Enhanced renal prostaglandin production in the dog. I. Effects on renal function.

PubMed

Tannenbaum, J; Splawinski, J A; Oates, J A; Nies, A S

1975-01-01

The changes in renal function produced by endogenous synthesis of prostaglandins by the kidney were evaluated by infusing sodium arachidonate, the prescursor of the prostaglandins, into one renal artery of the dog. These changes were compared with those produced by similar infusions on performed prostaglandin (PG) E2 and F2alpha.PGE2given at 0.01-0.3 mug/kg min--1 produced dose-related increases in urine flow, sodium and potassium excretion, free water clearance, and renal blood flow. The glomerular filtration rage increased only at the lowest dose and the calculated filtration fraction fell. Arachidonic acid at 1.0-30.0 mug/kg min--1 similarly produced dose-related increases in electrolyte excretion, but the increase in renal blood flow was much less than that produced by PGE2 and there were no changes in glomerular filtration rate, filtration fraction, or free water clearances. PGF2alpha had essentially no effects at infusion rates of 0.03-1.0 mug/kg min--1. All renal effects of arachidonic acid were inhibited by simultaneous infusions of an inhibitor of prostaglandin synthetase, 5, 8, 11,14-eicosatetraynoic acid (20:4). None of the effects produced by PGE2 were inhibited by 20:4. These results indicate that enhanced endogenous renal prostaglandin synthesis, which can be produced by arachidonate infusion, results in significant alterations of renal function. This finding strengthens the hypothesis that renal prostaglandins formed in vivo have physiological importance as regulators of renal function.

Renal albumin absorption in physiology and pathology.

PubMed

Birn, H; Christensen, E I

2006-02-01

Albumin is the most abundant plasmaprotein serving multiple functions as a carrier of metabolites, hormones, vitamins, and drugs, as an acid/base buffer, as antioxidant and by supporting the oncotic pressure and volume of the blood. The presence of albumin in urine is considered to be the result of the balance between glomerular filtration and tubular reabsorption. Albuminuria has been accepted as an independent risk factor and a marker for renal as well as cardiovascular disease, and during the past decade, evidence has suggested that albumin itself may cause progression of renal disease. Thus, the reduction of proteinuria and, in particular, albuminuria has become a target in itself to prevent deterioration of renal function. Studies have shown albumin and its ligands to induce expression of inflammatory and fibrogenic mediators, and it has been hypothesized that increased filtration of albumin causes excessive tubular reabsorption, resulting in inflammation and fibrosis, resulting in the loss of renal function. In addition, it is known that tubular dysfunction in itself may cause albuminuria owing to decreased reabsorption of filtered albumin, and, recently, it has been suggested that significant amounts of albumin fragments are excreted in the urine as a result of tubular degradation. Thus, although both tubular and glomerular dysfunction influences renal handling of albumin, it appears that tubular reabsorption plays a central role in mediating the effects of albumin on renal function. The present paper will review the mechanisms for tubular albumin uptake and the possible implications for the development of renal disease.

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

PubMed Central

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

2015-01-01

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

Impact of high doses of 6% hydroxyethyl starch 130/0.42 and 4% gelatin on renal function in a pediatric animal model.

PubMed

Witt, Lars; Glage, Silke; Lichtinghagen, Ralf; Pape, Lars; Boethig, Dietmar; Dennhardt, Nils; Heiderich, Sebastian; Leffler, Andreas; Sümpelmann, Robert

2016-03-01

Despite serious renal side effects in critically ill adult patients, artificial colloids are still fundamental components of perioperative fluid therapy in infants and children, although the impact of 6% hydroxyethyl starch (HES) and 4% gelatin (GEL) on renal function during pediatric surgery has not been identified yet. To determine the impact of high doses of artificial colloids on renal function, we conducted an experimental animal study and hypothesized that neither the infusion of HES nor of GEL would have a serious impact on renal function. Fifteen sedated piglets were randomly assigned to receive an infusion of either 50 ml · kg(-1) HES or GEL, or a balanced electrolyte solution (crystalloid group). Before and 1 week after infusion, serum and urine renal function tests were recorded and renal biopsies were taken. Serum and urine renal function tests revealed no increase after administration of HES and GEL, and only a discrete increase in serum creatinine (median 9.8 μmol · l(-1), 95% CI 4.0-19.1) in the crystalloid group. Histopathological examination indicated a sparsely, multifocal infiltration of mononuclear cells in all groups and an unspecific pyelectasia of one animal in the GEL group. After high doses of HES or GEL in piglets, no relevant impact on renal function could be found. These results confirm that AKI after HES or GEL is very unlikely in hemodynamically stable perioperative patients with normal renal function. © 2015 John Wiley & Sons Ltd.

Multimarker assessment for the prediction of renal function improvement after percutaneous revascularization for renal artery stenosis

PubMed Central

Partovi, Sasan; Zeller, Thomas; Breidthardt, Tobias; Kaech, Max; Boeddinghaus, Jasper; Puelacher, Christian; Nestelberger, Thomas; Aschwanden, Markus; Mueller, Christian

2016-01-01

Background Identifying patients likely to have improved renal function after percutaneous transluminal renal angioplasty and stenting (PTRA) for renal artery stenosis (RAS) is challenging. The purpose of this study was to use a comprehensive multimarker assessment to identify those patients who would benefit most from correction of RAS. Methods In 127 patients with RAS and decreased renal function and/or hypertension referred for PTRA, quantification of hemodynamic cardiac stress using B-type natriuretic peptide (BNP), renal function using estimated glomerular filtration rate (eGFR), parenchymal renal damage using resistance index (RI), and systemic inflammation using C-reactive protein (CRP) were performed before intervention. Results Predefined renal function improvement (increase in eGFR ≥10%) at 6 months occurred in 37% of patients. Prognostic accuracy as quantified by the area under the receiver-operating characteristics curve for the ability of BNP, eGFR, RI and CRP to predict renal function improvement were 0.59 (95% CI, 0.48–0.70), 0.71 (95% CI, 0.61–0.81), 0.52 (95% CI, 0.41–0.65), and 0.56 (95% CI, 0.44–0.68), respectively. None of the possible combinations increased the accuracy provided by eGFR (lower eGFR indicated a higher likelihood for eGFR improvement after PTRA, P=ns for all). In the subgroup of 56 patients with pre-interventional eGFR <60 mL/min/1.73 m2, similar findings were obtained. Conclusions Quantification of renal function, but not any other pathophysiologic signal, provides at least moderate accuracy in the identification of patients with RAS in whom PTRA will improve renal function. PMID:27280085

Genomic integration of ERRγ-HNF1β regulates renal bioenergetics and prevents chronic kidney disease.

PubMed

Zhao, Juanjuan; Lupino, Katherine; Wilkins, Benjamin J; Qiu, Chengxiang; Liu, Jian; Omura, Yasuhiro; Allred, Amanda L; McDonald, Caitlin; Susztak, Katalin; Barish, Grant D; Pei, Liming

2018-05-22

Mitochondrial dysfunction is increasingly recognized as a critical determinant of both hereditary and acquired kidney diseases. However, it remains poorly understood how mitochondrial metabolism is regulated to support normal kidney function and how its dysregulation contributes to kidney disease. Here, we show that the nuclear receptor estrogen-related receptor gamma (ERRγ) and hepatocyte nuclear factor 1 beta (HNF1β) link renal mitochondrial and reabsorptive functions through coordinated epigenomic programs. ERRγ directly regulates mitochondrial metabolism but cooperatively controls renal reabsorption via convergent binding with HNF1β. Deletion of ERRγ in renal epithelial cells (RECs), in which it is highly and specifically expressed, results in severe renal energetic and reabsorptive dysfunction and progressive renal failure that recapitulates phenotypes of animals and patients with HNF1β loss-of-function gene mutations. Moreover, ERRγ expression positively correlates with renal function and is decreased in patients with chronic kidney disease (CKD). REC-ERRγ KO mice share highly overlapping renal transcriptional signatures with human patients with CKD. Together these findings reveal a role for ERRγ in directing independent and HNF1β-integrated programs for energy production and use essential for normal renal function and the prevention of kidney disease.

Renal function monitoring in patients prescribed dabigatran in the Compass Health Primary Health Organisation: a quality improvement audit.

PubMed

McBain, Lynn; Kyle, Anna

2018-03-09

To assess annual renal function monitoring and clinical indications for use in patients prescribed dabigatran. A quality improvement activity included all patients in the Compass Health Primary Health Organisation (PHO) prescribed dabigatran. Information recorded: demographics; indication for use; daily dose; height; weight; serum creatinine; and estimated glomerular filtration rate (eGFR). The first audit occurred during July 2013 - May 2014, the second during May 2014 - October 2016. Across the PHO, all patients prescribed dabigatran were reviewed: 941 patients and 1,564 respectively. At the time of the second pass audit, renal function monitoring improved from 88% to 90%, and 96% were prescribed dabigatran for an approved indication. Results showed a continuing high level of renal function monitoring across the PHO in 90% of patients prescribed dabigatran. Practitioners were reminded to use creatinine clearance as a marker of renal function. Dabigatran was prescribed for an approved indication in 96% of patients. Our results are in line with recommended best practice and clinical guidelines.

Impact of Iodinated Contrast on Renal Function and Hemodynamics in Rats with Chronic Hyperglycemia and Chronic Kidney Disease

PubMed Central

Fernandes, Sheila Marques; Martins, Daniel Malisani; da Fonseca, Cassiane Dezoti; Watanabe, Mirian; Vattimo, Maria de Fátima Fernandes

2016-01-01

Iodinated contrast (IC) is clinically used in diagnostic and interventional procedures, but its use can result in contrast-induced acute kidney injury (CI-AKI). Chronic kidney disease (CKD) and chronic hyperglycemia (CH) are important predisposing factors to CI-AKI. The aim of this study was to investigate the impact of iodinated contrast on the renal function and hemodynamics in rats with chronic hyperglycemia and chronic kidney disease. A total of 30 rats were divided into six groups; Sham: control of chronic renal disease; Citrate: control of chronic hyperglycemia (CH); Nx5/6: rats with 5/6 nephrectomy; Chronic Hyperglycemia: rats receiving Streptozotocin 65 mg/kg; Nx5/6 + IC: rats Nx5/6 received 6 mL/kg of IC; CH + IC: Chronic hyperglycemia rats receiving 6 mL/kg of IC. Renal function (inulin clearance; urinary neutrophil gelatinase-associated lipocalin, NGAL) and hemodynamics (arterial blood pressure; renal blood flow; renal vascular resistance) were evaluated. Iodinated contrast significantly increased urinary NGAL and reduced inulin clearance, while the hemodynamics parameters showed changes in arterial blood pressure, renal blood flow, and renal vascular resistance in both CKD and CH groups. The results suggest that the iodinated contrast in risk factors models has important impact on renal function and hemodynamics. NGAL was confirmed to play a role of highlight in diagnosis of CI-AKI. PMID:27034930

Renal Function, Bisphenol A, and Alkylphenols: Results from the National Health and Nutrition Examination Survey (NHANES 2003–2006)

PubMed Central

You, Li; Zhu, Xiangzhu; Shrubsole, Martha J.; Fan, Hong; Chen, Jing; Dong, Jie; Hao, Chuan-Ming; Dai, Qi

2011-01-01

Background Urinary excretion of bisphenol A (BPA) and alkylphenols (APs) was used as a biomarker in most previous studies, but no study has investigated whether urinary excretion of these environmental phenols differed by renal function. Objective We estimated the association between renal function and urinary excretion of BPA and APs. Methods Analyses were conducted using data from the National Health and Nutrition Examination Survey (NHANES) 2003–2006. Renal function was measured as estimated glomerular filtration rate (eGFR) calculated by the Modification of Diet in Renal Disease (MDRD) Study equation and by the newly developed Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Regression models were used to calculate geometric means of urinary BPA and APs excretion by eGFR category (≥ 90, 60–90, < 60 mL/min/m2) after adjusting for potential confounding factors. Results When we used the MDRD Study equation, participants without known renal disease (n = 2,573), 58.2% (n = 1,499) had mildly decreased renal function or undiagnosed chronic kidney disease. The adjusted geometric means for urinary BPA excretion decreased with decreasing levels of eGFR (p for trend = 0.04). The associations appeared primarily in females (p for trend = 0.03). Urinary triclosan excretion decreased with decreasing levels of eGFR (p for trend < 0.01) for both males and females, and the association primarily appeared in participants < 65 years of age. The association between BPA and eGFR was nonsignificant when we used the CKD-EPI equation. Conclusions Urinary excretion of triclosan, and possibly BPA, decreased with decreasing renal function. The associations might differ by age or sex. Further studies are necessary to replicate our results and understand the mechanism. PMID:21147601

Can renal dysfunction after infra-renal aortic aneurysm repair be modified by multi-antioxidant supplementation?

PubMed

Wijnen, M H W A; Vader, H L; Van Den Wall Bake, A W L; Roumen, R M H

2002-08-01

Renal failure after lower torso ischemia is a serious problem, partly caused by hypotension and indirect reperfusion injury. This injury is partly due to the formation of oxygen free radicals by activated neutrophils. This injury results in albuminuria and renal function impairment. There are indications that free radical damage in indirect reperfusion injury can be diminished by administering extra antioxidants before and during reperfusion. In this prospective randomised study we have looked at the influence of a multi-antioxidant supplementation on renal function in patients undergoing an elective open infrarenal abdominal aneurysm repair. The patients received either standard treatment (n=22) or standard treatment with additional antioxidants perioperatively (Allopurinol, vitamin E and C, N-acetylcysteine and mannitol). For renal function we have looked at the albumin/creatinine ratio in urine and 24 hr creatinine clearance. Despite significantly increased serum total antioxidant capacity, the group receiving extra antioxidants showed no decrease in the albumin/creatinine ratio in urine. There was however a significantly higher creatinine clearance in this group at day 2. The results indicate that the diminished renal function after infrarenal aneurysm repair may be influenced by antioxidant therapy.

Assessment of renal function and electrolytes in patients with thyroid dysfunction in Addis Ababa, Ethiopia: a cross sectional study.

PubMed

Abebe, Nardos; Kebede, Tedla; Wolde, Mistire

2016-01-01

Studies demonstrated that abnormal thyroid functions may result in decreased or increased kidney size, kidney weight, and affect renal functions. In this regard, studies on the association of abnormal thyroid functions and renal function tests are scarcely found in Ethiopia. To assess renal function and electrolytes in patients with thyroid dysfunction, in Addis Ababa, Ethiopia. Cross sectional study was conducted from March 21/2015-May 27/2015 at Arsho Advanced Medical Laboratory. During the study period, 71 patients with thyroid dysfunction were eligible, and socio demographic data collected by structured questionnaire. Then blood sample was collected for thyroid function tests, renal function and blood electrolyte analysis. The collected data was analyzed by SPSS version 20. ANOVA and binary logistic regression were employed to evaluate the mean deference and associations of thyroid hormone with renal function and electrolyte balances. Among the renal function tests, serum uric acid, and creatinine mean values were significantly decreased in hyperthyroid patients; whereas, eGFR mean value was significantly increased in hyperthyroid study patients (P<0.05). Meanwhile, from the electrolyte measurements made, only the mean serum sodium value was significantly increased in hyperthyroid study participants. Binary logistic regression analysis on the association of thyroid dysfunction with electrolyte balance and renal function tests indicated that serum sodium, creatinine, eGFR values and hyperthyroidism have a statistical significant association at AOR 95% CI of 0.141(0.033-0.593, P=0.008); 16.236(3.481-75.739, P=0.001), and 13.797(3.261-58.67, P=0.001) respectively. The current study reveals, thyroid abnormalities may lead to renal function alterations and also may disturb electrolyte balance. Knowledge of this significant association has worthwhile value for clinicians, to manage their patients' optimally.

Long-term verification of functional and structural renal damage after renal sympathetic denervation.

PubMed

Dörr, Oliver; Liebetrau, Christoph; Möllmann, Helge; Gaede, Luise; Troidl, Christian; Wiebe, Jens; Renker, Matthias; Bauer, Timm; Hamm, Christian; Nef, Holger

2016-06-01

Previous studies of renal sympathetic denervation (RSD) excluded patients with impaired renal function to avoid potential RSD-related renal damage. Measurement of the highly sensitive biomarkers neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) has shown that RSD does not aggravate renal damage during the early post-procedural period. The aim of the present study was to examine the effect of RSD on blood pressure (BP) reduction and renal function after a long-term follow-up. A total of 62 consecutive patients undergoing RSD were included in this study. Serum NGAL and KIM-1 were collected prior to RSD and at 24 hr, 48 hr, and 3 months after RSD. BP measurements, antihypertensive medication use, and safety events were followed over a three-year period. Follow-up data were available over 36.9[±3.4] months in 47 of 62 (75.8%) of the initially included patients. At this time point a significant systolic BP reduction of 23 mm Hg (P > 0.001) was documented, and there were no significant changes in serum creatinine (P = 0.14), blood urea nitrogen (P = 0.33), or estimated glomerular filtration rate (eGFR) (P = 0.2) values. There were also no significant changes documented in patients with impaired renal function (eGFR < 45 mL/min) during the early post- procedural period or the long-term follow-up (P = 0.34). The results of the present study show a sustained effect of RSD on BP reduction after a three-year follow-up, and there was no evidence of renal failure. These results provide verification of the long-term safety and effectiveness of RSD, even in patients with impaired renal function. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

RENAL MICROVASCULAR DISEASE DETERMINES THE RESPONSES TO REVASCULARIZATION IN EXPERIMENTAL RENOVASCULAR DISEASE

PubMed Central

Chade, Alejandro R.; Kelsen, Silvia

2011-01-01

Background Percutaneous trasluminal renal angioplasty (PTRA) is the most frequent therapeutic approach to resolve renal artery stenosis (RAS). However, renal function recovers in only 30% of the cases. The causes of these poor outcomes are still unknown. We hypothesize that preserving the renal microcirculation distal to RAS will improve the responses to PTRA. Methods and Results RAS was induced in 28 pigs. In 14, vascular endothelial growth factor (VEGF)-165 was infused intra-renally (RAS+VEGF, 0.05 µg/kg). Single-kidney function was assessed in all pigs in vivo using ultra-fast CT after 6 weeks. Half of the RAS/RAS+VEGF completed their observation, and the other half underwent PTRA, VEGF was repeated, and CT studies repeated 4 weeks later. Pigs were then euthanized, the stenotic kidney removed, renal microvascular (MV) architecture reconstructed ex-vivo using 3D micro-CT, and renal fibrosis quantified. Degree of RAS and hypertension were similar in RAS and RAS+VEGF. Renal function and MV density were decreased in RAS but improved in RAS+VEGF. PTRA largely resolved RAS, but the improvements of hypertension and renal function were greater in RAS+VEGF+PTRA than in RAS+PTRA, accompanied by a 34% increase in MV density and decreased fibrosis. Conclusion Preservation of the MV architecture and function in the stenotic kidney improved the responses to PTRA, indicating that renal MV integrity plays a role in determining the responses to PTRA. This study indicates that damage and early loss of renal MV is an important determinant of the progression of renal injury in RAS and instigates often irreversible damage. PMID:20587789

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

A quantitative systems physiology model of renal function and blood pressure regulation: Model description.

PubMed

Hallow, K M; Gebremichael, Y

2017-06-01

Renal function plays a central role in cardiovascular, kidney, and multiple other diseases, and many existing and novel therapies act through renal mechanisms. Even with decades of accumulated knowledge of renal physiology, pathophysiology, and pharmacology, the dynamics of renal function remain difficult to understand and predict, often resulting in unexpected or counterintuitive therapy responses. Quantitative systems pharmacology modeling of renal function integrates this accumulated knowledge into a quantitative framework, allowing evaluation of competing hypotheses, identification of knowledge gaps, and generation of new experimentally testable hypotheses. Here we present a model of renal physiology and control mechanisms involved in maintaining sodium and water homeostasis. This model represents the core renal physiological processes involved in many research questions in drug development. The model runs in R and the code is made available. In a companion article, we present a case study using the model to explore mechanisms and pharmacology of salt-sensitive hypertension. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Impaired left ventricular systolic function and increased brachial-ankle pulse-wave velocity are independently associated with rapid renal function progression.

PubMed

Chen, Szu-Chia; Lin, Tsung-Hsien; Hsu, Po-Chao; Chang, Jer-Ming; Lee, Chee-Siong; Tsai, Wei-Chung; Su, Ho-Ming; Voon, Wen-Chol; Chen, Hung-Chun

2011-09-01

Heart failure and increased arterial stiffness are associated with declining renal function. Few studies have evaluated the association between left ventricular ejection fraction (LVEF) and brachial-ankle pulse-wave velocity (baPWV) and renal function progression. The aim of this study was to assess whether LVEF<40% and baPWV are associated with a decline in the estimated glomerular filtration rate (eGFR) and the progression to a renal end point of ≥25% decline in eGFR. This longitudinal study included 167 patients. The baPWV was measured with an ankle-brachial index-form device. The change in renal function was estimated by eGFR slope. The renal end point was defined as ≥25% decline in eGFR. Clinical and echocardiographic parameters were compared and analyzed. After a multivariate analysis, serum hematocrit was positively associated with eGFR slope, and diabetes mellitus, baPWV (P=0.031) and LVEF<40% (P=0.001) were negatively associated with eGFR slope. Forty patients reached the renal end point. Multivariate, forward Cox regression analysis found that lower serum albumin and hematocrit levels, higher triglyceride levels, higher baPWV (P=0.039) and LVEF<40% (P<0.001) were independently associated with progression to the renal end point. Our results show that LVEF<40% and increased baPWV are independently associated with renal function decline and progression to the renal end point.

Renal impairment as a surgical indication in primary hyperparathyroidism: do the data support this recommendation?

PubMed

Hendrickson, Chase D; Castro Pereira, Daniel J; Comi, Richard J

2014-08-01

Management of primary hyperparathyroidism has evolved over the past two decades, yet impaired renal function has consistently been a surgical indication. This recommendation has been based upon the historical association between primary hyperparathyroidism and renal impairment, and a review of the literature is needed to determine whether such a recommendation is warranted. PubMed was utilized to identify English-language articles published between January 1990 and February 2014 using keywords related to hyperparathyroidism and renal function. The keywords were "primary hyperparathyroidism," "surgery," "parathyroidectomy," "kidney," "renal," "glomerular filtration rate," and "creatinine." Of the 1926 articles obtained with this search, all articles germane to the topic that quantified the relationship between primary hyperparathyroidism and renal function were included. All references within these articles were investigated for inclusion. When helpful, data tables were constructed to summarize the results succinctly. A secondary elevation of PTH levels has not been consistently shown to occur at the threshold currently indicated for surgical intervention. While renal impairment is seen with more significant disease, mild asymptomatic primary hyperparathyroidism has not been conclusively associated with renal impairment. Furthermore, there is no evidence to suggest that surgically curing primary hyperparathyroidism via a parathyroidectomy has any impact upon renal function.

Renal uptake of radioactive mercury (/sup 197/HgCl/sub 2/): method for testing the functional value of each kidney. Technique--results--and clinical application in urology and nephrology

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

Raynaud, C.

The first three chapters consider measurement of mercury renal uptake by external counting, by quantitative scintigraphy, and by the gamma camera. Some topics discussed in the remaining 14 chapters are as follows: renal depth; phantoms; precautions regarding the liver, spleen, and intestine; stability of /sup 197/HgCl/sub 2/ solutions; use of mercury renal uptake in pediatric and adult urology; indications for mercury renal uptake in renal transplants; and appraisal of the radiological and chemical toxicity of /sup 197/HgCl/sub 2/. It was concluded that mercury renal uptake is an accurate and nontraumatizing method of measuring the functional value of each kidney. Itmore » makes it possible to determine whether a kidney is normal or pathological and to what extent its function is diminished or increased. (HLW)« less

Determination of split renal function using dynamic CT-angiography: preliminary results.

PubMed

Helck, Andreas; Schönermarck, Ulf; Habicht, Antje; Notohamiprodjo, Mike; Stangl, Manfred; Klotz, Ernst; Nikolaou, Konstantin; la Fougère, Christian; Clevert, Dirk Andrè; Reiser, Maximilian; Becker, Christoph

2014-01-01

To determine the feasibility of a dynamic CT angiography-protocol with regard to simultaneous assessment of renal anatomy and function. 7 healthy potential kidney donors (58 ± 7 years) underwent a dynamic computed tomography angiography (CTA) using a 128-slice CT-scanner with continuous bi-directional table movement, allowing the coverage of a scan range of 18 cm within 1.75 sec. Twelve scans of the kidneys (n = 14) were acquired every 3.5 seconds with the aim to simultaneously obtain CTA and renal function data. Image quality was assessed quantitatively (HU-measurements) and qualitatively (grade 1-4, 1 = best). The glomerular filtration rate (GFR) was calculated by a modified Patlak method and compared with the split renal function obtained with renal scintigraphy. Mean maximum attenuation was 464 ± 58 HU, 435 ± 48 HU and 277 ± 29 HU in the aorta, renal arteries, and renal veins, respectively. The abdominal aorta and all renal vessels were depicted excellently (grade 1.0). The image quality score for cortex differentiation was 1.6 ± 0.49, for the renal parenchyma 2.4 ± 0.49. GFR obtained from dynamic CTA correlated well with renal scintigraphy with a correlation coefficient of r = 0.84; P = 0.0002 (n = 14). The average absolute deviation was 1.6 mL/min. The average effective dose was 8.96 mSv. Comprehensive assessment of renal anatomy and function is feasible using a single dynamic CT angiography examination. The proposed protocol may help to improve management in case of asymmetric kidney function as well as to simplify evaluation of potential living kidney donors.

Neural control of renal function in health and disease.

PubMed

DiBona, G F

1994-04-01

The renal sympathetic innervation of the kidney exerts significant effects on multiple aspects of renal function, including renal haemodynamics, tubular sodium and water reabsorption and renin secretion. These effects constitute an important control system which is important in the physiological regulation of arterial pressure and total body fluid and sodium homeostasis. Abnormalities in this regulatory mechanism have pathophysiological consequences and are manifest in clinically relevant human disease states. Decreased renal sympathetic nerve activity results in impaired renin secretion, the inability to conserve sodium normally and an attenuated ability to dispose of both acute and chronic sodium loads. Increased renal sympathetic nerve activity contributes significantly to the excess renal sodium retention and related renal abnormalities observed in both hypertension and oedema forming conditions, such as cardiac failure, cirrhosis and nephrotic syndrome.

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

PubMed

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

2018-04-04

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

Functional Renal Imaging with 2-Deoxy-2-18F-Fluorosorbitol PET in Rat Models of Renal Disorders.

PubMed

Werner, Rudolf A; Wakabayashi, Hiroshi; Chen, Xinyu; Hirano, Mitsuru; Shinaji, Tetsuya; Lapa, Constantin; Rowe, Steven P; Javadi, Mehrbod S; Higuchi, Takahiro

2018-05-01

Precise regional quantitative assessment of renal function is limited with conventional 99m Tc-labeled renal radiotracers. A recent study reported that the PET radiotracer 2-deoxy-2- 18 F-fluorosorbitol ( 18 F-FDS) has ideal pharmacokinetics for functional renal imaging. Furthermore, 18 F-FDS is available via simple reduction from routinely used 18 F-FDG. We aimed to further investigate the potential of 18 F-FDS PET as a functional renal imaging agent using rat models of kidney disease. Methods: Two different rat models of renal impairment were investigated: induction of acute renal failure by intramuscular administration of glycerol in the hind legs, and induction of unilateral ureteral obstruction by ligation of the left ureter. At 24 h after these procedures, dynamic 30-min 18 F-FDS PET data were acquired using a dedicated small-animal PET system. Urine 18 F-FDS radioactivity 30 min after radiotracer injection was measured together with coinjected 99m Tc-diethylenetriaminepentaacetic acid urine activity. Results: Dynamic PET imaging demonstrated rapid 18 F-FDS accumulation in the renal cortex and rapid radiotracer excretion via the kidneys in healthy control rats. On the other hand, significantly delayed renal radiotracer uptake (continuous slow uptake) was observed in acute renal failure rats and unilateral ureteral obstruction kidneys. Measured urine radiotracer concentrations of 18 F-FDS and 99m Tc-diethylenetriaminepentaacetic acid correlated well with each other ( R = 0.84, P < 0.05). Conclusion: 18 F-FDS PET demonstrated favorable kinetics for functional renal imaging in rat models of kidney diseases. 18 F-FDS PET imaging, with its advantages of high spatiotemporal resolution and simple tracer production, could potentially complement or replace conventional renal scintigraphy in select cases and significantly improve the diagnostic performance of renal functional imaging. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Albumin infusion improves renal blood flow autoregulation in patients with acute decompensation of cirrhosis and acute kidney injury.

PubMed

Garcia-Martinez, Rita; Noiret, Lorette; Sen, Sambit; Mookerjee, Rajeshwar; Jalan, Rajiv

2015-02-01

In cirrhotic patients with renal failure, renal blood flow autoregulation curve is shifted to the right, which is consequent upon sympathetic nervous system activation and endothelial dysfunction. Albumin infusion improves renal function in cirrhosis by mechanisms that are incompletely understood. We aimed to determine the effect of albumin infusion on systemic haemodynamics, renal blood flow, renal function and endothelial function in patients with acute decompensation of cirrhosis and acute kidney injury. Twelve patients with refractory ascites and 10 patients with acute decompensation of cirrhosis and acute kidney injury were studied. Both groups were treated with intravenous albumin infusion, 40-60 g/days over 3-4 days. Cardiac and renal haemodynamics were measured. Endothelial activation/dysfunction was assessed using von Willebrand factor and serum nitrite levels. F2α Isoprostanes, resting neutrophil burst and noradrenaline levels were quantified as markers of oxidative stress, endotoxemia and sympathetic activation respectively. Albumin infusion leads to a shift in the renal blood flow autoregulation curve towards normalization, which resulted in a significant increase in renal blood flow. Accordingly, improvement of renal function was observed. In parallel, a significant decrease in sympathetic activation, inflammation/oxidative stress and endothelial activation/dysfunction was documented. Improvement of renal blood flow correlated with improvement in endothelial activation (r = 0.741, P < 0.001). The data suggest that albumin infusion improves renal function in acutely decompensated cirrhotic patients with acute kidney injury by impacting on renal blood flow autoregulation. This is possibly achieved through endothelial stabilization and a reduction in the sympathetic tone, endotoxemia and oxidative stress. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Evaluation of renal function in patients with a main renal stone larger than 1 cm and perioperative renal functional change in minimally invasive renal stone surgery: a prospective, observational study.

PubMed

Piao, Songzhe; Park, Juhyun; Son, Hwancheol; Jeong, Hyeon; Cho, Sung Yong

2016-05-01

To compare the perioperative relative renal function and determine predictors of deterioration and recovery of separate renal function in patients with renal stones >10 mm and who underwent mini-percutaneous nephrolithotomy or retrograde intra-renal surgery. A main stone >10 mm or stones growing, high-risk stone formers and extracorporeal shock-wave lithotripsy-resistant stones were prospectively included in 148 patients. Patients with bilateral renal stones and anatomical deformities were excluded. Renal function was evaluated by estimated glomerular filtration rate, 99m-technetium dimercaptosuccinic acid and 99m-technetium diethylenetriamine pentaacetate prior to intervention and at postoperative 3 months. Logistic regression analyses were performed to find predictors of functional deterioration and recovery. The overall stone-free rate was 85.1 %. A third of patients (53/148, 35.8 %) with renal stones >10 mm showed deterioration of separate renal function. Mean renal function of operative sites showed 58.2 % (36.8 %/63.2 %) of that of contralateral sites in these patients. Abnormal separate renal function showed postoperative recovery in 31 patients (58.5 %). Three cases (5.7 %) showed deterioration of separate renal function despite no presence of remnant stones. Improvement rates of the abnormal separate renal function did not differ according to the type of surgery. The presence of hydronephrosis and three or more stones were significant predictors for renal function deterioration. Female gender and three or more stones were significantly correlated with postoperative recovery. Mini-percutaneous nephrolithotomy or retrograde intra-renal surgery was effective and safe for renal function preservation. Patients with multiple large stones should be considered for candidates of active surgical removal.

Validity of /sup 99m/Tc dimercaptosuccinic acid renal uptake for an assessment for individual kidney function

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

Kawamura, J.; Hosakawa, S.; Yoshida, O.

/sup 99m/Tc dimercaptosuccinic acid is a new renal scanning agent that provides a good quality of renal image as a result of preferential cortical accumulation and also makes feasible a quantitative assessment of separate kidney function, correlating well with renal plasma flow obtained from a /sup 131/I hippuran renogram of each kidney. By measuring the dimercaptosuccinic acid uptake, the cortical functioning nephrons can be determined independent of the activity from the urinary outflow tract. Such evaluations may replace the conventional split renal function study in which traumatic procedures, such as cystoscopy and ureteral catheterizations, are required. /sup 99m/Tc dimercaptosuccinic acidmore » scintigraphy causes less discomfort to the patient and can be performed repeatedly and routinely even in children and debilitated geriatric patients.« less

Mechanisms of Acute Kidney Injury Induced by Experimental Lonomia obliqua Envenomation

PubMed Central

Berger, Markus; Santi, Lucélia; Beys-da-Silva, Walter O.; Oliveira, Fabrício Marcus Silva; Caliari, Marcelo Vidigal; Yates, John R.; Ribeiro, Maria Aparecida; Guimarães, Jorge Almeida

2015-01-01

Background Lonomia obliqua caterpillar envenomation causes acute kidney injury (AKI), which can be responsible for its deadly actions. This study evaluates the possible mechanisms involved in the pathogenesis of renal dysfunction. Methods To characterize L. obliqua venom effects we subcutaneously injected rats and examined renal functional, morphological and biochemical parameters at several time points. We also performed discovery based proteomic analysis to measure protein expression to identify molecular pathways of renal disease. Results L. obliqua envenomation causes acute tubular necrosis, which is associated with renal inflammation; formation of hematic casts, resulting from intravascular hemolysis; increase in vascular permeability and fibrosis. The dilation of Bowman’s space and glomerular tuft is related to fluid leakage and intra-glomerular fibrin deposition, respectively, since tissue factor procoagulant activity increases in the kidney. Systemic hypotension also contributes to these alterations and to the sudden loss of basic renal functions, including filtration and excretion capacities, urinary concentration and maintenance of fluid homeostasis. In addition, envenomed kidneys increases expression of proteins involved in cell stress, inflammation, tissue injury, heme-induced oxidative stress, coagulation and complement system activation. Finally, the localization of the venom in renal tissue agrees with morphological and functional alterations, suggesting also a direct nephrotoxic activity. Conclusions Mechanisms of L. obliqua-induced AKI are complex involving mainly glomerular and tubular functional impairment and vascular alterations. These results are important to understand the mechanisms of renal injury and may suggest more efficient ways to prevent or attenuate the pathology of Lonomia’s envenomation. PMID:24798088

Preserving residual renal function in dialysis patients: an update on evidence to assist clinical decision making

PubMed Central

Jensen, Jens Dam; Peters, Christian Daugaard; Jespersen, Bente

2011-01-01

It has been documented that preservation of residual renal function in dialysis patients improves quality of life as well as survival. Clinical trials on strategies to preserve residual renal function are clearly lacking. While waiting for more results from clinical trials, patients will benefit from clinicians being aware of available knowledge. The aim of this review was to offer an update on current evidence assisting doctors in clinical practice. PMID:25949486

Effect of bariatric surgery-induced weight loss on renal and systemic inflammation and blood pressure: a 12-month prospective study.

PubMed

Fenske, Wiebke K; Dubb, Sukhpreet; Bueter, Marco; Seyfried, Florian; Patel, Karishma; Tam, Frederick W K; Frankel, Andrew H; le Roux, Carel W

2013-01-01

Bariatric surgery improves arterial hypertension and renal function; however, the underlying mechanisms and effect of different surgical procedures are unknown. In the present prospective study, we compared the 12-month follow-up results after Roux-en-Y gastric bypass, laparoscopic adjustable gastric banding, and laparoscopic sleeve gastrectomy on weight loss, hypertension, renal function, and inflammatory status. A total of 34 morbidly obese patients were investigated before, one and 12 months after Roux-en-Y gastric bypass (n = 10), laparoscopic adjustable gastric banding (n = 13), and laparoscopic sleeve gastrectomy (n = 11) for hypertension, kidney function, urinary and serum cytokine levels of macrophage migration inhibitory factor, monocyte chemotactic protein-1, and chemokine ligand-18. At 12 months after surgery, the patients in all 3 treatment arms showed a significant decrease in the mean body mass index, mean arterial pressure, and urinary and serum inflammatory markers (all P < .001). The reduction in urinary and serum cytokine levels correlated directly with body weight loss (P < .05). Patients with impaired renal function at baseline (corresponding to serum cystatin C >.8 mg/L) had a marked improvement in renal function 12 months after surgery (P < .05). Surgically induced weight loss is associated with a marked decrease in renal and systemic inflammation and arterial hypertension and improvement in renal function in patients with pre-existing renal impairment. These effects appear to be independent of surgical procedure. The improvement in renal inflammation could be 1 of the mechanisms contributing to the beneficial effects of bariatric surgery on arterial blood pressure, proteinuria, and renal function. Copyright © 2013 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Dehydration upon admission is a risk factor for incomplete recovery of renal function in children with haemolytic uremic syndrome.

PubMed

Ojeda, José M; Kohout, Isolda; Cuestas, Eduardo

2013-01-01

Haemolytic uremic syndrome (HUS) is the most common cause of acute renal failure and the second leading cause of chronic renal failure in children. The factors that affect incomplete renal function recovery prior to hospital admission are poorly understood. To analyse the risk factors that determine incomplete recovery of renal function prior to hospitalisation in children with HUS. A retrospective case-control study. age, sex, duration of diarrhoea, bloody stools, vomiting, fever, dehydration, previous use of antibiotics, and incomplete recovery of renal function (proteinuria, hypertension, reduced creatinine clearance, and chronic renal failure during follow-up). Patients of both sexes under 15 years of age were included. Of 36 patients, 23 were males (65.3%; 95%CI: 45.8 to 80.9), with an average age of 2.5 ± 1.4 years. Twenty-one patients required dialysis (58%; 95% CI: 40.8 to 75.8), and 13 (36.1%; 95% CI: 19.0 to 53.1) did not recover renal function. In the bivariate model, the only significant risk factor was dehydration (defined as weight loss >5%) [(OR: 5.3; 95% CI: 1.4 to 12.3; P=.0220]. In the multivariate analysis (Cox multiple regression), only dehydration was marginally significant (HR: 95.823; 95% CI: 93.175 to 109.948; P=.085). Our data suggest that dehydration prior to admission may be a factor that increases the risk of incomplete recovery of renal function during long-term follow-up in children who develop HUS D+. Consequently, in patients with diarrhoea who are at risk of HUS, dehydration should be strongly avoided during outpatient care to preserve long-term renal function. These results must be confirmed by larger prospective studies.

Acetylator Status Impacts Amifampridine Phosphate (Firdapse™) Pharmacokinetics and Exposure to a Greater Extent Than Renal Function.

PubMed

Haroldsen, Peter E; Sisic, Zlatko; Datt, Joe; Musson, Donald G; Ingenito, Gary

2017-07-01

The purpose of this study is to evaluate safety, tolerability, and pharmacokinetic (PK) properties of amifampridine phosphate (Firdapse™) and its major inactive 3-N-acetyl metabolite in renally impaired and healthy individuals with slow acetylator (SA) and rapid acetylator (RA) phenotypes. This was a Phase I, multicenter, open-label study of the PK properties and safety profile of amifampridine phosphate in individuals with normal, mild, moderate, or severely impaired renal function. Amifampridine phosphate was given as a single 10 mg (base equivalent) dose, and the plasma and urine PK properties of amifampridine and its 3-N-acetyl metabolite were determined. The safety profile was evaluated by monitoring adverse events (AEs), clinical laboratory tests, and physical examinations. Amifampridine clearance was predominantly metabolic through N-acetylation, regardless of renal function in both acetylator phenotypes. In individuals with normal renal function, mean renal clearance represented approximately 3% and 18% of the total clearance of amifampridine in RA and SA, respectively. Large differences in amifampridine exposure were observed between acetylation phenotypes across renal function levels. Mean amifampridine exposure values of AUC 0-∞ and C max were up to 8.8-fold higher in the SA group compared with the RA group across renal function levels. By comparison, mean AUC 0-∞ was less affected by renal function within an acetylator group, only 2- to 3-fold higher in individuals with severe renal impairment (RI) compared with those with normal renal function. Exposure to amifampridine in the SA group with normal renal function was higher (AUC 0-∞, approximately 1.8-fold; C max, approximately 4.1-fold) than the RA group with severe RI. Exposure to the inactive 3-N-acetyl metabolite was higher than amifampridine in both acetylator groups, independent of renal function level. The metabolite is cleared by renal excretion, and exposure was clearly dependent on renal function with 4.0- to 6.8-fold increases in AUC 0-∞ from normal to severe RI. No new tolerability findings were observed. A single dose of 10 mg of amifampridine phosphate was well tolerated, independent of renal function and acetylator status. The results indicate that the PK profile of amifampridine is affected by metabolic acetylator phenotype to a greater extent than by renal function level, supporting Firdapse™ administration in individuals with RI in line with current labeling recommendations. Amifampridine should be dosed to effect per the individual patient need, altering administration frequency and dose in normal through severe RI. The therapeutic dose of amifampridine phosphate should be tailored to the individual patient needs by gradual dose titration up to the present maximum recommended dose (60-80 mg/day) or until dose-limiting AEs intervene to avoid overdosing and underdosing. EudraCT identifier: 2013-005349-35. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Influence of fluid resuscitation on renal microvascular PO2 in a normotensive rat model of endotoxemia

PubMed Central

Johannes, Tanja; Mik, Egbert G; Nohé, Boris; Raat, Nicolaas JH; Unertl, Klaus E; Ince, Can

2006-01-01

Introduction Septic renal failure is often seen in the intensive care unit but its pathogenesis is only partly understood. This study, performed in a normotensive rat model of endotoxemia, tests the hypotheses that endotoxemia impairs renal microvascular PO2 (μPO2) and oxygen consumption (VO2,ren), that endotoxemia is associated with a diminished kidney function, that fluid resuscitation can restore μPO2, VO2,ren and kidney function, and that colloids are more effective than crystalloids. Methods Male Wistar rats received a one-hour intravenous infusion of lipopolysaccharide, followed by resuscitation with HES130/0.4 (Voluven®), HES200/0.5 (HES-STERIL® ® 6%) or Ringer's lactate. The renal μPO2 in the cortex and medulla and the renal venous PO2 were measured by a recently published phosphorescence lifetime technique. Results Endotoxemia induced a reduction in renal blood flow and anuria, while the renal μPO2 and VO2,ren remained relatively unchanged. Resuscitation restored renal blood flow, renal oxygen delivery and kidney function to baseline values, and was associated with oxygen redistribution showing different patterns for the different compounds used. HES200/0.5 and Ringer's lactate increased the VO2,ren, in contrast to HES130/0.4. Conclusion The loss of kidney function during endotoxemia could not be explained by an oxygen deficiency. Renal oxygen redistribution could for the first time be demonstrated during fluid resuscitation. HES130/0.4 had no influence on the VO2,ren and restored renal function with the least increase in the amount of renal work. PMID:16784545

Predictors of renal recovery in patients with pre-orthotopic liver transplant (OLT) renal dysfunction

PubMed Central

2013-01-01

Background Renal dysfunction occurs commonly in patients awaiting orthotopic liver transplantation (OLT) for end-stage liver disease. The use of simultaneous liver-kidney transplantation has increased in the MELD scoring era. As patients may recover renal function after OLT, identifying factors predictive of renal recovery is a critical issue, especially given the scarcity of available organs. Methods Employing the UNOS database, we sought to identify donor- and patient-related predictors of renal recovery among 1720 patients with pre-OLT renal dysfunction and transplanted from 1989 to 2005. Recovery of renal function post-OLT was defined as a composite endpoint of serum creatinine (SCr) ≤1.5 mg/dL at discharge and survival ≥29 days. Pre-OLT renal dysfunction was defined as any of the following: SCr ≥2 mg/dL at any time while awaiting OLT or need for renal replacement therapy (RRT) at the time of registration and/or OLT. Results Independent predictors of recovery of renal function post-OLT were absence of hepatic allograft dysfunction, transplantation during MELD era, recipient female sex, decreased donor age, decreased recipient ALT at time of OLT, decreased recipient body mass index at registration, use of anti-thymocyte globulin as induction therapy, and longer wait time from registration. Contrary to popular belief, a requirement for RRT, even for prolonged periods in excess of 8 weeks, was not an independent predictor of failure to recover renal function post-OLT. Conclusion These data indicate that the duration of renal dysfunction, even among those requiring RRT, is a poor way to discriminate reversible from irreversible renal dysfunction. PMID:23849513

A comparison of toxicities in acute myeloid leukemia patients with and without renal impairment treated with decitabine.

PubMed

Levine, Lauren B; Roddy, Julianna Vf; Kim, Miryoung; Li, Junan; Phillips, Gary; Walker, Alison R

2018-06-01

Purpose There are limited data regarding the clinical use of decitabine for the treatment of acute myeloid leukemia in patients with a serum creatinine of 2 mg/dL or greater. Methods We retrospectively evaluated 111 patients with acute myeloid leukemia who had been treated with decitabine and compared the development of toxicities during cycle 1 in those with normal renal function (creatinine clearance greater than or equal to 60 mL/min) to those with renal dysfunction (creatinine clearance less than 60 mL/min). Results Notable differences in the incidence of grade ≥3 cardiotoxicity (33% of renal dysfunction patients vs. 16% of normal renal function patients, p = 0.042) and respiratory toxicity (40% of renal dysfunction patients vs. 14% of normal renal function patients, p = 0.0037) were observed. The majority of heart failure, myocardial infarction, and atrial fibrillation cases occurred in the renal dysfunction group. The odds of developing grade ≥3 cardiotoxicity did not differ significantly between patients with and without baseline cardiac comorbidities (OR 1.43, p = 0.43). Conclusions This study noted a higher incidence of grade ≥3 cardiac and respiratory toxicities in decitabine-treated acute myeloid leukemia patients with renal dysfunction compared to normal renal function. This may prompt closer monitoring, regardless of baseline cardiac comorbidities. Further evaluation of decitabine in patients with renal dysfunction is needed.

Radiographic kidney measurements in captive cheetahs (Acinonyx jubatus).

PubMed

Hackendahl, Nicole C; Citino, Scott B

2005-06-01

The prevalence of chronic renal disease is substantial among captive cheetahs (Acinonyx jubatus). The purpose of this study was to determine kidney measurements from radiographs of captive cheetahs (n = 15) with normal renal function. The ratio of kidney length to length of the body of the second lumbar vertebrae has been established for domestic cats with normal renal function. The mean ratio of renal length to length of the second lumbar vertebra was 1.81 +/- 0.14 in cheetahs. This baseline data may allow an objective evaluation of radiographic kidney size in cheetahs. However, evaluation of a small number of cheetahs with confirmed renal failure resulted in a similar ratio.

[Robotic assisted laparoscopic living donor nephrectomy: preoperative assessment and results of 100 cases].

PubMed

Laplace, B; Ladrière, M; Claudon, M; Eschwege, P; Kessler, M; Hubert, J

2014-04-01

To assess short term morbidity and renal function after robotic laparoscopic living donor nephrectomy. We performed a retrospective analysis of 100 consecutives patients undergoing a robotic laparoscopic living donors nephrectomy. We analyzed isotopic measure of the renal function before and 4 months after surgery, the side, the number of arteries, the blood loss, the operative time and warm ischemia time. In the outcomes, we collected the complications, the length of stay, and for the receiver, the renal function recovery time, dialysis, survival and renal function at one year. Left kidney nephrectomy was performed in 85 patients and we observed 25 multiples renal arteries. Mean estimated blood loss was 0,8 g/dL. Mean operative time and warm ischemia time were respectively 174 ± 30 and 4.8 ± 1.7 minutes. Seven complications occured, with 2 major (Clavien-Dindo System). Mean length of stay was 5.1 ± 1.9 days. Mean glomerular filtration decrease was 26% and remains stable at one year after surgery. Grafts had an immediate renal function recovery for 99%, and were all functional after one year, with mean MDRD clearance of 57 ± 14mL/min. Robotic procedure in laparoscopic living donor nephrectomy seems to guarantee low morbidity and the stability of the renal function decrease of 26%. Copyright © 2013. Published by Elsevier Masson SAS.

Impact of Preoperative Abdominal Visceral Adipose Tissue Area and Nutritional Status on Renal Function After Donor Nephrectomy in Japanese Living Donors for Renal Transplantation.

PubMed

Hori, Shunta; Miyake, Makito; Morizawa, Yosuke; Nakai, Yasushi; Onishi, Kenta; Iida, Kota; Gotoh, Daisuke; Anai, Satoshi; Torimoto, Kazumasa; Aoki, Katsuya; Yoneda, Tatsuo; Tanaka, Nobumichi; Yoshida, Katsunori; Fujimoto, Kiyohide

2018-05-29

BACKGROUND Living kidney donors face the risk of renal dysfunction, resulting in end-stage renal disease, cardiovascular disease, or cerebrovascular disease, after donor nephrectomy. Reducing this risk is important to increasing survival of living donors. In this study, we investigated the effect of preoperative distribution of abdominal adipose tissue and nutritional status on postoperative renal function in living donors. MATERIAL AND METHODS Seventy-five living donors were enrolled in this retrospective study. Preoperative unenhanced computed tomography images were used to measure abdominal adipose tissue parameters. Prognostic nutritional index (PNI) was used to assess preoperative nutritional status. Donors were divided into 2 groups according to abdominal visceral adipose tissue (VAT) area at the level of the fourth and fifth lumbar vertebrae (<80 or ≥80 cm²). Postoperative renal function was compared in the 2 groups, and prognostic factors for development of chronic kidney disease (CKD) G3b were identified using multivariate analysis. RESULTS Donors with a VAT area ≥80 significantly more often had hypertension preoperatively. Although there was no significant difference in preoperative estimated glomerular filtration rate (eGFR) between the 2 groups, postoperative renal function was significantly decreased in donors with a VAT area ≥80 compared to those with a VAT area <80. In multivariate analysis, VAT area ≥80 and PNI <54 were independent factors predicting the development of CKD G3b after 12 months. CONCLUSIONS Our findings suggest that preoperative VAT and PNI affect postoperative renal function. Further research is required to establish appropriate exercise protocols and nutritional interventions during follow-up to improve outcomes in living donors.

Inappropriate Prescription and Renal Function Among Older Patients with Cognitive Impairment.

PubMed

Sönnerstam, Eva; Sjölander, Maria; Gustafsson, Maria

2016-12-01

Older people are more sensitive to drugs and adverse drug reactions than younger people because of age-related physiological changes such as impaired renal function. As people with dementia are particularly vulnerable to the effects of drugs, it is especially important to evaluate the dosages of renally cleared medications in this group. The aim of this study was to estimate the prevalence of impaired renal function and inappropriate prescriptions on the basis of renal function among older patients with dementia or cognitive impairment. The medical records of 428 patients aged ≥65 years who were admitted to two hospitals in northern Sweden were reviewed and renally cleared medications were identified. The Cockcroft-Gault equation was used to evaluate renal function. Doses were evaluated according to the Geriatric Dosage Handbook. Renal function was impaired (estimated glomerular filtration rate <60 ml/min) in 65.4 % of the study population. Impaired renal function was associated with increasing age. Among 547 prescriptions identified as renally cleared medications, 9.1 % were inappropriate based on the patient's renal function; 13.5 % of the 326 patients prescribed renally cleared medications had inappropriate prescriptions. Inappropriate prescriptions were more common among patients living in nursing homes. Impaired renal function is common and inappropriate prescription is prevalent among old people with cognitive impairment in northern Sweden. Continuous consideration of renal function is important when prescribing medications to this group.

Erythropoietin-enhanced endothelial progenitor cell recruitment in peripheral blood and renal vessels during experimental acute kidney injury in rats.

PubMed

Cakiroglu, Figen; Enders-Comberg, Sora Maria; Pagel, Horst; Rohwedel, Jürgen; Lehnert, Hendrik; Kramer, Jan

2016-03-01

Beneficial effects of erythropoietin (EPO) have been reported in acute kidney injury (AKI) when administered prior to induction of AKI. We studied the effects of EPO administration on renal function shortly after ischemic AKI. For this purpose, rats were subjected to renal ischemia for 30 min and EPO was administered at a concentration of 500 U/kg either i.v. as a single shot directly after ischemia or with an additional i.p. dose until 3 days after surgery. The results were compared with AKI rats without EPO application and a sham-operated group. Renal function was assessed by measurement of serum biochemical markers, histological grading, and using an isolated perfused kidney (IPK) model. Furthermore, we performed flow cytometry to analyze the concentration of endothelial progenitor cells (EPCs) in the peripheral blood and renal vessels. Following EPO application, there was only a statistically non-significant tendency of serum creatinine and urea to improve, particularly after daily EPO application. Renal vascular resistance and the renal perfusion rate were not significantly altered. In the histological analysis, acute tubular necrosis was only marginally ameliorated following EPO administration. In summary, we could not demonstrate a significant improvement in renal function when EPO was applied after AKI. Interestingly, however, EPO treatment resulted in a highly significant increase in CD133- and CD34-positive EPC both in the peripheral blood and renal vessels. © 2015 International Federation for Cell Biology.

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

PubMed

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

2017-06-01

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

Dynamic analysis of patterns of renal sympathetic nerve activity: implications for renal function.

PubMed

DiBona, Gerald F

2005-03-01

Methods of dynamic analysis are used to provide additional understanding of the renal sympathetic neural control of renal function. The concept of functionally specific subgroups of renal sympathetic nerve fibres conveying information encoded in the frequency domain is presented. Analog pulse modulation and pseudorandom binary sequence stimulation patterns are used for the determination of renal vascular frequency response. Transfer function analysis is used to determine the effects of non-renal vasoconstrictor and vasoconstrictor intensities of renal sympathetic nerve activity on dynamic autoregulation of renal blood flow.

Renal function assessment in heart failure.

PubMed

Pérez Calvo, J I; Josa Laorden, C; Giménez López, I

Renal function is one of the most consistent prognostic determinants in heart failure. The prognostic information it provides is independent of the ejection fraction and functional status. This article reviews the various renal function assessment measures, with special emphasis on the fact that the patient's clinical situation and response to the heart failure treatment should be considered for the correct interpretation of the results. Finally, we review the literature on the performance of tubular damage biomarkers. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

[Acetaminophen (paracetamol) causing renal failure: report on 3 pediatric cases].

PubMed

Le Vaillant, J; Pellerin, L; Brouard, J; Eckart, P

2013-06-01

Renal failure secondary to acetaminophen poisoning is rare and occurs in approximately 1-2 % of patients with acetaminophen overdose. The pathophysiology is still being debated, and renal acetaminophen toxicity consists of acute tubular necrosis, without complication if treated promptly. Renal involvement can sometimes occur without prior liver disease, and early renal manifestations usually occur between the 2nd and 7th day after the acute acetaminophen poisoning. While therapy is exclusively symptomatic, sometimes serious metabolic complications can be observed. The monitoring of renal function should therefore be considered as an integral part of the management of children with acute, severe acetaminophen intoxication. We report 3 cases of adolescents who presented with acute renal failure as a result of voluntary drug intoxication with acetaminophen. One of these 3 girls developed severe renal injury without elevated hepatic transaminases. None of the 3 girls' renal function required hemodialysis, but one of the 3 patients had metabolic complications after her acetaminophen poisoning. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

[Clinical assessment of renal function in oedemas during pregnancy (author's transl)].

PubMed

Voigt, R; Stoll, W; Arndt, J

1980-12-01

Oedemas during pregnancy make differential diagnosis imperative, since it will be necessary to determine whether they occur primarily in connection with pregnancy or are secondary to a pre-existent renal disease. In the studies presented here were examined women without known pre-existing renal disease, to determine the influence exercised on the parameters of renal function by the oedemas occurring during pregnancy. Examination was effected weekly by means of the previously described programme for risk pregnancies during the individual stages of pregnancy. No statistically significant influence on ureterorenal function was seen in these women compared with groups of controls. The results are discussed on the basis of facts available from literature.

Utility of Cystatin C to monitor renal function in Duchenne muscular dystrophy

PubMed Central

Viollet, Laurence; Gailey, Susan; Thornton, David J.; Friedman, Neil R.; Flanigan, Kevin M.; Mahan, John D.; Mendell, Jerry R.

2009-01-01

Introduction: Creatinine as a marker of renal function has limited value in Duchenne muscular dystrophy (DMD) because of reduced muscle mass. Alternative methods of assessing renal function are sorely needed. Cystatin C, a nonglycosylated protein unaffected by muscle mass, is potentially an ideal biomarker of nephrotoxicity for this population but requires validation. Methods: 75 subjects were recruited: 35 DMD (mean age 10.8 ± 5.4 years, corticosteroids n = 19, ambulatory n = 26), 29 healthy controls, 10 with renal disease, and one DMD with renal failure. Results: Cystatin C levels in DMD were normal irrespective of age, ambulation or corticosteroid treatment. Serum cystatin C was 0.67 ± 0.11 mg/L compared to normal controls 0.69 ± 0.09. mg/L. In these same individuals serum creatinine was severely reduced (0.27 ± 0.12 mg/dL) versus normals (0.75 ± 0.15 mg/dL, p < 0.01). In one DMD subject in renal failure, cystatin C was elevated. Discussion: This study demonstrates the potential value of cystatin C as a biomarker for monitoring renal function in DMD. Its applicability extends to other neuromuscular diseases. PMID:19623638

Use of nonsteroidal anti-inflammatory drugs and renal failure in nursing home residents-results of the study "Inappropriate Medication in Patients with Renal Insufficiency in Nursing Homes".

