. Although RSV was associated with decreased lactate production, pH, BUN and serum creatinine values did not differ between resuscitation strategies. Conclusions Resuscitation with RSV significantly restored renal mitochondrial function and decreased oxidative damage following hemorrhagic shock. PMID:25895148

  12. The decreased growth performance and impaired immune function and structural integrity by dietary iron deficiency or excess are associated with TOR, NF-κB, p38MAPK, Nrf2 and MLCK signaling in head kidney, spleen and skin of grass carp (Ctenopharyngodon idella).

    PubMed

    Guo, Yan-Lin; Jiang, Wei-Dan; Wu, Pei; Liu, Yang; Zhou, Xiao-Qiu; Kuang, Sheng-Yao; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Feng, Lin

    2017-06-01

    This study was conducted to investigate the effects of dietary iron on the growth, and immune function and structural integrity in head kidney, spleen and skin as well as the underlying signaling of young grass carp (Ctenopharyngodon idella). Total 630 grass carp (242.32 ± 0.58 g) were fed diets containing graded levels of iron at 12.15 (basal diet), 35.38, 63.47, 86.43, 111.09, 136.37 mg/kg (diets 2-6 were added with ferrous fumarate) and 73.50 mg/kg (diet 7 was added with ferrous sulfate) diet for 60 days. Then, a challenge test was conducted by infection of Aeromonas hydrophila for 14 days. The results firstly showed that compared with optimal iron level, iron deficiency decreased lysozyme (LZ) and acid phosphatase (ACP) activities, complement 3 (C3), C4 and immunoglobulin M (IgM) contents and down-regulated the mRNA levels of antibacterial peptides, anti-inflammatory cytokines, inhibitor of κBα (IκBα), target of rapamycin (TOR) and ribosomal protein S6 kinase 1 (S6K1), whereas up-regulated the mRNA levels of pro-inflammatory cytokines, nuclear factor kappa B (NF-κB) p65, IκB kinases β (IKKβ) and eIF4E-binding protein (4E-BP) in head kidney and spleen of young grass carp (P < 0.05), indicating that iron deficiency impaired immune function in head kidney and spleen of fish. Secondly, iron deficiency down-regulated the mRNA levels of B-cell lymphoma-2 (Bcl-2), myeloid cell leukemia 1 (Mcl-1), and inhibitor of apoptosis protein (IAP), and decreased activities and mRNA levels of antioxidant enzymes, down-regulated the mRNA levels of NF-E2-related factor 2 (Nrf2) and tight junction complexes, and up-regulated mRNA levels of cysteinyl aspartic acid-protease (caspase) -2, -3, -7, -8, -9, apoptotic protease activating factor-1 (Apaf-1), Bcl-2 associated X protein (Bax), Fas ligand (FasL), p38 mitogen-activated protein kinase (p38MAPK), Kelch-like ECH-associating protein (Keap) 1a, Keap1b, claudin-12 and myosin light chain kinase (MLCK), and increased

  13. Pretransplantation recipient regulatory T cell suppressive function predicts delayed and slow graft function after kidney transplantation.

    PubMed

    Nguyen, Minh-Tri J P; Fryml, Elise; Sahakian, Sossy K; Liu, Shuqing; Michel, Rene P; Lipman, Mark L; Mucsi, Istvan; Cantarovich, Marcelo; Tchervenkov, Jean I; Paraskevas, Steven

    2014-10-15

    Delayed graft function (DGF) and slow graft function (SGF) are a continuous spectrum of ischemia-reperfusion-related acute kidney injury (AKI) that increases the risk for acute rejection and graft loss after kidney transplantation. Regulatory T cells (Tregs) are critical in transplant tolerance and attenuate murine AKI. In this prospective observational cohort study, we evaluated whether pretransplantation peripheral blood recipient Treg frequency and suppressive function are predictors of DGF and SGF after kidney transplantation. Deceased donor kidney transplant recipients (n=53) were divided into AKI (n=37; DGF, n=10; SGF, n=27) and immediate graft function (n=16) groups. Pretransplantation peripheral blood CD4CD25FoxP3 Treg frequency was quantified by flow cytometry. Regulatory T-cell suppressive function was measured by suppression of autologous effector T-cell proliferation by Treg in co-culture. Pretransplantation Treg suppressive function, but not frequency, was decreased in AKI recipients (P<0.01). In univariate and multivariate analyses accounting for the effects of cold ischemic time and donor age, Treg suppressive function discriminated DGF from immediate graft function recipients in multinomial logistic regression (odds ratio, 0.77; P<0.01), accurately predicted AKI in receiver operating characteristic curve (area under the curve, 0.82; P<0.01), and predicted 14-day estimated glomerular filtration rate in linear regression (P<0.01). Our results indicate that recipient peripheral blood Treg suppressive function is a potential independent pretransplantation predictor of DGF and SGF.

  14. 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

  15. Chronic Arachidonic Acid Administration Decreases Docosahexaenoic Acid- and Eicosapentaenoic Acid-Derived Metabolites in Kidneys of Aged Rats.

    PubMed

    Katakura, Masanori; Hashimoto, Michio; Inoue, Takayuki; Mamun, Abdullah Al; Tanabe, Yoko; Arita, Makoto; Shido, Osamu

    2015-01-01

    Arachidonic acid (ARA) metabolites produced by cyclo-oxygenase and lipoxygenase are important mediators maintaining physiological renal function. However, the effects of exogenous ARA on kidney function in vivo remain unknown. This study examined the effects of long-term oral ARA administration on normal renal function as well as inflammation and oxidative stress in aged rats. In addition, we measured levels of renal eicosanoids and docosanoids using liquid chromatography-tandem mass spectrometry. Control or ARA oil (240 mg/kg body weight/day) was orally administered to 21-month-old Wistar rats for 13 weeks. Levels of plasma creatinine, blood urea nitrogen, inflammatory and anti-inflammatory cytokines, reactive oxygen species, and lipid peroxidation were not significantly different between the two groups. The ARA concentration in the plasma, kidney, and liver increased in the ARA-administered group. In addition, levels of free-form ARA, prostaglandin E2, and 12- and 15-hydroxyeicosatetraenoic acid increased in the ARA-administered group, whereas renal concentration of docosahexaenoic acid and eicosapentaenoic acid decreased in the ARA-administered group. Levels of docosahexaenoic acid-derived protectin D1, eicosapentaenoic acid-derived 5-, and 18-hydroxyeicosapentaenoic acids, and resolvin E2 and E3 decreased in the ARA-administered group. Our results indicate that long-term ARA administration led to no serious adverse reactions under normal conditions and to a decrease in anti-inflammatory docosahexaenoic acid- and eicosapentaenoic acid-derived metabolites in the kidneys of aged rats. These results indicate that there is a possibility of ARA administration having a reducing anti-inflammatory effect on the kidney.

  16. Chronic Arachidonic Acid Administration Decreases Docosahexaenoic Acid- and Eicosapentaenoic Acid-Derived Metabolites in Kidneys of Aged Rats

    PubMed Central

    Katakura, Masanori; Hashimoto, Michio; Inoue, Takayuki; Mamun, Abdullah Al; Tanabe, Yoko; Arita, Makoto; Shido, Osamu

    2015-01-01

    Arachidonic acid (ARA) metabolites produced by cyclo-oxygenase and lipoxygenase are important mediators maintaining physiological renal function. However, the effects of exogenous ARA on kidney function in vivo remain unknown. This study examined the effects of long-term oral ARA administration on normal renal function as well as inflammation and oxidative stress in aged rats. In addition, we measured levels of renal eicosanoids and docosanoids using liquid chromatography–tandem mass spectrometry. Control or ARA oil (240 mg/kg body weight/day) was orally administered to 21-month-old Wistar rats for 13 weeks. Levels of plasma creatinine, blood urea nitrogen, inflammatory and anti-inflammatory cytokines, reactive oxygen species, and lipid peroxidation were not significantly different between the two groups. The ARA concentration in the plasma, kidney, and liver increased in the ARA-administered group. In addition, levels of free-form ARA, prostaglandin E2, and 12- and 15-hydroxyeicosatetraenoic acid increased in the ARA-administered group, whereas renal concentration of docosahexaenoic acid and eicosapentaenoic acid decreased in the ARA-administered group. Levels of docosahexaenoic acid-derived protectin D1, eicosapentaenoic acid-derived 5-, and 18-hydroxyeicosapentaenoic acids, and resolvin E2 and E3 decreased in the ARA-administered group. Our results indicate that long-term ARA administration led to no serious adverse reactions under normal conditions and to a decrease in anti-inflammatory docosahexaenoic acid- and eicosapentaenoic acid-derived metabolites in the kidneys of aged rats. These results indicate that there is a possibility of ARA administration having a reducing anti-inflammatory effect on the kidney. PMID:26485038

  17. 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.

  18. [Considerations when using creatinine as a measure of kidney function].

    PubMed

    Drion, I Iefke; Fokkert, M J Marion; Bilo, H J G Henk

    2013-01-01

    Reported serum creatinine concentrations can sometimes vary considerably, even when the renal function does less so or even not. This variation is partly due to true changes in actual serum concentration, and partly due to interferences in the measurement technique, thus not reflecting a true change in concentration. Increased or decreased endogenous creatinine production, ingested creatinine sources through meat eating or certain creatine formulations, and interference by either browning of chromogenic substances in Jaffe measurement techniques or promotors and inhibitors of enzymatic reaction methods do play a role. Reliable serum creatinine measurements are needed for renal function estimating equations. In screening circumstances and daily practice, chronic kidney disease staging is based on these estimated glomerular filtration rate values. Given the possible influences on reported serum creatinine concentrations, it is important for health care workers to remain critical when interpreting outcomes of renal function estimating equations and to not see every reported result based on an equation as a true reflection of renal function.

  19. Rifaximin Decreases the Incidence and Severity of Acute Kidney Injury and Hepatorenal Syndrome in Cirrhosis.

    PubMed

    Dong, Tien; Aronsohn, Andrew; Gautham Reddy, K; Te, Helen S

    2016-12-01

    While the effects of rifaximin have been shown to be protective against acute kidney injury (AKI) and hepatorenal syndrome (HRS) in alcohol-induced cirrhosis, its long-term effects on the renal function of other cirrhotic patients are unknown. To examine the long-term effects of rifaximin on the renal function of patients with cirrhosis from various etiologies. In a retrospective study, we examined cirrhotic patients at the University of Chicago Liver Clinic from January 1, 2011, to December 31, 2014. The study enrolled patients on rifaximin for ≥90 days, who were then matched by age, gender, and MELD score to a control group. Patients with malignancy and renal replacement therapy (RRT) at baseline were excluded. Data were censored at the last follow-up, termination of rifaximin therapy, initiation of RRT, death, or liver transplant. Eighty-eight rifaximin cases were identified and matched to 88 control cases. Baseline characteristics were similar, with the exceptions of more prevalent long-term midodrine use (≥90 days) (17.0 vs 4.5 %, p = 0.01) and baseline ascites (37.5 vs 23.8 %, p = 0.05) in the rifaximin group. There was no difference in the frequency of infections, deaths, liver transplants, or hospitalizations. After controlling for cofounders, the incidence rate ratio of AKI (IRR 0.71, p = 0.02) and HRS (IRR 0.21, p = 0.02), as well as the risk of requiring RRT (OR 0.23, p = 0.01), was lower in the rifaximin group. Long-term use of rifaximin is associated with a decrease incidence of AKI and HRS and a decrease risk of requiring RRT in a general population of cirrhotic patients.

  20. 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.

  1. 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

  2. Multicenter Phase 2 Trial of Sirolimus for Tuberous Sclerosis: Kidney Angiomyolipomas and Other Tumors Regress and VEGF- D Levels Decrease

    PubMed Central

    Dabora, Sandra L.; Franz, David Neal; Ashwal, Stephen; Sagalowsky, Arthur; DiMario, Francis J.; Miles, Daniel; Cutler, Drew; Krueger, Darcy; Uppot, Raul N.; Rabenou, Rahmin; Camposano, Susana; Paolini, Jan; Fennessy, Fiona; Lee, Nancy; Woodrum, Chelsey; Manola, Judith; Garber, Judy; Thiele, Elizabeth A.

    2011-01-01

    Background Tuberous sclerosis (TSC) related tumors are characterized by constitutively activated mTOR signaling due to mutations in TSC1 or TSC2. Methods We completed a phase 2 multicenter trial to evaluate the efficacy and tolerability of the mTOR inhibitor, sirolimus, for the treatment of kidney angiomyolipomas. Results 36 adults with TSC or TSC/LAM were enrolled and started on daily sirolimus. The overall response rate was 44.4% (95% confidence intervals [CI] 28 to 61); 16/36 had a partial response. The remainder had stable disease (47.2%, 17/36), or were unevaluable (8.3%, 3/36). The mean decrease in kidney tumor size (sum of the longest diameters [sum LD]) was 29.9% (95% CI, 22 to 37; n = 28 at week 52). Drug related grade 1–2 toxicities that occurred with a frequency of >20% included: stomatitis, hypertriglyceridemia, hypercholesterolemia, bone marrow suppression (anemia, mild neutropenia, leucopenia), proteinuria, and joint pain. There were three drug related grade 3 events: lymphopenia, headache, weight gain. Kidney angiomyolipomas regrew when sirolimus was discontinued but responses tended to persist if treatment was continued after week 52. We observed regression of brain tumors (SEGAs) in 7/11 cases (26% mean decrease in diameter), regression of liver angiomyolipomas in 4/5 cases (32.1% mean decrease in longest diameter), subjective improvement in facial angiofibromas in 57%, and stable lung function in women with TSC/LAM (n = 15). A correlative biomarker study showed that serum VEGF-D levels are elevated at baseline, decrease with sirolimus treatment, and correlate with kidney angiomyolipoma size (Spearman correlation coefficient 0.54, p = 0.001, at baseline). Conclusions Sirolimus treatment for 52 weeks induced regression of kidney angiomyolipomas, SEGAs, and liver angiomyolipomas. Serum VEGF-D may be a useful biomarker for monitoring kidney angiomyolipoma size. Future studies are needed to determine benefits and risks of longer duration

  3. High dietary fiber intake is associated with decreased inflammation and all-cause mortality in patients with chronic kidney disease

    PubMed Central

    Raj Krishnamurthy, Vidya M.; Wei, Guo; Baird, Bradley C.; Murtaugh, Maureen; Chonchol, Michel B.; Raphael, Kalani L.; Greene, Tom; Beddhu, Srinivasan

    2016-01-01

    Chronic kidney disease is considered an inflammatory state and a high fiber intake is associated with decreased inflammation in the general population. Here, we determined whether fiber intake is associated with decreased inflammation and mortality in chronic kidney disease, and whether kidney disease modifies the associations of fiber intake with inflammation and mortality. To do this, we analyzed data from 14,543 participants in the National Health and Nutrition Examination Survey III. The prevalence of chronic kidney disease (estimated glomerular filtration rate less than 60 ml/min per 1.73 m2) was 5.8%. For each 10-g/day increase in total fiber intake, the odds of elevated serum C-reactive protein levels were decreased by 11% and 38% in those without and with kidney disease, respectively. Dietary total fiber intake was not significantly associated with mortality in those without but was inversely related to mortality in those with kidney disease. The relationship of total fiber with inflammation and mortality differed significantly in those with and without kidney disease. Thus, high dietary total fiber intake is associated with lower risk of inflammation and mortality in kidney disease and these associations are stronger in magnitude in those with kidney disease. Interventional trials are needed to establish the effects of fiber intake on inflammation and mortality in kidney disease. PMID:22012132

  4. 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.

  5. 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.

  6. Taurine decreased uric acid levels in hyperuricemic rats and alleviated kidney injury.

    PubMed

    Feng, Ying; Sun, Fang; Gao, Yongchao; Yang, Jiancheng; Wu, Gaofeng; Lin, Shumei; Hu, Jianmin

    2017-07-29

    Hyperuricemia can lead to direct kidney damage. Taurine participates in several renal physiological processes and has been shown as a renoprotective agent. It has been reported that taurine could reduce uric acid levels in diabetic rats, but to date there was no research on the effects of taurine on hyperuricemic rats with kidney injury. In present study, hyperuricemic rat models were induced by intragastric administration of adenine and ethambutol hydrochloride for 10 days, and taurine (1% or 2%) were added in the drinking water 7 days in advance for consecutively 17 days. The results showed that taurine alleviated renal morphological and pathological changes as well as kidney dysfunction in hyperuricemic rats. Taurine could efficiently decrease the elevated xanthine oxidase activities in hyperuricemic rats, indicating its effect on the regulation of uric acid formation. The reabsorption and secretion of uric acid are dependent on a number of urate transporters. Expressions of three urate transporters were significantly down-regulated in hyperuricemic rats, while taurine prevented the decrease of mRNA and protein expression levels of these urate transporters. The results indicate that taurine might play a role in the regulation of renal uric acid excretion. Therefore, taurine could be a promising agent for the treatment of hyperuricemia. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. 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

  8. 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

  9. [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.

  10. 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

  11. 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.

  12. 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.

  13. Short-term Effects of Tolvaptan in Individuals With Autosomal Dominant Polycystic Kidney Disease at Various Levels of Kidney Function.

    PubMed

    Boertien, Wendy E; Meijer, Esther; de Jong, Paul E; ter Horst, Gert J; Renken, Remco J; van der Jagt, Eric J; Kappert, Peter; Ouyang, John; Engels, Gerwin E; van Oeveren, Willem; Struck, Joachim; Czerwiec, Frank S; Oberdhan, Dorothee; Krasa, Holly B; Gansevoort, Ron T

    2015-06-01

    A recent study showed that tolvaptan, a vasopressin V2 receptor antagonist, decreased total kidney volume (TKV) growth and estimated glomerular filtration rate (GFR) loss in autosomal dominant polycystic kidney disease (ADPKD) with creatinine clearance≥60mL/min. The aim of our study was to determine whether the renal hemodynamic effects and pharmacodynamic efficacy of tolvaptan in ADPKD are dependent on GFR. Clinical trial with comparisons before and after treatment. Patients with ADPKD with a wide range of measured GFRs (mGFRs; 18-148 mL/min) in a hospital setting. Participants were studied at baseline and after 3 weeks of treatment with tolvaptan given in increasing dosages, if tolerated (doses of 60, 90, and 120mg/d in weeks 1, 2, and 3, respectively). Change in markers for aquaresis (free-water clearance, urine and plasma osmolality, 24-hour urine volume, and plasma copeptin) and kidney injury (TKV and kidney injury biomarkers). GFR was measured by (125)I-iothalamate clearance; TKV, by magnetic resonance imaging; biomarker excretion, by enzyme-linked immunosorbent assay; and osmolality, by freezing point depression. In 27 participants (52% men; aged 46±10 years; mGFR, 69±39mL/min; TKV, 2.15 [IQR, 1.10-2.77] L), treatment with tolvaptan led to an increase in urine volume and free-water clearance and a decrease in urine osmolality, TKV, and kidney injury marker excretion. Changes in urine volume and osmolality with treatment were less in participants with lower baseline mGFRs (both P<0.01). However, change in fractional free-water clearance was greater at lower baseline mGFRs (P=0.001), suggesting that participants with decreased GFRs responded more to tolvaptan per functioning nephron. Limited sample size, no control group. In patients with ADPKD with decreased kidney function, response to tolvaptan is lower for TKV, urinary volume, and osmolality, but larger for fractional free-water clearance. This latter finding suggests that patients with ADPKD with

  14. Correlation of Point Shear Wave Velocity and Kidney Function in Chronic Kidney Disease.

    PubMed

    Grosu, Iulia; Bob, Flaviu; Sporea, Ioan; Popescu, Alina; Şirli, Roxana; Schiller, Adalbert

    2018-04-24

    Point shear wave elastography is a quantitative ultrasound-based imaging method used in the assessment of renal disease. Among point shear wave elastographic options, 2 techniques have been studied considerably: Virtual Touch quantification (VTQ; Siemens AG, Erlangen, Germany) and ElastPQ (EPQ; Philips Healthcare, Bothell, WA). Both rely on the tissue response to an acoustic beam generated by the ultrasound transducer. The data on renal VTQ are more extensive, whereas EPQ has been used less thus far in the assessment of the kidneys. This study aimed to evaluate the performance of EPQ in the kidney and compare it with VTQ. We studied 124 participants using EPQ: 22 with no renal disease and 102 with chronic kidney disease (CKD). Ninety-one were studied with both the EPQ and VTQ methods. We obtained 5 valid measurements in each kidney, expressed in meters per second. The mean kidney stiffness measurements ± SD obtained with EPQ in the healthy control group were as follows: right kidney, 1.23 ± 0.33 m/s; and left kidney, 1.26 ± 0.32 m/s (P = .6). In the patients with CKD (all stages), the mean kidney stiffness measurements obtained were significantly lower: right kidney, 1.09 ± 0.39 m/s; and left kidney, 1.04 ± 0.38 m/s (P = .4). We observed that, similar to VTQ, EPQ values decreased with CKD progression, based on analysis of variance results using different CKD stages. From a receiver operating characteristic curve analysis, the cutoff value for an estimated glomerular filtration rate of less than 45 mL/min was 1.24 m/s, and the value for an estimated glomerular filtration rate of less than 30 mL/min was 1.07 m/s. When using EPQ, the kidney shear wave velocity is decreased in patients with CKD, an observation similar to that obtained by using the VTQ method. © 2018 by the American Institute of Ultrasound in Medicine.

  15. 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.

  16. 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

  17. 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.

  18. Predonation Volume of Future Remnant Cortical Kidney Helps Predict Postdonation Renal Function in Live Kidney Donors.

    PubMed

    Fananapazir, Ghaneh; Benzl, Robert; Corwin, Michael T; Chen, Ling-Xin; Sageshima, Junichiro; Stewart, Susan L; Troppmann, Christoph

    2018-07-01

    Purpose To determine whether the predonation computed tomography (CT)-based volume of the future remnant kidney is predictive of postdonation renal function in living kidney donors. Materials and Methods This institutional review board-approved, retrospective, HIPAA-compliant study included 126 live kidney donors who had undergone predonation renal CT between January 2007 and December 2014 as well as 2-year postdonation measurement of estimated glomerular filtration rate (eGFR). The whole kidney volume and cortical volume of the future remnant kidney were measured and standardized for body surface area (BSA). Bivariate linear associations between the ratios of whole kidney volume to BSA and cortical volume to BSA were obtained. A linear regression model for 2-year postdonation eGFR that incorporated donor age, sex, and either whole kidney volume-to-BSA ratio or cortical volume-to-BSA ratio was created, and the coefficient of determination (R 2 ) for the model was calculated. Factors not statistically additive in assessing 2-year eGFR were removed by using backward elimination, and the coefficient of determination for this parsimonious model was calculated. Results Correlation was slightly better for cortical volume-to-BSA ratio than for whole kidney volume-to-BSA ratio (r = 0.48 vs r = 0.44, respectively). The linear regression model incorporating all donor factors had an R 2 of 0.66. The only factors that were significantly additive to the equation were cortical volume-to-BSA ratio and predonation eGFR (P = .01 and P < .01, respectively), and the final parsimonious linear regression model incorporating these two variables explained almost the same amount of variance (R 2 = 0.65) as did the full model. Conclusion The cortical volume of the future remnant kidney helped predict postdonation eGFR at 2 years. The cortical volume-to-BSA ratio should thus be considered for addition as an important variable to living kidney donor evaluation and selection guidelines.

  19. Decreased expression of Na+-H+ exchanger isoforms 1 and 3 in denervated spontaneously hypertensive rat kidney.

    PubMed

    Li, Jianling; He, Qiaoling; Li, Qingjie; Huang, Rongjie; Wei, Xiaoyan; Pan, Xiaofeng; Wu, Weifeng

    2018-05-22

    To determine whether the sympathetic nerve plays a role in the regulation of Na + -H + exchange (NHE) in the kidney of spontaneously hypertensive rats (SHR), we investigated the expression of NHE and NHE regulatory protein family (NHERF) in the denervated kidneys compared with intact kidneys. Twelve-week-old male SHR and age-matched Wistar Kyoto (WKY) rats were used. SHR were randomly assigned to the renal denervated (RDNX, n = 8) or Sham (n = 8) groups. The protein and mRNA expression of NHE1, NHE3, NHERF1 and NHERF2 were assessed in the kidney of the groups. Following the renal denervation, immunohistochemistry and western blot analysis showed that NHE1 and NHE3 protein were significantly decreased in the kidney compared with Sham group. NHERF1 protein expression was significantly increased in RDNX compared with Sham group, whereas NHERF2 protein expression was significantly decreased after renal denervation. Similar results were observed at the mRNA level of NHE1, NHE3, NHERF1 and NHERF2 expression. The present findings suggest that the renal sympathetic nervous system plays a role in the regulation of NHE1 and NHE3 in the kidney of SHR, and NHERF1 may be involved in the expression of NHE3 in the kidney of SHR.

  20. 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.

  1. 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.

  2. Association of Metabolic Syndrome With Kidney Function and Histology in Living Kidney Donors

    PubMed Central

    Ohashi, Y.; Thomas, G.; Nurko, S.; Stephany, B.; Fatica, R.; Chiesa, A.; Rule, A. D.; Srinivas, T.; Schold, J. D.; Navaneethan, S. D.; Poggio, E. D.

    2013-01-01

    The selection of living kidney donors is based on a formal evaluation of the state of health. However, this spectrum of health includes subtle metabolic derangements that can cluster as metabolic syndrome. We studied the association of metabolic syndrome with kidney function and histology in 410 donors from 2005 to 2012, of whom 178 donors were systematically followed after donation since 2009. Metabolic syndrome was defined as per the NCEP ATPIII criteria, but using a BMI > 25 kg/m2 instead of waist circumference. Following donation, donors received counseling on lifestyle modification. Metabolic syndrome was present in 50 (12.2%) donors. Donors with metabolic syndrome were more likely to have chronic histological changes on implant biopsies than donors with no metabolic syndrome (29.0% vs. 9.3%, p < 0.001). This finding was associated with impaired kidney function recovery following donation. At last follow-up, reversal of metabolic syndrome was observed in 57.1% of donors with predonation metabolic syndrome, while only 10.8% of donors developed de novo metabolic syndrome (p < 0.001). In conclusion, metabolic syndrome in donors is associated with chronic histological changes, and nephrectomy in these donors was associated with subsequent protracted recovery of kidney function. Importantly, weight loss led to improvement of most abnormalities that define metabolic syndrome. PMID:23865821

  3. Association of metabolic syndrome with kidney function and histology in living kidney donors.

    PubMed

    Ohashi, Y; Thomas, G; Nurko, S; Stephany, B; Fatica, R; Chiesa, A; Rule, A D; Srinivas, T; Schold, J D; Navaneethan, S D; Poggio, E D

    2013-09-01

    The selection of living kidney donors is based on a formal evaluation of the state of health. However, this spectrum of health includes subtle metabolic derangements that can cluster as metabolic syndrome. We studied the association of metabolic syndrome with kidney function and histology in 410 donors from 2005 to 2012, of whom 178 donors were systematically followed after donation since 2009. Metabolic syndrome was defined as per the NCEP ATPIII criteria, but using a BMI > 25 kg/m(2) instead of waist circumference. Following donation, donors received counseling on lifestyle modification. Metabolic syndrome was present in 50 (12.2%) donors. Donors with metabolic syndrome were more likely to have chronic histological changes on implant biopsies than donors with no metabolic syndrome (29.0% vs. 9.3%, p < 0.001). This finding was associated with impaired kidney function recovery following donation. At last follow-up, reversal of metabolic syndrome was observed in 57.1% of donors with predonation metabolic syndrome, while only 10.8% of donors developed de novo metabolic syndrome (p < 0.001). In conclusion, metabolic syndrome in donors is associated with chronic histological changes, and nephrectomy in these donors was associated with subsequent protracted recovery of kidney function. Importantly, weight loss led to improvement of most abnormalities that define metabolic syndrome. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

  4. The impact of gut microbiota on kidney function and pathogenesis.

    PubMed

    Mahmoodpoor, Fariba; Rahbar Saadat, Yalda; Barzegari, Abolfazl; Ardalan, Mohammadreza; Zununi Vahed, Sepideh

    2017-09-01

    Chronic kidney diseases (CKDs) are a global health problem. Besides diverse leading reasons in initiation and progression of CKDs, it is evident that they might largely originate from changes in the gut microbial community (microbiota). Mounting evidence indicates that a bidirectional relationship exists between host and microbiome in humans and animals with CKDs. Changes in the microbiota composition and structure (dysbiosis) produce excessive amounts of uremic toxins (e.g. indoxyl sulfate, p-cresyl sulfate and trimethylamine-N-oxide) but less reno-protective metabolites that are implicated in oxidative stress, uremia, inflammation, deterioration of kidney function, kidney diseases progression, a higher prevalence of cardiovascular risk, and mortality in patients with CKD. The present review focuses on the pathogenic association between gut microbiota and kidney diseases like CKD, IgA nephropathy, and kidney stone disease. Certainly, novel insights into the impact of the gut microbiota in kidney diseases can be helpful to develop therapeutic strategies in order to avoid and/or treat aforementioned conditions. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. 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.

  6. Generic Drugs - Decreasing Costs and Room for Increased Number of Kidney Transplantations.

    PubMed

    Spasovski, Goce

    2015-01-01

    Kidney transplantation is the best treatment option in comparison to dialysis, although patients are obliged to receive life-long medical treatment with immunosuppressive drugs (ISDs) for prevention of the graft rejection. Such immunosuppressive treatment may be costly and associated with multiple adverse effects. Since costs are viewed as one of the major constraints for the increasing number of transplantation, the use of generic ISDs may decrease the overall cost of transplantation and raise the possibility for its further development. An ideal ISD should have the security margin between toxic and therapeutic dose, and prevent development of acute or chronic rejection of the transplanted kidney. This is particularly important for drugs with a "narrow therapeutical index" (NTI), where small differences in dose or concentration lead to dose and concentration-dependent, serious therapeutic failures and/or adverse drug reactions. The NTI generic drug is approved if within 90%-112% of the area under the curve of the original product the pharmacokinetics fulfills the strict criteria of pharmaceutical equivalence and bioequivalence. Every generic has to be proven to be bioequivalent to the innovator product, and not to other generic products because of the possible generic "drift". Thus, the generic ISDs may be economically attractive, but theoretically, they may pose a risk to transplant patients. Such risks may be reduced if a long-term clinical studies showing cost-effectiveness of generic ISDs in de novo and prevalent transplant patients for every new generic ISD are performed. In conclusion, the increased number of solid organ transplantation goes in line with the increased health care expenditure for ISDs. The generic immunosuppressants could be a possible solution if safely substituted for innovator products or other generic drug of choice. The substantial cost reduction needs to be redirected into organ donation initiatives so that more patients can benefit

  7. ASSOCIATION OF KIDNEY FUNCTION AND EARLY KIDNEY INJURY WITH INCIDENT HYPERTENSION IN HIV-INFECTED WOMEN

    PubMed Central

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

    2016-01-01

    Subclinical kidney disease is associated with developing hypertension in the general population, but data are lacking among HIV-infected persons. We examined associations of kidney function and injury with incident hypertension in 823 HIV-infected and 267 HIV-uninfected women in the Women’s Interagency HIV Study, a multicenter, prospective cohort of HIV-infected and uninfected women in the United States. Baseline kidney biomarkers included estimated glomerular filtration rate using cystatin C (eGFR), urine albumin-to-creatinine ratio (ACR), and seven urine biomarkers of tubular injury: alpha-1-microglobulin, interleukin-18 (IL-18), kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, liver fatty acid binding protein, N-acetyl-beta-D-glucosaminidase (NAG), and alpha1-acid-glycoprotein (AAG). We used multivariable Poisson regression to evaluate associations of kidney biomarkers with incident hypertension, defined as two consecutive visits of anti-hypertensive medication use. Over a median follow-up of 9.6 years, 288 HIV-infected women (35%) developed hypertension. Among the HIV-infected women, higher ACR was independently associated with incident hypertension (RR=1.13 per ACR doubling, 95%CI: 1.07, 1.20), as was lower eGFR (RR=1.10 per 10 ml/min/1.73m2 lower eGFR, CI: 1.04, 1.17). No tubular injury and dysfunction biomarkers were independently associated with incident hypertension in HIV-infected women. In contrast, among the HIV-uninfected women, ACR was not associated with incident hypertension, whereas higher IL-18, AAG and NAG were significantly associated with incident hypertension. These findings suggest that early glomerular injury and kidney dysfunction may be involved in the pathogenesis of hypertension in HIV-infected persons. The associations of the tubular markers with hypertension in HIV-uninfected women should be validated in other studies. PMID:27993956

  8. Multiple New Loci Associated with Kidney Function and Chronic Kidney Disease: The CKDGen consortium

    PubMed Central

    Köttgen, Anna; Pattaro, Cristian; Böger, Carsten A.; Fuchsberger, Christian; Olden, Matthias; Glazer, Nicole L.; Parsa, Afshin; Gao, Xiaoyi; Yang, Qiong; Smith, Albert V.; O’Connell, Jeffrey R.; Li, Man; Schmidt, Helena; Tanaka, Toshiko; Isaacs, Aaron; Ketkar, Shamika; Hwang, Shih-Jen; Johnson, Andrew D.; Dehghan, Abbas; Teumer, Alexander; Paré, Guillaume; Atkinson, Elizabeth J.; Zeller, Tanja; Lohman, Kurt; Cornelis, Marilyn C.; Probst-Hensch, Nicole M.; Kronenberg, Florian; Tönjes, Anke; Hayward, Caroline; Aspelund, Thor; Eiriksdottir, Gudny; Launer, Lenore; Harris, Tamara B.; Rapmersaud, Evadnie; Mitchell, Braxton D.; Boerwinkle, Eric; Struchalin, Maksim; Cavalieri, Margherita; Singleton, Andrew; Giallauria, Francesco; Metter, Jeffery; de Boer, Ian; Haritunians, Talin; Lumley, Thomas; Siscovick, David; Psaty, Bruce M.; Zillikens, M. Carola; Oostra, Ben A.; Feitosa, Mary; Province, Michael; Levy, Daniel; de Andrade, Mariza; Turner, Stephen T.; Schillert, Arne; Ziegler, Andreas; Wild, Philipp S.; Schnabel, Renate B.; Wilde, Sandra; Muenzel, Thomas F.; Leak, Tennille S; Illig, Thomas; Klopp, Norman; Meisinger, Christa; Wichmann, H.-Erich; Koenig, Wolfgang; Zgaga, Lina; Zemunik, Tatijana; Kolcic, Ivana; Minelli, Cosetta; Hu, Frank B.; Johansson, Åsa; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H; Wright, Alan F; Campbell, Harry; Ellinghaus, David; Schreiber, Stefan; Aulchenko, Yurii S; Rivadeneira, Fernando; Uitterlinden, Andre G; Hofman, Albert; Imboden, Medea; Nitsch, Dorothea; Brandstätter, Anita; Kollerits, Barbara; Kedenko, Lyudmyla; Mägi, Reedik; Stumvoll, Michael; Kovacs, Peter; Boban, Mladen; Campbell, Susan; Endlich, Karlhans; Völzke, Henry; Kroemer, Heyo K.; Nauck, Matthias; Völker, Uwe; Polasek, Ozren; Vitart, Veronique; Badola, Sunita; Parker, Alexander N.; Ridker, Paul M.; Kardia, Sharon L. R.; Blankenberg, Stefan; Liu, Yongmei; Curhan, Gary C.; Franke, Andre; Rochat, Thierry; Paulweber, Bernhard; Prokopenko, Inga; Wang, Wei; Gudnason, Vilmundur; Shuldiner, Alan R.; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; Shlipak, Michael G.; van Duijn, Cornelia M.; Borecki, Ingrid; Krämer, Bernhard K.; Rudan, Igor; Gyllensten, Ulf; Wilson, James F.; Witteman, Jacqueline C.; Pramstaller, Peter P.; Rettig, Rainer; Hastie, Nick; Chasman, Daniel I.; Kao, W. H.; Heid, Iris M.; Fox, Caroline S.

    2010-01-01

    Chronic kidney disease (CKD) is a significant public health problem, and recent genetic studies have identified common CKD susceptibility variants. The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 Caucasian individuals from 20 population-based studies to identify new susceptibility loci for reduced renal function, estimated by serum creatinine (eGFRcrea), cystatin C (eGFRcys), and CKD (eGFRcrea <60 ml/min/1.73m2; n = 5,807 CKD cases). Follow-up of the 23 genome-wide significant loci (p<5×10−8) in 22,982 replication samples identified 13 novel loci for renal function and CKD (in or near LASS2, GCKR, ALMS1, TFDP2, DAB2, SLC34A1, VEGFA, PRKAG2, PIP5K1B, ATXN2, DACH1, UBE2Q2, and SLC7A9) and 7 creatinine production and secretion loci (CPS1, SLC22A2, TMEM60, WDR37, SLC6A13, WDR72, BCAS3). These results further our understanding of biologic mechanisms of kidney function by identifying loci potentially influencing nephrogenesis, podocyte function, angiogenesis, solute transport, and metabolic functions of the kidney. PMID:20383146

  9. Racial differences in kidney function among individuals with obesity and metabolic syndrome: results from the Kidney Early Evaluation Program (KEEP).

    PubMed

    Bomback, Andrew S; Kshirsagar, Abhijit V; Whaley-Connell, Adam T; Chen, Shu-Cheng; Li, Suying; Klemmer, Philip J; McCullough, Peter A; Bakris, George L

    2010-03-01

    Obesity and metabolic syndrome may differ by race. For participants in the National Kidney Foundation's Kidney Early Evaluation Program (KEEP), we examined whether African American and white participants with obesity and metabolic syndrome differ regarding albuminuria, estimated glomerular filtration rate (eGFR), anemia, and bone/mineral metabolism derangements in chronic kidney disease (CKD). 3 study cohorts were assembled: (1) eligible African American and white KEEP participants with body mass index > or = 30 kg/m(2), (2) a subgroup meeting criteria for metabolic syndrome, and (3) a subgroup with eGFR < 60 mL/min/1.73 m(2) and laboratory measurements for hemoglobin, parathyroid hormone, calcium, and phosphorus. Patient characteristics and kidney function assessments were compared and tested using chi(2) (categorical variables) and t test (continuous variables). Univariate and multivariate logistic regression analyses were performed to evaluate associations of race with kidney disease measures. Of 37,107 obese participants, 48% were African American and 52% were white. Whites were more likely to have metabolic syndrome components (hypertension, 87.1% vs 84.8%; dyslipidemia, 81.6% vs 66.7%; diabetes, 42.7% vs 34.9%) and more profoundly decreased eGFR than African Americans (CKD stages 3-5 prevalence, 23.6% vs 13.0%; P < 0.001). African Americans were more likely to have abnormal urinary albumin excretion (microalbuminuria, 12.5% vs 10.2%; OR, 1.60 [95% CI, 1.45-1.76]; macroalbuminuria, 1.3% vs 1.2%; OR, 1.61 [95% CI, 1.23-2.12]) and CKD stages 1-2 (10.3% vs 7.1%; OR, 1.54 [95% CI, 1.38-1.72]). For participants with CKD stages 3-5, anemia prevalence was 32.4% in African Americans and 14.1% in whites; corresponding values for secondary hyperparathyroidism were 66.2% and 46.6%, respectively. Obesity and metabolic syndrome may be heterogeneous disease states in African Americans and whites, possibly explaining differences in long-term kidney and cardiovascular

  10. The Effects of Early Postnatal Diuretics Treatment on Kidney Development and Long-Term Kidney Function in Wistar Rats.

    PubMed

    Bueters, Ruud R G; Jeronimus-Klaasen, Annelies; Maicas, Nuria; Florquin, Sandrine; van den Heuvel, Lambertus P; Schreuder, Michiel F

    2016-01-01

    Diuretics are administered to neonates to control fluid balance. We studied whether clinical doses affected kidney development and function and whether extrauterine growth retardation (EUGR) could be a modulator. Wistar rats were cross-fostered in normal food or food restricted litters at postnatal day (PND) 2 and treated daily with 0.9% NaCl, 5 mg/kg furosemide or 5 mg/kg hydrochlorothiazide (HCTZ) up to PND 8. Kidneys were evaluated on proliferation, apoptosis and a set of mRNA target genes at PND 8, glomerular- and glomerular generation count at PND 35, clinical pathology parameters at 3- and 9 months, neutrophil gelatinase-associated lipocalin at PND 8, 3 and 6 months, monthly blood pressure from 3 months onward and histopathology at study end. Treatment with furosemide or HCTZ did not have relevant effects on measured parameters. EUGR resulted in lower body weight from day 3 onwards (-29% at weaning; p < 0.001, -10% at necropsy; p < 0.001), less glomerular generations (4.4 ± 0.32 vs. 5.0 ± 0.423; p = 0.025, males only), decreased glomerular numbers (27,861 ± 3,468 vs. 30,527 ± 4,096; p = 0.026), higher creatinine clearance (0.84 ± 0.1 vs. 0.77 ± 0.09 ml/min/kg; p = 0.047) at 3 months and lower plasma creatinine (25.7 ± 1.8 vs. 27.5 ± 2.8 µmol/l; p = 0.043) at 9 months. Furosemide and HCTZ did not influence kidney development or function when administered in a clinically relevant dose to rat pups at a stage of ongoing nephrogenesis. EUGR led to impaired kidney development but did not modify furosemide or HCTZ findings. © 2016 S. Karger AG, Basel.

  11. Low-level cadmium exposure and effects on kidney function

    PubMed Central

    Wallin, Maria; Sallsten, Gerd; Lundh, Thomas; Barregard, Lars

    2014-01-01

    Objectives The nephrotoxicity of cadmium at low levels of exposure, measured by urinary cadmium, has recently been questioned since co-excretion of cadmium and proteins may have causes other than cadmium toxicity. The aim of this study was to explore the relation between kidney function and low or moderate cadmium levels, measured directly in kidney biopsies. Methods We analysed cadmium in kidney biopsies (K-Cd), blood (B-Cd) and urine (U-Cd) from 109 living kidney donors in a cross-sectional study. We measured glomerular filtration rate (GFR), cystatin C in serum, albumin, β-2-microglobulin (B2M), retinol-binding protein (RBP), α-1-microglobulin (A1M), N-acetyl-β-d-glucosaminidase and kidney injury molecule 1 (KIM-1) in 24 h and overnight urine. Results We found significant positive associations between A1M excretion and K-Cd in multiple regression models including age, sex, weight, smoking and urinary flow rate. This association was also present in never-smokers. A1M was also positively associated with B-Cd and U-Cd. GFR and the other biomarkers of kidney function were not associated with K-Cd. GFR estimated from serum cystatin C showed a very poor correlation with measured GFR. KIM-1, RBP and possibly albumin were positively associated with U-Cd, but only in overnight urine. No associations were found with B2M. Conclusions Our results suggest that A1M in urine is a sensitive biomarker for effects of low-level cadmium exposure. A few associations between other renal biomarkers and U-Cd, but not K-Cd, were probably caused by physiological co-excretion or chance. PMID:25286916

  12. Moderate acute pancreatitis with pleural effusion and impaired kidney functions

    NASA Astrophysics Data System (ADS)

    Lumbantoruan, O. H.; Dairi, L. B.

    2018-03-01

    Acute pancreatitis is a pancreatic inflammatory reaction that is clinically characterized by acute abdominal pain accompanied by elevated amylase and lipase enzymes. A 57-year-old female patient came to the emergency department with the main complaint of localized pain in the epigastric region within the last three days. Blood pressure 130/90mmHg, pulse 90x/i, RR 20x/i, temperature 37°C, sub-icteric on the eyes and tenderness in the epigastric region. Laboratory findings were leukocytosis, increased amylase, and lipase, elevated liver enzymes, hypoalbuminemia, elevated Kidney Functions, acidosis, and hypoglycemia. Abdominal CT-Scan revealed a partially lobulated edge with solid and necrotic components of the caput pancreas and widespread suspicion to the pancreatic corpus. The mass appeared to cause widening of the biliary and intrahepatic systems with minimal right pleural effusion. The liverwas slightly enlarged. The patient was with acute pancreatitis and treated with the installation of an open nasogastric tube, and resuscitated with ringer lactate fluid followed by IVFD D5%. Patients fasted for three days before giving a low fat, protein diet, antibiotic and proton pump inhibitors for seven days. After nine days, amylase and lipase levels decreased with significant clinical improvement. The next three days, the patient was discharged.

  13. Interconnected network motifs control podocyte morphology and kidney function.

    PubMed

    Azeloglu, Evren U; Hardy, Simon V; Eungdamrong, Narat John; Chen, Yibang; Jayaraman, Gomathi; Chuang, Peter Y; Fang, Wei; Xiong, Huabao; Neves, Susana R; Jain, Mohit R; Li, Hong; Ma'ayan, Avi; Gordon, Ronald E; He, John Cijiang; Iyengar, Ravi

    2014-02-04

    Podocytes are kidney cells with specialized morphology that is required for glomerular filtration. Diseases, such as diabetes, or drug exposure that causes disruption of the podocyte foot process morphology results in kidney pathophysiology. Proteomic analysis of glomeruli isolated from rats with puromycin-induced kidney disease and control rats indicated that protein kinase A (PKA), which is activated by adenosine 3',5'-monophosphate (cAMP), is a key regulator of podocyte morphology and function. In podocytes, cAMP signaling activates cAMP response element-binding protein (CREB) to enhance expression of the gene encoding a differentiation marker, synaptopodin, a protein that associates with actin and promotes its bundling. We constructed and experimentally verified a β-adrenergic receptor-driven network with multiple feedback and feedforward motifs that controls CREB activity. To determine how the motifs interacted to regulate gene expression, we mapped multicompartment dynamical models, including information about protein subcellular localization, onto the network topology using Petri net formalisms. These computational analyses indicated that the juxtaposition of multiple feedback and feedforward motifs enabled the prolonged CREB activation necessary for synaptopodin expression and actin bundling. Drug-induced modulation of these motifs in diseased rats led to recovery of normal morphology and physiological function in vivo. Thus, analysis of regulatory motifs using network dynamics can provide insights into pathophysiology that enable predictions for drug intervention strategies to treat kidney disease.

  14. Interconnected Network Motifs Control Podocyte Morphology and Kidney Function

    PubMed Central

    Azeloglu, Evren U.; Hardy, Simon V.; Eungdamrong, Narat John; Chen, Yibang; Jayaraman, Gomathi; Chuang, Peter Y.; Fang, Wei; Xiong, Huabao; Neves, Susana R.; Jain, Mohit R.; Li, Hong; Ma’ayan, Avi; Gordon, Ronald E.; He, John Cijiang; Iyengar, Ravi

    2014-01-01

    Podocytes are kidney cells with specialized morphology that is required for glomerular filtration. Diseases, such as diabetes, or drug exposure that causes disruption of the podocyte foot process morphology results in kidney pathophysiology. Proteomic analysis of glomeruli isolated from rats with puromycin-induced kidney disease and control rats indicated that protein kinase A (PKA), which is activated by adenosine 3′,5′-monophosphate (cAMP), is a key regulator of podocyte morphology and function. In podocytes, cAMP signaling activates cAMP response element–binding protein (CREB) to enhance expression of the gene encoding a differentiation marker, synaptopodin, a protein that associates with actin and promotes its bundling. We constructed and experimentally verified a β-adrenergic receptor–driven network with multiple feedback and feedforward motifs that controls CREB activity. To determine how the motifs interacted to regulate gene expression, we mapped multicompartment dynamical models, including information about protein subcellular localization, onto the network topology using Petri net formalisms. These computational analyses indicated that the juxtaposition of multiple feedback and feedforward motifs enabled the prolonged CREB activation necessary for synaptopodin expression and actin bundling. Drug-induced modulation of these motifs in diseased rats led to recovery of normal morphology and physiological function in vivo. Thus, analysis of regulatory motifs using network dynamics can provide insights into pathophysiology that enable predictions for drug intervention strategies to treat kidney disease. PMID:24497609

  15. Kidney Function in Obesity-Challenges in Indexing and Estimation.

    PubMed

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

    2018-01-01

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

  16. The Relationship Between Pulmonary Emphysema and Kidney Function in Smokers

    PubMed Central

    Chandra, Divay; Stamm, Jason A.; Palevsky, Paul M.; Leader, Joseph K.; Fuhrman, Carl R.; Zhang, Yingze; Bon, Jessica; Duncan, Steven R.; Branch, Robert A.; Weissfeld, Joel; Gur, David; Gladwin, Mark T.

    2012-01-01

    Background: It has been reported that the prevalence of kidney dysfunction may be increased in patients exposed to tobacco with airflow obstruction. We hypothesized that kidney dysfunction would associate with emphysema rather than with airflow obstruction measured by the FEV1. Methods: Five hundred eight current and former smokers completed a chest CT scan, pulmonary function tests, medical questionnaires, and measurement of serum creatinine. Glomerular filtration rates (eGFRs) were estimated using the method of the Chronic Kidney Disease Epidemiology Collaboration. Quantitative determinants of emphysema and airway dimension were measured from multidetector chest CT scans. Results: The mean age was 66 ± 7 years, and mean eGFR was 101 ± 22 mL/min/1.73 m2. Univariate and multivariate analysis showed a significant association between radiographically measured emphysema and eGFR: Participants with 10% more emphysema had an eGFR that was lower by 4.4 mL/min/1.73 m2 (P = .01), independent of airflow obstruction (FEV1), age, sex, race, height, BMI, diabetes mellitus, hypertension, coronary artery disease, patient-reported dyspnea, pack-years of smoking, and current smoking. There was no association between eGFR and either FEV1 or quantitative CT scan measures of airway dimension. Conclusions: More severe emphysema, rather than airflow obstruction, is associated with kidney dysfunction in tobacco smokers, independent of common risk factors for kidney disease. This finding adds to recent observations of associations between emphysema and comorbidities of COPD, including osteoporosis and lung cancer, which are independent of the traditional measure of reduced FEV1. The mechanisms and clinical implications of kidney dysfunction in patients with emphysema need further investigation. PMID:22459775

  17. [Lithium treatment in patients with impaired kidney function: Between Scylla and Charybdis].

    PubMed

    Dehning, Julia; Grunze, Heinz; Born, Christoph; Hausmann, Armand

    2017-05-01

    Introduction In quite a few patients with bipolar disorder there is no real alternative to lithium treatment despite impaired kidney function. Is it possible to continue lithium treatment despite kidney malfunction by changing dosage and/or frequency of administration? Case Report We report on a 65-year-old woman suffering from bipolar-I disorder who had been on lithium treatment for many decades. While on lithium, the glomerular filtration rate (GFR) decreased constantly. A decision had to be made whether to switch to a more tolerable o.d. administration or to taper off lithium. Conclusion With a single dose at bedtime, the serum levels remained stable; however, kidney function unfortunately did not improve. A relevant increase of GFR above the level of 60 mL/min/1,73 m 2 was only achieved after a 50% dose reduction leading also to a substantial decrease of lithium serum levels. A kidney protective lithium application in patients with reduced renal function is like sailing between Scylla and Charybdis. Georg Thieme Verlag KG Stuttgart · New York.

  18. Kidney Function after Methoxyflurane Analgesia during Labour

    PubMed Central

    Rosen, Michael; Latto, P.; Asscher, A. W.

    1972-01-01

    In a study of the effects of methoxyflurane on renal function, the urinary and blood urea concentrations, the urinary and plasma osmolalities, and the packed cell volume were studied in each of 50 mothers before and after delivery. Methoxyflurane 0·35% was used as an analgesic in 25 patients and the other 25 had 50% nitrous oxide and 50% oxygen (Entonox). There was no evidence of renal dysfunction in either group, nor were there any significant differences between the groups. In a further 200 mothers, of whom 100 had methoxyflurane and 100 had nitrous oxide analgesia, the urinary and blood urea concentrations were measured on the morning of discharge from hospital. There were no significant differences between the groups. These results suggest that methoxyflurane is not nephrotoxic when used as a self-administered analgesic. PMID:5007074

  19. Fibroblast Growth Factor 23: A Biomarker of Kidney Function Decline.

    PubMed

    Drew, David A; Katz, Ronit; Kritchevsky, Stephen; Ix, Joachim H; Shlipak, Michael G; Newman, Anne B; Hoofnagle, Andy; Fried, Linda; Sarnak, Mark J; Gutierrez, Orlando M

    2018-01-01

    Fibroblast growth factor 23 (FGF-23) is a hormone that regulates phosphorus levels and vitamin D metabolism. Previous studies have shown FGF-23 to be a risk factor for incident end-stage renal disease; however, there are less data on the association of FGF-23 with earlier kidney-related outcomes. Serum FGF-23 was assayed using an intact ELISA assay in 2,496 participants of the Healthy Aging and Body Composition Study, a cohort of well-functioning older adults. Kidney function was estimated by assaying cystatin C at baseline and years 3 and 10. The associations between FGF-23 and decline in kidney function (defined by estimated glomerular filtration rate (eGFR) decline ≥30% or ≥3 mL/min/year) and incident chronic kidney disease (CKD; incident eGFR <60 mL/min/1.73 m2 and ≥1 mL/min/year decline) were evaluated. Models were adjusted for demographics, baseline eGFR, urine albumin/creatinine ratio, comorbidity, and serum calcium, phosphorus, 25(OH) vitamin D and parathyroid hormone. The mean (SD) age was 75 (3) years, with 52% female and 38% black. There were 405 persons with 30% decline, 702 with >3 mL/min/year decline, and 536 with incident CKD. In fully adjusted continuous models, doubling of FGF-23 concentrations was not associated with kidney function decline (OR [95% CI] = 0.98 [0.82-1.19] for ≥30% decline and OR 1.17 [95% CI 1.00-1.37] for ≥3 mL/min/year decline), or incident CKD (incident rate ratio [IRR] 1.05 [95% CI 0.91-1.22]). In adjusted quartile analysis, the highest quartile of FGF-23 was significantly associated with incident CKD (IRR 1.27 [95% CI 1.02-1.58] for highest vs. lowest quartile). Higher FGF-23 concentrations were not consistently associated with decline in kidney function or incident CKD in community-dwelling older adults. © 2018 S. Karger AG, Basel.

  20. Effects of complete water fasting and regeneration diet on kidney function, oxidative stress and antioxidants.

    PubMed

    Mojto, V; Gvozdjakova, A; Kucharska, J; Rausova, Z; Vancova, O; Valuch, J

    2018-01-01

    The aim of the study was to observe the influence of 11-days complete water fasting (WF) and regeneration diet (RD) on renal function, body weight, blood pressure and oxidative stress. Therapeutic WF is considered a healing method. Ten volunteers drank only water for 11 days, followed by RD for the next 11 days. Data on body weight, blood pressure, kidney functions, antioxidants, lipid peroxidation, cholesterols, triacylglycerols and selected biochemical parameters were obtained. WF increased uric acid and creatinine and decreased glomerular filtration rate. After RD, the parameters were comparable to baseline values. Urea was not affected. Lipid peroxidation (TBARS) decreased and maintained stable after RD. Fasting decreased α-tocopherol and increased γ-tocopherol, no significant changes were found after RD. Coenzyme Q10 decreased after RD. HDL-cholesterol decreased in WF. Total- and LDL-cholesterol decreased after RD. Other biochemical parameters were within the range of reference values. The effect of the complete fasting on kidney function was manifested by hyperuricemia. Renal function was slightly decreased, however maintained within the reference values. After RD, it returned to baseline values. The positive effect of the complete water fasting was in the reduction of oxidative stress, body weight and blood pressure (Tab. 3, Ref. 25).