PubMed

Dörks, Michael; Herget-Rosenthal, Stefan; Schmiemann, Guido; Hoffmann, Falk

2016-04-01

Use of potentially inappropriate medications may result in increased morbidity, mortality and resource utilisation. Due to polypharmacy and age-related decline in renal function the elderly population is at particular risk. Therefore, the Beers Criteria include use of nonsteroidal anti-inflammatory drugs in chronic renal failure stage 4 and 5 as these drugs may worsen renal function. According to the summary of product characteristics, the nonsteroidal anti-inflammatory drugs ibuprofen and diclofenac are contraindicated in these patients. Objective was to assess the extent of nonsteroidal anti-inflammatory drug use in nursing homes with a focus on residents with severe renal failure. Multi-centre cross-sectional study in 21 German nursing homes. The study population comprised residents for whom at least one serum creatinine value and information about sex were available, so that creatinine clearance rate could be estimated. In all, 685 of 852 residents were included as they fulfilled the abovementioned criteria. Renal failure was severe (estimated creatinine clearance rate < 30 ml/min) in 106 residents (15.5 %). Approximately one-fifth was treated with at least one nonsteroidal anti-inflammatory drug in both the total study population (20.3 %) and that with severe renal failure (20.8 %). With one exception, all residents prescribed nonsteroidal anti-inflammatory drugs with severe renal failure were treated with at least one nonsteroidal anti-inflammatory drug that was contraindicated due to the underlying renal function. Notwithstanding their classification as potentially inappropriate medications and underlying contraindications, use of nonsteroidal anti-inflammatory drugs is common among nursing home residents with severe renal failure.

Nephrotic Syndrome and Idiopathic Membranous Nephropathy Associated with Autosomal-Dominant Polycystic Kidney Disease

PubMed Central

Peces, Ramón; Martínez-Ara, Jorge; Peces, Carlos; Picazo, Mariluz; Cuesta-López, Emilio; Vega, Cristina; Azorín, Sebastián; Selgas, Rafael

2011-01-01

We report the case of a 38-year-old male with autosomal-dominant polycystic kidney disease (ADPKD) and concomitant nephrotic syndrome secondary to membranous nephropathy (MN). A 3-month course of prednisone 60 mg daily and losartan 100 mg daily resulted in resistance. Treatment with chlorambucil 0.2 mg/kg daily, low-dose prednisone, plus an angiotensin-converting enzyme inhibitor (ACEI) and an angiotensin II receptor blocker (ARB) for 6 weeks resulted in partial remission of his nephrotic syndrome for a duration of 10 months. After relapse of the nephrotic syndrome, a 13-month course of mycophenolate mofetil (MFM) 2 g daily and low-dose prednisone produced complete remission for 44 months. After a new relapse, a second 24-month course of MFM and low-dose prednisone produced partial to complete remission of proteinuria with preservation of renal function. Thirty-six months after MFM withdrawal, complete remission of nephrotic-range proteinuria was maintained and renal function was preserved. This case supports the idea that renal biopsy is needed for ADPKD patients with nephrotic-range proteinuria in order to exclude coexisting glomerular disease and for appropriate treatment/prevention of renal function deterioration. To the best of our knowledge, this is the first reported case of nephrotic syndrome due to MN in a patient with ADPKD treated with MFM, with remission of proteinuria and preservation of renal function after more than 10 years. Findings in this patient also suggest that MFM might reduce cystic cell proliferation and fibrosis, preventing progressive renal scarring with preservation of renal function. PMID:21552769

Predictors of Recoverability of Renal Function after Pyeloplasty in Adults with Ureteropelvic Junction Obstruction.

PubMed

Li, Xiao-Dong; Wu, Yu-Peng; Wei, Yong; Chen, Shao-Hao; Zheng, Qing-Shui; Cai, Hai; Xue, Xue-Yi; Xu, Ning

2018-01-01

This study aimed to identify factors predicting the recoverability of renal function after pyeloplasty in adult patients with ureteropelvic junction obstruction. We retrospectively reviewed 138 adults with unilateral renal obstruction-induced hydronephrosis and who underwent Anderson-Hynes dismembered pyeloplasty from January 2013 to January 2016. Hydronephrosis was classified preoperatively according to the Society for Fetal Urology (SFU) grading system. All patients underwent Doppler ultrasonography, excretory urography, computed tomography, and technetium-99m-diethylenetriamine pentaacetic acid radioisotope (99mTc DTPA) renography before and after surgery. Renal resistive index (RRI) and 99mTc DTPA renography were repeated at 1, 3, 6, and 12 months. Multivariate analysis identified age, renal pelvic type, SFU grade, preoperative RRI, decline of RRI, and renal parenchyma to hydronephrosis area ratio (PHAR) as independent predictors of renal function recoverability after pyeloplasty. However, preoperative RRI and RRI decline were not significantly associated with recoverability of renal function in patients aged >35 years. Lower preoperative RRI, greater decline in RRI, higher PHAR, lower SFU grade, and extrarenal pelvis were associated with greater improvements in postoperative renal function. Preoperative differential renal function cannot independently predict the recoverability of postoperative renal function in adult patients with unilateral renal obstruction-induced hydronephrosis. SFU grade, renal pelvic type, PHAR, preoperative RRI, and decline in RRI were significantly associated with the recoverability of renal function in adult patients aged <35 years, while only SFU grade, renal pelvic type, and PHAR were significantly associated with renal function recoverability in patients aged ≥35 years. Renal function recovery was better in patients younger than 35 years when compared with older patients. © 2018 S. Karger AG, Basel.

Renal dopamine containing nerves. What is their functional significance?

PubMed

DiBona, G F

1990-06-01

Biochemical and morphological studies indicate that there are nerves within the kidney that contain dopamine and that various structures within the kidney contain dopamine receptors. However, the functional significance of these renal dopamine containing nerves in relation to renal dopamine receptors is unknown. The functional significance could be defined by demonstrating that an alteration in one or more renal functions occurring in response to reflex or electrical activation of efferent renal nerves is dependent on release of dopamine as the neurotransmitter from the renal nerve terminals acting on renal dopamine receptors. Thus, the hypothesis becomes: reflex or electrical activation of efferent renal nerves causes alterations in renal function (eg, renal blood flow, water and solute handling) that are inhibited by specific and selective dopamine receptor antagonists. As reviewed herein, the published experimental data do not support the hypothesis. Therefore, the view that alterations in one or more renal functions occurring in response to reflex or electrical activation of efferent renal nerves are dependent on release of dopamine as the neurotransmitter from the renal nerve terminals acting on renal dopamine receptors remains unproven.

Predictive factors for renal failure and a control and treatment algorithm

PubMed Central

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

2014-01-01

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

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

PubMed

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

2018-05-01

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

Evidence of Uncoupling between Renal Dysfunction and Injury in Cardiorenal Syndrome: Insights from the BIONICS Study

PubMed Central

Legrand, Matthieu; De Berardinis, Benedetta; Gaggin, Hanna K.; Magrini, Laura; Belcher, Arianna; Zancla, Benedetta; Femia, Alexandra; Simon, Mandy; Motiwala, Shweta; Sambhare, Rasika; Di Somma, Salvatore; Mebazaa, Alexandre; Vaidya, Vishal S.; Januzzi, James L.; (GREAT), from the Global Research on Acute Conditions Team

2014-01-01

Objective The objective of the study was to assess urinary biomarkers of renal injury for their individual or collective ability to predict Worsening renal function (WRF) in patients with acutely decompensated heart failure (ADHF). Methods In a prospective, blinded international study, 87 emergency department (ED) patients with ADHF were evaluated with biomarkers of cardiac stretch (B type natriuretic peptide [BNP] and its amino terminal equivalent [NT-proBNP], ST2), biomarkers of renal function (creatinine, estimated glomerular filtration rate [eGFR]) and biomarkers of renal injury (plasma neutrophil gelatinase associated lipocalin [pNGAL], urine kidney injury molecule-1 [KIM-1], urine N-acetyl-beta-D-glucosaminidase [NAG], urine Cystatin C, urine fibrinogen). The primary endpoint was WRF. Results 26% developed WRF; baseline characteristics of subjects who developed WRF were generally comparable to those who did not. Biomarkers of renal function and urine biomarkers of renal injury were not correlated, while urine biomarkers of renal injury correlated between each other. Biomarker concentrations were similar between patients with and without WRF except for baseline BNP. Although plasma NGAL was associated with the combined endpoint, none of the biomarker showed predictive accuracy for WRF. Conclusions In ED patients with ADHF, urine biomarkers of renal injury did not predict WRF. Our data suggest that a weak association exists between renal dysfunction and renal injury in this setting (Clinicaltrials.gov NCT#0150153). PMID:25386851

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

PubMed Central

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

1982-01-01

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

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

PubMed

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

2018-05-02

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

Cigarette smoking reduced renal function deterioration in hypertensive patients may be mediated by elevated homocysteine.

PubMed

Huang, Feifei; Chen, Jie; Liu, Xun; Han, Feng; Cai, Qingqing; Peng, Guicheng; Zhang, Kun; Chen, Weiqing; Wang, Jingfeng; Huang, Hui

2016-12-27

Elevated homocysteine (HCY) and smoking are both important risk factors for hypertensive patients. However, whether they have crossing effect on renal function deterioration of hypertensive patients and what is the underlying mechanism are unclear. In the present study, 3033 participants diagnosed as essential hypertension with estimated glomerular filtration rate (eGFR)> 30 ml/min/1.73 m2 from southern China were enrolled in this cross-sectional study. We collected the demographic and clinical data. In addition, the mediation effects were analyzed. The results showed that, comparing with non-smokers, smokers had significant higher levels of HCY (13.10 (11.20-16.87) vs. 11.00 (8.90-13.40) umol/L, P < 0.001) and lower eGFR (79.71 (66.83-91.05) vs. 82.89 (69.80-95.85) ml/min/1.73m2, P < 0.001). HCY levels and smoking were independently associated with decreased eGFR. Meanwhile, eGFR levels were significantly negatively correlated with HCY (P < 0.001), and this correlation might be stronger in current smokers. Current smoker consuming over 20 cigarettes per day would accelerate early renal function deterioration (OR = 1.859, P = 0.019). The mediation effects analysis further showed that the association between smoking and renal function deterioration was mediated by HCY. And elevated HCY was accounted for 56.94% of the estimated causal effect of smoking on renal function deterioration in hypertensive patients. Our findings indicated that cigarette smoking was associated with renal function deterioration in hypertensive patients, and the association between cigarette smoking and renal function deterioration was probably mediated by elevated HCY. Therefore, HCY-lowering therapy may be beneficial for renal function deterioration in hypertensive smoking patients.

Hydrocarbon exposure may cause glomerulonephritis and worsen renal function: evidence based on Hill's criteria for causality.

PubMed

Ravnskov, U

2000-08-01

Many observational and experimental studies point to hydrocarbon exposure as an important pathogenic factor in glomerulonephritis. The findings have made little impact on current concepts and patient care, possibly because the hypothesis of a direct causal effect of the exposure and the hypothesis that the exposure worsens renal function have not been considered separately. This review examines these two hypotheses using Hill's criteria for causality. The results from 14 cross-sectional, 18 case-control studies, two cohort studies, 15 experiments on laboratory animals and two on human beings together with many case reports satisfy all but one of Hill's criteria for both hypotheses. Of particular importance is the finding in the case-control and follow-up studies of an association between degree of exposure and stage of renal disease, and an inverse association between degree of exposure and renal function, indicating that the most important effect of hydrocarbon exposure is its effect on renal function. End-stage renal failure may be preventable in many patients with glomerulonephritis provided a possible exposure to toxic chemicals is discontinued.

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

PubMed

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

2016-11-01

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

Cyclic adenosine monophosphate modulates cell morphology and behavior of a cultured renal epithelial.

PubMed

Amsler, K

1990-07-01

The role of cyclic adenosine monophosphate (cAMP) dependent protein kinase (PKA) in modulating functions of differentiated renal cells is well established. Its importance in controlling their growth and differentiation is less clear. We have used somatic cell genetic techniques to probe the role of PKA in controlling morphology and behavior of a renal epithelial cell line, LLC-PK1, which acquires many properties characteristic of the renal proximal tubular cell. Mutants of this line altered in PKA activity have been isolated and their behavior compared to that of the parent line. The results indicate that PKA is involved, either directly or indirectly, in maintenance of cell morphology, cell-cell and cell-substratum interactions, density-dependent growth regulation, and expression of one function characteristic of the renal proximal tubular cell, Na-hexose symport. The relevance of these results to the role of PKA in controlling growth and differentiation of renal epithelial cells in vivo is discussed.

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

PubMed Central

2012-01-01

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

Renal artery stent fracture with refractory hypertension: a case report and review of the literature.

PubMed

Chua, Su-Kiat; Hung, Huei-Fong

2009-07-01

A 73-year-old man with resistant hypertension and impaired renal function underwent stenting for right renal artery (RRA) stenosis. Two years later, he presented with uncontrolled hypertension and worse renal function. Renal arteriogram revealed RRA stent fracture with in-stent restenosis. Another stent was deployed. Four months later, however, renal arteriogram revealed in-stent restenosis again. This time, balloon angioplasty alone was performed. He had been symptom-free with stable condition at 2-year follow-up. A literature review disclosed six renal artery stent fracture cases, including the present one, who developed in-stent stenosis resulted from stent fracture. Two major anatomy features of renal artery stenosis were suggestive for development of stent fracture: (1) renal artery entrapment by diaphragmatic crus, and (2) mobile kidney with acute angulation at proximal segment of the renal artery. It is important to detect this etiology of renal artery stenosis because stenting in these vessels may contribute to in-stent restenosis or stent fracture. Management of renal artery stent fracture, including endovascular treatment or aortorenal bypass, should be considered on a case-by-case basis in relation to clinical settings. Copyright 2009 Wiley-Liss, Inc.

Safety of Direct-Acting Antiviral Therapy Regarding Renal Function in Post-Liver Transplant Patients Infected with Hepatitis C Virus and a 100% 12-Week Sustained Virologic Response-A Single-Center Study.

PubMed

Peschel, G; Moleda, L; Baier, L; Selgrad, M; Schmid, S; Scherer, M N; Müller, M; Weigand, K

2018-06-01

Patients after liver transplantation (LT) with hepatitis C virus (HCV) infection often suffer from renal or hepatic impairment. Treating patients after LT with direct-acting antivirals (DAA) might result in decreasing renal function due to interaction of DAA and immunosuppressive therapy. In this single-center study we analyzed clinical parameters of 18 HCV-infected patients treated with DAA therapy after LT. The primary end points were change of renal function (glomerular filtration rate) and sustained virologic response 12 weeks after therapy (SVR12). For secondary end points, we investigated the influence of DAA therapy on transaminases, bilirubin, international normalized ratio, noninvasive fibrosis measurement, and Model for End-Stage Liver Disease (MELD) score. Five out of 18 patients treated with DAA suffered from renal impairment stage 2, and 7 patients of renal impairment stage 3. Renal function at SVR12 was not influenced by preexisting renal impairment (P > .5), type of immunosuppressant (P > .5), or type of DAA regimen (P > .5). All patients reached SVR12. The levels of transaminases and bilirubin declined rapidly, as expected. Ten out of 18 patients already suffered from cirrhosis or liver fibrosis >F3 according to noninvasive measurement before initiation of treatment. Single-point acoustic radiation force impulse imaging improved in 9 patients (P = .012). In 7 patients, MELD score improved owing to the decrease of bilirubin levels. In 6 patients it worsened. DAA therapy in LT patients was effective and safe in this single-center real-life cohort. Renal function was not influenced by the administered drug combinations, even in patients with preexisting renal impairment. Copyright © 2018. Published by Elsevier Inc.

Association between pulmonary function and renal function: findings from China and Australia.

PubMed

Yu, Dahai; Chen, Tao; Cai, Yamei; Zhao, Zhanzheng; Simmons, David

2017-05-01

The relationship between obstructive lung function and impaired renal function is unclear. This study investigated the dose-response relationship between obstructive lung function and impaired renal function. Two independent cross-sectional studies with representative sampling were applied. 1454 adults from rural Victoria, Australia (1298 with normal renal function, 156 with impaired renal function) and 5824 adults from Nanjing, China (4313 with normal renal function, 1511 with impaired renal function). Pulmonary function measurements included forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). Estimated glomerular filtration rate (eGFR), and impaired renal function marked by eGFR <60 mL/min/1.73m 2 were used as outcome. eGFR increased linearly with FEV1 in Chinese participants and with FVC in Australians. A non-linear relationship with peaked eGFR was found for FEV1 at 2.65 L among Australians and for FVC at 2.78 L among Chinese participants, respectively. A non-linear relationship with peaked eGFR was found for the predicted percentage value of forced expiratory volume in 1 s (PFEV1) at 81-82% and for the predicted percentage value of forced vital capacity (PFVC) at 83-84% among both Chinese and Australian participants, respectively. The non-linear dose-response relationships between lung capacity measurements (both for FEV1 and FVC) and risk of impaired renal function were consistently identified in both Chinese and Australian participants. An increased risk of impaired renal function was found below 3.05 L both for FEV1 and FVC, respectively. The non-linear relationship between PFEV and PVC and the risk of impaired renal function were consistently identified in both Chinese and Australian participants. An increased risk of impaired renal function was found below 76-77% for PFEV1 and 79-80% for PFVC, respectively. In both Australian and Chinese populations, the risk of impaired renal function increased both with FEV1 and FVC below 3.05 L, with PFEV1 below 76-77% or with PFVC below 79-80%, respectively. Obstructive lung function was associated with increased risk of reduced renal function. The screen for impaired renal function in patients with obstructive lung disease might be useful to ensure there was no impaired renal function before the commencement of potentially nephrotoxic medication where indicated (eg diuretics).

Renal denervation and hypertension - The need to investigate unintended effects and neural control of the human kidney.

PubMed

Grisk, Olaf

2017-05-01

Increased renal sympathetic nerve activity (RSNA) is present in human and experimental forms of arterial hypertension. Experimental denervation studies showed that renal nerves contribute to the development of hypertension. Clinical trials provided equivocal results on the antihypertensive efficacy of renal denervation in patients spurring discussions on technical aspects of renal denervation and further research on the role of renal nerves for the regulation of kidney function as well as the pathophysiology of hypertension. This review summarizes recent findings on adrenoceptor expression and function in the human kidney, adrenoceptor-dependent regulation of sodium chloride transport in the distal nephron, experimental data on chronic RSNA and the development of high arterial pressure and consequences of renal denervation that may limit its antihypertensive efficacy. Future research needs to reduce the gap between our knowledge on neural control of renal function in animals vs. humans to facilitate translation of experimental animal data to humans. More experimental studies on the temporal relationship between RSNA and arterial pressure in the chronic setting are needed to better define the pathogenetic role of heightened RSNA in different forms of arterial hypertension in order to improve the rational basis for renal denervation in antihypertensive therapy. Finally, research on unintended consequences of renal denervation including but not limited to reinnervation and denervation supersensitivity needs to be intensified to further assess the potential of renal denervation to slow the progression of renal disease and hypertension. Copyright © 2016 Elsevier B.V. All rights reserved.

Baseline renal insufficiency and risk of death among HIV-infected adults on antiretroviral therapy in Lusaka, Zambia

PubMed Central

Mulenga, Lloyd B.; Kruse, Gina; Lakhi, Shabir; Cantrell, Ronald A.; Reid, Stewart E.; Zulu, Isaac; Stringer, Elizabeth M.; Krishnasami, Zipporah; Mwinga, Alwyn; Saag, Michael S.; Stringer, Jeffrey S. A.; Chi, Benjamin H.

2009-01-01

Objective To examine the association between baseline renal insufficiency and mortality among adults initiating antiretroviral therapy (ART) in urban African setting. Design Open cohort evaluation Methods We examined mortality according to baseline renal function among adults initiating ART in Lusaka, Zambia. Renal function was assessed by the Cockcroft-Gault method, the Modification of Diet in Renal Disease (MDRD) equation, and serum creatinine. Results From April 2004 to September 2007, 25,779 individuals started ART with an available creatinine measurement at baseline. When creatinine clearance was calculated by the Cockcroft-Gault method, 8,456 (33.5%) had renal insufficiency: 73.5% were mild (60-89 mL/min), 23.4% moderate (30-59 mL/min), and 3.1% severe (<30 mL/min). Risk for mortality at or before 90 days was elevated for those with mildly (adjusted hazard ratio [AHR]=1.7; 95%CI=1.5-1.9), moderately (AHR=2.3; 95%CI=2.0-2.7), and severely (AHR=4.1; 95%CI=3.1-5.5) reduced creatinine clearance. Mild (AHR=1.4; 95%CI=1.2-1.6), moderate (AHR=1.9; 95%CI=1.5-2.3), and severe (AHR=3.6; 95%CI=2.4-5.5) insufficiency were also associated with increased mortality after 90 days, when compared to those with normal renal function. Trends were similar when renal function was estimated with MDRD or serum creatinine. Conclusions Renal insufficiency at time of ART initiation was prevalent and associated with increased mortality risk among adults in this population. These results have particular relevance for settings like Zambia, where tenofovir - a drug with known nephrotoxicity - has been adopted as part of first-line therapy. This emphasizes the need for resource-appropriate screening algorithms for renal disease, both as part of ART eligibility and pre-treatment assessment. PMID:18753939

Pre-emptive liver transplantation for primary hyperoxaluria (PH-I) arrests long-term renal function deterioration.

PubMed

Perera, M Thamara P R; Sharif, Khalid; Lloyd, Carla; Foster, Katharine; Hulton, Sally A; Mirza, Darius F; McKiernan, Patrick J

2011-01-01

Primary hyperoxaluria-I (PH-I) is a serious metabolic disease resulting in end-stage renal disease. Pre-emptive liver transplantation (PLT) for PH-I is an option for children with early diagnosis. There is still little information on its effect on long-term renal function in this situation. Long-term assessment of renal function was conducted using Schwartz's formula (estimated glomerular filtration rate-eGFR) in four children (Group A) undergoing PLT between 2002 and 2008, and a comparison was done with eight gender- and sex-matched controls (Group B) having liver transplantation for other indications. All patients received a liver graft from a deceased donor. Median follow-up for the two groups was 64 and 94 months, respectively. One child in Group A underwent re-transplantation due to hepatic artery thrombosis, while acute rejection was seen in one. A significant difference was seen in eGFR at transplant (81 vs 148 mL/min/1.73 m(2)) with greater functional impairment seen in the study population. In Group A, renal function reduced by 21 and 11% compared with 37 and 35% in Group B at 12 and 24 months, respectively. At 2 years post-transplantation, there was no significant difference in eGFR between the two groups (72 vs 100 mL/min/1.73 m(2), respectively; P = 0.06). Renal function remains relatively stable following pre-emptive LTx for PH-I. With early diagnosis of PH-I, isolated liver transplantation may prevent progression to end-stage renal disease and the need for renal transplantation.

Renal Function Descriptors in Neonates: Which Creatinine-Based Formula Best Describes Vancomycin Clearance?

PubMed

Bhongsatiern, Jiraganya; Stockmann, Chris; Yu, Tian; Constance, Jonathan E; Moorthy, Ganesh; Spigarelli, Michael G; Desai, Pankaj B; Sherwin, Catherine M T

2016-05-01

Growth and maturational changes have been identified as significant covariates in describing variability in clearance of renally excreted drugs such as vancomycin. Because of immaturity of clearance mechanisms, quantification of renal function in neonates is of importance. Several serum creatinine (SCr)-based renal function descriptors have been developed in adults and children, but none are selectively derived for neonates. This review summarizes development of the neonatal kidney and discusses assessment of the renal function regarding estimation of glomerular filtration rate using renal function descriptors. Furthermore, identification of the renal function descriptors that best describe the variability of vancomycin clearance was performed in a sample study of a septic neonatal cohort. Population pharmacokinetic models were developed applying a combination of age-weight, renal function descriptors, or SCr alone. In addition to age and weight, SCr or renal function descriptors significantly reduced variability of vancomycin clearance. The population pharmacokinetic models with Léger and modified Schwartz formulas were selected as the optimal final models, although the other renal function descriptors and SCr provided reasonably good fit to the data, suggesting further evaluation of the final models using external data sets and cross validation. The present study supports incorporation of renal function descriptors in the estimation of vancomycin clearance in neonates. © 2015, The American College of Clinical Pharmacology.

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.

Hypothyroidism presenting as reversible renal impairment: an interesting case report.

PubMed

Vikrant, Sanjay; Chander, Subhash; Kumar, Satish; Gupta, Dalip

2013-10-01

We describe an interesting case of reversible renal impairment secondary to hypothyroidism. A 57-years-old man was referred from peripheral institution for evaluation of elevated serum creatinine. He had vague complaints of weakness, lethargy and muscle ache but no urinary symptoms. He was found to have hypothyroidism, and thyroid hormone replacement therapy (THRT) was started which resulted in reversal of the renal dysfunction. There was marked improvement in estimated glomerular filtration rate. 99mTc DTPA renal scans done before and after THRT suggested hypothyroidism responsible for this reversible renal impairment. Several studies have described the pathophysiology of diminished renal function in hypothyroidism. Few studies or case reports have shown total amelioration of renal impairment as seen in our patient. The etiology is presumed to be multifactorial, in which hemodynamic effects and a direct effect of thyroid hormone on the kidney play an important role. We suggest that patients with renal impairment of unknown cause have thyroid function tests undertaken as part of routine investigation.

Ensete superbum ameliorates renal dysfunction in experimental diabetes mellitus.

PubMed

Sreekutty, M S; Mini, S

2016-01-01

Hyperglycemia mediated oxidative stress plays a key role in the pathogenesis of diabetic complications like nephropathy. In the present study, we evaluated the effect of ethanolic extract of Ensete superbum seeds (ESSE) on renal dysfunction and oxidative stress in streptozotocin-induced diabetic rats. Glucose, HbA1c, total protein, albumin, renal function markers (urea, uric acid and creatinine), and lipid peroxidation levels were evaluated. Renal enzymatic and non-enzymatic antioxidants were examined along with renal histopathological study. ESSE (400 mg/kg BW t) administration reduced glucose and HbA1c, and improved serum total protein and albumin in diabetic rats. ESSE in diabetic rats recorded decrement in renal function markers and renal lipid peroxidation products along with significant increment in enzymatic and non-enzymatic antioxidants. Renal morphological abnormalities of diabetic rats were markedly ameliorated by E. superbum. These results suggest that the antioxidant effect of E. superbum could ameliorate oxidative stress and delay/prevent the progress of diabetic nephropathy in diabetes mellitus.

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

Marques da Silva, A; Narciso, L

Purpose: Commercial workstations usually have their own software to calculate dynamic renal functions. However, usually they have low flexibility and subjectivity on delimiting kidney and background areas. The aim of this paper is to present a public domain software, called RenalQuant, capable to semi-automatically draw regions of interest on dynamic renal scintigraphies, extracting data and generating renal function quantification parameters. Methods: The software was developed in Java and written as an ImageJ-based plugin. The preprocessing and segmentation steps include the user’s selection of one time frame with higher activity in kidney’s region, compared with background, and low activity in themore » liver. Next, the chosen time frame is smoothed using a Gaussian low pass spatial filter (σ = 3) for noise reduction and better delimitation of kidneys. The maximum entropy thresholding method is used for segmentation. A background area is automatically placed below each kidney, and the user confirms if these regions are correctly segmented and positioned. Quantitative data are extracted and each renogram and relative renal function (RRF) value is calculated and displayed. Results: RenalQuant plugin was validated using retrospective 20 patients’ 99mTc-DTPA exams, and compared with results produced by commercial workstation software, referred as reference. The renograms intraclass correlation coefficients (ICC) were calculated and false-negative and false-positive RRF values were analyzed. The results showed that ICC values between RenalQuant plugin and reference software for both kidneys’ renograms were higher than 0.75, showing excellent reliability. Conclusion: Our results indicated RenalQuant plugin can be trustingly used to generate renograms, using DICOM dynamic renal scintigraphy exams as input. It is user friendly and user’s interaction occurs at a minimum level. Further studies have to investigate how to increase RRF accuracy and explore how to solve limitations in the segmentation step, mainly when background region has higher activity compared to kidneys. Financial support by CAPES.« less

Ascites, a New Cause for Bilateral Hydronephrosis: Case Report

PubMed Central

Jain, Deepika; Dorairajan, Smrita; Misra, Madhukar

2009-01-01

Bilateral hydronephrosis secondary to urinary obstruction leads to a buildup of back pressure in the urinary tract and may lead to impairment of renal function. We present a case of a 57-year-old male with a history of alcoholic liver cirrhosis, who presented with tense ascites and acute renal failure. Bilateral hydronephrosis was seen on abdominal ultrasound. Multiple large-volume paracenteses resulted in resolution of hydronephrosis and prompt improvement in renal function. PMID:19802498

Catheter-Based Radiorefrequency Renal Denervation Lowers Blood Pressure in Obese Hypertensive Dogs

PubMed Central

Henegar, Jeffrey R.; Zhang, Yongxing; Rama, Rita De; Hata, Cary; Hall, Michael E.

2014-01-01

BACKGROUND Obesity-induced hypertension appears to be due, in part, to increased renal sympathetic activity. Catheter-based renal denervation (RD) has been reported to lower arterial blood pressure (BP) in humans with resistant hypertension, many of whom are obese. This study was performed to assess the impact of radiofrequency–induced RD on renal function, BP, renal norepinephrine (NE), and histology of nerves along the renal artery in obese, hypertensive dogs, an experimental model that closely mimics cardiorenal and metabolic changes in obese hypertensive humans. METHODS After control measurements of cardiovascular and renal function were obtained in obese dogs fed a high-fat diet, bilateral RD was performed using the St. Jude Medical EnligHTN RD system. After RD, BP was measured continuously for 8 weeks, and glomerular filtration rate (GFR) was measured biweekly for 6 weeks. At the end of the study, renal arteries were collected for histological analysis, and kidneys were obtained for NE measurement. RESULTS Eight weeks after RD, systolic BP fell from 157±5mm Hg pre-RD to 133±3mm Hg (P < 0.01), and mean arterial pressure decreased by 9mm Hg compared with pre-RD (P < 0.01). There were no significant changes in GFR. Renal nerve injury was most prevalent 0.28–3.5mm from the renal artery lumen. RD caused injury in 46% of the renal nerves observed and reduced renal tissue NE by 42% (P < 0.01). CONCLUSIONS Catheter-based RD with the St. Jude Medical EnligHTN system lowers BP in obese dogs without significantly compromising renal function. PMID:24709437

Cross talk between primary human renal tubular cells and endothelial cells in cocultures.

PubMed

Tasnim, Farah; Zink, Daniele

2012-04-15

Interactions between renal tubular epithelial cells and adjacent endothelial cells are essential for normal renal functions but also play important roles in renal disease and repair. Here, we investigated cocultures of human primary renal proximal tubular cells (HPTC) and human primary endothelial cells to address the cross talk between these cell types. HPTC showed improved proliferation, marker gene expression, and enzyme activity in cocultures. Also, the long-term maintenance of epithelia formed by HPTC was improved, which was due to the secretion of transforming growth factor-β1 and its antagonist α2-macroglobulin. HPTC induced endothelial cells to secrete increased amounts of these factors, which balanced each other functionally and only displayed in combination the observed positive effects. In addition, in the presence of HPTC endothelial cells expressed increased amounts of hepatocyte growth factor and vascular endothelial growth factor, which have well-characterized effects on renal tubular epithelial cells as well as on endothelial cells. Together, the results showed that HPTC stimulated endothelial cells to express a functionally balanced combination of various factors, which in turn improved the performance of HPTC. The results give new insights into the cross talk between renal epithelial and endothelial cells and suggest that cocultures could be also useful models for the analysis of cellular communication in renal disease and repair. Furthermore, the characterization of defined microenvironments, which positively affect HPTC, will be helpful for improving the performance of this cell type in in vitro applications including in vitro toxicology and kidney tissue engineering.

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

PubMed

Braun, F; Brinkkötter, P T

2016-08-01

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

Treatment of Acute Renal Failure Secondary to Multiple Myeloma with Chemotherapy and Extended High Cut-Off Hemodialysis

PubMed Central

Hutchison, Colin A.; Bradwell, Arthur R.; Cook, Mark; Basnayake, Kolitha; Basu, Supratik; Harding, Stephen; Hattersley, John; Evans, Neil D.; Chappel, Mike J.; Sampson, Paul; Foggensteiner, Lukas; Adu, Dwomoa; Cockwell, Paul

2009-01-01

Background and objectives: Extended hemodialysis using a high cut-off dialyzer (HCO-HD) removes large quantities of free light chains in patients with multiple myeloma. However, the clinical utility of this method is uncertain. This study assessed the combination of chemotherapy and HCO-HD on serum free light chain concentrations and renal recovery in patients with myeloma kidney (cast nephropathy) and dialysis-dependent acute renal failure. Design, setting, participants, & measurements: An open-label study of the relationship between free light chain levels and clinical outcomes in 19 patients treated with standard chemotherapy regimens and HCO-HD. Results: There were sustained early reductions in serum free light chain concentrations (median 85% [range 50 to 97]) in 13 patients. These 13 patients became dialysis independent at a median of 27 d (range 13 to 120). Six patients had chemotherapy interrupted because of early infections and did not achieve sustained early free light chain reductions; one of these patients recovered renal function (at 105 d) the remaining 5 patients did not recover renal function. Patients who recovered renal function had a significantly improved survival (P < 0.012). Conclusion: In dialysis-dependent acute renal failure secondary to myeloma kidney, patients who received uninterrupted chemotherapy and extended HCO-HD had sustained reductions in serum free light chain concentrations and recovered independent renal function. PMID:19339414

Assessment of the relationship between renal volume and renal function after minimally-invasive partial nephrectomy: the role of computed tomography and nuclear renal scan.

PubMed

Bertolo, Riccardo; Fiori, Cristian; Piramide, Federico; Amparore, Daniele; Barrera, Monica; Sardo, Diego; Veltri, Andrea; Porpiglia, Francesco

2018-05-14

To evaluate the correlation between the loss of renal function as assessed by Tc99MAG-3 renal scan and the loss of renal volume as calculated by volumetric assessment on CT-scan in patients who underwent minimally-invasive partial nephrectomy (PN). PN prospectively-maintained database was retrospectively queried for patients who underwent minimally-invasive PN (2012-2017) for renal mass

Functional significance of the pattern of renal sympathetic nerve activation.

PubMed

Dibona, G F; Sawin, L L

1999-08-01

To assess the renal functional significance of the pattern of renal sympathetic nerve activation, computer-generated stimulus patterns (delivered at constant integrated voltage) were applied to the decentralized renal sympathetic nerve bundle and renal hemodynamic and excretory responses determined in anesthetized rats. When delivered at the same integrated voltage, stimulus patterns resembling those observed in in vivo multifiber recordings of renal sympathetic nerve activity (diamond-wave patterns) produced greater renal vasoconstrictor responses than conventional square-wave patterns. Within diamond-wave patterns, increasing integrated voltage by increasing amplitude produced twofold greater renal vasoconstrictor responses than by increasing duration. With similar integrated voltages that were subthreshold for renal vasoconstriction, neither diamond- nor square-wave pattern altered glomerular filtration rate, whereas diamond- but not square-wave pattern reversibly decreased urinary sodium excretion by 25 +/- 3%. At the same number of pulses per second, intermittent stimulation produced faster and greater renal vasoconstriction than continuous stimulation. At the same number of pulses per second, increases in rest period during intermittent stimulation proportionally augmented the renal vasoconstrictor response compared with that observed with continuous stimulation; the maximum augmentation of 55% occurred at a rest period of 500 ms. These results indicate that the pattern of renal sympathetic nerve stimulation (activity) significantly influences the rapidity, magnitude, and selectivity of the renal vascular and tubular responses.

Reversal of progressive necrotizing vasculitis with intravenous pulse cyclophosphamide and methylprednisolone.

PubMed

Fort, J G; Abruzzo, J L

1988-09-01

We describe a patient with polyarteritis nodosa who, despite therapy with daily doses of oral prednisone and cyclophosphamide, developed acute renal failure. Renal histopathologic examination demonstrated crescentic glomerulonephritis. Treatment with intravenous pulse cyclophosphamide and methylprednisolone resulted in clinical improvement and significant recovery of renal function.

Assessment of renal injury with a clinical dual head lithotriptor delivering 240 shock waves per minute.

PubMed

Handa, Rajash K; McAteer, James A; Evan, Andrew P; Connors, Bret A; Pishchalnikov, Yuri A; Gao, Sujuan

2009-02-01

Lithotriptors with 2 treatment heads deliver shock waves along separate paths. Firing 1 head and then the other in alternating mode has been suggested as a strategy to treat stones twice as rapidly as with conventional shock wave lithotripsy. Because the shock wave rate is known to have a role in shock wave lithotripsy induced injury, and given that treatment using 2 separate shock wave sources exposes more renal tissue to shock wave energy than treatment with a conventional lithotriptor, we assessed renal trauma in pigs following treatment at rapid rate (240 shock waves per minute and 120 shock waves per minute per head) using a Duet lithotriptor (Direx Medical Systems, Petach Tikva, Israel) fired in alternating mode. Eight adult female pigs (Hardin Farms, Danville, Indiana) each were treated with sham shock wave lithotripsy or 2,400 shock waves delivered in alternating mode (1,200 shock waves per head, 120 shock waves per minute per head and 240 shock waves per minute overall at a power level of 10) to the lower renal pole. Renal functional parameters, including glomerular filtration rate and effective renal plasma flow, were determined before and 1 hour after shock wave lithotripsy. The kidneys were perfusion fixed in situ and the hemorrhagic lesion was quantified as a percent of functional renal volume. Shock wave treatment resulted in no significant change in renal function and the response was similar to the functional response seen in sham shock wave treated animals. In 6 pigs treated with alternating mode the renal lesion was small at a mean +/- SEM of 0.22% +/- 0.09% of functional renal volume. Kidney tissue and function were minimally affected by a clinical dose of shock waves delivered in alternating mode (120 shock waves per minute per head and 240 shock waves per minute overall) with a Duet lithotriptor. These observations decrease concern that dual head lithotripsy at a rapid rate is inherently dangerous.

Renovascular disease, microcirculation, and the progression of renal injury: role of angiogenesis

PubMed Central

2011-01-01

Emerging evidence supports the pivotal role of renal microvascular disease as a determinant of tubulo-interstitial and glomerular fibrosis in chronic kidney disease. An intact microcirculation is vital to restore blood flow to the injured tissues, which is a crucial step to achieve a successful repair response. The purpose of this review is to discuss the impact and mechanisms of the functional and structural changes of the renal microvascular network, as well as the role of these changes in the progression and irreversibility of renal injury. Damage of the renal microcirculation and deterioration of the angiogenic response may constitute early steps in the complex pathways involved in progressive renal injury. There is limited but provocative evidence that stimulation of vascular proliferation and repair may stabilize renal function and slow the progression of renal disease. The feasibility of novel potential therapeutic interventions for stabilizing the renal microvasculature is also discussed. Targeted interventions to enhance endogenous renoprotective mechanisms focused on the microcirculation, such as cell-based therapy or the use of angiogenic cytokines have shown promising results in some experimental and clinical settings. PMID:21307362

Renal impairment in stroke patients: A comparison between the haemorrhagic and ischemic variants.

PubMed

Shrestha, Pratyush; Thapa, Shalima; Shrestha, Shikher; Lohani, Subash; Bk, Suresh; MacCormac, Oscar; Thapa, Lekhjung; Devkota, Upendra Prasad

2017-01-01

Background: Renal impairment is regularly seen in hospitalized stroke patients, affecting the outcome of patients, as well as causing difficulties in their management. A prospective cohort study was conducted to assess the trend of renal function in hospitalized ischemic and haemorrhagic stroke patients. The incidence of renal impairment in these subgroups, the contributing factors and the need for renal replacement in renal impaired patients was evaluated. Methods: Alternate day renal function testing was performed in hospitalized stroke patients. Estimated glomerular filtration rate (e-GFR) was calculated and the trend of renal function in the two stroke subgroups (haemorrhagic and ischemic) was assessed, with renal impairment defined as e-GFR < 60mL/ minute per 1.73m 2 . Results: Among 52 patients, 25 had haemorrhagic stroke (mean age 59.81 ± 14.67) and 27 had ischemic stroke (mean age 56.12 ± 13.08). The mean e-GFR (mL/minute per 1.732m 2 ) at admission in the haemorrhagic stroke subgroup was 64.79 ± 25.85 compared to 86.04 ± 26.09 in the ischemic stroke subgroup (p=0.005). Sixteen out of 25 (64%) patients in the haemorrhagic stroke subgroup and 9 out of 27 (33.3%) patients in the ischemic subgroup developed renal impairment (p=0.027). The location of the bleed (p=0.8), volume of hematoma (p=0.966) and surgical intervention (p=0.4) did not predispose the patients to renal impairment. One out of 16 patients with haemorrhagic stroke (who eventually died), and 2 out of 9 patients with ischemic stroke required renal replacement. Conclusion : Renal impairment is commonly seen in stroke patients, more so in patients who suffered haemorrhagic strokes.  The impairment, however, is transient and rarely requires renal replacement therapy.

Single dose pharmacokinetics of the transdermal rotigotine patch in patients with impaired renal function

PubMed Central

Cawello, Willi; Ahrweiler, Sascha; Sulowicz, Wladyslaw; Szymczakiewicz-Multanowska, Agnieszka; Braun, Marina

2012-01-01

AIM To evaluate the influence of different stages of chronic renal insufficiency on the pharmacokinetics and safety/tolerability of the transdermally applied dopamine agonist rotigotine in an open label group comparison including 32 subjects (healthy, mild, moderate or severe impairment of renal function and patients with end-stage renal insufficiency requiring haemodialysis). METHODS All subjects received a single transdermal 10 cm2 patch (24 h patch-on period) containing 4.5 mg rotigotine (nominal drug release 2 mg 24 h−1). Main evaluations included relative bioavailability and renal elimination of rotigotine and its metabolites. RESULTS Point estimates for the ratios between the groups with moderate to severe renal impairment and healthy subjects for the pharmacokinetic parameters AUC(0,tlast) and Cmax for the active substance unconjugated rotigotine were near 1:0.88 for AUC and 0.93 for Cmax for moderate renal impairment, 1.14 and 1.18 for severe renal impairment and 1.05 and 1.25 for end-stage renal insufficiency requiring haemodialysis. There was no correlation of these parameters with creatinine clearance. The amount of unconjugated rotigotine excreted into urine and renal clearance decreased with increasing severity of renal insufficiency but had no observable effect on total clearance as the amounts excreted were below 1% of the administered dose. Occurrence of adverse events did not increase with the degree of renal insufficiency. CONCLUSIONS The pharmacokinetic profiles of unconjugated rotigotine were similar in healthy subjects and subjects with impaired renal function indicating that no dose adjustments are required for transdermal rotigotine in patients with different stages of chronic renal insufficiency including patients on haemodialysis. PMID:21707699

Erythrocyte deformation in ischemic acute tubular necrosis and amelioration by splenectomy in the dog.

PubMed

Mandal, A K; Taylor, C A; Bell, R D; Hillman, N M; Jarnot, M D; Cunningham, J D; Phillips, L G

1991-11-01

Bilateral renal artery occlusion (RAO) for 120 minutes in dogs results in acute tubular necrosis (ATN) and peritubular capillary (PTC) congestion with rapidly deteriorating renal function. We have shown that prior splenectomy minimizes RAO-induced renal functional and histopathologic changes. The purpose of this study was to examine whether this renal protection is due to prevention of red blood cell echinocyte formation and resultant renal PTC congestion. Echinocytes (burr cells) are poorly deformable, impart high viscosity to the blood, and may hinder reperfusion by increasing resistance to renal capillary blood flow. Splenectomized (SPLX) or sham-SPLX dogs were treated with bilateral RAO for 120 minutes. After RAO, renal function and renal blood flow were monitored, and peripheral blood red blood cells were examined at 1 hour and at 24-hour intervals for 96 hours. Renal biopsies were taken 1 hour after RAO and the kidneys removed 96 hours after RAO. The RBCs and renal tissues were studied using scanning electron microscopy. Renal function was assessed by endogenous creatinine clearance. Sham-SPLX animals showed a marked and sustained decrease in creatinine clearance, consistently elevated serum creatinine levels and fractional excretion of sodium, and diffuse ATN and PTC congestion with echinocytes. These animals had a peak in circulating echinocytes 1 hour after RAO (p less than 0.05), which showed an excellent negative correlation with creatinine clearance (r = -0.999; p less than 0.001). On the contrary, SPLX animals had essentially no change in serum creatinine or fractional excretion of sodium, minimal tubular changes, no PTC congestion, and no rise in circulating echinocytes during the 96-hour observation. In vitro treatment of the postischemic red blood cells from sham animals with adenosine-inosine or fresh postischemic plasma from the SPLX animals showed almost complete reversal to discocytes (normal red blood cells), whereas in vitro treatment of postischemic red blood cells from the SPLX animals with fresh postischemic plasma from the sham animals resulted in a marked echinocytic response. We conclude that 1) a marked echinocyte response in the immediate postischemic period is an important mechanism in initiating ischemic ATN, 2) an echinocyte inducing factor may reside in the plasma of spleen-intact animals, and 3) mitigation of ATN and PTC congestion by splenectomy is, at least in part, consequential to attenuated echinocytic response in the immediate postischemic period.

Presence of transient hydronephrosis immediately after surgery has a limited influence on renal function 1 year after ileal neobladder construction.

PubMed

Narita, Takuma; Hatakeyama, Shingo; Koie, Takuya; Hosogoe, Shogo; Matsumoto, Teppei; Soma, Osamu; Yamamoto, Hayato; Yoneyama, Tohru; Tobisawa, Yuki; Yoneyama, Takahiro; Hashimoto, Yasuhiro; Ohyama, Chikara

2017-08-31

Urinary tract obstruction and postoperative hydronephrosis are risk factor for renal function deterioration after orthotopic ileal neobladder construction. However, reports of relationship between transient hydronephrosis and renal function are limited. We assess the influence of postoperative transient hydronephrosis on renal function in patients with orthotopic ileal neobladder construction. Between January 2006 and June 2013, we performed radical cystectomy in 164 patients, and 101 received orthotopic ileal neobladder construction. This study included data available from 64 patients with 128 renal units who were enrolled retrospectively. The hydronephrosis grade of each renal unit scored 0-4. The patients were divided into 4 groups according to the grade of hydronephrosis: control, low, intermediate, and high. The grade of postoperative hydronephrosis was compared with renal function 1 month and 1 year after surgery. There were no significant differences in renal function before surgery between groups. One month after surgery, the presence of hydronephrosis was significantly associated with decreased renal function. However, 1 year after urinary diversion hydronephrosis grades were improved significantly, and renal function was comparable between groups. Postoperative hydronephrosis at 1 month had no significant influence on renal function 1 year after ileal neobladder construction. Limitations include retrospective design, short follow-up periods, and a sample composition. The presence of transient hydronephrosis immediately after surgery may have limited influence on renal function 1 year after ileal neobladder construction.

Effects of short-term addition of NSAID to diuretics and/or RAAS-inhibitors on blood pressure and renal function.

PubMed

Nygård, Peder; Jansman, Frank G A; Kruik-Kollöffel, Willemien J; Barnaart, Alex F W; Brouwers, Jacobus R B J

2012-06-01

The combined post-operative use of diuretics and/or renin-angiotensin-aldosterone system (RAAS) inhibitors may increase the risk of nonsteroidal anti-inflammatory drug (NSAID) associated renal failure because of a drug-drug interaction. The aim of this study was to investigate the effect of the short-term (<4 days) post-operative combined use of NSAIDs with diuretics and/or RAAS inhibitors on renal function and blood pressure. One teaching hospital in the Netherlands. The study-design was a prospective, observational cohort-study. Based on postoperative treatment with NSAIDs, the intervention-group was compared to a control-group (no NSAIDs treatment). Systolic blood pressure and renal function expressed by the estimated glomular filtration rate (eGFR) calculated with the modification of renal desease formula. 97 patients were included in the intervention-group, 53 patients in the control-group. Patient characteristics were comparable except for one variable: 'combined use of a diuretic with a RAAS inhibitor' which was higher in the control-group (62 vs. 43 %, p = 0.046). Odds ratio for clinically relevant increase in systolic blood pressure was 0.66 (CI95 % 0.3-1.5). Odds ratio for clinical relevant decrease in renal function was 2.44 (CI95 % 1.1-5.2). On day 4 eGFR of 3 patients in the intervention- and 1 in the control-group was <50 ml/min/1.73 m(2). Odds ratios showed no significant difference of a clinically relevant increase in systolic blood pressure but showed a higher risk for a clinically relevant decrease in renal function in the intervention group. However this decrease resulted in a relevant impaired renal function (<50 ml/min/1.73 m(2)) in only 3 patients in the interventiongroup and 1 patient in the control-group. In the post-operative patient, without preexisting impaired renal function, concurrent diuretics and/or renin-angiotensinaldosterone system inhibitor therapy can be combined with short-term NSAID treatment.

Induced Autologous Stem Cell Transplantation for Treatment of Rabbit Renal Interstitial Fibrosis

PubMed Central

Ruan, Guang-Ping; Xu, Fan; Li, Zi-An; Zhu, Guang-Xu; Pang, Rong-Qing; Wang, Jin-Xiang; Cai, Xue-Min; He, Jie; Yao, Xiang; Ruan, Guang-Hong; Xu, Xin-Ming; Pan, Xing-Hua

2013-01-01

Introduction Renal interstitial fibrosis (RIF) is a significant cause of end-stage renal failure. The goal of this study was to characterize the distribution of transplanted induced autologous stem cells in a rabbit model of renal interstitial fibrosis and evaluate its therapeutic efficacy for treatment of renal interstitial fibrosis. Methods A rabbit model of renal interstitial fibrosis was established. Autologous fibroblasts were cultured, induced and labeled with green fluorescent protein (GFP). These labeled stem cells were transplanted into the renal artery of model animals at 8 weeks. Results Eight weeks following transplantation of induced autologous stem cells, significant reductions (P < 0.05) were observed in serum creatinine (SCr) (14.8 ± 1.9 mmol/L to 10.1 ± 2.1 mmol/L) and blood urea nitrogen (BUN) (119 ± 22 µmol/L to 97 ± 13 µmol/L), indicating improvement in renal function. Conclusions We successfully established a rabbit model of renal interstitial fibrosis and demonstrated that transplantation of induced autologous stem cells can repair kidney damage within 8 weeks. The repair occurred by both inhibition of further development of renal interstitial fibrosis and partial reversal of pre-existing renal interstitial fibrosis. These beneficial effects lead to the development of normal tissue structure and improved renal function. PMID:24367598

Impact of pretransplant renal function on survival after liver transplantation.

PubMed

Gonwa, T A; Klintmalm, G B; Levy, M; Jennings, L S; Goldstein, R M; Husberg, B S

1995-02-15

To determine the effect of pretransplant liver function on survival following orthotopic liver transplantation and to quantify the effects of cyclosporine administration on long-term renal function in patients undergoing liver transplant, we performed an analysis of a prospectively maintained database. Data from 569 consecutive patients undergoing liver transplantation alone who were treated with CsA for immunosuppression were used for this study. Actuarial graft and patient survival rates were calculated using Kaplan-Meier statistics. Glomerular filtration rates, serum creatinine, and the use of various immunosuppressives were analyzed for this study. The initial analysis demonstrated that patients presenting for liver transplant with hepatorenal syndrome have a significantly decreased acturial patient survival after liver transplant at 5 years compared with patients without hepatorenal syndrome (60% vs. 68%, P < 0.03). Patients with hepatorenal syndrome recovered their renal function after liver transplant. Patients who had hepatorenal syndrome were sicker and required longer stays in the intensive care unit, longer hospitalizations, and more dialysis treatments after transplantation compared with patients who did not have hepatorenal syndrome. The incidence of end-stage renal disease after liver transplantation in patients who had hepatorenal syndrome was 7%, compared with 2% in patients who did not have hepatorenal syndrome. To more fully examine the effect of pretransplant renal function on posttransplant survival, the non-hepatorenal syndrome patients were divided into quartiles depending upon their pretransplant renal function. The patients with the lowest pretransplant renal function had the same survival as the patients with the highest pretransplant renal function. In addition, there was no increased incidence of acute or chronic rejection in any of the groups. The patients with the lower pretransplant renal function were treated with more azathioprine to maintain renal function and had a negligible decrease in glomerular filtration rate following transplant. Conversely, patients with the highest level of renal function pretransplant had a 40% decline in renal function in the first year, but maintained stable renal function up to 4 years after transplant. We conclude that pretransplant renal function other than hepato-renal syndrome has no effect on patient survival after orthotopic liver transplant. Renal function after liver transplant is stable after an initial decline, despite continued administration of CsA.(ABSTRACT TRUNCATED AT 400 WORDS)

Impaired renal function and development in Belgrade rats

PubMed Central

Veuthey, Tania; Hoffmann, Dana; Vaidya, Vishal S.

2013-01-01

Belgrade rats carry a disabling mutation in the iron transporter divalent metal transporter 1 (DMT1). Although DMT1 plays a major role in intestinal iron absorption, the transporter is also highly expressed in the kidney, where its function remains unknown. The goal of this study was to characterize renal physiology of Belgrade rats. Male Belgrade rats died prematurely with ∼50% survival at 20 wk of age. Necropsy results indicated marked glomerular nephritis and chronic end-stage renal disease. By 15 wk of age, Belgrade rats displayed altered renal morphology associated with sclerosis and fibrosis. Creatinine clearance was significantly lower compared with heterozygote littermates. Urinary biomarkers of kidney injury, including albumin, fibrinogen, and kidney injury molecule-1, were significantly elevated. Pilot morphological studies suggest that nephrogenesis is delayed in Belgrade rat pups due to their low iron status and fetal growth restriction. Such defects in renal development most likely underlie the compromised renal metabolism observed in adult b/b rats. Belgrade rat kidney nonheme iron levels were not different from controls but urinary iron and transferrin levels were higher. These results further implicate an important role for the transporter in kidney function not only in iron reabsorption but also in glomerular filtration of the serum protein. PMID:24226520

Clinical course of dengue fever and its impact on renal function in renal transplant recipients and patients with chronic kidney disease.

PubMed

Arun Thomas, E T; George, Jacob; Sruthi, Devi; Vineetha, N S; Gracious, Noble

2018-04-01

Dengue fever is a mosquito-borne viral disease endemic in many tropical and sub-tropical countries. There is only limited data in the literature about dengue fever in renal transplant recipients and patients with chronic kidney disease. This study compares the clinical course of dengue fever and its impact on renal function in renal transplant recipients, patients with chronic kidney disease and patients with normal base line renal function. An observational study was conducted from 1 st May to 31 st July 2017, at a tertiary care centre of South India. A major epidemic of dengue had occurred during the study period. Twelve renal transplant recipients, 22 patients with CKD and 58 patients with normal baseline renal function (control group) admitted with dengue fever were prospectively studied. Nadir WBC count was lowest in renal transplant recipients (2575 + 1187/mm 3 ), [P<0.001]. Renal transplant recipients took more time for normalisation of platelet count (6 + 4.5 days), [P<0.001]. All 22 patients with CKD and 11 of 12 renal transplant recipients had worsening of renal function where as only 17 of 58 patients in the control group had worsening [P<0.001]. Sixteen patients with CKD, one renal transplant recipient and none among control group required hemodialysis [P<0.001]. Dialysis requiring patients had more hemoconcentration (52.5+ 19.9% increase in haemoglobin), [P<0.001]. Seven patients with CKD were dialysis dependent at the end of 2 weeks. Clinical features of dengue fever were different in renal transplant recipients and patients with CKD. Severe worsening of renal function was common in CKD patients. Worsening of renal function in renal transplant recipients was less severe and transient. This article is protected by copyright. All rights reserved.