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

    PubMed

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

    2017-02-01

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

  2. Origin and function of myofibroblasts in kidney fibrosis.

    PubMed

    LeBleu, Valerie S; Taduri, Gangadhar; O'Connell, Joyce; Teng, Yingqi; Cooke, Vesselina G; Woda, Craig; Sugimoto, Hikaru; Kalluri, Raghu

    2013-08-01

    Myofibroblasts are associated with organ fibrosis, but their precise origin and functional role remain unknown. We used multiple genetically engineered mice to track, fate map and ablate cells to determine the source and function of myofibroblasts in kidney fibrosis. Through this comprehensive analysis, we identified that the total pool of myofibroblasts is split, with 50% arising from local resident fibroblasts through proliferation. The nonproliferating myofibroblasts derive through differentiation from bone marrow (35%), the endothelial-to-mesenchymal transition program (10%) and the epithelial-to-mesenchymal transition program (5%). Specific deletion of Tgfbr2 in α-smooth muscle actin (αSMA)(+) cells revealed the importance of this pathway in the recruitment of myofibroblasts through differentiation. Using genetic mouse models and a fate-mapping strategy, we determined that vascular pericytes probably do not contribute to the emergence of myofibroblasts or fibrosis. Our data suggest that targeting diverse pathways is required to substantially inhibit the composite accumulation of myofibroblasts in kidney fibrosis.

  3. Origin and Function of Myofibroblasts in Kidney Fibrosis

    PubMed Central

    LeBleu, Valerie S.; Taduri, Gangadhar; O’Connell, Joyce; Teng, Yingqi; Cooke, Vesselina G.; Woda, Craig; Sugimoto, Hikaru; Kalluri, Raghu

    2014-01-01

    Myofibroblasts are associated with organ fibrosis but their precise origin and functional role remain unknown. We employed multiple genetically engineered mice to track, fate-map and ablate cells to determine the source and function of myofibroblasts in kidney fibrosis. Such comprehensive analysis identified that the total pool of myofibroblasts is split, with 50% arising from local resident fibroblasts via proliferation. The non-proliferating myofibroblasts derive via differentiation from bone marrow (35%), endothelial to mesenchymal transition (EndMT) program (10%) and epithelial to mesenchymal transition (EMT) program (5%). Specific deletion of Tgfbr2 in αSMA+ cells revealed the importance of this pathway in recruitment of myofibroblasts via differentiation. Using genetic mouse models and fate-mapping strategy we determined that vascular pericytes likely do not contribute to the emergence of myofibroblasts or fibrosis. This study suggests that targeting diverse pathways is required to significantly inhibit composite accumulation of myofibroblasts in kidney fibrosis. PMID:23817022

  4. Resveratrol improves mitochondrial function in the remnant kidney from 5/6 nephrectomized rats.

    PubMed

    Hui, Yan; Lu, Miaomiao; Han, Yarong; Zhou, Hongli; Liu, Wei; Li, Lijing; Jin, Ruixia

    2017-05-01

    Mitochondrial dysfunction is involved in the pathogenesis of chronic kidney disease (CKD). Resveratrol has been demonstrated to be beneficial for the recovery of kidney diseases. In this study, the 5/6 nephrectomized rat was used as a CKD model and the TGF-β1-exposed mouse mesangial cells were used as an in vitro model. Pathological examination showed that resveratrol treatment attenuated glomerular injury in the remnant kidney of 5/6 nephrectomized rat. Additionally, resveratrol improved mitochondrial function in vivo and in vitro, as evidenced by increasing mitochondrial membrane potential, increasing ATP, decreasing reactive oxygen species production and enhancing activities of complex I and III. Furthermore, the dysregulated expressions of electron transport chain proteins and fission/fusion proteins in the kidney of 5/6 nephrectomize rats and TGF-β1-exposed mesangial cells were restored by resveratrol. Finally, upregulated sirt1 and PGC-1α deacetylation were found after treatment with resveratrol in vivo and in vitro, which may contribute to the mitochondrial protective effects of resveratrol. The results demonstrate that resveratrol protects the mitochondria of kidney in 5/6 nephrectomized rats and TGF-β1 induced mesangial cells. The study provides new insights into the renoprotective mechanisms of resveratrol. Copyright © 2017 Elsevier GmbH. All rights reserved.

  5. Kidney Function and Fracture Risk: The Atherosclerosis Risk in Communities (ARIC) Study.

    PubMed

    Daya, Natalie; Voskertchian, Annie; Schneider, Andrea L C; Ballew, Shoshana; McAdams DeMarco, Mara; Coresh, Josef; Appel, Lawrence J; Selvin, Elizabeth; Grams, Morgan E

    2016-02-01

    People with end-stage renal disease are at high risk for bone fracture. Less is known about fracture risk in milder chronic kidney disease and whether chronic kidney disease-associated fracture risk varies by sex or assessment with alternative kidney markers. Prospective cohort study. 10,955 participants from the Atherosclerosis Risk in Communities (ARIC) Study followed up from 1996 to 2011. Kidney function as assessed by creatinine-based estimated glomerular filtration rate (eGFRcr), urine albumin-creatinine ratio, and alternative filtration markers. Fracture-related hospitalizations determined by diagnostic code. Baseline kidney markers; hospitalizations identified by self-report during annual telephone contact and active surveillance of local hospital discharge lists. Mean age of participants was 63 years, 56% were women, and 22% were black. During a median follow-up of 13 years, there were 722 incident fracture-related hospitalizations. Older age, female sex, and white race were associated with higher risk for fracture (P<0.001). The relationship between eGFRcr and fracture risk was nonlinear: <60mL/min/1.73m(2), lower eGFRcr was associated with higher fracture risk (adjusted HR per 10mL/min/1.73m(2) lower, 1.24; 95% CI, 1.05-1.47); there was no statistically significant association for ≥60mL/min/1.73m(2) in the primary analysis. In contrast, there was a graded association between other markers of kidney function and subsequent fracture, including albumin-creatinine ratio (HR per doubling, 1.10; 95% CI, 1.06-1.14), cystatin C-based eGFR (HR per 1-SD decrease, 1.15; 95% CI, 1.06-1.25), and 1/β2-microglobulin (HR per 1-SD decrease, 1.26, 95% CI, 1.15-1.37). No bone mineral density assessment; one-time measurement of kidney function. Both low eGFR and higher albuminuria were significant risk factors for fracture in this community-based population. The shape of the association in the upper ranges of eGFR varied by the filtration marker used in estimation

  6. 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.

  7. Dietary fiber, kidney function, inflammation, and mortality risk.

    PubMed

    Xu, Hong; Huang, Xiaoyan; Risérus, Ulf; Krishnamurthy, Vidya M; Cederholm, Tommy; Arnlöv, Johan; Lindholm, Bengt; Sjögren, Per; Carrero, Juan Jesús

    2014-12-05

    In the United States population, high dietary fiber intake has been associated with a lower risk of inflammation and mortality in individuals with kidney dysfunction. This study aimed to expand such findings to a Northern European population. Dietary fiber intake was calculated from 7-day dietary records in 1110 participants aged 70-71 years from the Uppsala Longitudinal Study of Adult Men (examinations performed during 1991-1995). Dietary fiber was adjusted for total energy intake by the residual method. Renal function was estimated from the concentration of serum cystatin C, and deaths were registered prospectively during a median follow-up of 10.0 years. Dietary fiber independently and directly associated with eGFR (adjusted difference, 2.6 ml/min per 1.73 m(2) per 10 g/d higher; 95% confidence interval [95% CI], 0.3 to 4.9). The odds of C-reactive protein >3 mg/L were lower (linear trend, P=0.002) with higher fiber quartiles. During follow-up, 300 participants died (incidence rate of 2.87 per 100 person-years at risk). Multiplicative interactions were observed between dietary fiber intake and kidney dysfunction in the prediction of mortality. Higher dietary fiber was associated with lower mortality in unadjusted analysis. These associations were stronger in participants with kidney dysfunction (eGFR<60 ml/min per 1.73 m(2)) (hazard ratio [HR], 0.58; 95% CI, 0.35 to 0.98) than in those without (HR, 1.30; 95% CI, 0.76 to 2.22; P value for interaction, P=0.04), and were mainly explained by a lower incidence of cancer-related deaths (0.25; 95% CI, 0.10 to 0.65) in individuals with kidney dysfunction versus individuals with an eGFR≥60 ml/min per 1.73 m(2) (1.61; 95% CI, 0.69 to 3.74; P value for interaction, P=0.01). High dietary fiber was associated with better kidney function and lower inflammation in community-dwelling elderly men from Sweden. High dietary fiber was also associated with lower (cancer) mortality risk, especially in individuals with kidney

  8. Dietary Fiber, Kidney Function, Inflammation, and Mortality Risk

    PubMed Central

    Xu, Hong; Huang, Xiaoyan; Risérus, Ulf; Krishnamurthy, Vidya M.; Cederholm, Tommy; Ärnlöv, Johan; Lindholm, Bengt; Sjögren, Per

    2014-01-01

    Background and objectives In the United States population, high dietary fiber intake has been associated with a lower risk of inflammation and mortality in individuals with kidney dysfunction. This study aimed to expand such findings to a Northern European population. Design, setting, participants, & measurements Dietary fiber intake was calculated from 7-day dietary records in 1110 participants aged 70–71 years from the Uppsala Longitudinal Study of Adult Men (examinations performed during 1991–1995). Dietary fiber was adjusted for total energy intake by the residual method. Renal function was estimated from the concentration of serum cystatin C, and deaths were registered prospectively during a median follow-up of 10.0 years. Results Dietary fiber independently and directly associated with eGFR (adjusted difference, 2.6 ml/min per 1.73 m2 per 10 g/d higher; 95% confidence interval [95% CI], 0.3 to 4.9). The odds of C-reactive protein >3 mg/L were lower (linear trend, P=0.002) with higher fiber quartiles. During follow-up, 300 participants died (incidence rate of 2.87 per 100 person-years at risk). Multiplicative interactions were observed between dietary fiber intake and kidney dysfunction in the prediction of mortality. Higher dietary fiber was associated with lower mortality in unadjusted analysis. These associations were stronger in participants with kidney dysfunction (eGFR<60 ml/min per 1.73 m2) (hazard ratio [HR], 0.58; 95% CI, 0.35 to 0.98) than in those without (HR, 1.30; 95% CI, 0.76 to 2.22; P value for interaction, P=0.04), and were mainly explained by a lower incidence of cancer-related deaths (0.25; 95% CI, 0.10 to 0.65) in individuals with kidney dysfunction versus individuals with an eGFR≥60 ml/min per 1.73 m2 (1.61; 95% CI, 0.69 to 3.74; P value for interaction, P=0.01). Conclusions High dietary fiber was associated with better kidney function and lower inflammation in community-dwelling elderly men from Sweden. High dietary fiber was also

  9. 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.

  10. Lead nitrate induced unallied expression of liver and kidney functions in male albino rats.

    PubMed

    Chougule, Priti; Patil, Bhagyashree; Kanase, Aruna

    2005-06-01

    To determine the effects of lead where lead accumulates maximum (liver followed by kidney), liver and kidney functions were studied using low oral dose of lead nitrate for prolonged duration. Dose of 20 mg lead nitrate/kg body wt/day was used in male albino rats. AST and ALT levels altered independently. When ALT remained unaltered after 7 and 21 days of treatment, it is decreased by 13.21% after 14 days treatment. AST was marginally lowered after 7 days, increased after 14 days and increased marginally after 21 days. Bilirubin (conjugated, unconjugated and total) decreased after 7 and 14 days and increased after 21 days. Urea increase was directly proportional to duration. Creatinine remained unaltered.

  11. Wound Healing in Patients With Impaired Kidney Function

    PubMed Central

    Maroz, Natallia; Simman, Richard

    2014-01-01

    Renal impairment has long been known to affect wound healing. However, information on differences in the spectrum of wound healing depending on the type of renal insufficiency is limited. Acute kidney injury (AKI) may be observed with different wound types. On one hand, it follows acute traumatic conditions such as crush injury, burns, and post-surgical wounds, and on the other hand, it arises as simultaneous targeting of skin and kidneys by autoimmune-mediated vasculitis. Chronic kidney disease (CKD) and end-stage renal disease (ESRD) often occur in older people, who have limited physical mobility and predisposition for developing pressure-related wounds. The common risk factors for poor wound healing, generally observed in patients with CKD and ESRD, include poorly controlled diabetes mellitus, neuropathy, peripheral vascular disease, chronic venous insufficiency, and aging. ESRD patients have a unique spectrum of wounds related to impaired calcium–phosphorus metabolism, including calciphylaxis, in addition to having the risk factors presented by CKD patients. Overall, there is a wide range of uremic toxins: they may affect local mechanisms of wound healing and also adversely affect the functioning of multiple systems. In the present literature review, we discuss the association between different types of renal impairments and their effects on wound healing and examine this association from different aspects related to the management of wounds in renal impairment patients. PMID:26199882

  12. Colistin Use in Patients With Reduced Kidney Function.

    PubMed

    Fiaccadori, Enrico; Antonucci, Elio; Morabito, Santo; d'Avolio, Antonio; Maggiore, Umberto; Regolisti, Giuseppe

    2016-08-01

    Colistin (polymyxin E) is a mainly concentration-dependent bactericidal antimicrobial active against multidrug-resistant Gram-negative bacteria. After being abandoned over the past 30 years due to its neuro- and nephrotoxicity, colistin has been reintroduced recently as a last-resort drug for the treatment of multidrug-resistant Gram-negative bacteria infections in combination with other antimicrobials. Unfortunately, although renal toxicity is a well-known dose-related adverse effect of colistin, relatively few studies are currently available on its peculiar pharmacodynamic/pharmacokinetic properties in clinical settings at high risk for drug accumulation, such as acute or chronic kidney disease. In these specific contexts, the risk for underdosing is also substantial because colistin can be easily removed by dialysis/hemofiltration, especially when the most efficient modalities of renal replacement therapy (RRT) are used in critically ill patients. For this reason, recent recommendations in patients undergoing RRT have shifted toward higher dosing regimens, and therapeutic drug monitoring is advised. This review aims to summarize the main issues related to chemical structure, pharmacodynamics/pharmacokinetics, and renal toxicity of colistin. Moreover, recent data and current recommendations concerning colistin dosing in patients with reduced kidney function, with special regard to those receiving RRT such as dialysis or hemofiltration, are also discussed. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  13. Gynecologic symptoms and sexual function in female kidney allograft recipients.

    PubMed

    Karayalcin, R; Genc, V; Oztuna, D; Huseynova, N; Ersoz, S

    2010-09-01

    There is little information in the literature about changing menstrual patterns, sexuality, and fertility after kidney transplantation. The purpose of this study was to describe gynecologic symptoms, menstrual characteristics, sexual functions, details of pregnancies and gynecologic care before and after women underwent renal transplantation. A detailed Turkish questionnaire was prepared for gynecologic evaluation. Fifty women of reproductive age who underwent renal transplantation took part in this study. The questionnaires were filled out at the time of the postoperative follow-up. The mean age and body mass index of all study participants at the time of interview was 33.9 years (range, 18-52) and 23.5 kg/m(2) (range, 16.5-33.3), respectively. There were no differences between bleeding between periods, heavy period, painful period, and period duration before and after transplantation. Eight women left active working life after grafting on their own accord. Thirteen women ceased sexual activity after transplantation. None of the women reported pregnancy after grafting. A total of 98% of women reported that they were never instructed about regular gynecologic care. We found that restrictions in the lives of women with transplanted kidneys included ceasing sexual activity and leaving active working life and that these were due to fear of possible organ damage. Women with transplanted kidneys must be informed about posttransplant sex life and the requirement for regular examinations by a gynecologist. Hence, close collaborations should be formed between patients, primary care physicians, and gynecologists. 2010 Elsevier Inc. All rights reserved.

  14. Serum iron level and kidney function: a Mendelian randomization study.

    PubMed

    Del Greco M, Fabiola; Foco, Luisa; Pichler, Irene; Eller, Philipp; Eller, Kathrin; Benyamin, Beben; Whitfield, John B; Pramstaller, Peter P; Thompson, John R; Pattaro, Cristian; Minelli, Cosetta

    2017-02-01

    Iron depletion is a known consequence of chronic kidney disease (CKD), but there is contradicting epidemiological evidence on whether iron itself affects kidney function and whether its effect is protective or detrimental in the general population. While epidemiological studies tend to be affected by confounding and reverse causation, Mendelian randomization (MR) can provide unconfounded estimates of causal effects by using genes as instruments. We performed an MR study of the effect of serum iron levels on estimated glomerular filtration rate (eGFR), using genetic variants known to be associated with iron. MR estimates of the effect of iron on eGFR were derived based on the association of each variant with iron and eGFR from two large genome-wide meta-analyses on 48 978 and 74 354 individuals. We performed a similar MR analysis for ferritin, which measures iron stored in the body, using variants associated with ferritin. A combined MR estimate across all variants showed a 1.3% increase in eGFR per standard deviation increase in iron (95% confidence interval 0.4–2.1%; P = 0.004). The results for ferritin were consistent with those for iron. Secondary MR analyses of the effects of iron and ferritin on CKD did not show significant associations but had very low statistical power. Our study suggests a protective effect of iron on kidney function in the general population. Further research is required to confirm this causal association, investigate it in study populations at higher risk of CKD and explore its underlying mechanism of action.

  15. Kidney Function Can Improve in Patients with Hypertensive CKD

    PubMed Central

    Gadegbeku, Crystal; Lipkowitz, Michael S.; Rostand, Stephen; Lewis, Julia; Wright, Jackson T.; Appel, Lawrence J.; Greene, Tom; Gassman, Jennifer; Astor, Brad C.

    2012-01-01

    The typical assumption is that patients with CKD will have progressive nephropathy. Methodological issues, such as measurement error and regression to the mean, have made it difficult to document whether kidney function might improve in some patients. Here, we used data from 12 years of follow-up in the African American Study of Kidney Disease and Hypertension to determine whether some patients with CKD can experience a sustained improvement in GFR. We calculated estimated GFR (eGFR) based on serum creatinine measurements during both the trial and cohort phases. We defined clearly improved patients as those with positive eGFR slopes that we could not explain by random measurement variation under Bayesian mixed-effects models. Of 949 patients with at least three follow-up eGFR measurements, 31 (3.3%) demonstrated clearly positive eGFR slopes. The mean slope among these patients was +1.06 (0.12) ml/min per 1.73 m2 per yr, compared with −2.45 (0.07) ml/min per 1.73 m2 per yr among the remaining patients. During the trial phase, 24 (77%) of these 31 patients also had clearly positive slopes of 125I-iothalamate–measured GFR during the trial phase. Low levels of proteinuria at baseline and randomization to the lower BP goal (mean arterial pressure ≤92 mmHg) associated with improved eGFR. In conclusion, the extended follow-up from this study provides strong evidence that kidney function can improve in some patients with hypertensive CKD. PMID:22402803

  16. Predicting timing of clinical outcomes in patients with chronic kidney disease and severely decreased glomerular filtration rate.

    PubMed

    Grams, Morgan E; Sang, Yingying; Ballew, Shoshana H; Carrero, Juan Jesus; Djurdjev, Ognjenka; Heerspink, Hiddo J L; Ho, Kevin; Ito, Sadayoshi; Marks, Angharad; Naimark, David; Nash, Danielle M; Navaneethan, Sankar D; Sarnak, Mark; Stengel, Benedicte; Visseren, Frank L J; Wang, Angela Yee-Moon; Köttgen, Anna; Levey, Andrew S; Woodward, Mark; Eckardt, Kai-Uwe; Hemmelgarn, Brenda; Coresh, Josef

    2018-06-01

    Patients with chronic kidney disease and severely decreased glomerular filtration rate (GFR) are at high risk for kidney failure, cardiovascular disease (CVD) and death. Accurate estimates of risk and timing of these clinical outcomes could guide patient counseling and therapy. Therefore, we developed models using data of 264,296 individuals in 30 countries participating in the international Chronic Kidney Disease Prognosis Consortium with estimated GFR (eGFR)s under 30 ml/min/1.73m 2 . Median participant eGFR and urine albumin-to-creatinine ratio were 24 ml/min/1.73m 2 and 168 mg/g, respectively. Using competing-risk regression, random-effect meta-analysis, and Markov processes with Monte Carlo simulations, we developed two- and four-year models of the probability and timing of kidney failure requiring kidney replacement therapy (KRT), a non-fatal CVD event, and death according to age, sex, race, eGFR, albumin-to-creatinine ratio, systolic blood pressure, smoking status, diabetes mellitus, and history of CVD. Hypothetically applied to a 60-year-old white male with a history of CVD, a systolic blood pressure of 140 mmHg, an eGFR of 25 ml/min/1.73m 2 and a urine albumin-to-creatinine ratio of 1000 mg/g, the four-year model predicted a 17% chance of survival after KRT, a 17% chance of survival after a CVD event, a 4% chance of survival after both, and a 28% chance of death (9% as a first event, and 19% after another CVD event or KRT). Risk predictions for KRT showed good overall agreement with the published kidney failure risk equation, and both models were well calibrated with observed risk. Thus, commonly-measured clinical characteristics can predict the timing and occurrence of clinical outcomes in patients with severely decreased GFR. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  17. Incremental peritoneal dialysis: Clinical outcomes and residual kidney function preservation.

    PubMed

    Borràs Sans, Mercè; Chacón Camacho, Andrea; Cerdá Vilaplana, Carla; Usón Nuño, Ana; Fernández, Elvira

    2016-01-01

    Initiation of peritoneal dialysis (PD) with 3 exchanges has become common practice in recent years, despite the lack of published clinical data. To describe experience with incremental peritoneal dialysis (IPD) at a single site. A total of 46 IPD patients undergoing 2-year clinical, laboratory, treatment and progression follow-up. To 25% of patients were trasplanted on IPD. Mean time on IPD before transfer to conventional PD of 24 months, half of the patients because of fluid balance. Good clinical and biochemical results with a peritonitis rate of one episode per 99 months. There was an improvement in the loss of residual kidney function compared to the pre-dialysis period (-7.06 vs. -1.58ml/min/year; P=.0001). IPD with 3 peritoneal exchanges offers good results. Most patients remain stable during the first 2 years and there is an improvement in the loss of residual kidney function compared to the pre-dialysis period. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  18. Association between kidney function and telomere length: the Heart and Soul Study

    PubMed Central

    Bansal, Nisha; Whooley, Mary A.; Regan, Mathilda; McCulloch, Charles E.; Ix, Joachim H.; Epel, Elissa; Blackburn, Elizabeth; Lin, Jue; Hsu, Chi-yuan

    2013-01-01

    Background Telomere attrition is a novel risk factor for cardiovascular disease. Studies of telomere length in relation to kidney function are limited. We explored the association of kidney function with telomere length and telomere shortening. Methods The Heart and Soul study is a longitudinal study of patients with stable coronary heart disease (CHD). Measures of baseline kidney function included: serum creatinine, creatinine-derived estimated glomerular filtration rate (eGFRCKD-EPI), 24-hour urine measured creatinine clearance, cystatin C, cystatin C-derived estimated glomerular filtration rate (eGFRcys) and urine albumin to creatinine ratio. Telomere length was measured from peripheral blood leukocytes at baseline (N=954) and 5 years later (N=608). Linear regression models were used to test the association of kidney function with i) baseline telomere length and ii) change in telomere length over 5 years. Results At baseline, mean eGFRCKD-EPI was 72.6 (± 21.5) ml/min/1.73 m2, eGFRcys was 71.0 (± 23.1) ml/min/1.73 m2 and ACR was 8.6 (±12.3) mg/gm. Only lower baseline eGFRCKD-EPI was associated with shorter baseline telomere length (9.1 [95% CI 1.2–16.9] fewer base pairs for every 5 ml/min/1.73 m2 lower eGFRCKD-EPI). Lower baseline eGFRCKD-EPI (and all other measures of kidney function) predicted more rapid telomere shortening (10.8 [95% CI 4.3–17.3] decrease in base pairs over 5 years for every 5 ml/min/1.73 m2 lower eGFRCKD-EPI). After adjustment for age, these associations were no longer statistically significant. Conclusions In patients with CHD, reduced kidney function is associated with i) shorter baseline telomere length and ii) more rapid telomere shortening over 5 years, however these associations are entirely explained by older age. PMID:23108000

  19. 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

  20. Decreasing GABA function within the medial prefrontal cortex or basolateral amygdala decreases sociability.

    PubMed

    Paine, Tracie A; Swedlow, Nathan; Swetschinski, Lucien

    2017-01-15

    Decreased sociability is a symptom of psychiatric conditions including autism-spectrum disorder and schizophrenia. Both of these conditions are associated with decreases in GABA function, particularly in the medial prefrontal cortex (PFC) and the basolateral amygdala (BLA); structures that are components of the social brain. Here, we determined if decreasing GABA transmission within either the PFC or the BLA decreases social behavior. Rats were implanted with cannulae aimed at either the medial PFC or the BLA and then were tested on up to 4 behavioral tests following bilateral infusions of 0.5μl bicuculline methiodide (BMI, a GABA A receptor antagonist) at doses of 0, 25, or 50ng/μl. Rats were tested in the social interaction test, the social preference test, the sucrose preference test and for locomotor activity (BLA infusions only). Intra-BLA or PFC BMI infusions decreased the amount of time and the number of social interactions in the social interaction test. Further, in the social preference test, rats infused with 50ng BMI no longer exhibited a preference to explore a social over a non-social stimulus. The change in sociability was not due to a change in reward processing or locomotor behavior. Decreasing GABA transmission in either the medial PFC or BLA decreased sociability. Thus, changes in GABA signaling observed in conditions such as autism or schizophrenia may mediate the social withdrawal characteristic of these conditions. Moreover, they suggest that social withdrawal may be treated by drugs that potentiate GABA transmission. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Biosignals Analysis for Kidney Function Effect Analysis of Fennel Aromatherapy

    PubMed Central

    Kim, Bong-Hyun; Cho, Dong-Uk; Seo, Ssang-Hee

    2015-01-01

    Human effort in order to enjoy a healthy life is diverse. IT technology to these analyzes, the results of development efforts, it has been applied. Therefore, I use the care and maintenance diagnostic health management and prevention than treatment. In particular, the aromatherapy treatment easy to use without the side effects there is no irritation, are widely used in modern society. In this paper, we measured the aroma effect by applying a biosignal analysis techniques; an experiment was performed to analyze. In particular, we design methods and processes of research based on the theory aroma that affect renal function. Therefore, in this paper, measuring the biosignals and after fennel aromatherapy treatment prior to the enforcement of the mutual comparison, through the analysis, studies were carried out to analyze the effect of fennel aromatherapy therapy on kidney function. PMID:25977696

  2. Persistent Postconcussive Symptoms Are Accompanied by Decreased Functional Brain Oxygenation.

    PubMed

    Helmich, Ingo; Saluja, Rajeet S; Lausberg, Hedda; Kempe, Mathias; Furley, Philip; Berger, Alisa; Chen, Jen-Kai; Ptito, Alain

    2015-01-01

    Diagnostic methods are considered a major concern in the determination of mild traumatic brain injury. The authors examined brain oxygenation patterns in subjects with severe and minor persistent postconcussive difficulties and a healthy control group during working memory tasks in prefrontal brain regions using functional near-infrared spectroscopy. The results demonstrated decreased working memory performances among concussed subjects with severe postconcussive symptoms that were accompanied by decreased brain oxygenation patterns. An association appears to exist between decreased brain oxygenation, poor performance of working memory tasks, and increased symptom severity scores in subjects suffering from persistent postconcussive symptoms.

  3. Kidney Function and Fracture Risk: The Atherosclerosis Risk in Communities (ARIC) Study

    PubMed Central

    Schneider, Andrea L.C.; Ballew, Shoshana; McAdams DeMarco, Mara; Coresh, Josef; Appel, Lawrence J.; Selvin, Elizabeth; Grams, Morgan E.

    2015-01-01

    Background People with end-stage renal disease are at high risk of bone fracture. Less is known about fracture risk in milder chronic kidney disease (CKD), and whether CKD-associated fracture risk varies by sex or assessment with alternative kidney markers. Study Design Prospective cohort study. Setting & Participants 10,955 participants from the Atherosclerosis Risk in Communities (ARIC) Study followed up from 1996 to 2011. Predictor Kidney function as assessed by creatinine-based estimated glomerular filtration rate (eGFRcr), urine albumin-creatinine ratio (ACR), and alternative filtration markers. Outcomes Fracture-related hospitalizations determined by diagnostic code. Measurements Baseline kidney markers; hospitalizations identified by self-report during annual telephone contact and active surveillance of local hospital discharge lists. Results Mean age of participants was 63 years, 56% were female, and 22% were black. During a median follow-up of 13 years, there were 722 incident fracture-related hospitalizations. Older age, female sex, and white race were associated with higher risk of fracture (p<0.001). The relationship between eGFRcr and fracture risk was non-linear: below 60 ml/min/1.73 m2, lower eGFRcr was associated with higher fracture risk (adjusted HR per 10 ml/min/1.73 m2 lower, 1.24; 95% CI, 1.05–1.47); there was no statistically significant association above 60 ml/min/1.73 m2 in the primary analysis. In contrast, there was a graded association between other markers of kidney function and subsequent fracture, including ACR (HR per doubling, 1.10; 95% CI, 1.06–1.14), cystatin C–based eGFR (HR per 1-SD decrease, 1.15; 95% CI, 1.06–1.25), and 1/β2-microglobulin (HR per 1-SD decrease, 1.26, 95% CI, 1.15–1.37). Limitations No bone mineral density assessment; one-time measure of kidney function. Conclusions Both low eGFR and higher albuminuria were significant risk factors for fracture in this community-based population. The shape of the

  4. Vitamin C, glutathione, or lipoic acid did not decrease brain or kidney mercury in rats exposed to mercury vapor.

    PubMed

    Aposhian, H Vasken; Morgan, Daniel L; Queen, H L Sam; Maiorino, Richard M; Aposhian, Mary M

    2003-01-01

    Some medical practitioners prescribe GSH and vitamin C alone or in combination with DMPS or DMSA for patients with mercury exposure that is primarily due to the mercury vapor emitted by dental amalgams. This study tested the hypothesis that GSH, vitamin C, or lipoic acid alone or in combination with DMPS or DMSA would decrease brain mercury. Young rats were exposed to elemental mercury by individual nose cone, at the rate of 4.0 mg mercury per m3 air for 2 h per day for 7 consecutive days. After a 7-day equilibrium period, DMPS, DMSA, GSH, vitamin C, lipoic acid alone, or in combination was administered for 7 days and the brain and kidneys of the animals removed and analyzed for mercury by cold vapor atomic absorption. None of these regimens reduced the mercury content of the brain. Although DMPS or DMSA was effective in reducing kidney mercury concentrations, GSH, vitamin C, lipoic acid alone, or in combination were not. One must conclude that the palliative effect, if any, of GSH, vitamin C, or lipoic acid for treatment of mercury toxicity due to mercury vapor exposure does not involve mercury mobilization from the brain and kidney.

  5. Marine benthic ecological functioning over decreasing taxonomic richness

    NASA Astrophysics Data System (ADS)

    Törnroos, Anna; Bonsdorff, Erik; Bremner, Julie; Blomqvist, Mats; Josefson, Alf B.; Garcia, Clement; Warzocha, Jan

    2015-04-01

    Alterations to ecosystem function due to reductions in species richness are predicted to increase as humans continue to affect the marine environment, especially in coastal areas, which serve as the interface between land and sea. The potential functional consequences due to reductions in species diversity have attracted considerable attention recently but little is known about the consequence of such loss in natural communities. We examined how the potential for function is affected by natural reductions in taxon richness using empirical (non-simulated) coastal marine benthic macrofaunal data from the Skagerrak-Baltic Sea region (N. Europe), where taxon richness decreases 25-fold, from 151 to 6 taxa. To estimate functional changes we defined multiple traits (10 traits and 51 categories) on which trait category richness, functional diversity (FD) and number of taxa per trait category were calculated. Our results show that decrease in taxon richness leads to an overall reduction in function but functional richness remains comparatively high even at the lowest level of taxon richness. Although the taxonomic reduction was sharp, up to 96% of total taxon richness, we identified both potential thresholds in functioning and subtler changes where function was maintained along the gradient. The functional changes were not only caused by reductions in taxa per trait category, some categories were maintained or even increased. Primarily, the reduction in species richness altered trait categories related to feeding, living and movement and thus potentially could have an effect on various ecosystem processes. This highlights the importance of recognising ecosystem multifunctionality, especially at low taxonomic richness. We also found that in this system rare species (singletons) did not stand for the functional complexities and changes. Our findings were consistent with theoretical and experimental predictions and suggest that a large proportion of the information about

  6. Long-term Renal Function in Living Kidney Donors Who Had Histological Abnormalities at Donation.

    PubMed

    Fahmy, Lara M; Massie, Allan B; Muzaale, Abimereki D; Bagnasco, Serena M; Orandi, Babak J; Alejo, Jennifer L; Boyarsky, Brian J; Anjum, Saad K; Montgomery, Robert A; Dagher, Nabil N; Segev, Dorry L

    2016-06-01

    Recent evidence suggests that living kidney donors are at an increased risk of end-stage renal disease. However, predicting which donors will have renal dysfunction remains challenging, particularly among those with no clinical evidence of disease at the time of donation. Although renal biopsies are not routinely performed as part of the donor evaluation process, they may yield valuable information that improves the ability to predict renal function in donors. We used implantation protocol biopsies to evaluate the association between histological abnormalities in the donated kidney and postdonation renal function (estimated glomerular filtration rate, eGFR) of the remaining kidney in living kidney donors. Longitudinal analysis using mixed-effects linear regression was used to account for multiple eGFR measures per donor. Among 310 donors between 1997 and 2012, median (IQR) follow-up was 6.2 (2.5-8.7; maximum 14.0) years. In this cohort, the overall prevalence of histological abnormalities was 65.8% (19.7% abnormal glomerulosclerosis, 23.9% abnormal interstitial fibrosis and tubular atrophy (IFTA), 4.8% abnormal mesangial matrix increase, 32.0% abnormal arteriolar hyalinosis, and 32.9% abnormal vascular intimal thickening). IFTA was associated with a 5-mL/min/1.73 m decrease of postdonation eGFR after adjusting for donor age at donation, sex, race, preoperative systolic blood pressure, preoperative eGFR, and time since donation (P < 0.01). In this single-center study, among healthy individuals cleared for living donation, IFTA was associated with decreased postdonation eGFR, whereas no other subclinical histological abnormalities provided additional information.

  7. Long-Term Renal Function in Living Kidney Donors who had Histological Abnormalities at Donation

    PubMed Central

    Fahmy, Lara M.; Massie, Allan B.; Muzaale, Abimereki D.; Bagnasco, Serena M.; Orandi, Babak J.; Alejo, Jennifer L.; Boyarsky, Brian J.; Anjum, Saad K.; Montgomery, Robert A.; Dagher, Nabil N.; Segev, Dorry L.

    2016-01-01

    Background Recent evidence suggests that living kidney donors are at an increased risk of end-stage renal disease. However, predicting which donors will have renal dysfunction remains challenging, particularly among those with no clinical evidence of disease at the time of donation. Although renal biopsies are not routinely performed as part of the donor evaluation process, they may yield valuable information that improves the ability to predict renal function in donors. Methods We used implantation protocol biopsies to evaluate the association between histological abnormalities in the donated kidney and postdonation renal function (estimated glomerular filtration rate, eGFR) of the remaining kidney in living kidney donors. Longitudinal analysis using mixed-effects linear regression was used to account for multiple eGFR measures per donor. Results Among 310 donors between 1997 and 2012, median (IQR) follow-up was 6.2 (2.5–8.7; maximum 14.0) years. In this cohort, the overall prevalence of histological abnormalities was 65.8% (19.7% abnormal glomerulosclerosis, 23.9% abnormal interstitial fibrosis and tubular atrophy (IFTA), 4.8% abnormal mesangial matrix increase, 32.0% abnormal arteriolar hyalinosis, and 32.9% abnormal vascular intimal thickening). IFTA was associated with a 5-mL/min/1.73m2 decrease of postdonation eGFR after adjusting for donor age at donation, sex, race, preoperative systolic blood pressure, preoperative eGFR, and time since donation (p<0.01). Conclusions In this single-center study, among healthy individuals cleared for living donation, IFTA was associated with decreased postdonation eGFR, while no other subclinical histological abnormalities provided additional information. PMID:27152920

  8. 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

  9. 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

  10. 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.

  11. Acute Knockdown of Uncoupling Protein-2 Increases Uncoupling via the Adenine Nucleotide Transporter and Decreases Oxidative Stress in Diabetic Kidneys

    PubMed Central

    Friederich-Persson, Malou; Aslam, Shakil; Nordquist, Lina; Welch, William J.; Wilcox, Christopher S.; Palm, Fredrik

    2012-01-01

    Increased O2 metabolism resulting in chronic hypoxia is common in models of endstage renal disease. Mitochondrial uncoupling increases O2 consumption but the ensuing reduction in mitochondrial membrane potential may limit excessive oxidative stress. The present study addressed the hypothesis that mitochondrial uncoupling regulates mitochondria function and oxidative stress in the diabetic kidney. Isolated mitochondria from kidney cortex of control and streptozotocin-induced diabetic rats were studied before and after siRNA knockdown of uncoupling protein-2 (UCP-2). Diabetes resulted in increased UCP-2 protein expression and UCP-2-mediated uncoupling, but normal mitochondria membrane potential. This uncoupling was inhibited by GDP, which also increased the membrane potential. siRNA reduced UCP-2 protein expression in controls and diabetics (−30–50%), but paradoxically further increased uncoupling and markedly reduced the membrane potential. This siRNA mediated uncoupling was unaffected by GDP but was blocked by ADP and carboxyatractylate (CAT). Mitochondria membrane potential after UCP-2 siRNA was unaffected by GDP but increased by CAT. This demonstrated that further increased mitochondria uncoupling after siRNA towards UCP-2 is mediated through the adenine nucleotide transporter (ANT). The increased oxidative stress in the diabetic kidney, manifested as increased thiobarbituric acids, was reduced by knocking down UCP-2 whereas whole-body oxidative stress, manifested as increased circulating malondialdehyde, remained unaffected. All parameters investigated were unaffected by scrambled siRNA. In conclusion, mitochondrial uncoupling via UCP-2 regulates mitochondria membrane potential in diabetes. However, blockade of the diabetes-induced upregulation of UCP- 2 results in excessive uncoupling and reduced oxidative stress in the kidney via activation of ANT. PMID:22768304

  12. NiaoDuQing granules relieve chronic kidney disease symptoms by decreasing renal fibrosis and anemia

    PubMed Central

    Wang, Xu; Yu, Suyun; Jia, Qi; Chen, Lichuan; Zhong, Jinqiu; Pan, Yanhong; Shen, Peiliang; Shen, Yin; Wang, Siliang; Wei, Zhonghong; Cao, Yuzhu; Lu, Yin

    2017-01-01

    NiaoDuQing (NDQ) granules, a traditional Chinese medicine, has been clinically used in China for over fourteen years to treat chronic kidney disease (CKD). To elucidate the mechanisms underlying the therapeutic benefits of NDQ, we designed an approach incorporating chemoinformatics, bioinformatics, network biology methods, and cellular and molecular biology experiments. A total of 182 active compounds were identified in NDQ granules, and 397 putative targets associated with different diseases were derived through ADME modelling and target prediction tools. Protein-protein interaction networks of CKD-related and putative NDQ targets were constructed, and 219 candidate targets were identified based on topological features. Pathway enrichment analysis showed that the candidate targets were mostly related to the TGF-β, the p38MAPK, and the erythropoietin (EPO) receptor signaling pathways, which are known contributors to renal fibrosis and/or renal anemia. A rat model of CKD was established to validate the drug-target mechanisms predicted by the systems pharmacology analysis. Experimental results confirmed that NDQ granules exerted therapeutic effects on CKD and its comorbidities, including renal anemia, mainly by modulating the TGF-β and EPO signaling pathways. Thus, the pharmacological actions of NDQ on CKD symptoms correlated well with in silico predictions. PMID:28915563

  13. Mesenchymal Stem Cells Contribute to Improvement of Renal Function in a Canine Kidney Injury Model.

    PubMed

    Lee, Seung-Jun; Ryu, Min-Ok; Seo, Min-Soo; Park, Sang-Bum; Ahn, Jin-Ok; Han, Sei-Myoung; Kang, Kyung-Sun; Bhang, Dong-Ha; Youn, Hwa-Young

    2017-01-01

    The kidney excretes waste materials and regulates important metabolic functions, and renal disorders constitute a significant medical problem and can result in fatalities. In the present study, mesenchymal stem cells derived from canine umbilical cord blood (cUCB-MSCs) were isolated and evaluated for their ability to improve renal function in a canine model of acute kidney injury (AKI). The canine AKI model was developed by i.v. injection of cisplatin and gentamycin into 14 male beagle dogs. cUCB-MSCs were administered into the renal corticomedullary junction following AKI induction. Survival time, clinical signs, blood analysis and histological parameters were analyzed. The group treated with AKI plus cUCB-MSCs had decreased blood urea nitrogen and creatinine levels, and showed an extended life-span and improved histological manifestations. MSCs were detected around the tubules of these kidneys at the histological level. Taken together, our findings suggest that cUCB-MSCs could be an alternative therapeutic agent for canine AKI. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  14. Kidney function and cognitive decline in an oldest-old Chinese population.

    PubMed

    Bai, Kunhao; Pan, Yujing; Lu, Fanghong; Zhao, Yingxin; Wang, Jinwei; Zhang, Luxia

    2017-01-01

    Early-stage chronic kidney disease has been suggested to be correlated with cognitive decline, but the association has rarely been explored in the oldest old. This prospective study included 284 Chinese participants aged 80 years or older with serum creatinine levels <150 µmol/L. The median follow-up time was 3.3 years, and 247 (87.0%) participants provided valid data at their last visit. Kidney function was evaluated by measuring the estimated glomerular filtration rate (eGFR) at baseline, and cognitive function was evaluated using the Mini-Mental State Examination (MMSE) at both baseline and annual visits. A reliable decrease in the MMSE score over the follow-up period was observed based on a Reliable Change Index of 1.645 (equivalent to a 90% confidence interval [CI]), which was used to define cognitive decline. Poisson regression models were built to analyze the association between baseline kidney function and cognitive decline. A total of 18 (7.3%) cases of incident cognitive decline were observed during the follow-up period. After adjusting for potential confounders, the relative risk of developing cognitive decline was 4.03 (95% CI 1.09-13.81) among participants with an eGFR of 30-59 mL/min/1.73 m 2 compared to participants with an eGFR of ≥60 mL/min/1.73 m 2 . Early-stage chronic kidney disease was correlated with cognitive decline in an oldest-old Chinese population.

  15. Tumor necrosis factor-α, kidney function, and hypertension.

    PubMed

    Mehaffey, Eamonn; Majid, Dewan S A

    2017-10-01

    Hypertension is considered to be a low-grade inflammatory condition characterized by the presence of various proinflammatory cytokines. Tumor necrosis factor-α (TNF-α) is a constituent of the proinflammatory cytokines that is associated with salt-sensitive hypertension (SSH) and related renal injury. Elevated angiotensin II (ANG II) and other factors such as oxidative stress conditions promote TNF-α formation. Many recent studies have provided evidence that TNF-α exerts a direct renal action by regulating hemodynamic and excretory function in the kidney. The cytokine incites a strong natriuretic response and plays a part in regulation of the intrarenal renin-angiotensin system. The exact mechanistic role of TNF-α in the development of SSH is as yet poorly understood. While TNF-α antagonism has been shown to attenuate hypertensive responses in many hypertensive animal models, contrasting findings demonstrate that the direct systemic administration of TNF-α usually induces hypotensive as well as natriuretic responses, indicating a counterregulatory role of TNF-α in SSH. Differential activities of two cell surface receptors of TNF-α (receptor type 1 and type 2) may explain the contradictory functions of TNF-α in the setting of hypertension. This short review will evaluate ongoing research studies that investigate the action of TNF-α within the kidney and its role as an influential pathophysiological variable in the development of SSH and renal injury. This information may help to develop specific TNF-α receptor targeting as an effective treatment strategy in this clinical condition. Copyright © 2017 the American Physiological Society.

  16. Decreased function of survival motor neuron protein impairs endocytic pathways

    PubMed Central

    Dimitriadi, Maria; Derdowski, Aaron; Kalloo, Geetika; Maginnis, Melissa S.; O’Hern, Patrick; Bliska, Bryn; Sorkaç, Altar; Nguyen, Ken C. Q.; Cook, Steven J.; Poulogiannis, George; Atwood, Walter J.; Hall, David H.; Hart, Anne C.

    2016-01-01

    Spinal muscular atrophy (SMA) is caused by depletion of the ubiquitously expressed survival motor neuron (SMN) protein, with 1 in 40 Caucasians being heterozygous for a disease allele. SMN is critical for the assembly of numerous ribonucleoprotein complexes, yet it is still unclear how reduced SMN levels affect motor neuron function. Here, we examined the impact of SMN depletion in Caenorhabditis elegans and found that decreased function of the SMN ortholog SMN-1 perturbed endocytic pathways at motor neuron synapses and in other tissues. Diminished SMN-1 levels caused defects in C. elegans neuromuscular function, and smn-1 genetic interactions were consistent with an endocytic defect. Changes were observed in synaptic endocytic proteins when SMN-1 levels decreased. At the ultrastructural level, defects were observed in endosomal compartments, including significantly fewer docked synaptic vesicles. Finally, endocytosis-dependent infection by JC polyomavirus (JCPyV) was reduced in human cells with decreased SMN levels. Collectively, these results demonstrate for the first time, to our knowledge, that SMN depletion causes defects in endosomal trafficking that impair synaptic function, even in the absence of motor neuron cell death. PMID:27402754

  17. Decreased function of survival motor neuron protein impairs endocytic pathways.

    PubMed

    Dimitriadi, Maria; Derdowski, Aaron; Kalloo, Geetika; Maginnis, Melissa S; O'Hern, Patrick; Bliska, Bryn; Sorkaç, Altar; Nguyen, Ken C Q; Cook, Steven J; Poulogiannis, George; Atwood, Walter J; Hall, David H; Hart, Anne C

    2016-07-26

    Spinal muscular atrophy (SMA) is caused by depletion of the ubiquitously expressed survival motor neuron (SMN) protein, with 1 in 40 Caucasians being heterozygous for a disease allele. SMN is critical for the assembly of numerous ribonucleoprotein complexes, yet it is still unclear how reduced SMN levels affect motor neuron function. Here, we examined the impact of SMN depletion in Caenorhabditis elegans and found that decreased function of the SMN ortholog SMN-1 perturbed endocytic pathways at motor neuron synapses and in other tissues. Diminished SMN-1 levels caused defects in C. elegans neuromuscular function, and smn-1 genetic interactions were consistent with an endocytic defect. Changes were observed in synaptic endocytic proteins when SMN-1 levels decreased. At the ultrastructural level, defects were observed in endosomal compartments, including significantly fewer docked synaptic vesicles. Finally, endocytosis-dependent infection by JC polyomavirus (JCPyV) was reduced in human cells with decreased SMN levels. Collectively, these results demonstrate for the first time, to our knowledge, that SMN depletion causes defects in endosomal trafficking that impair synaptic function, even in the absence of motor neuron cell death.

  18. Elevated Levels of Peripheral Kynurenine Decrease Bone Strength in Rats with Chronic Kidney Disease

    PubMed Central

    Kalaska, Bartlomiej; Pawlak, Krystyna; Domaniewski, Tomasz; Oksztulska-Kolanek, Ewa; Znorko, Beata; Roszczenko, Alicja; Rogalska, Joanna; Brzoska, Malgorzata M.; Lipowicz, Pawel; Doroszko, Michal; Pryczynicz, Anna; Pawlak, Dariusz

    2017-01-01

    The diagnosis and treatment of bone disorders in patients with chronic kidney disease (CKD) represent a clinical challenge. CKD leads to mineral and bone complications starting early in the course of renal failure. Recently, we have observed the positive relationship between intensified central kynurenine turnover and bone strength in rats with subtotal 5/6 nephrectomy (5/6 Nx)-induced CKD. The aim of the present study was to determine the association between peripheral kynurenine pathway metabolites and bone strength in rats with 5/6 Nx-induced CKD. The animals were sacrificed 1 and 3 months after 5/6 Nx or sham operation. Nephrectomized rats presented higher concentrations of serum creatinine, urea nitrogen, and parathyroid hormone both 1 and 3 months after nephrectomy. These animals revealed higher concentrations of kynurenine and 3-hydroxykynurenine in the serum and higher gene expression of aryl hydrocarbon receptor (AhR) as a physiological receptor for kynurenine and AhR-dependent cytochrome in the bone tissue. Furthermore, nephrectomy significantly increased the number of osteoclasts in the bone without affecting their resorptive activity measured in serum. These changes were particularly evident in rats 1 month after 5/6 Nx. The main bone biomechanical parameters of the tibia were unchanged between nephrectomized and sham-operated rats but were significantly increased in older compared to younger animals. A similar trend was observed for geometrical parameters measured with calipers, bone mineral density based on Archimedes' method and image of bone microarchitecture obtained from micro-computed tomography analyses of tibial cortical bone. In nephrectomized animals, peripheral kynurenine levels correlated negatively with the main parameters of bone biomechanics, bone geometry, and bone mineral density values. In conclusion, our data suggest that CKD-induced elevated levels of peripheral kynurenine cause pathological changes in bone structure via AhR pathway

  19. Oxidative stress is associated with decreased heart rate variability in patients with chronic kidney disease.

    PubMed

    Fadaee, Shannon B; Beetham, Kassia S; Howden, Erin J; Stanton, Tony; Isbel, Nicole M; Coombes, Jeff S

    2017-09-01

    Elevated oxidative stress and reduced heart rate variability (HRV) is prevalent in patients with chronic kidney disease (CKD) and is associated with increased morbidity and mortality. Previous studies have identified a positive association between elevated oxidative stress and autonomic dysfunction, however this relationship has not yet been investigated in the CKD population. Plasma was collected from 78 patients with stage 3-4 CKD (estimated glomerular filtration rate 25-60 ml/min/1.73 m 2 ) for the assessment of oxidative stress, including plasma total F2-isoprostanes, glutathione peroxidase activity and total antioxidant capacity. Time and frequency HRV parameters were measured from a three lead electrocardiogram. Participants with elevated F2-isoprostanes had reduced HRV compared to patients with normal levels of F2-isoprostanes. A number of HRV parameters were found to be inversely correlated with F2-isoprostanes in all CKD patients, including SDNN (r = -0.337; P < 0.01), VLF (r = -0.281, P = 0.01), LF (r = -0.315, P < 0.01) and total power (r = -0.288, P = 0.01). Multiple linear regression found F2-isoprostanes to be an independent predictor of SDNN (r 2  = 0.287, β = -0.272, P = 0.01). Oxidative stress is significantly and independently associated with HRV in patients with CKD. Identifying oxidative stress in the pathogenesis of autonomic dysfunction may help target therapeutic strategies.

  20. Endoplasmic reticulum stress in kidney function and disease.

    PubMed

    Taniguchi, Mai; Yoshida, Hiderou

    2015-07-01

    Recently, a number of papers have reported that endoplasmic reticulum (ER) stress is involved in the onset of various kidney diseases, but the pathological mechanisms responsible have not been clarified. In this review, we summarize recent findings on this issue and try to clarify the pathology of ER stress-induced kidney diseases. ER stress is evoked in various kidney diseases, including diabetic nephropathy, renal fibrosis, inflammation or osmolar contrast-induced renal injury, ischemia-reperfusion, genetic mutations of renal proteins, proteinuria and cyclosporine A treatment. In some cases, chemical chaperones, such as 4-phenylbutyrate and taurodeoxycholic acid, relieve the symptoms, indicating that ER stress-induced apoptosis of renal cells is one of the major causes of certain kidney diseases. Actually, the ER stress response provides protection against some kidney diseases, although the PERK-ATF4-CHOP pathway of the ER stress response is proapoptotic in some kidney diseases. The disposal of unfolded proteins by autophagy is also protective for some ER stress-induced kidney diseases. Because ER stress is a major cause of some kidney diseases, the ER stress response and autophagy, which deal with unfolded proteins that accumulate in the ER, are promising therapeutic targets in acute and chronic kidney diseases.

  1. Correlates of Physical Functioning and Performance Across the Spectrum of Kidney Function.

    PubMed

    Segura-Ortí, E; Gordon, P L; Doyle, J W; Johansen, K L

    2018-06-01

    The aim of this study was to determine the extent to which poor physical functioning, low participation in physical activity, and muscle atrophy observed among patients on hemodialysis are evident in the earlier stages of chronic kidney disease (CKD). We enrolled adults in three groups: no CKD, Stages 3 to 4 CKD, and hemodialysis. Outcomes measured were physical activity, muscle size, thigh muscle strength, physical performance, and self-reported physical function. Patients with CKD had muscle area intermediate between the no CKD and hemodialysis groups, but they had low levels of physical activity that were similar to the hemodialysis group. Physical activity and muscle size were significantly associated with all outcomes. Kidney function was not significantly associated with muscle strength or physical performance after adjustment for physical activity and muscle size. In conclusion, interventions aimed to increase muscle mass and energy expenditure might have an impact on improving physical function of CKD patients.

  2. Cyclosporine before Coronary Artery Bypass Grafting Does Not Prevent Postoperative Decreases in Renal Function: A Randomized Clinical Trial.

    PubMed

    Ederoth, Per; Dardashti, Alain; Grins, Edgars; Brondén, Björn; Metzsch, Carsten; Erdling, André; Nozohoor, Shahab; Mokhtari, Arash; Hansson, Magnus J; Elmér, Eskil; Algotsson, Lars; Jovinge, Stefan; Bjursten, Henrik

    2018-04-01

    Acute kidney injury is a common complication after cardiac surgery, leading to increased morbidity and mortality. One suggested cause for acute kidney injury is extracorporeal circulation-induced ischemia-reperfusion injury. In animal studies, cyclosporine has been shown to reduce ischemia-reperfusion injury in the kidneys. We hypothesized that administering cyclosporine before extracorporeal circulation could protect the kidneys in patients undergoing cardiac surgery. The Cyclosporine to Protect Renal Function in Cardiac Surgery (CiPRICS) study was an investigator-initiated, double-blind, randomized, placebo-controlled, single-center study. The primary objective was to assess if cyclosporine could reduce acute kidney injury in patients undergoing coronary artery bypass grafting surgery with extracorporeal circulation. In the study, 154 patients with an estimated glomerular filtration rate of 15 to 90 ml · min · 1.73 m were enrolled. Study patients were randomized to receive 2.5 mg/kg cyclosporine or placebo intravenously before surgery. The primary endpoint was relative plasma cystatin C changes from the preoperative day to postoperative day 3. Secondary endpoints included biomarkers of kidney, heart, and brain injury. All enrolled patients were analyzed. The cyclosporine group (136.4 ± 35.6%) showed a more pronounced increase from baseline plasma cystatin C to day 3 compared to placebo (115.9 ± 30.8%), difference, 20.6% (95% CI, 10.2 to 31.2%, P < 0.001). The same pattern was observed for the other renal markers. The cyclosporine group had more patients in Risk Injury Failure Loss End-stage (RIFLE) groups R (risk), I (injury), or F (failure; 31% vs. 8%, P < 0.001). There were no differences in safety parameter distribution between groups. Administration of cyclosporine did not protect coronary artery bypass grafting patients from acute kidney injury. Instead, cyclosporine caused a decrease in renal function compared to placebo that resolved after

  3. Endothelial and kidney function in women with a history of preeclampsia and healthy parous controls: A case control study.