Diabetes-Induced Reactive Oxygen Species: Mechanism of Their Generation and Role in Renal Injury

PubMed Central

Fakhruddin, Selim; Alanazi, Wael

2017-01-01

Diabetes induces the onset and progression of renal injury through causing hemodynamic dysregulation along with abnormal morphological and functional nephron changes. The most important event that precedes renal injury is an increase in permeability of plasma proteins such as albumin through a damaged glomerular filtration barrier resulting in excessive urinary albumin excretion (UAE). Moreover, once enhanced UAE begins, it may advance renal injury from progression of abnormal renal hemodynamics, increased glomerular basement membrane (GBM) thickness, mesangial expansion, extracellular matrix accumulation, and glomerulosclerosis to eventual end-stage renal damage. Interestingly, all these pathological changes are predominantly driven by diabetes-induced reactive oxygen species (ROS) and abnormal downstream signaling molecules. In diabetic kidney, NADPH oxidase (enzymatic) and mitochondrial electron transport chain (nonenzymatic) are the prominent sources of ROS, which are believed to cause the onset of albuminuria followed by progression to renal damage through podocyte depletion. Chronic hyperglycemia and consequent ROS production can trigger abnormal signaling pathways involving diverse signaling mediators such as transcription factors, inflammatory cytokines, chemokines, and vasoactive substances. Persistently, increased expression and activation of these signaling molecules contribute to the irreversible functional and structural changes in the kidney resulting in critically decreased glomerular filtration rate leading to eventual renal failure. PMID:28164134

Acceptance and effects of a therapeutic renal food in pet cats with chronic kidney disease

PubMed Central

Fritsch, Dale A; Jewell, Dennis E

2015-01-01

Introduction Renal foods are used to manage chronic kidney disease (CKD) in dogs and cats, but their effectiveness may be limited by the ability to transition animals to them. Material and Methods In a prospective study, pet cats with previously undiagnosed kidney disease (20 International Renal Interest Society (IRIS) 1, 61 IRIS 2, 14 IRIS 3/4, 33 at risk for CKD) were transitioned to a renal food. Markers of renal function were measured and owners answered questionnaires about their pet over one year. Results All but eight cats (120/128; 94 per cent) successfully transitioned to the renal food. Most of the time, cats moderately or extremely liked the food (89 per cent), ate at least half (73 per cent) and were moderately or extremely enthusiastic while eating (68 per cent). Cats rarely disliked the food (2 per cent) or refused to eat it (1 per cent). Markers of renal function were unchanged in IRIS 1 and 2 cats and changed little in IRIS 3/4 cats. In all groups, owner-assessed quality of life improved initially and then remained stable. Mean bodyweight did not change in cats with CKD. Conclusions Most cats with CKD successfully transitioned to the renal food. The results also support previous studies that the renal food can help stabilise cats with CKD. PMID:26587240

Renal involvement in leprosy: evaluation of patients in Turkey

PubMed Central

Ozturk, Tulin; Can, Ilkay

2017-01-01

Introduction Renal involvement in leprosy has previously been described in the literature and can include amyloidosis, glomerulonephritis, nephrosclerosis, tubulointerstitial nephritis, and granulomas. Aim To evaluate renal involvement in Turkish patients with leprosy. Material and methods In total, 32 patients with lepromatous leprosy but without any co-morbidities and 35 healthy control subjects were evaluated for renal involvement at the Elazig Training and Research Hospital in Turkey. The laboratory tests and radiological results concerning renal function were taken from both the patients’ medical records and from current examinations. Results The levels of creatinine, urea, and leukocyturia in the lepromatous leprosy patients were significantly higher than in the controls (p < 0.001, p < 0.001; p = 0.001, p < 0.01; p = 0.036, p < 0.05, respectively). No significant differences in the proteinuria, hematuria, sodium, or potassium levels were found between the leprosy and control groups (p > 0.05). On ultrasonographic examination, the prevalence of renal cortical cysts and renal cortical echogenicity in the leprosy patients was significantly higher than in the controls (p = 0.020, p < 0.05, respectively). There were no significant differences in terms of nephrolithiasis, parapelvic cysts, or hydronephrosis between the leprosy and control groups (p > 0.05). Conclusions Evaluating the renal function in all leprosy patients is important to detect abnormalities and to prevent renal failure, which remains a potential cause of death in this disease. PMID:28670253

Prognostic Value of Pre-operative Renal Insufficiency in Urothelial Carcinoma: A Systematic Review and Meta-Analysis.

PubMed

Cao, Jian; Zhao, Xiaokun; Zhong, Zhaohui; Zhang, Lei; Zhu, Xuan; Xu, Ran

2016-10-11

The effect of pre-operative renal insufficiency on urothelial carcinoma (UC) prognosis has been investigated by numerous studies. While the majority report worse UC outcomes in patients with renal insufficiency, the results between the studies differed wildly. To enable us to better estimate the prognostic value of renal insufficiency on UC, we performed a systematic review and meta-analysis based on the published literature. A total of 16 studies which involved 5,232 patients with UC, investigated the relationship between pre-operative renal insufficiency and disease prognosis. Estimates of combined hazard ratio (HR) for bladder urothelial carcinoma recurrence, cancer-specific survival (CSS) and overall survival (OS) were 1.65 (95% CI, 1.11-2.19), 1.59 (95% CI, 1.14-2.05) and 1.45 (95% CI, 1.19-1.71), respectively; and for upper urinary tract urothelial carcinoma recurrence, CSS and OS were 2.27 (95% CI, 1.42-3.12), 1.02 (95% CI, 0.47-1.57) and 1.52 (95% CI, 1.05-1.99), respectively. Our results indicate that UC patients with pre-operative renal insufficiency tend to have higher recurrence rates and poorer survival compared to those with clinically normal renal function, thus renal function should be closely monitored in these patients. The impact of intervention for renal insufficiency on the prognosis of UC needs to be further studied.

Use of Oral Bisphosphonates by Older Adults with Fractures and Impaired Renal Function

PubMed Central

Sadowski, Cheryl A; Spencer, Tara; Yuksel, Nese

2011-01-01

Background: The manufacturers of oral bisphosphonates (alendronate, risedronate) recommend avoiding use of these drugs in patients with renal impairment. However, many patients who have osteoporosis or who are at risk of fracture are elderly and may have renal impairment. This situation poses a quandary for clinicians in deciding how best to manage osteoporosis in this high-risk population. Objective: To synthesize published evidence regarding the use and safety of oral bisphosphonates for patients with impaired renal function. Methods: The following databases were searched up to October 2010: PubMed, MEDLINE, Embase, the Cochrane Library, and International Pharmaceutical Abstracts. The following key words and terms were used for the searches: bisphosphonates, alendronate, risedronate, Fosamax, Actonel, “renal failure”, “renal insufficiency”, “chronic kidney disease”, and “end-stage renal disease”. The manufacturers of Fosamax and Actonel were asked to provide information about use of their products in patients with renal impairment, including unpublished pharmacokinetic studies or reports of adverse drug events. Results: The search yielded 2 post hoc analyses of safety data, 1 case–control study, 1 case series, 4 retrospective chart analyses, and 2 prospective studies. According to these publications, numerous patients with decreased renal function have received bisphosphonates and have experienced improvement in bone mineral density and/or reduction in risk of fractures, with no increase in adverse effects. Increased renal damage occurred in some individuals with underlying renal disorders, as described in case reports. Conclusions: Although the literature is limited, there is evidence that alendronate and risedronate are well tolerated and effective when used by individuals with renal impairment. Further research is required to confirm the benefits and risks of using these medications in patients with renal impairment. PMID:22479027

(99m)Tc-DTPA diuretic renal scintigraphy in cats with nephroureterolithiasis.

PubMed

Hecht, Silke; Lawson, Sarah M; Lane, India F; Sharp, Dorothy E; Daniel, Gregory B

2010-06-01

The purpose of this study was to evaluate results of diuretic renal scintigraphy in 32 feline kidneys with nephroureterolithiasis and variable degrees of renal pelvis/ureteral dilation. Six kidneys showed a non-obstructive scintigraphic pattern, with a downward slope of time-activity curves (TAC) and a median excretion half-time of radiopharmaceutical (T((1/2))) of 6.09 (5.08-8.43) min. Eight kidneys showed an obstructive pattern, with a continuous rise of TAC and median T((1/2)) of -7.91 (-43.13-0.00) min. In one kidney with presumptive partial obstruction scintigraphic results were equivocal. Seventeen kidneys, most of which had an individual kidney glomerular filtration rate below 0.5ml/min/kg, had non-diagnostic studies. Diuretic renal scintigraphy may be a useful adjunct modality in the diagnosis of ureteral obstruction in some cats if renal function is maintained. However, the large number of non-diagnostic studies in animals with decreased renal function represents a clear limitation of the technique. Copyright 2009 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

Geometric Alteration of Renal Arteries After Fenestrated Grafting and the Impact on Renal Function.

PubMed

Ou, Jiale; Chan, Yiu-Che; Chan, Crystal Yin-Tung; Cheng, Stephen W K

2017-05-01

This study aims to investigate the degree of geometric change on renal arteries and its impact on renal function after fenestrated endovascular aortic repair (fEVAR). Twenty-five patients with fEVAR were included. There were 47 renal arteries target vessels, and 43 of these (22 left and 21 right vessels) stented successfully. Their preoperative and first postoperative follow-up computed tomography (CT) images were reconstructed using the Aquarius workstation (TeraRecon, San Mateo, CA, USA). The superior mesenteric artery (SMA) or celiac axis (if SMA was stented) was appointed as reference origin. The longitudinal orientation of a renal artery or a stent was represented by a takeoff angle (ToA) between the renal artery or stent and the distal abdominal aorta. The postoperative stent ToAs were compared with those of preoperative renal arteries. Preoperative and short-term postoperative serum creatinine levels were measured. Renal function impairment was indicated as a >30% or >2.0 mg/dL rise in serum creatinine compared to the preoperative level. The relationship between postoperative renal function impairment and the stent orientation or geometric changes in renal arteries was correlated. The patency rate of renal arteries was 100% at the first postoperative CT review. The average ToAs of both renal arteries were significantly enlarged after stenting (P < 0.05). Seven stent deformations (16.3%) in four patients (16.0%) were observed. They were attributed to caudal misalignment of the fenestrated stent graft (n = 6) or inaccurate graft sizing (n = 1). There was no stent fracture or target vessel loss. Postoperatively, nine patients (36.0%) at day 1 and 10 patients (41.7%) after 3 months suffered the renal function impairment. This was found not to be associated with the stent angulation or angular change of the renal arteries (both P > 0.05). The three patients with stent deformation due to misalignment suffered postoperative renal function impairment and continuing deterioration in renal function. Implanted renal stents could angulate renal arteries more cephalad after fenestrated stenting. Postoperative renal function impairment was not associated with the stent orientation and changes in vessel orientation. Accurate fenestrated alignment is important to maintain stent performance and preserve renal function. Copyright © 2017 Elsevier Inc. All rights reserved.

A Single-Dose, Open-Label Study of the Pharmacokinetics, Safety, and Tolerability of Lisdexamfetamine Dimesylate in Individuals With Normal and Impaired Renal Function

PubMed Central

Ermer, James; Corcoran, Mary; Lasseter, Kenneth; Marbury, Thomas; Yan, Brian

2016-01-01

Background: Lisdexamfetamine (LDX) and d-amphetamine pharmacokinetics were assessed in individuals with normal and impaired renal function after a single LDX dose; LDX and d-amphetamine dialyzability was also examined. Methods: Adults (N = 40; 8/group) were enrolled in 1 of 5 renal function groups [normal function, mild impairment, moderate impairment, severe impairment/end-stage renal disease (ESRD) not requiring hemodialysis, and ESRD requiring hemodialysis] as estimated by glomerular filtration rate (GFR). Participants with normal and mild to severe renal impairment received 30 mg LDX; blood samples were collected predose and serially for 96 hours. Participants with ESRD requiring hemodialysis received 30 mg LDX predialysis and postdialysis separated by a washout period of 7–14 days. Predialysis blood samples were collected predose, serially for 72 hours, and from the dialyzer during hemodialysis; postdialysis blood samples were collected predose and serially for 48 hours. Pharmacokinetic end points included maximum plasma concentration (Cmax) and area under the plasma concentration versus time curve from time 0 to infinity (AUC0–∞) or to last assessment (AUClast). Results: Mean LDX Cmax, AUClast, and AUC0–∞ in participants with mild to severe renal impairment did not differ from those with normal renal function; participants with ESRD had higher mean Cmax and AUClast than those with normal renal function. d-amphetamine exposure (AUClast and AUC0–∞) increased and Cmax decreased as renal impairment increased. Almost no LDX and little d-amphetamine were recovered in the dialyzate. Conclusions: There seems to be prolonged d-amphetamine exposure after 30 mg LDX as renal impairment increases. In individuals with severe renal impairment (GFR: 15 ≤ 30 mL·min−1·1.73 m−2), the maximum LDX dose is 50 mg/d; in patients with ESRD (GFR: <15 mL·min−1·1.73 m−2), the maximum LDX dose is 30 mg/d. Neither LDX nor d-amphetamine is dialyzable. PMID:26926668

EET Enhances Renal Function in Obese Mice Resulting in Restoration of Mfn1/2 -HO-1 Signaling, and Decrease in Hypertension through Inhibition of Sodium Chloride Co-Transporter.

PubMed

Schragenheim, Joseph; Bellner, Lars; Cao, Jian; Singh, Shailendra P; Bamshad, David; McClung, John A; Maayan, Omri; Meissner, Aliza; Grant, Ilana; Stier, Charles T; Abraham, Nader G

2018-05-19

We have previously reported that epoxyeicosatrienoic acid (EET) has multiple beneficial effects on renal and adipose tissue function, in addition to its vasodilatory action; it increases insulin sensitivity and inhibits inflammation. In an examination of the signaling mechanisms by which EET reduces renal and peri-renal fat function, we hypothesized that EET ameliorates obesity-induced renal dysfunction by improving sodium excretion, reducing the sodium-chloride cotransporter NCC, lowering blood pressure, and enhancing mitochondrial and thermogenic gene levels in PGC-1α dependent mice. EET-agonist treatment normalized glucose metabolism, renal ENaC and NCC protein expression, urinary sodium excretion and blood pressure in obese (db/db) mice. A marked improvement in mitochondrial integrity, thermogenic genes, and PGC-1α-HO-1-adiponectin signaling occurred. Knockout of PGC-1α in EET-treated mice resulted in a reversal of these beneficial effects including a decrease in sodium excretion, elevation of blood pressure and an increase in the pro-inflammatory adipokine nephroblastoma overexpressed gene (NOV). In the elucidation of the effects of EET on peri-renal adipose tissue, EET increased adiponectin, mitochondrial integrity, thermogenic genes and decreased NOV, i.e. "Browning' peri-renal adipose phenotype that occurs under high fat diets. Taken together, these data demonstrate a critical role of an EET agonist in the restoration of healthy adipose tissue with reduced release of inflammatory molecules, such as AngII and NOV, thereby preventing their detrimental impact on sodium absorption and NCC levels and the development of obesity-induced renal dysfunction. Copyright © 2018. Published by Elsevier Inc.

Predictive abilities of cardiovascular biomarkers to rapid decline of renal function in Chinese community-dwelling population: a 5-year prospective analysis.

PubMed

Fu, Shihui; Liu, Chunling; Luo, Leiming; Ye, Ping

2017-11-09

Predictive abilities of cardiovascular biomarkers to renal function decline are more significant in Chinese community-dwelling population without glomerular filtration rate (GFR) below 60 ml/min/1.73m 2 , and long-term prospective study is an optimal choice to explore this problem. Aim of this analysis was to observe this problem during the follow-up of 5 years. In a large medical check-up program in Beijing, there were 948 participants with renal function evaluated at baseline and follow-up of 5 years. Physical examinations were performed by well-trained physicians. Blood samples were analyzed by qualified technicians in central laboratory. Median rate of renal function decline was 1.46 (0.42-2.91) mL/min/1.73m 2 /year. Rapid decline of renal function had a prevalence of 23.5% (223 participants). Multivariate linear and Logistic regression analyses confirmed that age, sex, baseline GFR, homocysteine and N-terminal pro B-type natriuretic peptide (NT-proBNP) had independently predictive abilities to renal function decline rate and rapid decline of renal function (p < 0.05 for all). High-sensitivity cardiac troponin T (hs-cTnT), carotid femoral pulse wave velocity and central augmentation index had no statistically independent association with renal function decline rate and rapid decline of renal function (p > 0.05 for all). Homocysteine and NT-proBNP rather than hs-cTnT had independently predictive abilities to rapid decline of renal function in Chinese community-dwelling population without GFR below 60 ml/min/1.73m 2 . Baseline GFR was an independent factor predicting the rapid decline of renal function. Arterial stiffness and compliance had no independent effect on rapid decline of renal function. This analysis has a significant implication for public health, and changing the homocysteine and NT-proBNP levels might slow the rapid decline of renal function.

The additive effects of atorvastatin and insulin on renal function and renal organic anion transporter 3 function in diabetic rats.

PubMed

Thongnak, Laongdao; Pongchaidecha, Anchalee; Jaikumkao, Krit; Chatsudthipong, Varanuj; Chattipakorn, Nipon; Lungkaphin, Anusorn

2017-10-19

Hyperglycemia-induced oxidative stress is usually found in diabetic condition. 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors, statins, are widely used as cholesterol-lowering medication with several "pleiotropic" effects in diabetic patients. This study aims to evaluate whether the protective effects of atorvastatin and insulin on renal function and renal organic anion transporter 3 (Oat3) function involve the modulation of oxidative stress and pancreatic function in type 1 diabetic rats. Type 1 diabetes was induced by intraperitoneal injection of streptozotocin (50 mg/kg BW). Atorvastatin and insulin as single or combined treatment were given for 4 weeks after diabetic condition had been confirmed. Diabetic rats demonstrated renal function and renal Oat3 function impairment with an increased MDA level and decreased SOD protein expression concomitant with stimulation of renal Nrf2 and HO-1 protein expression. Insulin plus atorvastatin (combined) treatment effectively restored renal function as well as renal Oat3 function which correlated with the decrease in hyperglycemia and oxidative stress. Moreover, pancreatic inflammation and apoptosis in diabetic rats were ameliorated by the combined drugs treatment. Therefore, atorvastatin plus insulin seems to exert the additive effect in improving renal functionby alleviating hyperglycemiaand the modulation of oxidative stress, inflammation and apoptosis.

P wave dispersion and maximum P wave duration are independently associated with rapid renal function decline.

PubMed

Su, Ho-Ming; Tsai, Wei-Chung; Lin, Tsung-Hsien; Hsu, Po-Chao; Lee, Wen-Hsien; Lin, Ming-Yen; Chen, Szu-Chia; Lee, Chee-Siong; Voon, Wen-Chol; Lai, Wen-Ter; Sheu, Sheng-Hsiung

2012-01-01

The P wave parameters measured by 12-lead electrocardiogram (ECG) are commonly used as noninvasive tools to assess for left atrial enlargement. There are limited studies to evaluate whether P wave parameters are independently associated with decline in renal function. Accordingly, the aim of this study is to assess whether P wave parameters are independently associated with progression to renal end point of ≥25% decline in estimated glomerular filtration rate (eGFR). This longitudinal study included 166 patients. The renal end point was defined as ≥25% decline in eGFR. We measured two ECG P wave parameters corrected by heart rate, i.e. corrected P wave dispersion (PWdisperC) and corrected P wave maximum duration (PWdurMaxC). Heart function and structure were measured from echocardiography. Clinical data, P wave parameters, and echocardiographic measurements were compared and analyzed. Forty-three patients (25.9%) reached renal end point. Kaplan-Meier curves for renal end point-free survival showed PWdisperC > median (63.0 ms) (log-rank P = 0.004) and PWdurMaxC > median (117.9 ms) (log-rank P<0.001) were associated with progression to renal end point. Multivariate forward Cox-regression analysis identified increased PWdisperC (hazard ratio [HR], 1.024; P = 0.001) and PWdurMaxC (HR, 1.029; P = 0.001) were independently associated with progression to renal end point. Our results demonstrate that increased PWdisperC and PWdurMaxC were independently associated with progression to renal end point. Screening patients by means of PWdisperC and PWdurMaxC on 12 lead ECG may help identify a high risk group of rapid renal function decline.

Mechanisms responsible for decreased glomerular filtration in hibernation and hypothermia

NASA Technical Reports Server (NTRS)

Tempel, G. E.; Musacchia, X. J.; Jones, S. B.

1977-01-01

Measurements of blood pressure, heart rate, red blood cell and plasma volumes, and relative distribution of cardiac output were made on hibernating and hypothermic adult male and female golden hamsters weighing 120-140 g to study the mechanisms underlying the elimination or marked depression of renal function in hibernation and hypothermia. The results suggest that the elimination or marked depression in renal function reported in hibernation and hypothermia may partly be explained by alterations in cardiovascular system function. Renal perfusion pressure which decreases nearly 60% in both hibernation and hypothermia and a decrease in plasma volume of roughly 35% in the hypothermic animal might both be expected to markedly alter glomerular function.

Echocardiographic predictors of change in renal function with intravenous diuresis for decompensated heart failure.

PubMed

Gannon, Stephen A; Mukamal, Kenneth J; Chang, James D

2018-06-14

The aim of this study was to identify echocardiographic predictors of improved or worsening renal function during intravenous diuresis for decompensated heart failure. Secondary aim included defining the incidence and clinical risk factors for acute changes in renal function with decongestion. A retrospective review of 363 patients admitted to a single centre for decompensated heart failure who underwent intravenous diuresis and transthoracic echocardiography was conducted. Clinical, echocardiographic, and renal function data were retrospectively collected. A multinomial logistic regression model was created to determine relative risk ratios for improved renal function (IRF) or worsening renal function (WRF). Within this cohort, 36% of patients experienced WRF, 35% had stable renal function, and 29% had IRF. Patients with WRF were more likely to have a preserved left ventricular ejection fraction compared with those with stable renal function or IRF (P = 0.02). Patients with IRF were more likely to have a dilated, hypokinetic right ventricle compared with those with stable renal function or WRF (P ≤ 0.01), although this was not significant after adjustment for baseline characteristics. Left atrial size, left ventricular linear dimensions, and diastolic function did not significantly predict change in renal function. An acute change in renal function occurred in 65% of patients admitted with decompensated heart failure. WRF was statistically more likely in patients with a preserved left ventricular ejection fraction. A trend towards IRF was noted in patients with global right ventricular dysfunction. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Use of prazosin in management of hypertension in patients with chronic renal failure and in renal transplant recipients.

PubMed Central

Curtis, J R; Bateman, F J

1975-01-01

Prazosin was used in combination with other antihypertensive drugs in the successful management of hypertension in seven patients with chronic renal failure and six renal transplant recipients, also with chronic renal failure. The addition of small doses of prazosin (mean 3 mg/day) to the antihypertensive regimen produced significant falls in systolic and diastolic blood pressures in both the lying and standing positions. The standing blood pressures were significantly lower than the lying blood pressures during prazosin treatment. Neither the mean blood urea concentrations nor the mean plasma creatinine concentrations changed significantly during prazosin administration. Chromium-51 edetic acid clearances did not change significantly during prazosin treatment in the seven patients in whom it was measured. Severe symptomatic postural hypotension occurred in one patient a week after starting prazosin 3 mg/day. This hypotensive episode was associated with a transient and reversible deterioration in renal function. Another patient developed a rash while on prazosin but it was probably related to propranolol rather than prazosin. Prazosin is thus an effective antihypertensive drug in patients with chronic renal failure, and it may be used with a variety of other drugs. It should be used cautiously, however, since patients with chronic renal failure may respond to small doses, and significant postural falls in blood pressure may result. There was no evidence that the use of prazosin resulted in progressive deterioration in the residual renal function of the patients with chronic renal failure. PMID:811312

Use of prazosin in management of hypertension in patients with chronic renal failure and in renal transplant recipients.

PubMed

Curtis, J R; Bateman, F J

1975-11-22

Prazosin was used in combination with other antihypertensive drugs in the successful management of hypertension in seven patients with chronic renal failure and six renal transplant recipients, also with chronic renal failure. The addition of small doses of prazosin (mean 3 mg/day) to the antihypertensive regimen produced significant falls in systolic and diastolic blood pressures in both the lying and standing positions. The standing blood pressures were significantly lower than the lying blood pressures during prazosin treatment. Neither the mean blood urea concentrations nor the mean plasma creatinine concentrations changed significantly during prazosin administration. Chromium-51 edetic acid clearances did not change significantly during prazosin treatment in the seven patients in whom it was measured. Severe symptomatic postural hypotension occurred in one patient a week after starting prazosin 3 mg/day. This hypotensive episode was associated with a transient and reversible deterioration in renal function. Another patient developed a rash while on prazosin but it was probably related to propranolol rather than prazosin. Prazosin is thus an effective antihypertensive drug in patients with chronic renal failure, and it may be used with a variety of other drugs. It should be used cautiously, however, since patients with chronic renal failure may respond to small doses, and significant postural falls in blood pressure may result. There was no evidence that the use of prazosin resulted in progressive deterioration in the residual renal function of the patients with chronic renal failure.

MR measures of renal perfusion, oxygen bioavailability and total renal blood flow in a porcine model: noninvasive regional assessment of renal function.

PubMed

Wentland, Andrew L; Artz, Nathan S; Fain, Sean B; Grist, Thomas M; Djamali, Arjang; Sadowski, Elizabeth A

2012-01-01

Magnetic resonance imaging (MRI) may be a useful adjunct to current methods of evaluating renal function. MRI is a noninvasive imaging modality that has the ability to evaluate the kidneys regionally, which is lacking in current clinical methods. Other investigators have evaluated renal function with MRI-based measurements, such as with techniques to measure cortical and medullary perfusion, oxygen bioavailability and total renal blood flow (TRBF). However, use of all three techniques simultaneously, and therefore the relationships between these MRI-derived functional parameters, have not been reported previously. To evaluate the ability of these MRI techniques to track changes in renal function, we scanned 11 swine during a state of hyperperfusion with acetylcholine and a saline bolus and subsequently scanned during a state of hypoperfusion with the prolonged use of isoflurane anesthesia. For each time point, measurements of perfusion, oxygen bioavailability and TRBF were acquired. Measurements of perfusion and oxygen bioavailability were compared with measurements of TRBF for all swine across all time points. Cortical perfusion, cortical oxygen bioavailability, medullary oxygen bioavailability and TRBF significantly increased with the acetylcholine challenge. Cortical perfusion, medullary perfusion, cortical oxygen bioavailability and TRBF significantly decreased during isoflurane anesthesia. Cortical perfusion (Spearman's correlation coefficient = 0.68; P < 1 × 10(-6)) and oxygen bioavailability (Spearman's correlation coefficient = -0.60; P < 0.0001) correlated significantly with TRBF, whereas medullary perfusion and oxygen bioavailability did not correlate with TRBF. Our results demonstrate expected changes given the pharmacologically induced changes in renal function. Maintenance of the medullary oxygen bioavailability in low blood flow states may reflect the autoregulation particular to this region of the kidney. The ability to non-invasively measure all three parameters of kidney function in a single MRI examination and to evaluate the relationships between these functional parameters is potentially useful for evaluating the state of the human kidneys in situ in future studies.

28 CFR 79.61 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

.... The term includes in situ lung cancers. (m) Readily available documentation means documents in the... injury means structural or functional damage to the kidney tubules that results in renal disease and... resulting in chronic renal dysfunction. (j) Nonmalignant respiratory disease means fibrosis of the lung...

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.

Post-Discharge Worsening Renal Function in Patients with Type 2 Diabetes and Recent Acute Coronary Syndrome.

PubMed

Morici, Nuccia; Savonitto, Stefano; Ponticelli, Claudio; Schrieks, Ilse C; Nozza, Anna; Cosentino, Francesco; Stähli, Barbara E; Perrone Filardi, Pasquale; Schwartz, Gregory G; Mellbin, Linda; Lincoff, A Michael; Tardif, Jean-Claude; Grobbee, Diederick E

2017-09-01

Worsening renal function during hospitalization for an acute coronary syndrome is strongly predictive of in-hospital and long-term outcome. However, the role of post-discharge worsening renal function has never been investigated in this setting. We considered the placebo cohort of the AleCardio trial comparing aleglitazar with standard medical therapy among patients with type 2 diabetes mellitus and a recent acute coronary syndrome. Patients who had died or had been admitted to hospital for heart failure before the 6-month follow-up, as well as patients without complete renal function data, were excluded, leaving 2776 patients for the analysis. Worsening renal function was defined as a >20% reduction in estimated glomerular filtration rate from discharge to 6 months, or progression to macroalbuminuria. The Cox regression analysis was used to determine the prognostic impact of 6-month renal deterioration on the composite of all-cause death and hospitalization for heart failure. Worsening renal function occurred in 204 patients (7.34%). At a median follow-up of 2 years the estimated rates of death and hospitalization for heart failure per 100 person-years were 3.45 (95% confidence interval [CI], 2.46-6.36) for those with worsening renal function, versus 1.43 (95% CI, 1.14-1.79) for patients with stable renal function. At the adjusted analysis worsening renal function was associated with the composite endpoint (hazard ratio 2.65; 95% CI, 1.57-4.49; P <.001). Post-discharge worsening renal function is not infrequent among patients with type 2 diabetes and acute coronary syndromes with normal or mildly depressed renal function, and is a strong predictor of adverse cardiovascular events. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Geyskes, G.G.; Oei, H.Y.; Puylaert, C.B.

Radioisotope renography was performed in 21 patients with hypertension and unilateral renal artery stenosis with and without premedication with 25 mg of captopril, and the results were compared with the effect of percutaneous transluminal angioplasty on the blood pressure, assessed 6 weeks after angioplasty. Angioplasty caused a considerable decrease in blood pressure in 15 of the 21 patients. In 12 of these 15 patients, captopril induced changes in the time-activity curves of the affected kidney only, suggesting deterioration of the excretory function of that kidney, while the function of the contralateral kidney remained normal. After angioplasty the asymmetry in themore » time-activity curves diminished despite identical pretreatment with captopril. Such captopril-induced unilateral impairment of the renal function was not seen in the six patients with unilateral renal artery stenosis whose blood pressure did not change after percutaneous transluminal angioplasty or in 13 patients with hypertension and normal renal arteries. The functional impairment of the affected kidneys was characterized by a decrease of /sup 99m/Tc-diethylenetriamine pentaacetic acid uptake and a delay of /sup 131/I-hippurate excretion, while the /sup 131/I-hippurate uptake remained unaffected. These data are in agreement with a reduced glomerular filtration rate and diuresis during preservation of the renal blood flow, changes that can be expected after converting enzyme inhibition in a kidney with low perfusion and an active, renin-mediated autoregulation of the glomerular filtration rate. These data suggest that functional captopril-induced unilateral changes, shown by split renal function studies with noninvasive gamma camera scintigraphy, can be used as a diagnostic test for renovascular hypertension caused by unilateral renal artery stenosis.« less

Atherosclerotic renal artery stenosis in the post-CORAL era part 1: the renal penumbra concept and next-generation functional diagnostic imaging.

PubMed

Sag, Alan Alper; Inal, Ibrahim; Okcuoglu, John; Rossignol, Patrick; Ortiz, Alberto; Afsar, Baris; Sos, Thomas A; Kanbay, Mehmet

2016-04-01

After three neutral trials in which renal artery stenting failed to improve renal function or reduce cardiovascular and renal events, the controversy surrounding diagnosis and treatment of atherosclerotic renal artery stenosis and renovascular hypertension has led to paradigm shifts in the diagnostic algorithm. Noninvasive determination of earlier events (cortex hypoxia and renal artery hemodynamic changes) will supersede late sequelae (calcific stenosis, renal cortical thinning). Therefore, this review proposes the concept of renal penumbra in defining at-risk ischemic renal parenchyma. The complex field of functional renal magnetic resonance imaging will be reviewed succinctly in a clinician-directed fashion. Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Prospective radionuclide renal function evaluation and its correlation with radiological findings in patients with Kock pouch urinary diversion

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

Chen, K.K.; Chang, L.S.; Chen, M.T.

1991-05-01

In an attempt to understand better the status of renal function after Kock pouch urinary diversion we conducted a prospective evaluation of renal function in 25 patients using the radionuclide 131iodine-hippurate. Studies were done before, and at 1 month and every 6 months for 30 months postoperatively. The radionuclide results were then compared to excretory urography and contrast study of the reservoir. Our renal function study included the determination of individual and total effective renal plasma flow (ml. per minute), the time to maximal radioactivity over the kidney (peak time in minutes) and a renogram. The mean total (both kidneys)more » effective renal plasma flow rates before (25 patients) and at month 1 (19), month 6 (14), month 12 (12), month 18 (6), month 24 (6) and month 30 (7) after operation were 385.5 +/- 112.2, 310.5 +/- 109.9, 362.7 +/- 69.2, 442.0 +/- 97.5, 468.2 +/- 82.5, 405.7 +/- 70.6 and 414.0 +/- 65.1, respectively. A comparison of individual and total effective renal plasma flow before and after operation revealed that only the change of the flow at each or both sides of the kidney before and at 1 month after the operation reached statistically significant differences, respectively (p less than 0.05, paired t test). Postoperatively 5 of 6 patients with hydronephrosis had abnormal peak time and a third segment on the renogram was performed on the corresponding side of the kidney. No reflux was noted on contrast study of the reservoir of any patient followed for up to 30 months. In conclusion, the radionuclide renal function evaluation showed a significant decrease of renal function 1 month after Kock pouch diversion, then it resumed and remained stable (neither improved nor deteriorated) for 30 months. Also the abnormal peak time and third segment on the renogram usually implicated a dilated upper urinary tract.« less

Effects of Renal Impairment on Steady-State Plasma Concentrations of Rivastigmine: A Population Pharmacokinetic Analysis of Capsule and Patch Formulations in Patients with Alzheimer's Disease.

PubMed

Lefèvre, Gilbert; Callegari, Francesca; Gsteiger, Sandro; Xiong, Yuan

2016-10-01

The glomerular filtration rate (GFR), a measure of renal function, decreases by approximately 10 mL/min every 10 years after the age of 40 years, which could lead to the accumulation of drugs and/or renal toxicity. Pharmacokinetic studies of drugs excreted both renally and non-renally are desirable in patients with impaired renal function, defined by parameters including estimated GFR (eGFR) and creatinine clearance (CL CR ). We describe here a population pharmacokinetic analysis of the possible effects of renal impairment on steady-state plasma concentrations of rivastigmine and its metabolite NAP226-90 after rivastigmine patch (5 cm 2 [4.6 mg/24 h], 10 cm 2 [9.5 mg/24 h], 15 cm 2 [13.3 mg/24 h], and 20 cm 2 [17.4 mg/24 h]) and capsule (1.5, 3, 4.5, and 6 mg/12 h) treatment in patients with Alzheimer's disease. The data used to conduct the current pharmacokinetic analysis were obtained from the pivotal phase III, 24-week, multicenter, randomized, double-blind, placebo- and active-controlled, parallel-group study (IDEAL). One blood sample was collected from each patient at steady-state to measure plasma concentrations of rivastigmine and NAP226-90 using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The steady-state plasma concentrations of rivastigmine and NAP226-90 were plotted against CL CR and eGFR data, and boxplots were constructed after stratification by renal function. The two groups (mild/no renal impairment vs. moderate/severe/end-stage renal impairment) showed comparable demographic covariates for all patch sizes and capsule doses. No correlation was observed between CL CR or eGFR and plasma concentrations of rivastigmine or NAP226-90. Boxplots of concentrations of rivastigmine or NAP226-90 for each dose largely overlapped for patch and capsule. Additionally, model-based estimates of plasma concentrations adjusted for body weight yielded similar results. The results of this study show that renal function does not affect rivastigmine or NAP226-90 steady-state plasma concentrations, and no dose adjustment in patients with renal impairment is required. CLINICALTRIALS.GOV: NCT00099242.

Population pharmacokinetics of pomalidomide in patients with relapsed or refractory multiple myeloma with various degrees of impaired renal function.

PubMed

Li, Yan; Wang, Xiaomin; O'Mara, Edward; Dimopoulos, Meletios A; Sonneveld, Pieter; Weisel, Katja C; Matous, Jeffrey; Siegel, David S; Shah, Jatin J; Kueenburg, Elisabeth; Sternas, Lars; Cavanaugh, Chloe; Zaki, Mohamed; Palmisano, Maria; Zhou, Simon

2017-01-01

Pomalidomide is an immunomodulatory drug for treatment of relapsed or refractory multiple myeloma (rrMM) in patients who often have comorbid renal conditions. To assess the impact of renal impairment on pomalidomide exposure, a population pharmacokinetics (PPK) model of pomalidomide in rrMM patients with various degrees of impaired renal function was developed. Intensive and sparse pomalidomide concentration data collected from two clinical studies in rrMM patients with normal renal function, moderately impaired renal function, severely impaired renal function not requiring dialysis, and with severely impaired renal function requiring dialysis were pooled over the dose range of 2 to 4 mg, to assess specifically the influence of the impaired renal function as a categorical variable and a continuous variable on pomalidomide clearance and plasma exposure. In addition, pomalidomide concentration data collected on dialysis days from both the withdrawal (arterial) side and from the returning (venous) side of the dialyzer, from rrMM patients with severely impaired renal function requiring dialysis, were used to assess the extent to which dialysis contributes to the removal of pomalidomide from blood circulation. PPK analyses demonstrated that moderate to severe renal impairment not requiring dialysis has no influence on pomalidomide clearance or plasma exposure, as compared to those patients with normal renal function, while pomalidomide exposure increased approximately 35% in patients with severe renal impairment requiring dialysis on nondialysis days. In addition, dialysis increased total body pomalidomide clearance from 5 L/h to 12 L/h, indicating that dialysis will significantly remove pomalidomide from the blood circulation. Thus, pomalidomide should be administered post-dialysis on the days of dialysis.

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

Gupta, Pushpender, E-mail: pugupta@wakehealth.edu; Allen, Brian C., E-mail: bcallen2@wakehealth.edu; Chen, Michael Y., E-mail: mchen@wakehealth.edu

Purpose: To evaluate renal function changes related to radiofrequency ablation (RFA) for the treatment of multifocal renal neoplasms. Methods: This is an institutional review board-approved, Health Insurance Portability and Accountability Act compliant retrospective study of all patients treated with computed tomography guided RFA for multifocal renal neoplasms at one institution. Fifty-seven subjects, mean age 70 (range 37-88) years, underwent RFA of 169 renal neoplasms (average size 2.0 cm). Subjects had between 2 and 8 (mean 2.96) neoplasms ablated. Estimated glomerular filtration rate (eGFR) was measured before and after RFA. Complications related to RFA were recorded. Results: eGFR decreased on averagemore » of 4.4 % per tumor treated and 6.7 % per ablation session (average 1.76 tumors treated per session). For subjects with the largest neoplasm measuring >3 cm, eGFR decreased an average of 14.5 % during the course of their treatment. If the largest neoplasm measured 2-3 cm, eGFR decreased an average of 7.7 %, and if the largest neoplasm measured <2 cm, eGFR decreased an average of 3.8 %. Subjects with reduced baseline renal function were more likely to have a greater decline in eGFR after RFA. There was a minor complication rate of 6.3 % (6 of 96 sessions), none of which required treatment, and a major complication rate of 4.2 % (4 of 96 sessions). Conclusion: RFA for the treatment of multifocal renal neoplasms results in mild decline of renal function.« less

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

PubMed

Davenport, Andrew

2017-10-01

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

[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.

Value of Nephrometry Score Constituents on Perioperative Outcomes and Split Renal Function in Patients Undergoing Minimally Invasive Partial Nephrectomy.

PubMed

Watts, Kara L; Ghosh, Propa; Stein, Solomon; Ghavamian, Reza

2017-01-01

To assess the relationship between individual nephrometry score (NS) constituents (RENAL) on perioperative outcomes and renal function of the surgical kidney in patients undergoing laparoscopic partial nephrectomy or robotic-assisted partial nephrectomy. Two hundred forty-five patients who underwent laparoscopic partial nephrectomy or robotic-assisted partial nephrectomy between 2005 and 2014 were retrospectively reviewed. Each renal mass' NS was calculated from preoperative computed tomography imaging. Multivariate regression analysis was used to evaluate the effect of NS variables on perioperative outcomes and change in overall renal function (as estimated by glomerular filtration rate) from preoperative to 1-year postoperative. A cohort analysis assessed the effect of NS variables on change in split renal function of the surgical kidney from pre- to postoperative based on nuclear medicine renal scintigraphy. Tumor radius (R), endophytic nature (E), and nearness to collecting system (N) variables significantly and incrementally predicted a longer operative time and warm ischemia time. Overall renal function based on glomerular filtration rate was not affected by any NS variable. However, percent function of the surgical kidney by renal scintigraphy significantly decreased postoperatively as R and E values increased. R, E, and N were associated with significant changes in warm ischemia time and operative time. R and E were associated with a significant decrease in split renal function of the surgical kidney at 1 year after surgery but not with overall renal function. R, E, and N are the NS constituents most relevant to perioperative outcomes and postoperative differential renal function after partial nephrectomy. Copyright © 2016. Published by Elsevier Inc.

Early detection of endothelial injury and dysfunction in conjunction with correction of hemodynamic maladjustment can effectively restore renal function in type 2 diabetic nephropathy.

PubMed

Futrakul, Narisa; Butthep, Punnee; Vongthavarawat, Varaphon; Futrakul, Prasit; Sirisalipoch, Sasitorn; Chaivatanarat, Tawatchai; Suwanwalaikorn, Sompongse

2006-01-01

This paper was aimed to investigate (1) the early marker of endothelial injury in type 2 diabetes, (2) the intrarenal hemodynamics and renal function, and (3) the therapeutic strategy aiming to restore renal function. Fifty patients (35 normoalbuminuric and 15 albuminuric type 2 diabetes) were examined. Blood was collected for determination of circulating vascular endothelial cells (CEC) and the serum was prepared for determination of transforming growth factor beta (TGFbeta), ratio of CEC/TGFbeta, and soluble vascular cell adhesion molecule. Intrarenal hemodynamics and renal function were also assessed. The results showed that increased number of circulating EC, elevated TGFbeta and depleted ratio of CEC/TGFbeta were significantly observed. Intrarenal hemodynamic study revealed a hemodynamic maladjustment characterized by preferential constriction of the efferent arteriole, intraglomerular hypertension and reduction in peritubular capillary flow. It was concluded that early marker of endothelial injury is reflected by increasing number of CEC. Such markers correlate with the glomerular endothelial dysfunction associated with hemodynamic maladjustment. Early detection of endothelial injury and appropriate correction of hemodynamic maladjustment by multidrug vasodilators can effectively restore renal function in type 2 diabetic nephropathy.

Utility of the RENAL index -Radius; Exophytic/endophytic; Nearness to sinus; Anterior/posterior; Location relative to polar lines- in the management of renal masses.

PubMed

Konstantinidis, C; Trilla, E; Lorente, D; Morote, J

2016-12-01

The growing incidence of renal masses and the wide range of available treatments require predictive tools that support the decision making process. The RENAL index -Radius; Exophytic/endophytic; Nearness to sinus; Anterior/posterior; Location relative to polar lines- helps standardise the anatomy of a renal mass by differentiating 3 groups of complexity. Since the introduction of the index, there have been a growing number of studies, some of which have been conflicting, that have evaluated the clinical utility of its implementation. To analyse the scientific evidence on the relationship between the RENAL index and the main strategies for managing renal masses. A search was conducted in the Medline database, which found 576 references on the RENAL index. In keeping with the PRISM Declaration, we selected 100 abstracts and ultimately reviewed 96 articles. The RENAL index has a high degree of interobserver correlation and has been validated as a predictive nomogram of histological results. In active surveillance, the index has been related to the tumour growth rate and probability of nephrectomy. In ablative therapy, the index has been associated with therapeutic efficacy, complications and tumour recurrence. In partial nephrectomy, the index has been related to the rate of complications, conversion to radical surgery, ischaemia time, function preservation and tumour recurrence, a finding also observed in radical nephrectomy. The RENAL index is an objective, reproducible and useful system as a predictive tool of highly relevant clinical parameters such as the rate of complications, ischaemia time, renal function and oncological results in the various currently accepted treatments for the management of renal masses. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Sympathetic neural control of the kidney in hypertension.

PubMed

DiBona, G F

1992-01-01

Efferent renal sympathetic nerve activity is elevated in human essential hypertension as well as in several forms of experimental hypertension in animals. In addition, bilateral complete renal denervation delays the development and/or attenuates the magnitude of the hypertension in several different forms of experimental hypertension in animals. Efferent renal sympathetic nerve activity is known to have dose-dependent effects on renal blood flow, the glomerular filtration rate, renal tubular sodium and water reabsorption, and the renin secretion rate, which are capable of contributing, singly or in combination, to the development, maintenance, and exacerbation of the hypertensive state. Of the many factors known to influence the central nervous system integrative regulation of efferent renal sympathetic nerve activity, two environmental factors, a high dietary sodium intake and environmental stress, are capable of significant interaction. This resultant increase in efferent renal sympathetic nerve activity and subsequent renal functional alterations can participate in the hypertensive process. This is especially evident in the presence of an underlying genetic predisposition to the development of hypertension. Thus, interactions between environmental and genetic influences can produce alterations in the sympathetic neural control of renal function that play an important role in hypertension.

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

PubMed

DiBona, G F

1986-01-17

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

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

PubMed

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

2015-12-01

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

Copeptin is associated with kidney length, renal function, and prevalence of simple cysts in a population-based study.

PubMed

Ponte, Belen; Pruijm, Menno; Ackermann, Daniel; Vuistiner, Philippe; Guessous, Idris; Ehret, Georg; Alwan, Heba; Youhanna, Sonia; Paccaud, Fred; Mohaupt, Markus; Péchère-Bertschi, Antoinette; Vogt, Bruno; Burnier, Michel; Martin, Pierre-Yves; Devuyst, Olivier; Bochud, Murielle

2015-06-01

Arginine vasopressin (AVP) has a key role in osmoregulation by facilitating water transport in the collecting duct. Recent evidence suggests that AVP may have additional effects on renal function and favor cyst growth in polycystic kidney disease. Whether AVP also affects kidney structure in the general population is unknown. We analyzed the association of copeptin, an established surrogate for AVP, with parameters of renal function and morphology in a multicentric population-based cohort. Participants from families of European ancestry were randomly selected in three Swiss cities. We used linear multilevel regression analysis to explore the association of copeptin with renal function parameters as well as kidney length and the presence of simple renal cysts assessed by ultrasound examination. Copeptin levels were log-transformed. The 529 women and 481 men had median copeptin levels of 3.0 and 5.2 pmol/L, respectively (P<0.001). In multivariable analyses, the copeptin level was associated inversely with eGFR (β=-2.1; 95% confidence interval [95% CI], -3.3 to -0.8; P=0.002) and kidney length (β=-1.2; 95% CI, -1.9 to -0.4; P=0.003) but positively with 24-hour urinary albumin excretion (β=0.11; 95% CI, 0.01 to 0.20; P=0.03) and urine osmolality (β=0.08; 95% CI, 0.05 to 0.10; P<0.001). A positive association was found between the copeptin level and the presence of renal cysts (odds ratio, 1.6; 95% CI, 1.1 to 2.4; P=0.02). These results suggest that AVP has a pleiotropic role in renal function and may favor the development of simple renal cysts. Copyright © 2015 by the American Society of Nephrology.

Copeptin Is Associated with Kidney Length, Renal Function, and Prevalence of Simple Cysts in a Population-Based Study

PubMed Central

Ponte, Belen; Pruijm, Menno; Ackermann, Daniel; Vuistiner, Philippe; Guessous, Idris; Ehret, Georg; Alwan, Heba; Youhanna, Sonia; Paccaud, Fred; Mohaupt, Markus; Péchère-Bertschi, Antoinette; Vogt, Bruno; Burnier, Michel; Martin, Pierre-Yves; Devuyst, Olivier

2015-01-01

Arginine vasopressin (AVP) has a key role in osmoregulation by facilitating water transport in the collecting duct. Recent evidence suggests that AVP may have additional effects on renal function and favor cyst growth in polycystic kidney disease. Whether AVP also affects kidney structure in the general population is unknown. We analyzed the association of copeptin, an established surrogate for AVP, with parameters of renal function and morphology in a multicentric population-based cohort. Participants from families of European ancestry were randomly selected in three Swiss cities. We used linear multilevel regression analysis to explore the association of copeptin with renal function parameters as well as kidney length and the presence of simple renal cysts assessed by ultrasound examination. Copeptin levels were log-transformed. The 529 women and 481 men had median copeptin levels of 3.0 and 5.2 pmol/L, respectively (P<0.001). In multivariable analyses, the copeptin level was associated inversely with eGFR (β=−2.1; 95% confidence interval [95% CI], −3.3 to −0.8; P=0.002) and kidney length (β=−1.2; 95% CI, −1.9 to −0.4; P=0.003) but positively with 24-hour urinary albumin excretion (β=0.11; 95% CI, 0.01 to 0.20; P=0.03) and urine osmolality (β=0.08; 95% CI, 0.05 to 0.10; P<0.001). A positive association was found between the copeptin level and the presence of renal cysts (odds ratio, 1.6; 95% CI, 1.1 to 2.4; P=0.02). These results suggest that AVP has a pleiotropic role in renal function and may favor the development of simple renal cysts. PMID:25270071

Can computed tomography volumetry of the renal cortex replace MAG3-scintigraphy in all patients for determining split renal function?

PubMed

Houbois, Christian; Haneder, Stefan; Merkt, Martin; Morelli, John N; Schmidt, Matthias; Hellmich, Martin; Mueller, Roman-Ulrich; Wahba, Roger; Maintz, David; Puesken, Michael

2018-06-01

The current gold standard for determination of split renal function (SRF) is Tc-99m-mercapto-acetyltriglycin (MAG3) scintigraphy. Initial studies comparing MAG3-scintigraphy and CT-based renal cortex volumetry (RCV) for calculation of SRF have shown similar results in highly selected patient collectives with normal renal function (i.e. living kidney donors). This study aims to compare MAG3-scintigraphy and CT-RCV within a large unselected patient collective including patients with impaired renal function. For this assessment, 279 datasets (131 men, 148 women; mean age: 54.2 ± 12.9 years, range: 24-84 years) of patients who underwent MAG3-scintigraphy and contrast-enhanced abdominal CT within two weeks were retrospectively analyzed. Two independent readers assessed the CT-RCV in all CT datasets using a semi-automated volumetry tool. The MAG3-scintigraphy and CT-RCV methods were compared, stratified for the eGFR. Statistical analysis included descriptive statistics as well as inter- observer agreement. The absolute mean difference between the percentage contribution of the left and the right kidneys in total MAG3-clearance was 8.6%. Independent of eGFR, an overall sufficient agreement between both methods was established in all patients. A relatively small, tolerable systemic error resulted in an underestimation (max. 2%) of the left renal contribution to overall RCV. The results demonstrate that CT-RCV is a potential clinical replacement for MAG3-scintigraphy for calculation of SRF: CT-RCV demonstrates clinically tolerable differences with MAG3-scintigraphy, independent of patient eGFR. The relative complexity of the RCV method utilized is a potential limitation and may have contributed to the acceptable but only fair to moderate level of intra-reader reliability. Copyright © 2018 Elsevier B.V. All rights reserved.

Effect of changing from first- to second-line antiretroviral therapy on renal function: a retrospective study based on data from a single health facility in Namibia.

PubMed

Kalemeera, Francis; Mbango, Christofina; Mubita, Mwangana; Naikaku, Esther; Gaida, Razia; Godman, Brian

2016-08-01

Tenofovir disoproxil fumarate (TDF) and lopinavir/ritonavir (LPV/r) can cause renal impairment with this combination co-administered during second-line combination antiretroviral therapy (cART) potentially associated with greater risk of nephrotoxicity. As a result, the aim of this study is to assess effects of second-line cART on renal function. Retrospective longitudinal study in patients receiving cART. 71 patients received TDF, zidovudine or stavudine, each combined with 3TC/NVP or 3TC/EFV. Before second-line cART, 46.5% had abnormal kidney function. First-line cART had no relationship with calculated creatinine clearance (CrCl). During second-line cART, more males than females had abnormal renal function and more females experienced increases in CrCl. Calculated CrCl during second-line cART related strongly with CrCl during first-line cART. Time spent on cART had a weak relationship with CrCl. Patients on first-line cART for several years without renal impairment may experience new onset impairment during second line cART. Patients with pre-existing renal impairment just before switching to second-line cART may experience a further decline.

Impaired renal function modifies the risk of severe hypoglycaemia among users of insulin but not glyburide: a population-based nested case-control study.

PubMed

Weir, Matthew A; Gomes, Tara; Mamdani, Muhammad; Juurlink, David N; Hackam, Daniel G; Mahon, Jeffrey L; Jain, Arsh K; Garg, Amit X

2011-06-01

Little evidence justifies the avoidance of glyburide in patients with impaired renal function. We aimed to determine if renal function modifies the risk of hypoglycaemia among patients using glyburide. We conducted a nested case-control study using administrative records and laboratory data from Ontario, Canada. We included outpatients 66 years of age and older with diabetes mellitus and prescriptions for glyburide, insulin or metformin. We ascertained hypoglycaemic events using administrative records and estimated glomerular filtration rates (eGFR) using serum creatinine concentrations. From a cohort of 19,620 patients, we identified 204 cases whose eGFR was ≥ 60 mL/min/1.73 m(2) (normal renal function) and 354 cases whose eGFR was < 60 mL/min/1.73 m(2) (impaired renal function). Compared to metformin, glyburide is associated with a greater risk of hypoglycaemia in patients with both normal [adjusted odds ratio (OR) 9.0, 95% confidence interval (95% CI) 4.9-16.4] and impaired renal function (adjusted OR 6.0, 95% CI 3.8-9.5). We observed a similar relationship when comparing insulin to metformin; the risk was greater in patients with normal renal function (adjusted OR 18.7, 95% CI 10.5-33.5) compared to those with impaired renal function (adjusted OR 7.9, 95% CI 5.0-12.4). Tests of interaction showed that among glyburide users, renal function did not significantly modify the risk of hypoglycaemia, but among insulin users, impaired renal function is associated with a lower risk. In this population-based study, impaired renal function did not augment the risk of hypoglycaemia associated with glyburide use.

Multimarker assessment for the prediction of renal function improvement after percutaneous revascularization for renal artery stenosis.

PubMed

Staub, Daniel; Partovi, Sasan; Zeller, Thomas; Breidthardt, Tobias; Kaech, Max; Boeddinghaus, Jasper; Puelacher, Christian; Nestelberger, Thomas; Aschwanden, Markus; Mueller, Christian

2016-06-01

Identifying patients likely to have improved renal function after percutaneous transluminal renal angioplasty and stenting (PTRA) for renal artery stenosis (RAS) is challenging. The purpose of this study was to use a comprehensive multimarker assessment to identify those patients who would benefit most from correction of RAS. In 127 patients with RAS and decreased renal function and/or hypertension referred for PTRA, quantification of hemodynamic cardiac stress using B-type natriuretic peptide (BNP), renal function using estimated glomerular filtration rate (eGFR), parenchymal renal damage using resistance index (RI), and systemic inflammation using C-reactive protein (CRP) were performed before intervention. Predefined renal function improvement (increase in eGFR ≥10%) at 6 months occurred in 37% of patients. Prognostic accuracy as quantified by the area under the receiver-operating characteristics curve for the ability of BNP, eGFR, RI and CRP to predict renal function improvement were 0.59 (95% CI, 0.48-0.70), 0.71 (95% CI, 0.61-0.81), 0.52 (95% CI, 0.41-0.65), and 0.56 (95% CI, 0.44-0.68), respectively. None of the possible combinations increased the accuracy provided by eGFR (lower eGFR indicated a higher likelihood for eGFR improvement after PTRA, P=ns for all). In the subgroup of 56 patients with pre-interventional eGFR <60 mL/min/1.73 m(2), similar findings were obtained. Quantification of renal function, but not any other pathophysiologic signal, provides at least moderate accuracy in the identification of patients with RAS in whom PTRA will improve renal function.

Osthole ameliorates renal ischemia-reperfusion injury by inhibiting inflammatory response.

PubMed

Zheng, Yi; Lu, Min; Ma, Lulin; Zhang, Shudong; Qiu, Min; Ma, Xin

2013-01-01

Renal ischemia-reperfusion (I/R) injury is a primary cause of acute renal failure that results in high mortality. This study aimed to investigate the effect of osthole, a natural coumarin derivative, on renal I/R injury in a rat model. Rats were randomly allocated to the sham operation + vehicle, I/R + vehicle, and I/R + osthole groups. Renal I/R injury was induced by clamping the left renal artery for 45 min followed by 12 h of reperfusion and a contralateral nephrectomy. Osthole (40 mg/kg) was intraperitoneally injected 30 min before inducing I/R. Renal function and histological damage were determined subsequently. Myeloperoxidase activity, monocyte/macrophage infiltration, as well as tumor necrosis factor-α, IL-1β, and activated p38 mitogen-activated protein kinase expression in kidneys were also assessed. Osthole treatment significantly ameliorated I/R-induced renal functional and morphological injuries. Moreover, osthole treatment attenuated myeloperoxidase activity, monocyte/macrophage infiltration, and tumor necrosis factor-α, IL-1β, and activated p38 mitogen-activated protein kinase expression in kidneys. Osthole treatment ameliorates renal I/R injury by inhibiting inflammatory responses in kidneys. Thus, osthole may represent a novel practical strategy to prevent renal I/R injury. Copyright © 2013 S. Karger AG, Basel.

Functional dilatation and medial remodeling of the renal artery in response to chronic increased blood flow.

PubMed

Roan, Jun-Neng; Yeh, Chin-Yi; Chiu, Wen-Cheng; Lee, Chou-Hwei; Chang, Shih-Wei; Jiangshieh, Ya-Fen; Tsai, Yu-Chuan; Lam, Chen-Fuh

2011-01-01

Renal blood flow (RBF) is tightly regulated by several intrinsic pathways in maintaining optimal kidney blood supply. Using a rat model of aortocaval (AC) fistula, we investigated remodeling of the renal artery following prolonged increased blood flow. An AC fistula was created in the infrarenal aorta of anesthetized rats, and changes of blood flow in the renal artery were assessed using an ultrasonic flow probe. Morphological changes and expression of endothelial nitric oxide synthase and matrix metalloproteinase-2 in the remodeled renal artery were analyzed. Blood flow in the renal artery increased immediately after creation of AC fistula, but normal RBF was restored 8 weeks later. The renal artery dilated significantly 8 weeks after operation. Expression of endothelial nitric oxide synthase and matrix metalloproteinase-2 was upregulated shortly after blood flow increase, and returned to baseline levels after 3 weeks. Histological sections showed luminal dilatation with medial thickening and endothelial cell-to-smooth muscle cell attachments in the remodeled renal artery. Increased RBF was accommodated by functional dilatation and remodeling in the medial layer of the renal artery in order to restore normal blood flow. Our results provide important mechanistic insight into the intrinsic regulation of the renal artery in response to increased RBF. Copyright © 2011 S. Karger AG, Basel.

Potential Use of Autologous Renal Cells from Diseased Kidneys for the Treatment of Renal Failure.

PubMed

George, Sunil K; Abolbashari, Mehran; Jackson, John D; Aboushwareb, Tamer; Atala, Anthony; Yoo, James J

2016-01-01

Chronic kidney disease (CKD) occurs when certain conditions cause the kidneys to gradually lose function. For patients with CKD, renal transplantation is the only treatment option that restores kidney function. In this study, we evaluated primary renal cells obtained from diseased kidneys to determine whether their normal phenotypic and functional characteristics are retained, and could be used for cell therapy. Primary renal cells isolated from both normal kidneys (NK) and diseased kidneys (CKD) showed similar phenotypic characteristics and growth kinetics. The expression levels of renal tubular cell markers, Aquaporin-1 and E-Cadherin, and podocyte-specific markers, WT-1 and Nephrin, were similar in both NK and CKD kidney derived cells. Using fluorescence- activated cell sorting (FACS), specific renal cell populations were identified and included proximal tubular cells (83.1% from NK and 80.3% from CKD kidneys); distal tubular cells (11.03% from NK and 10.9% from CKD kidneys); and podocytes (1.91% from NK and 1.78% from CKD kidneys). Ultra-structural analysis using scanning electron microscopy (SEM) revealed microvilli on the apical surface of cultured cells from NK and CKD samples. Moreover, transmission electron microscopy (TEM) analysis showed a similar organization of tight junctions, desmosomes, and other intracellular structures. The Na+ uptake characteristics of NK and CKD derived renal cells were also similar (24.4 mmol/L and 25 mmol/L, respectively) and no significant differences were observed in the protein uptake and transport characteristics of these two cell isolates. These results show that primary renal cells derived from diseased kidneys such as CKD have similar structural and functional characteristics to their counterparts from a normal healthy kidney (NK) when grown in vitro. This study suggests that cells derived from diseased kidney may be used as an autologous cell source for renal cell therapy, particularly in patients with CKD or end-stage renal disease (ESRD).

A retrospective analysis of laparoscopic partial nephrectomy with segmental renal artery clamping and factors that predict postoperative renal function.

PubMed

Li, Pu; Qin, Chao; Cao, Qiang; Li, Jie; Lv, Qiang; Meng, Xiaoxin; Ju, Xiaobing; Tang, Lijun; Shao, Pengfei

2016-10-01

To evaluate the feasibility and efficiency of laparoscopic partial nephrectomy (LPN) with segmental renal artery clamping, and to analyse the factors affecting postoperative renal function. We conducted a retrospective analysis of 466 consecutive patients undergoing LPN using main renal artery clamping (group A, n = 152) or segmental artery clamping (group B, n = 314) between September 2007 and July 2015 in our department. Blood loss, operating time, warm ischaemia time (WIT) and renal function were compared between groups. Univariable and multivariable linear regression analyses were applied to assess the correlations of selected variables with postoperative glomerular filtration rate (GFR) reduction. Volumetric data and estimated GFR of a subset of 60 patients in group B were compared with GFR to evaluate the correlation between these functional variables and preserved renal function after LPN. The novel technique slightly increased operating time, WIT and intra-operative blood loss (P < 0.001), while it provided better postoperative renal function (P < 0.001) compared with the conventional technique. The blocking method and tumour characteristics were independent factors affecting GFR reduction, while WIT was not an independent factor. Correlation analysis showed that estimated GFR presented better correlation with GFR compared with kidney volume (R(2) = 0.794 cf. R(2) = 0.199) in predicting renal function after LPN. LPN with segmental artery clamping minimizes warm ischaemia injury and provides better early postoperative renal function compared with clamping the main renal artery. Kidney volume has a significantly inferior role compared with eGFR in predicting preserved renal function. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

Functional MRI detects perfusion impairment in renal allografts with delayed graft function.

PubMed

Hueper, Katja; Gueler, Faikah; Bräsen, Jan Hinrich; Gutberlet, Marcel; Jang, Mi-Sun; Lehner, Frank; Richter, Nicolas; Hanke, Nils; Peperhove, Matti; Martirosian, Petros; Tewes, Susanne; Vo Chieu, Van Dai; Großhennig, Anika; Haller, Hermann; Wacker, Frank; Gwinner, Wilfried; Hartung, Dagmar

2015-06-15

Delayed graft function (DGF) after kidney transplantation is not uncommon, and it is associated with long-term allograft impairment. Our aim was to compare renal perfusion changes measured with noninvasive functional MRI in patients early after kidney transplantation to renal function and allograft histology in biopsy samples. Forty-six patients underwent MRI 4-11 days after transplantation. Contrast-free MRI renal perfusion images were acquired using an arterial spin labeling technique. Renal function was assessed by estimated glomerular filtration rate (eGFR), and renal biopsies were performed when indicated within 5 days of MRI. Twenty-six of 46 patients had DGF. Of these, nine patients had acute rejection (including borderline), and eight had other changes (e.g., tubular injury or glomerulosclerosis). Renal perfusion was significantly lower in the DGF group compared with the group with good allograft function (231 ± 15 vs. 331 ± 15 ml·min(-1)·100 g(-1), P < 0.001). Living donor allografts exhibited significantly higher perfusion values compared with deceased donor allografts (P < 0.001). Renal perfusion significantly correlated with eGFR (r = 0.64, P < 0.001), resistance index (r = -0.57, P < 0.001), and cold ischemia time (r = -0.48, P < 0.01). Furthermore, renal perfusion impairment early after transplantation predicted inferior renal outcome and graft loss. In conclusion, noninvasive functional MRI detects renal perfusion impairment early after kidney transplantation in patients with DGF. Copyright © 2015 the American Physiological Society.

Celiac disease or positive tissue transglutaminase antibodies in patients undergoing renal biopsies.

PubMed

Nurmi, Rakel; Metso, Martti; Pörsti, Ilkka; Niemelä, Onni; Huhtala, Heini; Mustonen, Jukka; Kaukinen, Katri; Mäkelä, Satu

2018-01-01

An association between celiac disease and renal diseases has been suggested, but the results are controversial. To investigate the prevalence of celiac disease autoimmunity among individuals undergoing renal biopsies and to evaluate whether co-existent celiac autoimmunity influences the clinical outcome of the renal disease. The prevalence of celiac autoimmunity (previous diagnosis of celiac disease or positive tissue transglutaminase antibodies) was determined in 827 consecutive patients undergoing kidney biopsies due to clinical indications. Up to 15 years' follow-up data on kidney function and co-morbidities were obtained. Celiac autoimmunity was found in 45 (5.4%) patients. Among the IgA nephropathy patients, 8.2% of had celiac autoimmunity. At the time of kidney biopsy and after a median follow-up of 5 to 6 years, renal function measured by estimated glomerular filtration rate (eGFR) was inferior in IgA nephropathy patients with celiac autoimmunity compared to those without it (P=0.048 and P=0.022, respectively). The prevalence of celiac autoimmunity seems to be high in patients undergoing renal biopsies, especially in patients with IgA nephropathy. Such autoimmunity may be associated with worse renal function in IgA nephropathy. Hence the co-existence of celiac disease should be taken into consideration when treating patients with renal diseases. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Renal function monitoring in heart failure – what is the optimal frequency? A narrative review

PubMed Central

Wright, David; Devonald, Mark Alexander John; Pirmohamed, Munir

2017-01-01

The second most common cause of hospitalization due to adverse drug reactions in the UK is renal dysfunction due to diuretics, particularly in patients with heart failure, where diuretic therapy is a mainstay of treatment regimens. Therefore, the optimal frequency for monitoring renal function in these patients is an important consideration for preventing renal failure and hospitalization. This review looks at the current evidence for optimal monitoring practices of renal function in patients with heart failure according to national and international guidelines on the management of heart failure (AHA/NICE/ESC/SIGN). Current guidance of renal function monitoring is in large part based on expert opinion, with a lack of clinical studies that have specifically evaluated the optimal frequency of renal function monitoring in patients with heart failure. Furthermore, there is variability between guidelines, and recommendations are typically nonspecific. Safer prescribing of diuretics in combination with other antiheart failure treatments requires better evidence for frequency of renal function monitoring. We suggest developing more personalized monitoring rather than from the current medication‐based guidance. Such flexible clinical guidelines could be implemented using intelligent clinical decision support systems. Personalized renal function monitoring would be more effective in preventing renal decline, rather than reacting to it. PMID:28901643

The kidney in congestive heart failure: 'are natriuresis, sodium, and diuretics really the good, the bad and the ugly?'.

PubMed

Verbrugge, Frederik H; Dupont, Matthias; Steels, Paul; Grieten, Lars; Swennen, Quirine; Tang, W H Wilson; Mullens, Wilfried

2014-02-01

This review discusses renal sodium handling in heart failure. Increased sodium avidity and tendency to extracellular volume overload, i.e. congestion, are hallmark features of the heart failure syndrome. Particularly in the case of concomitant renal dysfunction, the kidneys often fail to elicit potent natriuresis. Yet, assessment of renal function is generally performed by measuring serum creatinine, which has inherent limitations as a biomarker for the glomerular filtration rate (GFR). Moreover, glomerular filtration only represents part of the nephron's function. Alterations in the fractional reabsorptive rate of sodium are at least equally important in emerging therapy-refractory congestion. Indeed, renal blood flow decreases before the GFR is affected in congestive heart failure. The resulting increased filtration fraction changes Starling forces in peritubular capillaries, which drive sodium reabsorption in the proximal tubules. Congestion further stimulates this process by augmenting renal lymph flow. Consequently, fractional sodium reabsorption in the proximal tubules is significantly increased, limiting sodium delivery to the distal nephron. Orthosympathetic activation probably plays a pivotal role in those deranged intrarenal haemodynamics, which ultimately enhance diuretic resistance, stimulate neurohumoral activation with aldosterone breakthrough, and compromise the counter-regulatory function of natriuretic peptides. Recent evidence even suggests that intrinsic renal derangements might impair natriuresis early on, before clinical congestion or neurohumoral activation are evident. This represents a paradigm shift in heart failure pathophysiology, as it suggests that renal dysfunction-although not by conventional GFR measurements-is driving disease progression. In this respect, a better understanding of renal sodium handling in congestive heart failure is crucial to achieve more tailored decongestive therapy, while preserving renal function. © 2013 The Authors. European Journal of Heart Failure © 2013 European Society of Cardiology.

Coexistence of Anti-Glomerular Basement Membrane Glomerulonephritis and Membranous Nephropathy in a Female Patient with Preserved Renal Function.

PubMed

Ogawara, Aoi; Harada, Makoto; Ichikawa, Tohru; Fujii, Kazuaki; Ehara, Takashi; Kobayashi, Mamoru

2017-12-01

Renal prognosis for anti-glomerular basement membrane (GBM) glomerulonephritis is poor. The greater the amount of anti-GBM antibody binding the antigen (type IV collagen of the glomerular basement membrane), the greater the number of crescents that develop in glomeruli, resulting in progression of renal impairment. Immunofluorescence staining reveals linear IgG depositions on glomerular capillary walls. Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in middle-aged to elderly patients. Immune complex is deposited in the sub-epithelial space of the glomerulus resulting in the development of a membranous lesion. Immunofluorescence staining reveals granular IgG depositions on glomerular capillary walls. Coexisting anti-GBM glomerulonephritis and MN are rare and, here we report a case of coexisting anti-GBM glomerulonephritis and MN with preserved renal function. There are some cases of coexisting anti-GBM glomerulonephritis and MN do not show severely decreased renal function. A 76-year-old Japanese woman presented with nephrotic syndrome, microscopic hematuria, and was positive for anti-GBM antibody. Kidney biopsy revealed linear and granular IgG depositions in glomerular capillary walls, crescent formations, and electron-dense deposits in the sub-epithelial space. She was diagnosed with anti-GBM glomerulonephritis and MN. Steroid and cyclosporine therapy achieved complete remission, and kidney function was preserved. In conclusion, coexisting anti-GBM glomerulonephritis and MN can have preserved renal function. IgG subclass of deposited anti-GBM antibody may be associated with the severity of anti-GBM glomerulonephritis. In addition, in the case of nephrotic syndrome with hematuria, we should consider the possibility of coexisting anti-GBM glomerulonephritis and MN.

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

Wendler, J. J., E-mail: johann.wendler@med.ovgu.de; Porsch, M.; Huehne, S.

Irreversible electroporation (IRE) is a novel nonthermal tissue ablation technique by high current application leading to apoptosis without affecting extracellular matrix. Previous results of renal IRE shall be supplemented by functional MRI and differentiated histological analysis of renal parenchyma in a chronic treatment setting. Three swine were treated with two to three multifocal percutaneous IRE of the right kidney. MRI was performed before, 30 min (immediate-term), 7 days (short-term), and 28 days (mid-term) after IRE. A statistical analysis of the lesion surrounded renal parenchyma intensities was made to analyze functional differences depending on renal part, side and posttreatment time. Histologicalmore » follow-up of cortex and medulla was performed after 28 days. A total of eight ablations were created. MRI showed no collateral damage of surrounded tissue. The highest visual contrast between lesions and normal parenchyma was obtained by T2-HR-SPIR-TSE-w sequence of DCE-MRI. Ablation zones showed inhomogeneous necroses with small perifocal edema in the short-term and sharp delimitable scars in the mid-term. MRI showed no significant differences between adjoined renal parenchyma around ablations and parenchyma of untreated kidney. Histological analysis demonstrated complete destruction of cortical glomeruli and tubules, while collecting ducts, renal calyxes, and pelvis of medulla were preserved. Adjoined kidney parenchyma around IRE lesions showed no qualitative differences to normal parenchyma of untreated kidney. This porcine IRE study reveals a multifocal renal ablation, while protecting surrounded renal parenchyma and collecting system over a mid-term period. That offers prevention of renal function ablating centrally located or multifocal renal masses.« less

Significant association between renal function and area of amyloid deposition in kidney biopsy specimens in both AA amyloidosis associated with rheumatoid arthritis and AL amyloidosis.

PubMed

Kuroda, Takeshi; Tanabe, Naohito; Hasegawa, Eriko; Wakamatsu, Ayako; Nozawa, Yukiko; Sato, Hiroe; Nakatsue, Takeshi; Wada, Yoko; Ito, Yumi; Imai, Naofumi; Ueno, Mitsuhiro; Nakano, Masaaki; Narita, Ichiei

2017-06-01

The kidney is a major target organ for systemic amyloidosis, which results in proteinuria and an elevated serum creatinine level. The clinical manifestations and precursor proteins of amyloid A (AA) and light-chain (AL) amyloidosis are different, and the renal damage due to amyloid deposition also seems to differ. The purpose of this study was to clarify haw the difference in clinical features between AA and AL amyloidosis are explained by the difference in the amount and distribution of amyloid deposition in the renal tissues. A total of 119 patients participated: 58 patients with an established diagnosis of AA amyloidosis (AA group) and 61 with AL amyloidosis (AL group). We retrospectively investigated the correlation between clinical data, pathological manifestations, and the area occupied by amyloid in renal biopsy specimens. In most of the renal specimens the percentage area occupied by amyloid was less than 10%. For statistical analyses, the percentage area of amyloid deposition was transformed to a common logarithmic value (Log 10 %amyloid). The results of sex-, age-, and Log 10 %amyloid-adjusted analyses showed that systolic blood pressure (SBP) was higher in the AA group. In terms of renal function parameters, serum creatinine, creatinine clearance (Ccr) and estimated glomerular filtration rate (eGFR) indicated significant renal impairment in the AA group, whereas urinary protein indicated significant renal impairment in the AL group. Pathological examinations revealed amyloid was predominantly deposited at glomerular basement membrane (GBM) and easily transferred to the mesangial area in the AA group, and it was predominantly deposited at in the AL group. The degree of amyloid deposition in the glomerular capillary was significantly more severe in AL group. The frequency of amyloid deposits in extraglomerular mesangium was not significantly different between the two groups, but in AA group, the degree amyloid deposition was significantly more severe, and the deposition pattern in the glomerulus was nodular. Nodular deposition in extraglomerular mesangium leads to renal impairment in AA group. There are significant differences between AA and AL amyloidosis with regard to the renal function, especially in terms of Ccr, eGFR and urinary protein, even after Log10%amyloid was adjusted; showing that these inter-group differences in renal function would not be depend on the amount of renal amyloid deposits. These differences could be explained by the difference in distribution and morphological pattern of amyloid deposition in the renal tissue.

Creatinine, Arsenic Metabolism, and Renal Function in an Arsenic-Exposed Population in Bangladesh

PubMed Central

Peters, Brandilyn A.; Hall, Megan N.; Liu, Xinhua; Neugut, Y. Dana; Pilsner, J. Richard; Levy, Diane; Ilievski, Vesna; Slavkovich, Vesna; Islam, Tariqul; Factor-Litvak, Pam; Graziano, Joseph H.; Gamble, Mary V.

2014-01-01

Kidney disease is emerging as an arsenic (As)-linked disease outcome, however further evidence of this association is warranted. Our first objective for this paper was to examine the potential renal toxicity of As exposure in Bangladesh. Our second objective relates to examining whether the previously reported positive association between urinary creatinine (uCrn) and As methylation may be explained by renal function. We had hypothesized that these associations relate to supply and demand for s-adenosylmethionine, the methyl donor for both creatine synthesis and As methylation. Alternatively, renal function could influence both As and creatinine excretion, or the As metabolites may influence renal function, which in turn influences uCrn. We conducted a cross-sectional study (N = 478) of adults, composed of a sample recruited in 2001 and a sample recruited in 2003. We assessed renal function using plasma cystatin C, and calculated the estimated glomerular filtration rate (eGFR). Consistent with renal toxicity of As, log-uAs had a marginal inverse association with eGFR in the 2003 sample (b = −5.6, p = 0.07), however this association was not significant in the 2001 sample (b = −1.9, p = 0.24). Adjustment for eGFR did not alter the associations between uCrn and the %uAs metabolites, indicating that GFR does not explain these associations. Increased eGFR was associated with increased odds of having %uInAs >12.2% (2001: OR = 1.01, 95%CI (1.00,1.03); 2003: OR = 1.04, 95%CI (1.01,1.07)). In the 2003 sample only, there was a negative association between eGFR and %uDMA (b = −0.08, p = 0.02). These results may indicate differential effects of renal function on excretion of InAs and DMA. Alternatively, a certain methylation pattern, involving decreased %InAs and increased %DMA, may reduce renal function. Given that these studies were cross-sectional, we cannot distinguish between these two possibilities. Discrepancies between the samples may be due to the higher As exposure, poorer nutrition, and lower As methylation capacity in the 2003 sample. PMID:25438247

Creatinine, arsenic metabolism, and renal function in an arsenic-exposed population in Bangladesh.

PubMed

Peters, Brandilyn A; Hall, Megan N; Liu, Xinhua; Neugut, Y Dana; Pilsner, J Richard; Levy, Diane; Ilievski, Vesna; Slavkovich, Vesna; Islam, Tariqul; Factor-Litvak, Pam; Graziano, Joseph H; Gamble, Mary V

2014-01-01

Kidney disease is emerging as an arsenic (As)-linked disease outcome, however further evidence of this association is warranted. Our first objective for this paper was to examine the potential renal toxicity of As exposure in Bangladesh. Our second objective relates to examining whether the previously reported positive association between urinary creatinine (uCrn) and As methylation may be explained by renal function. We had hypothesized that these associations relate to supply and demand for s-adenosylmethionine, the methyl donor for both creatine synthesis and As methylation. Alternatively, renal function could influence both As and creatinine excretion, or the As metabolites may influence renal function, which in turn influences uCrn. We conducted a cross-sectional study (N = 478) of adults, composed of a sample recruited in 2001 and a sample recruited in 2003. We assessed renal function using plasma cystatin C, and calculated the estimated glomerular filtration rate (eGFR). Consistent with renal toxicity of As, log-uAs had a marginal inverse association with eGFR in the 2003 sample (b = -5.6, p = 0.07), however this association was not significant in the 2001 sample (b = -1.9, p = 0.24). Adjustment for eGFR did not alter the associations between uCrn and the %uAs metabolites, indicating that GFR does not explain these associations. Increased eGFR was associated with increased odds of having %uInAs >12.2% (2001: OR = 1.01, 95%CI (1.00,1.03); 2003: OR = 1.04, 95%CI (1.01,1.07)). In the 2003 sample only, there was a negative association between eGFR and %uDMA (b = -0.08, p = 0.02). These results may indicate differential effects of renal function on excretion of InAs and DMA. Alternatively, a certain methylation pattern, involving decreased %InAs and increased %DMA, may reduce renal function. Given that these studies were cross-sectional, we cannot distinguish between these two possibilities. Discrepancies between the samples may be due to the higher As exposure, poorer nutrition, and lower As methylation capacity in the 2003 sample.

Comparison of the Chronic Kidney Disease Epidemiology Collaboration, the Modification of Diet in Renal Disease study and the Cockcroft-Gault equation in patients with heart failure

PubMed Central

Szummer, Karolina; Evans, Marie; Carrero, Juan Jesus; Alehagen, Urban; Dahlström, Ulf; Benson, Lina; Lund, Lars H

2017-01-01

Background It is unknown how the creatinine-based renal function estimations differ for dose adjustment cut-offs and risk prediction in patients with heart failure. Method and results The renal function was similar with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) (median 59 mL/min/1.73 m2, IQR 42 to 77) and Modification of Diet in Renal Disease Study (MDRD) (59 mL/min/1.73 m2, IQR 43 to 75) and slightly lower with the Cockcroft-Gault (CG) equation (57 mL/min, IQR 39 to 82). Across the commonly used renal function stages, the CKD-EPI and the MDRD classified patients into the same stage in 87.2% (kappa coefficient 0.83, p<0.001); the CKD-EPI and the CG equation agreed in 52.3% (kappa coefficient 0.39, p<0.001). Hence, a differing number of patients will receive dose adjustment depending on which formula is used as cut-off. The CG equation predicted worse prognosis better (c-statistics 0.740, 95% CI 0.734 to 0.746) than CKD-EPI (0.697, 95% CI 0.690 to 0.703, p<0.001) and MDRD (0.680, 95% CI 0.734 to 0.746). Using net reclassification improvement (NRI), the CG identified 12.8% more patients at higher risk of death as compared with the CKD-EPI equation. Patients registered in the Swedish Heart Failure Registry (n= 40 736) with standardised creatinine values between 2000 and 2012 had their renal function estimated with the CKD-EPI, the MDRD and the CG. Agreement between the formulas was compared for categories. Prediction of death was assessed with c-statistics and with NRI. Conclusion The choice of renal function estimation formula has clinical implications and differing results at various cut-off levels. For prognosis, the CG predicts mortality better than the CKD-EPI and MDRD. PMID:28761677

Pharmacokinetic Properties of Fostamatinib in Patients With Renal or Hepatic Impairment: Results From 2 Phase I Clinical Studies.

PubMed

Martin, Paul; Oliver, Stuart; Gillen, Michael; Marbury, Thomas; Millson, David

2015-12-01

Phase III trials of fostamatinib, an oral spleen tyrosine kinase inhibitor, in the treatment of rheumatoid arthritis have been completed. Herein, we report the effects of renal and hepatic impairment on the pharmacokinetic (PK) properties of the active metabolite of fostamatinib, R406, in plasma, and on the urinary excretion of R406 and its metabolite N-glucuronide. Two Phase I, single-center, open-label clinical trials determined the PK properties and tolerability of fostamatinib in subjects with normal or impaired renal or hepatic function. Twenty-four subjects in the study in renal impairment (8 per group: normal renal function, moderate renal dysfunction, or end-stage renal disease [ESRD]), and 32 subjects in the study in hepatic impairment (8 per group: normal hepatic function or mild, moderate, or severe hepatic impairment) received a single 150-mg dose of fostamatinib. Patients with ESRD in the study in renal impairment participated in 2 treatment periods separated by a ≥1-week washout. In these patients, fostamatinib was administered after dialysis or 2 hours before dialysis. Geometric mean R406 Cmax and AUC values were less in the combined renally impaired group than in the group with normal renal function; Tmax was similar across groups. However, renal impairment had no apparent effect considered clinically relevant on unbound R406. In patients with ESRD, R406 exposure was less when fostamatinib was administered after compared with before dialysis. Urinary excretion of R406 N-glucuronide was decreased with increasing severity of renal impairment. Renal elimination of R406 was negligible in all groups. Varying degrees of hepatic impairment had no consistent effects on the PK properties of R406. R406 Cmax values were 10% to 15% less in all hepatically impaired groups than in the group with normal hepatic function. AUC and Tmax values were similar between the groups with normal and severely impaired hepatic function; in the groups with mild or moderate hepatic impairment, AUC was less and Tmax was greater. The geometric mean percentage of unbound R406 ranged from 0.64% to 1.95% and was greatest in the group with severe hepatic impairment. The urinary excretion of R406 was minimal. The amount of R406 N-glucuronide excreted in urine was greater in severely hepatically impaired patients. Fostamatinib 150 mg was generally well tolerated. In these patients, renal or hepatic impairment did not affect exposure to the active metabolite of fostamatinib, R406, to a clinically relevant extent. ClinicalTrials.gov identifiers: NCT01245790 (renal) and NCT01222455 (hepatic). Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

Influence of the renal artery ostium flow diverter on hemodynamics and atherogenesis

PubMed Central

Albert, Scott; Balaban, Robert S.; Neufeld, Edward B.; Rossmann, Jenn Stroud

2014-01-01

The structure and function of the renal artery ostium flow diverter on the caudal side of the renal branch point were previously reported; in this study, we further evaluate the diverter’s possible functions. The protrusion of this structure into the abdominal aorta suggests that the diverter may preferentially direct blood flow to the renal arteries, and that it may also influence flow patterns and recirculation known to be involved in atherogenesis. Three-dimensional computational fluid dynamics (CFD) simulations of steady and pulsatile blood flow are performed to investigate the influence of diverter size and position, and vascular geometry, on the flow patterns and fluid mechanical forces in the neighborhood of the diverter. CFD results show that the flow diverter does affect the blood distribution: depending on the diverter’s position, the flow to the renal arteries may be increased or reduced. Calculated results also demonstrate the diverter’s effect on the Wall Shear Stress (WSS) distribution, and suggest that the diverter contributes to an atherogenic environment in the abdominal aorta, while being atheroprotective in the renal arteries themselves. These results support previous clinical findings, and suggest directions for further clinical study. The results of this work have direct implications in understanding the physiological significance of the diverter, and its potential role in the pathophysiological development of atherosclerosis. PMID:24703300

Influence of the renal artery ostium flow diverter on hemodynamics and atherogenesis.

PubMed

Albert, Scott; Balaban, Robert S; Neufeld, Edward B; Rossmann, Jenn Stroud

2014-05-07

The structure and function of the renal artery ostium flow diverter on the caudal side of the renal branch point were previously reported; in this study, we further evaluate the diverter׳s possible functions. The protrusion of this structure into the abdominal aorta suggests that the diverter may preferentially direct blood flow to the renal arteries, and that it may also influence flow patterns and recirculation known to be involved in atherogenesis. Three-dimensional computational fluid dynamics (CFD) simulations of steady and pulsatile blood flow are performed to investigate the influence of diverter size and position, and vascular geometry, on the flow patterns and fluid mechanical forces in the neighborhood of the diverter. CFD results show that the flow diverter does affect the blood distribution; depending on the diverter׳s position, the flow to the renal arteries may be increased or reduced. Calculated results also demonstrate the diverter׳s effect on the wall shear stress (WSS) distribution, and suggest that the diverter contributes to an atherogenic environment in the abdominal aorta, while being atheroprotective in the renal arteries themselves. These results support previous clinical findings, and suggest directions for further clinical study. The results of this work have direct implications in understanding the physiological significance of the diverter, and its potential role in the pathophysiological development of atherosclerosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Pharmacokinetics and Safety of a Single Oral Dose of Mirogabalin in Japanese Subjects With Varying Degrees of Renal Impairment.

PubMed

Kato, Manabu; Tajima, Naoyuki; Shimizu, Takako; Sugihara, Masahiro; Furihata, Kenichi; Harada, Kazuhiro; Ishizuka, Hitoshi

2018-01-01

Mirogabalin (DS-5565) is a novel preferentially selective α 2 δ-1 ligand being developed for the treatment of diabetic peripheral neuropathic pain and postherpetic neuralgia. The current multicenter open-label study determined the effect of varying degrees of renal impairment on the pharmacokinetics and safety of a single dose of mirogabalin 5 mg in Japanese subjects. A total of 30 subjects (6 subjects per renal function category [normal, mild, moderate, or severe impairment; and end-stage renal disease (ESRD)]) were enrolled and completed the study. The AUC last increased with severity of renal impairment; the geometric least-squares mean ratios of AUC last compared with subjects with normal renal function were 1.3, 1.9, 3.6, and 5.3 for patients with mild, moderate, and severe impairment and ESRD, respectively. In accordance with this AUC last increase, apparent total body clearance (CL/F), renal clearance (CLr), and the cumulative percentage of mirogabalin dose excreted into urine all decreased with severity of renal impairment. There were no deaths and no severe treatment-related adverse events (TEAEs), serious TEAEs, or TEAEs resulting in study discontinuation. Mirogabalin was well tolerated in Japanese subjects with normal renal function and those with mild to severe renal impairment. It was also tolerated in subjects with ESRD but with a higher incidence of TEAEs. The most frequently reported TEAEs were dizziness (ESRD, n = 3), somnolence (ESRD, n = 2), and vomiting (ESRD, n = 2). Based on these data, a mirogabalin dose adjustment will be considered in Japanese subjects with moderate to severe renal impairment and those with ESRD. © 2017, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

Effects of carprofen on renal function during medetomidine-propofol-isoflurane anesthesia in dogs.

PubMed

Frendin, Jan H M; Boström, Ingrid M; Kampa, Naruepon; Eksell, Per; Häggström, Jens U; Nyman, Görel C

2006-12-01

To investigate effects of carprofen on indices of renal function and results of serum bio-chemical analyses and effects on cardiovascular variables during medetomidine-propofol-isoflurane anesthesia in dogs. 8 healthy male Beagles. A randomized crossover study was conducted with treatments including saline (0.9% NaCl) solution (0.08 mL/kg) and carprofen (4 mg/kg) administered IV. Saline solution or carprofen was administered 30 minutes before induction of anesthesia and immediately before administration of medetomidine (20 microg/kg, IM). Anesthesia was induced with propofol and maintained with inspired isoflurane in oxygen. Blood gas concentrations and ventilation were measured. Cardiovascular variables were continuously monitored via pulse contour cardiac output (CO) measurement. Renal function was assessed via glomerular filtration rate (GFR), renal blood flow (RBF), scintigraphy, serum biochemical analyses, urinalysis, and continuous CO measurements. Hematologic analysis was performed. Values did not differ significantly between the carprofen and saline solution groups. For both treatments, sedation and anesthesia caused changes in results of serum biochemical and hematologic analyses; a transient, significant increase in urine alkaline phosphatase activity; and blood flow diversion to the kidneys. The GFR increased significantly in both groups despite decreased CO, mean arterial pressure, and absolute RBF variables during anesthesia. Carprofen administered IV before anesthesia did not cause detectable, significant adverse effects on renal function during medetomidine-propofol-isoflurane anesthesia in healthy Beagles.

Factors associated with postoperative requirement of renal replacement therapy following off-pump coronary bypass surgery.

PubMed

Kato, Tomoko S; Machida, Yoichiro; Kuwaki, Kenji; Yamamoto, Taira; Amano, Atsushi

2017-02-01

Cardiopulmonary bypass usage provokes a systemic inflammatory response resulting in deterioration of renal function. However, risk factors for requiring renal replacement therapy (RRT) following off-pump coronary artery bypass graft surgery (CABG) have not yet been fully elucidated. We reviewed 718 consecutive patients undergoing elective off-pump CABG at our institution, excluding patients on chronic hemodialysis preoperatively. Sub-analysis of patients with preserved renal function, defined as a creatinine level below a cut-off value of 1.12 mg/dL (obtained by receiver operating characteristic curve), was also performed. Of the 718 patients, 41 (5.7 %) required RRT. There were 556 patients (77.4 %) with preserved renal function preoperatively, and 13 (2.4 %) of these required postoperative RRT. Multivariate analysis revealed that age (years) and preoperative serum creatinine (mg/dL) and brain natriuretic peptide (BNP) levels (pg/dL) were associated with RRT [odds ratios (OR) 1.052, 95 % confidence interval (CI) 9.064 and 1.001, respectively, all p < 0.05] in the total population, whereas low albumin concentration was the only independent predictor for RRT in patients with preserved renal function (OR 0.062, p < 0.0001). When creatinine levels were below 1.5 mg/dL, the predictive power of hypoalbuminemia for RRT requirement overwhelmed that of creatinine or BNP levels. Older age, preoperative elevated creatinine and BNP levels were associated with a requirement for RRT following off-pump CABG. In patients with preserved renal function, hypoalbuminemia was most significantly related to the RRT requirement.

Efficacy and Safety of Apixaban Compared With Warfarin in Patients With Atrial Fibrillation in Relation to Renal Function Over Time: Insights From the ARISTOTLE Randomized Clinical Trial.

PubMed

Hijazi, Ziad; Hohnloser, Stefan H; Andersson, Ulrika; Alexander, John H; Hanna, Michael; Keltai, Matyas; Parkhomenko, Alexander; López-Sendón, José L; Lopes, Renato D; Siegbahn, Agneta; Granger, Christopher B; Wallentin, Lars

2016-07-01

Renal impairment confers an increased risk of stroke, bleeding, and death in patients with atrial fibrillation. Little is known about the efficacy and safety of apixaban in relation to renal function changes over time. To evaluate changes of renal function over time and their interactions with outcomes during a median of 1.8 years of follow-up in patients with atrial fibrillation randomized to apixaban vs warfarin treatment. The prospective, randomized, double-blind Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) clinical trial randomized 18 201 patients with atrial fibrillation to apixaban or warfarin. Serial creatinine measurements were available in 16 869 patients. Worsening of renal function was defined as an annual decrease in estimated glomerular filtration more than 20%. The relations between treatment, outcomes, and renal function were investigated using Cox regression models, with renal function as a time-dependent covariate. Stroke or systemic embolism (primary outcome), major bleeding (safety outcome), and mortality were examined in relation to renal function over time estimated with both the Cockcroft-Gault and Chronic Kidney Disease Epidemiology Collaboration equations. Among 16 869 patients, the median age was 70 years and 65.2% of patients were men. Worsening in estimated glomerular filtration more than 20% was observed in 2294 patients (13.6%) and was associated with older age and more cardiovascular comorbidities. The risks of stroke or systemic embolism, major bleeding, and mortality were higher in patients with worsening renal function (HR, 1.53; 95% CI, 1.17-2.01 for stroke or systemic embolism; HR, 1.56; 95% CI, 1.27-1.93 for major bleeding; and HR, 2.31; 95% CI, 1.98-2.68 for mortality). The beneficial effects of apixaban vs warfarin on rates of stroke or systemic embolism and major bleeding were consistent in patients with normal or poor renal function over time and also in those with worsening renal function. In patients with atrial fibrillation, declining renal function was more common in elderly patients and those with cardiovascular comorbidities. Worsening renal function was associated with a higher risk of subsequent cardiovascular events and bleeding. The superior efficacy and safety of apixaban as compared with warfarin were similar in patients with normal, poor, and worsening renal function. clinicaltrials.gov Identifier: NCT00412984.

Comparison of endopyelotomy and laparoscopic pyeloplasty for poorly functioning kidneys with ureteropelvic junction obstruction

PubMed Central

Singh, Pratipal; Kapoor, Rakesh; Suri, Amit; Singh, Kamal Jeet; Mandhani, Anil; Dubey, Deepak; Srivastava, Aneesh; Kumar, Anant

2007-01-01

Endopyelotomy and laparoscopic pyeloplasty are established procedures for ureteropelvic junction obstruction (UPJO) and historically a high failure rate has been observed in poorly functioning units with UPJ obstruction. The aim of this study is to compare the results of laparoscopic pyeloplasty with endopyelotomy in poorly functioning renal units, i.e., GFR under 25 ml/min. Materials and Methods: Retrospective analysis of all the patients who underwent either laparoscopic pyeloplasty or endopyelotomy for ureteropelvic junction obstruction in poorly functioning units between January 1998 and June 2005 was done. Follow-up renal scans, done at three, six, 12 months and yearly thereafter, were studied. Success was defined as symptomatic relief and/ or improvement in function (10% over baseline) in renal scan. Results: There were 23 patients in the endopyelotomy group and 15 patients in the laparoscopic pyeloplasty group with mean age of 25.3 years (9-53) and 26 years (10-44), respectively. Mean pelvic volume was 41.2 8cc ± 9.5 and 39.1cc ± 9.85 in the endopyelotomy group and laparoscopic pyeloplasty group, respectively. Mean preoperative GFR was 17.4 ± 5.7 ml/min and 21 ± 4.5 ml/min in the endopyelotomy group and laparoscopic pyeloplasty group, respectively and mean postoperative GFR was 21 ± 3.5 ml/min and 22 ± 3.9 ml/min, respectively. Eighteen and 11 patients were symptomatic in ethe ndopyelotomy group and laparoscopic pyeloplasty group, respectively while symptomatic improvement was seen in 14 and 11 patients, respectively. Mean follow-up was 12 months in the laparoscopy group and 28 months in the endopyelotomy group. Success rate was better for laparoscopic surgery group (15/15 = 100%) than for endopyelotomy (18/23 = 78.26%). Conclusions: Though the improvement in renal function is less in patients with UPJO with poorly functioning kidneys undergoing endopyelotomy or laparoscopic pyeloplasty, laparoscopic pyeloplasty gives better results in the form of symptomatic relief; however, renal function remains stable whichever the approach chosen. PMID:19675751

Renal Function Recovery with Total Artificial Heart Support.

PubMed

Quader, Mohammed A; Goodreau, Adam M; Shah, Keyur B; Katlaps, Gundars; Cooke, Richard; Smallfield, Melissa C; Tchoukina, Inna F; Wolfe, Luke G; Kasirajan, Vigneshwar

2016-01-01

Heart failure patients requiring total artificial heart (TAH) support often have concomitant renal insufficiency (RI). We sought to quantify renal function recovery in patients supported with TAH at our institution. Renal function data at 30, 90, and 180 days after TAH implantation were analyzed for patients with RI, defined as hemodialysis supported or an estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73 m. Between January 2008 and December 2013, 20 of the 46 (43.5%) TAH recipients (age 51 ± 9 years, 85% men) had RI, mean preoperative eGFR of 48 ± 7 ml/min/1.73 m. Renal function recovery was noted at each follow-up interval: increment in eGFR (ml/min/1.73 m) at 30, 90, and 180 days was 21 ± 35 (p = 0.1), 16.5 ± 18 (p = 0.05), and 10 ± 9 (p = 0.1), respectively. Six patients (30%) required preoperative dialysis. Of these, four recovered renal function, one remained on dialysis, and one died. Six patients (30%) required new-onset dialysis. Of these, three recovered renal function and three died. Overall, 75% (15 of 20) of patients' renal function improved with TAH support. Total artificial heart support improved renal function in 75% of patients with pre-existing significant RI, including those who required preoperative dialysis.

Poly[ADP-Ribose] Polymerase-1 Expression Is Related To Cold Ischemia, Acute Tubular Necrosis, and Delayed Renal Function In Kidney Transplantation

PubMed Central

O'Valle, Francisco; Del Moral, Raimundo G. M.; Benítez, María del Carmén; Martín-Oliva, David; Gómez-Morales, Mercedes; Aguilar, David; Aneiros-Fernández, José; Hernández-Cortés, Pedro; Osuna, Antonio; Moreso, Francesc; Serón, Daniel; Oliver, Francisco J.; Del Moral, Raimundo G.

2009-01-01

Cold ischemia time especially impacts on outcomes of expanded-criteria donor (ECD) transplantation. Ischemia-reperfusion (IR) injury produces excessive poly[ADP-Ribose] Polymerase-1 (PARP-1) activation. The present study explored the hypothesis that increased tubular expression of PARP-1 contributes to delayed renal function in suboptimal ECD kidney allografts and in non-ECD allografts that develop posttransplant acute tubular necrosis (ATN). Materials and Methods Nuclear PARP-1 immunohistochemical expression was studied in 326 paraffin-embedded renal allograft biopsies (193 with different degrees of ATN and 133 controls) and in murine Parp-1 knockout model of IR injury. Results PARP-1 expression showed a significant relationship with cold ischemia time (r coefficient = 0.603), time to effective diuresis (r = 0.770), serum creatinine levels at biopsy (r = 0.649), and degree of ATN (r = 0.810) (p = 0.001, Pearson test). In the murine IR model, western blot showed an increase in PARP-1 that was blocked by Parp-1 inhibitor. Immunohistochemical study of PARP-1 in kidney allograft biopsies would allow early detection of possible delayed renal function, and the administration of PARP-1 inhibitors may offer a therapeutic option to reduce damage from IR in donor kidneys by preventing or minimizing ATN. In summary, these results suggest a pivotal role for PARP-1 in the ATN of renal transplantation. We propose the immunohistochemical assessment of PARP-1 in kidney allograft biopsies for early detection of a possible delayed renal function. PMID:19784367

Variation of renal function over time is associated with major bleeding in patients treated with direct oral anticoagulants for atrial fibrillation.

PubMed

Becattini, C; Giustozzi, M; Ranalli, M G; Bogliari, G; Cianella, F; Verso, M; Agnelli, G; Vedovati, M C

2018-05-01

Essential In patients on treatment with direct anticoagulants (DOACs) variation of renal function is common. The effect of variations of renal function over time on major bleeding is not well defined. Variation of renal function over time is an independent predictor of major bleeding. Identifying conditions associated with variation of renal function may increase safety of DOACs. Background Chronic kidney disease is a risk factor for major bleeding in patients with atrial fibrillation (AF) treated with warfarin. Objective To assess the effect of variations in renal function over time on the risk of major bleeding during treatment with direct oral anticoagulants (DOACs) in patients with non-valvular AF. Methods Consecutive AF patients were prospectively followed after they had received the first DOAC prescription. Estimated glomerular filtration rate (eGFR) was periodically assessed, and the incidence of major bleeding was recorded. A joint survival model was used to estimate the association between variation in eGFR and the risk of major bleeding. Results During a mean follow-up of 575 days, 44 major bleeds occurred in 449 patients (6.1% per patient-year). eGFR over time was inversely and independently associated with the risk of major bleeding; every 1 mL min -1 absolute decrease in eGFR was associated with a 2% increase in the risk of major bleeding (hazard ratio [HR] 1.02, 95% confidence interval [CI] 1.01-1.04). A similar effect of the variation in eGFR over time was observed on the risk of clinically relevant non-major bleeding (HR 1.02, 95% CI 1.01-1.03). Deterioration of renal function leading to a change in eGFR staging was associated with an increase in the risk of major bleeding (HR 2.43, 95% CI 1.33-4.45). Conclusions Variation in renal function over time is associated with the risk of major bleeding in AF patients treated with DOACs in real life. Identification of intervening clinical conditions associated with variation in renal function is essential to reduce the risk of major bleeding and to make DOAC treatment more safe. © 2018 International Society on Thrombosis and Haemostasis.

Protein disulfide isomerase regulates renal AT1 receptor function and blood pressure in rats.

PubMed

Wang, Xitao; Asghar, Mohammad

2017-08-01

The role and mechanism of renal protein disulfide isomerase (PDI) in blood pressure regulation has not been tested before. Here, we test this possibility in Sprague-Dawley rats. Rats were treated with PDI inhibitor bacitracin (100 mg·kg -1 ip·day -1 for 14 days), and then blood pressure and renal angiotensin II type 1 (AT 1 ) receptor function were determined in anesthetized rats. Renal AT 1 receptor function was determined as the ability of candesartan (an AT 1 receptor blocker) to increase diuresis and natriuresis. A second set of vehicle- and bacitracin-treated rats was used to determine biochemical parameters. Systolic blood pressure as well as diastolic blood pressure increased in bacitracin-treated compared with vehicle-treated rats. Compared with vehicle, bacitracin-treated rats showed increased diuresis and natriuresis in response to candesartan (10-µg iv bolus dose) suggesting higher AT 1 receptor function in these rats. These were associated with higher renin activities in the plasma and renal tissues. Furthermore, urinary 8-isoprostane and kidney injury molecule-1 levels were higher and urinary antioxidant capacity was lower in bacitracin-treated rats. Renal protein carbonyl and nitrotyrosine levels also were higher in bacitracin- compared with vehicle-treated rats, suggesting oxidative stress burden in bacitracin-treated rats. Moreover, PDI activity decreased and its protein levels increased in renal tissues of bacitracin-treated rats. Also, nuclear levels of Nrf2 transcription factor, which regulates redox homeostasis, were decreased in bacitracin-treated rats. Furthermore, tissue levels of Keap1, an Nrf2 inhibitory molecule, and tyrosine 216-phosphorylated GSK3β protein, an Nrf2 nuclear export protein, were increased in bacitracin-treated rats. These results suggest that renal PDI by regulating Keap1-Nrf2 pathway acts as an antioxidant, maintaining redox balance, renal AT 1 receptor function, and blood pressure in rats. Copyright © 2017 the American Physiological Society.

Improvement in Renal Function and Symptoms of Patients Treated with Laparoscopic Pyeloplasty for Ureteropelvic Junction Obstruction with Less Than 20% Split Renal Function.

PubMed

Nishi, Morihiro; Matsumoto, Kazumasa; Fujita, Tetsuo; Iwamura, Masatsugu

2016-11-01

To evaluate the efficacy of laparoscopic pyeloplasty (LPP) for lower functioning kidney, we investigated the outcome of this procedure for patients with ureteropelvic junction obstruction with decreased renal function, defined as less than 20% split renal function. Between October 1998 and June 2015, we performed transperitoneal dismembered LPP in 224 patients. Among them, 15 patients with less than 20% split renal function were included in this study. Patient characteristics, perioperative split renal functions, complications, and surgical outcomes were retrospectively investigated. Fourteen of 15 patients had preoperative symptoms, including flank pain in 13 patients and gross hematuria in 1 patient. Preoperative 99mTc-mercaptoacetyltriglycine (MAG3) renogram revealed no response to diuretic injection and median split renal function was 16.5%. Median operative time and blood loss were 170 minutes and 20 mL, respectively. There were no complications during the perioperative period. Postoperative MAG3 renogram at 6 and 12 months after the operation revealed significantly increased split renal function (median: 23.8% and 23.7%, p = 0.001 and 0.008, respectively) and response to diuretic injection in all patients. Preoperative symptoms disappeared and no recurrence was seen during the follow-up period for all patients except for one who experienced flank pain again 4 months after the surgery. He subsequently underwent open pyeloplasty, and flank pain disappeared soon after. LPP for patients with low split renal function and flank pain significantly improved symptoms and split renal functions. Although the long-term clinical effects of LPP are unknown, we recommend performing LPP before considering nephrectomy for patients with lower functioning kidney.

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

PubMed

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

2011-10-01

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

Renal function alterations during skeletal muscle disuse in simulated microgravity

NASA Technical Reports Server (NTRS)

Tucker, Bryan J.

1992-01-01

This project was to examine the alterations in renal functions during skeletal muscle disuse in simulated microgravity. Although this area could cover a wide range of investigative efforts, the limited funding resulted in the selection of two projects. These projects would result in data contributing to an area of research deemed high priority by NASA and would address issues of the alterations in renal response to vasoactive stimuli during conditions of skeletal muscle disuse as well as investigate the contribution of skeletal muscle disuse, conditions normally found in long term human exposure to microgravity, to the balance of fluid and macromolecules within the vasculature versus the interstitium. These two projects selected are as follows: investigate the role of angiotensin 2 on renal function during periods of simulated microgravity and skeletal muscle disuse to determine if the renal response is altered to changes in circulating concentrations of angiotensin 2 compared to appropriate controls; and determine if the shift of fluid balance from vasculature to the interstitium, the two components of extracellular fluid volume, that occur during prolonged exposure to microgravity and skeletal muscle disuse is a result, in part, to alterations in the fluid and macromolecular balance in the peripheral capillary beds, of which the skeletal muscle contains the majority of recruitment capillaries. A recruitment capillary bed would be most sensitive to alterations in Starling forces and fluid and macromolecular permeability.

7 T renal MRI: challenges and promises.

PubMed

de Boer, Anneloes; Hoogduin, Johannes M; Blankestijn, Peter J; Li, Xiufeng; Luijten, Peter R; Metzger, Gregory J; Raaijmakers, Alexander J E; Umutlu, Lale; Visser, Fredy; Leiner, Tim

2016-06-01

The progression to 7 Tesla (7 T) magnetic resonance imaging (MRI) yields promises of substantial increase in signal-to-noise (SNR) ratio. This increase can be traded off to increase image spatial resolution or to decrease acquisition time. However, renal 7 T MRI remains challenging due to inhomogeneity of the radiofrequency field and due to specific absorption rate (SAR) constraints. A number of studies has been published in the field of renal 7 T imaging. While the focus initially was on anatomic imaging and renal MR angiography, later studies have explored renal functional imaging. Although anatomic imaging remains somewhat limited by inhomogeneous excitation and SAR constraints, functional imaging results are promising. The increased SNR at 7 T has been particularly advantageous for blood oxygen level-dependent and arterial spin labelling MRI, as well as sodium MR imaging, thanks to changes in field-strength-dependent magnetic properties. Here, we provide an overview of the currently available literature on renal 7 T MRI. In addition, we provide a brief overview of challenges and opportunities in renal 7 T MR imaging.

Sympathetic nervous system influences on the kidney. Role in hypertension.

PubMed

DiBona, G F

1989-03-01

Efferent renal sympathetic nerve activity (ERSNA) is elevated in human essential hypertension as well as several forms of experimental hypertension in animals. In addition, bilateral complete renal denervation delays the development and/or attenuates the magnitude of the hypertension in several different forms of experimental hypertension in animals. Efferent renal sympathetic nerve activity is known to have dose-dependent effects on renal blood flow and glomerular filtration rate, renal tubular sodium and water reabsorption, and renin secretion rate that are capable of contributing, singly or in combination, to the development, maintenance, and exacerbation of the hypertensive state. Of the many factors known to influence the central nervous system integrative regulation of ERSNA, two environmental factors, dietary sodium intake and environmental stress, are capable of significant interaction. This resultant increase in ERSNA and subsequent renal functional alterations can participate in the hypertensive process. This is especially evident in the presence of an underlying genetic predisposition to the development of hypertension. Thus, interactions between environmental and genetic influences can produce alterations in the sympathetic neural control of renal function that play an important role in hypertension.

Pharmacokinetic disposition of 14C-glyburide in patients with varying renal function

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

Pearson, J.G.; Antal, E.J.; Raehl, C.L.

1986-03-01

The pharmacokinetics of 14C-labeled glyburide were studied in 13 men with varying degrees of renal impairment. Patients received a single, 5 mg oral dose of glyburide as a solution (10 microCi/ml/mg) after a high-carbohydrate breakfast. Serial plasma and breath samples were collected for 48 hours and urine and feces were collected for 5 to 7 days. Patients with normal to moderately impaired renal function (creatinine clearance (CLCR) of 29 to 131 ml/min/1.7 m2) had glyburide plasma t1/2 values of 2.0 to 5.0 hours, with no relationship between CLCR and glyburide clearance. One subject with severe renal impairment (CLCR = 5more » ml/min/1.7 m2) had decreased glyburide clearance that resulted in a t1/2 of 11 hours. The elimination of metabolites was more dependent on renal status but was only significantly affected in the patient with severe renal impairment.« less

Renal function had an independent relationship with coronary artery calcification in Chinese elderly men.

PubMed

Fu, Shihui; Zhang, Zhao; Luo, Leiming; Ye, Ping

2017-04-07

Although previous studies have analyzed the relationship between renal function and coronary artery calcification (CAC) in pre-dialysis and dialysis patients, limited studies have discussed the relationship between renal function and CAC in Chinese elderly men without obvious damage of renal function. The present study was designed to explore the relationship between renal function and CAC in Chinese elderly men without obvious damage of renal function. This cross-sectional study was carried out in 105 male participants older than 60 years with glomerular filtration rate (GFR) ≥ 45 ml/min/1.73 m 2 . CAC was detected by high-definition computerized tomography (HDCT), which is a highly sensitive technique for detecting the CAC and provides the most accurate CAC scores up to date. Age was 72 ± 8.4 years on average and ranged from 60 to 89 years. Simple correlation analysis indicated that all kinds of CAC scores including the Agatston, volume and mass scores inversely correlated with GFR values (p < 0.05 for all). In multivariate linear regression analysis, GFR values were independently associated with all these CAC scores (p < 0.05 for all). Renal function had an independent relationship with CAC detected by HDCT in Chinese elderly men, demonstrating that the relationship between renal function and CAC started at the early stage of renal function decline.

Prevalence of renal insufficiency in elderly cancer patients in a tertiary cancer center

PubMed Central

Pontes, Lucíola de Barros; Antunes, Yuri Philippe Pimentel Vieira; Bugano, Diogo Diniz Gomes; Karnakis, Theodora; del Giglio, Auro; Kaliks, Rafael Aliosha

2014-01-01

Objective To estimate the prevalence of abnormal glomerular filtration rate in elderly patients with solid tumors. Methods A retrospective study with patients aged >65 years diagnosed with solid tumors between January 2007 and December 2011 in a cancer center. The following data were collected: sex, age, serum creatinine at the time of diagnosis and type of tumor. Renal function was calculated using abbreviated Modification of Diet in Renal Disease (MDRD) formulae and then staged in accordance with the clinical practice guidelines published by the Working Group of the National Kidney Foundation. Results A total of 666 patients were included and 60% were male. The median age was 74.2 years (range: 65 to 99 years). The most prevalent diagnosis in the study population were colorectal (24%), prostate (20%), breast (16%) and lung cancer (16%). The prevalence of elevated serum creatinine (>1.0mg/dL) was 30%. However, when patients were assessed using abbreviated MDRD formulae, 66% had abnormal renal function, stratified as follows: 45% with stage 2, 18% with stage 3, 3% with stage 4 and 0.3% with stage 5. Conclusion To the best of our knowledge, this was the first study to estimate the frequency of renal insufficiency in elderly cancer patients in Brazil. The prevalence of abnormal renal function among our cohort was high. As suspected, the absolute creatinine level does underestimate renal function impairment and should not be used as predictor of chemotherapy metabolism, excretion and consequent toxicity. PMID:25295449

[Oliguria and acute renal dysfunction in a six-month-old infant].

PubMed

Cui, Ya-Jie; Song, Chun-Lan; Cheng, Yi-Bing

2017-02-01

The infant (a girl aged 6 months) was admitted to the hospital because of oliguria and acute renal dysfunction. The laboratory examination results showed serious metabolic acidosis and increased blood urea nitrogen and serum creatinine levels. The patient continued to be anuric after 10 days of treatment with continuous renal replacement therapy (CRRT). she died a day later. The family history showed that the patient's sister died of acute renal failure 6 months after birth. The genomic sequencing results showed AGXT mutation in the patient and confirmed the diagnosis of primary hyperoxaluria type 1 (PH1). Her parents were heterozygous carriers. PH1 should be considered when the children have abnormal renal function or recurrent renal calculi or have a family history of these symptoms. AGXT gene analysis is an important method for PH1 diagnosis.

Renal complications in multiple myeloma and related disorders: survivorship care plan of the International Myeloma Foundation Nurse Leadership Board.

PubMed

Faiman, Beth M; Mangan, Patricia; Spong, Jacy; Tariman, Joseph D

2011-08-01

Kidney dysfunction is a common clinical feature of symptomatic multiple myeloma. Some degree of renal insufficiency or renal failure is present at diagnosis or will occur during the course of the disease and, if not reversed, will adversely affect overall survival and quality of life. Chronic insults to the kidneys from other illnesses, treatment, or multiple myeloma itself can further damage renal function and increase the risk for additional complications, such as anemia. Patients with multiple myeloma who have light chain (Bence Jones protein) proteinuria may experience renal failure or progress to end-stage renal disease (ESRD) and require dialysis because of light chain cast nephropathy. Kidney failure in patients with presumed multiple myeloma also may result from amyloidosis, light chain deposition disease, or acute tubular necrosis caused by nephrotoxic agents; therefore, identification of patients at risk for kidney damage is essential. The International Myeloma Foundation's Nurse Leadership Board has developed practice recommendations for screening renal function, identifying positive and negative contributing risk and environmental factors, selecting appropriate therapies and supportive care measures to decrease progression to ESRD, and enacting dialysis to reduce and manage renal complications in patients with multiple myeloma.

Recovery of renal function in dialysis patients

PubMed Central

Agraharkar, Mahendra; Nair, Vasudevan; Patlovany, Matthew

2003-01-01

Background Although recovery of renal functions in dialysis dependent patients is estimated to be greater than 1%, there are no indicators that actually suggest such revival of renal function. Residual renal function in dialysis patients is unreliable and seldom followed. Therefore renal recovery (RR) in dialysis dependent patients may remain unnoticed. We present a group of dialysis dependent patients who regained their renal functions. The aim of this project is to determine any indicators that may identify the recovery of renal functions in dialysis dependent patients. Methods All the discharges from the chronic dialysis facilities were identified. Among these discharges deaths, transplants, voluntary withdrawals and transfers either to another modality or another dialysis facility were excluded in order to isolate the patients with RR. The dialysis flow sheets and medical records of these patients were subsequently reviewed. Results Eight patients with a mean age of 53.8 ± 6.7 years (± SEM) were found to have RR. Dialysis was initiated due to uremic symptoms in 6 patients and fluid overload in the remaining two. The patients remained dialysis dependent for 11.1 ± 4.2 months. All these patients had good urine output and 7 had symptoms related to dialysis. Their mean pre-initiation creatinine and BUN levels were 5.21 ± 0.6 mg/dl and 72.12 ± 11.12 mg/dl, respectively. Upon discontinuation, they remained dialysis free for 19.75 ± 5.97 months. The mean creatinine and BUN levels after cessation of dialysis were 2.85 ± 0.57 mg/dl and 29.62 ± 5.26 mg/dl, respectively, while the mean creatinine clearance calculated by 24-hour urine collection was 29.75 ± 4.78 ml/min. One patient died due to HIV complications. One patient resumed dialysis after nine months. Remaining continue to enjoy a dialysis free life. Conclusion RR must be considered in patients with good urine output and unresolved acute renal failure. Dialysis intolerance may be an indicator of RR among such patients. PMID:14563216

R1 autonomic nervous system in acute kidney injury.