    PubMed

    Lopes van Balen, Veronica A; Spaan, Julia J; Cornelis, Tom; Heidema, Wieteke M; Scholten, Ralph R; Spaanderman, Marc E A

    2018-03-01

    Preeclampsia (PE) is a pregnancy related endothelial disease characterized by hypertension and albuminuria. Postpartum endothelial dysfunction often persists in these women. We postulate that in women with a history of PE reduced endothelial dependent vasodilation coincides with attenuated kidney function, as both reflect endothelial dysfunction. We assessed endothelial and kidney function in women with a history of PE (n=79) and uncomplicated pregnancies (n=49) at least 4years postpartum. Women with hypertension, diabetes or kidney disease prior to pregnancy were excluded. Brachial artery flow mediated dilatation (FMD) was measured and analysed by a custom designed edge-detection and wall-tracking software. We measured albumin and creatinine levels in a 24-h urine sample and calculated glomerular filtration rate (GFR) by CKD-EPI. Women with a history of PE had lower FMD but comparable GFR and albumin creatinine ratio (ACR) compared with controls. Independent of obstetric history, in both controls and women with a history of PE respectively, GFR (r=0.19, p=0.17 and r=0.12, p=0.29) and albumin creatinine ratio (r=0.07, p=0.62 and r=0.06 p=0.57) did not correlate with FMD. At least 4years after pregnancy, women with a history of PE demonstrated decreased flow mediated dilatation when compared to healthy parous controls. In this study, decreased flow mediated dilation however did not coincide with decreased kidney function. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Decreased Functional Brain Connectivity in Adolescents with Internet Addiction

    PubMed Central

    Hong, Soon-Beom; Zalesky, Andrew; Cocchi, Luca; Fornito, Alex; Choi, Eun-Jung; Kim, Ho-Hyun; Suh, Jeong-Eun; Kim, Chang-Dai; Kim, Jae-Won; Yi, Soon-Hyung

    2013-01-01

    Background Internet addiction has become increasingly recognized as a mental disorder, though its neurobiological basis is unknown. This study used functional neuroimaging to investigate whole-brain functional connectivity in adolescents diagnosed with internet addiction. Based on neurobiological changes seen in other addiction related disorders, it was predicted that connectivity disruptions in adolescents with internet addiction would be most prominent in cortico-striatal circuitry. Methods Participants were 12 adolescents diagnosed with internet addiction and 11 healthy comparison subjects. Resting-state functional magnetic resonance images were acquired, and group differences in brain functional connectivity were analyzed using the network-based statistic. We also analyzed network topology, testing for between-group differences in key graph-based network measures. Results Adolescents with internet addiction showed reduced functional connectivity spanning a distributed network. The majority of impaired connections involved cortico-subcortical circuits (∼24% with prefrontal and ∼27% with parietal cortex). Bilateral putamen was the most extensively involved subcortical brain region. No between-group difference was observed in network topological measures, including the clustering coefficient, characteristic path length, or the small-worldness ratio. Conclusions Internet addiction is associated with a widespread and significant decrease of functional connectivity in cortico-striatal circuits, in the absence of global changes in brain functional network topology. PMID:23451272

  5. Dispersal-Based Microbial Community Assembly Decreases Biogeochemical Function

    SciTech Connect

    Graham, Emily B.; Stegen, James C.

    Ecological mechanisms influence relationships among microbial communities, which in turn impact biogeochemistry. In particular, microbial communities are assembled by deterministic (e.g., selection) and stochastic (e.g., dispersal) processes, and the relative balance of these two process types is hypothesized to alter the influence of microbial communities over biogeochemical function. We used an ecological simulation model to evaluate this hypothesis, defining biogeochemical function generically to represent any biogeochemical reaction of interest. We assembled receiving communities under different levels of dispersal from a source community that was assembled purely by selection. The dispersal scenarios ranged from no dispersal (i.e., selection-only) to dispersal ratesmore » high enough to overwhelm selection (i.e., homogenizing dispersal). We used an aggregate measure of community fitness to infer a given community’s biogeochemical function relative to other communities. We also used ecological null models to further link the relative influence of deterministic assembly to function. We found that increasing rates of dispersal decrease biogeochemical function by increasing the proportion of maladapted taxa in a local community. Niche breadth was also a key determinant of biogeochemical function, suggesting a tradeoff between the function of generalist and specialist species. Finally, we show that microbial assembly processes exert greater influence over biogeochemical function when there is variation in the relative contributions of dispersal and selection among communities. Taken together, our results highlight the influence of spatial processes on biogeochemical function and indicate the need to account for such effects in models that aim to predict biogeochemical function under future environmental scenarios.« less

  6. Dispersal-Based Microbial Community Assembly Decreases Biogeochemical Function

    DOE PAGES

    Graham, Emily B.; Stegen, James C.

    2017-11-01

    Ecological mechanisms influence relationships among microbial communities, which in turn impact biogeochemistry. In particular, microbial communities are assembled by deterministic (e.g., selection) and stochastic (e.g., dispersal) processes, and the relative balance of these two process types is hypothesized to alter the influence of microbial communities over biogeochemical function. We used an ecological simulation model to evaluate this hypothesis, defining biogeochemical function generically to represent any biogeochemical reaction of interest. We assembled receiving communities under different levels of dispersal from a source community that was assembled purely by selection. The dispersal scenarios ranged from no dispersal (i.e., selection-only) to dispersal ratesmore » high enough to overwhelm selection (i.e., homogenizing dispersal). We used an aggregate measure of community fitness to infer a given community’s biogeochemical function relative to other communities. We also used ecological null models to further link the relative influence of deterministic assembly to function. We found that increasing rates of dispersal decrease biogeochemical function by increasing the proportion of maladapted taxa in a local community. Niche breadth was also a key determinant of biogeochemical function, suggesting a tradeoff between the function of generalist and specialist species. Finally, we show that microbial assembly processes exert greater influence over biogeochemical function when there is variation in the relative contributions of dispersal and selection among communities. Taken together, our results highlight the influence of spatial processes on biogeochemical function and indicate the need to account for such effects in models that aim to predict biogeochemical function under future environmental scenarios.« less

  7. Common cold decreases lung function in infants with recurrent wheezing.

    PubMed

    Mallol, J; Aguirre, V; Wandalsen, G

    2010-01-01

    Common acute viral respiratory infections (colds) are the most frequent cause of exacerbations in infants with recurrent wheezing (RW). However, there is no quantitative information about the effect of colds on the lung function of infants with RW. This study was undertaken to determine the effect of common cold on forced expiratory parameters measured from raised lung volume in infants with RW. Spirometric lung function (expiratory flows from raised lung volume) was randomly assessed in 28 infants with RW while they had a common cold and when asymptomatic. It was found that during colds there was a significant decrease in all forced expiratory parameters and this was much more evident for flows (FEF(50%), FEF(75%) and FEF(25-75%)) which were definitively abnormal (less than -1.65 z-score) in the majority of infants. There was not association between family asthma, tobacco exposure, and other factors, with the extent of lung function decrease during colds. Tobacco during pregnancy but not a history of family asthma was significantly associated to lower expiratory flows; however, the association was significant only when infants were asymptomatic. This study shows that common colds cause a marked reduction of lung function in infants with RW. 2009 SEICAP. Published by Elsevier Espana. All rights reserved.

  8. Left Ventricular Mass Progression Despite Stable Blood Pressure and Kidney Function in Stage 3 CKD

    PubMed Central

    Seifert, Michael E.; Fuentes, Lisa de las; Ginsberg, Charles; Rothstein, Marcos; Dietzen, Dennis J.; Cheng, Steven C.; Ross, Will; Windus, David; Dávila-Román, Victor G.; Hruska, Keith A.

    2014-01-01

    Background/Aims Progressive chronic kidney disease (CKD) is associated with worsening cardiovascular risk not explained by traditional risk factors. Left ventricular hypertrophy (LVH) is an important cardiovascular risk factor, but its progression has not been documented in early CKD. We explored whether progression of LVH in early CKD would occur despite stable kidney function. Methods We conducted a post hoc analysis of a 12-m nth study of lanthanum carbonate in stage 3 CKD, which included longitudinal assessments of cardiovascular biomarkers. Primary outcome for the analysis was the change in LV mass indexed to height in meters2.7 (LVM/Ht2.7). Secondary outcomes were changes in blood pressure (BP), pulse-wave velocity, LV systolic/diastolic function, fibroblast growth factor-23 (FGF23), klotho, and eGFR. Results 31 of 38 original subjects had sufficient data for analysis. LVM/Ht2.7 increased (47 ± 13 vs. 53 ± 13 g/m2.7, P=0.006) over 12 months despite stable BP, stable eGFR and normal LV systolic function. Vascular stiffness and LV diastolic dysfunction persisted throughout the study. Klotho levels decreased (748 ± 289 to 536 ± 410 pg/ml, P=0.03) but were unrelated to changes in LVM/Ht2.7. The change in FGF23/klotho ratio was strongly correlated with changes in LVM/Ht2.7 (r2 0.582, P=0.03). Conclusion Subjects with stage 3 CKD exhibited increasing LV mass, persistent LV diastolic dysfunction and vascular stiffness despite stable kidney function, BP and LV systolic function. Abnormal FGF23 signaling due to reduced klotho expression may be associated with increasing LV mass. These findings deserve further evaluation in a larger population, given the adverse prognostic value of these cardiovascular biomarkers. PMID:24818573

  9. Bardoxolone Methyl Decreases Megalin and Activates Nrf2 in the Kidney

    PubMed Central

    Chertow, Glenn M.; Hebbar, Sudarshan; Vaziri, Nosratola D.; Ward, Keith W.; Meyer, Colin J.

    2012-01-01

    Inflammation and oxidative stress are hallmarks and mediators of the progression of CKD. Bardoxolone methyl, a potent activator of the nuclear factor erythroid 2–related factor 2 (Nrf2)–mediated antioxidant and anti-inflammatory response, increases estimated GFR and decreases BUN, serum phosphorus, and uric acid concentrations in patients with moderate to severe CKD. However, it also increases albuminuria, which is associated with inflammation and disease progression. Therefore, we investigated whether this bardoxolone methyl–induced albuminuria may result from the downregulation of megalin, a protein involved in the tubular reabsorption of albumin and lipid-bound proteins. Administration of bardoxolone methyl to cynomolgus monkeys significantly decreased the protein expression of renal tubular megalin, which inversely correlated with the urine albumin-to-creatinine ratio. Moreover, daily oral administration of bardoxolone methyl to monkeys for 1 year did not lead to any adverse effects on renal histopathologic findings but did reduce serum creatinine and BUN, as observed in patients with CKD. Finally, the bardoxolone methyl–induced decrease in megalin corresponded with pharmacologic induction of renal Nrf2 targets, including NAD(P)H:quinone oxidoreductase 1 enzyme activity and glutathione content. This result indicates that Nrf2 may have a role in megalin regulation. In conclusion, these data suggest that the increase in albuminuria that accompanies bardoxolone methyl administration may result, at least in part, from reduced expression of megalin, which seems to occur without adverse effects and with strong induction of Nrf2 targets. PMID:22859857

  10. Bardoxolone methyl decreases megalin and activates nrf2 in the kidney.

    PubMed

    Reisman, Scott A; Chertow, Glenn M; Hebbar, Sudarshan; Vaziri, Nosratola D; Ward, Keith W; Meyer, Colin J

    2012-10-01

    Inflammation and oxidative stress are hallmarks and mediators of the progression of CKD. Bardoxolone methyl, a potent activator of the nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant and anti-inflammatory response, increases estimated GFR and decreases BUN, serum phosphorus, and uric acid concentrations in patients with moderate to severe CKD. However, it also increases albuminuria, which is associated with inflammation and disease progression. Therefore, we investigated whether this bardoxolone methyl-induced albuminuria may result from the downregulation of megalin, a protein involved in the tubular reabsorption of albumin and lipid-bound proteins. Administration of bardoxolone methyl to cynomolgus monkeys significantly decreased the protein expression of renal tubular megalin, which inversely correlated with the urine albumin-to-creatinine ratio. Moreover, daily oral administration of bardoxolone methyl to monkeys for 1 year did not lead to any adverse effects on renal histopathologic findings but did reduce serum creatinine and BUN, as observed in patients with CKD. Finally, the bardoxolone methyl-induced decrease in megalin corresponded with pharmacologic induction of renal Nrf2 targets, including NAD(P)H:quinone oxidoreductase 1 enzyme activity and glutathione content. This result indicates that Nrf2 may have a role in megalin regulation. In conclusion, these data suggest that the increase in albuminuria that accompanies bardoxolone methyl administration may result, at least in part, from reduced expression of megalin, which seems to occur without adverse effects and with strong induction of Nrf2 targets.

  11. Low birth weight is associated with impaired murine kidney development and function.

    PubMed

    Barnett, Christina; Nnoli, Oluwadara; Abdulmahdi, Wasan; Nesi, Lauren; Shen, Michael; Zullo, Joseph A; Payne, David L; Azar, Tala; Dwivedi, Parth; Syed, Kunzah; Gromis, Jonathan; Lipphardt, Mark; Jules, Edson; Maranda, Eric L; Patel, Amy; Rabadi, May M; Ratliff, Brian B

    2017-08-01

    BackgroundLow birth weight (LBW) neonates have impaired kidney development that leaves them susceptible to kidney disease and hypertension during adulthood. The study here identifies events that blunt nephrogenesis and kidney development in the murine LBW neonate.MethodsWe examined survival, kidney development, GFR, gene expression, and cyto-/chemokines in the LBW offspring of malnourished (caloric and protein-restricted) pregnant mice.ResultsMalnourished pregnant mothers gave birth to LBW neonates that had 40% reduced body weight and 54% decreased survival. Renal blood perfusion was reduced by 37%, whereas kidney volume and GFR were diminished in the LBW neonate. During gestation, the LBW neonatal kidney had 2.2-fold increased apoptosis, 76% decreased SIX2+ progenitor cells, downregulation of mesenchymal-to-epithelial signaling factors Wnt9b and Fgf8, 64% less renal vesicle formation, and 32% fewer nephrons than controls. At birth, increased plasma levels of IL-1β, IL-6, IL-12(p70), and granulocyte-macrophage colony-stimulating factor in the LBW neonate reduced SIX2+ progenitor cells.ConclusionIncreased pro-inflammatory cytokines in the LBW neonate decrease SIX2+ stem cells in the developing kidney. Reduced renal stem cells (along with the decreased mesenchymal-to-epithelial signaling) blunt renal vesicle generation, nephron formation, and kidney development. Subsequently, the mouse LBW neonate has reduced glomeruli volume, renal perfusion, and GFR.

  12. [Recovery characteristic of donor's and receptor's renal function from age over 55 years living donors donate kidneys].

    PubMed

    Hu, Xiao-Peng; Yin, Hang; Zhang, Xiao-Dong; Wang, Wei; Ren, Liang; Yang, Xiao-Yong; Li, Xiao-Bei; Liu, Hang; Wang, Yong

    2009-10-20

    To observe and research clinical characteristics and curative effect and safety of renal transplantation from living elderly donors donating kidneys. Retrospective study on the 19 living kidney donors who were over 55 years old and on the renal transplantation operations completed by our center for the past few years. Among the 19 donors, with an average age of 58 years old. Their mean creatinine clearance was 81.7 +/- 2.2 ml/min. Among the 19 acceptors, with an average age of 34 years old. All kidney before the open circulation transplant performed routine 0 point puncture and histological examination. All donors smoothly spent their perioperative period without any surgical complications. All the donors keep their blood Cr in a normal range one week after the operation. There was no significant difference between posttransplantation one week and six month and one year in blood Cr and Ccr. Blood pressure and blood sugar didn't not have significant changes, urine protein(-). All receptors' renal functions recovered in early stages without DGF. 7 receptors who had Ccr lower than 80 ml/min had their blood Cr decreased slowly. Among the 19 kidneys donated, 3 donors' glomerulosclerosises were higher than 10 percent. The kidney source shortage is the main factor that restricts the development of the renal transplantation currently, undoubtedly, the application of elderly donors will expand the kidney source and save more uremic patients. Renal transplantation is safe and feasible with the help of living elderly donors.

  13. Decrease in pulmonary function and oxygenation after lung resection.

    PubMed

    Brocki, Barbara Cristina; Westerdahl, Elisabeth; Langer, Daniel; Souza, Domingos S R; Andreasen, Jan Jesper

    2018-01-01

    Respiratory deficits are common following curative intent lung cancer surgery and may reduce the patient's ability to be physically active. We evaluated the influence of surgery on pulmonary function, respiratory muscle strength and physical performance after lung resection. Pulmonary function, respiratory muscle strength (maximal inspiratory/expiratory pressure) and 6-min walk test (6MWT) were assessed pre-operatively, 2 weeks post-operatively and 6 months post-operatively in 80 patients (age 68±9 years). Video-assisted thoracoscopic surgery was performed in 58% of cases. Two weeks post-operatively, we found a significant decline in pulmonary function (forced vital capacity -0.6±0.6 L and forced expiratory volume in 1 s -0.43±0.4 L; both p<0.0001), 6MWT (-37.6±74.8 m; p<0.0001) and oxygenation (-2.9±4.7 units; p<0.001), while maximal inspiratory and maximal expiratory pressure were unaffected. At 6 months post-operatively, pulmonary function and oxygenation remained significantly decreased (p<0.001), whereas 6MWT was recovered. We conclude that lung resection has a significant short- and long-term impact on pulmonary function and oxygenation, but not on respiratory muscle strength. Future research should focus on mechanisms negatively influencing post-operative pulmonary function other than impaired respiratory muscle strength.

  14. Dietary intake of fiber, fruit and vegetables decreases the risk of incident kidney stones in women: a Women's Health Initiative report.

    PubMed

    Sorensen, Mathew D; Hsi, Ryan S; Chi, Thomas; Shara, Nawar; Wactawski-Wende, Jean; Kahn, Arnold J; Wang, Hong; Hou, Lifang; Stoller, Marshall L

    2014-12-01

    We evaluated the relationship between dietary fiber, fruit and vegetable intake, and the risk of kidney stone formation. Overall 83,922 postmenopausal women from the Women's Health Initiative observational study were included in the analysis and followed prospectively. Cox proportional hazards regression analyses were used to evaluate the associations between total dietary fiber, fruit and vegetable intake, and the risk of incident kidney stone formation, adjusting for nephrolithiasis risk factors (age, race/ethnicity, geographic region, diabetes mellitus, calcium supplementation, hormone therapy use, body mass index and calibrated caloric intake; and dietary water, sodium, animal protein and calcium intake). Women with a history of kidney stones (3,471) were analyzed separately. Mean age of the women was 64±7 years, 85% were white and 2,937 (3.5%) experienced a kidney stone in a median followup of 8 years. In women with no history of kidney stones higher total dietary fiber (6% to 26% decreased risk, p <0.001), greater fruit intake (12% to 25% decreased risk, p <0.001) and greater vegetable intake (9% to 22% decreased risk, p=0.002) were associated with a decreased risk of incident kidney stone formation in separate adjusted models. In women with a history of stones there were no significant protective effects of fiber, fruit or vegetable intake on the risk of kidney stone recurrence. Greater dietary intake of fiber, fruits and vegetables was associated with a reduced risk of incident kidney stones in postmenopausal women. The protective effects were independent of other known risk factors for kidney stones. In contrast, there was no reduction in risk in women with a history of stones. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  15. Measuring dynamic kidney function in an undergraduate physiology laboratory.

    PubMed

    Medler, Scott; Harrington, Frederick

    2013-12-01

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

  16. Estimating residual kidney function in dialysis patients without urine collection

    PubMed Central

    Shafi, Tariq; Michels, Wieneke M.; Levey, Andrew S.; Inker, Lesley A.; Dekker, Friedo W.; Krediet, Raymond T.; Hoekstra, Tiny; Schwartz, George J.; Eckfeldt, John H.; Coresh, Josef

    2016-01-01

    Residual kidney function contributes substantially to solute clearance in dialysis patients but cannot be assessed without urine collection. We used serum filtration markers to develop dialysis-specific equations to estimate urinary urea clearance without the need for urine collection. In our development cohort, we measured 24-hour urine clearances under close supervision in 44 patients and validated these equations in 826 patients from the Netherlands Cooperative Study on the Adequacy of Dialysis. For the development and validation cohorts, median urinary urea clearance was 2.6 and 2.4 mL/min, respectively. During the 24-hour visit in the development cohort, serum β-trace protein concentrations remained in steady state but concentrations of all other markers increased. In the validation cohort, bias (median measured minus estimated clearance) was low for all equations. Precision was significantly better for β-trace protein and β2-microglobulin equations and the accuracy was significantly greater for β-trace protein, β2-microglobulin and cystatin C equations, compared with the urea plus creatinine equation. Area under the receiver operator characteristic curve for detecting measured urinary urea clearance by equation-estimated urinary urea clearance (both 2 mL/min or more) were 0.821, 0.850 and 0.796 for β-trace protein, β2-microglobulin and cystatin C equations, respectively; significantly greater than the 0.663 for the urea plus creatinine equation. Thus, residual renal function can be estimated in dialysis patients without urine collections. PMID:26924062

  17. 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.

  18. Extrusion decreases the negative effects of kidney bean on enzyme and transport activities of the rat small intestine.

    PubMed

    Marzo, F; Milagro, F I; Urdaneta, E; Barrenetxe, J; Ibañez, F C

    2011-10-01

    The objective of the present study was to evaluate the influence of raw and extruded kidney bean (Phaseolus vulgaris L. var. Pinto) consumption on the gut physiology of young growing rats. The intestinal enzyme activity (sucrase, maltase, Na(+) /K(+) ATPase, aminopeptidase N, dipeptidylpeptidase IV, alkaline phosphatase) and the uptake of sugar (d-galactose) and amino acids (l-leucine) were measured in brush border membrane vesicles. Five groups of growing male Wistar rats were fed ad libitum for 15 days on five different 10% protein diets: one containing casein as the main source of protein (Control, C), and four containing raw (RKB1, RKB6) or extruded kidney bean (EKB1, EKB6) at 1% and 6% of total protein content respectively. Extrusion treatment significantly reduced the content of bioactive factors (phytates, tannins) and abolished lectins, trypsin, chymotrypsin, and α-amylase inhibitory activities. Rats fed raw beans (especially RKB6) showed lower growth rate and food intake as compared to those fed extruded legumes, probably due to the high levels of lectins and other anti-nutritive factors in the raw beans. Gut enzymatic activities and uptake of d-galactose and l-leucine were lower in RKB6 and RKB1-fed animals, although they significantly improved in the groups fed extruded beans. Enzymatic activity and uptake in EKB1 were similar to those of casein-fed rats, whereas the uptake and growth rate of EKB6 were different to the control. This is attributable to the higher non-thermolabile biofactor content in the EKB6 diet, especially phytates and tannins, than in EKB1. This article shows the dose-dependent toxicological effects of bioactive factors contained in kidney beans on gut function. The extrusion process reduced their adverse impact on gut physiology and growth rate. © 2010 Blackwell Verlag GmbH.

  19. Receptors for atrial natriuretic peptide are decreased in the kidney of rats with streptozotocin-induced diabetes mellitus.

    PubMed Central

    Sechi, L A; Valentin, J P; Griffin, C A; Lee, E; Bartoli, E; Humphreys, M H; Schambelan, M

    1995-01-01

    To determine whether decreased renal responsiveness to atrial natriuretic peptide (ANP) in diabetes is mediated by alterations in the renal ANP receptor, ANP receptor density and affinity were measured 17-20 d after streptozotocin injection and compared with values in vehicle-treated controls and streptozotocin-treated rats made euglycemic with insulin. Plasma ANP concentration was significantly greater in hyperglycemic diabetic rats than in control or euglycemic diabetic rats. Both in glomeruli and inner medulla, ANP receptor dissociation constant did not differ among the three study groups, whereas the maximum binding capacity was decreased significantly in hyperglycemic diabetics in comparison with controls and euglycemic diabetics. Glomerular clearance receptors were also decreased significantly in hyperglycemic diabetic rats in comparison with control and euglycemic diabetic rats. To determine whether the decreased number of renal ANP receptors in diabetic rats was associated with a decreased biological response, we measured ANP-dependent cyclic GMP (cGMP) accumulation by isolated glomeruli and inner medullary collecting duct cells in vitro. cGMP accumulation was significantly less in hyperglycemic diabetic rats than in controls or euglycemic diabetic rats both in the presence or absence of the phosphodiesterase inhibitor zaprinast. cGMP phosphodiesterase activity in inner medullary collecting duct cells obtained from control and hyperglycemic diabetic rats did not differ. Thus, the decreased number of biologically active ANP receptors in the kidneys of diabetic rats is accompanied by decreased biological responsiveness in vitro and provides a potential explanation for the reduction in renal sensitivity to ANP in this condition. Images PMID:7769090

  20. 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.

  1. 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.

  2. Metoprolol decreases the plasma exposure of metformin via the induction of liver, kidney and muscle uptake in rats.

    PubMed

    Ma, Yan-Rong; Shi, A-Xi; Qin, Hong-Yan; Zhang, Tiffany; Wu, Yan-Fang; Zhang, Guo-Qiang; Wu, Xin-An

    2016-12-01

    Drug interactions are one of the commonest causes of side effects, particularly in long-term therapy. The aim of the current study was to investigate the possible effects of metoprolol on the pharmacokinetics of metformin in rats and to clarify the mechanism of drug interaction. In this study, rats were treated with metformin alone or in combination with metoprolol. Plasma, urine and tissue concentrations of metformin were determined by HPLC. Western blotting and real-time qPCR were used to evaluate the expression of rOCTs and rMATE1. The results showed that, after single or 7-day repeated administration, the plasma concentrations of metformin in the co-administration group were significantly decreased compared with that in the metformin group. However, the parameter V/F of metformin in the co-administration group was markedly increased compared with that in the metformin group. The hepatic, renal and muscular K p of metformin were markedly elevated after co-administration with metoprolol. Consistently, metformin uptake in rat kidney slices was significantly induced by metoprolol. In addition, multiple administrations of metoprolol significantly reduced the expression of rMATE1 in rat kidney as well as the urinary excretion of metformin. Importantly, after long-term administration, lactic acid and uric acid levels in the co-administration group were increased by 25% and 26%, respectively, compared with that in the metformin group. These results indicate that metoprolol can decrease the plasma concentration of metformin via the induction of hepatic, renal and muscular uptake, and long-term co-administration of metformin and metoprolol can cause elevated lactic acid and uric acid levels. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  3. The Tacrolimus Metabolism Rate Influences Renal Function after Kidney Transplantation

    PubMed Central

    Thölking, Gerold; Fortmann, Christian; Koch, Raphael; Gerth, Hans Ulrich; Pabst, Dirk; Pavenstädt, Hermann; Kabar, Iyad; Hüsing, Anna; Wolters, Heiner

    2014-01-01

    The effective calcineurin inhibitor (CNI) tacrolimus (Tac) is an integral part of the standard immunosuppressive regimen after renal transplantation (RTx). However, as a potent CNI it has nephrotoxic potential leading to impaired renal function in some cases. Therefore, it is of high clinical impact to identify factors which can predict who is endangered to develop CNI toxicity. We hypothesized that the Tac metabolism rate expressed as the blood concentration normalized by the dose (C/D ratio) is such a simple predictor. Therefore, we analyzed the impact of the C/D ratio on kidney function after RTx. Renal function was analyzed 1, 2, 3, 6, 12 and 24 months after RTx in 248 patients with an immunosuppressive regimen including basiliximab, tacrolimus, mycophenolate mofetil and prednisolone. According to keep the approach simple, patients were split into three C/D groups: fast, intermediate and slow metabolizers. Notably, compared with slow metabolizers fast metabolizers of Tac showed significantly lower estimated glomerular filtration rate (eGFR) values at all the time points analyzed. Moreover, fast metabolizers underwent more indication renal biopsies (p = 0.006) which revealed a higher incidence of CNI nephrotoxicity (p = 0.015) and BK nephropathy (p = 0.024) in this group. We herein identified the C/D ratio as an easy calculable risk factor for the development of CNI nephrotoxicity and BK nephropathy after RTx. We propose that the simple C/D ratio should be taken into account early in patient’s risk management strategies. PMID:25340655

  4. Decrease in pulmonary function and oxygenation after lung resection

    PubMed Central

    Westerdahl, Elisabeth; Langer, Daniel; Souza, Domingos S.R.; Andreasen, Jan Jesper

    2018-01-01

    Respiratory deficits are common following curative intent lung cancer surgery and may reduce the patient's ability to be physically active. We evaluated the influence of surgery on pulmonary function, respiratory muscle strength and physical performance after lung resection. Pulmonary function, respiratory muscle strength (maximal inspiratory/expiratory pressure) and 6-min walk test (6MWT) were assessed pre-operatively, 2 weeks post-operatively and 6 months post-operatively in 80 patients (age 68±9 years). Video-assisted thoracoscopic surgery was performed in 58% of cases. Two weeks post-operatively, we found a significant decline in pulmonary function (forced vital capacity −0.6±0.6 L and forced expiratory volume in 1 s −0.43±0.4 L; both p<0.0001), 6MWT (−37.6±74.8 m; p<0.0001) and oxygenation (−2.9±4.7 units; p<0.001), while maximal inspiratory and maximal expiratory pressure were unaffected. At 6 months post-operatively, pulmonary function and oxygenation remained significantly decreased (p<0.001), whereas 6MWT was recovered. We conclude that lung resection has a significant short- and long-term impact on pulmonary function and oxygenation, but not on respiratory muscle strength. Future research should focus on mechanisms negatively influencing post-operative pulmonary function other than impaired respiratory muscle strength. PMID:29362707

  5. Dramatic decreases in brain reward function during nicotine withdrawal.

    PubMed

    Epping-Jordan, M P; Watkins, S S; Koob, G F; Markou, A

    1998-05-07

    Tobacco smoking is a worldwide public health problem. In the United States alone, over 400,000 deaths and $50 billion in medical costs annually are directly attributed to smoking. Accumulated evidence indicates that nicotine is the component of tobacco smoke that leads to addiction, but the means by which nicotine produces addiction remain unclear. Nicotine is less effective as a positive reinforcer than other drugs of abuse in non-dependent animals. Nevertheless, nicotine-withdrawal symptoms, including depressed mood, anxiety, irritability and craving in dependent subjects may contribute to the addictive liability of nicotine. We show here that spontaneous nicotine withdrawal in rats resulted in a significant decrease in brain reward function, as measured by elevations in brain reward thresholds, which persisted for four days. Further, systemic injections of a competitive nicotinic-receptor antagonist led to a dose-dependent increase in brain reward thresholds in chronic nicotine-treated rats. The decreased function in brain reward systems during nicotine withdrawal is comparable in magnitude and duration to that of other major drugs of abuse, and may constitute an important motivational factor that contributes to craving, relapse and continued tobacco consumption in humans.

  6. Physical function was related to mortality in patients with chronic kidney disease and dialysis.

    PubMed

    Morishita, Shinichiro; Tsubaki, Atsuhiro; Shirai, Nobuyuki

    2017-10-01

    Previous studies have shown that exercise improves aerobic capacity, muscular functioning, cardiovascular function, walking capacity, and health-related quality of life (QOL) in patients with chronic kidney disease (CKD) and dialysis. Recently, additional studies have shown that higher physical activity contributes to survival and decreased mortality as well as physical function and QOL in patients with CKD and dialysis. Herein, we review the evidence that physical function and physical activity play an important role in mortality for patients with CKD and dialysis. During November 2016, Medline and Web of Science databases were searched for published English medical reports (without a time limit) using the terms "CKD" or "dialysis" and "mortality" in conjunction with "exercise capacity," "muscle strength," "activities of daily living (ADL)," "physical activity," and "exercise." Numerous studies suggest that higher exercise capacity, muscle strength, ADL, and physical activity contribute to lower mortality in patients with CKD and dialysis. Physical function is associated with mortality in patients with CKD and dialysis. Increasing physical function may decrease the mortality rate of patients with CKD and dialysis. Physicians and medical staff should recognize the importance of physical function in CKD and dialysis. In addition, exercise is associated with reduced mortality among patients with CKD and dialysis. © 2017 International Society for Hemodialysis.

  7. Muscle function in Turner syndrome: normal force but decreased power.

    PubMed

    Soucek, Ondrej; Lebl, Jan; Matyskova, Jana; Snajderova, Marta; Kolouskova, Stanislava; Pruhova, Stepanka; Hlavka, Zdenek; Sumnik, Zdenek

    2015-02-01

    Although hypogonadism and SHOX gene haploinsufficiency likely cause the decreased bone mineral density and increased fracture rate associated with Turner syndrome (TS), the exact mechanism remains unclear. We tested the hypothesis that muscle dysfunction in patients with TS contributes to increased fracture risk. The secondary aim was to determine whether menarche, hormone therapy duration, positive fracture history and genotype influence muscle function parameters in patients with TS. A cross-sectional study was conducted in a single university hospital referral centre between March 2012 and October 2013. Sixty patients with TS (mean age of 13·7 ± 4·5 years) were compared to the control group of 432 healthy girls. A Leonardo Mechanograph(®) Ground Reaction Force Platform was used to assess muscle force (Fmax ) by the multiple one-legged hopping test and muscle power (Pmax ) by the single two-legged jump test. While the Fmax was normal (mean weight-specific Z-score of 0·11 ± 0·77, P = 0·27), the Pmax was decreased in patients with TS (Z-score of -0·93 ± 1·5, P < 0·001) compared with healthy controls. The muscle function parameters were not significantly influenced by menarcheal stage, hormone therapy duration, fracture history or genotype (linear regression adjusted for age, weight and height; P > 0·05 for all). Fmax , a principal determinant of bone strength, is normal in patients with TS. Previously described changes in bone quality and structure in TS are thus not likely related to inadequate mechanical loading but rather represent a primary bone deficit. A decreased Pmax indicates impaired muscle coordination in patients with TS. © 2014 John Wiley & Sons Ltd.

  8. Tissue-Engineering Approaches to Restore Kidney Function.

    PubMed

    Katari, Ravi; Edgar, Lauren; Wong, Theresa; Boey, Angela; Mancone, Sarah; Igel, Daniel; Callese, Tyler; Voigt, Marcia; Tamburrini, Riccardo; Zambon, Joao Paulo; Perin, Laura; Orlando, Giuseppe

    2015-10-01

    Kidney transplantation for the treatment of chronic kidney disease has established outcome and quality of life. However, its implementation is severely limited by a chronic shortage of donor organs; consequently, most candidates remain on dialysis and on the waiting list while accruing further morbidity and mortality. Furthermore, those patients that do receive kidney transplants are committed to a life-long regimen of immunosuppressive drugs that also carry significant adverse risk profiles. The disciplines of tissue engineering and regenerative medicine have the potential to produce alternative therapies which circumvent the obstacles posed by organ shortage and immunorejection. This review paper describes some of the most promising tissue-engineering solutions currently under investigation for the treatment of acute and chronic kidney diseases. The various stem cell therapies, whole embryo transplantation, and bioengineering with ECM scaffolds are outlined and summarized.

  9. No effect of mercury exposure on kidney function during ongoing artisanal gold mining activities in Colombia.

    PubMed

    Rodríguez, Luz Helena Sánchez; Rodríguez-Villamizar, Laura Andrea; Flórez-Vargas, Oscar; Fiallo, Yolanda Vargas; Ordoñez, Álvaro; Gutiérrez, Myriam Del Carmen

    2017-01-01

    This cross-sectional study examined whether people who are exposed to mercury (Hg) vapours in ongoing artisanal gold mining activities have alteration in kidney function monitoring parameters. The study enrolled 164 miners and 127 participant controls. The Hg concentrations for miners and control participants were measured in blood (B-Hg; median 7.0 vs. 2.5 µg/L), urine (U-Hg; median 3.9 vs. 1.5 µg/g creatinine) and hair (H-Hg; median 0.8 vs. 0.4 µg/g hair). The biomarkers of renal function were creatinine, albumin and excretion of β-2 microglobulin. Glomerular filtration rate (eGFR) was calculated using the chronic kidney disease epidemiology collaboration equation. Significant statistical differences were found in Hg concentrations and eGFR levels between the two study groups ( p < 0.01) but not with the other biomarkers of renal function. A multiple regression model was applied to explore the relationship of eGFR levels and Hg concentrations. However, no association was found between the prevalence of reduced eGFR (<71.96 mL/min/1.73 m 2 ) and the B-Hg or U-Hg levels after adjustment for covariates. Nevertheless, it was observed that having B-Hg levels above 10 µg Hg/L decreased the eGFR by 1.7 mL/min/1.73 m 2 (confidence interval 95% -5.1 to 1.7) compared to having levels below 2.0 µg Hg/L. Our results found no support for kidney damage associated with Hg vapour exposure in ongoing artisanal gold mining, whose population has a level of Hg exposure from low to moderate (B-Hg from 3.4 to 11.0 µg/L and U-Hg from 1.3 to 9.6 µg/g creatinine).

  10. 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.

  11. 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 ...

  12. Kidney function in the Spinifex hopping mouse, Notomys alexis.

    PubMed

    Gordge, L; Roberts, J R

    2008-06-01

    Notomys alexis (Spinifex hopping mouse) is found in the arid zone of Australia. The structure and function of the kidneys allow this species to conserve water. This study investigated the rate at which N. alexis can reduce urine volume and increase the concentration of electrolytes and solutes when water deprived. It also looked at the response to rehydration, following a period of water deprivation. The laboratory mouse, Mus musculus domesticus, was used for comparison. N. alexis is able to reduce urine volume and increase urine concentration more rapidly than M. m. domesticus when water deprived. This appears to occur prior to any measurable changes in plasma electrolyte concentrations and is not due to reductions in glomerular filtration rate. Gradual water deprivation over a period of 10 days allowed N. alexis to adjust so that urine composition was similar in many ways to animals that had ad libitum access to water, whereas M. m. domesticus required significant water supplementation to maintain body weight at 85% of initial body weight. Ability to concentrate urine rapidly is characteristic of a well-insulated renal medulla [Bankir, L., DeRouffignac, C., 1985. Urinary concentrating ability: insights from comparative anatomy. Am. J. Physiol. 249, R643-666]. However, a well-insulated medulla is normally associated with slow dilution of urine when animals are rehydrated. N. alexis was able to produce dilute urine very rapidly following rehydration of water deprived animals. Physiological control of renal function appears to be complex. Although M. m. domesticus is able to produce concentrated urine, it is unable to survive without free water and responds more slowly to water deprivation.

  13. Estimating residual kidney function in dialysis patients without urine collection.

    PubMed

    Shafi, Tariq; Michels, Wieneke M; Levey, Andrew S; Inker, Lesley A; Dekker, Friedo W; Krediet, Raymond T; Hoekstra, Tiny; Schwartz, George J; Eckfeldt, John H; Coresh, Josef

    2016-05-01

    Residual kidney function contributes substantially to solute clearance in dialysis patients but cannot be assessed without urine collection. We used serum filtration markers to develop dialysis-specific equations to estimate urinary urea clearance without the need for urine collection. In our development cohort, we measured 24-hour urine clearances under close supervision in 44 patients and validated these equations in 826 patients from the Netherlands Cooperative Study on the Adequacy of Dialysis. For the development and validation cohorts, median urinary urea clearance was 2.6 and 2.4 ml/min, respectively. During the 24-hour visit in the development cohort, serum β-trace protein concentrations remained in steady state but concentrations of all other markers increased. In the validation cohort, bias (median measured minus estimated clearance) was low for all equations. Precision was significantly better for β-trace protein and β2-microglobulin equations and the accuracy was significantly greater for β-trace protein, β2-microglobulin, and cystatin C equations, compared with the urea plus creatinine equation. Area under the receiver operator characteristic curve for detecting measured urinary urea clearance by equation-estimated urinary urea clearance (both 2 ml/min or more) were 0.821, 0.850, and 0.796 for β-trace protein, β2-microglobulin, and cystatin C equations, respectively; significantly greater than the 0.663 for the urea plus creatinine equation. Thus, residual renal function can be estimated in dialysis patients without urine collections. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  14. Antigravity suit inflation: kidney function and cardiovascular and hormonal responses in men.

    PubMed

    Geelen, G; Kravik, S E; Hadj-Aissa, A; Leftheriotis, G; Vincent, M; Bizollon, C A; Sem-Jacobsen, C W; Greenleaf, J E; Gharib, C

    1989-02-01

    To investigate the effects of lower body positive pressure (LBPP) on kidney function while controlling certain cardiovascular and endocrine responses, seven men [35 +/- 2 (SE) yr] underwent 30 min of sitting and then 4.5 h of 70 degrees head-up tilt. An antigravity suit was applied (60 Torr legs, 30 Torr abdomen) during the last 3 h of tilt. A similar noninflation experiment was conducted where the suited subjects were tilted for 3.5 h. To provide adequate urine flow, the subjects were hydrated during the course of both experiments. Immediately after inflation, mean arterial pressure increased by 8 +/- 3 Torr and pulse rate decreased by 16 +/- 3 beats/min. Plasma renin activity and aldosterone were maximally suppressed (P less than 0.05) after 2.5 h of inflation. Plasma vasopressin decreased by 40-50% (P less than 0.05) and plasma sodium and potassium remained unchanged during both experiments. Glomerular filtration rate was not increased significantly by inflation, whereas inflation induced marked increases (P less than 0.05) in effective renal plasma flow (ERPF), urine flow, osmolar and free water clearances, and total and fractional sodium excretion. No such changes occurred during control. Thus, LBPP induces 1) a significant increase in ERPF and 2) significant changes in kidney excretory patterns similar to those observed during water immersion or the early phase of bed rest, situations that also result in central vascular volume expansion.

  15. Decreased shoulder function and pain common in recreational badminton players.

    PubMed

    Fahlström, M; Söderman, K

    2007-06-01

    The aim of this study was to describe the prevalence and consequences of painful conditions in the shoulder region in recreational badminton players. A questionnaire study was performed on 99 players, of whom 57 were also assessed with Constant score. Previous or present pain in the dominant shoulder was reported by 52% of the players. Sixteen percent of the players had on-going shoulder pain associated with badminton play. A majority of these players reported that their training habits were affected by the pain. Total Constant score was lower in the painful shoulders. Furthermore, range of active pain-free shoulder abduction was decreased. However, isometric shoulder strength test showed no differences when compared with pain-free shoulders. Even though the pain caused functional problems, the players were still playing with on-going symptoms. The diagnoses were mostly unknown, although history and clinical tests indicate problems resembling subacromial impingement.

  16. 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

  17. Association of pulse wave velocity and pulse pressure with decline in kidney function.

    PubMed

    Kim, Chang Seong; Kim, Ha Yeon; Kang, Yong Un; Choi, Joon Seok; Bae, Eun Hui; Ma, Seong Kwon; Kim, Soo Wan

    2014-05-01

    The association between arterial stiffness and decline in kidney function in patients with mild to moderate chronic kidney disease (CKD) is not well established. This study investigated whether pulse wave velocity (PWV) and pulse pressure (PP) are independently associated with glomerular filtration rate (GFR) and rapid decline in kidney function in early CKD. Carotid femoral PWV (cfPWV), brachial-ankle PWV (baPWV), and PP were measured in a cohort of 913 patients (mean age, 63±10 years; baseline estimated GFR, 84±18 mL/min/1.73 m(2) ). Estimated GFR was measured at baseline and at follow-up. The renal outcome examined was rapid decline in kidney function (estimated GFR loss, >3 mL/min/1.73 m(2) per year). The median follow-up duration was 3.2 years. Multivariable adjusted linear regression model indicated that arterial PWV (both cfPWV and baPWV) and PP increased as estimated GFR declined, but neither was associated with kidney function after adjustment for various covariates. Multivariable logistic regression analysis found that cfPWV and baPWV were not associated with rapid decline in kidney function (odds ratio [OR], 1.39, 95% confidence interval [CI], 0.41-4.65; OR, 2.51, 95% CI, 0.66-9.46, respectively), but PP was (OR, 1.22, 95% CI, 1.01-1.48; P=.045). Arterial stiffness assessed using cfPWV and baPWV was not correlated with lower estimated GFR and rapid decline in kidney function after adjustment for various confounders. Thus, PP is an independent risk factor for rapid decline in kidney function in populations with relatively preserved kidney function (estimated GFR ≥30 mL/min/1.73 m(2) ). ©2014 Wiley Periodicals, Inc.

  18. 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.

  19. 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.

  20. 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.

  1. Definition of chronic kidney disease and measurement of kidney function in original research papers: a review of the literature.

    PubMed

    Anderson, Jocelyn; Glynn, Liam G

    2011-09-01

    Over the past decade, chronic kidney disease (CKD) has become an area of intensive clinical and epidemiological research. Despite the clarity provided by the Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines, there appears to be within the CKD research literature significant disagreement on how to define CKD and measure kidney function. The objectives of this study were to investigate the variety of methods used to define CKD and to measure kidney function in original research papers as well as to investigate whether the quality of the journal had any effect on the quality of the methodology used. This was a descriptive review and not a meta-analysis. Information was extracted from each article including publication details (including the journal's impact factor), definition of CKD, method used to estimate kidney function and quantity of serum creatinine readings used to define CKD. An electronic search of MEDLINE through OVID was completed using the search term CKD. The search was limited to articles in English published in 2009. Studies were included in the review only if they were original research articles including patients with CKD. Articles were excluded if they reported data from a paediatric population, a population solely on dialysis or if there was no full-text access through OVID. Each article was assessed for quality with respect to using KDOQI CKD definition criteria. A description of the pooled data was completed and chi-square tests were used to investigate the relation between article quality and journal quality. Analysis was carried out using SPSS (15.0) and a P-value of <0.05 was considered to indicate statistical significance. The final review included 301 articles. There were a variety of methods used to define CKD in original research articles. Less than 20% (n = 59) of the articles adhered to the established international criteria for defining CKD. The majority of articles (52.1%) did not indicate the quantity of serum creatinine

  2. Does Ramadan Fasting Affect Hydration Status and Kidney Function in CKD Patients?

    PubMed

    Hassan, Shadia; Hassan, Fadi; Abbas, Nur; Hassan, Kamal; Khatib, Nihal; Edgim, Rabia; Fadol, Rawia; Khazim, Khaled

    2018-01-01

    This study is the first of its kind to examine the impact of the Ramadan fasting on hydration status, plasma brain natriuretic peptide (BNP) levels, and kidney function in chronic kidney disease (CKD) patient. This prospective cohort study included 2 groups of patients with CKD grades 2-4: thirty-one Muslim patients who fasted the month of Ramadan (fasting group) and 26 Muslim patients who did not fast (control group). One week before the Ramadan fast, in the last week of the month of Ramadan (4 weeks), and 4 weeks after the end of the Ramadan month (8 weeks), hydration status and blood analysis of urea, creatinine and BNP levels were measured. Among fasting patients, serum urea levels increased significantly (p = 0.024) during the last week of fasting and returned to basal levels at 4 weeks after the end of the Ramadan month, the estimated glomerular filtration rate did not change significantly at the end of fasting (p = 0.411), the hydration status indices and plasma BNP levels were significantly decreased after fasting (p ≤ 0.021) but returned to basal values 4 weeks thereafter. Patients with CKD grades 2-4 can fast throughout the month of Ramadan with no significant deterioration of renal functions and with a reasonable degree of safety. © 2018 S. Karger AG, Basel.

  3. Understanding Trends in Kidney Function 1 Year after Kidney Transplant in the United States.

    PubMed

    Huang, Yihung; Tilea, Anca; Gillespie, Brenda; Shahinian, Vahakn; Banerjee, Tanushree; Grubbs, Vanessa; Powe, Neil; Rios-Burrows, Nilka; Pavkov, Meda; Saran, Rajiv

    2017-08-01

    Lower eGFR 1 year after kidney transplant is associated with shorter allograft and patient survival. We examined how practice changes in the past decade correlated with time trends in average eGFR at 1 year after kidney transplant in the United States in a cohort of 189,944 patients who received a kidney transplant between 2001 and 2013. We calculated the average eGFR at 1 year after transplant for the recipient cohort of each year using the appropriate Modification of Diet in Renal Disease equation depending on the prevailing methodology of creatinine measurement, and used linear regression to model the effects of practice changes on the national post-transplant eGFR trend. Between the 2001-2005 period and the 2011-2013 period, average 1-year post-transplant eGFR remained essentially unchanged, with differences of 1.34 (95% confidence interval, 1.03 to 1.65) ml/min per 1.73 m 2 and 0.66 (95% confidence interval, 0.32 to 1.01) ml/min per 1.73 m 2 among deceased and living donor kidney transplant recipients, respectively. Over time, the mean age of recipients increased and more marginal organs were used; adjusting for these trends unmasked a larger temporal improvement in post-transplant eGFR. However, changes in immunosuppression practice had a positive effect on average post-transplant eGFR and balanced out the negative effect of recipient/donor characteristics. In conclusion, average 1-year post-transplant eGFR remained stable, despite increasingly unfavorable attributes in recipients and donors. With an aging ESRD population and continued organ shortage, preservation of average post-transplant eGFR will require sustained improvement in immunosuppression and other aspects of post-transplant care. Copyright © 2017 by the American Society of Nephrology.

  4. 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.

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

    PubMed Central

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

    2018-01-01

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

  6. 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 e

  7. Increased podocyte Sirtuin-1 function attenuates diabetic kidney injury.

    PubMed

    Hong, Quan; Zhang, Lu; Das, Bhaskar; Li, Zhengzhe; Liu, Bohan; Cai, Guangyan; Chen, Xiangmei; Chuang, Peter Y; He, John Cijiang; Lee, Kyung

    2018-06-01

    Podocyte injury and loss contribute to the progression of glomerular diseases, including diabetic kidney disease. We previously found that the glomerular expression of Sirtuin-1 (SIRT1) is reduced in human diabetic glomeruli and that the podocyte-specific loss of SIRT1 aggravated albuminuria and worsened kidney disease progression in diabetic mice. SIRT1 encodes an NAD-dependent deacetylase that modifies the activity of key transcriptional regulators affected in diabetic kidneys, including NF-κB, STAT3, p53, FOXO4, and PGC1-α. However, whether the increased glomerular SIRT1 activity is sufficient to ameliorate the pathogenesis of diabetic kidney disease has not been explored. We addressed this by inducible podocyte-specific SIRT1 overexpression in diabetic OVE26 mice. The induction of SIRT1 overexpression in podocytes for six weeks in OVE26 mice with established albuminuria attenuated the progression of diabetic glomerulopathy. To further validate the therapeutic potential of increased SIRT1 activity against diabetic kidney disease, we developed a new, potent and selective SIRT1 agonist, BF175. In cultured podocytes BF175 increased SIRT1-mediated activation of PGC1-α and protected against high glucose-mediated mitochondrial injury. In vivo, administration of BF175 for six weeks in OVE26 mice resulted in a marked reduction in albuminuria and in glomerular injury in a manner similar to podocyte-specific SIRT1 overexpression. Both podocyte-specific SIRT1 overexpression and BT175 treatment attenuated diabetes-induced podocyte loss and reduced oxidative stress in glomeruli of OVE26 mice. Thus, increased SIRT1 activity protects against diabetes-induced podocyte injury and effectively mitigates the progression of diabetic kidney disease. Published by Elsevier Inc.

  8. TECHNIQUES FOR COMBINED PROCUREMENT OF HEARTS AND KIDNEYS WITH SATISFACTORY EARLY FUNCTION OF RENAL ALLOGRAFTS

    PubMed Central

    Shaw, Byers W.; Rosenthal, J. Thomas; Griffith, Bartley F.; Haresty, Robert L.; Broznik, Brian; Hakala, Thomas; Bahnson, Henry T.; Starzl, Thomas E.

    2009-01-01

    SUMMARY Methods for combination of donor nephrectomy with donor cardiectomy are outlined. The satisfactory early function of 29 of 34 transplanted kidneys harvested with these techniques supports their wider application and should encourage their wider acceptance. PMID:6351307

  9. 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.

  10. 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.

  11. A Teaching Aid for Physiologists--Simulation of Kidney Function

    ERIC Educational Resources Information Center

    Packer, J. S.; Packer, J. E.

    1977-01-01

    Presented is the development of a simulation model of the facultative water transfer mechanism of the mammalian kidney. Discussion topics include simulation philosophy, simulation facilities, the model, and programming the model as a teaching aid. Graphs illustrate typical program displays. A listing of references concludes the article. (MA)

  12. Paracetamol (acetaminophen) decreases hydrogen sulfide tissue concentration in brain but increases it in the heart, liver and kidney in mice.

    PubMed

    Wiliński, Bogdan; Wiliński, Jerzy; Somogyi, Eugeniusz; Góralska, Marta; Piotrowska, Joanna

    2011-01-01

    The biological action ofN-acetyl-p-aminophenol - paracetamol (acetaminophen) has been demonstrated to involve different mechanisms and is still not clear. Hydrogen sulfide (H2S) has been shown to play an important role in many physiological and pathological processes including nociception. The interaction between acetaminophen and endogenous H2S is unknown. Twenty four female CBA strain mice were administered intraperitoneal injections of N-acetyl-p-aminophenol solution: paracetemol in doses of 30 mg/kg b.w. per day (group D1, n = 8) or 100 mg/kg b.w. per day (group D2, n = 8).. The control group (n = 8) received physiological saline in portions of the same volume--0.2 ml. The measurements of tissue H2S concentration were performed with the Siegel spectrophotometric modified method. In the brain, the H2S tissue level decreased, but more significantly in the lower drug dose group. Conversely, there was a significant rise in the H2S tissue concentration in D1 and D2 groups in heart and kidney with the increase more pronounced in the group with the lower paracetamol dose. In the liver only the higher acetaminophen dose elicited a change in H2S concentration, increasing after administration of acetaminophen at 100 mg/kg. Our study demonstrates that paracetamol induces H2S tissue concentration changes in different mouse organs.

  13. 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.

  14. 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.

  15. 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.

  16. A novel protocol for antibiotic prophylaxis based on preoperative kidney function in patients undergoing open heart surgery under cardiopulmonary bypass.

    PubMed

    Odaka, Mizuho; Minakata, Kenji; Toyokuni, Hideaki; Yamazaki, Kazuhiro; Yonezawa, Atsushi; Sakata, Ryuzo; Matsubara, Kazuo

    2015-08-01

    This study aimed to develop and assess the effectiveness of a protocol for antibiotic prophylaxis based on preoperative kidney function in patients undergoing open heart surgery. We established a protocol for antibiotic prophylaxis based on preoperative kidney function in patients undergoing open heart surgery. This novel protocol was assessed by comparing patients undergoing open heart surgery before (control group; n = 30) and after its implementation (protocol group; n = 31) at Kyoto University Hospital between July 2012 and January 2013. Surgical site infections (SSIs) were observed in 4 control group patients (13.3 %), whereas no SSIs were observed in the protocol group patients (P < 0.05). The total duration of antibiotic use decreased significantly from 80.7 ± 17.6 h (mean ± SD) in the control group to 55.5 ± 14.9 h in the protocol group (P < 0.05). Similarly, introduction of the protocol significantly decreased the total antibiotic dose used in the perioperative period (P < 0.05). Furthermore, antibiotic regimens were changed under suspicion of infection in 5 of 30 control group patients, whereas none of the protocol group patients required this additional change in the antibiotic regimen (P < 0.05). Our novel antibiotic prophylaxis protocol based on preoperative kidney function effectively prevents SSIs in patients undergoing open heart surgery.

  17. 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.

  18. 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.

  19. 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.

  20. The biomechanics of the kidney: the isothermal function of the capsule adipose renis.

    PubMed

    Rados, N; Keros, P; Trnski, D; Muftić, O

    1993-01-01

    The paper describes the research in the field of thermodynamics. It deals with the function of capsule adipose renis. This homogenous tissue of low temperature acts as an independent thermal conductor. In fact, by encapsulating the kidney, it acts as a vacuum-flask, providing insulation for the kidney from two surrounding thermal areas, the warmer being on the interperitoneum and the cooler on the skin surface.

  1. Infections and reduced functioning kidney mass induce chronic rejection in rat kidney allografts.

    PubMed

    Heemann, U W; Azuma, H; Tullius, S G; Schmid, C; Philipp, T; Tilney, N L

    1996-07-01

    The etiology of chronic rejection of kidney allografts is unknown, although hyperfiltration, acute rejection, viral infection and initial graft ischemia have been implicated. To test whether endothelial activation may be the link between these factors and chronic rejection, the endotoxin (lipopolysaccharide-LPS), a potent activator of endothelial cells, was evaluated in an established chronic rejection model. Bilaterally nephrectomized Lewis recipients of orthotopically transplanted Fisher 344 kidneys were treated briefly with low dose cyclosporine (1.5 mg/kg/day x 10). Recipients were given a non-lethal dose of LPS (2 mg) i.p. at 8 weeks and compared to allografted controls treated with vehicle. Urine protein was measured every 4 weeks. Rats in the treated group were sacrificed at 12 and 16 weeks, control animals at 12, 16 and 24 weeks (20/group) and examined histologically. In the chronically rejecting control allografts, progressive interstitial and glomerular sclerosis and vascular intimal proliferation had become apparent by 12 weeks. Infiltration of glomeruli, particularly by macrophages (M phi), and the coincident presence of cytokines were prominent, peaking at 16 weeks. LPS treatment accelerated and intensified these changes; proteinuria was more pronounced (16 weeks: 79 mg/24 h vs. 49 mg/24 h, p < 0.05). Numbers of infiltrating M phi peaked at 12 weeks in LPS treated hosts (69 c/FV vs. 27 c/FV in untreated controls, p < 0.01), accompanied by an increased upregulation of MHC class II and cytokine expression, particularly TNF alpha and PDGF around arteries and areas of infiltration. BY 16 weeks, 35 +/- 3% of glomeruli in LPS treated recipients had become sclerotic vs. 15 +/- 6% (p < 0.05) in controls, again associated with increased expression of cytokines (PDGF, TNF alpha, TGF beta), adhesion molecules (ICAM-1) and extracellular matrix proteins. Overall, the extent of chronic rejection of grafts in LPS treated rats at 16 weeks was similar to that

  2. Effect of Extended Release Niacin on Cardiovascular Events and Kidney Function in Chronic Kidney Disease: A Post-Hoc Analysis of the AIM-HIGH Trial

    PubMed Central

    Kalil, Roberto S.; Wang, Jeffrey H.; de Boer, Ian H.; Mathew, Roy O.; Ix, Joachim H.; Asif, Arif; Shi, Xuefeng; Boden, William E.

    2014-01-01

    Chronic kidney disease (CKD) in patients is strongly associated with cardiovascular morbidity and mortality, and prevalent abnormal lipid metabolism. The AIM-HIGH trial examined the benefits of adding extended-release niacin (ERN) to simvastatin in patients with established coronary heart disease. Here we conducted a post-hoc analysis of the AIM-HIGH trial examining whether participants derived cardiovascular or renal benefits when stratified by renal function. Of 3414 participants, 505 had stage 3 CKD at baseline. Among the CKD subset, demographics and cardiovascular disease (CVD) risk factors were well balanced in the ERN and placebo arms. Compared to placebo, CKD participants receiving ERN had a significant decrease in triglycerides by a median of 59.0 mg/dL, and high density lipoprotein-cholesterol significantly increased by a mean of 11.3 mg/dL over a mean follow-up of 3 years. CVD events were similar between CKD participants in both arms. However, all-cause mortality was significantly higher in the ERN group (hazard ratio of 1.73). Mean change in eGFR among ERN-treated CKD participants was not significantly different between study arms. Thus, among AIM-HIGH participants with CKD, the addition of ERN to simvastatin for secondary prevention of CVD improved triglyceride and high density lipoprotein-cholesterol concentrations but did not improve cardiovascular outcomes or kidney function, and was associated with higher all-cause mortality. PMID:25651367

  3. Effect of extended-release niacin on cardiovascular events and kidney function in chronic kidney disease: a post hoc analysis of the AIM-HIGH trial.

    PubMed

    Kalil, Roberto S; Wang, Jeffrey H; de Boer, Ian H; Mathew, Roy O; Ix, Joachim H; Asif, Arif; Shi, Xuefeng; Boden, William E

    2015-06-01

    Chronic kidney disease (CKD) in patients is strongly associated with cardiovascular morbidity and mortality, and prevalent abnormal lipid metabolism. The AIM-HIGH trial examined the benefits of adding extended-release niacin (ERN) to simvastatin in patients with established coronary heart disease. Here we conducted a post hoc analysis of the AIM-HIGH trial examining whether participants derived cardiovascular or renal benefits when stratified by renal function. Of 3414 participants, 505 had stage 3 CKD at baseline. Among the CKD subset, demographics and cardiovascular disease (CVD) risk factors were well balanced in the ERN and placebo arms. Compared with placebo, CKD participants receiving ERN had a significant decrease in triglycerides by a median of 59.0 mg/dl, and high-density lipoprotein cholesterol significantly increased by a mean of 11.3 mg/dl over a mean follow-up of 3 years. CVD events were similar between CKD participants in both arms. However, all-cause mortality was significantly higher in the ERN group (hazard ratio of 1.73). Mean change in eGFR among ERN-treated CKD participants was not significantly different between study arms. Thus, among AIM-HIGH participants with CKD, the addition of ERN to simvastatin for secondary prevention of CVD improved triglyceride and high-density lipoprotein-cholesterol concentrations but did not improve cardiovascular outcomes or kidney function, and was associated with higher all-cause mortality.

  4. 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

  5. Comparative analysis of two porcine kidney decellularization methods for maintenance of functional vascular architectures.

    PubMed

    Zambon, Joao Paulo; Ko, In Kap; Abolbashari, Mehran; Huling, Jennifer; Clouse, Cara; Kim, Tae Hyoung; Smith, Charesa; Atala, Anthony; Yoo, James J

    2018-06-05

    Kidney transplantation is currently the only definitive solution for the treatment of end-stage renal disease (ESRD), however transplantation is severely limited by the shortage of available donor kidneys. Recent progress in whole organ engineering based on decellularization/recellularization techniques has enabled pre-clinical in vivo studies using small animal models; however, these in vivo studies have been limited to short-term assessments. We previously developed a decellularization system that effectively removes cellular components from porcine kidneys. While functional re-endothelialization on the porcine whole kidney scaffold was able to improve vascular patency, as compared to the kidney scaffold only, the duration of patency lasted only a few hours. In this study, we hypothesized that significant damage in the microvasculatures within the kidney scaffold resulted in the cessation of blood flow, and that thorough investigation is necessary to accurately evaluate the vascular integrity of the kidney scaffolds. Two decellularization protocols [sodium dodecyl sulfate (SDS) with DNase (SDS + DNase) or Triton X-100 with SDS (TRX + SDS)] were used to evaluate and optimize the levels of vascular integrity within the kidney scaffold. Results from vascular analysis studies using vascular corrosion casting and angiograms demonstrated that the TRX + SDS method was able to better maintain intact and functional microvascular architectures such as glomeruli within the acellular matrices than that by the SDS + DNase treatment. Importantly, in vitro blood perfusion of the re-endothelialized kidney construct revealed improved vascular function of the scaffold by TRX + SDS treatment compared with the SDS + DNase. Our results suggest that the optimized TRX + SDS decellularization method preserves kidney-specific microvasculatures and may contribute to long-term vascular patency following implantation. Kidney transplantation is the only curative

  6. Genome-wide association and functional follow-up reveals new loci for kidney function.

    PubMed

    Pattaro, Cristian; Köttgen, Anna; Teumer, Alexander; Garnaas, Maija; Böger, Carsten A; Fuchsberger, Christian; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Taliun, Daniel; Li, Man; Gao, Xiaoyi; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C; O'Seaghdha, Conall M; Glazer, Nicole; Isaacs, Aaron; Liu, Ching-Ti; Smith, Albert V; O'Connell, Jeffrey R; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Johnson, Andrew D; Gierman, Hinco J; Feitosa, Mary; Hwang, Shih-Jen; Atkinson, Elizabeth J; Lohman, Kurt; Cornelis, Marilyn C; Johansson, Åsa; Tönjes, Anke; Dehghan, Abbas; Chouraki, Vincent; Holliday, Elizabeth G; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y; Murgia, Federico; Trompet, Stella; Imboden, Medea; Kollerits, Barbara; Pistis, Giorgio; Harris, Tamara B; Launer, Lenore J; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D; Boerwinkle, Eric; Schmidt, Helena; Cavalieri, Margherita; Rao, Madhumathi; Hu, Frank B; Demirkan, Ayse; Oostra, Ben A; de Andrade, Mariza; Turner, Stephen T; Ding, Jingzhong; Andrews, Jeanette S; Freedman, Barry I; Koenig, Wolfgang; Illig, Thomas; Döring, Angela; Wichmann, H-Erich; Kolcic, Ivana; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H; Wright, Alan F; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Endlich, Karlhans; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G; Rivadeneira, Fernando; Aulchenko, Yurii S; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Ketkar, Shamika; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Giulianini, Franco; Krämer, Bernhard K; Portas, Laura; Ford, Ian; Buckley, Brendan M; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Metzger, Marie; Mitchell, Paul; Ciullo, Marina; Kim, Stuart K; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J Wouter; Probst-Hensch, Nicole M; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; Siscovick, David S; van Duijn, Cornelia M; Borecki, Ingrid; Kardia, Sharon L R; Liu, Yongmei; Curhan, Gary C; Rudan, Igor; Gyllensten, Ulf; Wilson, James F; Franke, Andre; Pramstaller, Peter P; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline C M; Hayward, Caroline; Ridker, Paul; Parsa, Afshin; Bochud, Murielle; Heid, Iris M; Goessling, Wolfram; Chasman, Daniel I; Kao, W H Linda; Fox, Caroline S

    2012-01-01

    Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.

  7. Genome-Wide Association and Functional Follow-Up Reveals New Loci for Kidney Function

    PubMed Central

    Fuchsberger, Christian; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Taliun, Daniel; Li, Man; Gao, Xiaoyi; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C.; O'Seaghdha, Conall M.; Glazer, Nicole; Isaacs, Aaron; Liu, Ching-Ti; Smith, Albert V.; O'Connell, Jeffrey R.; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Johnson, Andrew D.; Gierman, Hinco J.; Feitosa, Mary; Hwang, Shih-Jen; Atkinson, Elizabeth J.; Lohman, Kurt; Cornelis, Marilyn C.; Johansson, Åsa; Tönjes, Anke; Dehghan, Abbas; Chouraki, Vincent; Holliday, Elizabeth G.; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y.; Murgia, Federico; Trompet, Stella; Imboden, Medea; Kollerits, Barbara; Pistis, Giorgio; Harris, Tamara B.; Launer, Lenore J.; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D.; Boerwinkle, Eric; Schmidt, Helena; Cavalieri, Margherita; Rao, Madhumathi; Hu, Frank B.; Demirkan, Ayse; Oostra, Ben A.; de Andrade, Mariza; Turner, Stephen T.; Ding, Jingzhong; Andrews, Jeanette S.; Freedman, Barry I.; Koenig, Wolfgang; Illig, Thomas; Döring, Angela; Wichmann, H.-Erich; Kolcic, Ivana; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E.; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H.; Wright, Alan F.; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Endlich, Karlhans; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K.; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G.; Rivadeneira, Fernando; Aulchenko, Yurii S.; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Ketkar, Shamika; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Giulianini, Franco; Krämer, Bernhard K.; Portas, Laura; Ford, Ian; Buckley, Brendan M.; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Metzger, Marie; Mitchell, Paul; Ciullo, Marina; Kim, Stuart K.; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J. Wouter; Probst-Hensch, Nicole M.; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R.; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; Siscovick, David S.; van Duijn, Cornelia M.; Borecki, Ingrid; Kardia, Sharon L. R.; Liu, Yongmei; Curhan, Gary C.; Rudan, Igor; Gyllensten, Ulf; Wilson, James F.; Franke, Andre; Pramstaller, Peter P.; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline C. M.; Hayward, Caroline; Ridker, Paul; Parsa, Afshin; Bochud, Murielle; Heid, Iris M.; Goessling, Wolfram; Chasman, Daniel I.; Kao, W. H. Linda; Fox, Caroline S.

    2012-01-01

    Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD. PMID:22479191

  8. Magnesium-based interventions for normal kidney function and chronic kidney disease.

    PubMed

    Massy, Ziad A; Nistor, Ionut; Apetrii, Mugurel; Brandenburg, Vincent M; Bover, Jordi; Evenepoel, Pieter; Goldsmith, David; Mazzaferro, Sandro; Urena-Torres, Pablo; Vervloet, Marc G; Cozzolino, Mario; Covic, Adrian; Era-Edta, On Behalf Of Ckd-Mbd Working Group Of

    2016-04-01

    Magnesium (Mg) is one of the most important cations in the body, playing an essential role in biological systems as co-factor for more than 300 essential enzymatic reactions. In the general population, low levels of Mg are associated with a high risk of cardio-vascular disease (CVD). Despite the accumulating literature data, the effect of Mg administration on mortality in chronic kidney disease (CKD) patients has never been investigated as a primary end-point. We conducted a systematic search of studies assessing the benefits and harms of Mg in CKD (stages 1 to 5 and 5D), and considered all randomized controlled trials (RCTs) and quasi-RCTs evaluating Mg-based interventions in CKD. As a phosphate binder, Mg salts offer a plausible opportunity for doubly favorable effects via reduction of intestinal phosphate absorption and addition of potentially beneficial effects via increasing circulating Mg levels. Mg supplementation might have a favorable effect on vascular calcification, although evidence for this is very slight. Although longitudinal data describe an association between low serum Mg levels and increased total and cardiovascular mortality, in patients with CKD, the existing RCTs reporting the effect of Mg supplementation on mortality failed to demonstrate any favorable effect. As with many other variables that influence hard end-points in nephrology, the role of Mg in CKD patients needs to be investigated in more depth. Additional research that is well-designed and directly targeting the role of Mg is needed as a consequence of limited existing evidence.

  9. Reference values of renal tubular function tests are dependent on age and kidney function.

    PubMed

    Bech, Anneke P; Wetzels, Jack F M; Nijenhuis, Tom

    2017-12-01

    Electrolyte disorders due to tubular disorders are rare, and knowledge about validated clinical diagnostic tools such as tubular function tests is sparse. Reference values for tubular function tests are based on studies with small sample size in young healthy volunteers. Patients with tubular disorders, however, frequently are older and can have a compromised renal function. We therefore evaluated four tubular function tests in individuals with different ages and renal function. We performed furosemide, thiazide, furosemide-fludrocortisone, and desmopressin tests in healthy individuals aged 18-50 years, healthy individuals aged more than 50 years and individuals with compromised renal function. For each tubular function test we included 10 individuals per group. The responses in young healthy individuals were in line with previously reported values in literature. The maximal increase in fractional chloride excretion after furosemide was below the lower limit of young healthy individuals in 5/10 older subjects and in 2/10 patients with compromised renal function. The maximal increase in fractional chloride excretion after thiazide was below the lower limit of young healthy individuals in 6/10 older subjects and in 7/10 patients with compromised renal function. Median maximal urine osmolality after desmopressin was 1002 mosmol/kg H 2 O in young healthy individuals, 820 mosmol/kg H 2 O in older subjects and 624 mosmol/kg H 2 O in patients with compromised renal function. Reference values for tubular function tests obtained in young healthy adults thus cannot simply be extrapolated to older patients or patients with compromised kidney function. Larger validation studies are needed to define true reference values in these patient categories. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

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

    PubMed

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

    2018-06-01

    Patients with severely decreased glomerular filtration rate (GFR) (i.e., chronic kidney disease [CKD] G4+) are at increased risk for kidney failure, cardiovascular disease (CVD) events (including heart failure), and death. However, little is known about the variability of outcomes and optimal therapeutic strategies, including initiation of kidney replacement therapy (KRT). Kidney Disease: Improving Global Outcomes (KDIGO) organized a Controversies Conference with an international expert group in December 2016 to address this gap in knowledge. In collaboration with the CKD Prognosis Consortium (CKD-PC) a global meta-analysis of cohort studies (n = 264,515 individuals with CKD G4+) was conducted to better understand the timing of clinical outcomes in patients with CKD G4+ and risk factors for different outcomes. The results confirmed the prognostic value of traditional CVD risk factors in individuals with severely decreased GFR, although the risk estimates vary for kidney and CVD outcomes. A 2- and 4-year model of the probability and timing of kidney failure requiring KRT was also developed. The implications of these findings for patient management were discussed in the context of published evidence under 4 key themes: management of CKD G4+, diagnostic and therapeutic challenges of heart failure, shared decision-making, and optimization of clinical trials in CKD G4+ patients. Participants concluded that variable prognosis of patients with advanced CKD mandates individualized, risk-based management, factoring in competing risks and patient preferences. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  11. Low serum bicarbonate and kidney function decline: the Multi-Ethnic Study of Atherosclerosis (MESA).

    PubMed

    Driver, Todd H; Shlipak, Michael G; Katz, Ronit; Goldenstein, Leonard; Sarnak, Mark J; Hoofnagle, Andrew N; Siscovick, David S; Kestenbaum, Bryan; de Boer, Ian H; Ix, Joachim H

    2014-10-01

    Among populations with established chronic kidney disease (CKD), metabolic acidosis is associated with more rapid progression of kidney disease. The association of serum bicarbonate concentrations with early declines in kidney function is less clear. Retrospective cohort study. 5,810 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with a baseline estimated glomerular filtration rate (eGFR) > 60mL/min/1.73 m(2) using the CKD-EPI (CKD Epidemiology Collaboration) creatinine-cystatin C equation. Serum bicarbonate concentrations. Rapid kidney function decline (eGFR decline > 5% per year) and incident reduced eGFR (eGFR < 60mL/min/1.73 m(2) with minimum rate of eGFR loss of 1 mL/min/1.73 m(2) per year). Average bicarbonate concentration was 23.2 ± 1.8mEq/L. 1,730 (33%) participants had rapid kidney function decline, and 487 had incident reduced eGFR during follow-up. Each 1-SD lower baseline bicarbonate concentration was associated with 12% higher adjusted odds of rapid kidney function decline (95% CI, 6%-20%) and higher risk of incident reduced eGFR (adjusted incidence rate ratio, 1.11; 95% CI, 1.03-1.20) in models adjusting for demographics, baseline eGFR, albuminuria, and CKD risk factors. The OR for the associations of bicarbonate level < 21 mEq/L relative to 23-24 mEq/L was 1.35 (95% CI, 1.05-1.73) for rapid kidney function decline, and the incidence rate ratio was 1.16 (95% CI, 0.83-1.62) for incident reduced eGFR. Cause of metabolic acidosis cannot be determined in this study. Lower serum bicarbonate concentrations are associated independently with rapid kidney function decline independent of eGFR or albuminuria in community-living persons with baseline eGFR > 60 mL/min/1.73 m(2). If confirmed, our findings suggest that metabolic acidosis may indicate either early kidney disease that is not captured by eGFR or albuminuria or may have a causal role in the development of eGFR < 60 mL/min/1.73 m(2). Copyright © 2014 National Kidney Foundation, Inc

  12. Effect of low carbohydrate high protein (LCHP) diet on lipid metabolism, liver and kidney function in rats.

    PubMed

    Kostogrys, Renata B; Franczyk-Żarów, Magdalena; Maślak, Edyta; Topolska, Kinga

    2015-03-01

    The objective of this study was to compare effects of Western diet (WD) with low carbohydrate high protein (LCHP) diet on lipid metabolism, liver and kidney function in rats. Eighteen rats were randomly assigned to three experimental groups and fed for the next 2 months. The experimental diets were: Control (7% of soybean oil, 20% protein), WD (21% of butter, 20% protein), and LCHP (21% of butter and 52.4% protein) diet. The LCHP diet significantly decreased the body weight of the rats. Diet consumption was differentiated among groups, however significant changes were observed since third week of the experiment duration. Rats fed LCHP diet ate significantly less (25.2g/animal/day) than those from Control (30.2g/animal/day) and WD (27.8 g/animal/day) groups. Additionally, food efficiency ratio (FER) tended to decrease in LCHP fed rats. Serum homocysteine concentration significantly decreased in rats fed WD and LCHP diets. Liver weights were significantly higher in rats fed WD and LCHP diets. At the end of the experiment (2 months) the triacylglycerol (TAG) was significantly decreased in animals fed LCHP compared to WD. qRT-PCR showed that SCD-1 and FAS were decreased in LCHP fed rats, but WD diet increased expression of lipid metabolism genes. Rats receiving LCHP diet had two fold higher kidney weight and 54.5% higher creatinin level compared to Control and WD diets. In conclusion, LCHP diet decreased animal's body weight and decreased TAG in rat's serum. However, kidney damage in LCHP rats was observed. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. 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.

  14. Multi-color autofluorescence and scattering spectroscopy provides rapid assessment of kidney function following ischemic injury

    NASA Astrophysics Data System (ADS)

    Raman, Rajesh N.; Pivetti, Chris D.; Ramsamooj, Rajendra; Troppmann, Christoph; Demos, Stavros G.

    2018-02-01

    A major source of kidneys for transplant comes from deceased donors whose tissues have suffered an unknown amount of warm ischemia prior to retrieval, with no quantitative means to assess function before transplant. Toward addressing this need, non-contact monitoring of optical signatures in rat kidneys was performed in vivo during ischemia and reperfusion. Kidney autofluorescence images were captured under ultraviolet illumination (355 nm, 325 nm, and 266 nm) in order to provide information on related metabolic and non-metabolic response. In addition, light scattering images under 355 nm, 325 nm, and 266 nm, 500 nm illumination were monitored to report on changes in kidney optical properties giving rise to the observed autofluorescence signals during these processes. During reperfusion, various signal ratios were generated from the recorded signals and then parametrized. Time-dependent parameters derived from the ratio of autofluorescence under 355 nm excitation to that under 266 nm excitation, as well as from 500 nm scattered signal, were found capable of discriminating dysfunctional kidneys from those that were functional (p < 0.01) within hours of reperfusion. Kidney dysfunction was confirmed by subsequent survival study and histology following autopsy up to a week later. Physiologic changes potentially giving rise to the observed signals, including those in cellular metabolism, vascular response, tissue microstructure, and microenvironment chemistry, are discussed.

  15. Pilot study of probiotic dietary supplementation for promoting healthy kidney function in patients with chronic kidney disease.

    PubMed

    Ranganathan, Natarajan; Ranganathan, Pari; Friedman, Eli A; Joseph, Anthony; Delano, Barbara; Goldfarb, David S; Tam, Paul; Rao, A Venketeshwer; Anteyi, Emmanuel; Musso, Carlos Guido

    2010-09-01

    Uremic syndrome consists of nitrogenous waste retention, deficiency in kidney-derived hormones, and reduced acid excretion, and, if untreated, may progress to coma and eventual death. Previous experience suggests that oral administration of a probiotic formulation of selected microbial strains may extend renoprotection via intraintestinal extraction of toxic waste solutes in patients with chronic kidney disease (CKD)stages 3 and 4. This report presents preliminary data from a pilot study. This was a 6-month prospective, randomized, double-blind, placebo-controlled crossover trial of a probiotic bacterial formulation conducted in four countries, at five institutions, on 46 outpatients with CKD stages 3 an nd 4: USA (n=10), Canada (n=113), Nigeria (n=115), and Argentina (n=8). Outcomes were compared using biochemical parameters:blood urea nitrogen (BUN), serum creatinine, and uric acid. General well-being was assessed as a secondary parameter by a quality of life (QQOL) questionnaire on a subjective scale of 1-10. Oral ingestion of probiotics (90 billion colony forming units [CFUs]/day) was well tolerated and safe during the entire trial period at all sites. BUN levels decreased in 29 patients (63%, P<0.05), creatinine levels decreased in 20 patients (43%, no statistical significance), and uric acid levels decreased in 15 patients (33%, no statistical significance). Almost all subjects expressed a perceived substantial overall improvement in QOL (86%, P<0.05). The main outcomes of this preliminary trial include a significant reduction of BUN, enhanced well-being, and absence of serious adverse effects, thus supporting the use of the chosen probiotic formulation for bowel-based toxic solute extraction. QOL and BUN levels showed statistically significant differences in outcome (P<0.05) between placebo and probiotic treatment periods at all four sites (46 patients). A major limitation of this trial is the small sample size nd elated inconsistencies.

  16. 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

  17. Plasma homocysteine and cerebral small vessel disease as possible mediators between kidney and cognitive functions in patients with diabetes mellitus.

    PubMed

    Sonoda, Mika; Shoji, Tetsuo; Kuwamura, Yukinobu; Okute, Yujiro; Naganuma, Toshihide; Shima, Hideaki; Motoyama, Koka; Morioka, Tomoaki; Mori, Katsuhito; Fukumoto, Shinya; Shioi, Atsushi; Shimono, Taro; Fujii, Hisako; Kabata, Daijiro; Shintani, Ayumi; Emoto, Masanori; Inaba, Masaaki

    2017-06-29

    Cognitive impairment is more prevalent in those with decreased kidney function. We tested a hypothesis that an increased homocysteine and/or cerebral small vessel diseases (SVDs) mediate the link between kidney and cognitive functions in a cross-sectional study in 143 type 2 diabetes patients without diagnosis of dementia or prior stroke. The exposure and outcome variables were estimated glomerular filtration rate (eGFR) and cognitive performance evaluated with Modified Mini-Mental State (3 MS) examination, respectively. The candidate mediators were plasma homocysteine concentration, and SVDs including silent cerebral infarction, cerebral microbleed, periventricular hyperintensity, and deep and subcortical white matter hyperintensity by magnetic resonance imaging. In multiple regression models adjusted for 12 potential confounders, eGFR was positively associated with 3 MS score, inversely with homocysteine, but not significantly with the presence of any type of SVD. The association of eGFR with 3 MS remained significant when each of the SVDs was added to the model, whereas it disappeared when homocysteine was included in place of SVD. Mediation analysis indicated nearly significant mediation of homocysteine (P = 0.062) but no meaningful mediations of SVDs (P = 0.842-0.930). Thus, homocysteine, not SVDs, was shown to be the possible mediator between kidney and cognitive functions in patients with type 2 diabetes mellitus.

  18. 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.

  19. Natural killer cell function predicts severe infection in kidney transplant recipients.

    PubMed

    Dendle, Claire; Gan, Poh-Yi; Polkinghorne, Kevan R; Ngui, James; Stuart, Rhonda L; Kanellis, John; Thursky, Karin; Mulley, William R; Holdsworth, Stephen

    2018-04-30

    The aim of this study was to determine if natural killer cell number (CD3 - /CD16 ± /CD56 ± ) and cytotoxic killing function predicts severity and frequency of infection in kidney transplant recipients. A cohort of 168 kidney transplant recipients with stable graft function underwent assessment of natural killer cell number and functional killing capacity immediately prior to entry into this prospective study. Participants were followed for 2 years for development of severe infection, defined as hospitalization for infection. Area under receiver operating characteristic (AUROC) curves were used to evaluate the accuracy of natural killer cell number and function for predicting severe infection. Adjusted odds ratios were determined by logistic regression. Fifty-nine kidney transplant recipients (35%) developed severe infection and 7 (4%) died. Natural killer cell function was a better predictor of severe infection than natural killer cell number: AUROC 0.84 and 0.75, respectively (P = .018). Logistic regression demonstrated that after adjustment for age, transplant function, transplant duration, mycophenolate use, and increasing natural killer function (odds ratio [OR] 0.82, 95% confidence interval [CI] 0.74-0.90; P < .0001) but not natural killer number (OR 0.96, 95% CI 0.93-1.00; P = .051) remained significantly associated with a reduced likelihood of severe infection. Natural killer cell function predicts severe infection in kidney transplant recipients. © 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.

  20. Polygenic overlap between kidney function and large artery atherosclerotic stroke

    PubMed Central

    Holliday, Elizabeth G.; Traylor, Matthew; Malik, Rainer; Bevan, Stephen; Maguire, Jane; Koblar, Simon A.; Sturm, Jonathan; Hankey, Graeme J.; Oldmeadow, Christopher; McEvoy, Mark; Sudlow, Cathie; Rothwell, Peter M.; Coresh, Josef; Hamet, Pavel; Tremblay, Johanne; Turner, Stephen T.; de Andrade, Mariza; Rao, Madhumathi; Schmidt, Reinhold; Crick, Peter A.; Robino, Antonietta; Peralta, Carmen A.; Jukema, J. Wouter; Mitchell, Paul; Rosas, Sylvia E.; Wang, Jie Jin; Scott, Rodney J.; Dichgans, Martin; Mitchell, Braxton D.; Linda Kao, W. H.; Fox, Caroline S.; Levi, Christopher; Attia, John; Markus, Hugh S

    2014-01-01

    Background and Purpose Epidemiological studies show strong associations between kidney dysfunction and risk of ischaemic stroke, the mechanisms of which are incompletely understood. We investigated whether these associations may reflect shared heritability due to a common polygenic basis and whether this differed for ischaemic stroke subtypes. Methods Polygenic models were derived using GWAS meta-analysis results for three kidney traits: estimated glomerular filtration rate using serum creatinine (eGFRcrea: N=73,998), eGFR using cystatin C (eGFRcys: N=22,937) and urinary albumin to creatinine ratio (UACR: N=31,580). For each, SNPs passing ten P-value thresholds were used to form profile scores in 4,561 ischaemic stroke cases and 7,094 controls from the UK, Germany and Australia. Scores were tested for association with ischaemic stroke and its three aetiological subtypes: large artery atherosclerosis (LAA), cardioembolism (CE) and small vessel disease (SVD). Results Polygenic scores correlating with higher eGFRcrea were associated with reduced risk of LAA, with five scores reaching P<0.05 (peak P=0.004) and all showing the epidemiologically expected direction of effect. A similar pattern was observed for polygenic scores reflecting higher UACR, of which three associated with LAA (peak P=0.01) and all showed the expected directional association. One UACR-based score also associated with SVD (P=0.03). The global pattern of results was unlikely to have occurred by chance (P=0.02). Conclusions This study suggests possible polygenic correlation between renal dysfunction and ischaemic stroke. The shared genetic components may be specific to stroke subtypes, particularly large artery atherosclerotic stroke. Further study of the genetic relationships between these disorders appears merited. PMID:25352485

  1. Antibody and complement reduce renal hemodynamic function in isolated perfused rat kidney.

    PubMed

    Jocks, T; Zahner, G; Helmchen, U; Kneissler, U; Stahl, R A

    1996-01-01

    To evaluate the effect of antibody and complement on renal hemodynamic changes, glomerular injury was induced in isolated perfused kidneys by an anti-thymocyte antibody (ATS) and rat serum (RS). Glomerular filtration rate (GFR), renal vascular resistance (RVR), and renal perfusate flow (RPF) were assessed over an 80-min period. The possible role of thromboxane (Tx) was tested by the application of the Tx synthesis inhibitor UK-38485 and the Tx receptor blocker daltroban. Perfusion of kidneys with ATS and RS significantly reduced GFR at 10 min (control, 501 +/- 111; ATS + RS, 138 +/- 86 ml.g kidney-1.min-1, significance of F = 0.000) after RS. Similarly, RPF (ml.g kidney-1.min-1) fell from 19.2 +/- 1.8 to 6.1 +/- 2.0 (significance of F = 0.000), whereas RVR (mmHg.ml-1.g.min) increased threefold from 5.2 +/- 0.4 to 17.9 +/- 5.0 at 10 min. These changes were ameliorated by the pretreatment of the rats with daltroban and UK-38485. Addition of erythrocytes to the perfusate increased RVR and GFR, whereas RPF decreased compared with cell-free perfused kidneys. ATS and RS in this preparation also decrease GFR and RPF. The hemodynamic alterations appeared without changes in filtration fraction. Compared with untreated, perfused control kidneys, glomerular Tx formation was significantly increased in ATS and RS perfused kidneys. These data demonstrate that antibody and RS induce impairment of renal hemodynamics, which are mediated by increased Tx formation.

  2. Low Serum Bicarbonate and Kidney Function Decline: The Multi-Ethnic Study of Atherosclerosis (MESA)

    PubMed Central

    Driver, Todd H.; Shlipak, Michael G.; Katz, Ronit; Goldenstein, Leonard; Sarnak, Mark J.; Hoofnagle, Andrew N.; Siscovick, David S.; Kestenbaum, Bryan; de Boer, Ian H.; Ix, Joachim H.

    2014-01-01

    Background Among populations with established chronic kidney disease (CKD), metabolic acidosis is associated with more rapid progression of kidney disease. The association of serum bicarbonate concentrations with early declines in kidney function is less clear. Study Design Retrospective cohort study. Setting & Participants 6380 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with a baseline estimated glomerular filtration rate (eGFR) >60 mL/min/1.73m2 using the CKD-EPI (CKD Epidemiology Collaboration) creatinine–cystatin C equation. Predictors Serum bicarbonate concentrations. Outcomes Rapid kidney function decline (eGFR decline >5% per year) and incident reduced eGFR (eGFR<60 mL/min/1.73 m2 with minimum rate of eGFR loss of 1 mL/min/1.73 m2 per year). Results The average bicarbonate concentration was 23.2 ± 1.8 mEq/L. 1730 (33%) participants had rapid kidney function decline, and 487 had incident reduced eGFR during follow-up. Each 1-SD lower baseline bicarbonate concentration was associated with 12% higher adjusted odds of rapid kidney function decline (95% CI, 6%–20%) and higher risk of incident reduced eGFR (adjusted incidence rate ratio, 1.11; 95% CI, 1.03–1.20) in models adjusting for demographics, baseline eGFR, albuminuria, and CKD risk factors. The OR for the associations of bicarbonate <21mEq/L relative to 23–24 mEq/L was 1.35 (95% CI, 1.05–1.73) for rapid kidney function decline, and the incidence rate ratio was 1.16 (95% CI, 0.83–1.62) for incident reduced eGFR. Limitations Etiology of metabolic acidosis cannot be determined in this study. Conclusions Lower serum bicarbonate concentrations are independently associated with rapid kidney function decline independent of eGFR or albuminuria in community-living persons with a baseline eGFR >60 mL/min/1.73 m2. If confirmed, our findings suggest that metabolic acidosis may indicate either early kidney disease that is not captured by eGFR or albuminuria, or may have a causal role

  3. Renal function changes after percutaneous nephrolithotomy in patients with renal calculi with a solitary kidney compared to bilateral kidneys.

    PubMed

    Shi, Xiaolei; Peng, Yonghan; Li, Ling; Li, Xiao; Wang, Qi; Zhang, Wei; Dong, Hao; Shen, Rong; Lu, Chaoyue; Liu, Min; Gao, Xiaofeng; Sun, Yinghao

    2018-05-26

    To evaluate renal function changes and risk factors for acute kidney injury (AKI) after percutaneous nephrolithotomy (PCNL) in patients with renal calculi with a solitary kidney (SK) or normal bilateral kidneys (BKs). Between 2012 and 2016, 859 patients undergoing PCNL were retrospectively reviewed at Changhai Hospital. In all, 53 patients with a SK were paired with 53 patients with normal BKs via a propensity score-matched analysis. Data for the following variables were collected: age, sex, body mass index, stone size, distribution, operation time, perioperative outcomes, and complications. The complications were graded according to the modified Clavien-Dindo system. Univariable and multivariable logistic regression models were constructed to evaluate risk factors for predicting AKI. The SK and BKs groups were comparable in terms of age, sex ratio, stone size, stone location distribution, comorbidities, and American Society of Anesthesiologists Physical Status classification. The initial and final stone-free rates were comparable between the SK and BKs groups (initial: 52.83% vs 58.49%, P = 0.696; final: 84.91% vs 92.45%, P = 0.359). There was no difference between the two groups for complications, according to the Clavien-Dindo grades. The estimated glomerular filtration rate (eGFR) increased dramatically after the stone burden was immediately relieved, and during the 6-month follow-up eGFR was lower in the SK group compared with the BKs group. We found a modest improvement in renal function immediately after PCNL in the BKs group, and renal function gain was delayed in the SK group. Through logistic regression analysis, we discovered that a SK, preoperative creatinine and diabetes were independent risk factors for predicting AKI after PCNL. Considering the overall complication rates, PCNL is generally a safe procedure for treating renal calculi amongst patients with a SK or normal BKs. Follow-up renal function analysis showed a modest improvement in patients of

  4. Frailty, Kidney Function, and Polypharmacy: The Atherosclerosis Risk in Communities (ARIC) Study.

    PubMed

    Ballew, Shoshana H; Chen, Yan; Daya, Natalie R; Godino, Job G; Windham, B Gwen; McAdams-DeMarco, Mara; Coresh, Josef; Selvin, Elizabeth; Grams, Morgan E

    2017-02-01

    Frail individuals are at increased risk for poor outcomes, including adverse drug events. Kidney function is often compromised in frailty and is a key consideration in medication choice and dosing; however, creatinine-based measures of kidney function may be biased in frail individuals. Observational study. 4,987 community-dwelling older men and women with complete data who participated in visit 5 of the Atherosclerosis Risk in Communities (ARIC) Study (2011-2013). Kidney measures included glomerular filtration rate (GFR) estimated using serum creatinine (eGFR cr ) and serum cystatin C level (eGFR cys ) and urine albumin-creatinine ratio. Frailty, defined using established criteria of 3 or more frailty characteristics (weight loss, slowness, exhaustion, weakness, and low physical activity). 341 (7%) participants were classified as frail, 1,475 (30%) had eGFR cr <60mL/min/1.73m 2 , 2,480 (50%) had eGFR cys <60mL/min/1.73m 2 , and 1,006 (20%) had albuminuria with albumin excretion ≥ 30mg/g. Among frail participants, prevalences of eGFR cr and eGFR cys <60mL/min/1.73m 2 were 45% and 77%, respectively. Adjusted for covariates, frailty showed a moderate association with eGFR cr and a strong association with eGFR cys and albumin-creatinine ratio. Frail individuals with eGFR cr of 60 to <75mL/min/1.73m 2 were frequently reclassified to lower eGFR categories using eGFR cys (49% to 45-<60, 32% to 30-<45, and 3% to <30mL/min/1.73m 2 ). Hyperpolypharmacy (taking ≥10 classes of medications) was more common in frail individuals (54% vs 38% of nonfrail), including classes requiring kidney clearance (eg, digoxin) and associated with falls and subsequent complications (eg, hypnotic/sedatives and anticoagulants). Cross-sectional study design. Frail individuals had a high prevalence of reduced kidney function, with large discrepancies when reduced kidney function was classified by eGFR cys versus eGFR cr . Given the substantial medication burden and uncertainty in chronic

  5. 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

  6. Local CD34-positive capillaries decrease in mouse models of kidney disease associating with the severity of glomerular and tubulointerstitial lesions.

    PubMed

    Masum, Md Abdul; Ichii, Osamu; Elewa, Yaser Hosny Ali; Nakamura, Teppei; Kon, Yasuhiro

    2017-09-04

    The renal vasculature plays important roles in both homeostasis and pathology. In this study, we examined pathological changes in the renal microvascular in mouse models of kidney diseases. Glomerular lesions (GLs) in autoimmune disease-prone male BXSB/MpJ-Yaa (Yaa) mice and tubulointerstitial lesions (TILs) in male C57BL/6 mice subjected to unilateral ureteral obstruction (UUO) for 7 days were studied. Collected kidneys were examined using histopathological techniques. A nonparametric Mann-Whitney U test (P < 0.05) was performed to compare healthy controls and the experimental mice. The Kruskal-Wallis test was used to compare three or more groups, and multiple comparisons were performed using Scheffe's method when significant differences were observed (P < 0.05). Yaa mice developed severe autoimmune glomerulonephritis, and the number of CD34 + glomerular capillaries decreased significantly in GLs compared to that in control mice. However, UUO-treated mice showed severe TILs only, and CD34 + tubulointerstitial capillaries were decreased significantly in TILs with the progression of tubulointerstitial fibrosis compared to those in untreated control kidneys. Infiltrations of B-cells, T-cells, and macrophages increased significantly in the respective lesions of both disease models (P < 0.05). In observations of vascular corrosion casts by scanning electron microscopy and of microfil rubber-perfused thick kidney sections by fluorescence microscopy, segmental absences of capillaries were observed in the GLs and TILs of Yaa and UUO-treated mice, respectively. Further, transmission electron microscopy revealed capillary endothelial injury in the respective lesions of both models. The numbers of CD34 + glomerular and tubulointerstitial capillaries were negatively correlated with all examined parameters in GLs (P < 0.05) and TILs (P < 0.01), respectively. From the analysis of mouse models, we identified inverse pathological correlations between the number of

  7. Loss of CD28 on Peripheral T Cells Decreases the Risk for Early Acute Rejection after Kidney Transplantation

    PubMed Central

    Dedeoglu, Burç; Meijers, Ruud W. J.; Klepper, Mariska; Hesselink, Dennis A.; Baan, Carla C.; Litjens, Nicolle H. R.; Betjes, Michiel G. H.

    2016-01-01

    Background End-stage renal disease patients have a dysfunctional, prematurely aged peripheral T-cell system. Here we hypothesized that the degree of premature T-cell ageing before kidney transplantation predicts the risk for early acute allograft rejection (EAR). Methods 222 living donor kidney transplant recipients were prospectively analyzed. EAR was defined as biopsy proven acute allograft rejection within 3 months after kidney transplantation. The differentiation status of circulating T cells, the relative telomere length and the number of CD31+ naive T cells were determined as T-cell ageing parameters. Results Of the 222 patients analyzed, 30 (14%) developed an EAR. The donor age and the historical panel reactive antibody score were significantly higher (p = 0.024 and p = 0.039 respectively) and the number of related donor kidney transplantation was significantly lower (p = 0.018) in the EAR group. EAR-patients showed lower CD4+CD28null T-cell numbers (p<0.01) and the same trend was observed for CD8+CD28null T-cell numbers (p = 0.08). No differences regarding the other ageing parameters were found. A multivariate Cox regression analysis showed that higher CD4+CD28null T-cell numbers was associated with a lower risk for EAR (HR: 0.65, p = 0.028). In vitro, a significant lower percentage of alloreactive T cells was observed within CD28null T cells (p<0.001). Conclusion Immunological ageing-related expansion of highly differentiated CD28null T cells is associated with a lower risk for EAR. PMID:26950734

  8. Common variants in Mendelian kidney disease genes and their association with renal function.

    PubMed

    Parsa, Afshin; Fuchsberger, Christian; Köttgen, Anna; O'Seaghdha, Conall M; Pattaro, Cristian; de Andrade, Mariza; Chasman, Daniel I; Teumer, Alexander; Endlich, Karlhans; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Kim, Young J; Taliun, Daniel; Li, Man; Feitosa, Mary; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C; Glazer, Nicole; Isaacs, Aaron; Rao, Madhumathi; Smith, Albert V; O'Connell, Jeffrey R; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Hwang, Shih-Jen; Atkinson, Elizabeth J; Lohman, Kurt; Cornelis, Marilyn C; Johansson, Asa; Tönjes, Anke; Dehghan, Abbas; Couraki, Vincent; Holliday, Elizabeth G; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y; Murgia, Federico; Trompet, Stella; Imboden, Medea; Kollerits, Barbara; Pistis, Giorgio; Harris, Tamara B; Launer, Lenore J; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D; Boerwinkle, Eric; Schmidt, Helena; Hofer, Edith; Hu, Frank; Demirkan, Ayse; Oostra, Ben A; Turner, Stephen T; Ding, Jingzhong; Andrews, Jeanette S; Freedman, Barry I; Giulianini, Franco; Koenig, Wolfgang; Illig, Thomas; Döring, Angela; Wichmann, H-Erich; Zgaga, Lina; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H; Wright, Alan F; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G; Rivadeneira, Fernando; Aulchenko, Yurii S; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Stengel, Bénédicte; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Krämer, Bernhard K; Portas, Laura; Ford, Ian; Buckley, Brendan M; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Mitchell, Paul; Ciullo, Marina; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J Wouter; Probst-Hensch, Nicole M; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; van Duijn, Cornelia M; Borecki, Ingrid; Kardia, Sharon L R; Liu, Yongmei; Curhan, Gary C; Rudan, Igor; Gyllensten, Ulf; Wilson, James F; Franke, Andre; Pramstaller, Peter P; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline; Hayward, Caroline; Ridker, Paul M; Bochud, Murielle; Heid, Iris M; Siscovick, David S; Fox, Caroline S; Kao, W Linda; Böger, Carsten A

    2013-12-01

    Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.

  9. Common Variants in Mendelian Kidney Disease Genes and Their Association with Renal Function

    PubMed Central

    Fuchsberger, Christian; Köttgen, Anna; O’Seaghdha, Conall M.; Pattaro, Cristian; de Andrade, Mariza; Chasman, Daniel I.; Teumer, Alexander; Endlich, Karlhans; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Kim, Young J.; Taliun, Daniel; Li, Man; Feitosa, Mary; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C.; Glazer, Nicole; Isaacs, Aaron; Rao, Madhumathi; Smith, Albert V.; O’Connell, Jeffrey R.; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Hwang, Shih-Jen; Atkinson, Elizabeth J.; Lohman, Kurt; Cornelis, Marilyn C.; Johansson, Åsa; Tönjes, Anke; Dehghan, Abbas; Couraki, Vincent; Holliday, Elizabeth G.; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y.; Murgia, Federico; Trompet, Stella; Imboden, Medea; Kollerits, Barbara; Pistis, Giorgio; Harris, Tamara B.; Launer, Lenore J.; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D.; Boerwinkle, Eric; Schmidt, Helena; Hofer, Edith; Hu, Frank; Demirkan, Ayse; Oostra, Ben A.; Turner, Stephen T.; Ding, Jingzhong; Andrews, Jeanette S.; Freedman, Barry I.; Giulianini, Franco; Koenig, Wolfgang; Illig, Thomas; Döring, Angela; Wichmann, H.-Erich; Zgaga, Lina; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E.; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H.; Wright, Alan F.; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K.; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G.; Rivadeneira, Fernando; Aulchenko, Yurii S.; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Stengel, Bénédicte; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Krämer, Bernhard K.; Portas, Laura; Ford, Ian; Buckley, Brendan M.; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Mitchell, Paul; Ciullo, Marina; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J. Wouter; Probst-Hensch, Nicole M.; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R.; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; van Duijn, Cornelia M.; Borecki, Ingrid; Kardia, Sharon L.R.; Liu, Yongmei; Curhan, Gary C.; Rudan, Igor; Gyllensten, Ulf; Wilson, James F.; Franke, Andre; Pramstaller, Peter P.; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline; Hayward, Caroline; Ridker, Paul M.; Bochud, Murielle; Heid, Iris M.; Siscovick, David S.; Fox, Caroline S.; Kao, W. Linda; Böger, Carsten A.

    2013-01-01

    Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research. PMID:24029420

  10. Genetic polymorphisms of Interleukin-18 are not associated with allograft function in kidney transplant recipients.

    PubMed

    do Nascimento, Wenna Gleyce Araújo; Cilião, Daiani Alves; Genre, Julieta; Gondim, Dikson Dibe; Alves, Renata Gomes; Hassan, Neife Deghaide; Lima, Francisco Pignataro; Pereira, Maurício Galvão; Donadi, Eduardo Antônio; de Oliveira Crispim, Janaina Cristiana

    2014-06-01

    Interleukin 18 (IL-18) is a proinflammatory cytokine that plays a role in host defense by upregulating both innate and acquired immune responses. Analysis of IL18 polymorphisms may be clinically important since their roles have been recognized in a variety of inflammatory and autoimmune disorders. However, the role of this cytokine polymorphisms in kidney transplant still remains unclear. In this study, we evaluated the associations between IL18 polymorphisms and graft function assessed by creatinine clearance in kidney transplant recipients. A total of 82 kidney transplant recipients and 183 healthy controls were enrolled, and frequencies of alleles, genotypes and haplotypes for IL18 polymorphisms were determined and compared with creatinine clearance. The -607C/A (rs1946518) and -137C/G (rs187238) variant alleles in the IL18 gene were determined by polymerase chain reaction. In our study, no significant association was found between the IL18 variants and creatinine clearance (p > 0.05). Nonetheless, polymorphism analysis revealed an increase in the frequency of the IL18 major haplotype -607C/-137G in kidney transplant patients (odds ratio 2.57, 95% confidence interval 1.45-4.55, p = 0.0014). Finally, we found that IL18 polymorphisms did not influence the renal function and that IL18 haplotype -607C/-137G seems to be associated with kidney transplant recipients.

  11. Genetic polymorphisms of Interleukin-18 are not associated with allograft function in kidney transplant recipients

    PubMed Central

    do Nascimento, Wenna Gleyce Araújo; Cilião, Daiani Alves; Genre, Julieta; Gondim, Dikson Dibe; Alves, Renata Gomes; Hassan, Neife Deghaide; Lima, Francisco Pignataro; Pereira, Maurício Galvão; Donadi, Eduardo Antônio; de Oliveira Crispim, Janaina Cristiana

    2014-01-01

    Interleukin 18 (IL-18) is a proinflammatory cytokine that plays a role in host defense by upregulating both innate and acquired immune responses. Analysis of IL18 polymorphisms may be clinically important since their roles have been recognized in a variety of inflammatory and autoimmune disorders. However, the role of this cytokine polymorphisms in kidney transplant still remains unclear. In this study, we evaluated the associations between IL18 polymorphisms and graft function assessed by creatinine clearance in kidney transplant recipients. A total of 82 kidney transplant recipients and 183 healthy controls were enrolled, and frequencies of alleles, genotypes and haplotypes for IL18 polymorphisms were determined and compared with creatinine clearance. The -607C/A (rs1946518) and -137C/G (rs187238) variant alleles in the IL18 gene were determined by polymerase chain reaction. In our study, no significant association was found between the IL18 variants and creatinine clearance (p > 0.05). Nonetheless, polymorphism analysis revealed an increase in the frequency of the IL18 major haplotype -607C/-137G in kidney transplant patients (odds ratio 2.57, 95% confidence interval 1.45–4.55, p = 0.0014). Finally, we found that IL18 polymorphisms did not influence the renal function and that IL18 haplotype -607C/-137G seems to be associated with kidney transplant recipients. PMID:25071398

  12. 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.

  13. Pharmacological strategies for kidney function preservation: are there differences by ethnicity?

    PubMed

    Lakkis, Jay; Weir, Matthew R

    2004-01-01

    The prevalence of chronic kidney disease (CKD) is on the rise in all ethnic groups. This is because of the increased prevalence of obesity, diabetes mellitus, the metabolic syndrome, and the inadequate control of elevated blood pressure and other cardiovascular-renal risk factors, especially in ethnic minority populations. The implications of the aforementioned trends in risk factor prevalence and control are profound. Moreover, these trends negatively impact patient quality of life and place an enormous financial burden on the health care system for the provision of care to patients with CKD, end-stage renal disease (ESRD), and/or cardiovascular disease (CVD). Thus, it is of utmost importance to devise strategies that prevent kidney disease and delay progressive loss of kidney function in persons with CKD. Proven strategies include pharmacological interventions that lower blood pressure to less than target levels (<130/80 mm Hg), attainment of optimal glycemic control (Hb A1c <7%), and reducing urinary protein excretion. It is also possible, although yet unproven, that correction of anemia and aggressive treatment of dyslipidemia may forestall the loss of kidney function. In general, ethnic minorities are underrepresented in most large trials. Recently, a few outcome clinical trials in blacks have reinforced the lessons of kidney function preservation already learned in nonblack populations. That is, the reversible risk factors for CKD appear to be virtually identical and, at least in nondiabetic CKD, pharmacological targeting of the renin-angiotensin-aldosterone system (RAAS) with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers preserves kidney function better than non-RAAS blood pressure-lowering regimens, especially when significant proteinuria exists. Although more CKD studies in ethnic minorities are needed, until they become available, the best available evidence from the existing clinical trial database should be applied to

  14. Kidney Dysplasia

    MedlinePlus

    ... Disease Ectopic Kidney Medullary Sponge Kidney Kidney Dysplasia Kidney Dysplasia What is kidney dysplasia? Kidney dysplasia is a condition in which ... Kidney dysplasia in one kidney What are the kidneys and what do they do? The kidneys are ...

  15. Graft function assessment in mouse models of single- and dual- kidney transplantation.

    PubMed

    Wang, Lei; Wang, Ximing; Jiang, Shan; Wei, Jin; Buggs, Jacentha; Fu, Liying; Zhang, Jie; Liu, Ruisheng

    2018-05-23

    Animal models of kidney transplantation (KTX) are widely used in studying immune response of hosts to implanted grafts. Additionally, KTX can be used in generating kidney-specific knockout animal models by transplantation of kidneys from donors with global knockout of a gene to wild type recipients or vise verse. Dual kidney transplantation (DKT) provides a more physiological environment for recipients than single kidney transplantation (SKT). However, DKT in mice is rare due to technical challenges. In this study, we successfully performed DKT in mice and compared the hemodynamic response and graft function with SKT. The surgical time, complications and survival rate of DKT were not significantly different from SKT, where survival rates were above 85%. Mice with DKT showed less injury and quicker recovery with lower plasma creatinine (Pcr) and higher GFR than SKT mice (Pcr = 0.34 and 0.17 mg/dl in DKT vs. 0.50 and 0.36 mg/dl in SKT at 1 and 3 days, respectively; GFR = 215 and 131 µl/min for DKT and SKT, respectively). In addition, the DKT exhibited better renal functional reserve and long-term outcome of renal graft function than SKT based on the response to acute volume expansion. In conclusion, we have successfully generated a mouse DKT model. The hemodynamic responses of DKT better mimic physiological situations with less kidney injury and better recovery than SKT because of reduced confounding factors such as single nephron hyperfiltration. We anticipate DKT in mice will provide an additional tool for evaluation of renal significance in physiology and disease.

  16. Embryonic kidney function in a chronic renal failure model in rodents.

    PubMed

    Fujimoto, Eisuke; Yamanaka, Shuichiro; Kurihara, Sho; Tajiri, Susumu; Izuhara, Luna; Katsuoka, Yuichi; Yokote, Shinya; Matsumoto, Kei; Kobayashi, Eiji; Okano, Hirotaka James; Chikaraishi, Tatsuya; Yokoo, Takashi

    2017-08-01

    Rapid advancements have been made in alternative treatments for renal diseases. Our goal for renal regeneration is to establish a kidney graft derived from human embryonic tissues. In this study, we investigated the effects of host renal failure on the structure and activity of transplanted embryonic kidney and bladder, and found that diuretics effectively induced urine production in the transplanted kidney. Uremic conditions were reproduced using a 5/6 renal infarction rat model. An embryonic kidney plus bladder (embryonic day 15) was isolated from a pregnant Lewis rat and transplanted into the para-aortic area of a 5/6 renal-infarcted Lewis rat. Following growth, the embryonic bladder was successfully anastomosed to the host ureter. We assessed graft function in terms of survival rates and found no differences between normal (n = 5) and renal failure (n = 8) groups (median survival: 70.5 vs 74.5 h; p = 0.331) in terms of survival, indicating that the grafts prolonged rat survival, even under renal failure conditions. Furosemide (n = 9) significantly increased urine volume compared with saline-treated controls (n = 7; p < 0.05), confirming that the grafts were functional. We also demonstrated the possibilities of an in vivo imaging system for determining the viability of transplanted embryonic kidney with bladder. The results of this study demonstrate that transplanted embryonic kidney and bladder can grow and function effectively, even under uremic conditions.

  17. The kidney disease quality of life cognitive function subscale and cognitive performance maintenance hemodialysis patients

    USDA-ARS?s Scientific Manuscript database

    Background: Cognitive impairment is common but often undiagnosed in patients with end-stage renal disease, in part reflecting limited validated and easily administered tools to assess cognitive function in dialysis patients. Accordingly, we assessed the utility of the Kidney Disease Quality of Life ...