PubMed

Hering, Dagmara; Winklewski, Pawel J

2017-02-01

Acute kidney injury (AKI) is a rapid loss of kidney function resulting in accumulation of end metabolic products and associated abnormalities in fluid, electrolyte and acid-base homeostasis. The pathophysiology of AKI is complex and multifactorial involving numerous vascular, tubular and inflammatory pathways. Neurohumoral activation with heightened activity of the sympathetic nervous system and renin-angiotensin-aldosterone system play a critical role in this scenario. Inflammation and/or local renal ischaemia are underlying mechanisms triggering renal tissue hypoxia and resultant renal microcirculation dysfunction; a common feature of AKI occurring in numerous clinical conditions leading to a high morbidity and mortality rate. The contribution of renal nerves to the pathogenesis of AKI has been extensively demonstrated in a series of experimental models over the past decades. While this has led to better knowledge of the pathogenesis of human AKI, therapeutic approaches to improve patient outcomes are scarce. Restoration of autonomic regulatory function with vagal nerve stimulation resulting in anti-inflammatory effects and modulation of centrally-mediated mechanisms could be of clinical relevance. Evidence from experimental studies suggests that a therapeutic splenic ultrasound approach may prevent AKI via activation of the cholinergic anti-inflammatory pathway. This review briefly summarizes renal nerve anatomy, basic insights into neural control of renal function in the physiological state and the involvement of the autonomic nervous system in the pathophysiology of AKI chiefly due to sepsis, cardiopulmonary bypass and ischaemia/reperfusion experimental model. Finally, potentially preventive experimental pre-clinical approaches for the treatment of AKI aimed at sympathetic inhibition and/or parasympathetic stimulation are presented. © 2016 John Wiley & Sons Australia, Ltd.

Renal function monitoring in heart failure - what is the optimal frequency? A narrative review.

PubMed

Al-Naher, Ahmed; Wright, David; Devonald, Mark Alexander John; Pirmohamed, Munir

2018-01-01

The second most common cause of hospitalization due to adverse drug reactions in the UK is renal dysfunction due to diuretics, particularly in patients with heart failure, where diuretic therapy is a mainstay of treatment regimens. Therefore, the optimal frequency for monitoring renal function in these patients is an important consideration for preventing renal failure and hospitalization. This review looks at the current evidence for optimal monitoring practices of renal function in patients with heart failure according to national and international guidelines on the management of heart failure (AHA/NICE/ESC/SIGN). Current guidance of renal function monitoring is in large part based on expert opinion, with a lack of clinical studies that have specifically evaluated the optimal frequency of renal function monitoring in patients with heart failure. Furthermore, there is variability between guidelines, and recommendations are typically nonspecific. Safer prescribing of diuretics in combination with other antiheart failure treatments requires better evidence for frequency of renal function monitoring. We suggest developing more personalized monitoring rather than from the current medication-based guidance. Such flexible clinical guidelines could be implemented using intelligent clinical decision support systems. Personalized renal function monitoring would be more effective in preventing renal decline, rather than reacting to it. © 2017 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Renal volume assessed by magnetic resonance imaging volumetry correlates with renal function in living kidney donors pre- and postdonation: a retrospective cohort study.

PubMed

Lange, Daniel; Helck, Andreas; Rominger, Axel; Crispin, Alexander; Meiser, Bruno; Werner, Jens; Fischereder, Michael; Stangl, Manfred; Habicht, Antje

2018-07-01

Renal function of potential living kidney donors is routinely assessed with scintigraphy. Kidney anatomy is evaluated by imaging techniques such as magnetic resonance imaging (MRI). We evaluated if a MRI-based renal volumetry is a good predictor of kidney function pre- and postdonation. We retrospectively analyzed the renal volume (RV) in a MRI of 100 living kidney donors. RV was correlated with the tubular excretion rate (TER) of MAG3-scintigraphy, a measured creatinine clearance (CrCl), and the estimated glomerular filtration rate (eGFR) by Cockcroft-Gault (CG), CKD-EPI, and modification of diet in renal disease (MDRD) formula pre- and postdonation during a follow-up of 3 years. RV correlated significantly with the TER (total: r = 0.6735, P < 0.0001). Correlation between RV and renal function was the highest for eGFR by CG (r = 0.5595, P < 0.0001), in comparison with CrCl, MDRD-GFR, and CKD-EPI-GFR predonation. RV significantly correlated with CG-GFR postdonation and predicted CG-GFR until 3 years after donation. MRI renal volumetry might be an alternative technique for the evaluation of split renal function and prediction of renal function postdonation in living kidney donors. © 2018 Steunstichting ESOT.

Effect of Neutral-pH, Low–Glucose Degradation Product Peritoneal Dialysis Solutions on Residual Renal Function, Urine Volume, and Ultrafiltration: A Systematic Review and Meta-Analysis

PubMed Central

Yohanna, Seychelle; Alkatheeri, Ali M.A.; Brimble, Scott K.; McCormick, Brendan; Iansavitchous, Arthur; Blake, Peter G.

2015-01-01

Background and objectives Neutral-pH, low–glucose degradation products solutions were developed in an attempt to lessen the adverse effects of conventional peritoneal dialysis solutions. A systematic review was performed evaluating the effect of these solutions on residual renal function, urine volume, peritoneal ultrafiltration, and peritoneal small-solute transport (dialysate to plasma creatinine ratio) over time. Design, setting, participants, & measurements Multiple electronic databases were searched from January of 1995 to January of 2013. Randomized trials reporting on any of four prespecified outcomes were selected by consensus among multiple reviewers. Results Eleven trials of 643 patients were included. Trials were generally of poor quality. The meta-analysis was performed using a random effects model. The use of neutral-pH, low-glucose degradation products solutions resulted in better preserved residual renal function at various study durations, including >1 year (combined analysis: 11 studies; 643 patients; standardized mean difference =0.17 ml/min; 95% confidence interval, 0.01 to 0.32), and greater urine volumes (eight studies; 598 patients; mean difference =128 ml/d; 95% confidence interval, 58 to 198). There was no significant difference in peritoneal ultrafiltration (seven studies; 571 patients; mean difference =−110; 95% confidence interval, −312 to 91) or dialysate to plasma creatinine ratio (six studies; 432 patients; mean difference =0.03; 95% confidence interval, 0.00 to 0.06). Conclusions The use of neutral-pH, low–glucose degradation products solutions results in better preservation of residual renal function and greater urine volumes. The effect on residual renal function occurred early and persisted beyond 12 months. Additional studies are required to evaluate the use of neutral-pH, low–glucose degradation products solutions on hard clinical outcomes. PMID:26048890

Renal Function of Rats in Response to 37 Days of Head-Down Tilt

NASA Technical Reports Server (NTRS)

Wang, Tommy J.; Wade, Charles E.; Dalton, Bonnie P. (Technical Monitor)

2001-01-01

Spaceflight induces changes in human renal function, suggesting similar changes may occur in rats. Since rats continue to be the prime mammalian model for study in space, the effects of chronic microgravity on rat renal function should be clarified. Acute studies in rats using the ground-based microgravity simulation model, head-down tilt (HDT), have shown increases in glomerular filtration rate (GFR), electrolyte excretion, and a diuresis. However, long term effects of HDT have not been studied extensively. This study was performed to elucidate rat renal function following long-term simulated microgravity. Chronic exposure to HDT will cause an increase in GFR and electrolyte excretion in rats, similar to acute exposures, and lead to a decrease in the fractional excretion of filtered electrolytes. Experimental animals (HDT, n=10) were tail-suspended for 37 days and renal function compared to ambulatory controls (AMB, n=10). On day 37 of HDT, GFR, osmolal clearance, and electrolyte excretion were decreased, while plasma osmolality and free water clearance were increased. Urine output remained similar between groups. The fractional excretion of the filtered electrolytes was unchanged except for a decrease in the percentage of filtered calcium excreted. Chronic exposure to HDT results in decreased GFR and electrolyte excretion, but the fractional excretion of filtered electrolytes remained primarily unaffected.

Enzyme replacement therapy of Fabry disease.

PubMed

Clarke, Joe T R; Iwanochko, R Mark

2005-08-01

Fabry disease is an X-linked lysosomal storage disease caused by deficiency of the enzyme alpha-galactosidase A and results in pain, progressive renal impairment, cardiomyopathy, and cerebrovascular disease. The results of two major randomized, double-blind, placebo-controlled clinical trials and open-label extensions have shown that replacement of the deficient enzyme with either of two preparations of recombinant human alpha-galactosidase A, agalsidase-alfa, and agalsidase-beta is safe. Biweekly i.v. infusions of 0.2 mg/kg of agalsidase-alfa were associated with a significant decrease in pain and stabilization of renal function. Biweekly infusions of 1 mg/kg of agalsidase-beta were associated with virtually complete clearing of accumulated glycolipid substrate from renal and cutaneous capillary endothelial cells. Several smaller, open-label studies, along with observations made in the course of monitoring large numbers of patients on enzyme replacement therapy, indicated that treatment stabilizes renal function and produces significant improvements in myocardial mass and function. Treatment of Fabry disease by enzyme replacement has a significant impact on at least some serious complications of the disease.

Mesenchymal stem cell therapy promotes the improvement and recovery of renal function in a preclinical model

PubMed Central

Urt-Filho, Antônio; Oliveira, Rodrigo Juliano; Hermeto, Larissa Correa; Pesarini, João Renato; de David, Natan; Cantero, Wilson de Barros; Falcão, Gustavo; Marks, Guido; Antoniolli-Silva, Andréia Conceição Milan Brochado

2016-01-01

Abstract Acute renal failure (ARF) is an extremely important public health issue in need of novel therapies. The present study aimed to evaluate the capacity of mesenchymal stem cell (MSC) therapy to promote the improvement and recovery of renal function in a preclinical model. Wistar rats were used as the experimental model, and our results show that cisplatin (5mg/kg) can efficiently induce ARF, as measured by changes in biochemical (urea and creatinine) and histological parameters. MSC therapy performed 24h after the administration of chemotherapy resulted in normalized plasma urea and creatinine levels 30 and 45d after the onset of kidney disease. Furthermore, MSC therapy significantly reduced histological changes (intratubular cast formation in protein overload nephropathy and tubular hydropic degeneration) in this ARF model. Thus, considering that current therapies for ARF are merely palliative and that MSC therapy can promote the improvement and recovery of renal function in this model system, we suggest that innovative/alternative therapies involving MSCs should be considered for clinical studies in humans to treat ARF. PMID:27275667

Stress and sodium intake in neural control of renal function in hypertension.

PubMed

DiBona, G F

1991-04-01

The interaction between genetic and environmental factors is important in the pathophysiology of hypertension. By examining the effects of two environmental factors--acute psychoemotional stress and dietary sodium intake--in rats with genetic hypertension, an important influence on central neural mechanisms governing the renal sympathetic neural control of renal function has been demonstrated. Additional studies of the central opioid systems have demonstrated an important role of opioid peptides in modulating the renal functional responses to acute psychoemotional stress. The observed renal functional alterations--antidiuresis, antinatriuresis, and renal vasoconstriction--are known to be capable of contributing to the initiation, development, and maintenance of the hypertensive process.

Effects of Renal Denervation on Renal Artery Function in Humans: Preliminary Study

PubMed Central

Doltra, Adelina; Hartmann, Arthur; Stawowy, Philipp; Goubergrits, Leonid; Kuehne, Titus; Wellnhofer, Ernst; Gebker, Rolf; Schneeweis, Christopher; Schnackenburg, Bernhard; Esler, Murray; Fleck, Eckart; Kelle, Sebastian

2016-01-01

Aim To study the effects of RD on renal artery wall function non-invasively using magnetic resonance. Methods and Results 32 patients undergoing RD were included. A 3.0 Tesla magnetic resonance of the renal arteries was performed before RD and after 6-month. We quantified the vessel sharpness of both renal arteries using a quantitative analysis tool (Soap-Bubble®). In 17 patients we assessed the maximal and minimal cross-sectional area of both arteries, peak velocity, mean flow, and renal artery distensibility. In a subset of patients wall shear stress was assessed with computational flow dynamics. Neither renal artery sharpness nor renal artery distensibility differed significantly. A significant increase in minimal and maximal areas (by 25.3%, p = 0.008, and 24.6%, p = 0.007, respectively), peak velocity (by 16.9%, p = 0.021), and mean flow (by 22.4%, p = 0.007) was observed after RD. Wall shear stress significantly decreased (by 25%, p = 0.029). These effects were observed in blood pressure responders and non-responders. Conclusions RD is not associated with adverse effects at renal artery level, and leads to an increase in cross-sectional areas, velocity and flow and a decrease in wall shear stress. PMID:27003912

Serum creatinine levels are significantly influenced by renal size in the normal pediatric population.

PubMed

Di Zazzo, Giacomo; Stringini, Gilda; Matteucci, Maria Chiara; Muraca, Maurizio; Malena, Saverio; Emma, Francesco

2011-01-01

Clinical and experimental data have shown that differences in nephron endowment result in differences in renal mass and predisposition to chronic renal failure, hypertension, and proteinuria. We hypothesized that a significant proportion of the variance in GFR, as estimated by serum creatinine, is attributable to differences in renal size in normal children. A total of 1748 normal renal ultrasounds that were performed in children older than 6 months were reviewed. For each ultrasound, serum creatinine, serum blood urea nitrogen, and systolic and diastolic office BP were recorded. Renal size was evaluated as a function of renal length and thickness. All data were normalized for height, weight, age, and gender. When expressed as SD scores, a significant correlation was found between kidney size and serum creatinine (P < 0.0001) and between kidney size and serum blood urea nitrogen (P < 0.002). When dividing kidney size data per quintiles, a difference of 0.51 SD score in serum creatinine was observed between the lowest and highest quintile. No significant correlation was found with office BP measurements. These data show that, even in the normal pediatric population, differences in renal function are significantly explained by differences in renal mass. Methodologic limitations of this study are likely to underestimate this relationship.

Cytochrome P450 and Lipoxygenase Metabolites on Renal Function

PubMed Central

Imig, John D.; Hye Khan, Md. Abdul

2018-01-01

Arachidonic acid metabolites have a myriad of biological actions including effects on the kidney to alter renal hemodynamics and tubular transport processes. Cyclooxygenase metabolites are products of an arachidonic acid enzymatic pathway that has been extensively studied in regards to renal function. Two lesser-known enzymatic pathways of arachidonic acid metabolism are the lipoxygenase (LO) and cytochrome P450 (CYP) pathways. The importance of LO and CYP metabolites to renal hemodynamics and tubular transport processes is now being recognized. LO and CYP metabolites have actions to alter renal blood flow and glomerular filtration rate. Proximal and distal tubular sodium transport and fluid and electrolyte homeostasis are also significantly influenced by renal CYP and LO levels. Metabolites of the LO and CYP pathways also have renal actions that influence renal inflammation, proliferation, and apoptotic processes at vascular and epithelial cells. These renal LO and CYP pathway actions occur through generation of specific metabolites and cell-signaling mechanisms. Even though the renal physiological importance and actions for LO and CYP metabolites are readily apparent, major gaps remain in our understanding of these lipid mediators to renal function. Future studies will be needed to fill these major gaps regarding LO and CYP metabolites on renal function. PMID:26756638

Renal perfusion index reflects cardiac systolic function in chronic cardio-renal syndrome.

PubMed

Lubas, Arkadiusz; Ryczek, Robert; Kade, Grzegorz; Niemczyk, Stanisław

2015-04-17

Cardiac dysfunction can modify renal perfusion, which is crucial to maintain sufficient kidney tissue oxygenation. Renal cortex perfusion assessed by dynamic ultrasound method is related both to renal function and cardiac hemodynamics. The aim of the study was to test the hypothesis that Renal Perfusion Index (RPI) can more closely reflect cardiac hemodynamics and differentiate etiology of chronic cardio-renal syndrome. Twenty-four patients with hypertension and chronic kidney disease (CKD) at 2-4 stage (12 with hypertensive nephropathy and 12 with CKD prior to hypertension) were enrolled in the study. Blood tests, 24-h ABPM, echocardiography, and ultrasonography with estimation of Total renal Cortical Perfusion intensity and Renal Perfusion Index (RPI) were performed. In the group of all patients, RPI correlated with left ventricular stoke volume (LVSV), and cardiac index, but not with markers of renal function. In multiple stepwise regression analysis CKD-EPI(Cys-Cr) (b=-0.360), LVSV (b=0.924) and MAP (b=0.376) together independently influenced RPI (R2=0.74; p<0.0001). RPI<0.567 allowed for the identification of patients with chronic cardio-renal syndrome with sensitivity of 41.7% and specificity of 83.3%. Renal perfusion index relates more strongly to cardiac output than to renal function, and could be helpful in recognizing chronic cardio-renal syndrome. Applicability of RPI in diagnosing early abnormalities in the cardio-renal axis requires further investigation.

The Effect of Patient and Surgical Characteristics on Renal Function After Partial Nephrectomy.

PubMed

Winer, Andrew G; Zabor, Emily C; Vacchio, Michael J; Hakimi, A Ari; Russo, Paul; Coleman, Jonathan A; Jaimes, Edgar A

2018-06-01

The purpose of the study was to identify patient and disease characteristics that have an adverse effect on renal function after partial nephrectomy. We conducted a retrospective review of 387 patients who underwent partial nephrectomy for renal tumors between 2006 and 2014. A line plot with a locally weighted scatterplot smoothing was generated to visually assess renal function over time. Univariable and multivariable longitudinal regression analyses incorporated a random intercept and slope to evaluate the association between patient and disease characteristics with renal function after surgery. Median age was 60 years and most patients were male (255 patients [65.9%]) and white (343 patients [88.6%]). In univariable analysis, advanced age at surgery, larger tumor size, male sex, longer ischemia time, history of smoking, and hypertension were significantly associated with lower preoperative estimated glomerular filtration rate (eGFR). In multivariable analysis, independent predictors of reduced renal function after surgery included advanced age, lower preoperative eGFR, and longer ischemia time. Length of time from surgery was strongly associated with improvement in renal function among all patients. Independent predictors of postoperative decline in renal function include advanced age, lower preoperative eGFR, and longer ischemia time. A substantial number of subjects had recovery in renal function over time after surgery, which continued past the 12-month mark. These findings suggest that patients who undergo partial nephrectomy can experience long-term improvement in renal function. This improvement is most pronounced among younger patients with higher preoperative eGFR. Copyright © 2017 Elsevier Inc. All rights reserved.

Long-Term Renal Function Recovery following Radical Nephrectomy for Kidney Cancer: Results from a Multicenter Confirmatory Study.

PubMed

Zabor, Emily C; Furberg, Helena; Lee, Byron; Campbell, Steven; Lane, Brian R; Thompson, R Houston; Antonio, Elvis Caraballo; Noyes, Sabrina L; Zaid, Harras; Jaimes, Edgar A; Russo, Paul

2018-04-01

We sought to confirm the findings from a previous single institution study of 572 patients from Memorial Sloan Kettering Cancer Center in which we found that 49% of patients recovered to the preoperative estimated glomerular filtration rate within 2 years following radical nephrectomy for renal cell carcinoma. A multicenter retrospective study was performed in 1,928 patients using data contributed from 3 independent centers. The outcome of interest was postoperative recovery to the preoperative estimated glomerular filtration rate. Data were analyzed using cumulative incidence and competing risks regression with death from any cause treated as a competing event. This study demonstrated that 45% of patients had recovered to the preoperative estimated glomerular filtration rate by 2 years following radical nephrectomy. Furthermore, this study confirmed that recovery of renal function differed according to preoperative renal function such that patients with a lower preoperative estimated glomerular filtration rate had an increased chance of recovery. This study also suggested that larger tumor size and female gender were significantly associated with an increased chance of renal function recovery. In this multicenter retrospective study we confirmed that in the long term a large proportion of patients recover to preoperative renal function following radical nephrectomy for kidney tumors. Recovery is more likely among those with a lower preoperative estimated glomerular filtration rate. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2009-12-01

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

A clinician's perspective of the role of renal sympathetic nerves in hypertension

PubMed Central

Briasoulis, Alexandros; Bakris, George L.

2015-01-01

The renal sympathetic nerves have significant contribution to the control of different aspects of kidney function. Early animal studies of renal denervation in a large number of different models of hypertension showed that that RDN improved BP control. Recently, data from prospective cohorts and randomized studies showed that renal denervation therapy (RDN) is a safe procedure but is associated with only modest reduction of ambulatory blood pressure (BP) in patients on intensive medical therapy. The main goal of this article is to review the results of preclinical and clinical studies on the contribution of the renal sympathetic nervous system to hypertension and the therapeutic applications of catheter-based renal denervation. PMID:25859218

Renal Artery Embolization - A First Line Treatment Option For End-Stage Hydronephrosis

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

Mitra, Kakali; Prabhudesai, Vikramaditya; James, R. Lester

Conventionally poorly functioning hydronephrotic kidneys have been removed if they are symptomatic. In our unit, patients are offered renal artery embolization as an alternative treatment option. Patients and Methods: Fifteen patients (11 male, 4 female) with a mean age of 32.9 yr (20-51 yrs) have undergone renal artery embolization for symptomatic hydronephrosis with poor function. Mean follow-up was 64.13 weeks (range 14-200). All patients had loin pain and hydronephrosis. Twelve patients had primary pelvi-ureteric junction obstruction (PUJO). Two patients had poorly functioning hydronephrotic kidneys secondary to chronic calculous obstruction. One patient had chronic pain in an obstructed but reasonably functioningmore » kidney following a previous pyeloplasty for PUJO which demanded intervention. Mean split function on renography was 11% (range 0-46%). Selective renal artery embolization was carried out under antibiotic cover using a 7 Fr balloon occlusion catheter and absolute alcohol, steel coils, and polyvinyl alcohol particles.Results: Nine patients developed post-embolization syndrome of self-limiting pain and pyrexia with no evidence of sepsis. One patient required readmission with this condition. One patient developed a hematoma at the puncture site. Mean hospital stay was 2.3 days. Fourteen patients are happy with the result and are completely pain free. One patient has minor discomfort but is delighted with the result. Nine patients have had follow-up ultrasound confirming resolution of the hydronephrosis. Conclusion: Renal artery embolization is an effective, safe, well-tolerated minimally invasive treatment option in end-stage hydronephrosis and we routinely offer it as an alternative to nephrectomy.« less

Renal angioplasty and stenting under protection: the way for the future?

PubMed

Henry, Michel; Henry, Isabelle; Klonaris, Christos; Polydorou, Antonio; Rath, Pathrap; Lakshmi, Gopalakrishnan; Rajacopal, Sriram; Hugel, Michèle

2003-11-01

The purpose of this study was to evaluate the feasibility and safety of renal artery angioplasty and stenting utilizing a distal protection device to reduce the risk of intraprocedural artery embolism and avoid deterioration of the renal function. Fifty-six hypertensive patients (32 men; mean age, 66 +/- 11.8 years; range, 22-87) with atherosclerotic renal artery stenosis (8 bilateral) underwent angioplasty and stenting with distal protection in 65 renal arteries (58 ostial lesions). Five patients had a solitary kidney, 18 a renal insufficiency. The lesion was crossed either with a GuardWire temporary occlusion balloon (n = 38), which was inflated to provide parenchyma protection or with a filter (EPI Filter; n = 26), or with Angioguard (n = 1), which allows a continuous flow. Generated debris was aspirated and analyzed. Blood pressure and serum creatinine levels were followed. Immediate technical success was 100%. All lesions except one were stented, either directly (43 ostial lesions) or after predilatation (22 ostial lesions). Visible debris were aspirated with the PercuSurge in all patients or removed with filters in 80% of the patients. Mean particle number and diameter were 98.1 +/- 60.0 per procedure (range, 13-208) and 201.0 +/- 76.0 microm (range, 38-6,206), respectively. Mean renal artery occlusion time was 6.55 +/- 2.46 min (range, 2.29-13.21) with the PercuSurge device. Mean time in situ (filters) was 4.25 +/- 1.12 min. Mean follow-up was 22.6 +/- 17.6 months (range, 1-47). Systolic and diastolic blood pressure declined from 169.0 +/- 15.2 and 104.0 +/- 13.0 mm Hg, respectively, to 149.7 +/- 12.4 and 92.7 +/- 6.7 mm Hg after the procedure. The mean creatinine level remains constant during the follow-up. At 6-month follow-up (45 patients), renal function did not deteriorate in any patient, whereas 8 patients with baseline renal insufficiency improved after the procedure. At 3 years (19 patients), renal function deteriorated only in 1 patient with renal insufficiency and in 1 patient treated for bilateral renal stenosis, one side without protection. These preliminary results suggest the feasibility and safety of distal protection during renal interventions to protect against atheroembolism and to avoid renal function deterioration. This technique's beneficial effects should be evaluated by randomized studies. Copyright 2003 Wiley-Liss, Inc.

Longitudinal Assessment of Vascular Function With Sunitinib in Patients With Metastatic Renal Cell Carcinoma.

PubMed

Catino, Anna B; Hubbard, Rebecca A; Chirinos, Julio A; Townsend, Ray; Keefe, Stephen; Haas, Naomi B; Puzanov, Igor; Fang, James C; Agarwal, Neeraj; Hyman, David; Smith, Amanda M; Gordon, Mary; Plappert, Theodore; Englefield, Virginia; Narayan, Vivek; Ewer, Steven; ElAmm, Chantal; Lenihan, Daniel; Ky, Bonnie

2018-03-01

Sunitinib, used widely in metastatic renal cell carcinoma, can result in hypertension, left ventricular dysfunction, and heart failure. However, the relationships between vascular function and cardiac dysfunction with sunitinib are poorly understood. In a multicenter prospective study of 84 metastatic renal cell carcinoma patients, echocardiography, arterial tonometry, and BNP (B-type natriuretic peptide) measures were performed at baseline and at 3.5, 15, and 33 weeks after sunitinib initiation, correlating with sunitinib cycles 1, 3, and 6. Mean change in vascular function parameters and 95% confidence intervals were calculated. Linear regression models were used to estimate associations between vascular function and left ventricular ejection fraction, longitudinal strain, diastolic function (E/e'), and BNP. After 3.5 weeks of sunitinib, mean systolic blood pressure increased by 9.5 mm Hg (95% confidence interval, 2.0-17.1; P =0.02) and diastolic blood pressure by 7.2 mm Hg (95% confidence interval, 4.3-10.0; P <0.001) across all participants. Sunitinib resulted in increases in large artery stiffness (carotid-femoral pulse wave velocity) and resistive load (total peripheral resistance and arterial elastance; all P <0.05) and changes in pulsatile load (total arterial compliance and wave reflection). There were no statistically significant associations between vascular function and systolic dysfunction (left ventricular ejection fraction and longitudinal strain). However, baseline total peripheral resistance, arterial elastance, and aortic impedance were associated with worsening diastolic function and filling pressures over time. In patients with metastatic renal cell carcinoma, sunitinib resulted in early, significant increases in blood pressure, arterial stiffness, and resistive and pulsatile load within 3.5 weeks of treatment. Baseline vascular function parameters were associated with worsening diastolic but not systolic function. © 2018 American Heart Association, Inc.

Renal Tubular Cell Mitochondrial Dysfunction Occurs Despite Preserved Renal Oxygen Delivery in Experimental Septic Acute Kidney Injury

PubMed Central

Pollen, Sean; Greco, Elisabetta; Courtneidge, Holly; Hall, Andrew M.; Duchen, Michael R.; Tam, Frederick W. K.; Unwin, Robert J.; Singer, Mervyn

2018-01-01

Objective: To explain the paradigm of significant renal functional impairment despite preserved hemodynamics and histology in sepsis-induced acute kidney injury. Design: Prospective observational animal study. Setting: University research laboratory. Subjects: Male Wistar rats. Intervention: Using a fluid-resuscitated sublethal rat model of fecal peritonitis, changes in renal function were characterized in relation to global and renal hemodynamics, and histology at 6 and 24 hours (n = 6–10). Sham-operated animals were used as comparison (n = 8). Tubular cell mitochondrial function was assessed using multiphoton confocal imaging of live kidney slices incubated in septic serum. Measurements and Main Results: By 24 hours, serum creatinine was significantly elevated with a concurrent decrease in renal lactate clearance in septic animals compared with sham-operated and 6-hour septic animals. Renal uncoupling protein-2 was elevated in septic animals at 24 hours although tubular cell injury was minimal and mitochondrial ultrastructure in renal proximal tubular cells preserved. There was no significant change in global or renal hemodynamics and oxygen delivery/consumption between sham-operated and septic animals at both 6- and 24-hour timepoints. In the live kidney slice model, mitochondrial dysfunction was seen in proximal tubular epithelial cells incubated with septic serum with increased production of reactive oxygen species, and decreases in nicotinamide adenine dinucleotide and mitochondrial membrane potential. These effects were prevented by coincubation with the reactive oxygen species scavenger, 4-hydroxy-2,2,6,6-tetramethyl-piperidin-1-oxyl. Conclusions: Renal dysfunction in sepsis occurs independently of hemodynamic instability or structural damage. Mitochondrial dysfunction mediated by circulating mediators that induce local oxidative stress may represent an important pathophysiologic mechanism. PMID:29293148

Increased Blood Pressure Variability Prior to Chronic Kidney Disease Exacerbates Renal Dysfunction in Rats

PubMed Central

Freitas, Frederico F. C. T.; Araujo, Gilberto; Porto, Marcella L.; Freitas, Flavia P. S.; Graceli, Jones B.; Balarini, Camille M.; Vasquez, Elisardo C.; Meyrelles, Silvana S.; Gava, Agata L.

2016-01-01

Increased blood pressure variability (BPV), which can be experimentally induced by sinoaortic denervation (SAD), has emerged as a new marker of the prognosis of cardiovascular and renal outcomes. Considering that increased BPV can lead to organ-damage, the goal of the present study was to evaluate the effects of SAD on renal function in an experimental model of chronic kidney disease (CKD). SAD was performed in male Wistar rats 2 weeks before 5/6 nephrectomy and the animals were evaluated 4 weeks after the induction of CKD. Our data demonstrated that BPV was increased in SAD and CKD animals and that the combination of both conditions (SAD+CKD) exacerbated BPV. The baroreflex sensitivity index was diminished in the SAD and CKD groups; this reduction was more pronounced when SAD and CKD were performed together. 5/6 nephrectomy led to hypertension, which was higher in SAD+CKD animals. Regarding renal function, the combination of SAD and CKD resulted in reduced renal plasma and blood flow, increased renal vascular resistance and augmented uraemia when compared to CKD animals. Glomerular filtration rate and BPV were negatively correlated in SAD, CKD, and SAD+CKD animals. Moreover, SAD+CKD animals presented a higher level of glomerulosclerosis when compared to all other groups. Cardiac and renal hypertrophy, as well as oxidative stress, was also further increased when SAD and CKD were combined. These results show that SAD prior to 5/6 nephrectomy exacerbates renal dysfunction, suggesting that previous augmented BPV should be considered as an important factor to the progression of renal diseases. PMID:27721797

High-salt diets during pregnancy affected fetal and offspring renal renin-angiotensin system.

PubMed

Mao, Caiping; Liu, Rong; Bo, Le; Chen, Ningjing; Li, Shigang; Xia, Shuixiu; Chen, Jie; Li, Dawei; Zhang, Lubo; Xu, Zhice

2013-07-01

Intrauterine environments are related to fetal renal development and postnatal health. Influence of salty diets during pregnancy on renal functions and renin-angiotensin system (RAS) was determined in the ovine fetuses and offspring. Pregnant ewes were fed high-salt diet (HSD) or normal-salt diet (NSD) for 2 months during middle-to-late gestation. Fetal renal functions, plasma hormones, and mRNA and protein expressions of the key elements of renal RAS were measured in the fetuses and offspring. Fetal renal excretion of sodium was increased while urine volume decreased in the HSD group. Fetal blood urea nitrogen was increased, while kidney weight:body weight ratio decreased in the HSD group. The altered ratio was also observed in the offspring aged 15 and 90 days. Maternal and fetal plasma antidiuretic hormone was elevated without changes in plasma renin activity and Ang I levels, while plasma Ang II was decreased. The key elements of local renal RAS, including angiotensinogen, angiotensin converting enzyme (ACE), ACE2, AT1, and AT2 receptor expression in both mRNA and protein, except renin, were altered following maternal high salt intake. The results suggest that high intake of salt during pregnancy affected fetal renal development associated with an altered expression of the renal key elements of RAS, some alterations of fetal origins remained after birth as possible risks in developing renal or cardiovascular diseases.

Nervous kidney. Interaction between renal sympathetic nerves and the renin-angiotensin system in the control of renal function.

PubMed

DiBona, G F

2000-12-01

Increases in renal sympathetic nerve activity regulate the functions of the nephron, the vasculature, and the renin-containing juxtaglomerular granular cells. Because increased activity of the renin-angiotensin system can also influence nephron and vascular function, it is important to understand the interactions between the renal sympathetic nerves and the renin-angiotensin system in the control of renal function. These interactions can be intrarenal, for example, the direct (by specific innervation) and indirect (by angiotensin II) contributions of increased renal sympathetic nerve activity to the regulation of renal function. The effects of increased renal sympathetic nerve activity on renal function are attenuated when the activity of the renin-angiotensin system is suppressed or antagonized with ACE inhibitors or angiotensin II-type AT(1)-receptor antagonists. The effects of intrarenal administration of angiotensin II are attenuated after renal denervation. These interactions can also be extrarenal, for example, in the central nervous system, wherein renal sympathetic nerve activity and its arterial baroreflex control are modulated by changes in activity of the renin-angiotensin system. In addition to the circumventricular organs, whose permeable blood-brain barrier permits interactions with circulating angiotensin II, there are interactions at sites behind the blood-brain barrier that depend on the influence of local angiotensin II. The responses to central administration of angiotensin II-type AT(1)-receptor antagonists into the ventricular system or microinjected into the rostral ventrolateral medulla are modulated by changes in activity of the renin-angiotensin system produced by physiological changes in dietary sodium intake. Similar modulation is observed in pathophysiological models wherein activity of both the renin-angiotensin and sympathetic nervous systems is increased (eg, congestive heart failure). Thus, both renal and extrarenal sites of interaction between the renin-angiotensin system and renal sympathetic nerve activity are involved in influencing the neural control of renal function.

Relationship between histopathological changes in post partum renal biopsies and renal function tests of African women with early onset pre-eclampsia.

PubMed

Khedun, S M; Naicker, T; Moodley, J

2000-05-01

To improve the diagnostic accuracy of concurrent renal disease in hypertension of pregnancy, biopsy evaluation is essential. In addition, establishing underlying renal disease is important for prognosis on future pregnancies. We therefore designed a study to determine the diagnostic yield of postpartum renal biopsy and the nature and frequency of complications associated with this procedure. Also, to determine relationships, if any, between renal function tests and ultrastructural and histopathological findings. Fifty renal biopsies were performed in the immediate postpartum period in black African women with early onset pre-eclampsia. Each biopsy specimen was placed in a separate container and coded so that sampling was unknown to the electron microscopist. Each biopsy specimen was divided into three parts, and processed and stained for light, fluorescent and transmission electron microscopy using conventional techniques. Renal tissue biopsies were adequate for diagnostic purposes in all cases. There were no complications in any of the 50 patients studied. Ultrastructural examination confirmed the light microscopy findings. In addition the ultrastructural findings showed intramembranous deposits, foot process fusion and mesangial deposits. In 16 patients with normal renal function tests; the biopsies evaluation from these patients showed ultrastructural changes. In the remaining 34 patients with abnormal renal function tests of varying severity; biopsy evaluation from these patients showed both ultrastructural and histopathological changes. Renal biopsy procedure is safe, and ultrastructural and histological findings obtained from postpartum renal biopsies are more informative than the routine renal function tests.

Renal function decline predicted by left atrial expansion index in non-diabetic cohort with preserved systolic heart function.

PubMed

Hsiao, Shih-Hung; Chiou, Kuan-Rau

2017-05-01

Since natriuretic peptide and troponin are associated with renal prognosis and left atrial (LA) parameters are indicators of subclinical cardiovascular abnormalities, this study investigated whether LA expansion index can predict renal decline. This study analysed 733 (69% male) non-diabetic patients with sinus rhythm, preserved systolic function, and estimated glomerular filtration rate (eGFR) higher than 60 mL/min/1.73 m2. In all patients, echocardiograms were performed and LA expansion index was calculated. Renal function was evaluated annually. The endpoint was a downhill trend in renal function with a final eGFR of <60 mL/min/1.73 m2. Rapid renal decline was defined as an annual decline in eGFR >3 mL/min/1.73 m2. The median follow-up time was 5.2 years, and 57 patients (7.8%) had renal function declines (19 had rapid renal declines, and 38 had incidental renal dysfunction). Events were associated with left ventricular mass index, LA expansion index, and heart failure during the follow-up period. The hazard ratio was 1.426 (95% confidence interval, 1.276-1.671; P < 0.0001) per 10% decrease in LA expansion index and was independently associated with an increased event rate. Compared with the highest quartile for the LA expansion index, the lowest quartile had a 9.7-fold risk of renal function decline in the unadjusted model and a 6.9-fold risk after adjusting for left ventricular mass index and heart failure during the follow-up period. Left atrial expansion index is a useful early indicator of renal function decline and may enable the possibility of early intervention to prevent renal function from worsening. NCT01171040. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Thermal Versus Impedance-Based Ablation of Renal Cell Carcinoma: A Meta-analysis

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

Modabber, Milad, E-mail: mmodabber@gmail.com; Martin, Jason, E-mail: jason.martin@medportal.ca; Athreya, Sriharsha, E-mail: sathreya@stjosham.on.ca

2013-10-04

BackgroundPercutaneous radiofrequency ablation (RFA) of renal carcinoma has become an established treatment modality. However, thermal (TB) versus impedance-based (IB)-RF generators have not been previously compared.MethodsA literature search on the application of RFA for renal masses using TB or IB-RF generators was performed. The safety, efficacy, and long-term outcomes of TB versus IB-based RFA were assessed using the outcome measures of technical success, local recurrence rate, complications, and preservation of renal function.ResultsAcross the 27 included studies, pooled results suggested comparable results for technical success (TB-RFA 98.53 % vs. IB-RFA 98.78 %, P = 0.9813). Clinical efficacy results were also similar across both generators (91.0 % TB-RFAmore » vs. 91.5 % IB-RFA; P = 0.73). At follow-up, no differences in renal function (relative risk [RR] 0.5, 95 % confidence interval [CI] 0.45–5.48), and local recurrence (RR 0.717, 95 % CI 0.49–1.50) were observed. The pooled proportion of overall complication rates was 13.1 % for TB-RFA and 11.5 % for IB-RFA.ConclusionNo differences in the observed parameters were found either during surgery or at follow-up.« less

Sympathetic nervous system and the kidney in hypertension.

PubMed

DiBona, Gerald F

2002-03-01

Long-term control of arterial pressure has been attributed to the kidney by virtue of its ability to couple the regulation of blood volume to the maintenance of sodium and water balance by the mechanisms of pressure natriuresis and diuresis. In the presence of a defect in renal excretory function, hypertension arises as the consequence of the need for an increase in arterial pressure to offset the abnormal pressure natriuresis and diuresis mechanisms, and to maintain sodium and water balance. There is growing evidence that an important cause of the defect in renal excretory function in hypertension is an increase in renal sympathetic nerve activity (RSNA). First, increased RSNA is found in animal models of hypertension and hypertensive humans. Second, renal denervation prevents or alleviates hypertension in virtually all animal models of hypertension. Finally, increased RSNA results in reduced renal excretory function by virtue of effects on the renal vasculature, the tubules, and the juxtaglomerular granular cells. The increase in RSNA is of central nervous system origin, with one of the stimuli being the action of angiotensin II, probably of central origin. By acting on brain stem nuclei that are important in the control of peripheral sympathetic vasomotor tone (e.g. rostral ventrolateral medulla), angiotensin II increases the basal level of RSNA and impairs its arterial baroreflex regulation. Therefore, the renal sympathetic nerves may serve as the link between central sympathetic nervous system regulatory sites and the kidney in contributing to the renal excretory defect in the development of hypertension.

Renoprotective effects of hepatocyte growth factor in the stenotic kidney

PubMed Central

Stewart, Nicholas

2013-01-01

Renal microvascular (MV) damage and loss contribute to the progression of renal injury in renal artery stenosis (RAS). Hepatocyte growth factor (HGF) is a powerful angiogenic and antifibrotic cytokine that we showed to be decreased in the stenotic kidney. We hypothesized that renal HGF therapy will improve renal function mainly by protecting the renal microcirculation. Unilateral RAS was induced in 15 pigs. Six weeks later, single-kidney RBF and GFR were quantified in vivo using multidetector computed tomography (CT). Then, intrarenal rh-HGF or vehicle was randomly administered into the stenotic kidney (RAS, n = 8; RAS+HGF, n = 7). Pigs were observed for 4 additional weeks before CT studies were repeated. Renal MV density was quantified by 3D micro-CT ex vivo and histology, and expression of angiogenic and inflammatory factors, apoptosis, and fibrosis was determined. HGF therapy improved RBF and GFR compared with vehicle-treated pigs. This was accompanied by improved renal expression of angiogenic cytokines (VEGF, p-Akt) and tissue-healing promoters (SDF-1, CXCR4, MMP-9), reduced MV remodeling, apoptosis, and fibrosis, and attenuated renal inflammation. However, HGF therapy did not improve renal MV density, which was similarly reduced in RAS and RAS+HGF compared with controls. Using a clinically relevant animal model of RAS, we showed novel therapeutic effects of a targeted renal intervention. Our results show distinct actions on the existing renal microcirculation and promising renoprotective effects of HGF therapy in RAS. Furthermore, these effects imply plasticity of the stenotic kidney to recuperate its function and underscore the importance of MV integrity in the progression of renal injury in RAS. PMID:23269649

Longitudinal changes in kidney parenchymal volume associated with renal artery stenting.

PubMed

Modrall, J Gregory; Timaran, Carlos H; Rosero, Eric B; Chung, Jayer; Plummer, Mitchell; Valentine, R James; Trimmer, Clayton

2012-03-01

This study assessed the longitudinal changes in renal volume after renal artery stenting (RAS) to determine if renal mass is preserved by stenting. The study cohort consisted of 38 patients with longitudinal imaging available for renal volume quantification before and after RAS. Renal volume was estimated as (kidney length) × (width) × (depth/2) based on preoperative renal imaging. For each patient, the clinical response of blood pressure (BP) and renal function to RAS was categorized according to modified American Heart Association guidelines. Changes in renal volume were assessed using paired nonparametric analyses. The cohort was a median age of 69 years (interquartile range [IQR], 60-74 years). A favorable BP response was observed in 11 of 38 patients (28.9%). At a median interval between imaging studies of 21 months (IQR, 13-32 months), ipsilateral renal volume was significantly increased from baseline (146.8 vs 133.8 cm(3);P = .02). This represents a 6.9% relative increase in ipsilateral kidney volume from baseline. A significant negative correlation between preoperative renal volume and the relative change in renal volume postoperatively (r = -0.42; P = .0055) suggests that smaller kidneys experienced the greatest gains in renal volume after stenting. It is noteworthy that the 25 patients with no change in BP or renal function-clinical failures using traditional definitions-experienced a 12% relative increase in ipsilateral renal volume after RAS. Multivariate analysis determined that stable or improved renal volume after stenting was an independent predictor of stable or improved long-term renal function (odds ratio, 0.008; 95% confidence interval, 0.000-0.206; P = .004). These data lend credence to the belief that RAS preserves renal mass in some patients. This benefit of RAS even extends to those patients who would be considered treatment failures by traditional definitions. Patients with stable or increased renal volume after RAS had more stable renal function during long-term follow-up, whereas patients with renal volume loss after stenting were prone to deterioration of renal function. Published by Mosby, Inc.

MitoQ blunts mitochondrial and renal damage during cold preservation of porcine kidneys.

PubMed

Parajuli, Nirmala; Campbell, Lia H; Marine, Akira; Brockbank, Kelvin G M; Macmillan-Crow, Lee Ann

2012-01-01

Cold preservation has greatly facilitated the use of cadaveric kidneys for transplantation but damage occurs during the preservation episode. It is well established that oxidant production increases during cold renal preservation and mitochondria are a key target for injury. Our laboratory has demonstrated that cold storage of renal cells and rat kidneys leads to increased mitochondrial superoxide levels and mitochondrial electron transport chain damage, and that addition of Mitoquinone (MitoQ) to the preservation solutions blunted this injury. In order to better translate animal studies, the inclusion of large animal models is necessary to develop safe preclinical protocols. Therefore, we tested the hypothesis that addition of MitoQ to cold storage solution preserves mitochondrial function by decreasing oxidative stress, leading to less renal tubular damage during cold preservation of porcine kidneys employing a standard criteria donor model. Results showed that cold storage significantly induced oxidative stress (nitrotyrosine), renal tubular damage, and cell death. Using High Resolution Respirometry and fresh porcine kidney biopsies to assess mitochondrial function we showed that MitoQ significantly improved complex II/III respiration of the electron transport chain following 24 hours of cold storage. In addition, MitoQ blunted oxidative stress, renal tubular damage, and cell death after 48 hours. These results suggested that MitoQ decreased oxidative stress, tubular damage and cell death by improving mitochondrial function during cold storage. Therefore this compound should be considered as an integral part of organ preservation solution prior to transplantation.

MitoQ Blunts Mitochondrial and Renal Damage during Cold Preservation of Porcine Kidneys

PubMed Central

Parajuli, Nirmala; Campbell, Lia H.; Marine, Akira; Brockbank, Kelvin G. M.; MacMillan-Crow, Lee Ann

2012-01-01

Cold preservation has greatly facilitated the use of cadaveric kidneys for transplantation but damage occurs during the preservation episode. It is well established that oxidant production increases during cold renal preservation and mitochondria are a key target for injury. Our laboratory has demonstrated that cold storage of renal cells and rat kidneys leads to increased mitochondrial superoxide levels and mitochondrial electron transport chain damage, and that addition of Mitoquinone (MitoQ) to the preservation solutions blunted this injury. In order to better translate animal studies, the inclusion of large animal models is necessary to develop safe preclinical protocols. Therefore, we tested the hypothesis that addition of MitoQ to cold storage solution preserves mitochondrial function by decreasing oxidative stress, leading to less renal tubular damage during cold preservation of porcine kidneys employing a standard criteria donor model. Results showed that cold storage significantly induced oxidative stress (nitrotyrosine), renal tubular damage, and cell death. Using High Resolution Respirometry and fresh porcine kidney biopsies to assess mitochondrial function we showed that MitoQ significantly improved complex II/III respiration of the electron transport chain following 24 hours of cold storage. In addition, MitoQ blunted oxidative stress, renal tubular damage, and cell death after 48 hours. These results suggested that MitoQ decreased oxidative stress, tubular damage and cell death by improving mitochondrial function during cold storage. Therefore this compound should be considered as an integral part of organ preservation solution prior to transplantation. PMID:23139796

The renin-angiotensin system in thyroid disorders and its role in cardiovascular and renal manifestations.

PubMed

Vargas, Félix; Rodríguez-Gómez, Isabel; Vargas-Tendero, Pablo; Jimenez, Eugenio; Montiel, Mercedes

2012-04-01

Thyroid disorders are among the most common endocrine diseases and affect virtually all physiological systems, with an especially marked impact on cardiovascular and renal systems. This review summarizes the effects of thyroid hormones on the renin-angiotensin system (RAS) and the participation of the RAS in the cardiovascular and renal manifestations of thyroid disorders. Thyroid hormones are important regulators of cardiac and renal mass, vascular function, renal sodium handling, and consequently blood pressure (BP). The RAS acts globally to control cardiovascular and renal functions, while RAS components act systemically and locally in individual organs. Various authors have implicated the systemic and local RAS in the mediation of functional and structural changes in cardiovascular and renal tissues due to abnormal thyroid hormone levels. This review analyzes the influence of thyroid hormones on RAS components and discusses the role of the RAS in BP, cardiac mass, vascular function, and renal abnormalities in thyroid disorders.

Changes in Renal Function and Blood Pressure in Patients with Stone Disease

NASA Astrophysics Data System (ADS)

Worcester, Elaine M.

2007-04-01

Stone disease is a rare cause of renal failure, but a history of kidney stones is associated with an increased risk for chronic kidney disease, particularly in overweight patients. Loss of renal function seems especially notable for patients with stones associated with cystinuria, hyperoxaluria, and renal tubular acidosis, in whom the renal pathology shows deposits of mineral obstructing inner medullary collecting ducts, often diffusely. However, even idiopathic calcium oxalate stone formers have a mild but significant decrease in renal function, compared to age, sex and weight-matched normals, and appear to lose renal function with age at a slightly faster rate than non-stone formers. There is also an increased incidence of hypertension among stone formers, although women are more likely to be affected than men.

Monitoring of circulating antibodies in a renal transplantation population: preliminary results.

PubMed

Rodríguez Ferrero, M L; Arroyo, D; Panizo, N; Vicario, J L; Balas, A; Anaya, F

2012-11-01

The presence of circulating antibodies (CA) against human leukocyte antigen (HLA) and major-histocompatibility-complex class I-related chain A (MICA) antigens has been associated with worse renal function and reduced kidney allograft survival. We sought to describe the presence of donor-specific anti-HLA antibodies, non-donor specific antibodies, and antibodies against MICA antigens among a cohort of renal transplant recipients with respect to their evolution effects on renal function and occurrence of an acute rejection episode (AR) after transplantation. This prospective study of 22 renal transplant recipients of deceased donor kidneys underwent studies of antibodies before and 3 months after grafting using Luminex technology. Ten patients (five men and five women) showed preexistent CA. Comparing patients with versus without preformed CA, we did not observe a significant difference in donor and recipient age or gender. Eight patients (80%) with CA had undergone induction treatment with anti-human-activated T-lymphocyte rabbit immunoglobulin and 2 (20%) with basiliximab. There were no differences between groups regarding the incidence of acute rejection episodes (ARE n = 3 each). There was one case of Banff grade IIB ARE in a patient without preexisting CA; the other episodes were low-grade cellular responses. There were no differences in other variables including cold ischemia time, HLA mismatches, panel-reactive antibody levels, number of transfusions, cytomegalovirus infection or renal function at discharge and 3 months later. Retransplantation was the only factor associated with preformed CA. Retransplantation and preformed CA were associated with CA at 3 months after transplantation. CA monitoring is important for highly sensitized renal transplants, although our experience failed to show a difference in graft survival or renal function in the first 3 months' follow-up. Copyright © 2012 Elsevier Inc. All rights reserved.

Effect of renal impairment on the pharmacokinetics, pharmacodynamics, and safety of empagliflozin, a sodium glucose cotransporter 2 inhibitor, in Japanese patients with type 2 diabetes mellitus.

PubMed

Sarashina, Akiko; Ueki, Kohjiro; Sasaki, Tomohiro; Tanaka, Yuko; Koiwai, Kazuki; Sakamoto, Wataru; Woerle, Hans J; Salsali, Afshin; Broedl, Uli C; Macha, Sreeraj

2014-11-01

The purpose of this study was to assess the effect of renal impairment on the pharmacokinetic, pharmacodynamic, and safety profiles of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in Japanese patients with type 2 diabetes mellitus (T2DM). In an open-label, parallel-group study, 32 Japanese patients with T2DM and different degrees of renal function (n = 8 per renal function category: normal renal function, estimated glomerular filtration rate [eGFR; Japanese equation] ≥90 mL/min/1.73 m(2); mild renal impairment, eGFR of 60-<90 mL/min/1.73 m(2); moderate renal impairment, eGFR of 30-<60 mL/min/1.73 m(2); and severe renal impairment, eGFR of 15-<30 mL/min/1.73 m(2)) received a single 25 mg dose of empagliflozin. Empagliflozin exposure increased with increasing renal impairment. Maximum empagliflozin plasma concentrations were similar among all renal function groups. Adjusted geometric mean ratios for extent of exposure (AUC0-∞) to empagliflozin versus normal renal function were 128.8% (95% CI, 106.0-156.6%), 143.8% (95% CI, 118.3-174.8%), and 152.3% (95% CI, 125.3-185.2%) for patients with mild, moderate, and severe renal impairment, respectively. Decreases in renal clearance of empagliflozin correlated with eGFR. Urinary glucose excretion decreased with increasing renal impairment and correlated with eGFR (adjusted mean [SE] change from baseline: 75.0 [4.84] g, 62.6 [5.75] g, 57.9 [4.86] g, and 23.7 [5.24] g for patients with normal renal function and mild, moderate, and severe renal impairment, respectively). Only 2 patients (6%) had adverse events; both were mild. Pharmacokinetic data suggest that no dose adjustment of empagliflozin is necessary in Japanese patients with T2DM and renal impairment because increases in exposure were <2-fold. Urinary glucose excretion decreased with increasing renal impairment. ClinicalTrials.gov identifier: NCT01581658. Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.

The rebirth of interest in renal tubular function.

PubMed

Lowenstein, Jerome; Grantham, Jared J

2016-06-01

The measurement of glomerular filtration rate by the clearance of inulin or creatinine has evolved over the past 50 years into an estimated value based solely on plasma creatinine concentration. We have examined some of the misconceptions and misunderstandings of the classification of renal disease and its course, which have followed this evolution. Furthermore, renal plasma flow and tubular function, which in the past were estimated by the clearance of the exogenous aryl amine, para-aminohippurate, are no longer measured. Over the past decade, studies in experimental animals with reduced nephron mass and in patients with reduced renal function have identified small gut-derived, protein-bound uremic retention solutes ("uremic toxins") that are poorly filtered but are secreted into the lumen by organic anion transporters (OATs) in the proximal renal tubule. These are not effectively removed by conventional hemodialysis or peritoneal dialysis. Residual renal function, urine produced in patients with advanced renal failure or undergoing dialysis treatment, may represent, at least in part, secretion of fluid and uremic toxins, such as indoxyl sulfate, mediated by proximal tubule OATs and might serve as a useful survival function. In light of this new evidence of the physiological role of proximal tubule OATs, we suggest that measurement of renal tubular function and renal plasma flow may be of considerable value in understanding and managing chronic kidney disease. Data obtained in normal subjects indicate that renal plasma flow and renal tubular function might be measured by the clearance of the endogenous aryl amine, hippurate. Copyright © 2016 the American Physiological Society.

A study of Semen Strychni-induced renal injury and herb-herb interaction of Radix Glycyrrhizae extract and/or Rhizoma Ligustici extract on the comparative toxicokinetics of strychnine and brucine in rats.

PubMed

Gu, Liqiang; Wang, Xiaofan; Liu, Zhenzhen; Ju, Ping; Zhang, Lunhui; Zhang, Yuanyuan; Ma, Bingjie; Bi, Kaishun; Chen, Xiaohui

2014-06-01

Recently, the renal injury caused by Semen strychni and its major toxic constituents, strychnine and brucine, was reported in many clinical cases. Hence, this study was conducted to investigate the renal injury induced by Semen Strychni and the protective effects of Radix Glycyrrhizae and Rhizoma Ligustici. The protective mechanisms were related to the comparative toxicokinetics of strychnine and brucine. Serum and urine uric acid and creatinine were used as renal function markers to evaluate the condition of kidney, and renal injury was directly reflected by histopathological changes. Compared with rats in blank group and protective herb groups, rats in Semen Strychni high-dose group showed significant differences in the results of renal function markers, and various glomerular and tubular degenerations were found in the histopathological study. The decreased AUC (only strychnine) and Cmax, the increased Tmax by Radix Glycyrrhizae and the decreased T1/2 by Radix Glycyrrhizae and Rhizoma Ligustici were found in model groups. Results indicated that high dose of Semen Strychni might induce renal injury. Radix Glycyrrhizae and Rhizoma Ligustici might work together and have effects on the elimination of strychnine and brucine. The protective effects of Radix Glycyrrhizae might also be explained by the slow absorption of the alkaloids. Copyright © 2014 Elsevier Ltd. All rights reserved.