  18. Urinary miR-16 transactivated by C/EBPβ reduces kidney function after ischemia/reperfusion–induced injury

    PubMed Central

    Chen, Hsi-Hsien; Lan, Yi-Fan; Li, Hsiao-Fen; Cheng, Ching-Feng; Lai, Pei-Fang; Li, Wei-Hua; Lin, Heng

    2016-01-01

    Ischemia-reperfusion (I/R) induced acute kidney injury (AKI) is regulated by transcriptional factors and microRNAs (miRs). However, modulation of miRs by transcriptional factors has not been characterized in AKI. Here, we found that urinary miR-16 was 100-fold higher in AKI patients. MiR-16 was detected earlier than creatinine in mouse after I/R. Using TargetScan, the 3′UTR of B-cell lymphoma 2 (BCL-2) was found complementary to miR-16 to decrease the fluorescent reporter activity. Overexpression of miR-16 in mice significantly attenuated renal function and increased TUNEL activity in epithelium tubule cells. The CCAAT enhancer binding protein beta (C/EBP-β) increased the expression of miR-16 after I/R injury. The ChIP and luciferase promoter assay indicated that about −1.0 kb to −0.5 kb upstream of miR-16 genome promoter region containing C/EBP-β binding motif transcriptionally regulated miR-16 expression. Meanwhile, the level of pri-miR-16 was higher in mice infected with lentivirus containing C/EBP-β compared with wild-type (WT) mice and overexpression of C/EBP-β in the kidney of WT mice reduced kidney function, increased kidney apoptosis, and elevated urinary miR-16 level. Our results indicated that miR-16 was transactivated by C/EBP-β resulting in aggravated I/R induced AKI and that urinary miR-16 may serve as a potential biomarker for AKI. PMID:27297958

  19. Role of mechanistic target of rapamycin (mTOR) in renal function and ischaemia-reperfusion induced kidney injury.

    PubMed

    Alshaman, Reem; Truong, Luan; Oyekan, Adebayo

    2016-11-01

    Despite the presence of many studies on the role of mechanistic target of rapamycin (mTOR) in cardiorenal tissues, the definitive role of mTOR in the pathogenesis of renal injury subsequent to ischaemia-reperfusion (IR) remains unclear. The aims of the current study were to characterize the role of mTOR in normal kidney function and to investigate the role of mTOR activation in IR-induced kidney injury. In euvolemic anaesthetized rats, treatment with the mTOR inhibitor rapamycin increased blood pressure (121 ± 2 to 144 ± 3 mmHg; P<.05), decreased glomerular filtration rate (GFR; 1.6 ± 0.3 to 0.5 ± 0.2 mL/min; P<.05) and increased urinary sodium excretion (UNaV; 14 ± 1 to 109 ± 25 mmol/L per hour; P<.05). In rats subjected to IR, autophagy induction, p-mTOR expression and serum creatinine increased (1.9 ± 0.2 to 3 ± 0.3 mg/dL; P<.05); treatment with rapamycin blunted p-mTOR expression but further increased autophagy induction and serum creatinine (3 ± 0.3 to 5 ± 0.6 mg/dL; P<.05). In contrast, clenbuterol, an mTOR activator, blunted the effect of rapamycin on serum creatinine (4 ± 0.6 vs 2.3 ± 0.3 mg/dL; P<.05), autophagy induction and p-mTOR expression. IR also increased 24 hour protein excretion (9 ± 3 to 17 ± 2 mg/day; P<.05) and kidney injury molecule-1 (KIM-1) expression, and rapamycin treatment further increased KIM-1 expression. Clenbuterol exacerbated protein excretion (13 ± 2 to 26 ± 4 mg/day; P<.05) and antagonized the effect of rapamycin on KIM-1 expression. Histopathological data demonstrated kidney injury in IR rats that was worsened by rapamycin treatment but attenuated by clenbuterol treatment. Thus, mTOR signalling is crucial for normal kidney function and protecting the kidney against IR injury through autophagy suppression. © 2016 John Wiley & Sons Australia, Ltd.

  20. Antigravity suit inflation - Kidney function and cardiovascular and hormonal responses in men

    NASA Technical Reports Server (NTRS)

    Geelen, Ghislaine; Kravik, Stein E.; Hadj-Aissa, Aoumeur; Leftheriotis, Georges; Vincent, Madeleine

    1989-01-01

    The effect of the lower body positive pressure (LBPP) on kidney function in normal men was investigated in experiments in which the subjects underwent 30 min of sitting and then were subjected to 4.5 h of 70-deg head-up tilt. During the last 3 h of the tilt period, an antigravity suit (60 T legs, 30 T abdomen) was applied. The results showed that LBPP induces a significant increase in effective renal plasma flow and significant changes in the kidney excretory patterns, which were similar to those observed during a water immersion or the early phase of bed rest.

  1. Impact of chronic kidney disease on quality of life, lung function, and functional capacity.

    PubMed

    Teixeira, Carolina Guimarães; Duarte, Maria do Carmo M B; Prado, Cecília Maciel; Albuquerque, Emídio Cavalcanti de; Andrade, Lívia B

    2014-01-01

    To evaluate the impact of the chronic kidney disease (CKD) on quality of life, from the children's and their parents' perspective, respiratory muscle strength, lung function, and functional capacity in children and adolescents. Cross-sectional study of children with CKD aged 8 to 17 years. Those incapable of taking the tests were excluded. After an interview, quality of life by Pediatric Quality of Life Inventory) (PedsQL(TM)), muscular strength, pulmonary function tests, and the 6-minute walking test (6MWT) were applied. Student's t-test, ANOVA (difference in means), and Pearson's coefficient of correlation were used. The level of significance was set at 5%. Of the 40 patients, the mean distance walked at the 6MWT was 396 meters, and the mean final score at the quality of life test as perceived by the children and parents was 50.9 and 51, respectively. From the children's perspective, the transplanted patients had a higher quality of life score when compared to those undergoing hemodialysis (p<0.001); those who practiced physical activity had better quality of life when compared to the sedentary children (p<0.001). From the children's and the parents' perspectives, the male gender had a higher quality of life score (p<0.05). There was a positive correlation between the distance walked at the 6MWT and age, height, final PedsQL(TM), forced vital capacity (FVC), and forced expiratory volume in the first second (FEV1), as well as a negative correlation between FEV1/FVC and the distance walked. A significant reduction in the quality of life and the functional capacity was observed in children with CKD, influenced by the type of treatment, gender, and sedentary life style. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  2. A decreased soluble Klotho level with normal eGFR, FGF23, serum phosphate, and FEP in an ADPKD patient with enlarged kidneys due to multiple cysts.

    PubMed

    Kanai, Takahiro; Shiizaki, Kazuhiro; Betsui, Hiroyuki; Aoyagi, Jun; Yamagata, Takanori

    2018-05-16

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disorder. ADPKD is characterized clinically by the presence of multiple bilateral renal cysts that lead to chronic renal failure. The cysts evolve from renal tubular epithelial cells that express the Klotho gene. Notably, Klotho acts as a co-receptor for fibroblast growth factor 23 (FGF23); in this context, it induces phosphaturia and maintains serum phosphate at a normal level. Many reports have shown that decreases in the soluble Klotho level and increases in the FGF23 level are associated with glomerular filtration rate (GFR) decline, but a recent study observed these changes in patient with normal eGFR. It remains unclear whether the decrease in the Klotho level precedes the increase in FGF23. Here, we present an ADPKD patient with enlarged kidneys due to multiple cysts who had a decreased soluble Klotho level but a normal eGFR and a normal FGF23 level. The patient's serum phosphate level was normal, as was the fractional excretion of phosphate (FEP). This appears to be the first reported case to show a decreased soluble Klotho level plus normal eGFR, FGF23, and FEP. These results suggest that Klotho decreases before FGF23 increases and further suggest that Klotho is not required to maintain normal serum phosphate levels in ADPKD if the FEP and serum phosphate levels are normal.

  3. Low back pain and kidney mobility: local osteopathic fascial manipulation decreases pain perception and improves renal mobility.

    PubMed

    Tozzi, P; Bongiorno, D; Vitturini, C

    2012-07-01

    a) To calculate and compare a Kidney Mobility Score (KMS) in asymptomatic and Low Back Pain (LBP) individuals through real-time Ultrasound (US) investigation. b) To assess the effect of Osteopathic Fascial Manipulation (OFM), consisting of Still Technique (ST) and Fascial Unwinding (FU), on renal mobility in people with non-specific LBP. c) To evaluate 'if' and 'to what degree' pain perception may vary in patients with LBP, after OFM is applied. 101 asymptomatic people (F 30; M 71; mean age 38.9 ± 8) were evaluated by abdominal US screening. The distance between the superior renal pole of the right kidney and the ipsilateral diaphragmatic pillar was calculated in both maximal expiration (RdE) and maximal inspiration (RdI). The mean of the RdE-RdI ratios provided a Kidney Mobility Score (KMS) in the cohort of asymptomatic people. The same procedure was applied to 140 participants (F 66; M 74; mean age 39.3 ± 8) complaining of non-specific LBP: 109 of whom were randomly assigned to the Experimental group and 31 to the Control group. For both groups, a difference of RdE and RdI values was calculated (RD = RdE-RdI), before (RD-T0) and after (RD-T1) treatment was delivered, to assess the effective range of right kidney mobility. A blind assessment of each patient was carried using US screening. Both groups completed a Short-Form McGill Pain Assessment Questionnaire (SF-MPQ) on the day of recruitment (SF-MPQ T0) as well as on the third day following treatment (SF-MPQ T1). An Osteopathic assessment of the thoraco-lumbo-pelvic region to all the Experimental participants was performed, in order to identify specific areas of major myofascial tension. Each individual of the Experimental group received OFM by the same Osteopath who had previously assessed them. A sham-treatment was applied to the Control group for the equivalent amount of time. a) The factorial ANOVA test showed a significant difference (p-value < 0.05) between KMS in asymptomatic individuals (1.92

  4. Shock wave lithotripsy (SWL) induces significant structural and functional changes in the kidney

    NASA Astrophysics Data System (ADS)

    Evan, Andrew P.; Willis, Lynn R.; Lingeman, James E.

    2003-10-01

    The foundation for understanding SWL-injury has been well-controlled renal structural and functional studies in pigs, a model that closely mimics the human kidney. A clinical dose (2000 shocks at 24 kV) of SWL administered by the Dornier HM3 induces a predictable, unique vascular injury at F2 that is associated with transient renal vasoconstriction, seen as a reduction in renal plasma flow, in both treated and untreated kidneys. Unilateral renal denervation studies links the fall in blood flow in untreated kidneys to autonomic nerve activity in the treated kidney. SWL-induced trauma is associated with an acute inflammatory process, termed Lithotripsy Nephritis and tubular damage at the site of damage that leads to a focal region of scar. Lesion size increases with shock number and kV level. In addition, risk factors like kidney size and pre-existing renal disease (e.g., pyelonephritis), can exaggerate the predicted level of renal impairment. Our new protection data show that lesion size can be greatly reduced by a pretreatment session with low kV and shock number. The mechanisms of soft tissue injury probably involves shear stress followed by acoustic cavitation. Because of the perceived enhanced level of bioeffects from 3rd generation lithotripters, these observations are more relevant than ever.

  5. The effect of antiepileptic drugs on the kidney function and structure.

    PubMed

    Hamed, Sherifa Ahmed

    2017-09-01

    Long-term use of antiepileptic drugs (AEDs) is associated with number of somatic conditions. Data from experimental, cross-sectional and prospective studies have evidence for the deleterious effect of some AEDs on the kidney. Areas covered: This review summarized the current knowledge of the effect of AEDs on the kidney including evidence and mechanisms. Fanconi syndrome was reported with valproate (VPA) therapy in severely disabled children with epilepsy. Renal tubular acidosis and urolithiasis were reported with acetazolamide, topirmate and zonisamide, drugs with carbonic anhydrase inhibition properties. Increased levels of urinary N-acetyl-beta-D-glucosaminidase (NAG) to urinary creatinine (U-NAG/UCr), urinary excretion of α1-micrglobulin, β-galactosidase activity; and urinary malondialdehyde to creatinine (MDA/Cr), markers of renal glomerular and tubular injury, were reported with chronic use of some AEDs (VPA, carbamazepine and phenytoin). The mechanism(s) of kidney dysfunction/injury induced by AEDs is unknown. Experimental and clinical studies have shown that VPA induces oxidative stress, mitochondrial deficits, carnitine deficiency and inflammation and fibrosis in renal tissue in mice and in vitro studies. Expert commentary: It seems reasonable to monitor kidney function during treating patients with epilepsy at high risk of kidney injury (e.g. on combined therapy with more than one AED, severely disabled children, etc).

  6. Environmental exposures and pediatric kidney function and disease: A systematic review.

    PubMed

    Zheng, Laura Y; Sanders, Alison P; Saland, Jeffrey M; Wright, Robert O; Arora, Manish

    2017-10-01

    Environmental chemical exposures have been implicated in pediatric kidney disease. No appraisal of the available evidence has been conducted on this topic. We performed a systematic review of the epidemiologic studies that assessed association of environmental exposures with measures of kidney function and disease in pediatric populations. The search period went through July 2016. We found 50 studies that met the search criteria and were included in this systematic review. Environmental exposures reviewed herein included lead, cadmium, mercury, arsenic, fluoride, aflatoxin, melamine, environmental tobacco, bisphenol A, dental procedures, phthalates, ferfluorooctanoic acid, triclosan, and thallium/uranium. Most studies assessed environmental chemical exposure via biomarkers but four studies assessed exposure via proximity to emission source. There was mixed evidence of association between metal exposures, and other non-metal environmental exposures and pediatric kidney disease and other kidney disease biomarkers. The evaluation of causality is hampered by the small numbers of studies for each type of environmental exposure, as well as lack of study quality and limited prospective evidence. There is a need for well-designed epidemiologic studies of environmental chemical exposures and kidney disease outcomes. Copyright © 2017. Published by Elsevier Inc.

  7. 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

  8. Gastrointestinal bleeding risk of selective serotonin reuptake inhibitors by level of kidney function: a population-based cohort study.

    PubMed

    Iwagami, Masao; Tomlinson, Laurie A; Mansfield, Kathryn E; Douglas, Ian J; Smeeth, Liam; Nitsch, Dorothea

    2018-06-04

    To estimate the risk of gastrointestinal (GI) bleeding associated with serotonin reuptake inhibitors (SSRIs) by level of kidney function. We conducted a cohort study using the Clinical Practice Research Datalink linked to Hospital Episode Statistics. We identified patients with chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73m 2 for ≥3 months), and a comparison group of patients without it. Patients with CKD were further classified as stage 3a (eGFR 45-59 mL/min/1.73m 2 ), 3b (30-44 mL/min/1.73m 2 ), and 4/5 (<30 mL/min/1.73m 2 ). We excluded prevalent SSRI users at cohort entry. Exposure was time-dependent SSRI prescription and outcome was first hospitalisation for GI bleeding. We estimated adjusted rate ratio (aRR) and rate difference (aRD) of GI bleeding comparing periods with and without SSRI prescription at each level of kidney function. The aRRs and aRDs were: (i) no CKD (N=202,121) aRR: 1.66 (95%CI 1.37-2.01), aRD: 2.0/1000 person-years (5.5 versus 3.5/1000 person-years in period with and without SSRIs); (ii) CKD stage 3a (N=153,316) aRR: 1.86 (1.62-2.15), aRD: 4.2/1000 person-years (8.3 versus 4.1/1000 person-years); (iii) CKD stage 3b (N=46,482) aRR: 1.61 (1.27-2.04), aRD: 4.8/1000 person-years (9.9 versus 5.1/1000 person-years); and (iv) CKD stage 4/5 (N=11,197) aRR: 1.84 (1.14-2.96), aRD: 7.9/1000 person-years (15.3 versus 7.4/1000 person-years). While there was no evidence of increase in the aRR (p-trend=0.922), there was strong evidence that the aRD increased as kidney function deteriorated (p-trend=0.001). While the relative risk was constant, the excess risk of GI bleeding associated with SSRIs markedly increased among patients with decreased kidney function. This article is protected by copyright. All rights reserved.

  9. Kidney function and urine protein composition in healthy volunteers during space station fitness tests.

    PubMed

    Fomina, Elena V; Lisova, Natalia Iu; Kireev, Kirill S; Tiys, Evgeny S; Kononikhin, Alexey S; Larina, Irina M

    2015-05-01

    There is a close physiological connection between muscular activity and kidney function. During physical exercise (PE) the qualitative and quantitative composition of urine changes. This paper explores the influence of moderate PE on urine protein composition. The study of urine protein composition will help to make corrections to the existing methods of countermeasures. There were 10 healthy men who exercised on a treadmill similar to the one onboard the International Space Station. We analyzed their urinary proteome composition, potassium level, sodium level, and their level of osmotically active substances before and after PE. After moderate PE, a small increase in urine flow speed and a constant glomerular filtration rate were noted. The average-group index of total protein excretion within the urine was reliably increased. From the 148 proteins identified in the urine, 64 were associated with known tissue origin. We found that protein penetration into the urine had a positive correlation with their tissue expression. Selectivity of the glomerular barrier during PE decreased and high-molecular weight proteins penetrated through the glomerular barrier more easily after PE. Performance of moderate intensity physical exercise of short duration did not lead to an increase in the glomerular filtration rate nor did diuresis increase above the limits of baseline variability. However, the protein excretion rate increased after PE. We also observed that protein composition drift indicated a change in the set of biological processes in which a given protein participated, in some cases activating, in some cases inactivating them.

  10. Endothelial mineralocorticoid receptor ablation does not alter blood pressure, kidney function or renal vessel contractility

    PubMed Central

    Laursen, Sidsel B.; Finsen, Stine; Marcussen, Niels; Quaggin, Susan E.

    2018-01-01

    Aldosterone blockade confers substantial cardiovascular and renal protection. The effects of aldosterone on mineralocorticoid receptors (MR) expressed in endothelial cells (EC) within the renal vasculature have not been delineated. We hypothesized that lack of MR in EC may be protective in renal vasculature and examined this by ablating the Nr3c2 gene in endothelial cells (EC-MR) in mice. Blood pressure, heart rate and PAH clearance were measured using indwelling catheters in conscious mice. The role of the MR in EC on contraction and relaxation was investigated in the renal artery and in perfused afferent arterioles. Urinary sodium excretion was determined by use of metabolic cages. EC-MR transgenics had markedly decreased MR expression in isolated aortic endothelial cells as compared to littermates (WT). Blood pressure and effective renal plasma flow at baseline and following AngII infusion was similar between groups. No differences in contraction and relaxation were observed between WT and EC-MR KO in isolated renal arteries during baseline or following 2 or 4 weeks of AngII infusion. The constriction or dilatations of afferent arterioles between genotypes were not different. No changes were found between the groups with respect to urinary excretion of sodium after 4 weeks of AngII infusion, or in urinary albumin excretion and kidney morphology. In conclusion, deletion of the EC-MR does not confer protection towards the development of hypertension, endothelial dysfunction of renal arteries or renal function following prolonged AngII-infusion. PMID:29466427

  11. Kidney function and blood pressure in preschool-aged children exposed to cadmium and arsenic - potential alleviation by selenium

    SciTech Connect

    Skröder, Helena; Hawkesworth, Sophie; Kippler, Maria

    Background: Early-life exposure to toxic compounds may cause long-lasting health effects, but few studies have investigated effects of childhood exposure to nephrotoxic metals on kidney and cardiovascular function. Objectives: To assess effects of exposure to arsenic and cadmium on kidney function and blood pressure in pre-school-aged children, and potential protection by selenium. Methods: This cross-sectional study was part of the 4.5 years of age (range: 4.4–5.4 years) follow-up of the children from a supplementation trial in pregnancy (MINIMat) in rural Bangladesh, and nested studies on early-life metal exposures. Exposure to arsenic, cadmium and selenium from food and drinking water wasmore » assessed by concentrations in children's urine, measured by ICP-MS. Kidney function was assessed by the estimated glomerular filtration rate (eGFR, n=1106), calculated from serum cystatin C, and by kidney volume, measured by ultrasound (n=375). Systolic and diastolic blood pressure was measured (n=1356) after five minutes rest. Results: Multivariable-adjusted regression analyzes showed that exposure to cadmium, but not arsenic, was inversely associated with eGFR, particularly in girls. A 0.5 µg/L increase in urinary cadmium among the girls (above spline knot at 0.12) was associated with a decrease in eGFR of 2.6 ml/min/1.73 m{sup 2}, corresponding to 0.2SD (p=0.022). A slightly weaker inverse association with cadmium was also indicated for kidney volume, but no significant associations were found with blood pressure. Stratifying on children's urinary selenium (below or above median of 12.6 µg/L) showed a three times stronger inverse association of U-Cd with eGFR (all children) in the lower selenium stratum (B=−2.8; 95% CI: −5.5, −0.20; p=0.035), compared to those with higher selenium (B=−0.79; 95% CI: −3.0, 1.4; p=0.49). Conclusions: Childhood cadmium exposure seems to adversely affect kidney function, but not blood pressure, in this population of young

  12. 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.

  13. Effects of Single and Combined Losartan and Tempol Treatments on Oxidative Stress, Kidney Structure and Function in Spontaneously Hypertensive Rats with Early Course of Proteinuric Nephropathy

    PubMed Central

    Grujic-Milanovic, Jelica; Miloradovic, Zoran; Ivanov, Milan; Jovovic, Djurdjica; Vajic, Una-Jovana; Zivotic, Maja; Markovic-Lipkovski, Jasmina; Mihailovic-Stanojevic, Nevena

    2016-01-01

    Oxidative stress has been widely implicated in both hypertension and chronic kidney disease (CKD). Hypertension is a major risk factor for CKD progression. In the present study we have investigated the effects of chronic single tempol (membrane-permeable radical scavenger) or losartan (angiotensin II type 1 receptor blocker) treatment, and their combination on systemic oxidative status (plasma thiobarbituric acid-reactive substances (pTBARS) production, plasma antioxidant capacity (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid, pABTS), erythrocyte antioxidant enzymes activities) and kidney oxidative stress (kTBARS, kABTS, kidney antioxidant enzymes activities), kidney function and structure in spontaneously hypertensive rats (SHR) with the early course of adriamycin-induced nephropathy. Adult SHR were divided into five groups. The control group received vehicle, while the other groups received adriamycin (2 mg/kg, i.v.) twice in a 21-day interval, followed by vehicle, losartan (L,10 mg/kg/day), tempol (T,100 mg/kg/day) or combined T+L treatment (by gavage) during a six-week period. Adriamycin significantly increased proteinuria, plasma lipid peroxidation, kidney protein oxidation, nitrite excretion, matrix metalloproteinase-1 (MMP-1) protein expression and nestin immunostaining in the kidney. Also, it decreased kidney antioxidant defense, kidney NADPH oxidase 4 (kNox4) protein expression and abolished anti-inflammatory response due to significant reduction of kidney NADPH oxidase 2 (kNox2) protein expression in SHR. All treatments reduced protein-to-creatinine ratio (marker of proteinuria), pTBARS production, kidney protein carbonylation, nitrite excretion, increased antioxidant capacity and restored kidney nestin expression similar to control. Both single treatments significantly improved systemic and kidney antioxidant defense, bioavailability of renal nitric oxide, reduced kMMP-1 protein expression and renal injury, thus retarded CKD progression

  14. Effects of Single and Combined Losartan and Tempol Treatments on Oxidative Stress, Kidney Structure and Function in Spontaneously Hypertensive Rats with Early Course of Proteinuric Nephropathy.

    PubMed

    Karanovic, Danijela; Grujic-Milanovic, Jelica; Miloradovic, Zoran; Ivanov, Milan; Jovovic, Djurdjica; Vajic, Una-Jovana; Zivotic, Maja; Markovic-Lipkovski, Jasmina; Mihailovic-Stanojevic, Nevena

    2016-01-01

    Oxidative stress has been widely implicated in both hypertension and chronic kidney disease (CKD). Hypertension is a major risk factor for CKD progression. In the present study we have investigated the effects of chronic single tempol (membrane-permeable radical scavenger) or losartan (angiotensin II type 1 receptor blocker) treatment, and their combination on systemic oxidative status (plasma thiobarbituric acid-reactive substances (pTBARS) production, plasma antioxidant capacity (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid, pABTS), erythrocyte antioxidant enzymes activities) and kidney oxidative stress (kTBARS, kABTS, kidney antioxidant enzymes activities), kidney function and structure in spontaneously hypertensive rats (SHR) with the early course of adriamycin-induced nephropathy. Adult SHR were divided into five groups. The control group received vehicle, while the other groups received adriamycin (2 mg/kg, i.v.) twice in a 21-day interval, followed by vehicle, losartan (L,10 mg/kg/day), tempol (T,100 mg/kg/day) or combined T+L treatment (by gavage) during a six-week period. Adriamycin significantly increased proteinuria, plasma lipid peroxidation, kidney protein oxidation, nitrite excretion, matrix metalloproteinase-1 (MMP-1) protein expression and nestin immunostaining in the kidney. Also, it decreased kidney antioxidant defense, kidney NADPH oxidase 4 (kNox4) protein expression and abolished anti-inflammatory response due to significant reduction of kidney NADPH oxidase 2 (kNox2) protein expression in SHR. All treatments reduced protein-to-creatinine ratio (marker of proteinuria), pTBARS production, kidney protein carbonylation, nitrite excretion, increased antioxidant capacity and restored kidney nestin expression similar to control. Both single treatments significantly improved systemic and kidney antioxidant defense, bioavailability of renal nitric oxide, reduced kMMP-1 protein expression and renal injury, thus retarded CKD progression

  15. Kidney Transplantation Is Superior to Hemodialysis and Peritoneal Dialysis in Terms of Cognitive Function, Anxiety, and Depression Symptoms in Chronic Kidney Disease.

    PubMed

    Ozcan, H; Yucel, A; Avşar, U Z; Cankaya, E; Yucel, N; Gözübüyük, H; Eren, F; Keles, M; Aydınlı, B

    2015-06-01

    Cognitive impairment, anxiety and depression are important problems for patients with chronic kidney failure. Cognitive impairment, anxiety, and depression may be related to various factors, such as complications of hemo/peritoneal dialysis, uremic encephalopathy, psychosocial burden of the disease, and various comorbidities in patients with chronic kidney failure. Successful kidney transplantation (KT) improves kidney, endocrine, metabolic, and vascular systems, mental functions, and the quality of life of the patients. A total of 181 patients with chronic kidney failure were studied: 54 currently on hemodialysis, 58 on peritoneal dialysis, and 69 with KT. All participants were given a detailed sociodemographic form, including data about the reason of kidney failure, duration of treatment (hemodialysis, peritoneal dialysis, and KT), and comorbid illnesses. Participants were evaluated with the use of the Hospital Anxiety and Depression Scale (HADS) for evaluating depressive and anxiety symptoms and the Brief Cognitive State Examination (BCSE) for detecting possible cognitive impairment. Patients with KT had lower levels of anxiety and depression symptoms than patients with hemodialysis and peritoneal dialysis. The KT group scored better than the hemodialysis and peritoneal dialysis groups on the BCSE. The peritoneal dialysis group scored higher on the BCSE than the hemodialysis group. The hemodialysis group scored higher on the HADS than the peritoneal dialysis group. In this study it was found that KT patients have better cognitive and mood regulation outcomes than hemodialysis and peritoneal dialysis patients with chronic kidney failure. With this knowledge we suggest that patients with kidney failure should have KT for having better cognitive functions and mood state as soon as possible. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. 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.

  17. One-Year Conservative Care Using Sodium Bicarbonate Supplementation Is Associated with a Decrease in Electronegative LDL in Chronic Kidney Disease Patients: A Pilot Study.

    PubMed

    Rizzetto, Felipe; Mafra, Denise; Barra, Ana Beatriz; Pires de Melo, Gisella; Abdalla, Dulcinéia Saes Parra; Leite, Maurilo

    2017-10-01

    Chronic kidney disease (CKD) patients develop metabolic acidosis when approaching stages 3 and 4, a period in which accelerated atherogenesis may ensue. Studies in vitro show that low pH may increase low-density lipoprotein (LDL) oxidation, suggesting a role for chronic metabolic acidosis in atherosclerosis. The present study attempted to evaluate the effects of conservative care using oral sodium bicarbonate (NaHCO 3 ) supplementation on the electronegative LDL [LDL(-)], a minimally oxidized LDL, plasma levels in CKD patients. Thirty-one CKD patients were followed by a multidisciplinary team during 15 months of care in which 1.0 mmol/kg/day oral NaHCO 3 supplementation was first given in the third month. Blood samples were collected 3 months before the initiation of oral NaHCO 3 supplementation (T1), at the time of the beginning of supplementation (T2), and thereafter, each 4 months (T3, T4 and T5) until month 15 of care. Blood parameters and LDL(-) were measured from these collections. After 12 months of conservative care, creatinine clearance (MDRD) was kept stable, and serum bicarbonate (HCO 3 - ) increased from 20.5 ± 2.9 to 22.6 ± 1.1 mM ( p < 0.003). LDL(-) plasma levels declined from 4.5 ± 3.3 to 2.1 ± 0.9 U/L ( p < 0.007) after reaching mean serum HCO 3 - levels of 22.6 ± 1.1 mM. Conservative care using oral NaHCO 3 supplementation was able to stabilize renal function and decrease serum levels of LDL(-), a modified proatherogenic lipoprotein, only when mean serum HCO 3 - levels approached 22 mM. This study constitutes evidence that alkali therapy, in addition to its beneficial effect on renal disease progression, might serve as a preventive strategy to attenuate atherogenesis in CKD patients.

  18. Frailty, Kidney Function, and Polypharmacy: The Atherosclerosis Risk in Communities (ARIC) Study

    PubMed Central

    Ballew, Shoshana H.; Chen, Yan; Daya, Natalie R.; Godino, Job G.; Windham, B. Gwen; McAdams-DeMarco, Mara; Coresh, Josef; Selvin, Elizabeth; Grams, Morgan E.

    2016-01-01

    Background Frail individuals are at increased risk for poor outcomes, including adverse drug events. Kidney function is often compromised in frailty and is a key consideration in medication choice and dosing; however, creatinine-based measures of kidney function may be biased in frail individuals. Study Design Observational study. Setting & Participants 4,987 community-dwelling older men and women with complete data who participated in visit 5 of the Atherosclerosis Risk in Communities (ARIC) Study (2011–2013). Predictor Kidney measures included glomerular filtration rate (GFR) estimated using serum creatinine (eGFRcr) and serum cystatin C (eGFRcys) and urine albumin-creatinine ratio (ACR). Outcomes Frailty, defined using established criteria of 3 or more frailty characteristics (weight loss, slowness, exhaustion, weakness, and low physical activity). Results In total, 341 participants (7%) were classified as frail, 1475 (30%) had eGFRcr <60 ml/min/1.73 m2, 2480 (50%) had eGFRcys <60 ml/min/1.73 m2, and 1006 (20%) had albuminuria ≥30 mg/g. Among frail participants, prevalences of eGFRcr and eGFRcys <60 ml/min/1.73 m2 were 45% and 77%, respectively. Adjusted for covariates, frailty showed a moderate association with eGFRcr and a strong association with eGFRcys and ACR. Frail individuals with eGFRcr 60–<75 ml/min/1.73 m2 were frequently reclassified to lower eGFR categories using eGFRcys (49% to 45–<60, 32% to 30–<45, and 3% to <30 ml/min/1.73 m2). Hyperpolypharmacy (taking ≥10 classes of medications) was more common in frail individuals (54% vs 38% of non-frail), including classes requiring kidney clearance (e.g., digoxin) and associated with falls and subsequent complications (e.g., hypnotic/sedatives, anticoagulants). Limitations Cross-sectional study design. Conclusions Frail individuals had a high prevalence of reduce kidney function, with large discrepancies when reduced kidney function was classified by eGFRcys versus eGFRcr. Given the substantial

  19. Association between Soluble Klotho and Change in Kidney Function: The Health Aging and Body Composition Study.

    PubMed

    Drew, David A; Katz, Ronit; Kritchevsky, Stephen; Ix, Joachim; Shlipak, Michael; Gutiérrez, Orlando M; Newman, Anne; Hoofnagle, Andy; Fried, Linda; Semba, Richard D; Sarnak, Mark

    2017-06-01

    CKD appears to be a condition of soluble klotho deficiency. Despite known associations between low soluble klotho levels and conditions that promote kidney damage, such as oxidative stress and fibrosis, little information exists regarding the longitudinal association between soluble klotho levels and change in kidney function. We assayed serum soluble α -klotho in 2496 participants within the Health Aging and Body Composition study, a cohort of older adults. The associations between soluble klotho levels and decline in kidney function (relative decline: eGFR decline ≥30%; absolute decline: eGFR decline >3 ml/min per year) and incident CKD (incident eGFR <60 ml/min per 1.73 m 2 and >1 ml/min per year decline) were evaluated. We adjusted models for demographics, baseline eGFR, urine albumin-to-creatinine ratio, comorbidity, and measures of mineral metabolism. Among participants, the mean (SD) age was 75 (3) years, 52% were women, and 38% were black. Median (25th, 75th percentiles) klotho level was 630 (477, 817) pg/ml. In fully adjusted models, each two-fold higher level of klotho associated with lower odds of decline in kidney function (odds ratio, 0.78 [95% confidence interval, 0.66 to 0.93] for 30% decline in eGFR, and 0.85 [95% confidence interval, 0.73 to 0.98] for >3 ml/min per year decline in eGFR), but not of incident CKD (incident rate ratio, 0.90 [95% confidence interval, 0.78 to 1.04]). Overall, a higher soluble klotho level independently associated with a lower risk of decline in kidney function. Future studies should attempt to replicate these results in other cohorts and evaluate the underlying mechanism. Copyright © 2017 by the American Society of Nephrology.

  20. Perceived Discrimination and Longitudinal Change in Kidney Function Among Urban Adults.

    PubMed

    Beydoun, May A; Poggi-Burke, Angedith; Zonderman, Alan B; Rostant, Ola S; Evans, Michele K; Crews, Deidra C

    2017-09-01

    Perceived discrimination has been associated with psychosocial distress and adverse health outcomes. We examined associations of perceived discrimination measures with changes in kidney function in a prospective cohort study, the Healthy Aging in Neighborhoods of Diversity across the Life Span. Our study included 1620 participants with preserved baseline kidney function (estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m) (662 whites and 958 African Americans, aged 30-64 years). Self-reported perceived racial discrimination and perceived gender discrimination (PGD) and a general measure of experience of discrimination (EOD) ("medium versus low," "high versus low") were examined in relation to baseline, follow-up, and annual rate of change in eGFR using multiple mixed-effects regression (γbase, γrate) and ordinary least square models (γfollow). Perceived gender discrimination "high versus low PGD" was associated with a lower baseline eGFR in all models (γbase = -3.51 (1.34), p = .009 for total sample). Among white women, high EOD was associated with lower baseline eGFR, an effect that was strengthened in the full model (γbase = -5.86 [2.52], p = .020). Overall, "high versus low" PGD was associated with lower follow-up eGFR (γfollow = -3.03 [1.45], p = .036). Among African American women, both perceived racial discrimination and PGD were linked to lower follow-up kidney function, an effect that was attenuated with covariate adjustment, indicating mediation through health-related, psychosocial, and lifestyle factors. In contrast, EOD was not linked to follow-up eGFR in any of the sex by race groups. Perceived racial and gender discrimination are associated with lower kidney function assessed by glomerular filtration rate and the strength of associations differ by sex and race groups. Perceived discrimination deserves further investigation as a psychosocial risk factors for kidney disease.

  1. Measuring Dynamic Kidney Function in an Undergraduate Physiology Laboratory

    ERIC Educational Resources Information Center

    Medler, Scott; Harrington, Frederick

    2013-01-01

    Most undergraduate physiology laboratories are very limited in how they treat renal physiology. It is common to find teaching laboratories equipped with the capability for high-resolution digital recordings of physiological functions (muscle twitches, ECG, action potentials, respiratory responses, etc.), but most urinary laboratories still rely on…

  2. Acute kidney failure

    MedlinePlus

    Kidney failure; Renal failure; Renal failure - acute; ARF; Kidney injury - acute ... There are many possible causes of kidney damage. They include: ... cholesterol (cholesterol emboli) Decreased blood flow due to very ...

  3. 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.

  4. Ginger polyphenols attenuate cyclosporine-induced disturbances in kidney function: Potential application in adjuvant transplant therapy.

    PubMed

    Adekunle, Isiaka Ayofe; Imafidon, Christian Eseigbe; Oladele, Ayowole Abraham; Ayoka, Abiodun Oladele

    2018-06-01

    Cyclosporine (CYA), a common immuno-suppressant drug that is used in organ transplants, is associated with nephrotoxic effects. Scientific exploration of natural products of plant origin should be considered; especially, in a world with increasing prevalence of kidney diseases. Effects of ginger polyphenols (GP) in Wistar rats with CYA-induced perturbations in electrolyte balance and kidney function was determined. Fifty Wistar rats were recruited for this study such that graded doses of GP were administered following CYA-induced kidney injury and comparisons were made against control and toxic groups at p < 0.05. Distilled water, CYA (50 mg/kg p.o. for 10 days) and GP (100, 200 and 400 mg/kg p.o. for 21 days) were administered to the rats at 0.2 ml/100 g. CYA administration induced kidney injury as characterized by significant deleterious alterations in plasma and urine levels of creatinine, urea, Na + and K + electrolyte balance as well as creatinine clearance. Also, there was a significant derangement in feeding pattern and relative kidney weight. Using GSH and SOD as antioxidant indicators, there was significant disturbance of the anti-oxidant system while histopathological results showed evidence of interstitial vacuolations with atrophic glomeruli. These conditions were significantly attenuated (p < 0.05) following administration of graded doses of GP. It was, therefore, concluded that GP could potentially be a therapeutic choice for patients with CYA-induced kidney injury. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. [Causes of death with a functioning graft among kidney allograft recipients].

    PubMed

    Vega, Jorge; Videla, Christian; Borja, Hernán; Goecke, Helmuth; Martínez, Felipe; Betancour, Pablo

    2012-03-01

    Death with a functioning graft (DWGF) is now one of the main causes of renal transplant (RTx) loss. To determine whether the causes of DWGF, characteristics of donors and recipients and complications of RTx have changed in the last two decades. Cooperative study of a cohort of 418 kidney grafts performed between 1968 and 2010. Patients were divided into two groups according to whether their kidney transplants were performed between 1968 and 1992 (Group 1) or 1993 and 2010 (Group 2). Sixty eight patients experienced DWGF. Infections were the leading cause of DWGF in both groups (38 and 41%, respectively), followed by cardiovascular diseases (24 and 23% respectively), gastrointestinal disorders (21 and 26% respectively) and cancer (17 and 10% respectively). There were no significant differences in causes of death between the two groups according to the time elapsed since the renal transplantation. In patients in Group 1, the interval between diagnosis of renal failure and dialysis (HD) and the interval between the start of HD and kidney transplantation were significantly lower than in Group 2. The former had also an increased number of acute rejections in the first five years of kidney transplantation (p < 0.001). In Group 2, patients more often received their kidneys from deceased donors, had previous kidney transplantation, higher rate of antibodies to a panel of lymphocytes and an increased incidence of cardiovascular disorders after five years of RTx. The proportion of graft loss due to DWGF has increased over the last 2 decades, but its causes have not changed significantly. Infections are the most common causes of DWGF followed by cardiovascular and digestive diseases.

  6. Increased resistin in brain dead organ donors is associated with delayed graft function after kidney transplantation

    PubMed Central

    2013-01-01

    Introduction Resistin increases during several inflammatory diseases and after intracerebral bleeding or head trauma. Resistin activates the endothelium and may initiate an inflammatory response. No data are available on resistin in brain dead donors (DBD) that regularly manifest a pronounced inflammatory state. Methods We analyzed plasma resistin in 63 DBDs and correlated results with donor variables and the postoperative course following kidney transplantation using organs from these donors. Endocan and monocyte chemotactic protein (MCP)-1 were also studied. Twenty-six live kidney donors (LD) and the corresponding kidney transplantations were used as controls. Results DBDs had higher resistin (median/range 30.75 ng/ml, 5.41–173.6) than LD (7.71 ng/ml, 2.41–15.74, p < 0.0001). Resistin in DBD correlated with delayed graft function (DGF) in the kidney recipients (r = 0.321, p < 0.01); receiver operating characteristic curve revealed an area under the curve of 0.765 (95% confidence interval [CI] 0.648–0.881, p < 0.01) and a cut-off value for resistin of 25 ng/ml; MCP-1 and endocan were higher in DBDs (p < 0.0001) but did not correlate with DGF or acute rejection. No relationship was found between the studied molecules and the postoperative course of LD kidney transplants. Conclusions High resistin levels in the DBD before organ retrieval are associated with DGF after kidney transplantation. The resistin increase seems related to the inflammatory state after brain death but not to the cause of death. PMID:24070260

  7. Disease Progression Modeling to Evaluate the Effects of Enzyme Replacement Therapy on Kidney Function in Adult Patients with the Classic Phenotype of Fabry Disease.

    PubMed

    Nowak, Albina; Koch, Gilbert; Huynh-Do, Uyen; Siegenthaler, Martin; Marti, Hans-Peter; Pfister, Marc

    2017-01-01

    Fabry disease (FD) is a rare inherited lysosomal storage disease with common and serious kidney complications. Enzyme replacement therapies (ERT) with agalsidase-α and -β were investigated to characterize their therapeutic effect on kidney function in FD patients with Classic phenotype. The prospective FD cohort consisted of 98 genetically confirmed patients (females, n = 61, males, n = 37). The median [interquartile range] follow-up time (time difference from first to last visit) was 9 [6, 12] years. The median age of ERT start was 36 [21 - 54] years for females and 39 [28 - 49] years for males. A disease progression model was developed to (i) characterize the time course of estimated glomerular filtration rate (eGFR) and (ii) evaluate therapeutic effects of ERT on kidney function. Change in eGFR over time was best described by the linear model. Females had stable kidney function with and without ERT (eGFR slopes of -0.07 ml/min/1.73m^2 per year and 0.52 ml/min/1.73m^2 per year, respectively). Males with ERT showed an eGFR decrease of -3.07 ml/min/1.73m^2 per year. Mathematical disease progression modeling indicates that there is no clear therapeutic effect of ERT on kidney function in adult patients with Classic Phenotype of FD. Interpretation of these findings should take into account that the study is not randomized and lacks a placebo controlled group. Further investigations are warranted to clarify whether earlier ERT initiation before 18 years of age, higher ERT dose or more intensive therapies can preserve kidney function. © 2017 The Author(s)Published by S. Karger AG, Basel.

  8. Ectopic Kidney

    MedlinePlus

    ... Ectopic Kidney Medullary Sponge Kidney Kidney Dysplasia Ectopic Kidney What is an ectopic kidney? An ectopic kidney is a birth defect in ... has an ectopic kidney. 1 What are the kidneys and what do they do? The kidneys are ...

  9. Effects of PEG-PLA-nano Artificial Cells Containing Hemoglobin on Kidney Function and Renal Histology in Rats

    PubMed Central

    Liu, Zun Chang; Chang, Thomas M.S.

    2012-01-01

    This study is to investigate the long-term effects of PEG-PLA nano artificial cells containing hemoglobin (NanoRBC) on renal function and renal histology after 1/3 blood volume top loading in rats. The experimental rats received one of the following infusions: NanoRBC in Ringer lactate, Ringer lactate, stroma-free hemoglobin (SFHB), polyhemoglobin (PolyHb), autologous rat whole blood (rat RBC). Blood samples were taken before infusions and on days 1, 7 and 21 after infusions for biochemistry analysis. Rats were sacrificed on day 21 after infusions and kidneys were excised for histology examination. Infusion of SFHB induced significant decrease in renal function damage evidenced by elevated serum urea, creatinine and uric acid throughout the 21 days. Kidney histology in SFHb infusion group revealed focal tubular necrosis and intraluminal cellular debris in the proximal tubules, whereas the glomeruli were not observed damaged. In all the other groups, NanoRBC, PolyHb, Ringer lactate and rat RBC, there were no abnormalities in renal biochemistry or histology. In conclusion, injection of NanoRBC did not have adverse effects on renal function nor renal histology. PMID:18979292

  10. Symptomatic BK Virus Infection Is Associated with Kidney Function Decline and Poor Overall Survival in Allogeneic Hematopoietic Stem Cell Recipients

    PubMed Central

    Abudayyeh, Ala; Hamdi, Amir; Lin, Heather; Abdelrahim, Maen; Rondon, Gabriela; Andersson, Borje S; Afrough, Aimaz; Martinez, Charles S; Tarrand, Jeffrey J; Kontoyiannis, Dimitrios P.; Marin, David; Gaber, A. Osama; Salahudeen, Abdulla; Oran, Betul; Chemaly, Roy F.; Olson, Amanda; Jones, Roy; Popat, Uday; Champlin, Richard E; Shpall, Elizabeth J.; Winkelmayer, Wolfgang C.; Rezvani, Katayoun

    2017-01-01

    Nephropathy due to BK virus infection is an evolving challenge in patients undergoing hematopoietic stem cell transplantation. We hypothesized that BKV infection was a marker of Kidney Function Decline and a poor prognostic factor in HSCT recipients who experience this complication. In this retrospective study, we analyzed all patients who underwent their first allogeneic hematopoietic stem cell transplantation at our institution between 2004 and 2012. We evaluated the incidence of persistent kidney function decline, which was defined as a confirmed reduction in estimated glomerular filtration rate of at least 25% from baseline using the CKD-EPI equation. Cox proportional hazard regression was used to model the cause-specific hazard of kidney function decline and Fine and Gray’s method was used to account for the competing risks of death. Among 2477 recipients of a first allogeneic hematopoietic stem cell transplantation, BK viruria was detected in 25% (n=629) and kidney function decline in 944 (38.1%). On multivariate analysis, after adjusting for age, sex, acute graft-versus-host disease, chronic graft versus host disease, preparative conditioning regimen, and graft source, BK viruria remained a significant risk factor for kidney function decline (P <0.001). In addition, patients with BKV infection and kidney function decline experienced worse overall survival. Post-allogeneic hematopoietic stem cell transplantation, BKV infection was strongly and independently associated with subsequent kidney function decline and worse patient survival after HSCT. PMID:26608093

  11. Effects of Mediterranean diets on kidney function: a report from the PREDIMED trial.

    PubMed

    Díaz-López, Andrés; Bulló, Mònica; Martínez-González, Miguel Ángel; Guasch-Ferré, Marta; Ros, Emilio; Basora, Josep; Covas, María-Isabel; del Carmen López-Sabater, Maria; Salas-Salvadó, Jordi

    2012-09-01

    Epidemiologic observations have linked healthy dietary patterns to improved kidney function. We assessed the effects of the Mediterranean diet (MedDiet) on kidney function in both a cross-sectional assessment and after a 1-year intervention in a cohort of the PREDIMED (Prevención con Dieta Mediterránea) Study, a multicenter 3-arm randomized clinical trial to determine the efficacy of the MedDiet on primary cardiovascular prevention. Community-dwelling men aged 55-80 years and women aged 60-80 years at high risk of cardiovascular disease from Reus, Spain. Participants were randomly assigned to 3 ad libitum diets: a MedDiet supplemented with virgin olive oil (MedDiet + olive oil), a MedDiet supplemented with mixed nuts (MedDiet + nuts), or a control low-fat diet. Estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (ACR). Nutrient intake, adherence to the MedDiet, lifestyle variables, cardiovascular risk factors, serum urea and creatinine concentrations, eGFR, and urinary ACR were evaluated at baseline and after intervention for 1 year. Baseline kidney function markers were similar across quartiles of adherence to the MedDiet in 785 participants (55% women; mean age, 67 years). After a 1-year intervention in 665 participants, the 3 dietary approaches were associated with improved kidney function, with similar average increases in eGFR (4.7 [95% CI, 3.2-6.2], 3.5 [95% CI, 1.9-5.0], and 4.1 [95% CI, 2.8-5.5] mL/min/1.73 m(2) for the MedDiet + olive oil, MedDiet + nuts, and control groups, respectively [P < 0.001 vs baseline for each; P = 0.9 for differences among groups]), but no changes in ACRs after adjustment for various confounders. Generalization of results to other age groups or ethnicities. GFR was not directly measured. The results do not support the notion that the MedDiet has a beneficial effect on kidney function over and above that of advice for a low-fat diet in elderly individuals at high cardiovascular risk. Copyright

  12. Overweight young female kidney donors have low renal functional reserve post-donation.

    PubMed

    van Londen, Marco; Schaeffers, Anouk W M A; de Borst, Martin H; Joles, Jaap A; Navis, Gerjan; Lely, A Titia

    2018-01-03

    Maintenance of adequate renal function after living kidney donation is important for donor outcome. Overweight donors in particular may have an increased risk for end stage kidney disease (ESKD), and young female donors have an increased preeclampsia risk. Both of these risks may associate with low post-donation renal functional reserve (RFR). Because we previously found that higher BMI and lower post-donation RFR were associated, we now studied the relationship between BMI and RFR in young female donors. RFR, the rise in GFR (125I-Iothalamate clearance) during dopamine, was measured in female donors (<45 years) before and after kidney donation. Donors who are overweight (BMI>25) and non-overweight donors were compared by t-test; the association was subsequently explored with regression analysis. We included 105 female donors (age 41 [36-44] (median[IQR])) with a BMI of 25 [22-27] kg/m2. Pre-donation GFR was 118 (17) ml/min (mean(SD)) rising to 128 (19) ml/min during dopamine; mean RFR was 10 (10) ml/min. Post-donation GFR was 76 (13) ml/min, rising to 80 (12); RFR was 4 (6) ml/min (p<0.001 vs. pre-donation). In overweight donors, RFR was fully lost after donation (1 ml/min vs. 10 ml/min pre-donation, p<0.001), and BMI was inversely associated with RFR after donation, independent of confounders (St. β 0.37, p=0.02). Reduced RFR might associate with the risk of preeclampsia and ESKD in kidney donors. Prospective studies should explore whether RFR is related to preeclampsia and whether BMI reduction prior to conception is of benefit to overweight female kidney donors during and after pregnancy.

  13. rs3212227 SNP in the IL12B Gene Prevents Delayed Graft Function after Kidney Transplantation.

    PubMed

    Perovic, Vladimir; Markovic, Milos; Kravljaca, Milica; Milosevic, Emina; Djoric, Milica; Pravica, Vera; Naumovic, Radomir

    2018-05-10

    Transplantation is the best treatment option for end stage kidney disease. The most common early complications in post-transplant period are acute rejection (AR) of the graft and delayed graft function (DGF). The underlying mechanisms in these events are heterogeneous and at least in part involve cytokine genes which regulate immune response to allograft. We have investigated whether functional single nucleotide polymorphisms (SNP) in the genes encoding IFN-γ (IFNG), TNF (TNFA), IL-10 (IL10) and p40 subunit of IL-12/IL-23 (IL12B) could predict risk of AR and DGF in kidney allograft recipients. Our study involved 152 kidney transplant recipients on standard immunosuppressive regimen which included calcineurin inhibitors, mycophenolic acid derivatives and corticosteroids. Genotyping of IFNG, TNFA, IL10 and IL12B was performed using commercial TaqMan assays. We found association between the carriers of AA genotype of IL12B +1188A/C polymorphism (rs3212227) and a lower rate of DGF (p = 0.037, OR = 0.45, 95% CI = 0.21-0.96), implying protective role of A allele in the pathogenesis of DGF in kidney transplant recipients, whereas no such association was observed with AR. None of the analyzed SNPs in TNFA (-308G/A), IFNG (+874T/A), IL10 (-1082G/A, -819T/C, -592C/A) were associated with AR or DGF in our patients. Our study shows a preliminary evidence that the AA genotype of rs3212227 SNP in the IL12B gene might be associated with a lower risk for DGF after kidney transplantation. In the future, additional well-designed large studies are required for the validation of our results. Copyright © 2018 IMSS. Published by Elsevier Inc. All rights reserved.

  14. The value of Doppler ultrasound in predicting delayed graft function occurrence after kidney transplantation.

    PubMed

    Mocny, Grzegorz; Bachul, Piotr; Chang, Ea-Sle; Kulig, Piotr

    The aim of this study was to assess the predictive value of blood flow velocity and vascular resistance measured by Doppler ultrasound in terms of pulsatility index (PI) and resistive index (RI) respectively, in the occurrence of delayed graft function (DGF) after kidney transplantation. This prospective study enrolled kidney transplant recipients operated from January 2005 to April 2009 in the 1st Department of General, Oncological and Gastroenterological Surgery, Jagiellonian University Medical College, Kraków, Poland. The medical records of 53 kidney transplant recipients from deceased donors were reviewed. PI and RI values of the graft arcuate artery were calculated immediately after blood flow restoration and on the 1st, 2nd, 4th and 8th post-operative day. DGF was observed in 20 patients (37.7%), while 33 patients (62.3%) had immediate restoration of the kidney function. The mean intraoperative values of RI and PI from patients with DGF were significantly higher in comparison to patients without DGF (0.9 vs. 0.74, p <0.001; 1.76 vs. 1.54, p = 0.019, respectively). Post-operatively, the RI and PI values remained stable and significantly higher in DGF group. The highest sensitivity of RI to predict DGF occurrence was observed intraoperatively and on the first postoperative day, with values of 77.8% and 72.2%, respectively. The risk of DGF occurrence with intraoperative RI value ≥0.9 increased by 13-fold, and with intraoperative PI value ≥1.9 by 12-fold. This increase was even more prominent during the first post-operative day with RI value ≥0.9 or PI value ≥1.9 with 19-fold increase in the risk of DGF occurrence. According to our study, the utilization of Doppler ultrasound with measurement of hemodynamic parameters (PI, RI), play a crucial role in predicting the outcomes of kidney transplantation.

  15. Predictive assessment of kidney functional recovery following ischemic injury using optical spectroscopy

    SciTech Connect

    Raman, Rajesh N.; Pivetti, Christopher D.; Ramsamooj, Rajendra

    Functional changes in rat kidneys during the induced ischemic injury and recovery phases were explored using multimodal autofluorescence and light scattering imaging. We aim to evaluate the use of noncontact optical signatures for rapid assessment of tissue function and viability. Specifically, autofluorescence images were acquired in vivo under 355, 325, and 266 nm illumination while light scattering images were collected at the excitation wavelengths as well as using relatively narrowband light centered at 500 nm. The images were simultaneously recorded using a multimodal optical imaging system. We also analyzed to obtain time constants, which were correlated to kidney dysfunction asmore » determined by a subsequent survival study and histopathological analysis. This analysis of both the light scattering and autofluorescence images suggests that changes in tissue microstructure, fluorophore emission, and blood absorption spectral characteristics, coupled with vascular response, contribute to the behavior of the observed signal, which may be used to obtain tissue functional information and offer the ability to predict posttransplant kidney function.« less

  16. Longitudinal analysis of physical activity, fluid intake, and graft function among kidney transplant recipients

    PubMed Central

    Gordon, Elisa J.; Prohaska, Thomas R.; Gallant, Mary P.; Sehgal, Ashwini R.; Strogatz, David; Yucel, Recai; Conti, David; Siminoff, Laura A.

    2010-01-01

    Summary Self-care is recommended to kidney transplant recipients as a vital component to maintain long-term graft function. However, little is known about the effects of physical activity, fluid intake, and smoking history on graft function. This longitudinal study examined the relationship between self-care practices on graft function among 88 new kidney transplant recipients in Chicago, IL and Albany, NY between 2005 and 2008. Participants were interviewed, completed surveys, and medical charts were abstracted. Physical activity, fluid intake, and smoking history at baseline were compared with changes in estimated glomerular filtration rate (eGFR) (every 6 months up to 1 year) using bivariate and multivariate regression analysis, while controlling for sociodemographic and clinical transplant variables. Multivariate analyses revealed that greater physical activity was significantly (P < 0.05) associated with improvement in GFR at 6 months; while greater physical activity, absence of smoking history, and nonwhite ethnicity were significant (P < 0.05) predictors of improvement in GFR at 12 months. These results suggest that increasing physical activity levels in kidney recipients may be an effective behavioral measure to help ensure graft functioning. Our findings suggest the need for a randomized controlled trial of exercise, fluid intake, and smoking history on GFR beyond 12 months. PMID:19619168

  17. Longitudinal analysis of physical activity, fluid intake, and graft function among kidney transplant recipients.

    PubMed

    Gordon, Elisa J; Prohaska, Thomas R; Gallant, Mary P; Sehgal, Ashwini R; Strogatz, David; Yucel, Recai; Conti, David; Siminoff, Laura A

    2009-10-01

    Self-care is recommended to kidney transplant recipients as a vital component to maintain long-term graft function. However, little is known about the effects of physical activity, fluid intake, and smoking history on graft function. This longitudinal study examined the relationship between self-care practices on graft function among 88 new kidney transplant recipients in Chicago, IL and Albany, NY between 2005 and 2008. Participants were interviewed, completed surveys, and medical charts were abstracted. Physical activity, fluid intake, and smoking history at baseline were compared with changes in estimated glomerular filtration rate (eGFR) (every 6 months up to 1 year) using bivariate and multivariate regression analysis, while controlling for sociodemographic and clinical transplant variables. Multivariate analyses revealed that greater physical activity was significantly (P < 0.05) associated with improvement in GFR at 6 months; while greater physical activity, absence of smoking history, and nonwhite ethnicity were significant (P < 0.05) predictors of improvement in GFR at 12 months. These results suggest that increasing physical activity levels in kidney recipients may be an effective behavioral measure to help ensure graft functioning. Our findings suggest the need for a randomized controlled trial of exercise, fluid intake, and smoking history on GFR beyond 12 months.

  18. Predictive assessment of kidney functional recovery following ischemic injury using optical spectroscopy

    DOE PAGES

    Raman, Rajesh N.; Pivetti, Christopher D.; Ramsamooj, Rajendra; ...

    2017-05-03

    Functional changes in rat kidneys during the induced ischemic injury and recovery phases were explored using multimodal autofluorescence and light scattering imaging. We aim to evaluate the use of noncontact optical signatures for rapid assessment of tissue function and viability. Specifically, autofluorescence images were acquired in vivo under 355, 325, and 266 nm illumination while light scattering images were collected at the excitation wavelengths as well as using relatively narrowband light centered at 500 nm. The images were simultaneously recorded using a multimodal optical imaging system. We also analyzed to obtain time constants, which were correlated to kidney dysfunction asmore » determined by a subsequent survival study and histopathological analysis. This analysis of both the light scattering and autofluorescence images suggests that changes in tissue microstructure, fluorophore emission, and blood absorption spectral characteristics, coupled with vascular response, contribute to the behavior of the observed signal, which may be used to obtain tissue functional information and offer the ability to predict posttransplant kidney function.« less

  19. The effects of hard water consumption on kidney function: Insights from mathematical modelling

    NASA Astrophysics Data System (ADS)

    Tambaru, David; Djahi, Bertha S.; Ndii, Meksianis Z.

    2018-03-01

    Most water sources in Nusa Tenggara Timur contain higher concentration of calcium and magnesium ions, which is known as hard water. Long-term consumption of hard water can cause kidney dysfunction, which may lead to the other diseases such as cerebrovascular disease, diabetes and others. Therefore, understanding the effects of hard water consumption on kidney function is of importance. This paper studies the transmission dynamics of kidney dysfunction due to the consumption of hard water using a mathematical model. We propose a new deterministic mathematical model comprising human and water compartments and conduct a global sensitivity analysis to determine the most influential parameters of the model. The Routh-Hurwitz criterion is used to examine the stability of the steady states. The results shows that the model has two steady states, which are locally stable. Moreover, we found that the most influential parameters are the maximum concentration of magnesium and calcium in the water, the increase rate of calcium and magnesium concentration in the water and the rate of effectiveness of water treatment. The results suggest that better water treatments are required to reduce the concentration of magnesium and calcium in the water. This aid in minimizing the probability of humans to attract kidney dysfunction. Furthermore, water-related data need to be collected for further investigation.

  20. Decreased mortality of Lake Michigan Chinook salmon after bacterial kidney disease challenge: evidence for pathogen-driven selection?

    PubMed

    Purcell, Maureen K; Murray, Anthony L; Elz, Anna; Park, Linda K; Marcquenski, Susan V; Winton, James R; Alcorn, Stewart W; Pascho, Ronald J; Elliott, Diane G

    2008-12-01

    In the late 1960s, Chinook salmon Oncorhynchus tshawytscha from the Green River, Washington, were successfully introduced into Lake Michigan. During spring from 1988 to 1992, large fish die-offs affecting Chinook salmon occurred in the lake. Multiple ecological factors probably contributed to the severity of the fish kills, but the only disease agent found regularly was Renibacterium salmoninarum, the causative agent of bacterial kidney disease. In this study, survival after challenge by R. salmoninarum was compared between two Chinook salmon stocks: a Lake Michigan stock from Wisconsin (WI) and the progenitor stock from the Green River. We found that the WI stock had significantly greater survival than the Green River stock. Next, the WI and Green River stocks were exposed to the marine pathogen Listonella anguillarum (formerly Vibrio anguillarum), one of the causative agents of vibriosis; survival after this challenge was significantly poorer for the WI stock than for the Green River stock. A close genetic relationship between the Green River and WI stocks was confirmed by analyzing 13 microsatellite loci. These results collectively suggest that disease susceptibility of Lake Michigan Chinook salmon has diverged from that of the source population, possibly in response to pathogen-driven selection.

  1. Decreased mortality of lake michigan chinook salmon after bacterial kidney disease challenge: Evidence for pathogen-driven selection?

    USGS Publications Warehouse

    Purcell, M.K.; Murray, A.L.; Elz, A.; Park, L.K.; Marcquenski, S.V.; Winton, J.R.; Alcorn, S.W.; Pascho, R.J.; Elliott, D.G.

    2008-01-01

    In the late 1960s, Chinook salmon Oncorhynchus tshawytscha from the Green River, Washington, were successfully introduced into Lake Michigan. During spring from1988 to 1992, large fish die-offs affecting Chinook salmon occurred in the lake. Multiple ecological factors probably contributed to the severity of the fish kills, but the only disease agent found regularly was Renibacterium salmoninarum, the causative agent of bacterial kidney disease. in this study, survival after challenge by R. salmoninarum was compared between two Chinook salmon stocks: a Lake Michigan stock from Wisconsin (WI) and the progenitor stock from the Green River. We found that the WI stock had significantly greater survival than the Green River stock. Next, the WI and Green River stocks were exposed to the marine pathogen Listonella anguillarum (formerly Vibrio anguillarum), one of the causative agents of vibriosis; survival after this challenge was significantly poorer for the WI stock than for the Green River stock. A close genetic relationship between the Green River and WI stocks was confirmed by analyzing 13 microsatellite loci. These results collectively suggest that disease susceptibility of Lake Michigan Chinook salmon has diverged from that of the source population, possibly in response to pathogen-driven selection. ?? Copyright by the American Fisheries Society 2008.

  2. Impact of neuromuscular electrical stimulation on functional capacity of patients with chronic kidney disease on hemodialysis.

    PubMed

    Roxo, Renata Spósito; Xavier, Vivian Bertoni; Miorin, Luiz Antônio; Magalhães, Andrea Olivares; Sens, Yvoty Alves Dos Santos; Alves, Vera Lúcia Dos Santos

    2016-01-01

    Literature shows that patients undergoing hemodialysis present poor physical conditioning and low tolerance to exercise. They may also suffer from respiratory dysfunctions. The purpose of this study was to evaluate the effects of neuromuscular electrical stimulation on pulmonary function and functional capacity of patients with chronic kidney disease on hemodialysis. Forty adult patients with chronic kidney disease on hemodialysis were prospectively studied and randomized into two groups (control n = 20 and treatment n = 20). The treatment group underwent bilateral femoral quadriceps muscles electrical stimulation for 30 minutes during hemodialysis, three times per week, for two months. The patients were evaluated by pulmonary function test, maximum respiratory pressures, maximum one-repetition test, and six-minute walk test (6MWT), before and after the treatment protocol. The treatment group presented increased maximum inspiratory (MIP) (p = 0.02) and expiratory pressures (MEP) (p < 0.0001), muscular strength in maximum one-repetition test (p < 0.001), and distance covered in the 6MWT (p = 0.03), and decreased systolic blood pressure (p < 0.001) and respiratory frequency (p < 0.001) when compared with the control group. Electrical neuromuscular stimulation had a positive impact on pulmonary function and functional capacity, leading to better physical performance in patients on hemodialysis. Pacientes submetidos à hemodiálise apresentam baixo condicionamento físico além de serem acometidos por disfunções respiratórias. Objetivamos avaliar os efeitos da estimulação elétrica neuromuscular na função pulmonar e capacidade funcional de pacientes com doença renal crônica em hemodiálise. 40 adultos com doença renal crônica em hemodiálise foram estudados prospectivamente e randomizados em dois grupos (controle n = 20 e tratamento n = 20). O grupo tratamento realizou protocolo com estimulação elétrica neuromuscular em quadríceps femoral por 30 minutos

  3. Kidney function and sudden cardiac death in the community: The Atherosclerosis Risk in Communities (ARIC) Study.

    PubMed

    Suzuki, Takeki; Agarwal, Sunil K; Deo, Rajat; Sotoodehnia, Nona; Grams, Morgan E; Selvin, Elizabeth; Calkins, Hugh; Rosamond, Wayne; Tomaselli, Gordon; Coresh, Josef; Matsushita, Kunihiro

    2016-10-01

    Individuals with chronic kidney disease, particularly those requiring dialysis, are at high risk of sudden cardiac death (SCD). However, comprehensive data for the full spectrum of kidney function and SCD risk in the community are sparse. Furthermore, newly developed equations for estimated glomerular filtration rate (eGFR) and novel filtration markers might add further insight to the role of kidney function in SCD. We investigated the associations of baseline eGFRs using serum creatinine, cystatin C, or both (eGFRcr, eGFRcys, and eGFRcr-cys); cystatin C itself; and β2-microglobulin (B2M) with SCD (205 cases through 2001) among 13,070 black and white ARIC participants at baseline during 1990-1992 using Cox regression models accounting for potential confounders. Low eGFR was independently associated with SCD risk: for example, hazard ratio for eGFR <45 versus ≥90mL/(min 1.73m(2)) was 3.71 (95% CI 1.74-7.90) with eGFRcr, 5.40 (2.97-9.83) with eGFRcr-cys, and 5.24 (3.01-9.11) with eGFRcys. When eGFRcr and eGFRcys were included together in a single model, the association was only significant for eGFRcys. When three eGFRs, cystatin C, and B2M were divided into quartiles, B2M demonstrated the strongest association with SCD (hazard ratio for fourth quartile vs first quartile 3.48 (2.03-5.96) vs ≤2.7 for the other kidney markers). Kidney function was independently and robustly associated with SCD in the community, particularly when cystatin C or B2M was used. These results suggest the potential value of kidney function as a risk factor for SCD and the advantage of novel filtration markers over eGFRcr in this context. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. 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.

  5. 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

  6. 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

  7. 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

  8. Assessment of the Renal Function in Potential Donors of Living Kidney Transplants: Expanded Study.

    PubMed

    Macías, L B; Poblet, M S; Pérez, N N; Jerez, R I; Gonzalez Roncero, F M; Blanco, G B; Valdivia, M A P; Benjumea, A S; Gentil Govantes, M A

    2015-11-01

    It is very important to determine as accurately as possible the renal function in potential living renal transplant donors, especially those with limited renal function (CrCl <90 mL/m/1.73 m(2)), age older than 50 years, and cardiovascular risk factors that might favor the development of long-term kidney diseases. The objective of this study was to compare the direct measurement of glomerular filtration rate (GFR) using EDTA-Cr51 and the estimations based on creatinine (eGFR): Cr clearance (CCr) with 24-hour urine and estimated using Cockroft-Gault (adjusted by using body surface area-Mosteller formula-SC), MDRD-4, MDRD-6, and CKD-EPI to determine the usefulness of different methods from EDTA-Cr51to evaluate the kidney function. The kidney function evaluation has been made to 105 potential kidney donors using the EDTA-Cr51 method. The GFR obtained through the EDTA-Cr51 is compared with the CCr values in 24-hour urine and eGFR based on creatinine (Cockcroft-Gault, MDRD4, MDRD6, and CKD-EPI). Using the Bland Altman graphic we have observed that the most dispersed results are obtained with the eGFR using CCr in 24-hour urine and CKD-EPI. By means of Pasing & Bablock, we realized that MDRD-4 and MDRD-6 show the highest approximation to the reference method proposed to be substituted, whereas CCr shows a high dispersion. eGFR using MDRD-4 and MDRD-6 formulas reveal the best adjustment to the measure by EDTA-Cr51. This might represent the best option if a direct eGFR measure is not available. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. 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.

  10. Is High-Density Lipoprotein Cholesterol Causally Related to Kidney Function? Evidence From Genetic Epidemiological Studies.

    PubMed

    Coassin, Stefan; Friedel, Salome; Köttgen, Anna; Lamina, Claudia; Kronenberg, Florian

    2016-11-01

    A recent observational study with almost 2 million men reported an association between low high-density lipoprotein (HDL) cholesterol and worse kidney function. The causality of this association would be strongly supported if genetic variants associated with HDL cholesterol were also associated with kidney function. We used 68 genetic variants (single-nucleotide polymorphisms [SNPs]) associated with HDL cholesterol in genome-wide association studies including >188 000 subjects and tested their association with estimated glomerular filtration rate (eGFR) using summary statistics from another genome-wide association studies meta-analysis of kidney function including ≤133 413 subjects. Fourteen of the 68 SNPs (21%) had a P value <0.05 compared with the 5% expected by chance (Binomial test P=5.8×10 - 6 ). After Bonferroni correction, 6 SNPs were still significantly associated with eGFR. The genetic variants with the strongest associations with HDL cholesterol concentrations were not the same as those with the strongest association with kidney function and vice versa. An evaluation of pleiotropy indicated that the effects of the HDL-associated SNPs on eGFR were not mediated by HDL cholesterol. In addition, we performed a Mendelian randomization analysis. This analysis revealed a positive but nonsignificant causal effect of HDL cholesterol-increasing variants on eGFR. In summary, our findings indicate that HDL cholesterol does not causally influence eGFR and propose pleiotropic effects on eGFR for some HDL cholesterol-associated SNPs. This may cause the observed association by mechanisms other than the mere HDL cholesterol concentration. © 2016 The Authors.

  11. 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

  12. Dynamic Analysis of Kidney Function and Its Correlation with Nutritional Indicators in a Large Sample of Hospitalized Elderly Patients.

    PubMed

    Qingping, Li; Ribao, Wei; Yang, Wang; Tingyu, Su; Xi, Yang; Mengjie, Huang; Hui, Miao; Xiangmei, Chen

    2017-04-23

    BACKGROUND The aim of this study was to analyze changes in kidney function and its correlation with nutritional metabolism indicators in hospitalized elderly patients in a large medical center over the past 7 years. MATERIAL AND METHODS The renal function of patients over 60 years old in the Chinese PLA General Hospital in 2008, 2011, and 2014 were comparatively analyzed. The hemoglobin, serum albumin, triglycerides, cholesterol, uric acid, and urea nitrogen data were collected and used as the nutritional metabolism indicators. In addition, the correlation between these indicators and the eGFR was analyzed. RESULTS The numbers of patients who received kidney function assessments in the 3 years were 15 752, 23 539, and 49 828; their mean ages were 69.97±6.99, 69.51±7.11, and 69.45±7.74 years. The median values of serum creatinine were 75.4, 76.5, and 77.5 μmol/L in the men and 59.6, 60.7, and 62.1 μmol/L in the women. The eGFR in both sexes demonstrated a gradual decreasing trend over the 3 years. According to the CKD staging method, analysis of the different percentages of eGFR intervals in the patients showed that the percentages of the 3 groups with an eGFR lower than 60 mL/min/1.73 m² exhibited a rising trend annually. Correlational analysis of the nutritional indicators showed that the correlations between Hb, ALB, TG, TC, Ur, and BUN with an eGFR lower than 60 mL/min/1.73 m² were 0.582, 0.780, 1.219, 1.364, 2.180, and 3.677, respectively. CONCLUSIONS Serum creatinine showed a gradually increasing trend over the 3 study years. The CKD-EPI equation calculation results showed that the eGFR in elderly people of both sexes gradually decreased. Reduction of hemoglobin and albumin was a risk factor for decreased kidney function, while increases in uric acid and blood lipids affected the progression of renal insufficiency.

  13. Environmental Exposure to Cadmium: Health Risk Assessment and its Associations with Hypertension and Impaired Kidney Function

    NASA Astrophysics Data System (ADS)

    Wu, Haiyun; Liao, Qilin; Chillrud, Steven N.; Yang, Qiang; Huang, Lei; Bi, Jun; Yan, Beizhan

    2016-07-01

    Cadmium (Cd) is a toxic metal. This study was aimed to estimate the potential health risks in a Cd-polluted district in China, and examine the relationship between urinary cadmium(UCd) and hypertension and impaired kidney function at low exposure levels (UCd: GM 1.3 μg/g creatinine). Blood pressure measurement, questionnaires, and collection of urinary samples were conducted from 217 residents. Environmental samples, food, and cigarette samples were collected and detected to estimate the risks posed by Cd and the contribution of inhalation, ingestion, and dermal contact pathways to these risks. A logistic regression model was used in examining associations between exposure and hypertension and impaired kidney function. Results show that this population is at high risk. For non-smokers, incremental lifetime cancer risk (ILCR) and hazard quotient (HQ) are 1.74E-04 and 2.96, and for smokers, they are 1.07E-03 and 52.5, respectively. Among all exposure pathways, smoking and foods cause the major increases in ILCR and HQ. UCd is significantly associated with hypertension (odds ratio (OR) = 1.468 95% confidence interval (CI): 1.104, 1.953; P = 0.008) and impaired kidney function (OR = 1.902, 95% CI: 1.054, 3.432; P = 0.033). The results demonstrate that Cd can potentially lead to adverse health effects.

  14. 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.

  15. 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.

  16. Association Between Delayed Graft Function and Graft Loss in Donation After Cardiac Death Kidney Transplants-A Paired Kidney Registry Analysis.

    PubMed

    Lim, Wai H; McDonald, Stephen P; Russ, Graeme R; Chapman, Jeremy R; Ma, Maggie Km; Pleass, Henry; Jaques, Bryon; Wong, Germaine

    2017-06-01

    Delayed graft function (DGF) is an established complication after donation after cardiac death (DCD) kidney transplants, but the impact of DGF on graft outcomes is uncertain. To minimize donor variability and bias, a paired donor kidney analysis was undertaken where 1 kidney developed DGF and the other did not develop DGF using data from the Australia and New Zealand Dialysis and Transplant Registry. Using paired DCD kidney data from the Australia and New Zealand Dialysis and Transplant Registry, we examined the association between DGF, graft and patient outcomes between 1994 and 2012 using adjusted Cox regression models. Of the 74 pairs of DCD kidneys followed for a median of 1.9 years (408 person-years), a greater proportion of recipients with DGF had experienced overall graft loss and death-censored graft loss at 3 years compared with those without DGF (14% vs 4%, P = 0.04 and 11% vs 0%, P < 0.01, respectively). Compared with recipients without DGF, the adjusted hazard ratio for overall graft loss at 3 years for recipients with DGF was 4.31 (95% confidence interval [95% CI], 1.13-16.44). The adjusted hazard ratio for acute rejection and all-cause mortality at 3 years in recipients who have experienced DGF were 0.98 (95% CI, 0.96-1.01) and 1.70 (95% CI, 0.36-7.93), respectively, compared with recipients without DGF. Recipients of DCD kidneys with DGF experienced a higher incidence of overall and death-censored graft loss compared with those without DGF. Strategies aim to reduce the risk of DGF could potentially improve graft survival in DCD kidney transplants.

  17. Icariin combined with human umbilical cord mesenchymal stem cells significantly improve the impaired kidney function in chronic renal failure.

    PubMed

    Li, Wen; Wang, Li; Chu, Xiaoqian; Cui, Huantian; Bian, Yuhong

    2017-04-01

    At present, the main therapy for chronic renal failure (CRF) is dialysis and renal transplantation, but neither obtains satisfactory results. Human umbilical cord mesenchymal stem cells (huMSCs) are isolated from the fetal umbilical cord which has a high self-renewal and multi-directional differentiation potential. Icariin (ICA), a kidney-tonifying Chinese Medicine can enhance the multipotency of huMSCs. Therefore, this work seeks to employ the use of ICA-treated huMSCs for the treatment of chronic renal failure. Blood urea nitrogen and creatinine (Cr) analyses showed amelioration of functional parameters in ICA-treated huMSCs for the treatment of CRF rats at 3, 7, and 14 days after transplantation. ICA-treated huMSCs can obviously increase the number of cells in injured renal tissues at 3, 7, and 14 days after transplantation by optical molecular imaging system. Hematoxylin-eosin staining demonstrated that ICA-treated huMSCs reduced the levels of fibrosis in CRF rats at 14 days after transplantation. Superoxide dismutase and Malondialdehyde analyses showed that ICA-treated huMSCs reduced the oxidative damage in CRF rats. Moreover, transplantation with ICA-treated huMSCs decreased inflammatory responses, promoted the expression of growth factors, and protected injured renal tissues. Taken together, our findings suggest that ICA-treated huMSCs could improve the kidney function in CRF rats.

  18. Risk Factors for Rapid Kidney Function Decline Among African Americans: The Jackson Heart Study (JHS).

    PubMed

    Young, Bessie A; Katz, Ronit; Boulware, L Ebony; Kestenbaum, Bryan; de Boer, Ian H; Wang, Wei; Fülöp, Tibor; Bansal, Nisha; Robinson-Cohen, Cassianne; Griswold, Michael; Powe, Neil R; Himmelfarb, Jonathan; Correa, Adolfo

    2016-08-01

    Racial differences in rapid kidney function decline exist, but less is known regarding factors associated with rapid decline among African Americans. Greater understanding of potentially modifiable risk factors for early kidney function loss may help reduce the burden of kidney failure in this high-risk population. Prospective cohort study. 3,653 African American participants enrolled in the Jackson Heart Study (JHS) with kidney function data from 2 of 3 examinations (2000-2004 and 2009-2013). Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine using the CKD-EPI creatinine equation. Demographics, socioeconomic status, lifestyle, and clinical risk factors for kidney failure. Rapid decline was defined as a ≥30% decline in eGFR during follow-up. We quantified the association of risk factors with rapid decline in multivariable models. Clinical (systolic blood pressure and albuminuria [albumin-creatinine ratio]) and modifiable risk factors. Mean age was 54±12 (SD) years, 37% were men, average body mass index was 31.8±7.1kg/m(2), 19% had diabetes mellitus (DM), and mean eGFR was 96.0±20mL/min/1.73m(2) with an annual rate of decline of 1.27mL/min/1.73m(2). Those with rapid decline (11.5%) were older, were more likely to be of low/middle income, and had higher systolic blood pressures and greater DM than those with nonrapid decline. Factors associated with ≥30% decline were older age (adjusted OR per 10 years older, 1.51; 95% CI, 1.34-1.71), cardiovascular disease (adjusted OR, 1.53; 95% CI, 1.12-2.10), higher systolic blood pressure (adjusted OR per 17mmHg greater, 1.22; 95% CI, 1.06-1.41), DM (adjusted OR, 2.63; 95% CI, 2.02-3.41), smoking (adjusted OR, 1.60; 95% CI, 1.10-2.31), and albumin-creatinine ratio > 30mg/g (adjusted OR, 1.55; 95% CI, 1.08-1.21). Conversely, results did not support associations of waist circumference, C-reactive protein level, and physical activity with rapid decline. No midstudy creatinine measurement at

  19. Risk Factors for Rapid Kidney Function Decline Among African Americans: The Jackson Heart Study (JHS)

    PubMed Central

    Young, Bessie A.; Katz, Ronit; Boulware, Ebony; Kestenbaum, Bryan; de Boer, Ian H.; Wang, Wei; Fülöp, Tibor; Bansal, Nisha; Robinson-Cohen, Cassianne; Griswold, Michael; Powe, Neil N.; Himmelfarb, Jonathan; Correa, Adolfo

    2016-01-01

    Background Racial differences in rapid kidney function decline exist, but less is known regarding factors associated with rapid decline among African Americans. A greater understanding of potentially modifiable risk factors for early kidney function loss may help reduce the burden of kidney failure in this high-risk population. Study Design Prospective cohort study. Setting & Participants 3653 African-American participants enrolled in the Jackson Heart Study (JHS) with kidney function data from two of three examinations (2000-2004 and 2009-2013). Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine using the CKD-EPI creatinine equation. Predictors Demographics, socioeconomic status, lifestyle, clinical risk factors for kidney failure. Outcomes Rapid decline was defined as a ≥ 30% decline in eGFR during follow-up. We quantified the association of risk factors with rapid decline in multivariable models. Measurements Clinical (systolic blood pressure, albuminuria [albumin-creatinine ratio]) and modifiable risk factors. Results Mean age was 54 ± 12 (SD) years, 37% were male, average body mass index was 31.8 ± 7.1 kg/m2, 19% had diabetes mellitus (DM) and mean eGFR was 96.0 ±20 ml/min/1.73m2 with an annual rate of decline of 1.27 ml/min/1.73m2. Those with rapid decline (11.5%) were older, more likely to be of low/middle income, had higher systolic blood pressure, and greater DM than those with non-rapid decline. Factors associated with ≥30% decline were older age (adjusted OR per 10 years older, 1.51; 95% CI, 1.34-1.71); cardiovascular disease (adjusted OR, 1.53; 95% CI, 1.12-2.10), higher systolic blood pressure (adjusted OR per 17 mm Hg greater, 1.22; 95% CI, 1.06-1.41); DM (adjusted OR, 2.63; 95% CI, 2.02-3.41), smoking (adjusted OR, 1.60; 95% CI, 1.10-2.31), and albumin-creatinine ratio > 30 mg/g (adjusted OR, 1.55; 95% CI, 1.08-1.21). Conversely, results did not support associations of waist circumference, C-reactive protein, and

  20. Impact of Exercise Counseling on Physical Function in Chronic Kidney Disease: An Observational Study.

    PubMed

    Bohm, Clara J; Storsley, Leroy J; Hiebert, Brett M; Nelko, Serena; Tangri, Navdeep; Cheskin, Lawrence J; McAdams-DeMarco, Mara A; Rigatto, Claudio

    2018-01-01

    Individuals with chronic kidney disease (CKD) have low levels of physical activity and physical function. Although guidelines endorse exercise counseling for individuals with CKD, it is not yet part of routine care. We investigated the effect of attending a real-life exercise counseling clinic (ECC) on physical function in individuals with CKD. Retrospective analysis of prospectively collected observational data with quasi-experimental design. Patients with all stages of CKD registered in a large provincial renal program were eligible. The exposed cohort who attended the ECC between January 1, 2011, and March 15, 2014, included 214 individuals. The control cohort included 292 individuals enrolled in an observational study investigating longitudinal change in frailty during the same time period. Attendance at an ECC. Change in physical function as measured by Short Physical Performance Battery (SPPB) score, physical activity level (Human Activity Profile [HAP]/Physical Activity Scale for the Elderly [PASE]), and health-related quality of life (HRQOL; EQ5D/VAS) over 1 year. Eighty-seven individuals in the ECC cohort and 125 participants in the control cohort completed 1-year follow-up. Baseline median SPPB score was 10 (interquartile range [IQR]: 9-12) and 9 (IQR: 7-11) in the ECC and control cohorts, respectively ( P < .01). At 1 year, SPPB scores were 10 (IQR: 8-12) and 9 (IQR: 6-11) in the ECC and control cohorts, respectively ( P = .04). Mean change in SPPB over 1 year was not significantly different between groups: -0.33 (95% confidence interval [CI]: -0.81 to 0.15) in ECC and -0.22 (95% CI: -0.61 to 0.17) in control ( P = .72). There was no significant difference in the proportion of individuals in each cohort with an increase/decrease in SPPB score over time. There was no significant change in physical activity or HRQOL over time between groups. Quasi-experimental design, low rate of follow-up attendance. In this pragmatic study, exercise counseling had no

  1. Impact of Exercise Counseling on Physical Function in Chronic Kidney Disease: An Observational Study

    PubMed Central

    Storsley, Leroy J.; Hiebert, Brett M.; Nelko, Serena; Cheskin, Lawrence J.; McAdams-DeMarco, Mara A.; Rigatto, Claudio

    2018-01-01

    Background: Individuals with chronic kidney disease (CKD) have low levels of physical activity and physical function. Although guidelines endorse exercise counseling for individuals with CKD, it is not yet part of routine care. Objective: We investigated the effect of attending a real-life exercise counseling clinic (ECC) on physical function in individuals with CKD. Design: Retrospective analysis of prospectively collected observational data with quasi-experimental design. Setting and Participants: Patients with all stages of CKD registered in a large provincial renal program were eligible. The exposed cohort who attended the ECC between January 1, 2011, and March 15, 2014, included 214 individuals. The control cohort included 292 individuals enrolled in an observational study investigating longitudinal change in frailty during the same time period. Predictor/Factor: Attendance at an ECC. Outcomes and Measurements: Change in physical function as measured by Short Physical Performance Battery (SPPB) score, physical activity level (Human Activity Profile [HAP]/Physical Activity Scale for the Elderly [PASE]), and health-related quality of life (HRQOL; EQ5D/VAS) over 1 year. Results: Eighty-seven individuals in the ECC cohort and 125 participants in the control cohort completed 1-year follow-up. Baseline median SPPB score was 10 (interquartile range [IQR]: 9-12) and 9 (IQR: 7-11) in the ECC and control cohorts, respectively (P < .01). At 1 year, SPPB scores were 10 (IQR: 8-12) and 9 (IQR: 6-11) in the ECC and control cohorts, respectively (P = .04). Mean change in SPPB over 1 year was not significantly different between groups: −0.33 (95% confidence interval [CI]: −0.81 to 0.15) in ECC and −0.22 (95% CI: −0.61 to 0.17) in control (P = .72). There was no significant difference in the proportion of individuals in each cohort with an increase/decrease in SPPB score over time. There was no significant change in physical activity or HRQOL over time between groups

  2. Renal Allograft Function Is a Risk Factor of Left Ventricular Remodeling After Kidney Transplantation.

    PubMed

    Koo, T Y; Ahn, C; Yang, J

    2017-06-01

    Cardiovascular disease is the leading cause of morbidity and mortality in kidney transplantation (KT) patients. The prevalence of left ventricular hypertrophy increases with the progression of renal insufficiency. We investigated the association between the progression of renal insufficiency and left ventricular hypertrophy after KT. We reviewed KT patients at Seoul National University Hospital from January 1973 to December 2009. The creatinine elevation ratio (CER, the percentage change in the creatinine level from 1 month to 5 years after transplant) was calculated as follows: (creatinine level at 5 years minus creatinine level at 1 month)/creatinine level at 1 month × 100. The study population was classified into a high-CER group (CER ≥25%) and low-CER group (CER <25%). Mean left ventricular mass index (LVMI) values were 135.7 and 134.7 g/m 2 before KT and 101.7 and 123.7 g/m 2 at 5 years after KT in the low-CER and high-CER groups, respectively. The LVMI before or 1 year after KT was not different between the 2 groups, but the LVMI at 5 years post-transplant was higher in the high-CER group than in the low-CER group. The LVMI increased after its initial decrease in the high-CER group, whereas its reduction was maintained in the low-CER group during the 5 years after KT (P = .009, repeated-measures analysis of variance). These data suggest that deterioration of renal allograft function is associated with left ventricular remodeling after KT. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. 1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function

    PubMed Central

    Gorski, Mathias; van der Most, Peter J.; Teumer, Alexander; Chu, Audrey Y.; Li, Man; Mijatovic, Vladan; Nolte, Ilja M.; Cocca, Massimiliano; Taliun, Daniel; Gomez, Felicia; Li, Yong; Tayo, Bamidele; Tin, Adrienne; Feitosa, Mary F.; Aspelund, Thor; Attia, John; Biffar, Reiner; Bochud, Murielle; Boerwinkle, Eric; Borecki, Ingrid; Bottinger, Erwin P.; Chen, Ming-Huei; Chouraki, Vincent; Ciullo, Marina; Coresh, Josef; Cornelis, Marilyn C.; Curhan, Gary C.; d’Adamo, Adamo Pio; Dehghan, Abbas; Dengler, Laura; Ding, Jingzhong; Eiriksdottir, Gudny; Endlich, Karlhans; Enroth, Stefan; Esko, Tõnu; Franco, Oscar H.; Gasparini, Paolo; Gieger, Christian; Girotto, Giorgia; Gottesman, Omri; Gudnason, Vilmundur; Gyllensten, Ulf; Hancock, Stephen J.; Harris, Tamara B.; Helmer, Catherine; Höllerer, Simon; Hofer, Edith; Hofman, Albert; Holliday, Elizabeth G.; Homuth, Georg; Hu, Frank B.; Huth, Cornelia; Hutri-Kähönen, Nina; Hwang, Shih-Jen; Imboden, Medea; Johansson, Åsa; Kähönen, Mika; König, Wolfgang; Kramer, Holly; Krämer, Bernhard K.; Kumar, Ashish; Kutalik, Zoltan; Lambert, Jean-Charles; Launer, Lenore J.; Lehtimäki, Terho; de Borst, Martin; Navis, Gerjan; Swertz, Morris; Liu, Yongmei; Lohman, Kurt; Loos, Ruth J. F.; Lu, Yingchang; Lyytikäinen, Leo-Pekka; McEvoy, Mark A.; Meisinger, Christa; Meitinger, Thomas; Metspalu, Andres; Metzger, Marie; Mihailov, Evelin; Mitchell, Paul; Nauck, Matthias; Oldehinkel, Albertine J.; Olden, Matthias; WJH Penninx, Brenda; Pistis, Giorgio; Pramstaller, Peter P.; Probst-Hensch, Nicole; Raitakari, Olli T.; Rettig, Rainer; Ridker, Paul M.; Rivadeneira, Fernando; Robino, Antonietta; Rosas, Sylvia E.; Ruderfer, Douglas; Ruggiero, Daniela; Saba, Yasaman; Sala, Cinzia; Schmidt, Helena; Schmidt, Reinhold; Scott, Rodney J.; Sedaghat, Sanaz; Smith, Albert V.; Sorice, Rossella; Stengel, Benedicte; Stracke, Sylvia; Strauch, Konstantin; Toniolo, Daniela; Uitterlinden, Andre G.; Ulivi, Sheila; Viikari, Jorma S.; Völker, Uwe; Vollenweider, Peter; Völzke, Henry; Vuckovic, Dragana; Waldenberger, Melanie; Jin Wang, Jie; Yang, Qiong; Chasman, Daniel I.; Tromp, Gerard; Snieder, Harold; Heid, Iris M.; Fox, Caroline S.; Köttgen, Anna; Pattaro, Cristian; Böger, Carsten A.; Fuchsberger, Christian

    2017-01-01

    HapMap imputed genome-wide association studies (GWAS) have revealed >50 loci at which common variants with minor allele frequency >5% are associated with kidney function. GWAS using more complete reference sets for imputation, such as those from The 1000 Genomes project, promise to identify novel loci that have been missed by previous efforts. To investigate the value of such a more complete variant catalog, we conducted a GWAS meta-analysis of kidney function based on the estimated glomerular filtration rate (eGFR) in 110,517 European ancestry participants using 1000 Genomes imputed data. We identified 10 novel loci with p-value < 5 × 10−8 previously missed by HapMap-based GWAS. Six of these loci (HOXD8, ARL15, PIK3R1, EYA4, ASTN2, and EPB41L3) are tagged by common SNPs unique to the 1000 Genomes reference panel. Using pathway analysis, we identified 39 significant (FDR < 0.05) genes and 127 significantly (FDR < 0.05) enriched gene sets, which were missed by our previous analyses. Among those, the 10 identified novel genes are part of pathways of kidney development, carbohydrate metabolism, cardiac septum development and glucose metabolism. These results highlight the utility of re-imputing from denser reference panels, until whole-genome sequencing becomes feasible in large samples. PMID:28452372

  4. 1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function.

    PubMed

    Gorski, Mathias; van der Most, Peter J; Teumer, Alexander; Chu, Audrey Y; Li, Man; Mijatovic, Vladan; Nolte, Ilja M; Cocca, Massimiliano; Taliun, Daniel; Gomez, Felicia; Li, Yong; Tayo, Bamidele; Tin, Adrienne; Feitosa, Mary F; Aspelund, Thor; Attia, John; Biffar, Reiner; Bochud, Murielle; Boerwinkle, Eric; Borecki, Ingrid; Bottinger, Erwin P; Chen, Ming-Huei; Chouraki, Vincent; Ciullo, Marina; Coresh, Josef; Cornelis, Marilyn C; Curhan, Gary C; d'Adamo, Adamo Pio; Dehghan, Abbas; Dengler, Laura; Ding, Jingzhong; Eiriksdottir, Gudny; Endlich, Karlhans; Enroth, Stefan; Esko, Tõnu; Franco, Oscar H; Gasparini, Paolo; Gieger, Christian; Girotto, Giorgia; Gottesman, Omri; Gudnason, Vilmundur; Gyllensten, Ulf; Hancock, Stephen J; Harris, Tamara B; Helmer, Catherine; Höllerer, Simon; Hofer, Edith; Hofman, Albert; Holliday, Elizabeth G; Homuth, Georg; Hu, Frank B; Huth, Cornelia; Hutri-Kähönen, Nina; Hwang, Shih-Jen; Imboden, Medea; Johansson, Åsa; Kähönen, Mika; König, Wolfgang; Kramer, Holly; Krämer, Bernhard K; Kumar, Ashish; Kutalik, Zoltan; Lambert, Jean-Charles; Launer, Lenore J; Lehtimäki, Terho; de Borst, Martin; Navis, Gerjan; Swertz, Morris; Liu, Yongmei; Lohman, Kurt; Loos, Ruth J F; Lu, Yingchang; Lyytikäinen, Leo-Pekka; McEvoy, Mark A; Meisinger, Christa; Meitinger, Thomas; Metspalu, Andres; Metzger, Marie; Mihailov, Evelin; Mitchell, Paul; Nauck, Matthias; Oldehinkel, Albertine J; Olden, Matthias; Wjh Penninx, Brenda; Pistis, Giorgio; Pramstaller, Peter P; Probst-Hensch, Nicole; Raitakari, Olli T; Rettig, Rainer; Ridker, Paul M; Rivadeneira, Fernando; Robino, Antonietta; Rosas, Sylvia E; Ruderfer, Douglas; Ruggiero, Daniela; Saba, Yasaman; Sala, Cinzia; Schmidt, Helena; Schmidt, Reinhold; Scott, Rodney J; Sedaghat, Sanaz; Smith, Albert V; Sorice, Rossella; Stengel, Benedicte; Stracke, Sylvia; Strauch, Konstantin; Toniolo, Daniela; Uitterlinden, Andre G; Ulivi, Sheila; Viikari, Jorma S; Völker, Uwe; Vollenweider, Peter; Völzke, Henry; Vuckovic, Dragana; Waldenberger, Melanie; Jin Wang, Jie; Yang, Qiong; Chasman, Daniel I; Tromp, Gerard; Snieder, Harold; Heid, Iris M; Fox, Caroline S; Köttgen, Anna; Pattaro, Cristian; Böger, Carsten A; Fuchsberger, Christian

    2017-04-28

    HapMap imputed genome-wide association studies (GWAS) have revealed >50 loci at which common variants with minor allele frequency >5% are associated with kidney function. GWAS using more complete reference sets for imputation, such as those from The 1000 Genomes project, promise to identify novel loci that have been missed by previous efforts. To investigate the value of such a more complete variant catalog, we conducted a GWAS meta-analysis of kidney function based on the estimated glomerular filtration rate (eGFR) in 110,517 European ancestry participants using 1000 Genomes imputed data. We identified 10 novel loci with p-value < 5 × 10 -8 previously missed by HapMap-based GWAS. Six of these loci (HOXD8, ARL15, PIK3R1, EYA4, ASTN2, and EPB41L3) are tagged by common SNPs unique to the 1000 Genomes reference panel. Using pathway analysis, we identified 39 significant (FDR < 0.05) genes and 127 significantly (FDR < 0.05) enriched gene sets, which were missed by our previous analyses. Among those, the 10 identified novel genes are part of pathways of kidney development, carbohydrate metabolism, cardiac septum development and glucose metabolism. These results highlight the utility of re-imputing from denser reference panels, until whole-genome sequencing becomes feasible in large samples.

  5. Impaired renal function is associated with worse self-reported outcomes after kidney transplantation.

    PubMed

    Neri, Luca; Dukes, Jonathan; Brennan, Daniel C; Salvalaggio, Paulo R; Seelam, Susmitha; Desiraju, Srividya; Schnitzler, Mark

    2011-12-01

    We sought to determine the association between health-related quality of life (HRQOL) and graft function in renal transplant recipients. We enrolled 577 kidney transplant recipients aged 18-74 years (response rate 87%). Recipients with multiple or multi-organ transplantation, creatine kinase >200 U/L, acute renal failure or cellular rejection (n = 64), and without creatinine assessments in 3 months pre-enrollment (n = 127) were excluded. The questionnaire included Euro QOL 5 Dimensions (EQ-5D), Health Utility Index III (HUI-III), Kidney Disease Quality of Life-36 (KDQOL36) which include a generic section (RAND SF-12). Data on medical conditions, therapy regimens, and biochemistry results were extracted from clinical charts. We used general linear models adjusted for demographic, socioeconomic, and clinical characteristics to assess the association between HRQOL and severity of chronic kidney disease (CKD). Patients with more advanced CKD were more likely to be African-American, covered by public insurance, more likely to have shorter time after transplantation, higher phosphorus and lower hemoglobin, serum albumin, and calcium levels. All HRQOL scales were inversely associated with CKD severity. All associations were robust to adjustment for possible confounders. Several health-related quality of life dimensions may be affected by poor renal function after transplantation.

  6. The influence of contrast media on kidney function in patients with stable coronary artery disease.

    PubMed

    Reuter, Simon Bertram; Harutyunyan, Marina; Mygind, Naja Dam; Jørgensen, Erik; Kastrup, Jens

    2014-08-01

    To investigate the incidence of contrast media-induced nephropathy (CIN) in patients with stable coronary artery disease (CAD) referred for elective coronary intervention following hydration routines. The reversibility of CIN was followed in a 6 month-period. A total of 447 patients referred for elective coronary intervention due to suspected CAD were included. Blood samples were collected before and 24 h after intervention and medical records were obtained. Patients had no drinking fluid restrictions and were routinely treated with a 1000 ml saline infusion. All patients were invited to a 6-month examination and collection of blood samples. A total of 19 patients (4.3%) developed CIN. CIN patients had a pre-investigation higher estimated glomerular filtration rate (eGRF), lower level of kidney failure and lower creatinine level than non-CIN patients. Kidney function was not normalized in CIN patients 6 months after the intervention. Two patients still met the definition of CIN. With no restriction in fluid intake and supplementary infusion of saline, only a few patients with stable CAD developed early indications of CIN during elective coronary interventions. Kidney function and the amount of contrast media used was not a predictor of CIN development. The induced CIN was not completely normalized in a 6-month follow-up period.

  7. Loss of executive function after dialysis initiation in adults with chronic kidney disease.

    PubMed

    Kurella Tamura, Manjula; Vittinghoff, Eric; Hsu, Chi-Yuan; Tam, Karman; Seliger, Stephen L; Sozio, Stephen; Fischer, Michael; Chen, Jing; Lustigova, Eva; Strauss, Louise; Deo, Rajat; Go, Alan S; Yaffe, Kristine

    2017-04-01

    The association of dialysis initiation with changes in cognitive function among patients with advanced chronic kidney disease is poorly described. To better define this, we enrolled participants with advanced chronic kidney disease from the Chronic Renal Insufficiency Cohort in a prospective study of cognitive function. Eligible participants had a glomerular filtration rate of 20 ml/min/1.73m 2 or less, or dialysis initiation within the past two years. We evaluated cognitive function by a validated telephone battery at regular intervals over two years and analyzed test scores as z scores. Of 212 participants, 123 did not transition to dialysis during follow-up, 37 transitioned to dialysis after baseline, and 52 transitioned to dialysis prior to baseline. In adjusted analyses, the transition to dialysis was associated with a significant loss of executive function, but no significant changes in global cognition or memory. The estimated net difference in cognitive z scores at two years for participants who transitioned to dialysis during follow-up compared to participants who did not transition to dialysis was -0.01 (95% confidence interval -0.13, 0.11) for global cognition, -0.24 (-0.51, 0.03) for memory, and -0.33 (-0.60, -0.07) for executive function. Thus, among adults with advanced chronic kidney disease, dialysis initiation was associated with loss of executive function with no change in other aspects of cognition. Larger studies are needed to evaluate cognition during dialysis initiation. Published by Elsevier Inc.

  8. Decline of kidney function during the pre-dialysis period in chronic kidney disease patients: a systematic review and meta-analysis.

    PubMed

    Janmaat, Cynthia J; van Diepen, Merel; van Hagen, Cheyenne Ce; Rotmans, Joris I; Dekker, Friedo W; Dekkers, Olaf M

    2018-01-01

    Substantial heterogeneity exists in reported kidney function decline in pre-dialysis chronic kidney disease (CKD). By design, kidney function decline can be studied in CKD 3-5 cohorts or dialysis-based studies. In the latter, patients are selected based on the fact that they initiated dialysis, possibly leading to an overestimation of the true underlying kidney function decline in the pre-dialysis period. We performed a systematic review and meta-analysis to compare the kidney function decline during pre-dialysis in CKD stage 3-5 patients, in these two different study types. We searched PubMed, EMBASE, Web of Science and Cochrane to identify eligible studies reporting an estimated glomerular filtration rate (eGFR) decline (mL/min/1.73 m 2 ) in adult pre-dialysis CKD patients. Random-effects meta-analysis was performed to obtain weighted mean annual eGFR decline. We included 60 studies (43 CKD 3-5 cohorts and 17 dialysis-based studies). The meta-analysis yielded a weighted annual mean (95% CI) eGFR decline during pre-dialysis of 2.4 (95% CI: 2.2, 2.6) mL/min/1.73 m 2 in CKD 3-5 cohorts compared to 8.5 (95% CI: 6.8, 10.1) in dialysis-based studies (difference 6.0 [95% CI: 4.8, 7.2]). To conclude, dialysis-based studies report faster mean annual eGFR decline during pre-dialysis than CKD 3-5 cohorts. Thus, eGFR decline data from CKD 3-5 cohorts should be used to guide clinical decision making in CKD patients and for power calculations in randomized controlled trials with CKD progression during pre-dialysis as the outcome.

  9. Recurrent clot anuria following laparoscopic pyeloplasty in a solitary functioning kidney: managing with double guide wire technique

    PubMed Central

    Kumar, Santosh; Singh, Shivanshu; Parmar, Kalpesh Mahesh; Garg, Nitin

    2014-01-01

    Clot anuria in a solitary functioning kidney is an emergency situation. Haematuria with clot anuria in an early postoperative period represents a challenge, as treatment options are limited. Manipulation of the anastomotic site may lead to anastomotic disruption and urinoma while use of thrombolytic therapy poses the danger of increasing haematuria. We report a case of anuria due to clot retention in the upper tract following laparoscopic dismembered pyeloplasty in a solitary functioning kidney, managed successfully with double guide wire technique. PMID:25540210

  10. 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

  11. 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.

  12. Decreased Nephrin and GLEPP-1, But Increased VEGF, Flt-1, and Nitrotyrosine, Expressions in Kidney Tissue Sections From Women With Preeclampsia

    PubMed Central

    Zhao, Shuang; Gu, Xin; Groome, Lynn J.; Wang, Yuping

    2011-01-01

    Renal injury is a common pathophysiological feature in women with preeclampsia as evidenced by increased protein leakage (proteinuria) and glomerular injury (glomerular endotheliosis). Recently, podocyturia was found in preeclampsia, suggesting podocyte shedding occurs in this pregnancy disorder. However, podocyte function in preeclampsia is poorly understood. In this study, the authors have examined podocyte-specific protein expressions for nephrin, glomerular epithelial protein 1 (GLEPP-1), and ezrin in kidney biopsy tissue sections from women with preeclampsia. Expressions for vascular endothelial growth factor (VEGF) and its receptor Flt-1 and oxidative stress marker nitrotyrosine and antioxidant CuZn-superoxide dismutase (CuZn-SOD) were also examined. Kidney tissue sections from nonhypertensive and chronic hypertensive participants were stained as controls. The findings were (1) nephrin and GLEPP-1 were mainly expressed in glomerular podocytes; (2) ezrin was expressed in both glomerular podocytes and tubular epithelial cells; (3) compared to tissue sections from nonhypertensive and chronic hypertensive participants, nephrin and GLEPP-1 expressions were much reduced in tissue sections from preeclampsia and ezrin expression was reduced in podocytes; (4) enhanced VEGF, Flt-1, and nitrotyrosine, but reduced CuZn-SOD, expressions were observed in both glomerular podocytes and endothelial cells in tissue sections from preeclampsia; and (5) the expression pattern for nephrin, GLEPP-1, ezrin, VEGF, Flt-1, and CuZn-SOD were similar between tissue sections from nonhypertensive and chronic hypertensive participants. Although the authors could not conclude from this biopsy study whether the podocyte injury is the cause or effect of the preeclampsia phenotype, the data provide compelling evidence that podocyte injury accompanied by altered angiogenesis process and increased oxidative stress occurs in kidney of patients with preeclampsia. PMID:19528353

  13. 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

  14. A major X-linked locus affects kidney function in mice

    PubMed Central

    Leduc, Magalie S.; Savage, Holly S.; Stearns, Timothy M.; Cario, Clinton L.; Walsh, Kenneth A.; Paigen, Beverly; Berndt, Annerose

    2012-01-01

    Chronic kidney disease is a common disease with increasing prevalence in the western population. One common reason for chronic kidney failure is diabetic nephropathy. Diabetic nephropathy and hyperglycemia are characteristics of the mouse inbred strain KK/HlJ, which is predominantly used as a model for metabolic syndrome due to its inherited glucose intolerance and insulin resistance. We used KK/HlJ, an albuminuria-sensitive strain, and C57BL/6J, an albuminuria-resistant strain, to perform a quantitative trait locus (QTL) cross to identify the genetic basis for chronic kidney failure. Albumin-creatinine-ratio (ACR) was measured in 130 F2 male offspring. One significant QTL was identified on chromosome (Chr) X and four suggestive QTLs were found on Chrs 6, 7, 12, and 13. Narrowing of the QTL region was focused on the X-linked QTL and performed by incorporating genotype and expression analyses for genes located in the region. From the 485 genes identified in the X-linked QTL region, a few candidate genes were identified using a combination of bioinformatic evidence based on genomic comparison of the parental strains and known function in urine homeostasis. Finally, this study demonstrates the significance of the X chromosome in the genetic determination of albuminuria. PMID:23011808

  15. Cognitive Function and Kidney Disease: Baseline Data From the Systolic Blood Pressure Intervention Trial (SPRINT).

    PubMed

    Weiner, Daniel E; Gaussoin, Sarah A; Nord, John; Auchus, Alexander P; Chelune, Gordon J; Chonchol, Michel; Coker, Laura; Haley, William E; Killeen, Anthony A; Kimmel, Paul L; Lerner, Alan J; Oparil, Suzanne; Saklayen, Mohammad G; Slinin, Yelena M; Wright, Clinton B; Williamson, Jeff D; Kurella Tamura, Manjula

    2017-09-01

    Chronic kidney disease is common and is associated with cardiovascular disease, cerebrovascular disease, and cognitive function, although the nature of this relationship remains uncertain. Cross-sectional cohort using baseline data from the Systolic Blood Pressure Intervention Trial (SPRINT). Participants in SPRINT, a randomized clinical trial of blood pressure targets in older community-dwelling adults with cardiovascular disease, chronic kidney disease, or high cardiovascular disease risk and without diabetes or known stroke, who underwent detailed neurocognitive testing in the cognition substudy, SPRINT-Memory and Cognition in Decreased Hypertension (SPRINT-MIND). Urine albumin-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). Cognitive function, a priori defined as 5 cognitive domains based on 11 cognitive tests using z scores, and abnormal white matter volume quantified by brain magnetic resonance imaging. Of 9,361 SPRINT participants, 2,800 participated in SPRINT-MIND and 2,707 had complete data; 637 had brain imaging. Mean age was 68 years, 37% were women, 30% were black, and 20% had known cardiovascular disease. Mean eGFR was 70.8±20.9mL/min/1.73m 2 and median urine ACR was 9.7 (IQR, 5.7-22.5) mg/g. In adjusted analyses, higher ACR was associated with worse global cognitive function, executive function, memory, and attention, such that each doubling of urine ACR had the same association with cognitive performance as being 7, 10, 6, and 14 months older, respectively. Lower eGFR was independently associated with worse global cognitive function and memory. In adjusted models, higher ACR, but not eGFR, was associated with larger abnormal white matter volume. Cross-sectional only, no patients with diabetes were included. In older adults, higher urine ACR and lower eGFR have independent associations with global cognitive performance with different affected domains. Albuminuria concurrently identifies a higher burden of abnormal brain

  16. 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.

  17. Treatment with patiromer decreases aldosterone in patients with chronic kidney disease and hyperkalemia on renin-angiotensin system inhibitors.

    PubMed

    Weir, Matthew R; Bakris, George L; Gross, Coleman; Mayo, Martha R; Garza, Dahlia; Stasiv, Yuri; Yuan, Jinwei; Berman, Lance; Williams, Gordon H

    2016-09-01

    Elevated serum aldosterone can be vasculotoxic and facilitate cardiorenal damage. Renin-angiotensin system inhibitors reduce serum aldosterone levels and/or block its effects but can cause hyperkalemia. Patiromer, a nonabsorbed potassium binder, decreases serum potassium in patients with chronic kidney disease on renin-angiotensin system inhibitors. Here we examined the effect of patiromer treatment on serum aldosterone, blood pressure, and albuminuria in patients with chronic kidney disease on renin-angiotensin system inhibitors with hyperkalemia (serum potassium 5.1-6.5 mEq/l). We analyzed data from the phase 3 OPAL-HK study (4-week initial treatment phase of 243 patients; 8-week randomized withdrawal phase of 107 patients). In the treatment phase, the (mean ± standard error) serum potassium was decreased concordantly with the serum aldosterone (-1.99 ± 0.51 ng/dl), systolic/diastolic blood pressure (-5.64 ± 1.04 mm Hg/-3.84 ± 0.69 mm Hg), and albumin-to-creatinine ratio (-203.7 ± 54.7 mg/g), all in a statistically significant manner. The change in the plasma renin activity (-0.44 ± 0.63 μg/l/hr) was not significant. In the withdrawal phase, mean aldosterone levels were sustained with patiromer (+0.23 ± 1.07 ng/dl) and significantly increased with placebo (+2.78 ± 1.25 ng/dl). Patients on patiromer had significant reductions in mean systolic/diastolic blood pressure (-6.70 ± 1.59/-2.15 ± 1.06 mm Hg), whereas those on placebo did not (-1.21 ± 1.89 mm Hg/+1.72 ± 1.26 mm Hg). Significant changes in plasma renin activity were found only in the placebo group (-3.90 ± 1.41 μg/l/hr). Thus, patiromer reduced serum potassium and aldosterone levels independent of plasma renin activity in patients with chronic kidney disease and hyperkalemia on renin-angiotensin system inhibitors. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  18. Tuberculosis after kidney transplantation is associated with significantly impaired allograft function.