Renal impairment and heart failure with preserved ejection fraction early post-myocardial infarction

PubMed Central

Jorapur, Vinod; Lamas, Gervasio A; Sadowski, Zygmunt P; Reynolds, Harmony R; Carvalho, Antonio C; Buller, Christopher E; Rankin, James M; Renkin, Jean; Steg, Philippe Gabriel; White, Harvey D; Vozzi, Carlos; Balcells, Eduardo; Ragosta, Michael; Martin, C Edwin; Srinivas, Vankeepuram S; Wharton III, William W; Abramsky, Staci; Mon, Ana C; Kronsberg, Shari S; Hochman, Judith S

2010-01-01

AIM: To study if impaired renal function is associated with increased risk of peri-infarct heart failure (HF) in patients with preserved ejection fraction (EF). METHODS: Patients with occluded infarct-related arteries (IRAs) between 1 to 28 d after myocardial infarction (MI) were grouped into chronic kidney disease (CKD) stages based on estimated glomerular filtration rate (eGFR). Rates of early post-MI HF were compared among eGFR groups. Logistic regression was used to explore independent predictors of HF. RESULTS: Reduced eGFR was present in 71.1% of 2160 patients, with significant renal impairment (eGFR < 60 mL/min every 1.73 m2) in 14.8%. The prevalence of HF was higher with worsening renal function: 15.5%, 17.8% and 29.4% in patients with CKD stages 1, 2 and 3 or 4, respectively (P < 0.0001), despite a small absolute difference in mean EF across eGFR groups: 48.2 ± 10.0, 47.9 ± 11.3 and 46.2 ± 12.1, respectively (P = 0.02). The prevalence of HF was again higher with worsening renal function among patients with preserved EF: 10.1%, 13.6% and 23.6% (P < 0.0001), but this relationship was not significant among patients with depressed EF: 27.1%, 26.2% and 37.9% (P = 0.071). Moreover, eGFR was an independent correlate of HF in patients with preserved EF (P = 0.003) but not in patients with depressed EF (P = 0.181). CONCLUSION: A significant proportion of post-MI patients with occluded IRAs have impaired renal function. Impaired renal function was associated with an increased rate of early post-MI HF, the association being strongest in patients with preserved EF. These findings have implications for management of peri-infarct HF. PMID:20885993

Pharmacokinetics of sugammadex in subjects with moderate and severe renal impairment
.

PubMed

Min, K Chris; Lasseter, Kenneth C; Marbury, Thomas C; Wrishko, Rebecca E; Hanley, William D; Wolford, Dennis G; Udo de Haes, Joanna; Reitmann, Christina; Gutstein, David E

2017-09-01

Sugammadex rapidly reverses moderate and deep rocuronium- or vecuronium-induced neuromuscular blockade at doses of 4 mg/kg and 2 mg/kg, respectively. Sugammadex is renally eliminated. This study evaluated the pharmacokinetics of sugammadex in subjects with renal impairment versus those with normal renal function. This open-label, two-part, phase 1 study included adults with moderate (creatinine clearance (CL_cr) 30 - < 50 mL/min) and severe (CL_cr < 30 mL/min) renal impairment and healthy controls (CL_cr ≥ 80 mL/min). A single intravenous (IV) bolus injection of sugammadex 4 mg/kg was administered into a peripheral vein over 10 seconds directly by straight needle in part 1 (n = 24; 8/group), and via an IV catheter followed by a saline flush in part 2 (n = 18; 6/group). Plasma concentrations of sugammadex were collected after drug administration. Due to dosing issues in part 1, pharmacokinetic parameters were determined for part 2 only. Safety was assessed throughout the study. Pharmacokinetic data were obtained from 18 subjects. Mean sugammadex exposure (AUC_0-∞) in subjects with moderate and severe renal impairment was 2.42- and 5.42-times, respectively, that of healthy controls. Clearance decreased and apparent terminal half-life was prolonged with increasing renal dysfunction. Similar C_max values were observed in subjects with renal impairment and healthy controls. There were no serious adverse events. Sugammadex exposure is increased in subjects with moderate and severe renal insufficiency due to progressively decreased clearance as a function of worsening renal function. Sugammadex 4 mg/kg was well tolerated in subjects with renal impairment, with a safety profile similar to that of healthy subjects. These results indicate that dose adjustment of sugammadex is not required in patients with moderate renal impairment; however, current safety experience is insufficient to support the use of sugammadex in patients with CL_cr < 30 mL/min.
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Aspects of renal function in patients with colorectal cancer in a gastroenterology clinic of a county hospital in Western Romania.

PubMed

Velciov, Silvia; Hoinoiu, B; Hoinoiu, Teodora; Popescu, Alina; Gluhovschi, Cristina; Grădinaru, Oana; Popescu, Mădalină; Moţiu, Flavia; Timar, R; Gluhovschi, G H; Sporea, I

2013-01-01

Colorectal cancer represents the third cause of cancer. Since its detection in due time is important resolution, appropriate monitoring is mandatory. The present study deals with the relationship between colorectal cancer and renal function, as well as other associated risk factors. Chronic kidney disease (CKD) represents a risk factor of cancer, both in non-dialysed patients and especially in dialysed patients and in patients with renal transplant. It can get aggravated with cancer in general and particularly with colorectal cancer, partly related to the toxins that cannot be appropriately eliminated because of renal functional disturbances. At the same time, immunosuppressive therapy used for treating glomerular or secondary nephropathies represents an important risk factor of cancer. Some patients with colorectal cancer were found to present also impaired renal function, a fact whose significance is still little known. The object of the present paper is an analysis of the case records of a clinic of gastroenterology on the relationship between colorectal cancer and renal functional impairment. We found in the patients with colorectal cancer under study a glomerular filtration rate (GFR calculated with the EPI formula) of < 60 ml/min/1.73m2 in 31/180 patients, respectively 17.22% of the cases, a value that is similar to that in specialised literature. We also analysed associated risk factors that could be related to renal function impairment in these patients: age, gender, anaemia, diabetes mellitus and hypertension. These could represent, together with the colorectal cancer of the investigated patients, risk factors affecting on the one hand renal function, and on the other hand, potentially increasing the risk of cancer. Correction of these risk factors would have beneficial effects on patients. The relationship between renal functional impairment, respectively CKD, and colorectal cancer is to be regarded from the point of view of complex reciprocity: the impairment of the renal function is a factor of risk of colorectal cancer and colorectal cancer can influence renal function of these patients. This report of reciprocity based on important pathogenic mechanisms also interrelates with factors of risk consecutive to both renal function impairment and colorectal cancer.

Effects of preoperative administration of carprofen on renal function and hemostasis in dogs undergoing surgery for fracture repair.

PubMed

Bergmann, Hannes M L; Nolte, Ingo J A; Kramer, Sabine

2005-08-01

To evaluate effects of preoperative administration of carprofen on renal function and hemostasis in dogs undergoing general anesthesia for fracture repair. 26 client-owned dogs. Anesthesia was induced with levomethadone, diazepam, and propofol and maintained by administration of isoflurane in oxygen-nitrous oxide. Carprofen (4 mg/kg, SC) was administered 1 hour before induction to 13 dogs (group 1) and after extubation to the other 13 dogs (group 2). All dogs also received carprofen (4 mg/kg, SC, q 24 h) for the first 4 days after surgery. Renal function (glomerular filtration rate [GFR], urinary protein-to-urinary creatinine ratio [UP:UC], and results of urinalysis and biochemical analysis of plasma), hemostatic variables (bleeding time, platelet aggregation, prothrombin time [PT], activated partial thromboplastin time [APTT], and platelet count), and Hct were assessed before and at various time points after surgery. Analysis of results for renal function tests, most of the hemostatic and plasma biochemical variables, and Hct did not reveal significant differences between treatment groups. Values for GFR, UP:UC, PT, APTT, and platelet aggregation were outside reference ranges in many dogs before surgery and during the first 6 hours after surgery. In most dogs, these trauma-induced pathologic changes returned to within reference ranges during the 4-day period after surgery. Carprofen did not cause clinically relevant adverse effects in dogs anesthetized for fracture repair after 5 days of treatment, even when it was administered before surgery or given to patients with trauma-induced alterations in renal function or hemostasis.

eNOS gene Glu298Asp and 4b/a polymorphisms are associated with renal function parameters in Mexican patients with Fabry disease.

PubMed

Marin-Medina, A; Brambila-Tapia, A J L; Picos-Cárdenas, V J; Gallegos-Arreola, M P; Figuera, L E

2016-10-24

Fabry disease (FD) is an inherited X-linked lysosomal disease that causes renal failure in a high percentage of affected individuals. The eNOS gene encodes for endothelial nitric oxide synthase, which plays an important role in glomerular hemodynamics. This gene has two main polymorphisms (Glu298Asp and 4b/a) that have been studied in the context of many different diseases, including those involving cardiovascular and renal alterations. Considering the lack of information regarding eNOS variants and FD, we investigated whether there were associations between eNOS genetic variants and renal function parameters in Mexican patients with FD and renal impairment. In total, 15 FD patients with renal alterations were included in the present study, and associations between eNOS polymorphisms and renal function parameters (urea, creatinine, and GFR) were evaluated. The Asp298 and 4a alleles of the eNOS gene were found to be significantly associated with increased levels of urea and creatinine, and a decreased glomerular filtration rate in FD patients, and this association behaved in a co-dominant fashion. Our results coincide with previous reports showing an association between these polymorphisms and kidney disease, and along with other studies regarding their role in the nitric oxide pathway, suggest that these variants affect the severity of nephropathy in patients with FD.

Contributions of nuclear magnetic resonance to renal biochemistry

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

Ross, B.; Freeman, D.; Chan, L.

/sup 31/P NMR as a descriptive technique is of interest to nephrologists. Particular contributions of /sup 31/P NMR to our understanding of renal function may be enumerated.: Free metabolite levels are different from those classically accepted; in particular, ADP and Pi are low with implications for the control of renal metabolism and Pi transport, and, via the phosphorylation potential, for Na+ transport. Renal pH is heterogeneous; between cortex, outer medulla, and papilla, and between cell and lumen, a large pH gradient exists. Also, quantitation between cytosol and mitochondrion of the pH gradient is now feasible. In acute renal failure ofmore » either ischemic or nonischemic origin, both ATP depletion and acidification of the renal cell result in damage, with increasing evidence for the importance of the latter. Measurements of renal metabolic rate in vivo suggest the existence of a prodromal phase of acute renal failure, which could lead to its detection at an earlier and possibly reversible stage. Human renal cancers show a unique /sup 31/P NMR spectrum and a very acidic environment. Cancer chemotherapy may alter this and detection of such changes with NMR offers a method of therapeutic monitoring with significance beyond nephrology. Renal cortex and medulla have a different T1 relaxation time, possibly due to differences in lipid composition. It seems that NMR spectroscopy has much to offer to the future understanding of the relationship between renal biochemistry and function. 56 references.« less

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.

Renal Function and Outcomes With Use of Left Ventricular Assist Device Implantation and Inotropes in End-Stage Heart Failure: A Retrospective Single Center Study

PubMed Central

Verma, Sean; Bassily, Emmanuel; Leighton, Shane; Mhaskar, Rahul; Sunjic, Igor; Martin, Angel; Rihana, Nancy; Jarmi, Tambi; Bassil, Claude

2017-01-01

Background Left ventricular assist device (LVAD) and inotrope therapy serve as a bridge to transplant (BTT) or as destination therapy in patients who are not heart transplant candidates. End-stage heart failure patients often have impaired renal function, and renal outcomes after LVAD therapy versus inotrope therapy have not been evaluated. Methods In this study, 169 patients with continuous flow LVAD therapy and 20 patients with continuous intravenous inotrope therapy were analyzed. The two groups were evaluated at baseline and at 3 and 6 months after LVAD or inotrope therapy was started. The incidence of acute kidney injury (AKI), need for renal replacement therapy (RRT), BTT rate, and mortality for 6 months following LVAD or inotrope therapy were studied. Results between the groups were compared using Mann-Whitney U test and Chi-square with continuity correction or Fischer’s exact at the significance level of 0.05. Results Mean glomerular filtration rate (GFR) was not statistically different between the two groups, with P = 0.471, 0.429, and 0.847 at baseline, 3 and 6 months, respectively. The incidence of AKI, RRT, and BTT was not statistically different. Mortality was less in the inotrope group (P < 0.001). Conclusion Intravenous inotrope therapy in end-stage heart failure patients is non-inferior for mortality, incidence of AKI, need for RRT, and renal function for 6-month follow-up when compared to LVAD therapy. Further studies are needed to compare the effectiveness of inotropes versus LVAD implantation on renal function and outcomes over a longer time period. PMID:28611860

Reduction of severe mitral regurgitation with the MitraClip system improves renal function in two patients presenting with acute kidney injury and progressive renal failure due to cardio renal syndrome.

PubMed

Asdonk, T; Nickenig, G; Hammerstingl, C

2014-10-01

Mitral regurgitation (MR) is a frequent valve disorder in elderly patients, often accompanied by multiple comorbidities such as renal impairment. In these patients percutaneous mitral valve (MV) repair has become an established treatment option but the role of MR on renal dysfunction is not yet well defined. We here report on two cases presenting with severe MR and progressive renal failure caused by cardio renal syndrome, in which percutaneous MV treatment with the MitraClip system significantly improved renal function. These findings suggest that interventional MV repair can prevent progression of renal deterioration in patients suffering from combined advanced heart and renal failure. Further clinical studies are necessary to support our finding and to answer the question whether optimizing renal function by implantation of the MitraClip device is also of prognostic relevance in these patients. © 2014 Wiley Periodicals, Inc.

Quantitative analysis of the renal aging in rats. Stereological study.

PubMed

Melchioretto, Eduardo Felippe; Zeni, Marcelo; Veronez, Djanira Aparecida da Luz; Martins, Eduardo Lopes; Fraga, Rogério de

2016-05-01

To evaluate the renal function and the renal histological alterations through the stereology and morphometrics in rats submitted to the natural process of aging. Seventy two Wistar rats, divided in six groups. Each group was sacrificed in a different age: 3, 6, 9, 12, 18 and 24 months. It was performed right nephrectomy, stereological and morphometric analysis of the renal tissue (renal volume and weight, density of volume (Vv[glom]) and numerical density (Nv[glom]) of the renal glomeruli and average glomerular volume (Vol[glom])) and also it was evaluated the renal function for the dosage of serum creatinine and urea. There was significant decrease of the renal function in the oldest rats. The renal volume presented gradual increase during the development of the rats with the biggest values registered in the group of animals at 12 months of age and significant progressive decrease in older animals. Vv[glom] presented statistically significant gradual reduction between the groups and the Nv[glom] also decreased significantly. The renal function proved to be inferior in senile rats when compared to the young rats. The morphometric and stereological analysis evidenced renal atrophy, gradual reduction of the volume density and numerical density of the renal glomeruli associated to the aging process.

Cardiac Abnormalities in Primary Hyperoxaluria

PubMed Central

Mookadam, Farouk; Smith, Travis; Jiamsripong, Panupong; Moustafa, Sherif E; Monico, Carla G.; Lieske, John C.; Milliner, Dawn S.

2018-01-01

Background In patients with primary hyperoxaluria (PH), oxalate overproduction can result in recurrent urolithiasis and nephrocalcinosis, which in some cases results in a progressive decline in renal function, oxalate retention, and systemic oxalosis involving bone, retina, arterial media, peripheral nerves, skin, and heart. Oxalosis involving the myocardium or conduction system can potentially lead to heart failure and fatal arrhythmias. Methods and Results A retrospective review of our institution’s database was conducted for all patients with a confirmed diagnosis of PH between 1/1948 and 1/2006 (n=103). Electrocardiogram (ECG) and echocardiography were used to identify cardiac abnormalities. Ninety-three patients fulfilled the inclusion criteria, 58% were male. Mean follow-up was 11.9 (median 8.8) years. In 38 patients who received an ECG or echocardiography, 31 were found to have any cardiac abnormalities. Cardiac findings correlated with decline in renal function. Conclusions Our data suggests that physicians caring for patients with PH should pay close attention to cardiac status, especially if renal function is impaired. PMID:20921818

Nephrotic range proteinuria as a strong risk factor for rapid renal function decline during pre-dialysis phase in type 2 diabetic patients with severely impaired renal function.

PubMed

Kitai, Yuichiro; Doi, Yohei; Osaki, Keisuke; Sugioka, Sayaka; Koshikawa, Masao; Sugawara, Akira

2015-12-01

Proteinuria is an established risk factor for progression of renal disease, including diabetic nephropathy. The predictive power of proteinuria, especially nephrotic range proteinuria, for progressive renal deterioration has been well demonstrated in diabetic patients with normal to relatively preserved renal function. However, little is known about the relationship between severity of proteinuria and renal outcome in pre-dialysis diabetic patients with severely impaired renal function. 125 incident dialysis patients with type 2 diabetes were identified. This study was aimed at retrospectively evaluating the impact of nephrotic range proteinuria (urinary protein-creatinine ratio above 3.5 g/gCr) on renal function decline during the 3 months just prior to dialysis initiation. In total, 103 patients (82.4 %) had nephrotic range proteinuria. The median rate of decline in estimated glomerular filtration rate (eGFR) in this study population was 0.98 (interquartile range 0.51-1.46) ml/min/1.73 m(2) per month. Compared to patients without nephrotic range proteinuria, patients with nephrotic range proteinuria showed significantly faster renal function decline (0.46 [0.24-1.25] versus 1.07 [0.64-1.54] ml/min/1.73 m(2) per month; p = 0.007). After adjusting for gender, age, systolic blood pressure, serum albumin, calcium-phosphorus product, hemoglobin A1c, and use of an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker, patients with nephrotic range proteinuria showed a 3.89-fold (95 % CI 1.08-14.5) increased risk for rapid renal function decline defined as a decline in eGFR ≥0.5 ml/min/1.73 m(2) per month. Nephrotic range proteinuria is the predominant renal risk factor in type 2 diabetic patients with severely impaired renal function receiving pre-dialysis care.

Effects of renal function on pharmacokinetics and pharmacodynamics of lesinurad in adult volunteers.

PubMed

Gillen, Michael; Valdez, Shakti; Zhou, Dongmei; Kerr, Bradley; Lee, Caroline A; Shen, Zancong

2016-01-01

Lesinurad is a selective uric acid reabsorption inhibitor approved for the treatment of gout in combination with a xanthine oxidase inhibitor (XOI) in patients who have not achieved target serum uric acid (sUA) levels with an XOI alone. Most people with gout have chronic kidney disease. The pharmacokinetics, pharmacodynamics, and safety of lesinurad were assessed in subjects with impaired renal function. Two Phase I, multicenter, open-label, single-dose studies enrolled subjects with normal renal function (estimated creatinine clearance [eCrCl] >90 mL/min; N=12) or mild (eCrCl 60-89 mL/min; N=8), moderate (eCrCl 30-59 mL/min; N=16), or severe (eCrCl <30 mL/min; N=6) renal impairment. Subjects were given a single oral lesinurad dose of 200 mg (N=24) or 400 mg (N=18). Blood and urine samples were analyzed for plasma lesinurad concentrations and serum and urine uric acid concentrations. Safety was assessed by adverse events and laboratory data. Mild, moderate, and severe renal impairment increased lesinurad plasma area under the plasma concentration-time curve by 34%, 54%-65%, and 102%, respectively. Lesinurad plasma C max was unaffected by renal function status. Lower renal clearance and urinary excretion of lesinurad were associated with the degree of renal impairment. The sUA-lowering effect of a single dose of lesinurad was similar between mild renal impairment and normal function, reduced in moderate impairment, and greatly diminished in severe impairment. Lesinurad increased urinary urate excretion in normal function and mild renal impairment; the increase was less with moderate or severe renal impairment. Lesinurad was well tolerated by all subjects. Lesinurad exposure increased with decreasing renal function; however, the effects of lesinurad on sUA were attenuated in moderate to severe renal impairment.

Live Donor Renal Anatomic Asymmetry and Post-Transplant Renal Function

PubMed Central

Tanriover, Bekir; Fernandez, Sonalis; Campenot, Eric S.; Newhouse, Jeffrey H.; Oyfe, Irina; Mohan, Prince; Sandikci, Burhaneddin; Radhakrishnan, Jai; Wexler, Jennifer J.; Carroll, Maureen A.; Sharif, Sairah; Cohen, David J.; Ratner, Lloyd E.; Hardy, Mark A.

2014-01-01

Background Relationship between live donor renal anatomic asymmetry and post-transplant recipient function has not been studied extensively. Methods We analyzed 96 live-kidney donors, who had anatomical asymmetry (>10% renal length and/or volume difference calculated from CT angiograms) and their matching recipients. Split function differences (SFD) were quantified with 99mTc-DMSA renography. Implantation biopsies at time-zero were semi-quantitatively scored. A comprehensive model utilizing donor renal volume adjusted to recipient weight (Vol/Wgt), SFD, and biopsy score was used to predict recipient estimated glomerular filtration rate (eGFR) at one-year. Primary analysis consisted of a logistic regression model of outcome (odds of developing eGFR>60ml/min/1.73 m2 at one-year), a linear regression model of outcome (predicting recipient eGFR at one-year, using the CKD-EPI formula), and a Monte Carlo simulation based on the linear regression model (N=10,000 iterations). Results In the study cohort, the mean Vol/Wgt and eGFR at one-year were 2.04 ml/kg and 60.4 ml/min/1.73m2, respectively. Volume and split ratios between two donor kidneys were strongly correlated (r=0.79, p-value<0.001). The biopsy scores among SFD categories (<5%, 5–10%, >10%) were not different (p=0.190). On multivariate models, only Vol/Wgt was significantly associated with higher odds of having eGFR>60ml/min/1.73 m2 (OR=8.94, 95% CI 2.47–32.25, p=0.001) and had a strong discriminatory power in predicting the risk of eGFR<60ml/min/1.73m2 at one-year (ROC curve=0.78, 95% CI 0.68–0.89). Conclusion In the presence of donor renal anatomic asymmetry, Vol/Wgt appears to be a major determinant of recipient renal function at one-year post-transplantation. Renography can be replaced with CT volume calculation in estimating split renal function. PMID:25719258

[Should morphology of the upper pole in renal duplication with preserved function and associated ureterocele be taken into account during treatment planning?].

PubMed

Materny, Jacek; Chojnacka, Hanna; Urasińska, Elzbieta; Gawrych, Elzbieta

2011-01-01

The aim of this study was to assess structural changes of the upper pole in renal duplication with coexisting ureterocele with regard to primary and/or secondary lesions. These changes might be of importance in treatment planning. The material of this study consisted of clinical documentation and results of histopathology of 23 upper poles removed due to renal duplication with coexisting ureterocele. The qualification criterion was preserved function of the upper pole seen with 99mTc-DTPA (99mTechnetium diethylenetriaminepentaacetic acid)/99mTc-DMSA (99mTechnetium dimercaptosuccinic acid). Resection of the upper pole was indicated in patients with recurrent urinary tract infections and/or persistent vesicoureteral reflux to the lower pole following endoscopic surgery of the ureterocele and/or low function of the upper pole. Morphological lesions were classified as primary (dysplasia) or secondary lesions. The patients were operated at the Department of Pediatric and Oncologic Surgery, PMU, in 1990-2008. The study group consisted of 17 girls and 6 boys aged from 4 months to 9 years (mean 40 months). Recurrent urinary tract infections noted in 16 (70%) children were the most frequent indication for surgery. The preoperative mean function of the renal poles assessed with DTPA/DMSA represented 6% of the differential renal function. Dysplasia was identified in eight resected renal poles (34%) with coexisting secondary lesions in three of them. Secondary lesions only were seen in 15 poles (66%). There was no correlation between age and incidence of dysplasia during follow-up (Pearson's correlation coefficient r = 0.031). Secondary lesions are a quite frequent finding in resected upper poles. As 66% of the renal poles studied with histopathology revealed secondary lesions only, we believe that renal sparing treatment is justified in cases of urinary duplication with coexisting ureterocele.

The KUPNetViz: a biological network viewer for multiple -omics datasets in kidney diseases

PubMed Central

2013-01-01

Background Constant technological advances have allowed scientists in biology to migrate from conventional single-omics to multi-omics experimental approaches, challenging bioinformatics to bridge this multi-tiered information. Ongoing research in renal biology is no exception. The results of large-scale and/or high throughput experiments, presenting a wealth of information on kidney disease are scattered across the web. To tackle this problem, we recently presented the KUPKB, a multi-omics data repository for renal diseases. Results In this article, we describe KUPNetViz, a biological graph exploration tool allowing the exploration of KUPKB data through the visualization of biomolecule interactions. KUPNetViz enables the integration of multi-layered experimental data over different species, renal locations and renal diseases to protein-protein interaction networks and allows association with biological functions, biochemical pathways and other functional elements such as miRNAs. KUPNetViz focuses on the simplicity of its usage and the clarity of resulting networks by reducing and/or automating advanced functionalities present in other biological network visualization packages. In addition, it allows the extrapolation of biomolecule interactions across different species, leading to the formulations of new plausible hypotheses, adequate experiment design and to the suggestion of novel biological mechanisms. We demonstrate the value of KUPNetViz by two usage examples: the integration of calreticulin as a key player in a larger interaction network in renal graft rejection and the novel observation of the strong association of interleukin-6 with polycystic kidney disease. Conclusions The KUPNetViz is an interactive and flexible biological network visualization and exploration tool. It provides renal biologists with biological network snapshots of the complex integrated data of the KUPKB allowing the formulation of new hypotheses in a user friendly manner. PMID:23883183

The protective effect of baicalin against renal ischemia-reperfusion injury through inhibition of inflammation and apoptosis

PubMed Central

2014-01-01

Background Renal ischemia-reperfusion injury (IRI) increases the rates of acute kidney failure, delayed graft function, and early mortality after kidney transplantation. The pathophysiology involved includes oxidative stress, mitochondrial dysfunction, and immune-mediated injury. The anti-oxidation, anti-apoptosis, and anti-inflammation properties of baicalin, a flavonoid glycoside isolated from Scutellaria baicalensis, have been verified. This study therefore assessed the effects of baicalin against renal IRI in rats. Methods Baicalin was intraperitoneally injected 30 min before renal ischemia. Serum and kidneys were harvested 24 h after reperfusion. Renal function and histological changes were assessed. Markers of oxidative stress, the Toll-like receptor (TLR)2 and TLR4 signaling pathway, mitochondrial stress, and cell apoptosis were also evaluated. Results Baicalin treatment decreased oxidative stress and histological injury, and improved kidney function, as well as inhibiting proinflammatory responses and tubular apoptosis. Baicalin pretreatment also reduced the expression of TLR2, TLR4, MyD88, p-NF-κB, and p-IκB proteins, as well as decreasing caspase-3 activity and increasing the Bcl-2/Bax ratio. Conclusions Baicalin may attenuate renal ischemia-reperfusion injury by inhibiting proinflammatory responses and mitochondria-mediated apoptosis. These effects are associated with the TLR2/4 signaling pathway and mitochondrial stress. PMID:24417870

Carotid artery wall shear stress is independently correlated with renal function in the elderly.

PubMed

Guo, Yuqi; Wei, Fang; Wang, Juan; Zhao, Yingxin; Sun, Shangwen; Zhang, Hua; Liu, Zhendong

2018-01-12

Hemodynamic has increasingly been regarded as an important factor of renal function. However, the relationship between carotid artery wall shear stress (WSS) and renal function is not clarified. To investigate the relationship between carotid WSS and renal function, we recruited 761 older subjects aged 60 years and over from community-dwelling in the Shandong area, China. Carotid WSS, endothelial function, and estimated glomerular filtration rate (eGFR) were assessed in all subjects. Subjects were grouped by the interquartile of the carotid artery mean WSS. We found that the eGFRs derived from serum creatinine and/or cystatin C using three CKD-EPI equations were significantly higher and albumin/creatinine ratio was lower in the higher interquartile groups than in the lower interquartile groups ( P <0.05). The mean WSS was independently correlated with eGFRs even after adjustment for confounders. Similar findings were found between carotid artery peak WSS and eGFRs and albumin/creatinine ratio. In addition, we found that endothelial function was strongly related to carotid WSS and renal function after adjustment for confounders. In conclusion, there is an independent correlation of carotid WSS with renal function in the elderly. The local rheologic forces may play an important role in renal function changing. The correlation may be mediated by regulation of endothelial function.

The Renal Arterial Resistance Index Predicts Worsening Renal Function in Chronic Heart Failure Patients

PubMed Central

Iacoviello, Massimo; Monitillo, Francesco; Leone, Marta; Citarelli, Gaetano; Doronzo, Annalisa; Antoncecchi, Valeria; Puzzovivo, Agata; Rizzo, Caterina; Lattarulo, Maria Silvia; Massari, Francesco; Caldarola, Pasquale; Ciccone, Marco Matteo

2016-01-01

Background/Aim The renal arterial resistance index (RRI) is a Doppler measure, which reflects abnormalities in the renal blood flow. The aim of this study was to verify the value of RRI as a predictor of worsening renal function (WRF) in a group of chronic heart failure (CHF) outpatients. Methods We enrolled 266 patients in stable clinical conditions and on conventional therapy. Peak systolic velocity and end diastolic velocity of a segmental renal artery were obtained by pulsed Doppler flow, and RRI was calculated. Creatinine serum levels were evaluated at baseline and at 1 year, and the changes were used to assess WRF occurrence. Results During follow-up, 34 (13%) patients showed WRF. RRI was associated with WRF at univariate (OR: 1.13; 95% CI: 1.07–1.20) as well as at a forward stepwise multivariate logistic regression analysis (OR: 1.09; 95% CI: 1.03–1.16; p = 0.005) including the other univariate predictors. Conclusions Quantification of arterial renal perfusion provides a new parameter that independently predicts the WRF in CHF outpatients. Its possible role in current clinical practice to better define the risk of cardiorenal syndrome progression is strengthened. PMID:27994601

Physical Exercise and Patients with Chronic Renal Failure: A Meta-Analysis.

PubMed

Qiu, Zhenzhen; Zheng, Kai; Zhang, Haoxiang; Feng, Ji; Wang, Lizhi; Zhou, Hao

2017-01-01

Chronic renal failure is a severe clinical problem which has some significant socioeconomic impact worldwide and hemodialysis is an important way to maintain patients' health state, but it seems difficult to get better in short time. Considering these, the aim in our research is to update and evaluate the effects of exercise on the health of patients with chronic renal failure. The databases were used to search for the relevant studies in English or Chinese. And the association between physical exercise and health state of patients with chronic renal failure has been investigated. Random-effect model was used to compare the physical function and capacity in exercise and control groups. Exercise is helpful in ameliorating the situation of blood pressure in patients with renal failure and significantly reduces VO 2 in patients with renal failure. The results of subgroup analyses show that, in the age >50, physical activity can significantly reduce blood pressure in patients with renal failure. The activity program containing warm-up, strength, and aerobic exercises has benefits in blood pressure among sick people and improves their maximal oxygen consumption level. These can help patients in physical function and aerobic capacity and may give them further benefits.

Physical Exercise and Patients with Chronic Renal Failure: A Meta-Analysis

PubMed Central

Qiu, Zhenzhen; Zheng, Kai; Zhang, Haoxiang; Feng, Ji; Wang, Lizhi

2017-01-01

Chronic renal failure is a severe clinical problem which has some significant socioeconomic impact worldwide and hemodialysis is an important way to maintain patients' health state, but it seems difficult to get better in short time. Considering these, the aim in our research is to update and evaluate the effects of exercise on the health of patients with chronic renal failure. The databases were used to search for the relevant studies in English or Chinese. And the association between physical exercise and health state of patients with chronic renal failure has been investigated. Random-effect model was used to compare the physical function and capacity in exercise and control groups. Exercise is helpful in ameliorating the situation of blood pressure in patients with renal failure and significantly reduces VO2 in patients with renal failure. The results of subgroup analyses show that, in the age >50, physical activity can significantly reduce blood pressure in patients with renal failure. The activity program containing warm-up, strength, and aerobic exercises has benefits in blood pressure among sick people and improves their maximal oxygen consumption level. These can help patients in physical function and aerobic capacity and may give them further benefits. PMID:28316986

Residual Renal Function in Children Treated with Chronic Peritoneal Dialysis

PubMed Central

Roszkowska-Blaim, Maria

2013-01-01

Residual renal function (RRF) in patients with end-stage renal disease (ESRD) receiving renal replacement therapy is defined as the ability of native kidneys to eliminate water and uremic toxins. Preserved RRF improves survival and quality of life in adult ESRD patients treated with peritoneal dialysis. In children, RRF was shown not only to help preserve adequacy of renal replacement therapy but also to accelerate growth rate, improve nutrition and blood pressure control, reduce the risk of adverse myocardial changes, facilitate treatment of anemia and calcium-phosphorus balance abnormalities, and result in reduced serum and dialysate fluid levels of advanced glycation end-products. Factors contributing to RRF loss in children treated with peritoneal dialysis include the underlying renal disease such as hemolytic-uremic syndrome and hereditary nephropathy, small urine volume, severe proteinuria at the initiation of renal replacement therapy, and hypertension. Several approaches can be suggested to decrease the rate of RRF loss in pediatric patients treated with chronic peritoneal dialysis: potentially nephrotoxic drugs (e.g., aminoglycosides), episodes of hypotension, and uncontrolled hypertension should be avoided, urinary tract infections should be treated promptly, and loop diuretics may be used to increase salt and water excretion. PMID:24376376

A Review of Anesthetic Effects on Renal Function: Potential Organ Protection.

PubMed

Motayagheni, Negar; Phan, Sheshanna; Eshraghi, Crystal; Nozari, Ala; Atala, Anthony

2017-01-01

Renal protection is a critical concept for anesthesiologists, nephrologists, and urologists, since anesthesia and renal function are highly interconnected and can potentially interfere with one another. Therefore, a comprehensive understanding of anesthetic drugs and their effects on renal function remains fundamental to the success of renal surgeries, especially transplant procedures. Some experimental studies have shown that some anesthetics provide protection against renal ischemia/reperfusion (IR) injury, but there is limited clinical evidence. The effects of anesthetic drugs on renal failure are particularly important in the context of kidney transplantation, since the conditions of preservation following removal profoundly influence the recovery of organ function. Currently, preservation procedures are typically based on the usage of a cold-storage solution. Some anesthetic drugs induce anti-inflammatory, anti-necrotic, and anti-apoptotic effects. A more thorough understanding of anesthetic effects on renal function can present a novel approach for developing organ-protective strategies. The aim of this review is to discuss the effects of different anesthetic drugs on renal function, with particular focus on IR injury. Many studies have demonstrated the organ-protective effects of some anesthetic drugs, specifically propofol, which indicate the potential of some anesthetics to introduce novel organ protective targets. This is not surprising, since lipid emulsions are major components of propofol, which accumulating data show provide organ protective effects against IR injury. Key Messages: Thorough understanding of the interaction between anesthetic drugs and renal function remains fundamental to the delivery of safe perioperative care and to optimizing outcomes after renal surgeries, particularly transplant procedures. Anesthetics can be repurposed for organ protection with more information about their effects, especially during transplant procedures. Here, we review the effects of different anesthetic drugs - specifically those that contain lipids in their structure, with special reference to IR injury. © 2017 S. Karger AG, Basel.

Comparing renal function preservation after laparoscopic radio frequency ablation assisted tumor enucleation and laparoscopic partial nephrectomy for clinical T1a renal tumor: using a 3D parenchyma measurement system.

PubMed

Zhu, Liangsong; Wu, Guangyu; Huang, Jiwei; Wang, Jianfeng; Zhang, Ruiyun; Kong, Wen; Xue, Wei; Huang, Yiran; Chen, Yonghui; Zhang, Jin

2017-05-01

To compare the renal function preservation between laparoscopic radio frequency ablation assisted tumor enucleation and laparoscopic partial nephrectomy. Data were analyzed from 246 patients who underwent laparoscopic radio frequency ablation assisted tumor enucleation and laparoscopic partial nephrectomy for solitary cT1a renal cell carcinoma from January 2013 to July 2015. To reduce the intergroup difference, we used a 1:1 propensity matching analysis. The functional renal parenchyma volume preservation were measured preoperative and 12 months after surgery. The total renal function recovery and spilt GFR was compared. Multivariable logistic analysis was used for predictive factors for renal function decline. After 1:1 propensity matching, each group including 100 patients. Patients in the laparoscopic radio frequency ablation assisted tumor enucleation had a smaller decrease in estimate glomerular filtration rate at 1 day (-7.88 vs -20.01%, p < 0.001), 3 months (-2.31 vs -10.39%, p < 0.001), 6 months (-2.16 vs -7.99%, p = 0.015), 12 months (-3.26 vs -8.03%, p = 0.012) and latest test (-3.24 vs -8.02%, p = 0.040), also had better functional renal parenchyma volume preservation (89.19 vs 84.27%, p < 0.001), lower decrease of the spilt glomerular filtration rate (-9.41 vs -17.13%, p < 0.001) at 12 months. The functional renal parenchyma volume preservation, warm ischemia time and baseline renal function were the important independent factors in determining long-term functional recovery. The laparoscopic radio frequency ablation assisted tumor enucleation technology has unique advantage and potential in preserving renal parenchyma without ischemia damage compared to conventional laparoscopic partial nephrectomy, and had a better outcome, thus we recommend this technique in selected T1a patients.

Influence of percutaneous mitral valve repair using the MitraClip® system on renal function in patients with severe mitral regurgitation.

PubMed

Rassaf, Tienush; Balzer, Jan; Rammos, Christos; Zeus, Tobias; Hellhammer, Katharina; v Hall, Silke; Wagstaff, Rabea; Kelm, Malte

2015-04-01

In patients with mitral regurgitation (MR), changes in cardiac stroke volume, and thus renal preload and afterload may affect kidney function. Percutaneous mitral valve repair (PMVR) with the MitraClip® system can be a therapeutic alternative to surgical valve repair. The influence of MitraClip® therapy on renal function and clinical outcome parameters is unknown. Sixty patients with severe MR underwent PMVR using the MitraClip® system in an open-label observational study. Patients were stratified according to their renal function. All clips have been implanted successfully. Effective reduction of MR by 2-3 grades acutely improved KDOQI class. Lesser MR reduction (MR reduction of 0-1 grades) led to worsening of renal function in patients with pre-existing normal or mild (KDOQI 1-2) compared to severe (KDOQI 3-4) renal dysfunction. Reduction of MR was associated with improvement in Minnesota Living with Heart Failure Questionnaire (MLHFQ), NYHA-stadium, and 6-minute walk test. Successful PMVR was associated with an improvement in renal function. The improvement in renal function was associated with the extent of MR reduction and pre-existing kidney dysfunction. Our data emphasize the relevance of PVMR to stabilize the cardiorenal axis in patients with severe MR. © 2014 Wiley Periodicals, Inc.

Impact of renal dysfunction on outcomes of coronary artery bypass surgery: results from the Society of Thoracic Surgeons National Adult Cardiac Database.

PubMed

Cooper, William A; O'Brien, Sean M; Thourani, Vinod H; Guyton, Robert A; Bridges, Charles R; Szczech, Lynda A; Petersen, Rebecca; Peterson, Eric D

2006-02-28

Although patients with end-stage renal disease are known to be at high risk for mortality after coronary artery bypass graft (CABG) surgery, the impact of lesser degrees of renal impairment has not been well studied. The purpose of this study was to compare outcomes in patients undergoing CABG with a range from normal renal function to dependence on dialysis. We reviewed 483,914 patients receiving isolated CABG from July 2000 to December 2003, using the Society of Thoracic Surgeons National Adult Cardiac Database. Glomerular filtration rate (GFR) was estimated for patients with the use of the Modification of Diet in Renal Disease study formula. Multivariable logistic regression was used to determine the association of GFR with operative mortality and morbidities (stroke, reoperation, deep sternal infection, ventilation >48 hours, postoperative stay >2 weeks) after adjustment for 27 other known clinical risk factors. Preoperative renal dysfunction (RD) was common among CABG patients, with 51% having mild RD (GFR 60 to 90 mL/min per 1.73 m2, excludes dialysis), 24% moderate RD (GFR 30 to 59 mL/min per 1.73 m2, excludes dialysis), 2% severe RD (GFR <30 mL/min per 1.73 m2, excludes dialysis), and 1.5% requiring dialysis. Operative mortality rose inversely with declining renal function, from 1.3% for those with normal renal function to 9.3% for patients with severe RD not on dialysis and 9.0% for those who were dialysis dependent. After adjustment for other covariates, preoperative GFR was one of the most powerful predictors of operative mortality and morbidities. Preoperative RD is common in the CABG population and carries important prognostic importance. Assessment of preoperative renal function should be incorporated into clinical risk assessment and prediction models.

Safety, Tolerability, and Pharmacokinetics of Ribavirin in Hepatitis C Virus-Infected Patients with Various Degrees of Renal Impairment

PubMed Central

Wang, K.; Blotner, S.; Magnusson, M. O.; Wilkins, J. J.; Martin, P.; Solsky, J.; Nieforth, K.; Wat, C.; Grippo, J. F.

2013-01-01

Ribavirin (RBV) is an integral part of standard-of-care hepatitis C virus (HCV) treatments and many future regimens under investigation. The pharmacokinetics (PK), safety, and tolerability of RBV in chronically HCV-infected patients with renal impairment are not well defined and were the focus of an open-label PK study in HCV-infected patients receiving RBV plus pegylated interferon. Serial RBV plasma samples were collected over 12 h on day 1 of weeks 1 and 12 from patients with moderate renal impairment (creatinine clearance [CLCR], 30 to 50 ml/min; RBV, 600 mg daily), severe renal impairment (CLCR, <30 ml/min; RBV, 400 mg daily), end-stage renal disease (ESRD) (RBV, 200 mg daily), or normal renal function (CLCR, >80 ml/min; RBV, 800 to 1,200 mg daily). Of the 44 patients, 9 had moderately impaired renal function, 10 had severely impaired renal function, 13 had ESRD, and 12 had normal renal function. The RBV dose was reduced because of adverse events (AEs) in 71% and 53% of severe and moderate renal impairment groups, respectively. Despite this modification, patients with moderate and severe impairment had 12-hour (area under the concentration-time curve from 0 to 12 h [AUC0–12]) values 36% (38,452 ng · h/ml) and 25% (35,101 ng · h/ml) higher, respectively, than those with normal renal function (28,192 ng · h/ml). Patients with ESRD tolerated a 200-mg daily dose, and AUC0–12 was 20% lower (22,629 ng · h/ml) than in patients with normal renal function. PK modeling and simulation (M&S) indicated that doses of 200 mg or 400 mg alternating daily for patients with moderate renal impairment and 200 mg daily for patients with severe renal impairment were the most appropriate dose regimens in these patients. PMID:24080649

Renal involvement in leprosy: evaluation of patients in Turkey.

PubMed

Ozturk, Savas; Ozturk, Tulin; Can, Ilkay

2017-06-01

Renal involvement in leprosy has previously been described in the literature and can include amyloidosis, glomerulonephritis, nephrosclerosis, tubulointerstitial nephritis, and granulomas. To evaluate renal involvement in Turkish patients with leprosy. In total, 32 patients with lepromatous leprosy but without any co-morbidities and 35 healthy control subjects were evaluated for renal involvement at the Elazig Training and Research Hospital in Turkey. The laboratory tests and radiological results concerning renal function were taken from both the patients' medical records and from current examinations. The levels of creatinine, urea, and leukocyturia in the lepromatous leprosy patients were significantly higher than in the controls ( p < 0.001, p < 0.001; p = 0.001, p < 0.01; p = 0.036, p < 0.05, respectively). No significant differences in the proteinuria, hematuria, sodium, or potassium levels were found between the leprosy and control groups ( p > 0.05). On ultrasonographic examination, the prevalence of renal cortical cysts and renal cortical echogenicity in the leprosy patients was significantly higher than in the controls ( p = 0.020, p < 0.05, respectively). There were no significant differences in terms of nephrolithiasis, parapelvic cysts, or hydronephrosis between the leprosy and control groups ( p > 0.05). Evaluating the renal function in all leprosy patients is important to detect abnormalities and to prevent renal failure, which remains a potential cause of death in this disease.

Renal Oxidative Stress Induced by Long-Term Hyperuricemia Alters Mitochondrial Function and Maintains Systemic Hypertension

PubMed Central

Cristóbal-García, Magdalena; García-Arroyo, Fernando E.; Arellano-Buendía, Abraham S.; Madero, Magdalena; Rodríguez-Iturbe, Bernardo; Pedraza-Chaverrí, José; Zazueta, Cecilia; Johnson, Richard J.; Sánchez Lozada, Laura-Gabriela

2015-01-01

We addressed if oxidative stress in the renal cortex plays a role in the induction of hypertension and mitochondrial alterations in hyperuricemia. A second objective was to evaluate whether the long-term treatment with the antioxidant Tempol prevents renal oxidative stress, mitochondrial alterations, and systemic hypertension in this model. Long-term (11-12 weeks) and short-term (3 weeks) effects of oxonic acid induced hyperuricemia were studied in rats (OA, 750 mg/kg BW), OA+Allopurinol (AP, 150 mg/L drinking water), OA+Tempol (T, 15 mg/kg BW), or vehicle. Systolic blood pressure, renal blood flow, and vascular resistance were measured. Tubular damage (urine N-acetyl-β-D-glucosaminidase) and oxidative stress markers (lipid and protein oxidation) along with ATP levels were determined in kidney tissue. Oxygen consumption, aconitase activity, and uric acid were evaluated in isolated mitochondria from renal cortex. Short-term hyperuricemia resulted in hypertension without demonstrable renal oxidative stress or mitochondrial dysfunction. Long-term hyperuricemia induced hypertension, renal vasoconstriction, tubular damage, renal cortex oxidative stress, and mitochondrial dysfunction and decreased ATP levels. Treatments with Tempol and allopurinol prevented these alterations. Renal oxidative stress induced by hyperuricemia promoted mitochondrial functional disturbances and decreased ATP content, which represent an additional pathogenic mechanism induced by chronic hyperuricemia. Hyperuricemia-related hypertension occurs before these changes are evident. PMID:25918583

The renal concentrating mechanism and the clinical consequences of its loss

PubMed Central

Agaba, Emmanuel I.; Rohrscheib, Mark; Tzamaloukas, Antonios H.

2012-01-01

The integrity of the renal concentrating mechanism is maintained by the anatomical and functional arrangements of the renal transport mechanisms for solute (sodium, potassium, urea, etc) and water and by the function of the regulatory hormone for renal concentration, vasopressin. The discovery of aquaporins (water channels) in the cell membranes of the renal tubular epithelial cells has elucidated the mechanisms of renal actions of vasopressin. Loss of the concentrating mechanism results in uncontrolled polyuria with low urine osmolality and, if the patient is unable to consume (appropriately) large volumes of water, hypernatremia with dire neurological consequences. Loss of concentrating mechanism can be the consequence of defective secretion of vasopressin from the posterior pituitary gland (congenital or acquired central diabetes insipidus) or poor response of the target organ to vasopressin (congenital or nephrogenic diabetes insipidus). The differentiation between the three major states producing polyuria with low urine osmolality (central diabetes insipidus, nephrogenic diabetes insipidus and primary polydipsia) is done by a standardized water deprivation test. Proper diagnosis is essential for the management, which differs between these three conditions. PMID:23293407

28 CFR 79.61 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) Cor pulmonale means heart disease, including hypertrophy of the right ventricle, due to pulmonary... Criteria for Claims by Ore Transporters § 79.61 Definitions. (a) Chronic renal disease means the chronic... injury means structural or functional damage to the kidney tubules that results in renal disease and...

28 CFR 79.51 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) Cor pulmonale means heart disease, including hypertrophy of the right ventricle, due to pulmonary... Criteria for Claims by Uranium Millers § 79.51 Definitions. (a) Chronic renal disease means the chronic... or functional damage to the kidney tubules that results in renal disease and dysfunction. (g) Miller...

28 CFR 79.51 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) Cor pulmonale means heart disease, including hypertrophy of the right ventricle, due to pulmonary... Criteria for Claims by Uranium Millers § 79.51 Definitions. (a) Chronic renal disease means the chronic... or functional damage to the kidney tubules that results in renal disease and dysfunction. (g) Miller...

28 CFR 79.61 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) Cor pulmonale means heart disease, including hypertrophy of the right ventricle, due to pulmonary... Criteria for Claims by Ore Transporters § 79.61 Definitions. (a) Chronic renal disease means the chronic... injury means structural or functional damage to the kidney tubules that results in renal disease and...

Why, when and how should immunosuppressive therapy considered in patients with immunoglobulin A nephropathy?

PubMed Central

Rasche, F. M.; Rasche, W. G.; Schiekofer, S.; Boldt, A.; Sack, U.; Fahnert, J.

2016-01-01

Summary IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Lifelong mesangial deposition of IgA1 complexes subsist inflammation and nephron loss, but the complex pathogenesis in detail remains unclear. In regard to the heterogeneous course, classical immunosuppressive and specific therapeutic regimens adapted to the loss of renal function will here be discussed in addition to the essential common renal supportive therapy. Renal supportive therapy alleviates secondary, surrogate effects or sequelae on renal function and proteinuria of high intraglomerular pressure and subsequent nephrosclerosis by inhibition of the renin angiotensin system (RAASB). In patients with physiological (ΔGFR < 1·5 ml/min/year) or mild (ΔGFR 1·5–5 ml/min/year) decrease of renal function and proteinuric forms (> 1 g/day after RAASB), corticosteroids have shown a reduction of proteinuria and might protect further loss of renal function. In patients with progressive loss of renal function (ΔGFR > 3 ml/min within 3 months) or a rapidly progressive course with or without crescents in renal biopsy, cyclophosphamide with high‐dose corticosteroids as induction therapy and azathioprine maintenance has proved effective in one randomized controlled study of a homogeneous cohort in loss of renal function (ΔGFR). Mycophenolic acid provided further maintenance in non‐randomized trials. Differentiated, precise, larger, randomized, placebo‐controlled studies focused on the loss of renal function in the heterogeneous forms of IgAN are still lacking. Prospectively, fewer toxic agents will be necessary in the treatment of IgAN. PMID:27283488

Relationship of MTHFR gene polymorphisms with renal and cardiac disease

PubMed Central

Trovato, Francesca M; Catalano, Daniela; Ragusa, Angela; Martines, G Fabio; Pirri, Clara; Buccheri, Maria Antonietta; Di Nora, Concetta; Trovato, Guglielmo M

2015-01-01

AIM: To investigate the effects of different methylenetetrahydrofolate reductase (MTHFR) 677C>T gene polymorphism and hyperhomocysteinemia for the development of renal failure and cardiovascular events, which are controversial. METHODS: We challenged the relationship, if any, of MTHFR 677C>T and MTHFR 1298A>C polymorphisms with renal and heart function. The present article is a reappraisal of these concepts, investigating within a larger population, and including a subgroup of dialysis patients, if the two most common MTHFR polymorphisms, C677T and A1298C, as homozygous, heterozygous or with a compound heterozygous state, show different association with chronic renal failure requiring hemodialysis. MTHFR polymorphism could be a favorable evolutionary factor, i.e., a protective factor for many ominous conditions, like cancer and renal failure. A similar finding was reported in fatty liver disease in which it is suggested that MTHFR polymorphisms could have maintained and maintain their persistence by an heterozygosis advantage mechanism. We studied a total of 630 Italian Caucasian subject aged 54.60 ± 16.35 years, addressing to the increased hazard of hemodialysis, if any, according to the studied MTHFR genetic polymorphisms. RESULTS: A favorable association with normal renal function of MTHFR polymorphisms, and notably of MTHFR C677T is present independently of the negative effects of left ventricular hypertrophy, increased Intra-Renal arterial Resistance and hyperparathyroidism. CONCLUSION: MTHFR gene polymorphisms could have a protective role on renal function as suggested by their lower frequency among our dialysis patients in end-stage renal failure; differently, the association with left ventricular hypertrophy and reduced left ventricular relaxation suggest some type of indirect, or concurrent mechanism. PMID:25664255

Endothelin-A receptor blockade slows the progression of renal injury in experimental renovascular disease.

PubMed

Kelsen, Silvia; Hall, John E; Chade, Alejandro R

2011-07-01

Endothelin (ET)-1, a potent renal vasoconstrictor with mitogenic properties, is upregulated by ischemia and has been shown to induce renal injury via the ET-A receptor. The potential role of ET-A blockade in chronic renovascular disease (RVD) has not, to our knowledge, been previously reported. We hypothesized that chronic ET-A receptor blockade would preserve renal hemodynamics and slow the progression of injury of the stenotic kidney in experimental RVD. Renal artery stenosis, a major cause of chronic RVD, was induced in 14 pigs and observed for 6 wk. In half of the pigs, chronic ET-A blockade was initiated (RVD+ET-A, 0.75 mg·kg(-1)·day(-1)) at the onset of RVD. Single-kidney renal blood flow, glomerular filtration rate, and perfusion were quantified in vivo after 6 wk using multidetector computer tomography. Renal microvascular density was quantified ex vivo using three-dimensional microcomputer tomography, and growth factors, inflammation, apoptosis, and fibrosis were determined in renal tissue. The degree of stenosis and increase in blood pressure were similar in RVD and RVD+ET-A pigs. Renal hemodynamics, function, and microvascular density were decreased in the stenotic kidney but preserved by ET-A blockade, accompanied by increased renal expression of vascular endothelial growth factor, hepatocyte growth factor, and downstream mediators such as phosphorilated-Akt, angiopoietins, and endothelial nitric oxide synthase. ET-A blockade also reduced renal apoptosis, inflammation, and glomerulosclerosis. This study shows that ET-A blockade slows the progression of renal injury in experimental RVD and preserves renal hemodynamics, function, and microvascular density in the stenotic kidney. These results support a role for ET-1/ET-A as a potential therapeutic target in chronic RVD.

Endothelin-A receptor blockade slows the progression of renal injury in experimental renovascular disease

PubMed Central

Kelsen, Silvia; Hall, John E.

2011-01-01

Endothelin (ET)-1, a potent renal vasoconstrictor with mitogenic properties, is upregulated by ischemia and has been shown to induce renal injury via the ET-A receptor. The potential role of ET-A blockade in chronic renovascular disease (RVD) has not, to our knowledge, been previously reported. We hypothesized that chronic ET-A receptor blockade would preserve renal hemodynamics and slow the progression of injury of the stenotic kidney in experimental RVD. Renal artery stenosis, a major cause of chronic RVD, was induced in 14 pigs and observed for 6 wk. In half of the pigs, chronic ET-A blockade was initiated (RVD+ET-A, 0.75 mg·kg−1·day−1) at the onset of RVD. Single-kidney renal blood flow, glomerular filtration rate, and perfusion were quantified in vivo after 6 wk using multidetector computer tomography. Renal microvascular density was quantified ex vivo using three-dimensional microcomputer tomography, and growth factors, inflammation, apoptosis, and fibrosis were determined in renal tissue. The degree of stenosis and increase in blood pressure were similar in RVD and RVD+ET-A pigs. Renal hemodynamics, function, and microvascular density were decreased in the stenotic kidney but preserved by ET-A blockade, accompanied by increased renal expression of vascular endothelial growth factor, hepatocyte growth factor, and downstream mediators such as phosphorilated-Akt, angiopoietins, and endothelial nitric oxide synthase. ET-A blockade also reduced renal apoptosis, inflammation, and glomerulosclerosis. This study shows that ET-A blockade slows the progression of renal injury in experimental RVD and preserves renal hemodynamics, function, and microvascular density in the stenotic kidney. These results support a role for ET-1/ET-A as a potential therapeutic target in chronic RVD. PMID:21478482

Well Preserved Renal Function in Children With Untreated Chronic Liver Disease.

PubMed

Berg, Ulla B; Németh, Antal

2018-04-01

On the basis of studies with hepatorenal syndrome, it is widely regarded that renal function is impacted in chronic liver disease (CLD). Therefore, we investigated renal function in children with CLD. In a retrospective study of 277 children with CLD, renal function was investigated as glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), measured as clearance of inulin and para-amino hippuric acid or clearance of iohexol. The data were analyzed with regard to different subgroups of liver disease and to the grade of damage. Hyperfiltration (>+2 SD of controls) was found in the subgroups of progressive familial intrahepatic cholestasis (44%), glycogenosis (75%), and acute fulminant liver failure (60%). Patients with biliary atresia, most other patients with metabolic disease and intrahepatic cholestasis, and those with vascular anomalies and cryptogenic cirrhosis had normal renal function. Decreased renal function was found in patients with Alagille's syndrome (64% < -2 SD). Increased GFR and ERPF was found in patients with elevated transaminases, low prothrombin level, high bile acid concentration, and high aspartate-aminotransferase-to-platelet ratio. Most children with CLD had surprisingly well preserved renal function and certain groups had even hyperfiltration. The finding that children with decompensated liver disease and ongoing liver failure had stable kidney function suggests that no prognostic markers of threatening hepatorenal syndrome were at hand. Moreover, estimation of GFR based on serum creatinine fails to reveal hyperfiltration.

Renal transplantation across the donor-specific antibody barrier: Graft outcome and cancer risk after desensitization therapy.

PubMed

Yang, Ching-Yao; Lee, Chih-Yuan; Yeh, Chi-Chuan; Tsai, Meng-Kun

2016-06-01

Desensitization regimens including use of intravenous immune globulin and rituximab have been reported to overcome renal transplant hyperacute rejection. A retrospective case-control study was performed to assess the results and complications of renal transplantation with desensitization therapy for donor-specific antibody (DSA) in a transplant center in Asia, where donor exchange was usually not allowed. Between January 2007 and December 2013, 22 patients with DSA received live-donor renal transplantation after desensitization (DSA group). During the same period, the DSA group was compared to the NSA group (152 renal transplants) who had no specific antibody to the donors (66 from deceased donors and 86 from living relatives). Rejection, renal function, graft and patient survival rates, infection, and cancer incidence were reviewed and analyzed from medical records. The DSA group (46.8%) had significantly higher acute rejection rates than the NSA group (13.7%) at the 1-year follow-up. The estimated renal function, 5-year graft, and patient survival rates were comparable between the groups. The DSA group (19.6%) had significantly higher 5-year de novo cancer incidence than the NSA group (8.5%; p = 0.028); three patients of the DSA group developed urothelial carcinoma 17.0 ± 3.0 months after transplantation. By using stepwise Cox regression analysis, desensitization therapy was identified as the sole independent risk factor for post-transplant urothelial carcinoma. When compared to renal transplantation without DSA, desensitization therapy for DSA resulted in equivalent renal transplant outcome but potentially increased risk of urothelial carcinoma after transplantation. Copyright © 2015. Published by Elsevier B.V.