    PubMed

    Costa, Silvana Daher; de Sandes-Freitas, Tainá Veras; Jacinto, Camilla Neves; Martiniano, Lorena Vasconcelos Mesquita; Amaral, Yago Sucupira; Paes, Fernando José Villar Nogueira; Sales, Maria Luiza de Mattos Brito Oliveira; Esmeraldo, Ronaldo de Matos; Daher, Elizabeth de Francesco

    2017-10-01

    This study aimed to evaluate renal function before, during, and after the course of tuberculosis (TB) disease in kidney transplant recipients, and assess the risk factors for non-recovery of baseline renal function. We performed a retrospective, single-center cohort study, including all patients with confirmed or presumed TB diagnosis after kidney transplant (n=34, 2.1%). Renal function was assessed by serum creatinine (Cr) and glomerular filtration rate (GFR) adjusted for deaths and graft losses. A significant increase was seen in serum Cr during TB disease and treatment: 1.5 mg/dL at baseline (Cr base ), 1.7 mg/dL at diagnosis (P<.001 vs. Cr base ), and 2.4 mg/dL during the peak (P<.001 vs. Cr base ). According to acute kidney injury (AKI) Kidney Disease: Improving Global Outcomes (KDIGO) classification, 29 (85%) patients had AKI: 16 stage 1, 2 stage 2, and 11 stage 3. Three months after the end of the TB treatment, five patients (14.7%) had lost their graft and two others (5.9%) had died. The GFR was lower than the baseline (42.4 mL/min vs 51.6 mL/min, P=.007). In the univariate analysis, peak Cr (odds ratio [OR] 1.276, 95% confidence interval [CI] 0.955-1.705, P=.100), AKI KDIGO stages 2 or 3 (OR 4.958, 95% CI 1.062-23.157, P=.042), severe disease (OR 5.700, 95% CI 1.147-28.330, P=.033), and acute rejection (AR) episodes after TB diagnosis (OR 3.937, 95% CI 0.551-28.116, P=.172) were associated with non-recovery of baseline renal function. No variable was identified in the multivariable model. Post-transplantation TB was associated with a high incidence of AKI, and complete recovery of baseline renal function was not achieved after treatment. The severity of TB disease, AKI, and AR episodes that occurred after TB diagnosis are potential causes for this outcome. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. 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.

  20. 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

  1. 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.

  2. Neural regulation of the kidney function in rats with cisplatin induced renal failure

    PubMed Central

    Goulding, Niamh E.; Johns, Edward J.

    2015-01-01

    Aim: Chronic kidney disease (CKD) is often associated with a disturbed cardiovascular homeostasis. This investigation explored the role of the renal innervation in mediating deranged baroreflex control of renal sympathetic nerve activity (RSNA) and renal excretory function in cisplatin-induced renal failure. Methods: Rats were either intact or bilaterally renally denervated 4 days prior to receiving cisplatin (5 mg/kg i.p.) and entered a chronic metabolic study for 8 days. At day 8, other groups of rats were prepared for acute measurement of RSNA or renal function with either intact or denervated kidneys. Results: Following the cisplatin challenge, creatinine clearance was 50% lower while fractional sodium excretion and renal cortical and medullary TGF-β1 concentrations were 3–4 fold higher in both intact and renally denervated rats compared to control rats. In cisplatin-treated rats, the maximal gain of the high-pressure baroreflex curve was only 20% that of control rats, but following renal denervation not different from that of renally denervated control rats. Volume expansion reduced RSNA by 50% in control and in cisplatin-treated rats but only following bilateral renal denervation. The volume expansion mediated natriuresis/diuresis was absent in the cisplatin-treated rats but was normalized following renal denervation. Conclusions: Cisplatin-induced renal injury impaired renal function and caused a sympatho-excitation with blunting of high and low pressure baroreflex regulation of RSNA, which was dependent on the renal innervation. It is suggested that in man with CKD there is a dysregulation of the neural control of the kidney mediated by its sensory innervation. PMID:26175693

  3. 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

  4. Kidney Facts

    MedlinePlus

    ... Page Transplant Living > Kidney KIDNEY TRANSPLANT LEARNING CENTER Kidney The kidneys are a vital organ in the ... your body. Location of the kidneys How the kidney works Your kidneys play a vital role in ...

  5. Solitary Kidney

    MedlinePlus

    ... Solitary Kidney Your Kidneys & How They Work Solitary Kidney What is a solitary kidney? When a person has only one kidney or ... ureter are removed (bottom right). What are the kidneys and what do they do? The kidneys are ...

  6. 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.

  7. Bird functional diversity decreases with time since disturbance: Does patchy prescribed fire enhance ecosystem function?.

    PubMed

    Sitters, Holly; Di Stefano, Julian; Christie, Fiona; Swan, Matthew; York, Alan

    2016-01-01

    Animal species diversity is often associated with time since disturbance, but the effects of disturbances such as fire on functional diversity are unknown. Functional diversity measures the range, abundance, and distribution of trait values in a community, and links changes in species composition with the consequences for ecosystem function. Improved understanding of the relationship between time since fire (TSF) and functional diversity is critical given that the frequency of both prescribed fire and wildfire is expected to increase. To address this knowledge gap, we examined responses of avian functional diversity to TSF and two direct measures of environmental heterogeneity, plant diversity, and structural heterogeneity. We surveyed birds across a 70-year chronosequence spanning four vegetation types in southeast Australia. Six bird functional traits were used to derive four functional diversity indices (richness, evenness, divergence, and dispersion) and the effects of TSF, plant diversity and structural heterogeneity on species richness and the functional diversity indices were examined using mixed models. We used a regression tree method to identify traits associated with species more common in young vegetation. Functional richness and dispersion were negatively associated with TSF in all vegetation types, suggesting that recent prescribed fire generates heterogeneous vegetation and provides greater opportunities for resource partitioning. Species richness was not significantly associated with TSF, and is probably an unreliable surrogate for functional diversity in fire-prone systems. A positive, relationship between functional evenness and structural heterogeneity was comnon to all vegetation types, suggesting that fine-scale (tens of meters) structural variation can enhance ecosystem function. Species more common in young vegetation were primarily linked by their specialist diets, indicating that ecosystem services such as seed dispersal and insect control

  8. 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.

  9. Cardiovascular and Renal Outcomes With Canagliflozin According to Baseline Kidney Function: Data from the CANVAS Program.

    PubMed

    Neuen, Brendon L; Ohkuma, Toshiaki; Neal, Bruce; Matthews, David R; de Zeeuw, Dick; Mahaffey, Kenneth W; Fulcher, Greg; Desai, Mehul; Li, Qiang; Deng, Hsiaowei; Rosenthal, Norm; Jardine, Meg J; Bakris, George; Perkovic, Vlado

    2018-06-25

    Background : Canagliflozin is approved for glucose lowering in type 2 diabetes and confers cardiovascular and renal benefits. We sought to assess whether it had benefits in people with chronic kidney disease (CKD), including those with an estimated glomerular filtration rate (eGFR) between 30 and 45 mL/min/1.73 m 2 in whom the drug is not currently approved for use. Methods : The CANagliflozin cardioVascular Assessment Study Program (CANVAS) randomized 10,142 participants with type 2 diabetes and eGFR greater than 30 mL/min/1.73 m 2 to canagliflozin or placebo. The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, with other cardiovascular, renal, and safety outcomes. This secondary analysis describes outcomes in participants with and without CKD, defined as eGFR <60 and ≥60 mL/min/1.73 m 2 , and according to baseline kidney function (eGFR <45, 45-<60, 60-<90, and ≥90 mL/min/1.73 m 2 ). Results : At baseline, 2039 (20.1%) participants had an eGFR <60 mL/min/1.73 m 2 , of whom 71.6% had a history of cardiovascular disease. The effect of canagliflozin on the primary outcome was similar in people with CKD (HR 0.70, 95% CI 0.55-0.90) and those with preserved kidney function (HR 0.92, 95% CI 0.79-1.07, P heterogeneity = 0.08). Relative effects on most cardiovascular and renal outcomes were similar across eGFR subgroups, with possible heterogeneity suggested only for the outcome of fatal/nonfatal stroke ( P heterogeneity = 0.01), as were results for almost all safety outcomes. Conclusions : The effect of canagliflozin on cardiovascular and renal outcomes was not modified by baseline level of kidney function in people with type 2 diabetes and a history or high risk of cardiovascular disease down to eGFR levels of 30 mL/min/1.73 m 2 Reassessing current limitations on the use of canagliflozin in CKD may allow additional individuals to benefit from this therapy. Clinical Trial Registration : URL: https

  10. Awareness, self-management behaviors, health literacy and kidney function relationships in specialty practice

    PubMed Central

    Devraj, Radhika; Borrego, Matthew E; Vilay, A Mary; Pailden, Junvie; Horowitz, Bruce

    2018-01-01

    AIM To determine the relationship between chronic kidney disease (CKD) awareness (CKD-A), self-management behaviors (CKD-SMB) knowledge, performance of CKD-SMBs, health literacy (HL) and kidney function. METHODS Participants were eligible patients attending an outpatient nephrology clinic. Participants were administered: Newest Vital Sign to measure HL, CKD self-management knowledge tool (CKD-SMKT) to assess knowledge, past performance of CKD-SMB, CKD-A. Estimated GFR (eGFR) was determined using the MDRD-4 equation. Duration of clinic participation and CKD cause were extracted from medical charts. RESULTS One-hundred-fifty patients participated in the study. eGFRs ranged from 17-152 mL/min per 1.73 m2. Majority (83%) of respondents had stage 3 or 4 CKD, low HL (63%), and were CKD aware (88%). Approximately 40% (10/25) of patients in stages 1 and 2 and 6.4% (8/125) in stages 3 and 4 were unaware of their CKD. CKD-A differed with stage (P < 0.001) but not by HL level, duration of clinic participation, or CKD cause. Majority of respondents (≥ 90%) correctly answered one or more CKD-SMKT items. Knowledge of one behavior, “controlling blood pressure” differed significantly by CKD-A. CKD-A was associated with past performance of two CKD-SMBs, “controlling blood pressure” (P = 0.02), and “keeping healthy body weight” (P = 0.01). Adjusted multivariate analyses between CKD-A and: (1) HL; and (2) CKD-SMB knowledge were non-significant. However, there was a significant relationship between CKD-A and kidney function after controlling for demographics, HL, and CKD-SMB (P < 0.05). CONCLUSION CKD-A is not associated with HL, or better CKD-SMBs. CKD-A is significantly associated with kidney function and substantially lower eGFR, suggesting the need for focused patient education in CKD stages 1. PMID:29359119

  11. Smad ubiquitination regulatory factor-2 in the fibrotic kidney: regulation, target specificity, and functional implication.

    PubMed

    Tan, Ruoyun; He, Weichun; Lin, Xia; Kiss, Lawrence P; Liu, Youhua

    2008-05-01

    Smad ubiquitination regulatory factor-2 (Smurf2) is an E3 ubiqutin ligase that plays a pivotal role in regulating TGF-beta signaling via selectively targeting key components of the Smad pathway for degradation. In this study, we have investigated the regulation of Smurf2 expression, its target specificity, and the functional implication of its induction in the fibrotic kidney. Immunohistochemical staining revealed that Smurf2 was upregulated specifically in renal tubules of kidney biopsies from patients with various nephropathies. In vitro, Smurf2 mRNA and protein were induced in human proximal tubular epithelial cells (HKC-8) upon TGF-beta1 stimulation. Ectopic expression of Smurf2 was sufficient to reduce the steady-state levels of Smad2, but not Smad1, Smad3, Smad4, and Smad7, in HKC-8 cells. Interestingly, Smurf2 was also able to downregulate the Smad transcriptional corepressors Ski, SnoN, and TG-interacting factor. Inhibition of the proteasomal pathway prevented Smurf2-mediated downregulation of Smad2 and Smad corepressors. Functionally, overexpression of Smurf2 enhanced the transcription of the TGF-beta-responsive promoter and augmented TGF-beta1-mediated E-cadherin suppression, as well as fibronectin and type I collagen induction in HKC-8 cells. These results indicate that Smurf2 specifically targets both positive and negative Smad regulators for destruction in tubular epithelial cells, thereby providing a complex fine-tuning of TGF-beta signaling. It appears that dysregulation of Smurf2 could contribute to an aberrant TGF-beta/Smad signaling in the pathogenesis of kidney fibrosis.

  12. Impact of Momordica charantia extract on kidney function and structure in mice.

    PubMed

    Mardani, Saeed; Nasri, Hamid; Hajian, Shabnam; Ahmadi, Ali; Kazemi, Reyhane; Rafieian-Kopaei, Mahmoud

    2014-01-01

    Bitter Melon (BM) is known for its hypoglycemic effect and is commonly used in populations. This study examined the effects and safety of bitter melon fruit in laboratory mice. In this experimental study 70 male mice (25-30 gr) were randomly divided into 7 groups. The mice were injected intraperitoneally with single doses of 0, 100, 500, 1000, 2000 and 4000 mg/kg and multiple doses 500 mg/kg daily for 7 days. The mice were then observed for 72 hours before sacrificing. Immediately kidneys were taken out for histological examinations. Tubular cell vacuolization and flattening as well as hyaline casts, debris and dilatation of tubular lumen were the morphologic lesions which were assessed with scores from 0 to 4, while zero score addressed normal renal tissue. Serum samples were assayed for kidney function (creatinine; Cr and Blood Urea Nitrogen; BUN). Blood and bitter melon antioxidant activities were measured, too. Data were analyzed with Stata software (Stata Corp. 2011. Stata Statistical Software: Release 12. College Station, TX: Stata Corp LP)using ANOVA and Bonferroni tests. All single dose groups showed normal behavior after the dosing and no statistical changes were observed in blood parameters (p>0.05). Histological examinations revealed normal organ structures, however, the group treated for 7 days showed statistically a significant change in BUN (p=0.002) and a borderline significance in Cr (p=0.051). Administration of up to 4000 mg/kg did not have any effect on the mice kidney function and histology, however chronic administration were nephrotoxic. More studies with different dosage regimens are suggested.

  13. Health status and renal function evaluation of kidney vendors: a report from Pakistan.

    PubMed

    Naqvi, S A A; Rizvi, S A H; Zafar, M N; Ahmed, E; Ali, B; Mehmood, K; Awan, M J; Mubarak, B; Mazhar, F

    2008-07-01

    Unrelated kidney transplants have lead to commerce and kidney vending in Pakistan. This study on 104 vendors reports demographics, history, physical and systemic examination, ultrasound findings, renal and liver function and GFR by Cockcroft-Gault. Results were compared with 184 age, sex and nephrectomy duration matched living-related donors controls. Comparison of vendors versus controls showed mean age of 30.55 +/- 8.1 versus 30.65 +/- 7.85 (p = 0.91) years, M:F of 4.5:1 versus 4.2:1 and nephrectomy period of 33.89 +/- 30 versus 32.01 +/- 29.71 (p = 0.60) months respectively. Of the vendors 67% were bonded laborers earning <50 $/month as compared to controls where 68% were skilled laborers and self-employed earning >100 $/month. History of vendors revealed jaundice in 8%, stone disease in 2% and urinary tract symptoms in 4.8%. Postnephrectomy findings between vendors versus donors showed BMI of 21.02 +/- 2.8 versus 23.02 +/- 4.2 (p = 0.0001), hypertension in 17% versus 9.2% (p = 0.04), serum creatinine (mg/dL) of 1.17+/-0.21 versus 1.02 +/- 0.27 (p = 0.0001), GFR (mL/min) of 70.94 +/- 14.2 versus 95.4 +/- 20.44 (p = 0.0001), urine protein/creatinine of 0.150 +/- 0.109 versus 0.10 +/- 0.10 (p = 0.0001), hepatitis C positivity in 27% versus 1.0% (p = 0.0001) and hepatitis B positive 5.7% versus 0.5% (p = 0.04), respectively. In conclusion, vendors had compromised renal function suggesting inferior selection and high risk for developing chronic kidney disease in long term.

  14. The Relationship between Maternal Nutrition during Pregnancy and Offspring Kidney Structure and Function in Humans: A Systematic Review

    PubMed Central

    Lee, Yu Qi; Collins, Clare E.; Gordon, Adrienne; Rae, Kym M.; Pringle, Kirsty G.

    2018-01-01

    The intrauterine environment is critical for fetal growth and organ development. Evidence from animal models indicates that the developing kidney is vulnerable to suboptimal maternal nutrition and changes in health status. However, evidence from human studies are yet to be synthesised. Therefore, the aim of the current study was to systematically review current research on the relationship between maternal nutrition during pregnancy and offspring kidney structure and function in humans. A search of five databases identified 9501 articles, of which three experimental and seven observational studies met the inclusion criteria. Nutrients reviewed to date included vitamin A (n = 3), folate and vitamin B12 (n = 2), iron (n = 1), vitamin D (n = 1), total energy (n = 2) and protein (n = 1). Seven studies were assessed as being of “positive” and three of “neutral” quality. A variety of populations were studied, with limited studies investigating maternal nutrition during pregnancy, while measurements of offspring kidney outcomes were diverse across studies. There was a lack of consistency in the timing of follow-up for offspring kidney structure and/or function assessments, thus limiting comparability between studies. Deficiencies in maternal folate, vitamin A, and total energy during pregnancy were associated with detrimental impacts on kidney structure and function, measured by kidney volume, proteinuria, eGFRcystC and mean creatinine clearance in the offspring. Additional experimental and longitudinal prospective studies are warranted to confirm this relationship, especially in Indigenous populations where the risk of renal disease is greater. PMID:29466283

  15. Improvement in Nutritional Status in Patients With Chronic Kidney Disease-4 by a Nutrition Education Program With No Impact on Renal Function and Determined by Male Sex.

    PubMed

    Pérez-Torres, Almudena; González Garcia, Elena; Garcia-Llana, Helena; Del Peso, Gloria; López-Sobaler, Ana María; Selgas, Rafael

    2017-09-01

    Protein-energy wasting (PEW) is associated with increased morbidity and mortality and a rapid deterioration of kidney function in patients with chronic kidney disease (CKD). However, there is little information regarding the effect of nutrition intervention. The aims of this study were to evaluate the efficacy and safety of a nutrition education program (NEP) in patients with nondialysis dependent CKD (NDD-CKD), based on the diagnostic criteria for PEW proposed by the International Society of Renal Nutrition and Metabolism. The design of the study was a 6-month longitudinal, prospective, and interventional study. The study was conducted from March 2008 to September 2011 in the Nephrology Department of La Paz University Hospital in Madrid, Spain. A total of 160 patients with NDD-CKD started the NEP, and 128 finished it. The 6-month NEP consisted of designing an individualized diet plan based on the patient's initial nutritional status, and 4 nutrition education sessions. Changes in nutritional status (PEW) and biochemical, anthropometric and body composition parameters. After 6 months of intervention, potassium and inflammation levels decreased, and an improved lipid profile was found. Body mass index lowered, with increased muscle mass and a stable fat mass. Men showed increased levels of albumin and prealbumin, and women showed decreased proteinuria levels. The prevalence of PEW decreased globally (27.3%-10.9%; P = .000), but differently in men (29.5%-6.5%; P = .000) and in women (25.4%-14.9%; P = .070), 3 of the women having worsened. Kidney function was preserved, despite increased protein intake. The NEP in NDD-CKD generally improved nutritional status as measured by PEW parameters, but individual poorer results indicated the need to pay special attention to female sex and low body mass index at the start of the program. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  16. Reagents for Astatination of Biomolecules. 5. Evaluation of hydrazone linkers in 211At- and 125I-labeled closo-decaborate(2-) conjugates of Fab′ as a means of decreasing kidney retention

    PubMed Central

    Wilbur, D. Scott; Chyan, Ming-Kuan; Hamlin, Donald K.; Nguyen, Holly; Vessella, Robert L.

    2011-01-01

    Evaluation of monoclonal antibody (MAb) fragments (e.g. Fab′, Fab or engineered fragments) as cancer-targeting reagents for therapy with the α-particle emitting radionuclide astatine-211 (211At) has been hampered by low in vivo stability of the label and a propensity of these proteins localize to kidneys. Fortunately, our group has shown that the low stability of the 211At label, generally a meta- or para-[211At]astatobenzoyl conjugate, on MAb Fab′ fragments can be dramatically improved by use of closo-decaborate(2-) conjugates. However, the higher stability of radiolabeled MAb Fab′ conjugates appears to result in retention of the radioactivity in kidneys. This investigation was conducted to evaluate whether the retention of radioactivity in kidney might be decreased by the use of acid-cleavable hydrazone between the Fab′ and the radiolabeled closo-decaborate(2-) moiety. Five conjugation reagents containing sulfhydryl-reactive maleimide groups, a hydrazone functionality and a closo-decaborate(2-) moiety were prepared. In four of the five conjugation reagents, a discrete polyethylene glycol (PEG) linker was used, and one substituent adjacent to the hydrazone was varied (phenyl, benzoate, anisole or methyl) to provide varying acid-sensitivity. In the initial studies, the five maleimido-closo-decaborate(2-) conjugation reagents were radioiodinated (125I or 131I), then conjugated with an anti-PSMA Fab′ (107-1A4 Fab′). Biodistributions of the five radioiodinated Fab′ conjugates were obtained in nude mice at 1, 4 and 24 h post injection (pi). In contrast to closo-decaborate(2-) conjugated to 107-1A4 Fab′ through a non-cleavable linker, two conjugates containing either a benzoate or a methyl substituent on the hydrazone functionality displayed clearance rates from kidney, liver and spleen that were similar to those obtained with directly radioiodinated Fab′ (i.e. no conjugate). The maleimido-closo-decaborate(2-) conjugation reagent containing a benzoate

  17. Estimated GFR reporting is associated with decreased nonsteroidal anti-inflammatory drug prescribing and increased renal function.

    PubMed

    Wei, Li; MacDonald, Thomas M; Jennings, Claudine; Sheng, Xia; Flynn, Robert W; Murphy, Michael J

    2013-07-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used; however, they are also nephrotoxic with both acute and chronic effects on kidney function. Here we determined NSAID prescribing before and after estimated GFR (eGFR) reporting and evaluate renal function in patients who used NSAIDs but stopped these after their first eGFR report. A population-based longitudinal analysis using a record-linkage database was conducted with the GFR estimated using the four-variable equation from the MDRD study and analyzed by trend test, paired t-test, and logistic regression modeling. Prescriptions for NSAIDs significantly decreased from 39,459 to 35,415 after implementation of eGFR reporting from the second quarter of 2005 compared with the first quarter of 2007. Reporting eGFR was associated with reduced NSAID prescriptions (adjusted odds ratio, 0.78). NSAID prescription rates in the 6 months before April 2006 were 18.8, 15.4, and 7.0% in patients with CKD stages 3, 4, and 5 and 15.5, 10.7, and 6.3%, respectively, after eGFR reporting commenced. In patients who stopped NSAID treatment, eGFR significantly increased from 45.9 to 46.9, 23.9 to 27.1, and 12.4 to 26.4 ml/min per 1.73 m(2) in 1340 stage 3 patients, 162 stage 4 patients, and 9 stage 5 patients, respectively. Thus, NSAID prescribing decreased after the implementation of eGFR reporting, and there were significant improvements in estimated renal function in patients who stopped taking NSAIDs. Hence, eGFR reporting may result in safer prescribing.

  18. 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.

  19. Effect of bardoxolone methyl on kidney function in patients with T2D and Stage 3b-4 CKD.

    PubMed

    Pergola, Pablo E; Krauth, Melissa; Huff, J Warren; Ferguson, Deborah A; Ruiz, Stacey; Meyer, Colin J; Warnock, David G

    2011-01-01

    Bardoxolone methyl, a novel synthetic triterpenoid, induces Nrf2, a transcription factor known to play a key role in decreasing oxidative stress and the production of pro-inflammatory molecules. This exploratory multi-center, open-label study assessed the clinical activity and safety of bardoxolone methyl in 20 patients with moderate to severe chronic kidney disease and type 2 diabetes. Patients received 25 mg of bardoxolone methyl daily for 28 days, followed by 75 mg daily for another 28 days. The study achieved its primary efficacy endpoint, as demonstrated by a significant increase from baseline in estimated glomerular filtration rate (eGFR) of 7.2 ml/min/1.73 m2 (p < 0.001). Improvements were seen in approximately 90% of patients and showed a dose- and time-dependent increase in eGFR. The eGFR change paralleled a significant reduction in serum creatinine (-0.3 mg/dl) and blood urea nitrogen (-4.9 mg/dl), along with an increase in creatinine clearance (+14.6 ml/min/1.73 m2), without a change in the 24-hour creatinine excretion rate. Markers of vascular injury and inflammation were improved by treatment with bardoxolone. No life-threatening adverse events or drug-related serious adverse events were reported. The results describe an apparent increase in kidney function following relatively short-term treatment with bardoxolone methyl, a promising new agent that warrants placebo-controlled studies to define its long-term effects on renal function. Copyright © 2011 S. Karger AG, Basel.

  20. A dosing algorithm for metformin based on the relationships between exposure and renal clearance of metformin in patients with varying degrees of kidney function.

    PubMed

    Duong, Janna K; Kroonen, M Y A M; Kumar, S S; Heerspink, H L; Kirkpatrick, C M; Graham, G G; Williams, K M; Day, R O

    2017-08-01

    The aims of this study were to investigate the relationship between metformin exposure, renal clearance (CL R ), and apparent non-renal clearance of metformin (CL NR /F) in patients with varying degrees of kidney function and to develop dosing recommendations. Plasma and urine samples were collected from three studies consisting of patients with varying degrees of kidney function (creatinine clearance, CL CR ; range, 14-112 mL/min). A population pharmacokinetic model was built (NONMEM) in which the oral availability (F) was fixed to 0.55 with an estimated inter-individual variability (IIV). Simulations were performed to estimate AUC 0-τ , CL R , and CL NR /F. The data (66 patients, 327 observations) were best described by a two-compartment model, and CL CR was a covariate for CL R . Mean CL R was 17 L/h (CV 22%) and mean CL NR /F was 1.6 L/h (69%).The median recovery of metformin in urine was 49% (range 19-75%) over a dosage interval. When CL R increased due to improved renal function, AUC 0-τ decreased proportionally, while CL NR /F did not change with kidney function. Target doses (mg/day) of metformin can be reached using CL CR /3 × 100 to obtain median AUC 0-12 of 18-26 mg/L/h for metformin IR and AUC 0-24 of 38-51 mg/L/h for metformin XR, with C max  < 5 mg/L. The proposed dosing algorithm can be used to dose metformin in patients with various degrees of kidney function to maintain consistent drug exposure. However, there is still marked IIV and therapeutic drug monitoring of metformin plasma concentrations is recommended.

  1. Association between Delayed graft function (DGF) biomarkers and long-term outcomes after living donor kidney transplantation.

    PubMed

    Sahraei, Zahra; Mehdizadeh, Mona; Salamzadeh, Jamshid; Nafar, Mohsen; Eshraghi, Azadeh

    2018-05-21

    The Association between preoperative Urine Neutrophil Gelatinase-associated Lipocalin (uNGAL) and interlukin-18 (uIL-18) with poor 1-year allograft function has been shown in deceased-donor kidney transplant recipients previously, and also these markers could predict 3-month allograft function. However, it is unknown whether there is any association between these postoperative biomarkers with important recipient outcomes beyond this time in live-donor transplants. NGAL and IL-18 four and 24 hours were measured in live-donor kidney transplant recipients after transplantation. The relationships between changes in these markers with clinical outcomes as well as kidney function were examined at 1 month and 2 years. Also, the association between delayed graft function with clinical outcome and serum creatinine (SrCr) were evaluated during this period. The Mean age for kidney recipients was 23.9 years. There was significant interaction between uNGAL 24 hr (pvalue=0.01) and uIL-18 four and 24 hr after transplantation (pvalue=0.04, 0.03; respectively) with patients' outcome after 1 month and changes in uNGAL with outcomes after 2 years (pvalue= 0.04). Changes in urine NGAL postoperative is associated with worse outcome 2 years after kidney transplantation, suggesting its potential role for identifying patients that are at high risk for diminished allograft function, outcome and survival. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Decreased frequency of peripheral CD4(+) CD161(+) Th(17) -precursor cells in kidney transplant recipients on long-term therapy with Belatacept.

    PubMed

    Vondran, Florian Wolfgang Rudolf; Timrott, Kai; Kollrich, Sonja; Klempnauer, Juergen; Schwinzer, Reinhard; Becker, Thomas

    2012-04-01

    Clinical trials have pointed out the promising role of co-stimulation blocker Belatacept for improvement of graft function and avoidance of undesired side-effects associated with calcineurin-inhibitors (CNI). However, due to the worldwide limited availability of appropriate patients, almost no data exist to assess the effects of sustained application of this immunomodulator on the recipient's immune system. The aim of this study was to reveal specific alterations in the composition of immunologic subpopulations potentially involved in development of tolerance or chronic graft rejection following long-term Belatacept therapy. For this, peripheral lymphocyte subsets of kidney recipients treated with Belatacept (n=5; average 7.8years) were determined by flow-cytometry and compared with cells from matched patients on CNI (n=9) and healthy controls (n=10). T cells capable of producing IL-17 and serum levels of soluble CD30 were quantified. Patients on CNI showed a higher frequency of CD4(+) CD161(+) Th(17) -precursors and IL-17-producing CD4(+) T cells than Belatacept patients and controls. Significantly higher serum levels of soluble CD30 were observed in CNI patients, indicating a possible involvement of the CD30/CD30L-system in Th(17) -differentiation. No differences were found concerning CD4(+) CD25(+) CD127(low) FoxP3(+) regulatory T cells. In conclusion, patients on therapy with Belatacept did not show a comparable Th(17) -profile to that seen in individuals with chronic intake of CNI. The distinct effects of Belatacept on Th(17) -immunity might prove beneficial for the long-term outcome following kidney transplantation. © 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation.

  3. 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

  4. Analysis of renal blood flow and renal volume in normal fetuses and in fetuses with a solitary functioning kidney.

    PubMed

    Hindryckx, An; Raaijmakers, Anke; Levtchenko, Elena; Allegaert, Karel; De Catte, Luc

    2017-12-01

    To evaluate renal blood flow and renal volume for the prediction of postnatal renal function in fetuses with solitary functioning kidney (SFK). Seventy-four SFK fetuses (unilateral renal agenesis [12], multicystic dysplastic kidney [36], and severe renal dysplasia [26]) were compared with 58 healthy fetuses. Peak systolic velocity (PSV), pulsatility index (PI), and resistance index (RI) of the renal artery (RA) were measured; 2D and 3D (VOCAL) volumes were calculated. Renal length and glomerular filtration rate (GFR) were obtained in SFK children (2 years). Compared with the control group, the PSV RA was significantly lower in nonfunctioning kidneys and significantly higher in SFK. Volume measurements indicated a significantly larger volume of SFK compared with healthy kidneys. All but 4 children had GFR above 70 mL/min/1.73 m 2 , and compensatory hypertrophy was present in 69% at 2 years. PSV RA and SFK volume correlated with postnatal renal hypertrophy. No correlation between prenatal and postnatal SFK volume and GFR at 2 years was demonstrated. Low PSV RA might have a predictive value for diagnosing a nonfunctioning kidney in fetuses with a SFK. We demonstrated a higher PSV RA and larger renal volume in the SFK compared with healthy kidneys. © 2017 John Wiley & Sons, Ltd.

  5. Microvascular resistance in response to iodinated contrast media in normal and functionally impaired kidneys.

    PubMed

    Kurihara, Osamu; Takano, Masamichi; Uchiyama, Saori; Fukuizumi, Isamu; Shimura, Tetsuro; Matsushita, Masato; Komiyama, Hidenori; Inami, Toru; Murakami, Daisuke; Munakata, Ryo; Ohba, Takayoshi; Hata, Noritake; Seino, Yoshihiko; Shimizu, Wataru

    2015-12-01

    Contrast-induced nephropathy (CIN) is considered to result from intrarenal vasoconstriction, and occurs more frequently in impaired than in normal kidneys. It was hypothesized that iodinated contrast media would markedly change renal blood flow and vascular resistance in functionally impaired kidneys. Thirty-six patients were enrolled (32 men; mean age, 75.3 ± 7.6 years) undergoing diagnostic coronary angiography and were divided into two groups based on the presence of chronic kidney disease (CKD), defined as an estimated glomerular filtration rate (eGFR) of < 60 mL/min per 1.73 m(2) (CKD and non-CKD groups, n = 18 in both). Average peak velocity (APV) and renal artery resistance index (RI) were measured by Doppler flow wire before and after administration of the iodinated contrast media. The APV and the RI were positively and inversely correlated with the eGFR at baseline, respectively (APV, R = 0.545, P = 0.001; RI, R = -0.627, P < 0.001). Mean RI was significantly higher (P = 0.015) and APV was significantly lower (P = 0.026) in the CKD than in the non-CKD group. Both APV (P < 0.001) and RI (P = 0.002) were significantly changed following contrast media administration in the non-CKD group, but not in the CKD group (APV, P = 0.258; RI, P = 0.707). Although renal arterial resistance was higher in patients with CKD, it was not affected by contrast media administration, suggesting that patients with CKD could have an attenuated response to contrast media. © 2015 The Authors. Clinical and Experimental Pharmacology and Physiology Published by Wiley Publishing Asia Pty Ltd.

  6. Monosodium glutamate intake affect the function of the kidney through NMDA receptor.

    PubMed

    Mahieu, Stella; Klug, Maximiliano; Millen, Néstor; Fabro, Ana; Benmelej, Adriana; Contini, Maria Del Carmen

    2016-03-15

    We investigated whether the chronic intake of monosodium glutamate (MSG) with food affects kidney function, and renal response to glycine. We also established if the NMDA receptors are involved in the changes observed. Male Wistar rats (5weeks old) were fed a diet supplemented with MSG (3g/kg b.w./day), five days a week, and spontaneous ingestion of a 1% MSG solution during 16weeks. NaCl rats were fed a diet with NaCl (1g/kg b.w./day) and 0.35% NaCl solution at the same frequency and time. Control group was fed with normal chow and tap water. We utilized clearance techniques to examine glomerular filtration rate (GFR) and cortical renal plasma flow (CRPF) response to glycine and glycine+MK-801 (antagonist NMDA-R), and we determined NMDA-R1 in kidney by immunohistochemistry. The addition of MSG in the diet of rats increased both GFR and CRPF with an increase of absolute sodium reabsorption. However, hyperfiltration was accompanied with a normal response to glycine infusion. Immunostain of kidney demonstrate that the NMDA receptor is upregulated in rats fed with MSG diet. NMDA-R antagonist MK-801 significantly reduced both the GFR and CRPF; however the percentage of reduction was significantly higher in the group MSG. MK-801 also reduces fractional excretion of water, sodium and potassium in the three groups. Renal NMDAR may be conditioned by the addition of MSG in the diet, favoring the hyperfiltration and simultaneously Na retention in the body. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. 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.

  8. Thyroid functional disease: an under-recognized cardiovascular risk factor in kidney disease patients

    PubMed Central

    Rhee, Connie M.; Brent, Gregory A.; Kovesdy, Csaba P.; Soldin, Offie P.; Nguyen, Danh; Budoff, Matthew J.; Brunelli, Steven M.; Kalantar-Zadeh, Kamyar

    2015-01-01

    Thyroid functional disease, and in particular hypothyroidism, is highly prevalent among chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. In the general population, hypothyroidism is associated with impaired cardiac contractility, endothelial dysfunction, atherosclerosis and possibly higher cardiovascular mortality. It has been hypothesized that hypothyroidism is an under-recognized, modifiable risk factor for the enormous burden of cardiovascular disease and death in CKD and ESRD, but this has been difficult to test due to the challenge of accurate thyroid functional assessment in uremia. Low thyroid hormone levels (i.e. triiodothyronine) have been associated with adverse cardiovascular sequelae in CKD and ESRD patients, but these metrics are confounded by malnutrition, inflammation and comorbid states, and hence may signify nonthyroidal illness (i.e. thyroid functional test derangements associated with underlying ill health in the absence of thyroid pathology). Thyrotropin is considered a sensitive and specific thyroid function measure that may more accurately classify hypothyroidism, but few studies have examined the clinical significance of thyrotropin-defined hypothyroidism in CKD and ESRD. Of even greater uncertainty are the risks and benefits of thyroid hormone replacement, which bear a narrow therapeutic-to-toxic window and are frequently prescribed to CKD and ESRD patients. In this review, we discuss mechanisms by which hypothyroidism adversely affects cardiovascular health; examine the prognostic implications of hypothyroidism, thyroid hormone alterations and exogenous thyroid hormone replacement in CKD and ESRD; and identify areas of uncertainty related to the interplay between hypothyroidism, cardiovascular disease and kidney disease requiring further investigation. PMID:24574542

  9. Association of Slow Graft Function with Long-Term Outcomes in Kidney Transplant Recipients.

    PubMed

    Wang, Connie J; Tuffaha, Ahmad; Phadnis, Milind A; Mahnken, Jonathan D; Wetmore, James B

    2018-04-03

    BACKGROUND Whether slow graft function (SGF) represents an intermediate phenotype between immediate graft function (IGF) and delayed graft function (DGF) in kidney transplant recipients is unknown. MATERIAL AND METHODS In a retrospective cohort analysis of 1,222 kidney transplant recipients, we classified patients as having IGF, SGF, and DGF using two different schemas. SGF was defined as serum creatinine (Cr) ≥3.0 mg/dL by postoperative day 5 in Schema 1, and in Schema 2, SGF was defined as Cr >1.5 mg/dL plus a creatinine reduction ratio <20% between postoperative days 1 and 3. A complementary log-log model was used to examine the association of graft function with graft survival and patient survival. RESULTS Mean age of study patients was 51.5±13.3 years, 59.9% were male, and 66.7% were white. In Schema 1, SGF and DGF were associated with comparable increases in risk of graft failure compared to IGF (hazard ratio (HR) 1.46, 95% confidence intervals (CI) 1.02-2.10 for SGF and HR 1.56, CI 1.11-2.22 for IGF); estimates were similar for Schema 2 (HR 1.52, CI 1.05-2.20 for SGF and HR 1.54, CI 1.10-2.17 for IGF). However, for mortality, outcomes for SGF were similarly to IGF, both SGF and IGF were associated with lower risk relative to DGF (HR 0.54, CI 0.36-0.80 for SGF in Schema 1; HR 0.58, CI 0.39-0.85 for SGF in Schema 2). CONCLUSIONS These findings suggest that SGF may be a marker for graft failure but not for mortality, and SGF may therefore represent a phenotype separate from IGF and DGF.

  10. Cardiorespiratory fitness and sports activities in children and adolescents with solitary functioning kidney.

    PubMed

    Tancredi, Giancarlo; Lambiase, Caterina; Favoriti, Alessandra; Ricupito, Francesca; Paoli, Sara; Duse, Marzia; De Castro, Giovanna; Zicari, Anna Maria; Vitaliti, Giovanna; Falsaperla, Raffaele; Lubrano, Riccardo

    2016-04-27

    An increasing number of children with chronic disease require a complete medical examination to be able to practice physical activity. Particularly children with solitary functioning kidney (SFK) need an accurate functional evaluation to perform sports activities safely. The aim of our study was to evaluate the influence of regular physical activity on the cardiorespiratory function of children with solitary functioning kidney. Twenty-nine patients with congenital SFK, mean age 13.9 ± 5.0 years, and 36 controls (C), mean age 13.8 ± 3.7 years, underwent a cardiorespiratory assessment with spirometry and maximal cardiopulmonary exercise testing. All subjects were divided in two groups: sedentary (S) and trained (T) patients, by means of a standardized questionnaire about their weekly physical activity. We found that mean values of maximal oxygen consumption (VO2max) and exercise time (ET) were higher in T subjects than in S subjects. Particularly SFK-T presented mean values of VO2max similar to C-T and significantly higher than C-S (SFK-T: 44.7 ± 6.3 vs C-S: 37.8 ± 3.7 ml/min/kg; p < 0.0008). We also found significantly higher mean values of ET (minutes) in minutes in SFK-T than C-S subjects (SFK-T: 12.9 ± 1.6 vs C-S: 10.8 ± 2.5 min; p <0.02). Our study showed that regular moderate/high level of physical activity improve aerobic capacity (VO2max) and exercise tolerance in congenital SFK patients without increasing the risks for cardiovascular accidents and accordingly sports activities should be strongly encouraged in SFK patients to maximize health benefits.

  11. Impact of decreased serum albumin levels on acute kidney injury in patients with acute decompensated heart failure: a potential association of atrial natriuretic peptide.

    PubMed

    Takaya, Yoichi; Yoshihara, Fumiki; Yokoyama, Hiroyuki; Kanzaki, Hideaki; Kitakaze, Masafumi; Goto, Yoichi; Anzai, Toshihisa; Yasuda, Satoshi; Ogawa, Hisao; Kawano, Yuhei; Kangawa, Kenji

    2017-08-01

    Although hypoalbuminemia at admission is a risk for acute kidney injury (AKI) and mortality in patients with acute decompensated heart failure (ADHF), the clinical significance of decreased serum albumin levels (DAL) during ADHF therapy has not been elucidated. This study aimed to evaluate whether DAL was associated with AKI, and whether intravenous atrial natriuretic peptide (ANP) administration, which provides an effective treatment for ADHF but promotes albumin extravasation, was associated with DAL and AKI. A total of 231 consecutive patients with ADHF were enrolled. AKI was defined as ≥0.3 mg/dl absolute or 1.5-fold increase in serum creatinine levels within 48 h. AKI occurred in 73 (32%) of the 231 patients during ADHF therapy. The median value of decreases in serum albumin levels was 0.3 g/dl at 7 days after admission. When DAL was defined as ≥0.3 g/dl decrease in serum albumin levels, DAL occurred in 113 patients, and was independently associated with AKI. Of the 231 patients, 73 (32%) were treated with intravenous ANP. DAL occurred more frequently in patients receiving ANP than in those not receiving ANP (77 vs. 36%, p < 0.001), and ANP was independently associated with DAL. The incidence of AKI was higher in patients receiving ANP than in those not receiving ANP (48 vs. 24%, p < 0.001). ANP was independently associated with AKI. In conclusion, DAL is associated with AKI. Intravenous ANP administration may be one of the promoting factors of DAL, which leads to AKI, indicating a possible novel mechanism of AKI.

  12. 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

  13. 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.

  14. Pretransplant Recipient Circulating CD4+CD127lo/- Tumor Necrosis Factor Receptor 2+ Regulatory T Cells: A Surrogate of Regulatory T Cell-Suppressive Function and Predictor of Delayed and Slow Graft Function After Kidney Transplantation.

    PubMed

    Nguyen, Minh-Tri J P; Fryml, Elise; Sahakian, Sossy K; Liu, Shuqing; Cantarovich, Marcelo; Lipman, Mark; Tchervenkov, Jean I; Paraskevas, Steven

    2016-02-01

    Delayed graft function (DGF) and slow graft function (SGF) are ischemia-reperfusion-associated acute kidney injuries (AKI) that decrease long-term graft survival after kidney transplantation. Regulatory T (Treg) cells are protective in murine AKI, and their suppressive function predictive of AKI in kidney transplantation. The conventional Treg cell function coculture assay is however time-consuming and labor intensive. We sought a simpler alternative to measure Treg cell function and predict AKI. In this prospective observational cohort study, pretransplant recipient circulating CD4+CD25+CD127lo/- and CD4+CD127lo/- tumor necrosis factor receptor 2 (TNFR2)+ Treg cells were measured by flow cytometry in 76 deceased donor kidney transplant recipients (DGF, n = 18; SGF, n = 34; immediate graft function [IGF], n = 24). In a subset of 37 recipients, pretransplant circulating Treg cell-suppressive function was also quantified by measuring the suppression of autologous effector T-cell proliferation by Treg cell in coculture. The TNFR2+ expression on CD4+CD127lo/- T cells correlated with Treg cell-suppressive function (r = 0.63, P < 0.01). In receiver operating characteristic curves, percentage and absolute number of CD4+CD127lo/-TNFR2+ Treg cell predicted DGF from non-DGF (IGF + SGF) with area under the curves of 0.75 and 0.77, respectively, and also AKI (DGF + SGF) from IGF with area under the curves of 0.76 and 0.72, respectively (P < 0.01). Prediction of AKI (DGF + SGF) from IGF remained significant in multivariate logistic regression accounting for cold ischemic time, donor age, previous transplant, and pretransplant dialysis modality. Pretransplant recipient circulating CD4+CD127lo/-TNFR2+ Treg cell is potentially a simpler alternative to Treg cell function as a pretransplant recipient immune marker for AKI (DGF + SGF), independent from donor and organ procurement characteristics.

  15. 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.

  16. Decreased sudomotor function is involved in the formation of atopic eczema in the cubital fossa.

    PubMed

    Takahashi, Aya; Murota, Hiroyuki; Matsui, Saki; Kijima, Akiko; Kitaba, Shun; Lee, Jeong-Beom; Katayama, Ichiro

    2013-12-01

    Eczema in the cubital fossa, which is susceptible to sweat, is frequently observed in atopic dermatitis (AD). However, there has been no direct evidence that sweating causes eczema in the cubital fossa. To investigate this issue, axon reflex-mediated sweating volume (AXR) and skin barrier function in the cubital fossa were measured in subjects with AD and in healthy volunteers, and were applied to clinical feature of the cubital fossa. AXR in the cubital fossa decreased in AD subjects; it positively correlated only with water-holding capacity in healthy subjects but not in patients with in AD. Furthermore, AD subjects with lichenoid eczema and either prurigo or papules over the cubital fossa showed extremely decreased AXR. These results suggest that decreased sweating is a major source of water in the stratum corneum, and decreased sudomotor function may be involved in both the cause and aggravation of representative atopic eczema in the cubital fossa.

  17. Effect of glycemic index and carbohydrate intake on kidney function in healthy adults.

    PubMed

    Juraschek, Stephen P; Chang, Alex R; Appel, Lawrence J; Anderson, Cheryl A M; Crews, Deidra C; Thomas, Letitia; Charleston, Jeanne; Miller, Edgar R

    2016-07-08

    Replacing carbohydrate with protein acutely increases glomerular filtration rate (GFR) but is associated with faster, long-term kidney disease progression. The effects of carbohydrate type (i.e. glycemic index, GI) on kidney function are unknown. We conducted an ancillary study of a randomized, crossover feeding trial in overweight/obese adults without diabetes or kidney disease (N = 163). Participants were fed each of four healthy, DASH-like diets for 5 weeks, separated by 2-week washout periods. Weight was kept constant. The four diets were: high GI (GI ≥65) with high %carb (58 % kcal) (reference diet), low GI (≤45) with low %carb (40 % kcal), low GI with high %carb; and high GI with low %carb. Plasma was collected at baseline and after each feeding period. Study outcomes were cystatin C, β2-microglobulin (β2M), and estimated GFR based on cystatin C (eGFRcys). Mean (SD) age was 52 (11) years; 52 % were women; 50 % were black. At baseline, mean (SD) cystatin C, β2M, and eGFRcys were 0.8 (0.1) mg/L, 1.9 (0.4) mg/L, and 104 (16) mL/min/1.73 m(2). Compared to the high GI/high %carb diet, reducing GI, %carb, or both increased eGFRcys by 1.9 mL/min/1.73 m(2) (95 % CI: 1.1, 2.7; P < 0.001), 3.0 mL/min/1.73 m(2) (1.9, 4.0; P < 0.001), and 4.5 mL/min/1.73 m(2) (3.5, 5.4; P < 0.001), respectively. Increases in eGFRcys from reducing GI were significantly associated with increases in eGFRcys from reducing %carb (P < 0.001). Results for cystatin C and β2M reflected eGFRcys. Reducing GI increased GFR. Reducing %carb by increasing calories from protein and fat, also increased GFR. Future studies on GI should examine the long-term effects of this increase in GFR on kidney injury markers and clinical outcomes. Clinical Trials.gov, number: NCT00608049 (first registered January 23, 2008).

  18. Multiple Novel Loci are Associated with Indices of Renal Function and Chronic Kidney Disease

    PubMed Central

    Köttgen, Anna; Glazer, Nicole L; Dehghan, Abbas; Hwang, Shih-Jen; Katz, Ronit; Li, Man; Yang, Qiong; Gudnason, Vilmundur; Launer, Lenore J; Harris, Tamara B; Smith, Albert V; Arking, Dan E; Astor, Brad C; Boerwinkle, Eric; Ehret, Georg B; Ruczinski, Ingo; Scharpf, Robert B; Chen, Yii-Der Ida; de Boer, Ian H; Haritunians, Talin; Lumley, Thomas; Sarnak, Mark; Siscovick, David; Benjamin, Emelia J; Levy, Daniel; Upadhyay, Ashish; Aulchenko, Yurii S; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, André G; van Duijn, Cornelia M; Chasman, Daniel I; Paré, Guillaume; Ridker, Paul M; Kao, WH Linda; Witteman, Jacqueline C; Coresh, Josef; Shlipak, Michael G; Fox, Caroline S

    2011-01-01

    Chronic kidney disease (CKD) has a heritable component and is an important global public health problem because of its high prevalence and morbidity.1 We conducted genome-wide association studies (GWAS) to identify susceptibility loci for glomerular filtration rate estimated by serum creatinine (eGFRcrea), cystatin C (eGFRcys), and CKD (eGFRcrea<60 ml/min/1.73m2) in European-ancestry participants of four populations-based cohorts (ARIC, CHS, FHS, RS; n=19,877, 2,388 CKD cases), and tested for external replication in 21,466 participants (1,932 CKD cases). Significant associations (p<5*10−8) were identified for SNPs with [1] CKD at the UMOD locus; [2] eGFRcrea at the UMOD, SHROOM3, and GATM/SPATA5L1 loci; [3] eGFRcys at the CST and STC1 loci. UMOD encodes the most common protein in human urine, Tamm-Horsfall protein,2 and rare mutations in UMOD cause Mendelian forms of kidney disease.3 Our findings provide new insights into CKD pathogenesis and underscore the importance of common genetic variants influencing renal function and disease. PMID:19430482

  19. Novel Functional Complexity of Polycystin-1 by GPS Cleavage In Vivo: Role in Polycystic Kidney Disease

    PubMed Central

    Kurbegovic, Almira; Kim, Hyunho; Xu, Hangxue; Yu, Shengqiang; Cruanès, Julie; Maser, Robin L.; Boletta, Alessandra; Trudel, Marie

    2014-01-01

    Polycystin-1 (Pc1) cleavage at the G protein-coupled receptor (GPCR) proteolytic site (GPS) is required for normal kidney morphology in humans and mice. We found a complex pattern of endogenous Pc1 forms by GPS cleavage. GPS cleavage generates not only the heterodimeric cleaved full-length Pc1 (Pc1cFL) in which the N-terminal fragment (NTF) remains noncovalently associated with the C-terminal fragment (CTF) but also a novel (Pc1) form (Pc1deN) in which NTF becomes detached from CTF. Uncleaved Pc1 (Pc1U) resides primarily in the endoplasmic reticulum (ER), whereas both Pc1cFL and Pc1deN traffic through the secretory pathway in vivo. GPS cleavage is not a prerequisite, however, for Pc1 trafficking in vivo. Importantly, Pc1deN is predominantly found at the plasma membrane of renal epithelial cells. By functional genetic complementation with five Pkd1 mouse models, we discovered that CTF plays a crucial role in Pc1deN trafficking. Our studies support GPS cleavage as a critical regulatory mechanism of Pc1 biogenesis and trafficking for proper kidney development and homeostasis. PMID:24958103

  20. Decreased plant productivity resulting from plant group removal experiment constrains soil microbial functional diversity.

    PubMed

    Zhang, Ximei; Johnston, Eric R; Barberán, Albert; Ren, Yi; Lü, Xiaotao; Han, Xingguo

    2017-10-01

    Anthropogenic environmental changes are accelerating the rate of biodiversity loss on Earth. Plant diversity loss is predicted to reduce soil microbial diversity primarily due to the decreased variety of carbon/energy resources. However, this intuitive hypothesis is supported by sparse empirical evidence, and most underlying mechanisms remain underexplored or obscure altogether. We constructed four diversity gradients (0-3) in a five-year plant functional group removal experiment in a steppe ecosystem in Inner Mongolia, China, and quantified microbial taxonomic and functional diversity with shotgun metagenome sequencing. The treatments had little effect on microbial taxonomic diversity, but were found to decrease functional gene diversity. However, the observed decrease in functional gene diversity was more attributable to a loss in plant productivity, rather than to the loss of any individual plant functional group per se. Reduced productivity limited fresh plant resources supplied to microorganisms, and thus, intensified the pressure of ecological filtering, favoring genes responsible for energy production/conversion, material transport/metabolism and amino acid recycling, and accordingly disfavored many genes with other functions. Furthermore, microbial respiration was correlated with the variation in functional composition but not taxonomic composition. Overall, the amount of carbon/energy resources driving microbial gene diversity was identified to be the critical linkage between above- and belowground communities, contrary to the traditional framework of linking plant clade/taxonomic diversity to microbial taxonomic diversity. © 2017 John Wiley & Sons Ltd.

  1. Biodiversity increases functional and compositional resistance, but decreases resilience in phytoplankton communities.

    PubMed

    Baert, Jan M; De Laender, Frederik; Sabbe, Koen; Janssen, Colin R

    2016-12-01

    There is now ample evidence that biodiversity stabilizes aggregated ecosystem functions, such as primary production, in changing environments. In primary producer systems, this stabilizing effect is found to be driven by higher functional resistance (i.e., reduced changes in functions by environmental changes) rather than through higher functional resilience (i.e., rapid recovery following environmental changes) in more diverse systems. The stability of aggregated ecosystem functions directly depends on changes in species composition and by consequence their functional contributions to ecosystem functions. Still, it remains only theoretically explored how biodiversity can stabilize ecosystem functions by affecting compositional stability. Here, we demonstrate how biodiversity effects on compositional stability drive biodiversity effects on functional stability in diatom communities. In a microcosm experiment, we exposed 39 communities of five different levels of species richness (1, 2, 4, 6, and 8 species) to three concentrations of a chemical stressor (0, 25, and 250 μg/L atrazine) for four weeks, after which all communities were transferred to atrazine-free medium for three more weeks. Biodiversity simultaneously increased, increasing functional and compositional resistance, but decreased functional and compositional resilience. These results confirm the theoretically proposed link between biodiversity effects on functional and compositional stability in primary producer systems, and provide a mechanistic underpinning for observed biodiversity-stability relationships. Finally, we discuss how higher compositional stability can be expected to become increasingly important in stabilizing ecosystem functions under field conditions when multiple environmental stressors fluctuate simultaneously. © 2016 by the Ecological Society of America.

  2. Environmentally persistent free radicals decrease cardiac function before and after ischemia/reperfusion injury in vivo

    PubMed Central

    Lord, Kevin; Moll, David; Lindsey, John K.; Mahne, Sarah; Raman, Girija; Dugas, Tammy; Cormier, Stephania; Troxlair, Dana; Lomnicki, Slawo; Dellinger, Barry; Varner, Kurt

    2011-01-01

    Exposure to airborne particles is associated with increased cardiovascular morbidity and mortality. During the combustion of chlorine-containing hazardous materials and fuels, chlorinated hydrocarbons chemisorb to the surface of transition metal-oxide-containing particles, reduce the metal, and form an organic free radical. These radical-particle systems can survive in the environment for days and are called environmentally persistent free radicals (EPFRs). This study determined whether EPFRs could decrease left ventricular function before and after ischemia and reperfusion (I/R) in vivo. Male Brown Norway rats were dosed (8 mg/kg, i.t.) 24 hr prior to testing with particles containing the EPFR of 1, 2-dichlorobenzene (DCB230). DCB230 treatment decreased systolic and diastolic function. DCB230 also produced pulmonary and cardiac inflammation. After ischemia, systolic, but not diastolic function was significantly decreased in DCB230-treated rats. Ventricular function was not affected by I/R in control rats. There was greater oxidative stress in the heart and increased 8-isoprostane (biomarker of oxidative stress) in the plasma of treated vs control rats after I/R. These data demonstrate for the first time that DCB230 can produce inflammation and significantly decrease cardiac function at baseline and after I/R in vivo. Furthermore, these data suggest that EPFRs may be a risk factor for cardiac toxicity in healthy individuals and individuals with ischemic heart disease. Potential mechanisms involving cytokines/chemokines and/or oxidative stress are discussed. PMID:21385100

  3. Glutathione S-transferase iso-enzymes in perfusate from pumped kidneys are associated with delayed graft function

    PubMed Central

    Hall, Isaac E.; Bhangoo, Ronik S.; Reese, Peter P.; Doshi, Mona D.; Weng, Francis L.; Hong, Kwangik; Lin, Haiqun; Han, Gang; Hasz, Rick D.; Goldstein, Michael J.; Schröppel, Bernd; Parikh, Chirag R.