Effect of calyx capsule-ethanol extract Hibiscus sabdariffa L. on renal function of healthy volunteers

NASA Astrophysics Data System (ADS)

Harun, N.; Darmawan, E.; Nurani, L. H.

2017-11-01

Hibiscus sabdariffa contains flavonoid, triterpenoid, anthocyanin which function as immunostimulant. H. sabdariffa is considered safe for animal renal; nonetheless, there are known side effects of which need to be further investigated for human renal. This research aims to investigate the effect of calyx capsule-ethanol extract H. sabdariffa for renal function of healthy male and female for 30 days period by monitoring Scr and Clcr component in their blood samples. The method of this experimental research was by pre and post-treatment by involving 20 healthy volunteers who have met inclusion and exclusion criteria. The volunteers have completed the informed consent for this experiment. Furthermore, volunteers were divided into two groups (10 male and 10 female). Each group was given orally 500 mg of calyx capsule-ethanol extract H. sabdariffa per day for 30 days period. Blood tests were taken on day 0, day 30 after consuming the capsule and day 45 (15 days after the last day of capsule intake) in order to measure the Scr and Clcr concentration in the blood samples by using Jaffe dan Cockcroft-Gault method. The results of each sampling day were further analyzed statistically and compared using Repeated ANOVA dan Friedman test. The results suggest that there was a difference in the renal function on day 0, 30 and 45 samplings. However, there was no significant difference in Scr dan Clcr concentrations on female and male volunteers (p>0.05). Specifically, the type of gender affects Scr concentration (p<0.05) however, it does not affect Clcr concentration (p>0.05). In addition, age and Body Mass Index (BMI) does not affect Scr and Clcr concentrations (p>0.05). The side effects discovered through the monitoring increased in mixturition and bloatedness. Calyx capsule-ethanol extract H. sabdariffa does not affect on renal function of healthy volunteers.

Clinical proof-of-concept trial to assess the therapeutic effect of sirolimus in patients with autosomal dominant polycystic kidney disease: SUISSE ADPKD study

PubMed Central

Serra, Andreas L; Kistler, Andreas D; Poster, Diane; Struker, Marian; Wüthrich, Rudolf P; Weishaupt, Dominik; Tschirch, Frank

2007-01-01

Background Currently there is no effective treatment available to retard cyst growth and to prevent the progression to end-stage renal failure in patients with autosomal dominant polycystic kidney disease (ADPKD). Evidence has recently been obtained from animal experiments that activation of the mammalian target of rapamycin (mTOR) signaling pathway plays a crucial role in cyst growth and renal volume expansion, and that the inhibition of mTOR with rapamycin (sirolimus) markedly slows cyst development and renal functional deterioration. Based on these promising results in animals we have designed and initiated the first randomized controlled trial (RCT) to examine the effectiveness, safety and tolerability of sirolimus to retard disease progression in ADPKD. Method/design This single center, randomised controlled, open label trial assesses the therapeutic effect, safety and tolerability of the mTOR inhibitor sirolimus (Rapamune®) in patients with autosomal dominant polycystic kidney disease and preserved renal function. The primary outcome will be the inhibition of kidney volume growth measured by magnetic resonance imaging (MRI) volumetry. Secondary outcome parameters will be preservation of renal function, safety and tolerability of sirolimus. Discussion The results from this proof-of-concept RCT will for the first time show whether treatment with sirolimus effectively retards cyst growth in patients with ADPKD. Trial registration NCT00346918 PMID:17868472

How the use of creatine supplements can elevate serum creatinine in the absence of underlying kidney pathology

PubMed Central

Williamson, Lydia; New, David

2014-01-01

Serum creatinine is a widely used marker in the assessment of renal function. Elevated creatinine levels suggest kidney dysfunction, prompting the need for further investigation. This report describes a case in which the consumption of the bodybuilding supplement creatine ethyl ester resulted in raised serum creatinine in the absence of true underlying kidney pathology. The abnormalities reversed after discontinuation of the supplement. A case of pseudo renal failure was recognised and kidney function was concluded to be normal. This report aims to address the mechanisms by which the ingestion of creatine ethyl ester can mimic the blood results expected in advanced renal failure, and confronts the problems faced when relying on serum creatinine as a diagnostic tool. PMID:25239988

How the use of creatine supplements can elevate serum creatinine in the absence of underlying kidney pathology.

PubMed

Williamson, Lydia; New, David

2014-09-19

Serum creatinine is a widely used marker in the assessment of renal function. Elevated creatinine levels suggest kidney dysfunction, prompting the need for further investigation. This report describes a case in which the consumption of the bodybuilding supplement creatine ethyl ester resulted in raised serum creatinine in the absence of true underlying kidney pathology. The abnormalities reversed after discontinuation of the supplement. A case of pseudo renal failure was recognised and kidney function was concluded to be normal. This report aims to address the mechanisms by which the ingestion of creatine ethyl ester can mimic the blood results expected in advanced renal failure, and confronts the problems faced when relying on serum creatinine as a diagnostic tool. 2014 BMJ Publishing Group Ltd.

Renal function and acute heart failure outcome.

PubMed

Llauger, Lluís; Jacob, Javier; Miró, Òscar

2018-06-05

The interaction between acute heart failure (AHF) and renal dysfunction is complex. Several studies have evaluated the prognostic value of this syndrome. The aim of this systematic review, which includes non-selected samples, was to investigate the impact of different renal function variables on the AHF prognosis. The categories included in the studies reviewed included: creatinine, blood urea nitrogen (BUN), the BUN/creatinine quotient, chronic kidney disease, the formula to estimate the glomerular filtration rate, criteria of acute renal injury and new biomarkers of renal damage such as neutrophil gelatinase-associated lipocalin (NGAL and cystatin c). The basal alterations of the renal function, as well as the acute alterations, transient or not, are related to a worse prognosis in AHF, it is therefore necessary to always have baseline, acute and evolutive renal function parameters. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

Variability in the reporting of renal function endpoints in immunosuppression trials in renal transplantation: time for consensus?

PubMed

Knight, Simon R; Hussain, Samia

2016-12-01

Early measures of graft function are increasingly used to assess efficacy in clinical trials of kidney transplant immunosuppression. This study aimed to assess the variability and quality of reporting of these endpoints in contemporary trials. Data regarding renal function endpoints were extracted from 213 reports from randomized controlled trials comparing immunosuppressive interventions in renal transplant recipients published between 2010 and 2014. A total of 174 (81.7%) reports included a measure of renal function; in 44 (20.7%), this was the primary endpoint. A total of 103 manuscripts (48.4%) reported serum creatinine, 142 (66.6%) reported estimated glomerular filtration rate (eGFR), and 26 (12.2%) reported measured GFR. Formulas used for GFR estimation were modification of diet in renal disease (42.3%), Cockroft-Gault (23.5%), Nankivell (15.0%), and CKD-EPI (0.9%). Six studies (2.8%) did not report the formula used to estimate GFR. A total of 13.9% of endpoints had missing data. In 10 studies, disagreement was found in the significance of findings using different measures of renal function. There is a great deal of variability in the reporting of renal function endpoints, with a significant proportion of studies using underperforming or inappropriate estimates. There is a need for consensus as to the best tool for monitoring and reporting renal function post-transplant, and in particular for use in clinical trials and registries. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Risk factors and co-morbidities associated with changes in renal function among antiretroviral treatment-naïve adults in South Africa: A chart review.

PubMed

Assaram, Shirelle; Mashamba-Thompson, Tivani P; Magula, Nombulelo P

2018-01-01

Our systematic scoping review has demonstrated a research gap in antiretroviral treatment (ART) nephrotoxicity as well as in the long-term outcomes of renal function for patients on ART in South Africa. Bearing in mind the high prevalence of human immunodeficiency virus (HIV) in South Africa, this is of great concern. To determine the risk factors and co-morbidities associated with changes in renal function in HIV-infected adults in South Africa. We conducted a retrospective study of 350 ART-naïve adult patients attending the King Edward VIII HIV clinic, Durban, South Africa. Data were collected at baseline (pre-ART) and at six, 12, 18 and 24 months on ART. Renal function was assessed in the 24-month period using the Modification of Diet in Renal Disease equation and was categorised into normal renal function (estimated glomerular filtration rate [eGFR] ≥ 60), moderate renal impairment (eGFR 30-59), severe renal impairment (eGFR 15-29) and kidney failure (eGFR < 15 mL/min/1.73 m 2 ). Generalised linear models for binary data were used to model the probability of renal impairment over the five time periods, controlling for repeated measures within participants over time. Risk ratios and 95% confidence intervals (CI) were reported for each time point versus baseline. The cohort was 64% female, and 99% were Black. The median age was 36 years. At baseline, 10 patients had hypertension (HPT), six had diabetes, 61 were co-infected with tuberculosis (TB) and 157 patients had a high body mass index (BMI) with 25.4% being categorised as overweight and 19.4% as obese. The majority of the patients (59.3%) were normotensive. At baseline, the majority of the patients (90.4%) had normal renal function (95% CI: 86% - 93%), 7.0% (CI: 5% - 10%) had moderate renal impairment, 1.3% (CI: 0% - 3%) had severe renal impairment and 1.3% (CI: 0% - 3%) had renal failure. As BMI increased by one unit, the risk of renal impairment increased by 1.06 (CI: 1.03-1.10) times. The association of HPT with abnormal renal function was found to be insignificant, p > 0.05. The vast majority of patients were initiated on tenofovir disoproxil fumarate (TDF) (90.6%), in combination with lamivudine (3TC) (100%) and either efavirenz (EFV) (56.6%) or nevirapine (NVP) (43.4%). This study reports a low prevalence of baseline renal impairment in HIV-infected ART-naïve outpatients. An improvement in renal function after the commencement of ART has been demonstrated in this population. However, the long-term outcomes of patients with HIV-related renal disease are not known.

Poly[ADP-ribose] polymerase-1 expression is related to cold ischemia, acute tubular necrosis, and delayed renal function in kidney transplantation.

PubMed

O'Valle, Francisco; Del Moral, Raimundo G M; Benítez, María del Carmén; Martín-Oliva, David; Gómez-Morales, Mercedes; Aguilar, David; Aneiros-Fernández, José; Hernández-Cortés, Pedro; Osuna, Antonio; Moreso, Francesc; Serón, Daniel; Oliver, Francisco J; Del Moral, Raimundo G

2009-09-28

Cold ischemia time especially impacts on outcomes of expanded-criteria donor (ECD) transplantation. Ischemia-reperfusion (IR) injury produces excessive poly[ADP-Ribose] Polymerase-1 (PARP-1) activation. The present study explored the hypothesis that increased tubular expression of PARP-1 contributes to delayed renal function in suboptimal ECD kidney allografts and in non-ECD allografts that develop posttransplant acute tubular necrosis (ATN). Nuclear PARP-1 immunohistochemical expression was studied in 326 paraffin-embedded renal allograft biopsies (193 with different degrees of ATN and 133 controls) and in murine Parp-1 knockout model of IR injury. PARP-1 expression showed a significant relationship with cold ischemia time (r coefficient = 0.603), time to effective diuresis (r = 0.770), serum creatinine levels at biopsy (r = 0.649), and degree of ATN (r = 0.810) (p = 0.001, Pearson test). In the murine IR model, western blot showed an increase in PARP-1 that was blocked by Parp-1 inhibitor. Immunohistochemical study of PARP-1 in kidney allograft biopsies would allow early detection of possible delayed renal function, and the administration of PARP-1 inhibitors may offer a therapeutic option to reduce damage from IR in donor kidneys by preventing or minimizing ATN. In summary, these results suggest a pivotal role for PARP-1 in the ATN of renal transplantation. We propose the immunohistochemical assessment of PARP-1 in kidney allograft biopsies for early detection of a possible delayed renal function.

Two distinct clinical courses of renal involvement in rheumatoid patients with AA amyloidosis.

PubMed

Uda, Hiroshi; Yokota, Akira; Kobayashi, Kumiko; Miyake, Tadao; Fushimi, Hiroaki; Maeda, Akira; Saiki, Osamu

2006-08-01

We conducted a prospective study to investigate whether a correlation exists between the clinical course of renal involvement and the pathological findings of renal amyloidosis in patients with rheumatoid arthritis (RA). Patients with RA of more than 5 years' duration and who did not show renal manifestations were selected and received a duodenal biopsy for the diagnosis of amyloidosis. After the diagnosis of AA amyloidosis, patients received a renal biopsy, and patterns of amyloid deposition were examined. We followed the renal functions (serum levels of blood urea nitrogen and creatinine) of patients diagnosed with AA amyloidosis for 5 years. We diagnosed 53 patients with AA amyloidosis and monitored the renal function of 38 of them for > 5 years. The histological patterns were examined; in the 38 patients there were appreciable variations in the patterns of amyloid deposition. In 27 patients, amyloid deposits were found exclusively in the glomerulus (type 1). In the other 11 patients, however, amyloid deposits were found selectively around blood vessels and were totally absent in the glomerulus (type 2). In type 1 patients with glomerular involvement, renal function deteriorated rapidly regardless of disease state; most patients received hemodialysis. In type 2 patients with purely vascular involvement, however, renal function did not deteriorate significantly. In patients with RA and AA amyloidosis, 2 distinct clinical courses in terms of renal involvement were identified. It is suggested that renal function does not deteriorate when amyloid deposition is totally lacking in the glomerulus.

Renal microvascular disease determines the responses to revascularization in experimental renovascular disease.

PubMed

Chade, Alejandro R; Kelsen, Silvia

2010-08-01

Percutaneous transluminal renal angioplasty (PTRA) is the most frequent therapeutic approach to resolving renal artery stenosis (RAS). However, renal function recovers in only 30% of the cases. The causes of these poor outcomes are still unknown. We hypothesized that preserving the renal microcirculation distal to RAS will improve the responses to PTRA. RAS was induced in 28 pigs. In 14, vascular endothelial growth factor (VEGF)-165 0.05 microg/kg was infused intrarenally (RAS+VEGF). Single-kidney function was assessed in all pigs in vivo using ultrafast CT after 6 weeks. Observation of half of the RAS and RAS+VEGF pigs was completed. The other half underwent PTRA and repeated VEGF, and CT studies were repeated 4 weeks later. Pigs were then euthanized, the stenotic kidney removed, renal microvascular (MV) architecture reconstructed ex vivo using 3D micro-CT, and renal fibrosis quantified. The degree of RAS and hypertension were similar in RAS and RAS+VEGF. Renal function and MV density were decreased in RAS but improved in RAS+VEGF. PTRA largely resolved RAS, but the improvements of hypertension and renal function were greater in RAS+VEGF+PTRA than in RAS+PTRA, accompanied by a 34% increase in MV density and decreased fibrosis. Preservation of the MV architecture and function in the stenotic kidney improved the responses to PTRA, indicating that renal MV integrity plays a role in determining the responses to PTRA. This study indicates that damage and early loss of renal MV is an important determinant of the progression of renal injury in RAS and instigates often irreversible damage.

Localized renal cell carcinoma management: an update.

PubMed

Heldwein, Flavio L; McCullough, T Casey; Souto, Carlos A V; Galiano, Marc; Barret, Eric

2008-01-01

To review the current modalities of treatment for localized renal cell carcinoma. A literature search for keywords: renal cell carcinoma, radical nephrectomy, nephron sparing surgery, minimally invasive surgery, and cryoablation was performed for the years 2000 through 2008. The most relevant publications were examined. New epidemiologic data and current treatment of renal cancer were covered. Concerning the treatment of clinically localized disease, the literature supports the standardization of partial nephrectomy and laparoscopic approaches as therapeutic options with better functional results and oncologic success comparable to standard radical resection. Promising initial results are now available for minimally invasive therapies, such as cryotherapy and radiofrequency ablation. Active surveillance has been reported with acceptable results, including for those who are poor surgical candidates. This review covers current advances in radical and conservative treatments of localized kidney cancer. The current status of nephron-sparing surgery, ablative therapies, and active surveillance based on natural history has resulted in great progress in the management of localized renal cell carcinoma.

Cognitive Dysfunction in Patients with Renal Failure Requiring Hemodialysis

PubMed Central

Thimmaiah, Rohini; Murthy, K. Krishna; Pinto, Denzil

2012-01-01

Background and Objectives: Renal failure patients show significant impairment on measures of attention and memory, and consistently perform significantly better on neuropsychological measures of memory and attention, approximately 24 hours after hemodialysis treatment. The objectives are to determine the cognitive dysfunction in patients with renal failure requiring hemodialysis. Materials and Methods: A total of 60 subjects comprising of 30 renal failure patients and 30 controls were recruited. The sample was matched for age, sex, and socioeconomic status. The tools used were the Standardized Mini-Mental State Examination and the Brief Cognitive Rating Scale. Results: The patients showed high cognitive dysfunction in the pre-dialysis group, in all the five dimensions (concentration, recent memory, past memory, orientation and functioning, and self-care), and the least in the 24-hour post dialysis group. This difference was found to be statistically significant (P=0.001). Conclusion: Patients with renal failure exhibited pronounced cognitive impairment and these functions significantly improved after the introduction of hemodialysis. PMID:23439613

An improved method of renal tissue engineering, by combining renal dissociation and reaggregation with a low-volume culture technique, results in development of engineered kidneys complete with loops of Henle.

PubMed

Chang, C-Hong; Davies, Jamie A

2012-01-01

Tissue engineering of functional kidney tissue is an important goal for clinical restoration of renal function in patients damaged by infectious, toxicological, or genetic disease. One promising approach is the use of the self-organizing abilities of embryonic kidney cells to arrange themselves, from a simply reaggregated cell suspension, into engineered organs similar to fetal kidneys. The previous state-of-the-art method for this results in the formation of a branched collecting duct tree, immature nephrons (S-shaped bodies) beside and connected to it, and supportive stroma. It does not, though, result in the significant formation of morphologically detectable loops of Henle - anatomical features of the nephron that are critical to physiological function. We have combined the best existing technique for renal tissue engineering from cell suspensions with a low-volume culture technique that allows intact kidney rudiments to make loops of Henle to test whether engineered kidneys can produce these loops. The result is the formation of loops of Henle in engineered cultured 'fetal kidneys', very similar in both morphology and in number to those formed by intact organ rudiments. This brings the engineering technique one important step closer to production of a fully realistic organ. Copyright © 2012 S. Karger AG, Basel.

Aortic calcification burden predicts deterioration of renal function after radical nephrectomy.

PubMed

Fukushi, Ken; Hatakeyama, Shingo; Yamamoto, Hayato; Tobisawa, Yuki; Yoneyama, Tohru; Soma, Osamu; Matsumoto, Teppei; Hamano, Itsuto; Narita, Takuma; Imai, Atsushi; Yoneyama, Takahiro; Hashimoto, Yasuhiro; Koie, Takuya; Terayama, Yuriko; Funyu, Tomihisa; Ohyama, Chikara

2017-02-06

Radical nephrectomy for renal cell carcinoma (RCC) is a risk factor for the development of chronic kidney disease (CKD), and the possibility of postoperative deterioration of renal function must be considered before surgery. We investigated the contribution of the aortic calcification index (ACI) to the prediction of deterioration of renal function in patients undergoing radical nephrectomy. Between January 1995 and December 2012, we performed 511 consecutive radical nephrectomies for patients with RCC. We retrospectively studied data from 109 patients who had regular postoperative follow-up of renal function for at least five years. The patients were divided into non-CKD and pre-CKD based on a preoperative estimated glomerular filtration rate (eGFR) of ≥60 mL/min/1.73 m 2 or <60 mL/min/1.73 m 2 , respectively. The ACI was quantitatively measured by abdominal computed tomography before surgery. The patients in each group were stratified between low and high ACIs. Variables such as age, sex, comorbidities, and pre- and postoperative renal function were compared between patients with a low or high ACI in each group. Renal function deterioration-free interval rates were evaluated by Kaplan-Meier analysis. Factors independently associated with deterioration of renal function were determined using multivariate analysis. The median age, preoperative eGFR, and ACI in this cohort were 65 years, 68 mL/min/1.73 m 2 , and 8.3%, respectively. Higher ACI (≥8.3%) was significantly associated with eGFR decline in both non-CKD and pre-CKD groups. Renal function deterioration-free interval rates were significantly lower in the ACI-high than ACI-low strata in both of the non-CKD and pre-CKD groups. Multivariate analysis showed that higher ACI was an independent risk factor for deterioration of renal function at 5 years after radical nephrectomy. Aortic calcification burden is a potential predictor of deterioration of renal function after radical nephrectomy. This study was registered as a clinical trial: UMIN000023577.

Increased curvature of hollow fiber membranes could up-regulate differential functions of renal tubular cell layers.

PubMed

Shen, Chong; Meng, Qin; Zhang, Guoliang

2013-08-01

Tissue engineering devices as in vitro cell culture systems in scaffolds has encountered the bottleneck due to their much lower cell functions than real tissues/organs in vivo. Such situation has been improved in some extent by mimicking the cell microenvironments in vivo from either chemical or physical ways. However, microenvironmental curvature, commonly seen in real tissues/organs, has never been manipulated to regulate the cell performance in vitro. In this regard, this paper fabricated polysulfone membranes with or without polyethylene glycol modification to investigate the impact of curvature on two renal tubular cells. Regardless the varying membrane curvatures among hollow fiber membranes of different diameters and flat membrane of zero curvature, both renal cells could well attach at 4 h of seeding and form similar confluent layers at 6 days on each membrane. Nevertheless, the renal cells on hollow fibers, though showing confluent morphology as those on flat membranes, expressed higher renal functions and, moreover, the renal functions significantly increased with the membrane curvature among hollow fibers. Such upregulation on functions was unassociated with mass transport barrier of hollow fibers, because the cultures on lengthwise cut hollow fibers without mass transfer barrier showed same curvature effect on renal functions as whole hollow fibers. It could be proposed that the curvature of hollow fiber membrane approaching to the large curvature in kidney tubules increased the mechanical stress in the renal cells and thus might up-regulate the renal cell functions. In conclusion, the increase of substrate curvature could up-regulate the cell functions without altering the confluent cell morphology and this finding will facilitate the design of functional tissue engineering devices. Copyright © 2013 Wiley Periodicals, Inc.

Serum osteoprotegerin and renal function in the general population: the Tromsø Study.

PubMed

Vik, Anders; Brodin, Ellen E; Mathiesen, Ellisiv B; Brox, Jan; Jørgensen, Lone; Njølstad, Inger; Brækkan, Sigrid K; Hansen, John-Bjarne

2017-02-01

Serum osteoprotegerin (OPG) is elevated in patients with chronic kidney disease (CKD) and increases with decreasing renal function. However, there are limited data regarding the association between OPG and renal function in the general population. The aim of the present study was to explore the relation between serum OPG and renal function in subjects recruited from the general population. We conducted a cross-sectional study with 6689 participants recruited from the general population in Tromsø, Norway. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equations. OPG was modelled both as a continuous and categorical variable. General linear models and linear regression with adjustment for possible confounders were used to study the association between OPG and eGFR. Analyses were stratified by the median age, as serum OPG and age displayed a significant interaction on eGFR. In participants ≤62.2 years with normal renal function (eGFR ≥90 mL/min/1.73 m 2 ) eGFR increased by 0.35 mL/min/1.73 m 2 (95% CI 0.13-0.56) per 1 standard deviation (SD) increase in serum OPG after multiple adjustment. In participants older than the median age with impaired renal function (eGFR <90 mL/min/1.73 m 2 ), eGFR decreased by 1.54 (95% CI -2.06 to -1.01) per 1 SD increase in serum OPG. OPG was associated with an increased eGFR in younger subjects with normal renal function and with a decreased eGFR in older subjects with reduced renal function. Our findings imply that the association between OPG and eGFR varies with age and renal function.

Renal Interstitial Arteriosclerotic Lesions in Lupus Nephritis Patients: A Cohort Study from China

PubMed Central

Qin, Dan-dan; Wu, Li-hua; Song, Yan; Yu, Feng; Wang, Su-xia; Liu, Gang; Zhao, Ming-hui

2015-01-01

Objective The aim of this study was to evaluate renal arteriosclerotic lesions in patients with lupus nephritis and investigate their associations with clinical and pathological characteristics, especially cardio-vascular features. Design A retrospective cohort study. Participants Seventy-nine patients with renal biopsy-proven lupus nephritis, diagnosed between January 2000 and June 2008 from Peking University First Hospital. Results In clinico-pathological data, patients with arteriosclerosis had higher ratio of hypertension and more severe renal injury indices compared with patients with no renal vascular lesions. More importantly, patients with renal arteriosclerosis had worse cardiac structure and function under transthoracic echocardiographic examination. Patients with renal arteriosclerosis tend to have higher ratios of combined endpoints compared with those of no renal vascular lesions, although the difference didn’t reach statistical meanings (P = 0.104). Conclusion Renal arteriosclerotic lesion was common and associated with vascular immune complex deposits in lupus nephritis. It might have a certain degree of association with poor outcomes and cardiovascular events, which needs further explorations. PMID:26544865

A case of acute kidney injury caused by granulomatous interstitial nephritis associated with sarcoidosis.

PubMed

Horino, Taro; Matsumoto, Tatsuki; Inoue, Kosuke; Ichii, Osamu; Terada, Yoshio

2018-05-01

Sarcoidosis affects multiple organs including lung, heart and kidney. Sarcoidosis causes hypercalcemia, hypergammaglobulinemia, and rarely, granulomatous interstitial nephritis, resulting in renal stromal damage. Granulomatous interstitial nephritis is characterized as interstitial nephritis with noncaseating epithelioid granulomas. Diagnosing granulomatous interstitial nephritis before patient's death is challenging; hence, only few cases proven by renal biopsy have been reported till date. We present a case of acute kidney injury caused by granulomatous interstitial nephritis as a renal manifestation of sarcoidosis proven by renal biopsy, which can be confirmed by 18 F-fluorodeoxyglucose positron emission tomography/computed tomography. Glucocorticoid therapy was helpful for improving and maintaining her renal function over a 6-year period.

Predictors of renal recovery in patients with pre-orthotopic liver transplant (OLT) renal dysfunction.

PubMed

Iglesias, Jose; Frank, Elliot; Mehandru, Sushil; Davis, John M; Levine, Jerrold S

2013-07-13

Renal dysfunction occurs commonly in patients awaiting orthotopic liver transplantation (OLT) for end-stage liver disease. The use of simultaneous liver-kidney transplantation has increased in the MELD scoring era. As patients may recover renal function after OLT, identifying factors predictive of renal recovery is a critical issue, especially given the scarcity of available organs. Employing the UNOS database, we sought to identify donor- and patient-related predictors of renal recovery among 1720 patients with pre-OLT renal dysfunction and transplanted from 1989 to 2005. Recovery of renal function post-OLT was defined as a composite endpoint of serum creatinine (SCr) ≤1.5 mg/dL at discharge and survival ≥29 days. Pre-OLT renal dysfunction was defined as any of the following: SCr ≥2 mg/dL at any time while awaiting OLT or need for renal replacement therapy (RRT) at the time of registration and/or OLT. Independent predictors of recovery of renal function post-OLT were absence of hepatic allograft dysfunction, transplantation during MELD era, recipient female sex, decreased donor age, decreased recipient ALT at time of OLT, decreased recipient body mass index at registration, use of anti-thymocyte globulin as induction therapy, and longer wait time from registration. Contrary to popular belief, a requirement for RRT, even for prolonged periods in excess of 8 weeks, was not an independent predictor of failure to recover renal function post-OLT. These data indicate that the duration of renal dysfunction, even among those requiring RRT, is a poor way to discriminate reversible from irreversible renal dysfunction.

Renal function preservation with the mTOR inhibitor, Everolimus, after lung transplant.

PubMed

Schneer, Sonia; Kramer, Mordechai R; Fox, Benjamin; Rusanov, Viktoria; Fruchter, Oren; Rosengarten, Dror; Bakal, Ilana; Medalion, Benjamin; Raviv, Yael

2014-06-01

Chronic kidney disease (CKD) is a common complication of calcineurin inhibitors (CNIs) in solid organ transplantation. Previous data suggest that the use of everolimus as an immunosuppressant drug leads to improvement in renal function. The aim of our study was to establish the effect of everolimus in combination with lower doses of CNIs on renal function among lung transplant recipients. Data regarding renal function and pulmonary function were collected from 41 lung transplanted patients in whom treatment was converted to a combination of everolimus with lower doses of CNIs. Patients transferred to everolimus and low dose CNIs showed an improvement in renal function. Patients who continued treatment with everolimus showed improvement in renal function, as opposed to patients who discontinued the treatment. Subjects without proteinuria at baseline showed a better improvement compared with subjects with proteinuria. The incidence of graft rejection did not increase. We concluded that a protocol that includes everolimus and lower doses of CNIs is effective for preserving renal function in lung transplant recipients with CKD. We also believe that an early implementation of everolimus, before proteinuria occurs or creatinine clearance is reduced, could lead to better outcomes. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Mendelian randomization analysis associates increased serum urate, due to genetic variation in uric acid transporters, with improved renal function.

PubMed

Hughes, Kim; Flynn, Tanya; de Zoysa, Janak; Dalbeth, Nicola; Merriman, Tony R

2014-02-01

Increased serum urate predicts chronic kidney disease independent of other risk factors. The use of xanthine oxidase inhibitors coincides with improved renal function. Whether this is due to reduced serum urate or reduced production of oxidants by xanthine oxidase or another physiological mechanism remains unresolved. Here we applied Mendelian randomization, a statistical genetics approach allowing disentangling of cause and effect in the presence of potential confounding, to determine whether lowering of serum urate by genetic modulation of renal excretion benefits renal function using data from 7979 patients of the Atherosclerosis Risk in Communities and Framingham Heart studies. Mendelian randomization by the two-stage least squares method was done with serum urate as the exposure, a uric acid transporter genetic risk score as instrumental variable, and estimated glomerular filtration rate and serum creatinine as the outcomes. Increased genetic risk score was associated with significantly improved renal function in men but not in women. Analysis of individual genetic variants showed the effect size associated with serum urate did not correlate with that associated with renal function in the Mendelian randomization model. This is consistent with the possibility that the physiological action of these genetic variants in raising serum urate correlates directly with improved renal function. Further studies are required to understand the mechanism of the potential renal function protection mediated by xanthine oxidase inhibitors.

Effect of naringin on hemodynamic changes and left ventricular function in renal artery occluded renovascular hypertension in rats

PubMed Central

Visnagri, Asjad; Adil, Mohammad; Kandhare, Amit D.; Bodhankar, Subhash L.

2015-01-01

Background: Renal artery occlusion (RAO) induced hypertension is a major health problem associated with structural and functional variations of the renal and cardiac vasculature. Naringin a flavanone glycoside derived possesses metal-chelating, antioxidant and free radical scavenging properties. Objective: The objective of this study was to investigate the antihypertensive activity of naringin in RAO induced hypertension in rats. Material and Methods: Male Wistar rats (180-200 g) were divided into five groups Sham, RAO, naringin (20, 40 and 80 mg/kg). Animals were pretreated with naringin (20, 40 and 80 mg/kg p.o) for 4 weeks. On the last day of the experiment, left renal artery was occluded with renal bulldog clamp for 4 h. After assessment of hemodynamic and left ventricular function various biochemical (superoxide dismutase [SOD], glutathione [GSH] and malondialdehyde [MDA]) and histological parameters were determined in the kidney. Results: RAO group significantly (P < 0.001) increased hemodynamic parameters at 15, 30 and 45 min of clamp removal. Naringin (40 and 80 mg/kg) treated groups showed a significant decrease in hemodynamic parameters at 15 min. after clamp removal that remained sustained for 60 min. Naringin (40 and 80 mg/kg) treated groups showed significant improvement in left ventricular function at 15, 30 and 45 min after clamp removal. Alteration in level of SOD, GSH and MDA was significantly restored by naringin (40 and 80 mg/kg) treatment. It also reduced histological aberration induced in kidney by RAO. Conclusion: It is concluded that the antihypertensive activity of naringin may result through inhibition of oxidative stress. PMID:25883516

The iothalamate clearance in cats with experimentally induced renal failure.

PubMed

Ohashi, F; Kuroda, K; Shimada, T; Shimada, Y; Ota, M

1996-08-01

Plasma iothalamate (IOT) disappearance rates were measured after a single-injection of IOT (113.8 mg/kg, IV) in cats with experimentally induced renal failure. The disappearance rates especially fitted into the one compartment model. The mean value of plasma disappearance rates of IOT in these cats with induced renal failure (2.16 +/- 0.240 x 10(-3) micrograms/ml/min) was markedly lower than that of clinically healthy cats (4.10 +/- 1.00 x 10(-3) micrograms/ml/min). These results demonstrate that IOT clearance is available for evaluation of renal function in cats.

Neural control of renal function: cardiovascular implications.

PubMed

DiBona, G F

1989-06-01

The innervation of the kidney serves to function of its component parts, for example, the blood vessels, the nephron (glomerulus, tubule), and the juxtaglomerular apparatus. Alterations in efferent renal sympathetic nerve activity produce significant changes in renal blood flow, glomerular filtration rate, the reabsorption of water, sodium, and other ions, and the release of renin, prostaglandins, and other vasoactive substances. These functional effects contribute significantly to the renal regulation of total body sodium and fluid volumes with important implications for the control of arterial pressure. The renal nerves, both efferent and afferent, are known to be important contributors to the pathogenesis of hypertension. In addition, the efferent renal nerves participate in the mediation of the excessive renal sodium retention, which characterizes edema-forming states such as congestive heart failure. Thus, the renal nerves play an important role in overall cardiovascular homeostasis in both normal and pathological conditions.

The role of the renal specialist nurse in prevention of renal failure.

PubMed

Hurst, J

2002-01-01

This article will investigate the care required for those with reduced renal function before renal replacement therapy (RRT) commences. Renal nurses are often involved with the technical, monitoring and evaluative aspects of RRT for those with end stage renal failure. However, many patients may experience reduced renal function many years before reaching the stage of needing RRT. Renal nurses are already involved in the preparation of patients for RRT, but are not presently exercising their specialist skills in the period before this time by contributing to the prevention of end stage renal failure (ESRF). Screening programmes carried out in various parts of the world demonstrate that many members of the population have undetected renal insufficiency, and may benefit from intervention from the nephrology team to prevent further renal dysfunction. It is for this group of patients that this article will consider the potential for the renal nurse to expand their scope of practice.

Successful Surgical Treatment of Anuria Caused by Renal Artery Occlusion

PubMed Central

Flye, M. Wayne; Anderson, Robert w.; Fish, Jay C.; Silver, Donald

1982-01-01

Anuria resulting from obstruction of the renal arteries to both Kidneys or to a solitary kidney is unusual. The tolerance of the kidney to this ischemia is largely dependent upon the presence of collaterals, stimulated by pre-existing arterial disease. Our experience with six patients with anuria caused by renal artery occlusion supports the role of revascularization in the recovery of significant renal function. Four of these patients had hypertension, impaired renal function, and the existence of collateral circulation to an ischemic kidney, prior to occlusion, while two patients had normal renal function (serum creatinine = 0.5 and 0.9 mg/dl) before occlusion. The intervals of anuria for the two previously normal kidneys were six hours and five days, and 2 to 14 days in the four patients with vascular disease. Isotope scanning suggested renal artery occlusion in two patients, but arteriograms confirmed the diagnosis in all six. A thrombectomy restored blood flow through the two previously normal renal arteries. Grafts from the aorta or celiax axis were used for three patients and the splenic artery was used for the sixth patient. Urine flow began during or soon after operation in all patients. Dialysis was necessary for 30 and 45 days in the two patients with normal kidneys, but in only one of the four patients with previous disease (for ten days). Serum creatinine decreased to <2.0 mg/dl after operation, except in the man with a solitary kidney, who five years later has a creatinine of 3 mg/dl. All four patients with previous arterial disease died from cardiac failure within 1 to 30 months after operation. Therefore, anuria of acute onset should be evaluated by renal scan and arteriogram to detect those patients with proximal renal artery occlusion in preparation for revascularization. ImagesFig. 2a.Fig. 2b.Fig. 3.Fig. 4a.Fig. 4b.Fig. 5.Fig. 6a.Fig. 6b. PMID:7059245

Flavonoids in Kidney Health and Disease

PubMed Central

Vargas, Félix; Romecín, Paola; García-Guillén, Ana I.; Wangesteen, Rosemary; Vargas-Tendero, Pablo; Paredes, M. Dolores; Atucha, Noemí M.; García-Estañ, Joaquín

2018-01-01

This review summarizes the latest advances in knowledge on the effects of flavonoids on renal function in health and disease. Flavonoids have antihypertensive, antidiabetic, and antiinflammatory effects, among other therapeutic activities. Many of them also exert renoprotective actions that may be of interest in diseases such as glomerulonephritis, diabetic nephropathy, and chemically-induced kidney insufficiency. They affect several renal factors that promote diuresis and natriuresis, which may contribute to their well-known antihypertensive effect. Flavonoids prevent or attenuate the renal injury associated with arterial hypertension, both by decreasing blood pressure and by acting directly on the renal parenchyma. These outcomes derive from their interference with multiple signaling pathways known to produce renal injury and are independent of their blood pressure-lowering effects. Oral administration of flavonoids prevents or ameliorates adverse effects on the kidney of elevated fructose consumption, high fat diet, and types I and 2 diabetes. These compounds attenuate the hyperglycemia-disrupted renal endothelial barrier function, urinary microalbumin excretion, and glomerular hyperfiltration that results from a reduction of podocyte injury, a determinant factor for albuminuria in diabetic nephropathy. Several flavonoids have shown renal protective effects against many nephrotoxic agents that frequently cause acute kidney injury (AKI) or chronic kidney disease (CKD), such as LPS, gentamycin, alcohol, nicotine, lead or cadmium. Flavonoids also improve cisplatin- or methotrexate-induced renal damage, demonstrating important actions in chemotherapy, anticancer and renoprotective effects. A beneficial prophylactic effect of flavonoids has been also observed against AKI induced by surgical procedures such as ischemia/reperfusion (I/R) or cardiopulmonary bypass. In several murine models of CKD, impaired kidney function was significantly improved by the administration of flavonoids from different sources, alone or in combination with stem cells. In humans, cocoa flavanols were found to have vasculoprotective effects in patients on hemodialysis. Moreover, flavonoids develop antitumor activity against renal carcinoma cells with no toxic effects on normal cells, suggesting a potential therapeutic role in patients with renal carcinoma. PMID:29740333

Flavonoids in Kidney Health and Disease.

PubMed

Vargas, Félix; Romecín, Paola; García-Guillén, Ana I; Wangesteen, Rosemary; Vargas-Tendero, Pablo; Paredes, M Dolores; Atucha, Noemí M; García-Estañ, Joaquín

2018-01-01

This review summarizes the latest advances in knowledge on the effects of flavonoids on renal function in health and disease. Flavonoids have antihypertensive, antidiabetic, and antiinflammatory effects, among other therapeutic activities. Many of them also exert renoprotective actions that may be of interest in diseases such as glomerulonephritis, diabetic nephropathy, and chemically-induced kidney insufficiency. They affect several renal factors that promote diuresis and natriuresis, which may contribute to their well-known antihypertensive effect. Flavonoids prevent or attenuate the renal injury associated with arterial hypertension, both by decreasing blood pressure and by acting directly on the renal parenchyma. These outcomes derive from their interference with multiple signaling pathways known to produce renal injury and are independent of their blood pressure-lowering effects. Oral administration of flavonoids prevents or ameliorates adverse effects on the kidney of elevated fructose consumption, high fat diet, and types I and 2 diabetes. These compounds attenuate the hyperglycemia-disrupted renal endothelial barrier function, urinary microalbumin excretion, and glomerular hyperfiltration that results from a reduction of podocyte injury, a determinant factor for albuminuria in diabetic nephropathy. Several flavonoids have shown renal protective effects against many nephrotoxic agents that frequently cause acute kidney injury (AKI) or chronic kidney disease (CKD), such as LPS, gentamycin, alcohol, nicotine, lead or cadmium. Flavonoids also improve cisplatin- or methotrexate-induced renal damage, demonstrating important actions in chemotherapy, anticancer and renoprotective effects. A beneficial prophylactic effect of flavonoids has been also observed against AKI induced by surgical procedures such as ischemia/reperfusion (I/R) or cardiopulmonary bypass. In several murine models of CKD, impaired kidney function was significantly improved by the administration of flavonoids from different sources, alone or in combination with stem cells. In humans, cocoa flavanols were found to have vasculoprotective effects in patients on hemodialysis. Moreover, flavonoids develop antitumor activity against renal carcinoma cells with no toxic effects on normal cells, suggesting a potential therapeutic role in patients with renal carcinoma.

Effect of renal denervation on dynamic autoregulation of renal blood flow.

PubMed

DiBona, Gerald F; Sawin, Linda L

2004-06-01

Vasoconstrictor intensities of renal sympathetic nerve stimulation elevate the renal arterial pressure threshold for steady-state stepwise autoregulation of renal blood flow. This study examined the tonic effect of basal renal sympathetic nerve activity on dynamic autoregulation of renal blood flow in rats with normal (Sprague-Dawley and Wistar-Kyoto) and increased levels of renal sympathetic nerve activity (congestive heart failure and spontaneously hypertensive rats). Steady-state values of arterial pressure and renal blood flow before and after acute renal denervation were subjected to transfer function analysis. Renal denervation increased basal renal blood flow in congestive heart failure (+35 +/- 3%) and spontaneously hypertensive rats (+21 +/- 3%) but not in Sprague-Dawley and Wistar-Kyoto rats. Renal denervation significantly decreased transfer function gain (i.e., improved autoregulation of renal blood flow) and increased coherence only in spontaneously hypertensive rats. Thus vasoconstrictor intensities of renal sympathetic nerve activity impaired the dynamic autoregulatory adjustments of the renal vasculature to oscillations in arterial pressure. Renal denervation increased renal blood flow variability in spontaneously hypertensive rats and congestive heart failure rats. The contribution of vasoconstrictor intensities of basal renal sympathetic nerve activity to limiting renal blood flow variability may be important in the stabilization of glomerular filtration rate.

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

PubMed Central

Poucher, S M; Karim, F

1991-01-01

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

Repeated daclizumab administration to delay the introduction of calcineurin inhibitors in heart transplant patients with postoperative renal dysfunction.

PubMed

Sánchez Lázaro, Ignacio J; Almenar Bonet, Luis; Martínez Dolz, Luis; Buendía Fuentes, Francisco; Navarro Manchón, Josep; Agüero Ramón-Llin, Jaime; Vicente Sánchez, José Luis; Salvador Sanz, Antonio

2011-03-01

Daclizumab is an interleukin-2 receptor antagonist which is used for induction therapy in heart transplant patients. It has few side effects and is associated with a low infection rate. Postoperative renal failure after heart transplantation is common and potentially fatal. The administration of calcineurin inhibitors in the postoperative period can aggravate the situation. We report the cases of six patients who underwent heart transplantation and developed acute renal failure in the immediate postoperative period. All were administered daclizumab weekly to avoid the introduction of calcineurin inhibitors and to facilitate recovery of renal function. Calcineurin inhibitors were introduced only once renal function had improved. Renal function recovered in all cases and there was a low complication rate. The administration of repeated doses of daclizumab to patients who experience acute postoperative renal failure after heart transplantation may provide an alternative therapeutic approach that enables calcineurin inhibitors to be avoided and, consequently, renal function to recover. Copyright © 2010 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

MRI to assess renal structure and function.

PubMed

Artunc, Ferruh; Rossi, Cristina; Boss, Andreas

2011-11-01

In addition to excellent anatomical depiction, MRI techniques have expanded to study functional aspects of renal physiology, such as renal perfusion, glomerular filtration rate (GFR) or tissue oxygenation. This review will focus on current developments with an emphasis on clinical applicability. The method of GFR determination is largely heterogeneous and still has weaknesses. However, the technique of employing liver disappearance curves has been shown to be accurate in healthy persons and patients with chronic kidney disease. In potential kidney donors, complete evaluation of kidney anatomy and function can be accomplished in a single-stop investigation. Techniques without contrast media can be utilized to measure renal tissue oxygenation (blood oxygen level-dependent MRI) or perfusion (arterial spin labeling) and could aid in the diagnosis and treatment of ischemic renal diseases, such as renal artery stenosis. Diffusion imaging techniques may provide information on spatially restricted water diffusion and tumor cellularity. Functional MRI opens new horizons in studying renal physiology and pathophysiology in vivo. Although extensively utilized in research, labor-intensive postprocessing and lack of standardization currently limit the clinical applicability of functional MRI. Further studies are necessary to evaluate the clinical value of functional magnetic resonance techniques for early discovery and characterization of kidney disease.

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.

Effects of a Single Dose of Parecoxib on Inflammatory Response and Ischemic Tubular Injury Caused by Hemorrhagic Shock in Rats.

PubMed

Takaku, Mariana; da Silva, Andre Carnevali; Iritsu, Nathalie Izumi; Vianna, Pedro Thadeu Galvao; Castiglia, Yara Marcondes Machado

2018-01-01

Parecoxib, a selective COX-2 inhibitor, is used to improve analgesia in postoperative procedures. Here we evaluated whether pretreatment with a single dose of parecoxib affects the function, cell injury, and inflammatory response of the kidney of rats subjected to acute hemorrhage. Inflammatory response was determined according to serum and renal tissue cytokine levels (IL-1 α , IL-1 β , IL-6, IL-10, and TNF- α ). Forty-four adult Wistar rats anesthetized with sevoflurane were randomized into four groups: placebo/no hemorrhage (Plc/NH); parecoxib/no hemorrhage (Pcx/NH); placebo/hemorrhage (Plc/H); and parecoxib/hemorrhage (Pcx/H). Pcx groups received a single dose of intravenous parecoxib while Plc groups received a single dose of placebo (isotonic saline). Animals in hemorrhage groups underwent bleeding of 30% of blood volume. Renal function and renal histology were then evaluated. Plc/H showed the highest serum levels of cytokines, suggesting that pretreatment with parecoxib reduced the inflammatory response in rats subjected to hemorrhage. No difference in tissue cytokine levels between groups was observed. Plc/H showed higher percentage of tubular dilation and degeneration, indicating that parecoxib inhibited tubular injury resulting from renal hypoperfusion. Our findings indicate that pretreatment with a single dose of parecoxib reduced the inflammatory response and tubular renal injury without altering renal function in rats undergoing acute hemorrhage.

Design and Methodological Considerations of the Centers for Disease Control and Prevention Urologic and Renal Protocol for the Newborn and Young Child with Spina Bifida

PubMed Central

Routh, Jonathan C.; Cheng, Earl Y.; Austin, J. Christopher; Baum, Michelle A.; Gargollo, Patricio C.; Grady, Richard W.; Herron, Adrienne R.; Kim, Steven S.; King, Shelly J.; Koh, Chester J.; Paramsothy, Pangaja; Raman, Lisa; Schechter, Michael S.; Smith, Kathryn A.; Tanaka, Stacy T.; Thibadeau, Judy K.; Walker, William O.; Wallis, M. Chad; Wiener, John S.; Joseph, David B.

2016-01-01

Purpose Care of children with spina bifida has significantly advanced in the last half century, resulting in gains in longevity and quality of life for affected children and caregivers. Bladder dysfunction is the norm in patients with spina bifida and may result in infection, renal scarring and chronic kidney disease. However, the optimal urological management for spina bifida related bladder dysfunction is unknown. Materials and Methods In 2012 the Centers for Disease Control and Prevention convened a working group composed of pediatric urologists, nephrologists, epidemiologists, methodologists, community advocates and Centers for Disease Control and Prevention personnel to develop a protocol to optimize urological care of children with spina bifida from the newborn period through age 5 years. Results An iterative quality improvement protocol was selected. In this model participating institutions agree to prospectively treat all newborns with spina bifida using a single consensus based protocol. During the 5-year study period outcomes will be routinely assessed and the protocol adjusted as needed to optimize patient and process outcomes. Primary study outcomes include urinary tract infections, renal scarring, renal function and bladder characteristics. The protocol specifies the timing and use of testing (eg ultrasonography, urodynamics) and interventions (eg intermittent catheterization, prophylactic antibiotics, antimuscarinic medications). Starting in 2014 the Centers for Disease Control and Prevention began funding 9 study sites to implement and evaluate the protocol. Conclusions The Centers for Disease Control and Prevention Urologic and Renal Protocol for the Newborn and Young Child with Spina Bifida began accruing patients in 2015. Assessment in the first 5 years will focus on urinary tract infections, renal function, renal scarring and clinical process improvements. PMID:27475969

[Impaired renal function: be aware of exogenous factors].

PubMed

van der Meijden, Wilbert A G; Smak Gregoor, Peter J H

2013-01-01

Renal function is currently estimated using the Modification of Diet in Renal Disease (MDRD) formula, which is partly based on the serum creatinine level. Patients with impaired renal function are referred to nephrologists in accordance with the Dutch national transmural agreement for 'Chronic renal impairment'. A 54-year-old woman without significant history was referred to analyse a coincidentally found decline in the estimated glomerular filtration rate (eGFR). The patient had no complaints and used no medication except creatine supplements. Additional diagnostic testing showed no abnormalities. After cessation of creatine supplementation, the calculated renal function normalized. Serum creatinine is a reflection of muscle mass. The use of creatine-containing dietary supplements, such as creatine ethyl ester, can influence serum creatinine levels and therefore the eGFR as calculated with the MDRD formula. The use of supplements deserves attention when taking the history.

Worsening renal function defined as an absolute increase in serum creatinine is a biased metric for the study of cardio-renal interactions.

PubMed

Testani, Jeffrey M; McCauley, Brian D; Chen, Jennifer; Shumski, Michael; Shannon, Richard P

2010-01-01

Worsening renal function (WRF) during the treatment of decompensated heart failure, frequently defined as an absolute increase in serum creatinine >or=0.3 mg/dl, has been reported as a strong adverse prognostic factor in several studies. We hypothesized that this definition of WRF is biased by baseline renal function secondary to the exponential relationship between creatinine and renal function. We reviewed consecutive admissions with a discharge diagnosis of heart failure. An increase in creatinine >or=0.3 mg/dl (WRF(CREAT)) was compared to a decrease in GFR >or=20% (WRF(GFR)). Overall, 993 admissions met eligibility. WRF(CREAT) occurred in 31.5% and WRF(GFR) in 32.7%. WRF(CREAT) and WRF(GFR) had opposing relationships with baseline renal function (OR = 1.9 vs. OR = 0.51, respectively, p < 0.001). Both definitions had similar unadjusted associations with death at 30 days [WRF(GFR) OR = 2.3 (95% CI 1.1-4.8), p = 0.026; WRF(CREAT) OR = 2.1 (95% CI 1.0-4.4), p = 0.047]. Controlling for baseline renal insufficiency, WRF(GFR) added incrementally in the prediction of mortality (p = 0.009); however, WRF(CREAT) did not (p = 0.11). WRF, defined as an absolute change in serum creatinine, is heavily biased by baseline renal function. An alternative definition of WRF should be considered for future studies of cardio-renal interactions. Copyright 2010 S. Karger AG, Basel.

Desensitization protocol enabling pediatric crossmatch-positive renal transplantation: successful HLA-antibody-incompatible renal transplantation of two highly sensitized children.

PubMed

Adamusiak, Anna M; Stojanovic, Jelena; Shaw, Olivia; Vaughan, Robert; Sebire, Neil J; Drage, Martin; Kessaris, Nicos; Marks, Stephen D; Mamode, Nizam

2017-02-01

Renal transplantation improves quality of life (QoL) and survival in children requiring renal replacement therapy (RRT). Sensitization with development of a broad-spectrum of anti-HLA antibodies as a result of previous transplantation or after receiving blood products is an increasing problem. There are no published reports of desensitization protocols in children allowing renal transplantation from HLA-antibody-incompatible living donors. We adopted our well-established adult desensitization protocol for this purpose and undertook HLA antibody-incompatible living donor renal transplants in two children: a 14-year-old girl and a 13-year-old boy. After 2 and 1.5 years of follow-up, respectively, both patients have stable renal allograft function despite a rise in donor-specific antibodies in one case. HLA-incompatible transplantation should be considered in selected cases for sensitized children.

Renal subcapsular rim sign. Radionuclide pattern

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

Howman-Giles, R.; Gett, M.; Roy, P.

1986-04-01

The renal cortical rim sign is a radiological term describing the thin peripheral nephrogram of 2-4 mm thick which is from the peri-renal capsular collateral circulation in an otherwise nonfunctioning kidney. Radionuclides are used frequently in the estimation of renal function. A neonate with renal vein thrombosis demonstrated a rim sign on renal scan with Technetium DTPA. The rim sign on renal scan can be differentiated from severe hydronephrosis or multicystic kidney both of which may have a peripheral thin cortex which functions late on the renal scan. The rim sign in renal vein thrombosis was best visualized during themore » early blood pool phase when there was a considerable amount of radioactivity in the blood pool.« less

Effects of carprofen on renal function and results of serum biochemical and hematologic analyses in anesthetized dogs that had low blood pressure during anesthesia.

PubMed

Boström, Ingrid M; Nyman, Görel C; Lord, Peter E; Häggström, Jens; Jones, Bernt E V; Bohlin, Henrik P

2002-05-01

To investigate effects of IV administered carprofen on indices of renal function and results of serum biochemical and hematologic analyses in dogs anesthetized with acepromazine-thiopentone-isoflurane that had low blood pressure during anesthesia. 6 healthy Beagles. A randomized crossover study was conducted, using the following treatments: saline (0.9% NaCl solution)-saline, saline-carprofen, and carprofen-saline. Saline (0.08 ml/kg) and carprofen (4 mg/kg) were administered IV. The first treatment was administered 30 minutes before induction of anesthesia and immediately before administration of acepromazine (0.1 mg/kg, IM). Anesthesia was induced with thiopentone (25 mg/ml, IV) and maintained with inspired isoflurane (2% in oxygen). The second treatment was administered 30 minutes after onset of inhalation anesthesia. Blood gases, circulation, and ventilation were monitored. Renal function was assessed by glomerular filtration rate (GFR), using scintigraphy, serum biochemical analyses, and urinalysis. Hematologic analysis was performed. Statistical analysis was conducted, using ANOVA or Friedman ANOVA. Values did not differ significantly among the 3 treatments. For all treatments, sedation and anesthesia caused changes in results of serum biochemical and hematologic analyses, a decrease in mean arterial blood pressure to 65 mm Hg, an increase of 115 pmol/L in angiotensin II concentration, and an increase of 100 seconds in time required to reach maximum activity counts during scintigraphy. Carprofen administered IV before or during anesthesia did not cause detectable significant adverse effects on renal function or results of serum biochemical and hematologic analyses in healthy Beagles with low blood pressure during anesthesia.

Long-term outcome of patients with multiple [corrected] myeloma-related advanced renal failure following auto-SCT.

PubMed

Glavey, S V; Gertz, M A; Dispenzieri, A; Kumar, S; Buadi, F; Lacy, M; Hayman, S R; Kapoor, P; Dingli, D; McCurdy, A; Hogan, W J; Gastineau, D A; Leung, N

2013-11-01

Renal failure commonly complicates multiple myeloma (MM) and is associated with reduced survival. It is not clear whether auto-SCT results in improved renal function or attainment of independence from dialysis in patients with advanced renal impairment due to MM. We conducted a retrospective cohort study of all patients who underwent auto-SCT for MM complicated by advanced renal failure at our institution over a 10-year period (2000-2010). We aimed to assess the association between auto-SCT and renal outcome in patients with serum creatinine (SCr) over 3 mg/dL, attributable to MM, including those who were dialysis dependent. Thirty patients (2.8% of all auto-SCT patients) met inclusion criteria. Fourteen of 15 patients who were dialysis dependent before auto-SCT remained dialysis dependent in the long term despite hematological response (HR). Of the remaining 15 patients with SCr >3 mg/dL, an improvement in glomerular filtration rate (GFR) from 15 to 19.4 mL/min/1.73 m(2) was noted post auto-SCT (P=0.035); however, neither HR post auto-SCT or pre-existing renal function were independently associated with renal outcome. Auto-SCT was not associated with independence from dialysis in patients with renal failure due to MM at our institution. Although auto-SCT was associated with an improvement in GFR in patients with SCr >3 mg/dL, this improvement was not related to HR.

Impact of Impaired Renal Function on Gadolinium Retention After Administration of Gadolinium-Based Contrast Agents in a Mouse Model.

PubMed

Kartamihardja, A Adhipatria P; Nakajima, Takahito; Kameo, Satomi; Koyama, Hiroshi; Tsushima, Yoshito

2016-10-01

The aim of this study was to investigate the impact of impaired renal function on gadolinium (Gd) retention in various organs after Gd-based contrast agent injection. After local animal care and review committee approval, 23 normal mice and 26 with renal failure were divided into 4 treatment groups (Gd-DTPA-BMA, 5 mmol/kg; Gd-DOTA, 5 mmol/kg; GdCl3, 0.02 mmol/kg; and saline, 250 μL). Each agent was intravenously administered on weekdays for 4 weeks. Samples were collected on days 3 (short-term) and 45 (long-term) after the last injection. Gadolinium concentrations were quantified by inductively coupled plasma-mass spectrometry. Three mice with renal failure and 2 normal mice in the GdCl3 group and 1 mouse with renal failure in the Gd-DTPA-BMA group died. In the Gd-DTPA-BMA group, impaired renal function increased short-term Gd retention in the liver, bone, spleen, skin, and kidney (P < 0.01) but did not affect long-term Gd retention. Gd-DTPA-BMA showed higher Gd retention than Gd-DOTA. Although Gd retention in the Gd-DOTA group was generally low, impaired renal function increased only long-term hepatic Gd retention. Hepatic and splenic Gd retentions were significantly higher than other organs' Gd retention in the GdCl3 group (P < 0.01). Renal function did not affect brain Gd retention, regardless of the Gd compound used. The tendency of Gd retention varied according to the agent, regardless of renal function. Although renal impairment increased short-term Gd retention after Gd-DTPA-BMA administration, long-term Gd retention for Gd-based contrast agents was almost unaffected by renal function, suggesting that the chemical structures of retained Gd may not be consistent and some Gd is slowly eliminated after initially being retained.