    2014-01-01

    Accurate and reliable assessment tools are needed in transplantation. The objective of this prospective, multicenter study was to determine the associations of the alpha and pi iso-enzymes of glutathione S-transferase (GST), measured from perfusate solution at the start and end (base and post) of kidney allograft machine perfusion, with subsequent delayed graft function (DGF). We also compared GST iso-enzyme perfusate levels from discarded versus transplanted kidneys. A total of 428 kidneys were linked to outcomes as recorded by the United Network of Organ Sharing. DGF, defined as any dialysis in the first week of transplant, occurred in 141 recipients (32%). Alpha and pi-GST levels significantly increased during machine perfusion. The adjusted relative risks (95% confidence interval) of DGF with each log-unit increase in base and post pi-GST were 1.14 (1.0-1.28) and 1.33 (1.02-1.72), respectively. Alpha-GST was not independently associated with DGF. There were no significant differences in GST values between discarded and transplanted kidneys, though renal resistance was significantly higher in discarded kidneys. We found pi-GST at the end of machine perfusion to be independently associated with DGF. Further studies should elucidate the utility of GST for identifying injured kidneys with regard to organ allocation, discard and recipient management decisions. PMID:24612768

  4. Glutathione S-transferase iso-enzymes in perfusate from pumped kidneys are associated with delayed graft function.

    PubMed

    Hall, I E; Bhangoo, R S; Reese, P P; Doshi, M D; Weng, F L; Hong, K; Lin, H; Han, G; Hasz, R D; Goldstein, M J; Schröppel, B; Parikh, C R

    2014-04-01

    Accurate and reliable assessment tools are needed in transplantation. The objective of this prospective, multi-center study was to determine the associations of the alpha and pi iso-enzymes of glutathione S-transferase (GST), measured from perfusate solution at the start and end (base and post) of kidney allograft machine perfusion, with subsequent delayed graft function (DGF). We also compared GST iso-enzyme perfusate levels from discarded versus transplanted kidneys. A total of 428 kidneys were linked to outcomes as recorded by the United Network of Organ Sharing. DGF, defined as any dialysis in the first week of transplant, occurred in 141 recipients (32%). Alpha- and pi-GST levels significantly increased during machine perfusion. The adjusted relative risks (95% confidence interval) of DGF with each log-unit increase in base and post pi-GST were 1.14 (1.0-1.3) and 1.36 (1.1-1.8), respectively. Alpha-GST was not independently associated with DGF. There were no significant differences in GST values between discarded and transplanted kidneys, though renal resistance was significantly higher in discarded kidneys. We found pi-GST at the end of machine perfusion to be independently associated with DGF. Further studies should elucidate the utility of GST for identifying injured kidneys with regard to organ allocation, discard and recipient management decisions. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

  5. 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.

  6. Improved lipids, diastolic pressure and kidney function are potential contributors to familial longevity: a study on 60 Chinese centenarian families.

    PubMed

    He, Yong-Han; Pu, Shao-Yan; Xiao, Fu-Hui; Chen, Xiao-Qiong; Yan, Dong-Jing; Liu, Yao-Wen; Lin, Rong; Liao, Xiao-Ping; Yu, Qin; Yang, Li-Qin; Yang, Xing-Li; Ge, Ming-Xia; Li, Ying; Jiang, Jian-Jun; Cai, Wang-Wei; Kong, Qing-Peng

    2016-02-25

    Centenarians are a good healthy aging model. Interestingly, centenarians' offspring are prone to achieve longevity. Here we recruited 60 longevity families and investigated the blood biochemical indexes of family members to seek candidate factors associated with familial longevity. First, associations of blood indexes with age were tested. Second, associations of blood parameters in centenarians (CEN) with their first generation of offspring (F1) and F1 spouses (F1SP) were analyzed. Third, genes involved in regulating target factors were investigated. We found that total cholesterol (TC) and triglyceride (TG) increased with age (20-80 years), but decreased in CEN. Similarly, blood urea nitrogen (BUN) and blood creatinine (BCr) increased with age (20-80 years), but were maintained on a plateau in CEN. Importantly, we first revealed dual changes in blood pressure, i.e., decreased diastolic blood pressure but increased systolic blood pressure in CEN, which associated with altered CST3 expression. Genetic analysis revealed a significant association of blood uric acid (BUA) and BCr in CEN with F1 but not with F1SP, suggesting they may be heritable traits. Taken together, our results suggest serum lipids, kidney function and especially diastolic pressure rather than systolic pressure were improved in CEN or their offspring, suggesting these factors may play an important role in familial longevity.

  7. Polycystin 1 loss of function is directly linked to an imbalance in G-protein signaling in the kidney.

    PubMed

    Zhang, Bo; Tran, Uyen; Wessely, Oliver

    2018-03-22

    The development of the kidney relies on the establishment and maintenance of a precise tubular diameter of its functional units, the nephrons. This process is disrupted in polycystic kidney disease (PKD), resulting in dilations of the nephron and renal cyst formation. In the course of exploring G-protein-coupled signaling in the Xenopus pronephric kidney, we discovered that loss of the G-protein α subunit, Gnas, results in a PKD phenotype. Polycystin 1, one of the genes mutated in human PKD, encodes a protein resembling a G-protein-coupled receptor. Furthermore, deletion of the G-protein-binding domain present in the intracellular C terminus of polycystin 1 impacts functionality. A comprehensive analysis of all the G-protein α subunits expressed in the Xenopus pronephric kidney demonstrates that polycystin 1 recruits a select subset of G-protein α subunits and that their knockdown - as in the case of Gnas - results in a PKD phenotype. Mechanistically, the phenotype is caused by increased endogenous G-protein β/γ signaling and can be reversed by pharmacological inhibitors as well as knocking down Gnb1. Together, our data support the hypothesis that G proteins are recruited to the intracellular domain of PKD1 and that this interaction is crucial for its function in the kidney. © 2018. Published by The Company of Biologists Ltd.

  8. New insights into potential functions for the protein 4.1superfamily of proteins in kidney epithelium

    SciTech Connect

    Calinisan, Venice; Gravem, Dana; Chen, Ray Ping-Hsu

    2005-06-17

    Members of the protein 4.1 family of adapter proteins are expressed in a broad panel of tissues including various epithelia where they likely play an important role in maintenance of cell architecture and polarity and in control of cell proliferation. We have recently characterized the structure and distribution of three members of the protein 4.1 family, 4.1B, 4.1R and 4.1N, in mouse kidney. We describe here binding partners for renal 4.1 proteins, identified through the screening of a rat kidney yeast two-hybrid system cDNA library. The identification of putative protein 4.1-based complexes enables us to envision potential functions for 4.1more » proteins in kidney: organization of signaling complexes, response to osmotic stress, protein trafficking, and control of cell proliferation. We discuss the relevance of these protein 4.1-based interactions in kidney physio-pathology in the context of their previously identified functions in other cells and tissues. Specifically, we will focus on renal 4.1 protein interactions with beta amyloid precursor protein (beta-APP), 14-3-3 proteins, and the cell swelling-activated chloride channel pICln. We also discuss the functional relevance of another member of the protein 4.1 superfamily, ezrin, in kidney physiopathology.« less

  9. Reduced Abd-B Hox function during kidney development results in lineage infidelity.

    PubMed

    Magella, Bliss; Mahoney, Robert; Adam, Mike; Potter, S Steven

    2018-06-15

    Hox genes can function as key drivers of segment identity, with Hox mutations in Drosophila often resulting in dramatic homeotic transformations. In addition, however, they can serve other essential functions. In mammals, the study of Hox gene roles in development is complicated by the presence of four Hox clusters with a total of 39 genes showing extensive functional overlap. In this study, in order to better understand shared core Hox functions, we examined kidney development in mice with frameshift mutations of multiple Abd-B type Hox genes. The resulting phenotypes included dramatically reduced branching morphogenesis of the ureteric bud, premature depletion of nephron progenitors and abnormal development of the stromal compartment. Most unexpected, however, we also observed a cellular level lineage infidelity in nephron segments. Scattered cells within the proximal tubules, for example, expressed genes normally expressed only in collecting ducts. Multiple combinations of inappropriate nephron segment specific marker expression were found. In some cases, cells within a tubule showed incorrect identity, while in other cases cells showed ambiguous character, with simultaneous expression of genes associated with more than one nephron segment. These results give evidence that Hox genes have an overlapping core function at the cellular level in driving and/or maintaining correct differentiation decisions. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Sexual Function and Testosterone Level in Men With Conservatively Treated Chronic Kidney Disease.

    PubMed

    Fugl-Meyer, Kerstin S; Nilsson, Marie; Hylander, Britta; Lehtihet, Mikael

    2017-07-01

    Sexual dysfunctions are common, but underrecognized, in patients with chronic kidney disease (CKD) and are inversely associated with the glomerular filtration rate (GFR). Sexual dysfunctions may affect quality of life in males with CKD. The aim of this study was to analyze the relationship among sex hormones, sexual function, and sexual satisfaction in a group of men between 18 and 50 years of age with CKD Stages 1 to 5 not treated with hemodialysis or peritoneal dialysis. Fasting blood samples for hemoglobin, testosterone, prolactin, and luteinizing hormone and questionnaire surveys (Sexual Complaints Screener for Men, International Index of Erectile Function, and Aging Male Symptom scale) were evaluated in 100consecutive men. Higher CKD stage (i.e., lower renal function) had a statistically significant ( p < .01) correlation with lower total testosterone, free testosterone, and hemoglobin levels, and higher luteinizing hormone and prolactin levels. Sexual function/dysfunctions were not significantly associated with CKD stage, even after adjustment for age and serum testosterone. The results indicate that CKD stage is a factor affecting testosterone levels in combination with age in men between 18 and 50 years of age at different stages of CKD but not treated with hemodialysis or peritoneal dialysis. Sexual dysfunctions are common but not strongly correlated to testosterone levels, prolactin levels, and survey (Sexual Complaints Screener for Men, International Index of Erectile Function, and Aging Male Symptom scale) responses in patients with CKD.

  11. Nitric oxide decreases coagulation protein function in rabbits as assessed by thromboelastography.

    PubMed

    Nielsen, V G

    2001-02-01

    Nitric oxide (NO) is administered via infusion of donors such as nitroglycerin or in inhaled form for treatment of ischemia and pulmonary hypertension, respectively. In rabbits, the NO donor, DETANONOate, decreases whole blood clotting function as assessed by thromboelastographic variables (R, reaction time; alpha, angle; and G, a measure of clot strength). I hypothesized that DETANONOate-derived NO would adversely affect coagulation protein and platelet function. Blood obtained from ear arteries of conscious rabbits (n = 8) anticoagulated with sodium citrate. The blood was then incubated with 0 or 10mM DETANONOate for 30 min. After incubation and recalcification, thromboelastography was performed for 60 min under four conditions: 1) 0mM DETANONOate, 2) 0mM DETANONOate with platelet inhibition with cytochalasin D, 3) 10mM DETANONOate, and 4) 10mM DETANONOate with platelet inhibition. DETANONOate significantly (P < 0.05) increased R and decreased alpha and G in samples with or without platelet inhibition, compared with samples not exposed to DETANONOate. Lastly, the percentage of total G (G(T)) attributable to platelet function (G(P)) was significantly more in the absence of DETANONOate (G(P) = 92.3% +/- 1.6%; mean +/- SD) than after exposure to DETANONOate (G(P) = 90.2% +/- 2.3%). DETANONOate-derived NO significantly decreased coagulation protein function and platelet function. Coagulation protein function may be similarly affected in clinical situations involving the administration of NO or NO donors.

  12. 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.

  13. Relationship between cognitive function and prevalence of decrease in intrinsic academic motivation in adolescents.

    PubMed

    Mizuno, Kei; Tanaka, Masaaki; Fukuda, Sanae; Imai-Matsumura, Kyoko; Watanabe, Yasuyoshi

    2011-01-14

    Decrease in intrinsic motivation is a common complaint among elementary and junior high school students, and is related to poor academic performance. Since grade-dependent development of cognitive functions also influences academic performance by these students, we examined whether cognitive functions are related to the prevalence of decrease in intrinsic academic motivation. The study group consisted of 134 elementary school students from 4th to 6th grades and 133 junior high school students from 7th to 9th grades. Participants completed a questionnaire on intrinsic academic motivation. They also performed paper-and-pencil and computerized cognitive tests to measure abilities in motor processing, spatial construction, semantic fluency, immediate memory, short-term memory, delayed memory, spatial working memory, and selective, alternative, and divided attention. In multivariate logistic regression analyses adjusted for grade and gender, scores of none of the cognitive tests were correlated with the prevalence of decrease in intrinsic academic motivation in elementary school students. However, low digit span forward test score and score for comprehension of the story in the kana pick-out test were positively correlated with the prevalence of decrease in intrinsic academic motivation in junior high school students. The present findings suggest that decrease in capacity for verbal memory is associated with the prevalence of decrease in intrinsic academic motivation among junior high school students.

  14. Relationship between cognitive function and prevalence of decrease in intrinsic academic motivation in adolescents

    PubMed Central

    2011-01-01

    Background Decrease in intrinsic motivation is a common complaint among elementary and junior high school students, and is related to poor academic performance. Since grade-dependent development of cognitive functions also influences academic performance by these students, we examined whether cognitive functions are related to the prevalence of decrease in intrinsic academic motivation. Methods The study group consisted of 134 elementary school students from 4th to 6th grades and 133 junior high school students from 7th to 9th grades. Participants completed a questionnaire on intrinsic academic motivation. They also performed paper-and-pencil and computerized cognitive tests to measure abilities in motor processing, spatial construction, semantic fluency, immediate memory, short-term memory, delayed memory, spatial working memory, and selective, alternative, and divided attention. Results In multivariate logistic regression analyses adjusted for grade and gender, scores of none of the cognitive tests were correlated with the prevalence of decrease in intrinsic academic motivation in elementary school students. However, low digit span forward test score and score for comprehension of the story in the kana pick-out test were positively correlated with the prevalence of decrease in intrinsic academic motivation in junior high school students. Conclusions The present findings suggest that decrease in capacity for verbal memory is associated with the prevalence of decrease in intrinsic academic motivation among junior high school students. PMID:21235802

  15. Limited left atrial surgical ablation effectively treats atrial fibrillation but decreases left atrial function.

    PubMed

    Compier, Marieke G; Tops, Laurens F; Braun, Jerry; Zeppenfeld, Katja; Klautz, Robert J; Schalij, Martin J; Trines, Serge A

    2017-04-01

    Limited left atrial (LA) surgical ablation with bipolar radiofrequency is considered to be an effective procedure for treatment of atrial fibrillation (AF). We studied whether limited LA surgical ablation concomitant to cardiac surgery is able to maintain LA function. Thirty-six consecutive patients (age 66 ± 12 years, 53% male, 78% persistent AF) scheduled for valve surgery and/or coronary revascularization and concomitant LA surgical ablation were included. Epicardial pulmonary vein isolation (PVI) and additional endo-epicardial lines were performed using bipolar radiofrequency. An age- and gender-matched control group (n = 36, age 66 ± 9 years, 69% male, 81% paroxysmal AF) was selected from patients undergoing concomitant epicardial PVI only. Left atrial dimensions and function were assessed on two-dimensional echocardiography preoperatively and at 3- and 12-month follow-up. Sinus rhythm (SR) maintenance was 67% for limited LA ablation and 81% for PVI at 1-year follow-up (P = 0.18). Left atrial volume decreased from 72 ± 21 to 50 ± 14 mL (31%, P < 0.01) after limited LA ablation and from 65 ± 23 to 56 ± 20 mL (14%, P < 0.01) after PVI. Atrial transport function was restored in 54% of patients in SR after limited LA ablation compared with 100% of patients in SR after PVI. Atrial strain and contraction parameters (LA ejection fraction, A-wave velocity, reservoir function, and strain rate) significantly decreased after limited LA ablation. After PVI, strain and contraction parameters remained unchanged. Even limited LA ablation decreased LA volume, contraction, transport function, and compliance, indicating both reverse remodelling combined with significant functional deterioration. In contrast, surgical PVI decreased LA volume while function remained unchanged. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

  16. The investigation of specific biochemical markers in monitoring kidney function of drug addicts.

    PubMed

    Gąsiorowski, Jacek; Marchewka, Zofia; Łapiński, Łukasz; Szymańska, Beata; Głowacka, Krystyna; Knysz, Brygida; Długosz, Anna; Wiela-Hojeńska, Anna

    2013-12-05

    An increasingly important issue in the Polish population is drug abuse. It leads to extensive damage of parenchymal organs, including kidney. Establishing early markers of organ damage and their monitoring during rehabilitation therapy is therefore of pivotal importance. This study evaluated the utility of highly specific and selective markers (NGAL, IL-18, a and π-GST isoenzyme, and ß2-M). The influence of opioid drugs and other factors on kidney function (HIV and HCV infections, duration and the kind of drugs abused) was determined. Urine collected from 83 subjects who abused drugs and 33 healthy volunteers was tested with ELISA using specific antibodies (IBL, Biotron, Bioporto-Diagnostics). HIV infection was confirmed with western-blotting and HCV with PCR. CD4 lymphocytes were quantified with flow cytometry. RFLP and PCR were used to determine the viral load of HIV and HCV (genotype). A significant increase of IL-18, NGAL and β2M activity in heroin addicts compared to the control group was noted as well as the influence of HIV infection on NGAL and β2M excretion. A statistically significant (p=0.04) correlation between the viral load and IL-18 concentration was noted while no significant influence of the duration and the kind of drugs abused, the route of intake or the age of addicts was seen. Only the NGAL concentration was sex dependent and significantly higher in women. This study showed the specific, clinical utility of IL-18, NGAL, and β2M in the evaluation of renal function in drug addicts. Early detection of nephropathy with biochemical indicators might help prevent severe conditions that require hospitalization and intensive care.

  17. 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.

  18. The Role of Endothelin System in Renal Structure and Function during the Postnatal Development of the Rat Kidney.

    PubMed

    Albertoni Borghese, María F; Ortiz, María C; Balonga, Sabrina; Moreira Szokalo, Rocío; Majowicz, Mónica P

    2016-01-01

    Renal development in rodents, unlike in humans, continues during early postnatal period. We aimed to evaluate whether the pharmacological inhibition of Endothelin system during this period affects renal development, both at structural and functional level in male and female rats. Newborn rats were treated orally from postnatal day 1 to 20 with vehicle or bosentan (Actelion, 20 mg/kg/day), a dual endothelin receptor antagonist (ERA). The animals were divided in 4 groups: control males, control females, ERA males and ERA females. At day 21, we evaluated renal function, determined the glomerular number by a maceration method and by morphometric analysis and evaluated possible structural renal alterations by three methods: 〈alpha〉-Smooth muscle actin (α-SMA) immunohistochemistry, Masson's trichrome and Sirius red staining. The pharmacological inhibition of Endothelin system with a dual ERA during the early postnatal period of the rat did not leads to renal damage in the kidneys of male and female rats. However, ERA administration decreased the number of glomeruli, the juxtamedullary filtration surface area and the glomerular filtration rate and increased the proteinuria. These effects could predispose to hypertension or renal diseases in the adulthood. On the other hand, these effects were more pronounced in male rats, suggesting that there are sex differences that could be greater later in life. These results provide evidence that Endothelin has an important role in rat renal postnatal development. However these results do not imply that the same could happen in humans, since human renal development is complete at birth.

  19. Increased functional load on mouse kidney proximal tubule epithelial cells causes changes in nucleolar 3-D architecture.

    PubMed

    Chelidze, P V; Dzidziguri, D V; Tumanishvili, G D

    1998-05-01

    Ultrastructural 3-D analysis of nucleolar architecture and Ag-NOR protein distribution in mouse kidney-cortex proximal-tubule epithelium has been performed. A principal scheme of structural changes of the nucleolus and organization of its components during the intensification of pre-rRNA synthesis (dynamic model of a nucleolus) based on computer spatial modelling has been advanced. According to the nucleolar composition, three groups of cells, which differ from each other by rRNA synthesis, are defined in normal kidney. Most nephron proximal-section cells (about 52%) are characterized by lower activity of RNA synthesis. Such kind of cells are defined as group I (nucleolar diameter 0.7-1.5 microm) and always contain resting, ring-shaped or close to ring-shaped dense nucleoli, which have 2 or 3 fibrillar centers. Nucleoli of group II cells (about 37%, nucleolar diameter 1.5-2.5 microm) have a higher level of activity, contain 4-7 fibrillar centers, and their structural organization is close to reticulated forms due to the first indications of vacuolar network (identified as prereticulated nucleoli). The most active cells of group III (about 11%, nucleolar diameter 2.5-3.5 microm) include cells with typical reticulated nucleoli with a well expressed vacuolar network and numerous fibrillar centers (18-22). Increased functional load of the epithelium caused by unilateral nephrectomy and diuretic (4-chlor-H [2-furylmethyl] 5-sulphamyl-antranic acid) injection changed the proportion of the different cell groups: group I decreased (about 25%), whereas groups II and III increased (about 8% and 17%, respectively). The increase of nucleolar activity first causes a deformation of the individual fibrillar centers as well as complication and growth of their surface. Further, a progressive fragmentation of the fibrillar centers and the growth of their total volume is observed. The complication and growth of the total volume of Ag-positive zones is another indication of the

  20. Krüppel-like factor 6 regulates mitochondrial function in the kidney

    PubMed Central

    Mallipattu, Sandeep K.; Horne, Sylvia J.; D’Agati, Vivette; Narla, Goutham; Liu, Ruijie; Frohman, Michael A.; Dickman, Kathleen; Chen, Edward Y.; Ma’ayan, Avi; Bialkowska, Agnieszka B.; Ghaleb, Amr M.; Nandan, Mandayam O.; Jain, Mukesh K.; Daehn, Ilse; Chuang, Peter Y.; Yang, Vincent W.; He, John C.

    2015-01-01

    Maintenance of mitochondrial structure and function is critical for preventing podocyte apoptosis and eventual glomerulosclerosis in the kidney; however, the transcription factors that regulate mitochondrial function in podocyte injury remain to be identified. Here, we identified Krüppel-like factor 6 (KLF6), a zinc finger domain transcription factor, as an essential regulator of mitochondrial function in podocyte apoptosis. We observed that podocyte-specific deletion of Klf6 increased the susceptibility of a resistant mouse strain to adriamycin-induced (ADR-induced) focal segmental glomerulosclerosis (FSGS). KLF6 expression was induced early in response to ADR in mice and cultured human podocytes, and prevented mitochondrial dysfunction and activation of intrinsic apoptotic pathways in these podocytes. Promoter analysis and chromatin immunoprecipitation studies revealed that putative KLF6 transcriptional binding sites are present in the promoter of the mitochondrial cytochrome c oxidase assembly gene (SCO2), which is critical for preventing cytochrome c release and activation of the intrinsic apoptotic pathway. Additionally, KLF6 expression was reduced in podocytes from HIV-1 transgenic mice as well as in renal biopsies from patients with HIV-associated nephropathy (HIVAN) and FSGS. Together, these findings indicate that KLF6-dependent regulation of the cytochrome c oxidase assembly gene is critical for maintaining mitochondrial function and preventing podocyte apoptosis. PMID:25689250

  1. 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

  2. Epinephrine and left atrial and left ventricular diastolic function decrease in normal subjects.

    PubMed

    Fuenmayor, Abdel J; Solórzano, Moisés I; Gómez, Luisangelly

    2016-10-01

    We assessed the effect of epinephrine over left atrial and left ventricular diastolic function in subjects without structural heart disease. Twenty-seven, 34.6±17.2year-old patients without structural heart disease were included. Intravenous epinephrine (50 to 100ng/kg/min) was infused. Left atrial and ventricular functions were evaluated by means of echocardiography before and during the epinephrine infusion. No complications were observed. Significant increases in heart rate and systolic blood pressure were recorded. Both left atrial (minimal and maximal) volumes increased but increase in the minimal volume was more pronounced, and the ejection fraction diminished. Left atrial expansion index decreased and the fraction of left ventricular inflow volume resulting from atrial contraction increased. Two patients displayed abnormal left ventricular diastolic function. During epinephrine infusion, E/A and e' decreased, and isovolumetric relaxation time increased. In this group of young adults without structural heart disease, epinephrine infusion was safe, did not produce any complications, and induced a small but significant decrease in left atrial function and left ventricular diastolic function. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Kyphoplasty increases vertebral height, decreases both pain score and opiate requirements while improving functional status.

    PubMed

    Tolba, Reda; Bolash, Robert B; Shroll, Joshua; Costandi, Shrif; Dalton, Jarrod E; Sanghvi, Chirag; Mekhail, Nagy

    2014-03-01

    Vertebral compression fractures can result from advanced osteoporosis, or less commonly from metastatic or traumatic insults to the vertebral column, and result in disabling pain and decreased functional capacity. Various vertebral augmentation options including kyphoplasty aim at preventing the sequelae of pain and immobility that can develop as the result of the vertebral fractures. The mechanism for pain relief following kyphoplasty is not entirely understood, and the restoration of a portion of the lost vertebral height is a subject of debate. We retrospectively reviewed radiographic imaging, pain relief, analgesic intake and functional outcomes in 67 consecutive patients who underwent single- or multilevel kyphoplasty with the primary goal of quantifying the restoration of lost vertebral height. We observed a mean of 45% of the lost vertebral height restored postprocedurally. Secondarily, kyphoplasty was associated with significant decreases in pain scores, daily morphine consumption and improvement in patient-reported functional measures. © 2013 World Institute of Pain.

  4. Chemosensory interaction: acquired olfactory impairment is associated with decreased taste function.

    PubMed

    Landis, Basile N; Scheibe, Mandy; Weber, Cornelia; Berger, Robert; Brämerson, Annika; Bende, Mats; Nordin, Steven; Hummel, Thomas

    2010-08-01

    Olfaction, taste and trigeminal function are three distinct modalities. However, in daily life they are often activated concomitantly. In health and disease, it has been shown that in two of these senses, the trigeminal and olfactory senses, modification of one sense leads to changes in the other sense and vice versa. The objective of the study was to investigate whether and (if so) how, the third modality, taste, is influenced by olfactory impairment. We tested 210 subjects with normal (n = 107) or impaired (n = 103) olfactory function for their taste identification capacities. Validated tests were used for olfactory and gustatory testing (Sniffin' Sticks, Taste Strips). In an additional experiment, healthy volunteers underwent reversible olfactory cleft obstruction to investigate short-time changes of gustatory function after olfactory alteration. Mean gustatory identification (taste strip score) for the subjects with impaired olfaction was 19.4 +/- 0.6 points and 22.9 +/- 0.5 points for those with normal olfactory function (t = 4.6, p < 0.001). The frequencies of both, smell and taste impairments interacted significantly (Chi(2), F = 16.4, p < 0.001), and olfactory and gustatory function correlated (r (210) = 0.30, p < 0.001). Neither age nor olfactory impairment cause effects interfered with this olfactory-gustatory interaction. In contrast, after short-lasting induced olfactory decrease, gustatory function remained unchanged. The present study suggests that longstanding impaired olfactory function is associated with decreased gustatory function. These findings seem to extend previously described mutual chemosensory interactions also to smell and taste. It further raises the question whether chemical senses in general decrease mutually after acquired damage.

  5. Functional properties and in vitro trypsin digestibility of red kidney bean (Phaseolus vulgaris L.) protein isolate: Effect of high-pressure treatment.

    PubMed

    Yin, Shou-Wei; Tang, Chuan-He; Wen, Qi-Biao; Yang, Xiao-Quan; Li, Lin

    2008-10-15

    The effects of high-pressure (HP) treatment at 200-600MPa, prior to freeze-drying, on some functional properties and in vitro trypsin digestibility of vicilin-rich red kidney bean (Phaseolus vulgaris L.) protein isolate (KPI) were investigated. Surface hydrophobicity and free sulfhydryl (SH) and disulfide bond (SS) contents were also evaluated. HP treatment resulted in gradual unfolding of protein structure, as evidenced by gradual increases in fluorescence strength and SS formation from SH groups, and decrease in denaturation enthalpy change. The protein solubility of KPI was significantly improved at pressures of 400MPa or higher, possibly due to formation of soluble aggregate from insoluble precipitate. HP treatment at 200 and 400MPa significantly increased emulsifying activity index (EAI) and emulsion stability index (ESI); however, EAI was significantly decreased at 600MPa (relative to untreated KPI). The thermal stability of the vicilin component was not affected by HP treatment. Additionally, in vitro trypsin digestibility of KPI was decreased only at a pressure above 200MPa and for long incubation time (e.g., 120min). The data suggest that some physiochemical and functional properties of vicilin-rich kidney proteins can be improved by means of high-pressure treatment. Copyright © 2008 Elsevier Ltd. All rights reserved.

  6. Neurocognitive, Social-Behavioral, and Adaptive Functioning in Preschool Children with Mild to Moderate Kidney Disease

    PubMed Central

    Hooper, Stephen R.; Gerson, Arlene C.; Johnson, Rebecca J.; Mendley, Susan R.; Shinnar, Shlomo; Lande, Marc B.; Matheson, Matthew B.; Gipson, Debbie S.; Morgenstern, Bruce; Warady, Bradley A.; Furth, Susan L.

    2016-01-01

    Objective The negative impact of End Stage Kidney Disease on cognitive function in children is well established, but no studies have examined the neurocognitive, social-behavioral, and adaptive behavior skills of preschool children with mild to moderate chronic kidney disease (CKD). Methods Participants included 124 preschool children with mild to moderate CKD, ages 12-68 months (median=3.7 years), and an associated mean glomerular filtration rate (GFR) of 50.0 ml/min per 1.73m2. In addition to level of function and percent of participants scoring≥1SD below the test mean, regression models examined the associations between biomarkers of CKD (GFR, anemia, hypertension, seizures, abnormal birth history), and Developmental Level/IQ, attention regulation, and parent ratings of executive functions, social-behavior, and adaptive behaviors. Results Median scores for all measures were in the average range; however, 27% were deemed at-risk for a Developmental Level/IQ<85, 20% were at-risk for attention variability, and parent ratings indicated 30% and 37% to be at-risk for executive dysfunction and adaptive behavior problems, respectively. Approximately 43% were deemed at-risk on two or more measures. None of the disease-related variables were significantly associated with these outcomes, although the presence of hypertension approached significance for attention variability (p<.09). Abnormal birth history and lower maternal education were significantly related to lower Developmental Level/IQ; seizures were related to lower parental ratings of executive function and adaptive behavior; and abnormal birth history was significantly related to lower ratings of adaptive behavior. When predicting risk status, the logistic regression did evidence both higher GFR and the lack of anemia to be associated with more intact Developmental Level/IQ. Conclusions These findings suggest relatively intact functioning for preschool children with mild to moderate CKD, but the need for ongoing

  7. 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.

  8. Dietary Potential Renal Acid Load and Risk of Albuminuria and Reduced Kidney Function in the Jackson Heart Study.

    PubMed

    Banerjee, Tanushree; Tucker, Katherine; Griswold, Michael; Wyatt, Sharon B; Harman, Jane; Young, Bessie; Taylor, Herman; Powe, Neil R

    2018-07-01

    Diets high in sulfur-rich protein and low in fruit and vegetables affect human acid-base balance adversely and may have a harmful effect on progression of chronic kidney disease (CKD). Little is known about the relationship of participant characteristics, dietary acid load (DAL), and kidney injury in African-Americans with high risk of CKD progression. We examined the association of DAL with CKD in 3,257 African-Americans aged >20 years in Jackson Heart Study. DAL was measured with nutrient intakes assessed with a food frequency questionnaire, using a model described by Remer and Manz. We tested associations of participant characteristics with DAL using median regression, and associations of DAL with albuminuria (>17 mg/g for men, >25 mg/g for women), reduced kidney function (eGFR <60 mL/minute/1.73 m 2 ), or CKD defined as albuminuria or reduced kidney function using logistic regression. We further explored whether endothelin and aldosterone production in participants with hypertension mediated risk of albuminuria or reduced kidney function due to the intake of an acid-inducing diet. Younger adults, men, and those with higher body mass index had higher DAL. Higher DAL, compared with lower, was associated with greater odds of reduced kidney function (OR [95% CI]: 2.82 [1.40-4.75]). Higher DAL was also associated with greater risk of CKD, and this persisted after adjustment for confounders. Results were similar in adults with hypertension; the OR [95% CI] for highest, versus lowest, tertile of DAL with albuminuria was 1.66 [1.01-2.59]. Aldosterone and endothelin mediated the association between DAL and albuminuria; the OR [95% CI] in the highest tertile was no longer significant 1.53 [0.97-2.40] after their inclusion. Higher DAL was associated with higher prevalence of CKD and with reduced kidney function. DAL may be an important target for future interventions in African-Americans at high risk of CKD. Copyright © 2018 National Kidney Foundation, Inc

  9. 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.

  10. 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

  11. Neural control of the kidney: functionally specific renal sympathetic nerve fibers.

    PubMed

    DiBona, G F

    2000-11-01

    The sympathetic nervous system provides differentiated regulation of the functions of various organs. This differentiated regulation occurs via mechanisms that operate at multiple sites within the classic reflex arc: peripherally at the level of afferent input stimuli to various reflex pathways, centrally at the level of interconnections between various central neuron pools, and peripherally at the level of efferent fibers targeted to various effectors within the organ. In the kidney, increased renal sympathetic nerve activity regulates the functions of the intrarenal effectors: the tubules, the blood vessels, and the juxtaglomerular granular cells. This enables a physiologically appropriate coordination between the circulatory, filtration, reabsorptive, excretory, and renin secretory contributions to overall renal function. Anatomically, each of these effectors has a dual pattern of innervation consisting of a specific and selective innervation by unmyelinated slowly conducting C-type renal sympathetic nerve fibers in addition to an innervation that is shared among all the effectors. This arrangement permits the maximum flexibility in the coordination of physiologically appropriate responses of the tubules, the blood vessels, and the juxtaglomerular granular cells to a variety of homeostatic requirements.

  12. Intraoperative red blood cell transfusion, delayed graft function, and infection after kidney transplant: an observational cohort study.

    PubMed

    Mazzeffi, Michael; Jonna, Srikar; Blanco, Natalia; Mavrothalassitis, Orestes; Odekwu, Obi; Fontaine, Magali; Rock, Peter; Tanaka, Kenichi; Thom, Kerri

    2018-06-01

    Kidney transplant patients are frequently anemic and at risk for red blood cell (RBC) transfusion. Previous studies suggest that pre-transplant RBC transfusion may improve kidney transplant outcomes; however, RBC transfusion is also associated with infection. The purpose of our study was to characterize the relationships between intraoperative RBC transfusion, delayed graft function (DGF), postoperative surgical site infection (SSI), and sepsis. Analysis was performed on a historical cohort of adult kidney transplant patients from a single medical center during a two-year period. Crude odds ratios for DGF, superficial and deep SSI, and sepsis were calculated for transfused patients and multivariate regression was used to control for potential confounders when significant relationships were identified. Four hundred forty-one patients had kidney transplant during the study period; 27.0% had RBC transfusion, 38.8% had DGF, 7.0% had superficial SSI, 7.9% had deep SSI, and 1.8% had sepsis. High dose RBC transfusion was associated with improved graft function, but this was negated after adjusting for confounders (OR = 0.86, 95% CI  0.26 to 2.88). There was no association between RBC transfusion and SSI. RBC transfusion was independently associated with sepsis (OR = 8.98, 95% CI  1.52 to 53.22), but the confidence interval was wide. Intraoperative RBC transfusion during kidney transplant is not associated with improved allograft function or incisional SSI, but is associated with postoperative sepsis. RBCs should not be liberally transfused during kidney transplant surgery to improve graft outcomes.

  13. Blood transfusion improves renal oxygenation and renal function in sepsis-induced acute kidney injury in rats.

    PubMed

    Zafrani, Lara; Ergin, Bulent; Kapucu, Aysegul; Ince, Can

    2016-12-20

    The effects of blood transfusion on renal microcirculation during sepsis are unknown. This study aimed to investigate the effect of blood transfusion on renal microvascular oxygenation and renal function during sepsis-induced acute kidney injury. Twenty-seven Wistar albino rats were randomized into four groups: a sham group (n = 6), a lipopolysaccharide (LPS) group (n = 7), a LPS group that received fluid resuscitation (n = 7), and a LPS group that received blood transfusion (n = 7). The mean arterial blood pressure, renal blood flow, and renal microvascular oxygenation within the kidney cortex were recorded. Acute kidney injury was assessed using the serum creatinine levels, metabolic cost, and histopathological lesions. Nitrosative stress (expression of endothelial (eNOS) and inducible nitric oxide synthase (iNOS)) within the kidney was assessed by immunohistochemistry. Hemoglobin levels, pH, serum lactate levels, and liver enzymes were measured. Fluid resuscitation and blood transfusion both significantly improved the mean arterial pressure and renal blood flow after LPS infusion. Renal microvascular oxygenation, serum creatinine levels, and tubular damage significantly improved in the LPS group that received blood transfusion compared to the group that received fluids. Moreover, the renal expression of eNOS was markedly suppressed under endotoxin challenge. Blood transfusion, but not fluid resuscitation, was able to restore the renal expression of eNOS. However, there were no significant differences in lactic acidosis or liver function between the two groups. Blood transfusion significantly improved renal function in endotoxemic rats. The specific beneficial effect of blood transfusion on the kidney could have been mediated in part by the improvements in renal microvascular oxygenation and sepsis-induced endothelial dysfunction via the restoration of eNOS expression within the kidney.

  14. Chronic kidney disease: Pathological and functional evaluation with intravoxel incoherent motion diffusion-weighted imaging.

    PubMed

    Mao, Wei; Zhou, Jianjun; Zeng, Mengsu; Ding, Yuqin; Qu, Lijie; Chen, Caizhong; Ding, Xiaoqiang; Wang, Yaqiong; Fu, Caixia

    2018-05-01

    Because chronic kidney disease (CKD) is a worldwide problem, accurate pathological and functional evaluation is required for planning treatment and follow-up. Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) can assess both capillary perfusion and tissue diffusion and may be helpful in evaluating renal function and pathology. To evaluate functional and pathological alterations in CKD by applying IVIM-DWI. Prospective study. In all, 72 CKD patients who required renal biopsy and 20 healthy volunteers. 1.5T. All subjects underwent IVIM-DWI of the kidneys, and image analysis was performed by two radiologists. The mean values of true diffusion coefficient (D), pseudo diffusion coefficient (D*), and perfusion fraction (f) were acquired from renal parenchyma. Correlation between IVIM-DWI parameters and estimated glomerular filtration rate (eGFR), as well as pathological damage, were assessed. One-way analysis of variance (ANOVA), paired sample t-test and Spearman correlation analysis. The paired sample t-test revealed that IVIM-DWI parameters were significantly lower in medulla than cortex for both patients and controls (P < 0.01). Regardless of whether eGFR was reduced, ANOVA revealed that f values of renal parenchyma were significantly lower in patients than controls (P < 0.05). Spearman correlation analysis revealed that there were positive correlations between eGFR and D (cortex, r = 0.466, P < 0.001; medulla, r = 0.491, P < 0.001), and between eGFR and f (cortex, r = 0.713, P < 0.001; medulla, r = 0.512, P < 0.001). Negative correlations were found between f and glomerular injury (cortex, r = -0.773, P < 0.001; medulla, r = -0.629, P < 0.001), and between f and tubulointerstitial lesion (cortex, r = -0.728, P < 0.001; medulla, r = -0.547, P < 0.001). IVIM-DWI might be feasible for noninvasive evaluation of renal function and pathology of CKD, especially in detection of renal insufficiency at an early stage. 1

  15. Antiproteinuric therapy and Fabry nephropathy: factors associated with preserved kidney function during agalsidase-beta therapy

    PubMed Central

    Warnock, David G; Thomas, Christie P; Vujkovac, Bojan; Campbell, Ruth C; Charrow, Joel; Laney, Dawn A; Jackson, Leslie L; Wilcox, William R; Wanner, Christoph

    2015-01-01

    Background Nephropathy is an important feature of classical Fabry disease, which results in alpha-galactosidase A deficiency and cellular globotriaosylceramide accumulation. We report the safety and efficacy of antiproteinuric therapy with ACE inhibitors or angiotensin II receptor blockers (ARBs) in a study of classical Fabry patients receiving recombinant agalsidase-beta therapy. Methods and design The goal was maintenance of urine protein to creatinine ratio (UPCR) <0.5 g/g or a 50% reduction in baseline UPCR for 24 patients at eight study sites. The change in estimated glomerular filtration rate (eGFR) was assessed over 21 months of treatment. Results 18 out of 24 patients achieved the UPCR goal with eGFR slopes that were significantly better than six patients who did not achieve the UPCR goal (−3.6 (−4.8 to −1.1) versus −7.0 (−9.0 to −5.6) mL/min/1.73 m2/year, respectively, p=0.018). Despite achieving the UPCR goal, 67% (12/18 patients) still progressed with an eGFR slope <−2 mL/min/1.73 m2/year. Regression analysis showed that increased age at initiation of agalsidase-beta therapy was significantly associated with worsened kidney outcome. Hypotension and hyperkalaemia occurred in seven and eight patients, respectively, which required modification of antiproteinuric therapy but was not associated with serious adverse events. Conclusions This study documents the effectiveness of agalsidase-beta (1 mg/kg/2 weeks) and antiproteinuric therapy with ACE inhibitors and/or ARB in patients with severe Fabry nephropathy. Patients had preservation of kidney function if agalsidase-beta treatment was initiated at a younger age, and UPCR maintained at or below 0.5 g/g with antiproteinuric therapy. Trial registration number NCT00446862. PMID:26490103

  16. 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.

  17. Role of residual kidney function and convective volume on change in beta2-microglobulin levels in hemodiafiltration patients.

    PubMed

    Penne, E Lars; van der Weerd, Neelke C; Blankestijn, Peter J; van den Dorpel, Marinus A; Grooteman, Muriel P C; Nubé, Menso J; Ter Wee, Piet M; Lévesque, Renée; Bots, Michiel L

    2010-01-01

    Removal of beta2-microglobulin (beta2M) can be increased by adding convective transport to hemodialysis (HD). The aim of this study was to investigate the change in beta2M levels after 6-mo treatment with hemodiafiltration (HDF) and to evaluate the role of residual kidney function (RKF) and the amount of convective volume with this change. Predialysis serum beta2M levels were evaluated in 230 patients with and 176 patients without RKF from the CONvective TRAnsport STudy (CONTRAST) at baseline and 6 mo after randomization for online HDF or low-flux HD. In HDF patients, potential determinants of change in beta2M were analyzed using multivariable linear regression models. Mean serum beta2M levels decreased from 29.5 +/- 0.8 (+/-SEM) at baseline to 24.3 +/- 0.6 mg/L after 6 mo in HDF patients and increased from 31.9 +/- 0.9 to 34.4 +/- 1.0 mg/L in HD patients, with the difference of change between treatment groups being statistically significant (regression coefficient -7.7 mg/L, 95% confidence interval -9.5 to -5.6, P < 0.001). This difference was more pronounced in patients without RKF as compared with patients with RKF. In HDF patients, beta2M levels remained unchanged in patients with GFR >4.2 ml/min/1.73 m2. The beta2M decrease was not related to convective volume. This study demonstrated effective lowering of beta2M levels by HDF, especially in patients without RKF. The role of the amount of convective volume on beta2M decrease appears limited, possibly because of resistance to beta2M transfer between body compartments.

  18. Role of Residual Kidney Function and Convective Volume on Change in β2-Microglobulin Levels in Hemodiafiltration Patients

    PubMed Central

    Penne, E. Lars; van der Weerd, Neelke C.; Blankestijn, Peter J.; van den Dorpel, Marinus A.; Grooteman, Muriel P.C.; Nubé, Menso J.; Lévesque, Renée; Bots, Michiel L.

    2010-01-01

    Background and objectives: Removal of β2-microglobulin (β2M) can be increased by adding convective transport to hemodialysis (HD). The aim of this study was to investigate the change in β2M levels after 6-mo treatment with hemodiafiltration (HDF) and to evaluate the role of residual kidney function (RKF) and the amount of convective volume with this change. Design, setting, participants, & measurements: Predialysis serum β2M levels were evaluated in 230 patients with and 176 patients without RKF from the CONvective TRAnsport STudy (CONTRAST) at baseline and 6 mo after randomization for online HDF or low-flux HD. In HDF patients, potential determinants of change in β2M were analyzed using multivariable linear regression models. Results: Mean serum β2M levels decreased from 29.5 ± 0.8 (±SEM) at baseline to 24.3 ± 0.6 mg/L after 6 mo in HDF patients and increased from 31.9 ± 0.9 to 34.4 ± 1.0 mg/L in HD patients, with the difference of change between treatment groups being statistically significant (regression coefficient −7.7 mg/L, 95% confidence interval −9.5 to −5.6, P < 0.001). This difference was more pronounced in patients without RKF as compared with patients with RKF. In HDF patients, β2M levels remained unchanged in patients with GFR >4.2 ml/min/1.73 m2. The β2M decrease was not related to convective volume. Conclusions: This study demonstrated effective lowering of β2M levels by HDF, especially in patients without RKF. The role of the amount of convective volume on β2M decrease appears limited, possibly because of resistance to β2M transfer between body compartments. PMID:19965537

  19. [Comparative studies on the toxicity of various dielectrics--petroleum derivatives used in the electroerosion technic. V. Functional, morphological and cytoenzymatic changes in the kidneys of rats chronically exposed to petroleum hydrocarbons].

    PubMed

    Starek, A; Kamiński, M

    1982-01-01

    The rats exposed for 14 weeks to odourless kerosene mists (concentration of 75 and 300 mg/m3) had their urinary chemical and morphotic composition determined. In addition, morphological and cytoenzymatic examinations of kidneys were carried out. The findings were: increased pH and protein concentration and single erythrocytes in urine and also: passive congestion of renal cortex and medulla, infiltrates composed of granulocytes and eosinophils and albuminous casts in renal tubules. Decreased activity of succinate dehydrogenase, glucoso-6-phosphatase, Mg++ stimulated adenosinotriphosphatase and increased activity of acid phosphatase were found. Those changes were localized in cortical part of the kidney especially in the main tubules epithelial cells. The observed functional, morphological and cytoenzymatic changes depended on the magnitude of exposure. The obtained results confirm that kerosene hydrocarbons may exhibit toxic effects on the kidney function and structure.

  20. Whole brain resting-state analysis reveals decreased functional connectivity in major depression.

    PubMed

    Veer, Ilya M; Beckmann, Christian F; van Tol, Marie-José; Ferrarini, Luca; Milles, Julien; Veltman, Dick J; Aleman, André; van Buchem, Mark A; van der Wee, Nic J; Rombouts, Serge A R B

    2010-01-01

    Recently, both increases and decreases in resting-state functional connectivity have been found in major depression. However, these studies only assessed functional connectivity within a specific network or between a few regions of interest, while comorbidity and use of medication was not always controlled for. Therefore, the aim of the current study was to investigate whole-brain functional connectivity, unbiased by a priori definition of regions or networks of interest, in medication-free depressive patients without comorbidity. We analyzed resting-state fMRI data of 19 medication-free patients with a recent diagnosis of major depression (within 6 months before inclusion) and no comorbidity, and 19 age- and gender-matched controls. Independent component analysis was employed on the concatenated data sets of all participants. Thirteen functionally relevant networks were identified, describing the entire study sample. Next, individual representations of the networks were created using a dual regression method. Statistical inference was subsequently done on these spatial maps using voxel-wise permutation tests. Abnormal functional connectivity was found within three resting-state networks in depression: (1) decreased bilateral amygdala and left anterior insula connectivity in an affective network, (2) reduced connectivity of the left frontal pole in a network associated with attention and working memory, and (3) decreased bilateral lingual gyrus connectivity within ventromedial visual regions. None of these effects were associated with symptom severity or gray matter density. We found abnormal resting-state functional connectivity not previously associated with major depression, which might relate to abnormal affect regulation and mild cognitive deficits, both associated with the symptomatology of the disorder.

  1. Whole Brain Resting-State Analysis Reveals Decreased Functional Connectivity in Major Depression

    PubMed Central

    Veer, Ilya M.; Beckmann, Christian F.; van Tol, Marie-José; Ferrarini, Luca; Milles, Julien; Veltman, Dick J.; Aleman, André; van Buchem, Mark A.; van der Wee, Nic J.; Rombouts, Serge A.R.B.

    2010-01-01

    Recently, both increases and decreases in resting-state functional connectivity have been found in major depression. However, these studies only assessed functional connectivity within a specific network or between a few regions of interest, while comorbidity and use of medication was not always controlled for. Therefore, the aim of the current study was to investigate whole-brain functional connectivity, unbiased by a priori definition of regions or networks of interest, in medication-free depressive patients without comorbidity. We analyzed resting-state fMRI data of 19 medication-free patients with a recent diagnosis of major depression (within 6 months before inclusion) and no comorbidity, and 19 age- and gender-matched controls. Independent component analysis was employed on the concatenated data sets of all participants. Thirteen functionally relevant networks were identified, describing the entire study sample. Next, individual representations of the networks were created using a dual regression method. Statistical inference was subsequently done on these spatial maps using voxel-wise permutation tests. Abnormal functional connectivity was found within three resting-state networks in depression: (1) decreased bilateral amygdala and left anterior insula connectivity in an affective network, (2) reduced connectivity of the left frontal pole in a network associated with attention and working memory, and (3) decreased bilateral lingual gyrus connectivity within ventromedial visual regions. None of these effects were associated with symptom severity or gray matter density. We found abnormal resting-state functional connectivity not previously associated with major depression, which might relate to abnormal affect regulation and mild cognitive deficits, both associated with the symptomatology of the disorder. PMID:20941370

  2. Avocado Oil Improves Mitochondrial Function and Decreases Oxidative Stress in Brain of Diabetic Rats.

    PubMed

    Ortiz-Avila, Omar; Esquivel-Martínez, Mauricio; Olmos-Orizaba, Berenice Eridani; Saavedra-Molina, Alfredo; Rodriguez-Orozco, Alain R; Cortés-Rojo, Christian

    2015-01-01

    Diabetic encephalopathy is a diabetic complication related to the metabolic alterations featuring diabetes. Diabetes is characterized by increased lipid peroxidation, altered glutathione redox status, exacerbated levels of ROS, and mitochondrial dysfunction. Although the pathophysiology of diabetic encephalopathy remains to be clarified, oxidative stress and mitochondrial dysfunction play a crucial role in the pathogenesis of chronic diabetic complications. Taking this into consideration, the aim of this work was to evaluate the effects of 90-day avocado oil intake in brain mitochondrial function and oxidative status in streptozotocin-induced diabetic rats (STZ rats). Avocado oil improves brain mitochondrial function in diabetic rats preventing impairment of mitochondrial respiration and mitochondrial membrane potential (ΔΨ m ), besides increasing complex III activity. Avocado oil also decreased ROS levels and lipid peroxidation and improved the GSH/GSSG ratio as well. These results demonstrate that avocado oil supplementation prevents brain mitochondrial dysfunction induced by diabetes in association with decreased oxidative stress.

  3. Decreased functional connectivity of insula-based network in young adults with internet gaming disorder.

    PubMed

    Zhang, Yanzhen; Mei, Wei; Zhang, John X; Wu, Qiulin; Zhang, Wei

    2016-09-01

    The insula is a region that integrates interoception and drug urges, but little is known about its role in behavioral addiction such as internet addiction. We investigated insula-based functional connectivity in participants with internet gaming disorder (IGD) and healthy controls (HC) using resting-state functional MRI. The right and left insula subregions (posterior, ventroanterior, and dorsoanterior) were used as seed regions in a connectivity analysis. Compared with the HC group, the IGD group showed decreased functional connectivity between left posterior insula and bilateral supplementary motor area and middle cingulated cortex, between right posterior insula and right superior frontal gyrus, and decreased functional integration between insular subregions. The finding of reduced functional connectivity between the interoception and the motor/executive control regions is interpreted to reflect reduced ability to inhibit motor responses to internet gaming or diminished executive control over craving for internet gaming in IGD. The results support the hypothesis that IGD is associated with altered insula-based network, similar to substance addiction such as smoking.

  4. Losartan Decreases Cardiac Muscle Fibrosis and Improves Cardiac Function in Dystrophin-Deficient Mdx Mice

    PubMed Central

    Spurney, Christopher F.; Sali, Arpana; Guerron, Alfredo D.; Iantorno, Micaela; Yu, Qing; Gordish-Dressman, Heather; Rayavarapu, Sree; van der Meulen, Jack; Hoffman, Eric P.; Nagaraju, Kanneboyina

    2014-01-01

    Recent studies showed that chronic administration of losartan, an angiotensin II type I receptor antagonist, improved skeletal muscle function in dystrophin-deficient mdx mice. In this study, C57BL/10ScSn-Dmdmdx/J female mice were either untreated or treated with losartan (n = 15) in the drinking water at a dose of 600 mg/L over a 6-month period. Cardiac function was assessed via in vivo high frequency echocardiography and skeletal muscle function was assessed using grip strength testing, Digiscan monitoring, Rotarod timing, and in vitro force testing. Fibrosis was assessed using picrosirius red staining and Image J analysis. Gene expression was evaluated using real-time polymerized chain reaction (RT-PCR). Percentage shortening fraction was significantly decreased in untreated (26.9% ± 3.5%) mice compared to losartan-treated (32.2% ± 4.2%; P < .01) mice. Systolic blood pressure was significantly reduced in losartan-treated mice (56 ± 6 vs 69 ± 7 mm Hg; P < .0005). Percentage cardiac fibrosis was significantly reduced in losartan-treated hearts (P < .05) along with diaphragm (P < .01), extensor digitorum longus (P < .05), and gastrocnemius (P < .05) muscles compared to untreated mdx mice. There were no significant differences in skeletal muscle function between treated and untreated groups. Chronic treatment with losartan decreases cardiac and skeletal muscle fibrosis and improves cardiac systolic function in dystrophin-deficient mdx mice. PMID:21304057

  5. Increasing protein production rates can decrease the rate at which functional protein is produced

    NASA Astrophysics Data System (ADS)

    Sharma, Ajeet; O'Brien, Edward

    The rate at which soluble, functional protein is produced by the ribosome has recently been found to vary in complex and unexplained ways as various translation-associated rates are altered through synonymous codon substitutions. We combine a well-established ribosome-traffic model with a master-equation model of co-translational domain folding to explore the scenarios that are possible for the protein production rate, J, and the functional-nascent protein production rate, F, as the rates associated with translation are altered. We find that while J monotonically increases as the rates of translation-initiation, -elongation and -termination increase, F can either increase or decrease. F exhibits non-monotonic behavior because increasing these rates can cause a protein to be synthesized more rapidly but provide less time for nascent-protein domains to co-translationally fold thereby producing less functional nascent protein immediately after synthesis. We further demonstrate that these non-monotonic changes in Faffect the post-translational, steady-state levels of functional protein in a similar manner. Our results provide a possible explanation for recent experimental observations that the specific activity of enzymatic proteins can decrease with increased synthesis rates and can in principle be used to rationally-design transcripts to maximize the production of functional nascent protein.

  6. 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.

  7. Kidney function