A Randomized 2x2 Factorial Clinical Trial of Renal Transplantation: Steroid-Free Maintenance Immunosuppression with Calcineurin Inhibitor Withdrawal after Six Months Associates with Improved Renal Function and Reduced Chronic Histopathology

PubMed Central

Stevens, R. Brian; Foster, Kirk W.; Miles, Clifford D.; Kalil, Andre C.; Florescu, Diana F.; Sandoz, John P.; Rigley, Theodore H.; Malik, Tamer; Wrenshall, Lucile E.

2015-01-01

Introduction The two most significant impediments to renal allograft survival are rejection and the direct nephrotoxicity of the immunosuppressant drugs required to prevent it. Calcineurin inhibitors (CNI), a mainstay of most immunosuppression regimens, are particularly nephrotoxic. Until less toxic antirejection agents become available, the only option is to optimize our use of those at hand. Aim To determine whether intensive rabbit anti-thymocyte globulin (rATG) induction followed by CNI withdrawal would individually or combined improve graft function and reduce graft chronic histopathology–surrogates for graft and, therefore, patient survival. As previously reported, a single large rATG dose over 24 hours was well-tolerated and associated with better renal function, fewer infections, and improved patient survival. Here we report testing whether complete CNI discontinuation would improve renal function and decrease graft pathology. Methods Between April 20, 2004 and 4-14-2009 we conducted a prospective, randomized, non-blinded renal transplantation trial of two rATG dosing protocols (single dose, 6 mg/kg vs. divided doses, 1.5 mg/kg every other day x 4; target enrollment = 180). Subsequent maintenance immunosuppression consisted of tacrolimus, a CNI, and sirolimus, a mammalian target of rapamycin inhibitor. We report here the outcome of converting patients after six months either to minimized tacrolimus/sirolimus or mycophenolate mofetil/sirolimus. Primary endpoints were graft function and chronic histopathology from protocol kidney biopsies at 12 and 24 months Results CNI withdrawal (on-treatment analysis) associated with better graft function (p <0.001) and lower chronic histopathology composite scores in protocol biopsies at 12 (p = 0.003) and 24 (p = 0.013) months, without affecting patient (p = 0.81) or graft (p = 0.93) survival, or rejection rate (p = 0.17). Conclusion CNI (tacrolimus) withdrawal at six months may provide a strategy for decreased nephrotoxicity and improved long-term function in steroid-free low immunological risk renal transplant patients. Trial Registration ClinicalTrials.gov NCT00556933 PMID:26465152

Recirculation zone length in renal artery is affected by flow spirality and renal-to-aorta flow ratio.

PubMed

Javadzadegan, Ashkan; Fulker, David; Barber, Tracie

2017-07-01

Haemodynamic perturbations such as flow recirculation zones play a key role in progression and development of renal artery stenosis, which typically originate at the aorta-renal bifurcation. The spiral nature of aortic blood flow, division of aortic blood flow in renal artery as well as the exercise conditions have been shown to alter the haemodynamics in both positive and negative ways. This study focuses on the combinative effects of spiral component of blood flow, renal-to-aorta flow ratio and the exercise conditions on the size and distribution of recirculation zones in renal branches using computational fluid dynamics technique. Our findings show that the recirculation length was longest when the renal-to-aorta flow ratio was smallest. Spiral flow and exercise conditions were found to be effective in reducing the recirculation length in particular in small renal-to-aorta flow ratios. These results support the hypothesis that in renal arteries with small flow ratios where a stenosis is already developed an artificially induced spiral flow within the aorta may decelerate the progression of stenosis and thereby help preserve kidney function.

Predictors of Renal Function Decline in Chinese Patients with Type 2 Diabetes Mellitus and in a Subgroup of Normoalbuminuria: A Retrospective Cohort Study.

PubMed

Hu, Ping; Zhou, Xiang-Hai; Wen, Xin; Ji, Linong

2016-10-01

Risk factors related to renal function decline in type 2 diabetes mellitus (T2DM) remain uncertain. This study aimed to investigate risk factors in relation to renal function decline in patients with T2DM and in a subgroup of patients with normoalbuminuria. This study was a retrospective cohort study, which included 451 patients with T2DM aged 63 ± 14 years admitted to a tertiary hospital in Beijing, China, between April and December 2010 and followed up for 6-60 months. Endpoint was renal function decline, defined as estimated glomerular filtration rate less than 60 mL/min 1.73 m 2 or at least twofold increase of serum creatinine. Cox proportional hazards analysis was used to estimate hazard ratios (HRs) for candidate risk factors of renal function decline. After a median follow-up of 3.3 years, 94 (20.8%) patients developed renal function decline. Increased age (HR, 1.045; 95% CI, 1.020-1.070), albuminuria (HR, 1.956; 95%CI, 1.271-3.011), mild renal dysfunction (HR, 4.521; 95%CI, 2.734-7.476), hyperfiltration (HR, 3.897; 95%CI, 1.572-9.663), and increased hemoglobin A1c (HR, 1.128; 95%CI, 1.020-1.249) were identified as major risk factors. Among a subgroup of 344 patients with normoalbuminuria at baseline, 53 (15.4%) patients developed renal function decline. Increased age (HR, 1.089; 95%CI, 1.050-1.129), mild renal dysfunction (HR, 4.667; 95%CI, 2.391-9.107), hyperfiltration (HR, 5.677; 95%CI, 1.544-20.872), smoking (HR, 2.886; 95%CI, 1.370-6.082), higher pulse pressure (HR, 1.022; 95%CI, 1.004-1.040), and increased fasting glucose (HR, 1.104; 95%CI, 1.020-1.194) were major risk factors. Risk factors of diabetic renal impairment in T2DM should be screened and evaluated at an early stage of diabetes. Albuminuria, mild renal dysfunction, hyperfiltration, increased blood glucose, increased pulse pressure, and smoking were all predictors for diabetic renal impairment and interventions that focus on these risk factors may reduce further decline in renal function.

Impact of feline AIM on the susceptibility of cats to renal disease

PubMed Central

Sugisawa, Ryoichi; Hiramoto, Emiri; Matsuoka, Shigeru; Iwai, Satomi; Takai, Ryosuke; Yamazaki, Tomoko; Mori, Nobuko; Okada, Yuki; Takeda, Naoki; Yamamura, Ken-ichi; Arai, Toshiro; Arai, Satoko; Miyazaki, Toru

2016-01-01

Renal failure is one of the most important social problems for its incurability and high costs for patients’ health care. Through clarification of the underlying mechanism for the high susceptibility of cats to renal disease, we here demonstrates that the effective dissociation of serum AIM protein from IgM is necessary for the recovery from acute kidney injury (AKI). In cats, the AIM-IgM binding affinity is 1000-fold higher than that in mice, which is caused by the unique positively-charged amino-acid cluster present in feline AIM. Hence, feline AIM does not dissociate from IgM during AKI, abolishing its translocation into urine. This results in inefficient clearance of lumen-obstructing necrotic cell debris at proximal tubules, thereby impairing AKI recovery. Accordingly, mice whose AIM is replaced by feline AIM exhibit higher mortality by AKI than in wild-type mice. Recombinant AIM administration into the mice improves their renal function and survival. As insufficient recovery from AKI predisposes patients to chronic, end-stage renal disease, feline AIM may be involved crucially in the high mortality of cats due to renal disease. Our findings could be the basis of the development of novel AKI therapies targeting AIM-IgM dissociation, and may support renal function in cats and prolong their lives. PMID:27731392

Impact of feline AIM on the susceptibility of cats to renal disease.

PubMed

Sugisawa, Ryoichi; Hiramoto, Emiri; Matsuoka, Shigeru; Iwai, Satomi; Takai, Ryosuke; Yamazaki, Tomoko; Mori, Nobuko; Okada, Yuki; Takeda, Naoki; Yamamura, Ken-Ichi; Arai, Toshiro; Arai, Satoko; Miyazaki, Toru

2016-10-12

Renal failure is one of the most important social problems for its incurability and high costs for patients' health care. Through clarification of the underlying mechanism for the high susceptibility of cats to renal disease, we here demonstrates that the effective dissociation of serum AIM protein from IgM is necessary for the recovery from acute kidney injury (AKI). In cats, the AIM-IgM binding affinity is 1000-fold higher than that in mice, which is caused by the unique positively-charged amino-acid cluster present in feline AIM. Hence, feline AIM does not dissociate from IgM during AKI, abolishing its translocation into urine. This results in inefficient clearance of lumen-obstructing necrotic cell debris at proximal tubules, thereby impairing AKI recovery. Accordingly, mice whose AIM is replaced by feline AIM exhibit higher mortality by AKI than in wild-type mice. Recombinant AIM administration into the mice improves their renal function and survival. As insufficient recovery from AKI predisposes patients to chronic, end-stage renal disease, feline AIM may be involved crucially in the high mortality of cats due to renal disease. Our findings could be the basis of the development of novel AKI therapies targeting AIM-IgM dissociation, and may support renal function in cats and prolong their lives.

Obstructive uropathy and acute renal failure due to ureteral calculus in renal graft: a case report.

PubMed

Lusenti, T; Fiorini, F; Barozzi, L

2009-09-01

Obstructive uropathy caused by kidney stones is quite rare in transplant kidneys. The authors report the case of a patient, previously gastrectomized for gastric carcinoma. He underwent renal transplantation using uretero-ureterostomy, and presented an episode of acute renal failure 7 years after surgery. Ultrasound (US) examination showed no sign of rejection but allowed detection of moderate hydronephrosis in the transplant kidney. Subsequent computed tomography (CT) revealed a kidney stone in the middle ureter at the crossing of the iliac vessels. The patient therefore urgently underwent percutaneous nephrostomy of the graft and recovered diuresis and renal function. The patient was transferred to the Transplant Center where he underwent ureterotomy with removal of the stone and subsequent ureteropyelostomy. Also transureteral resection of the prostate (TURP) was performed due to urinary retention of prostatic origin. Histological examination showed prostate carcinoma, Gleason stage 3, which was treated conservatively using radiotherapy without suspension of the administered low dose of immunotherapy. Calculosis is one of the least common causes of obstructive uropathy in transplant kidneys. In the described case, US examination performed after onset of renal insufficiency led to subsequent radiological investigation and resulting interventional procedures (nephrostomy and surgical removal of the stone) with complete recovery of pre-existing renal function.

Different methods of hilar clamping during partial nephrectomy: Impact on renal function.

PubMed

Lee, Jeong Woo; Kim, Hwanik; Choo, Minsoo; Park, Yong Hyun; Ku, Ja Hyeon; Kim, Hyeon Hoe; Kwak, Cheol

2014-03-01

To evaluate the impact of different hilar clamping methods on changes in renal function after partial nephrectomy. We analyzed the clinical data of 369 patients who underwent partial nephrectomy for a single renal tumor of size ≤4.0 cm and a normal contralateral kidney. Patients were separated into three groups depending on hilar clamping method: non-clamping, cold ischemia and warm ischemia. Estimated glomerular filtration rate was examined at preoperative, nadir and 1 year postoperatively. Percent change in estimated glomerular filtration rate was used as the parameter to assess the renal functional outcome. Percent change in nadir estimated glomerular filtration rate in the non-clamping group was significantly less compared with the cold ischemia and warm ischemia groups (P < 0.001). However, no significant differences among the groups were noted in percent change of estimated glomerular filtration rate at 1 year (P = 0.348). The cold ischemia group had a similar serial change of postoperative renal function compared with the warm ischemia group. Percent change in 1-year estimated glomerular filtration rate increased with increasing ischemia time in the cold ischemia (P for trend = 0.073) and warm ischemia groups (P for trend = 0.010). On multivariate analysis, hilar clamping (both warm ischemia and cold ischemia) were significantly associated with percent change in nadir estimated glomerular filtration rate, but not in 1-year estimated glomerular filtration rate. Non-clamping partial nephrectomy results in a lower percent change in nadir estimated glomerular filtration rate, whereas it carries an estimated glomerular filtration rate change at 1 year that is similar to partial nephrectomy with cold ischemia and warm ischemia. Cold ischemia and warm ischemia provide a similar effect on renal function. Therefore, when hilar clamping is required, minimization of ischemia time is necessary. © 2013 The Japanese Urological Association.

Hordenine protects against hyperglycemia-associated renal complications in streptozotocin-induced diabetic mice.

PubMed

Su, Shuhao; Cao, Meng; Wu, Guangyuan; Long, Zi; Cheng, Xiaodong; Fan, Junshu; Xu, Zhongrui; Su, Hongfei; Hao, Yiming; Li, Ge; Peng, Jie; Li, Shuang; Wang, Xin

2018-05-15

The worldwide prevalence of diabetes and associated metabolic diseases has dramatically increased. Pharmacological treatment of diabetes is still limited. Hordenine (HOR), a phenethylamine alkaloid, is a natural constituent in many plants. The present study was designed to explore the possible anti-diabetic effect of HOR in streptozotocin (STZ)-induced diabetic mice. Combined treatment of HOR and insulin significantly reduced fasting and postprandial blood glucose level in diabetic mice. HOR and insulin did not show evident protective effect against structural and functional injuries of pancreas. Renal histological and functional injuries were significantly improved by HOR or insulin treatment. Moreover, combined treatment of HOR and insulin resulted in a more significant amelioration of renal histological and functional injuries in diabetic mice. HOR induced a decrease of renal IL-1α/β and IL-6 expression, and a reduction of Col1α1 and MMP9 expression and PAS-stained mesangial expansion in glomeruli of diabetic mice. In diabetic mice, HOR significantly decreased Nrf2 expression and increased hnRNPF and hnRNPK expression in kidney. Moreover, HOR showed a synergistic effect with insulin on the expression of these regulators. Renal ROS level and TBARS content in diabetic mice were decreased by HOR. The reduction of renal expression of antioxidant enzymes in diabetic mice was inhibited by HOR and insulin. Furthermore, HOR and insulin function synergistically to play an antioxidant role against oxidative injury in diabetic nephropathy. In conclusion, to the best of our knowledge, we, for the first time, found the anti-diabetic, anti-inflammatory, and anti-fibrotic role of HOR in combination with insulin. HOR functions synergistically with insulin and prevents diabetic nephropathy. However, the molecular mechanism of the synergistic effect of HOR and insulin needs to be elucidated. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Vesicoureteral reflux in the primate IV: does reflux harm the kidney

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

Roberts, J.A.; Fischman, N.H.; Thomas, R.

1982-09-01

It has been said that vesicoureteral reflux causes renal scarring because of intrarenal reflux. We studied reflux in the monkey because of its similarity to man, especially in regard to the incidence of vesicoureteral reflux and chronic pyelonephritis. High pressure moderate grade reflux was produced and renal function followed by means of quantitative renal camera studies using /sup 131/I hippuran. There was no change in renal function from sterile reflux even when intrarenal reflux occurred. When, however, infection was introduced, renal function decreased. We concluded that sterile moderate vesicoureteral or intrarenal reflux does not harm the kidney.

Why and how to measure renal function in patients with liver disease.

PubMed

Piano, Salvatore; Romano, Antonietta; Di Pascoli, Marco; Angeli, Paolo

2017-01-01

Patients with advanced liver disease frequently have impaired renal function. Both acute kidney injury (AKI) and chronic kidney disease (CKD) are quite common in patients with cirrhosis and both are associated with a worse prognosis in these patients. A careful assessment of renal function is highly important in these patients to help physicians determine their diagnosis, prognosis and therapeutic management and to define transplantation strategies (liver transplantation alone vs simultaneous liver and kidney transplantation). Although they are still widely used in clinical practice, conventional biomarkers of renal function such as serum creatinine have several limitations in these patients. Recent progress has been made in the evaluation of renal function and new diagnostic criteria for AKI have been proposed. However, certain issues such as the noninvasive assessment of the glomerular filtration rate and/or improvement in the differential diagnosis between hepatorenal syndrome and acute tubular necrosis must still be addressed. The purposes of this paper are: (i) to highlight the importance of the evaluation of renal function in patients with cirrhosis; (ii) to review the state of the art in the assessment of renal function in these patients as well as advances that we expect will be made to improve the accuracy of available tools. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cigarette smoking causes epigenetic changes associated with cardiorenal fibrosis

PubMed Central

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

2016-01-01

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

Renal PKC-ε deficiency attenuates acute kidney injury and ischemic allograft injury via TNF-α-dependent inhibition of apoptosis and inflammation.

PubMed

Rong, Song; Hueper, Katja; Kirsch, Torsten; Greite, Robert; Klemann, Christian; Mengel, Michael; Meier, Matthias; Menne, Jan; Leitges, Michael; Susnik, Nathan; Meier, Martin; Haller, Hermann; Shushakova, Nelli; Gueler, Faikah

2014-09-15

Acute kidney injury (AKI) increases the risk of morbidity and mortality after major surgery and transplantation. We investigated the effect of PKC-ε deficiency on AKI and ischemic allograft damage after kidney transplantation. PKC-ε-deficient and wild type (WT) control mice were subjected to 35 min of renal pedicle clamping to induce AKI. PKC-ε deficiency was associated with a marked improvement in survival and an attenuated loss of kidney function. Furthermore, functional MRI experiments revealed better renal perfusion in PKC-ε-deficient mice than in WT mice one day after IRI. Acute tubular necrosis and neutrophil infiltration were markedly reduced in PKC-ε-deficient mice. To determine whether this resistance to ischemia-reperfusion injury resulted from changes in local renal cells or infiltrating leukocytes, we studied a life-supporting renal transplant model of ischemic graft injury. We transplanted kidneys from H(2b) PKC-ε-deficient mice (129/SV) and their corresponding WT littermates into major histocompatibility complex-incompatible H(2d) recipients (BALB/c) and induced ischemic graft injury by prolonged cold ischemia time. Recipients of WT allografts developed severe renal failure and died within 10 days of transplantation. Recipients of PKC-ε-deficient allografts had better renal function and survival; they had less generation of ROS and upregulation of proinflammatory proteins (i.e., ICAM-1, inducible nitric oxide synthase, and TNF-α) and showed less tubular epithelial cell apoptosis and inflammation in their allografts. These data suggest that local renal PKC-ε expression mediates proapoptotic and proinflammatory signaling and that an inhibitor of PKC-ε signaling could be used to prevent hypoxia-induced AKI. Copyright © 2014 the American Physiological Society.

A case of gain-of-function mutation in calcium-sensing receptor: supplemental hydration is required for renal protection.

PubMed

Suzuki, M; Aso, T; Sato, T; Michimata, M; Kazama, I; Saiki, H; Hatano, R; Ejima, Y; Miyama, N; Sato, A; Matsubara, M

2005-06-01

The calcium-sensing receptor (CaSR) regulates the extracellular calcium level, mainly by controlling parathyroid hormon secretion and renal calcium reabsorption. In gain-of-function CaSR mutations, the genetic abnormalities increase CaSR activity leading to the development of such clinical manifestations as hypercalciuric hypocalcemia and hypoparathyroidism. We report a Japanese case of CaSR gain-of-function mutation and represent a therapeutic intervention based on the functional characteristics of CaSR in renal tubule. DNA sequence analysis revealed a heterozygous G to T mutation identified in a 12-year-old Japanese girl presenting with sporadic onset of hypercalciuric hypocalcemia and hypoparathyroidism. The mutation is located in the N-terminal extracellular domain of the CaSR gene, one of the most important parts for the three-dimensional construction of the receptor, resulting in the substitution of phenylalanine for cysteine at amino acid 131 (C131F) in exon 3. Based on the diagnosis of the gain-of-function mutation in the CaSR, oral hydrochlorothiazide administration and supplemental hydration were started in addition to calcium supplementation. The combination therapy of thiazide and supplemental hydration markedly reduced both renal calcium excretion and urinary calcium concentration from 0.4-0.7 to less than 0.1 mg/mg (urinary calcium/creatinine ratio) and from 10-15 to 3-5 mg/dl (urinary calcium concentration), respectively. This therapy stopped the progression of renal calcification during the follow-up period. Supplemental hydration should be considered essential for the following reasons: (1) calcium supplementation activates the CaSR in the kidney and suppresses renal urinary concentrating ability, (2) the thiazide has a diuretic effect, (3) as calcium supplementation increases renal calcium excretion, the supplemental hydration decreases urinary calcium concentration by increasing urinary volume, thereby diminishing the risk of intratubular crystallization of calcium ion.

Comparison of the Chronic Kidney Disease Epidemiology Collaboration, the Modification of Diet in Renal Disease study and the Cockcroft-Gault equation in patients with heart failure.

PubMed

Szummer, Karolina; Evans, Marie; Carrero, Juan Jesus; Alehagen, Urban; Dahlström, Ulf; Benson, Lina; Lund, Lars H

2017-01-01

It is unknown how the creatinine-based renal function estimations differ for dose adjustment cut-offs and risk prediction in patients with heart failure. The renal function was similar with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) (median 59 mL/min/1.73 m 2 , IQR 42 to 77) and Modification of Diet in Renal Disease Study (MDRD) (59 mL/min/1.73 m 2 , IQR 43 to 75) and slightly lower with the Cockcroft-Gault (CG) equation (57 mL/min, IQR 39 to 82). Across the commonly used renal function stages, the CKD-EPI and the MDRD classified patients into the same stage in 87.2% (kappa coefficient 0.83, p<0.001); the CKD-EPI and the CG equation agreed in 52.3% (kappa coefficient 0.39, p<0.001). Hence, a differing number of patients will receive dose adjustment depending on which formula is used as cut-off. The CG equation predicted worse prognosis better (c-statistics 0.740, 95% CI 0.734 to 0.746) than CKD-EPI (0.697, 95% CI 0.690 to 0.703, p<0.001) and MDRD (0.680, 95% CI 0.734 to 0.746). Using net reclassification improvement (NRI), the CG identified 12.8% more patients at higher risk of death as compared with the CKD-EPI equation. Patients registered in the Swedish Heart Failure Registry (n= 40 736) with standardised creatinine values between 2000 and 2012 had their renal function estimated with the CKD-EPI, the MDRD and the CG. Agreement between the formulas was compared for categories. Prediction of death was assessed with c-statistics and with NRI. The choice of renal function estimation formula has clinical implications and differing results at various cut-off levels. For prognosis, the CG predicts mortality better than the CKD-EPI and MDRD.

Dosing of cytotoxic chemotherapy: impact of renal function estimates on dose.

PubMed

Dooley, M J; Poole, S G; Rischin, D

2013-11-01

Oncology clinicians are now routinely provided with an estimated glomerular filtration rate on pathology reports whenever serum creatinine is requested. The utility of using this for the dose determination of renally excreted drugs compared with other existing methods is needed to inform practice. Renal function was determined by [Tc(99m)]DTPA clearance in adult patients presenting for chemotherapy. Renal function was calculated using the 4-variable Modification of Diet in Renal Disease (4v-MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Cockcroft and Gault (CG), Wright and Martin formulae. Doses for renal excreted cytotoxic drugs, including carboplatin, were calculated. The concordance of the renal function estimates according to the CKD classification with measured Tc(99m)DPTA clearance in 455 adults (median age 64.0 years: range 17-87 years) for the 4v-MDRD, CKD-EPI, CG, Martin and Wright formulae was 47.7%, 56.3%, 46.2%, 56.5% and 60.2%, respectively. Concordance for chemotherapy dose for these formulae was 89.0%, 89.5%, 85.1%, 89.9% and 89.9%, respectively. Concordance for carboplatin dose specifically was 66.4%, 71.4%, 64.0%, 73.8% and 73.2%. All bedside formulae provide similar levels of concordance in dosage selection for the renal excreted chemotherapy drugs when compared with the use of a direct measure of renal function.

Alteration of renal function of rats following spaceflight.

PubMed

Wade, C E; Morey-Holton, E

1998-10-01

Following spaceflight, changes in renal function of humans have been suggested. To assess the effects of readaptation on renal function, urine was collected from male rats ( approximately 245 g) over a 2-wk period following a 14-day spaceflight. Rats were assigned to three groups: flight animals (n = 6), flight controls (n = 6) housed in the flight cages on the ground, and vivarium controls (n = 5) housed in standard shoe box cages. Animals were placed into individual metabolic cages for urine collection. Urine output was significantly increased for 3 days following flight. Excretion rates of Na+ and K+ were increased, resulting in an increased osmotic excretion rate. Creatinine excretion rate increased over the first two postflight days. Glomerular filtration rate increased immediately following spaceflight without changes in plasma creatinine, Na+, K+, or osmolality. Increased excretion of solute was thus the result of increased delivery and a decreased percent reabsorption of the filtered load. Osmolal clearance was increased immediately postflight while free water clearance was decreased. In growing rats, the diuresis after short-duration spaceflight is the result of an increase in solute excretion with an accompanying reduction in free water clearance.

Alteration of renal function of rats following spaceflight

NASA Technical Reports Server (NTRS)

Wade, C. E.; Morey-Holton, E.

1998-01-01

Following spaceflight, changes in renal function of humans have been suggested. To assess the effects of readaptation on renal function, urine was collected from male rats ( approximately 245 g) over a 2-wk period following a 14-day spaceflight. Rats were assigned to three groups: flight animals (n = 6), flight controls (n = 6) housed in the flight cages on the ground, and vivarium controls (n = 5) housed in standard shoe box cages. Animals were placed into individual metabolic cages for urine collection. Urine output was significantly increased for 3 days following flight. Excretion rates of Na+ and K+ were increased, resulting in an increased osmotic excretion rate. Creatinine excretion rate increased over the first two postflight days. Glomerular filtration rate increased immediately following spaceflight without changes in plasma creatinine, Na+, K+, or osmolality. Increased excretion of solute was thus the result of increased delivery and a decreased percent reabsorption of the filtered load. Osmolal clearance was increased immediately postflight while free water clearance was decreased. In growing rats, the diuresis after short-duration spaceflight is the result of an increase in solute excretion with an accompanying reduction in free water clearance.

Determinants of impaired renal and vascular function are associated with elevated levels of procoagulant factors in the general population.

PubMed

Dekkers, I A; de Mutsert, R; de Vries, A P J; Rosendaal, F R; Cannegieter, S C; Jukema, J W; le Cessie, S; Rabelink, T J; Lamb, H J; Lijfering, W M

2018-03-01

Essentials Why venous thrombosis is more prevalent in chronic kidney disease is unclear. We investigated whether renal and vascular function are associated with hypercoagulability. Coagulation factors showed a procoagulant shift with impaired renal and vascular function. This suggests that renal and vascular function play a role in the etiology of thrombosis. Background Impaired renal and vascular function have been associated with venous thrombosis, but the mechanism is unclear. Objectives We investigated whether estimated glomerular filtration rate (eGFR), urinary albumin-creatinine ratio (UACR), and pulse wave velocity (PWV) are associated with a procoagulant state. Methods In this cross-sectional analysis of the NEO Study, eGFR, UACR, fibrinogen, and coagulation factors (F)VIII, FIX and FXI were determined in all participants (n = 6536), and PWV was assessed in a random subset (n = 2433). eGFR, UACR and PWV were analyzed continuously and per percentile: per six categories for eGFR (> 50 th [reference] to < 1st) and UACR (< 50 th [reference] to > 99th), and per four categories (< 50 th [reference] to > 95th percentile) for PWV. Linear regression was used and adjusted for age, sex, total body fat, smoking, education, ethnicity, total cholesterol, C-reactive protein (CRP) and vitamin K antagonists use (FIX). Results Mean age was 55.6 years, mean eGFR 86.0 (12SD) mL 1.73 m - ² and median UACR 0.4 mg mmol -1 (25th, 75th percentile; 0.3, 0.7). All coagulation factors showed a procoagulant shift with lower renal function and albuminuria. For example, FVIII was 22 IU dL -1 (95% CI, 13-32) higher in the eGFR < 1st percentile compared with the > 50th percentile, and FVIII was 12 IU dL -1 (95% CI, 3-22) higher in the UACR > 99th percentile compared with the < 50th percentile. PWV was positively associated with coagulation factors FIX and FXI in continuous analysis; per m/s difference in PWV, FIX was 2.0 IU dL -1 (95% CI, 0.70-3.2) higher. Conclusions Impaired renal and vascular function was associated with higher levels of coagulation factors, underlining the role of renal function and vascular function in the development of venous thrombosis. © 2017 International Society on Thrombosis and Haemostasis.

Effects of positive acceleration /+Gz/ on renal function and plasma renin in normal man

NASA Technical Reports Server (NTRS)

Epstein, M.; Shubrooks, S. J., Jr.; Fishman, L. M.; Duncan, D. C.

1974-01-01

The effects of positive radial centrifugation (+Gz) on plasma resin activity (PRA) and renal function were assessed in 15 normal male subjects under carefully controlled conditions of Na, K, and water intake. Twenty minutes of +2.0 Gz resulted in significant decreases in the mean rate of sodium excretion and creatine clearance and in a doubling of PRA in seven sodium-depleted subjects (10 meq Na intake). In eight sodium-replete subjects (200 mq Na intake), 30 min of +2.0 Gz was also associated with a decrease in the mean rate of sodium excretion. As a consequence of a concurrent decrease in creatine clearance, the fractional excretion of sodium during centrifugation did not differ from control, suggesting that the changes in Na excretion were mediated primarily by renal hemodynamic factors, although enhanced renal tubular sodium reabsorption may also have played a role.

New Developments in Hepatorenal Syndrome.

PubMed

Mindikoglu, Ayse L; Pappas, Stephen C

2018-02-01

Hepatorenal syndrome (HRS) continues to be one of the major complications of decompensated cirrhosis, leading to death in the absence of liver transplantation. Challenges in precisely evaluating renal function in the patient with cirrhosis remain because of the limitations of serum creatinine (Cr) alone in estimating glomerular filtration rate (GFR); current GFR estimating models appear to underestimate renal dysfunction. Newer models incorporating renal biomarkers, such as the Cr-Cystatin C GFR Equation for Cirrhosis appear to estimate measured GFR more accurately. A major change in the diagnostic criteria for HRS based on dynamic serial changes in serum Cr that regard HRS type 1 as a special form of acute kidney injury promises the possibility of earlier identification of renal dysfunction in patients with cirrhosis. The diagnostic criteria of HRS still include the exclusion of other causes of kidney injury. Renal biomarkers have been disappointing in assisting with the differentiation of HRS from prerenal azotemia and other kidney disorders. Serum metabolomic profiling may be a more powerful tool to assess renal dysfunction, although the practical clinical significance of this remains unclear. As a result of the difficulties of assessing renal function in cirrhosis and the varying HRS diagnostic criteria and the rigor with which they are applied, the precise incidence and prevalence of HRS is unknown, but it is likely that HRS occurs more commonly than expected. The pathophysiology of HRS is rooted firmly in the setting of progressive reduction in renal blood flow as a result of portal hypertension and splanchnic vasodilation. Progressive marked renal cortical ischemia in patients with cirrhosis parallels the evolution of diuretic-sensitive ascites to diuretic-refractory ascites and HRS, a recognized continuum of renal dysfunction in cirrhosis. Alterations in nitrous oxide production, both increased and decreased, may play a major role in the pathophysiology of this evolution. The inflammatory cascade, triggered by bacterial translocation and endotoxemia, increasingly recognized as important in the manifestation of acute-on-chronic liver failure, also may play a significant role in the pathophysiology of HRS. The mainstay of treatment remains vasopressor therapy with albumin in an attempt to reverse splanchnic vasodilation and improve renal blood flow. Several meta-analyses have confirmed the value of vasopressors, chiefly terlipressin and noradrenaline, in improving renal function and reversing HRS type 1. Other interventions such as renal replacement therapy, transjugular intrahepatic portosystemic shunt, and artificial liver support systems have a very limited role in improving outcomes in HRS. Liver transplantation remains the definitive treatment for HRS. The frequency of simultaneous liver-kidney transplantation has increased dramatically in the Model for End-stage Liver Disease era, with changes in organ allocation policies. This has resulted in a more urgent need to predict native kidney recovery from HRS after liver transplantation alone, to avoid unnecessary simultaneous liver-kidney transplantation. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Renal intraspecific variation along an aridity gradient detected by new renal indices in a desert herbivorous rodent.

PubMed

Tejo Riquelme, Patricia A; Diaz Isenrath, Gabriela B; Andino, Natalia; Borghi, Carlos E

2014-07-01

Mammals that live in arid and semi-arid environments in South America present physiological mechanisms that enable them to conserve water. Body water is lost through the kidneys, lungs, skin, and intestines. Regarding renal adaptation for water conservation, several indices have been used to estimate the capacity of the kidneys to produce a maximum urine concentration. Most studies were conducted at an inter-specific level, with only few performed at the intraspecific level. In this work, we compare renal function and morphology among five populations of Southern mountain cavy, Microcavia australis, present along an aridity gradient. We hypothesized that individuals from drier zones would present morphological and functional renal modifications that imply a greater capability to conserve body water. These features were studied considering the classical indices (RMT, PMT, PMA, and RMA) and three new indices that consider area measurements; the latter showed to be more adequate to reflect intraspecific differences. Our results suggest that the morphological modifications of kidneys, that is, the greater areas of renal inner medulla, would be related to the aridity gradient where populations of Southern mountain cavy occur. © 2014 Wiley Periodicals, Inc.

Biotechnological challenges of bioartificial kidney engineering.

PubMed

Jansen, J; Fedecostante, M; Wilmer, M J; van den Heuvel, L P; Hoenderop, J G; Masereeuw, R

2014-11-15

With the world-wide increase of patients with renal failure, the development of functional renal replacement therapies have gained significant interest and novel technologies are rapidly evolving. Currently used renal replacement therapies insufficiently remove accumulating waste products, resulting in the uremic syndrome. A more preferred treatment option is kidney transplantation, but the shortage of donor organs and the increasing number of patients waiting for a transplant warrant the development of novel technologies. The bioartificial kidney (BAK) is such promising biotechnological approach to replace essential renal functions together with the active secretion of waste products. The development of the BAK requires a multidisciplinary approach and evolves at the intersection of regenerative medicine and renal replacement therapy. Here we provide a concise review embracing a compact historical overview of bioartificial kidney development and highlighting the current state-of-the-art, including implementation of living-membranes and the relevance of extracellular matrices. We focus further on the choice of relevant renal epithelial cell lines versus the use of stem cells and co-cultures that need to be implemented in a suitable device. Moreover, the future of the BAK in regenerative nephrology is discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

A two-hit mechanism for sepsis-induced impairment of renal tubule function

PubMed Central

Watts, Bruns A.; George, Thampi; Sherwood, Edward R.

2013-01-01

Renal insufficiency is a common and severe complication of sepsis, and the development of kidney dysfunction increases morbidity and mortality in septic patients. Sepsis is associated with a variety of defects in renal tubule function, but the underlying mechanisms are incompletely understood. We used a cecal ligation and puncture (CLP) model to examine mechanisms by which sepsis influences the transport function of the medullary thick ascending limb (MTAL). MTALs from sham and CLP mice were studied in vitro 18 h after surgery. The results show that sepsis impairs the ability of the MTAL to absorb HCO3− through two distinct mechanisms. First, sepsis induces an adaptive decrease in the intrinsic capacity of the tubules to absorb HCO3−. This effect is associated with an increase in ERK phosphorylation in MTAL cells and is prevented by pretreatment of CLP mice with a MEK/ERK inhibitor. The CLP-induced reduction in intrinsic HCO3− absorption rate appears to involve loss of function of basolateral Na+/H+ exchange. Second, sepsis enhances the ability of LPS to inhibit HCO3− absorption, mediated through upregulation of Toll-like receptor 4 (TLR4)-ERK signaling in the basolateral membrane. The two inhibitory mechanisms are additive and thus can function in a two-hit capacity to impair renal tubule function in sepsis. Both effects depend on ERK and are eliminated by interventions that prevent ERK activation. Thus the TLR4 and ERK signaling pathways represent potential therapeutic targets to treat or prevent sepsis-induced renal tubule dysfunction. PMID:23324175

Mesenchymal stem cells in renal function recovery after acute kidney injury: use of a differentiating agent in a rat model.

PubMed

La Manna, Gaetano; Bianchi, Francesca; Cappuccilli, Maria; Cenacchi, Giovanna; Tarantino, Lucia; Pasquinelli, Gianandrea; Valente, Sabrina; Della Bella, Elena; Cantoni, Silvia; Claudia, Cavallini; Neri, Flavia; Tsivian, Matvey; Nardo, Bruno; Ventura, Carlo; Stefoni, Sergio

2011-01-01

Acute kidney injury (AKI) is a major health care condition with limited current treatment options. Within this context, stem cells may provide a clinical approach for AKI. Moreover, a synthetic compound previously developed, hyaluronan monoesters with butyric acid (HB), able to induce metanephric differentiation, formation of capillary-like structures, and secretion of angiogenic cytokines, was tested in vitro. Thereafter, we investigated the effects of human mesenchymal stem cells from fetal membranes (FMhMSCs), both treated and untreated with HB, after induction of ischemic AKI in a rat model. At reperfusion following 45-min clamping of renal pedicles, each rat was randomly assigned to one of four groups: CTR, PBS, MSC, and MSC-HB. Renal function at 1, 3, 5, and 7 days was assessed. Histological samples were analyzed by light and electron microscopy and renal injury was graded. Cytokine analysis on serum samples was performed. FMhMSCs induced an accelerated renal functional recovery, demonstrated by biochemical parameters and confirmed by histology showing that histopathological alterations associated with ischemic injury were less severe in cell-treated kidneys. HB-treated rats showed a minor degree of inflammation, both at cytokine and TEM analyses. Better functional and morphological recovery were not associated to stem cells' regenerative processes, but possibly suggest paracrine effects on microenvironment that induce retrieval of renal damaged tissues. These results suggest that FMhMSCs could be useful in the treatment of AKI and the utilization of synthetic compounds could enhance the recovery induction ability of cells.

Renal Function and Outcomes With Use of Left Ventricular Assist Device Implantation and Inotropes in End-Stage Heart Failure: A Retrospective Single Center Study.

PubMed

Verma, Sean; Bassily, Emmanuel; Leighton, Shane; Mhaskar, Rahul; Sunjic, Igor; Martin, Angel; Rihana, Nancy; Jarmi, Tambi; Bassil, Claude

2017-07-01

Left ventricular assist device (LVAD) and inotrope therapy serve as a bridge to transplant (BTT) or as destination therapy in patients who are not heart transplant candidates. End-stage heart failure patients often have impaired renal function, and renal outcomes after LVAD therapy versus inotrope therapy have not been evaluated. In this study, 169 patients with continuous flow LVAD therapy and 20 patients with continuous intravenous inotrope therapy were analyzed. The two groups were evaluated at baseline and at 3 and 6 months after LVAD or inotrope therapy was started. The incidence of acute kidney injury (AKI), need for renal replacement therapy (RRT), BTT rate, and mortality for 6 months following LVAD or inotrope therapy were studied. Results between the groups were compared using Mann-Whitney U test and Chi-square with continuity correction or Fischer's exact at the significance level of 0.05. Mean glomerular filtration rate (GFR) was not statistically different between the two groups, with P = 0.471, 0.429, and 0.847 at baseline, 3 and 6 months, respectively. The incidence of AKI, RRT, and BTT was not statistically different. Mortality was less in the inotrope group (P < 0.001). Intravenous inotrope therapy in end-stage heart failure patients is non-inferior for mortality, incidence of AKI, need for RRT, and renal function for 6-month follow-up when compared to LVAD therapy. Further studies are needed to compare the effectiveness of inotropes versus LVAD implantation on renal function and outcomes over a longer time period.

Characterizing the interactions of organic nanoparticles with renal epithelial cells in vivo.

PubMed

Nair, Anil V; Keliher, Edmund J; Core, Amanda B; Brown, Dennis; Weissleder, Ralph

2015-01-01

Nanotechnology approaches are actively being pursued for drug delivery, novel diagnostics, implantable devices, and consumer products. While considerable research has been performed on the effects of these materials on targeted tumor or phagocytic cells, relatively little is known about their effects on renal cells. This becomes critical for supersmall nanoparticles (<10 nm), designed to be renally excreted. The active endocytic machinery of kidney proximal tubules avidly internalizes filtered proteins, which may also be the case for filtered nanoparticles. To test whether such interactions affect kidney function, we injected mice with either 5 nm dextran-based nanoparticles (DNP) that are similar in composition to FDA-approved materials or poly(amido amine) dendrimer nanoparticles (PNP) of comparable size. These fluorescently tagged nanoparticles were both filtered and internalized by renal tubular epithelial cells in a dose- and time-dependent fashion. The biological effects were quantitated by immunocytochemistry, measuring kidney injury markers and performing functional tests. DNP administration resulted in a dose-dependent increase in urinary output, while cellular albumin endocytosis was increased. The expression of megalin, a receptor involved in albumin uptake, was also increased, but AQP1 expression was unaffected. The effects after PNP administration were similar but additionally resulted in increased clathrin expression and increased endocytosis of dextran. We conclude that there are no major detrimental renal effects of DNP on overall kidney function, but changes in endocytosis-mediating protein expression do occur. These studies provide a framework for the testing of additional nanoparticle preparations as they become available.

Cost-Savings Analysis of Renal Scintigraphy, Stratified by Renal Function Thresholds: Mercaptoacetyltriglycine Versus Diethylene Triamine Penta-Acetic Acid.

PubMed

Parikh, Kushal R; Davenport, Matthew S; Viglianti, Benjamin L; Hubers, David; Brown, Richard K J

2016-07-01

To determine the financial implications of switching technetium (Tc)-99m mercaptoacetyltriglycine (MAG-3) to Tc-99m diethylene triamine penta-acetic acid (DTPA) at certain renal function thresholds before renal scintigraphy. Institutional review board approval was obtained, and informed consent was waived for this HIPAA-compliant, retrospective, cohort study. Consecutive adult subjects (27 inpatients; 124 outpatients) who underwent MAG-3 renal scintigraphy, in the period from July 1, 2012 to June 30, 2013, were stratified retrospectively by hypothetical serum creatinine and estimated glomerular filtration rate (eGFR) thresholds, based on pre-procedure renal function. Thresholds were used to estimate the financial effects of using MAG-3 when renal function was at or worse than a given cutoff value, and DTPA otherwise. Cost analysis was performed with consideration of raw material and preparation costs, with radiotracer costs estimated by both vendor list pricing and proprietary institutional pricing. The primary outcome was a comparison of each hypothetical threshold to the clinical reality in which all subjects received MAG-3, and the results were supported by univariate sensitivity analysis. Annual cost savings by serum creatinine threshold were as follows (threshold given in mg/dL): $17,319 if ≥1.0; $33,015 if ≥1.5; and $35,180 if ≥2.0. Annual cost savings by eGFR threshold were as follows (threshold given in mL/min/1.73 m(2)): $21,649 if ≤60; $28,414 if ≤45; and $32,744 if ≤30. Cost-savings inflection points were approximately 1.25 mg/dL (serum creatinine) and 60 mL/min/1.73m(2) (eGFR). Secondary analysis by proprietary institutional pricing revealed similar trends, and cost savings of similar magnitude. Sensitivity analysis confirmed cost savings at all tested thresholds. Reserving MAG-3 utilization for patients who have impaired renal function can impart substantial annual cost savings to a radiology department. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

The KUPNetViz: a biological network viewer for multiple -omics datasets in kidney diseases.

PubMed

Moulos, Panagiotis; Klein, Julie; Jupp, Simon; Stevens, Robert; Bascands, Jean-Loup; Schanstra, Joost P

2013-07-24

Constant technological advances have allowed scientists in biology to migrate from conventional single-omics to multi-omics experimental approaches, challenging bioinformatics to bridge this multi-tiered information. Ongoing research in renal biology is no exception. The results of large-scale and/or high throughput experiments, presenting a wealth of information on kidney disease are scattered across the web. To tackle this problem, we recently presented the KUPKB, a multi-omics data repository for renal diseases. In this article, we describe KUPNetViz, a biological graph exploration tool allowing the exploration of KUPKB data through the visualization of biomolecule interactions. KUPNetViz enables the integration of multi-layered experimental data over different species, renal locations and renal diseases to protein-protein interaction networks and allows association with biological functions, biochemical pathways and other functional elements such as miRNAs. KUPNetViz focuses on the simplicity of its usage and the clarity of resulting networks by reducing and/or automating advanced functionalities present in other biological network visualization packages. In addition, it allows the extrapolation of biomolecule interactions across different species, leading to the formulations of new plausible hypotheses, adequate experiment design and to the suggestion of novel biological mechanisms. We demonstrate the value of KUPNetViz by two usage examples: the integration of calreticulin as a key player in a larger interaction network in renal graft rejection and the novel observation of the strong association of interleukin-6 with polycystic kidney disease. The KUPNetViz is an interactive and flexible biological network visualization and exploration tool. It provides renal biologists with biological network snapshots of the complex integrated data of the KUPKB allowing the formulation of new hypotheses in a user friendly manner.

Renal function in atrial fibrillation patients switched from warfarin to a direct oral anticoagulant.

PubMed

Minhas, Anum S; Jiang, Qingmei; Gu, Xiaokui; Haymart, Brian; Kline-Rogers, Eva; Almany, Steve; Kozlowski, Jay; Krol, Gregory D; Kaatz, Scott; Froehlich, James B; Barnes, Geoffrey D

2016-11-01

All available direct oral anticoagulants (DOACs) are at least partially eliminated by the kidneys. These agents are increasingly being used as alternatives to warfarin for stroke prevention in patients with atrial fibrillation. The aim of this study was to identify changes in renal function and associated DOAC dosing implications in a multicenter cohort of atrial fibrillation patients switched from warfarin to DOAC treatment. We included all patients in the Michigan Anticoagulation Quality Improvement Initiative cohort who switched from warfarin to a DOAC with atrial fibrillation as their anticoagulant indication between 2009 and 2014, and who had at least two creatinine values. Compliance with FDA-recommended dosing based on renal function was assessed. Of the 189 patients switched from warfarin to a DOAC, 34 (18.0 %) had a baseline creatinine clearance <50 mL/min and 23 (12.2 %) experienced important fluctuations in renal function. Of these 23 patients, 6 (26.1 %) should have impacted the DOAC dosing, but only 1 patient actually received an appropriate dose adjustment. Additionally, 15 (7.9 %) of patients on DOACs had a dose change performed, but only one patient demonstrated a change in renal function to justify the dose adjustment. Most atrial fibrillation patients who switched from warfarin to a DOAC had stable renal function. However, the majority of patients who had a change in renal function did not receive the indicated dose change. As the use of DOACs expands, monitoring of renal function and appropriate dose adjustments are critical.

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

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

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

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.

Renal transplantation in patients with hepatitis C virus antibody. A long national experience

PubMed Central

Morales, Jose María; Marcén, Roberto; Andres, Amado; Domínguez-Gil, Beatriz; Campistol, Josep María; Gallego, Roberto; Gutierrez, Alex; Gentil, Miguel Angel; Oppenheimer, Federico; Samaniego, María Luz; Muñoz-Robles, Jorge; Serón, Daniel

2010-01-01

Background. Renal transplantation is the best therapy for patients with hepatitis C virus (HCV) infection with end-stage renal disease. Patient and graft survival are lower in the long term compared with HCV-negative patients. The current study evaluated the results of renal transplantation in Spain in a long period (1990–2002), focusing on graft failure. Methods. Data on the Spanish Chronic Allograft Nephropathy Study Group including 4304 renal transplant recipients, 587 of them with HCV antibody, were used to estimate graft and patient survival at 4 years with multivariate Cox models. Results. Among recipients alive with graft function 1 year post-transplant, the 4-year graft survival was 92.8% in the whole group; this was significantly better in HCV-negative vs HCV-positive patients (94.4% vs 89.5%, P < 0.005). Notably, HCV patients showed more acute rejection, a higher degree of proteinuria accompanied by a diminution of renal function, more graft biopsies and lesions of de novo glomerulonephritis and transplant glomerulopathy. Serum creatinine and proteinuria at 1 year, acute rejection, HCV positivity and systolic blood pressure were independent risk factors for graft loss. Patient survival was 96.3% in the whole group, showing a significant difference between HCV-negative vs HCV-positive patients (96.6% vs 94.5%, P < 0.05). Serum creatinine and diastolic blood pressure at 1 year, HCV positivity and recipient age were independent risk factors for patient death. Conclusions. Renal transplantation is an effective therapy for HCV-positive patients with good survival but inferior than results obtained in HCV-negative patients in the short term. Notably, HCV-associated renal damage appears early with proteinuria, elevated serum creatinine showing chronic allograft nephropathy, transplant glomerulopathy and, less frequently, HCV-associated de novo glomerulonephritis. We suggest that HCV infection should be recognized as a true risk factor for graft failure, and preventive measures could include pre-transplant therapy with interferon. PMID:20508864

Chronic kidney disease and worsening renal function in acute heart failure: different phenotypes with similar prognostic impact?

PubMed

Palazzuoli, Alberto; Lombardi, Carlo; Ruocco, Gaetano; Padeletti, Margherita; Nuti, Ranuccio; Metra, Marco; Ronco, Claudio

2016-12-01

Nearly a third of patients with acute heart failure experience concomitant renal dysfunction. This condition is often associated with increased costs of care, length of hospitalisation and high mortality. Although the clinical impact of chronic kidney disease (CKD) has been well established, the exact clinical significance of worsening renal function (WRF) during the acute and post-hospitalisation phases is not completely understood. Therefore, it is still unclear which of the common laboratory markers are able to identify WRF at an early stage. Recent studies comparing CKD with WRF showed contradictory results; this could depend on a different WRF definition, clinical characteristics, haemodynamic disorders and the presence of prior renal dysfunction in the population enrolled. The current definition of acute cardiorenal syndrome focuses on both the heart and kidney but it lacks precise laboratory marker cut-offs and a specific diagnostic approach. WRF and CKD could represent different pathophysiological mechanisms in the setting of acute heart failure; the traditional view includes reduced cardiac output with systemic and renal vasoconstriction. Nevertheless, it has become a mixed model that encompasses both forward and backward haemodynamic dysfunction. Increased central venous pressure, renal congestion with tubular obliteration, tubulo-glomerular feedback and increased abdominal pressure are all potential additional contributors. The impact of WRF on patients who experience preserved renal function and individuals affected with CKD is currently unknown. Therefore it is extremely important to understand the origins, the clinical significance and the prognostic impact of WRF on CKD. © The European Society of Cardiology 2015.

PAROTID FLUID TOTAL PROTEIN IN PATIENTS WITH UREMIA AND PROTEINURIA.

DTIC Science & Technology

Stimulated parotid fluid samples (238) were collected from 32 patients to determine if altered renal function was associated with deviations in...tubular necrosis, and 15 had normal renal function. There were no significant differences in parotid fluid protein concentration or minute secretion associated with the state of renal function. (Author)

Acute and cumulative effects of carboplatin on renal function.

PubMed Central

Sleijfer, D. T.; Smit, E. F.; Meijer, S.; Mulder, N. H.; Postmus, P. E.

1989-01-01

Carboplatin, a cisplatinum analogue, has no reported nephrotoxicity in phase I/II studies, assessed by creatinine clearance. We prospectively determined renal function in 10 untreated lung cancer patients with normal baseline renal function, treated with carboplatin 400 mg m-2 day 1 and vincristine 2 mg day 1 and 8 every 4 weeks (max. five cycles) by means of clearance studies with 125I-sodium thalamate and 131I-hippurate to determine GFR and ERPF respectively. Tubular damage was monitored by excretion of tubular enzymes and relative beta 2-microglobulin clearance. During the first course no changes in renal function were seen. After the second course a significant fall in GFR and ERPF started, ultimately leading to a median decrease in GFR of 19.0% (range 6.8-38.7%) and in ERPF of 14% (range 0-38.9%). No increases in the excretion of tubular enzymes or changes in the relative beta 2-microglobulin clearances were seen. We conclude from our data that carboplatin causes considerable loss of renal function. Monitoring renal function in patients treated with multiple courses of carboplatin is warranted. PMID:2679841

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.

Neural control of renal function: role of renal alpha adrenoceptors.

PubMed

DiBona, G F

1985-01-01

Adrenoceptors of various subtypes mediate the renal functional responses to alterations in efferent renal sympathetic nerve activity, the neural component, and renal arterial plasma catecholamine concentrations, the humoral component, of the sympathoadrenergic nervous system. Under normal physiologic as well as hypertensive conditions, the influence of the renal sympathetic nerves predominates over that of circulating plasma catecholamines. In most mammalian species, increases in efferent renal sympathetic nerve activity elicit renal vasoconstrictor responses mediated predominantly by renal vascular alpha-1 adrenoceptors, increases in renin release mediated largely by renal juxtaglomerular granular cell beta-1 adrenoceptors with involvement of renal vascular alpha-1 adrenoceptors only when renal vasoconstriction occurs, and direct increases in renal tubular sodium and water reabsorption mediated predominantly by renal tubular alpha-1 adrenoceptors. In most mammalian species, alpha-2 adrenoceptors do not play a significant role in the renal vascular or renin release responses to renal sympathoadrenergic stimulation. Although renal tubular alpha-2 adrenoceptors do not mediate the increases in renal tubular sodium and water reabsorption produced by increases in efferent renal sympathetic nerve activity, they may be involved through their inhibitory effect on adenylate cyclase in modulating the response to other hormonal agents that influence renal tubular sodium and water reabsorption via stimulation of adenylate cyclase.

Does lower limb exercise worsen renal artery hemodynamics in patients with abdominal aortic aneurysm?

PubMed

Sun, Anqiang; Tian, Xiaopeng; Zhang, Nan; Xu, Zaipin; Deng, Xiaoyan; Liu, Ming; Liu, Xiao

2015-01-01

Renal artery stenosis (RAS) and renal complications emerge in some patients after endovascular aneurysm repair (EVAR) to treat abdominal aorta aneurysm (AAA). The mechanisms for the causes of these problems are not clear. We hypothesized that for EVAR patients, lower limb exercise could negatively influence the physiology of the renal artery and the renal function, by decreasing the blood flow velocity and changing the hemodynamics in the renal arteries. To evaluate this hypothesis, pre- and post-operative models of the abdominal aorta were reconstructed based on CT images. The hemodynamic environment was numerically simulated under rest and lower limb exercise conditions. The results revealed that in the renal arteries, lower limb exercise decreased the wall shear stress (WSS), increased the oscillatory shear index (OSI) and increased the relative residence time (RRT). EVAR further enhanced these effects. Because these parameters are related to artery stenosis and atherosclerosis, this preliminary study concluded that lower limb exercise may increase the potential risk of inducing renal artery stenosis and renal complications for AAA patients. This finding could help elucidate the mechanism of renal artery stenosis and renal complications after EVAR and warn us to reconsider the management and nursing care of AAA patients.

Longer time spent in bed attempting to sleep is associated with rapid renal function decline: the Dongfeng-Tongji cohort study.

PubMed

Li, Yizhun; Yang, Liangle; Wang, Hao; Jiang, Haijing; Qiu, Gaokun; Liu, Yiyi; Xiao, Yang; Yang, Handong; Wu, Tangchun; Zhang, Xiaomin

2018-03-01

Prospective evidence on the relation between time in bed and renal dysfunction remains limited. We aimed to investigate the association of time spent in bed attempting to sleep (TSBS) with renal function decline in a middle-aged and elderly Chinese population. About 16,733 eligible participants with a mean age of 62.3 years at baseline were included. Rapid renal function decline was defined as (baseline eGFR - revisit eGFR)/years of follow-up ≥5 mL/min per 1.73 m 2 /year. A total of 1738 study participants experienced rapid renal function decline after a median 4.6-year follow-up. Logistic regression models were used for multivariate analyses. The adjusted odds ratio (OR) of rapid renal function decline was 1.18 (95% CI: 1.02, 1.37) for TSBS ≥9 h/night compared with TSBS 7 to <8 h/night. This association remained significant (OR = 1.19, 95% CI: 1.03, 1.38) after further adjustment for sleep quality, midday napping and usage of sleeping pills. Particularly, the association appeared to be prominent in individuals with diabetes. Longer TSBS (≥9 h) was independently associated with an increased risk of rapid renal function decline. Our findings emphasized the importance to have optimal TSBS. Key messages Our study firstly investigated the association between time spent in bed attempting to sleep (TSBS) and renal dysfunction in Chinese adults. Compared with individuals TSBS 7 to <8 h, individuals with TSBS ≥9 h had 19% increased risk for rapid renal function decline after adjustment for multivariate confounders. The association appeared to be prominent in individuals with diabetes.

Safety and efficacy of repaglinide in type 2 diabetic patients with and without impaired renal function.

PubMed

Hasslacher, Christoph

2003-03-01

To evaluate the influence of renal impairment on the safety and efficacy of repaglinide in type 2 diabetic patients. This multinational, open-label study comprised a 6-week run-in period, continuing prestudy antidiabetic medication, followed by a titration period (1-4 weeks) and a 3-month maintenance period. Patients with normal renal function (n = 151) and various degrees of renal impairment (n = 130) were treated with repaglinide (maximal dose of 4 mg, three times daily). Safety and efficacy assessments were performed at baseline (end of run-in) and at the end of study treatment. The type and severity of adverse events during repaglinide treatment were similar to the run-in period. The number of patients with adverse events was not significantly related to renal function during run-in or repaglinide treatment. Percentage of patients with hypoglycemic episodes increased significantly (P = 0.007) with increasing severity of renal impairment during run-in but not during repaglinide treatment (P = 0.074). Metabolic control (HbA(1c) and fasting blood glucose) with repaglinide was unchanged from that on previous antidiabetic medication. Final repaglinide dose tended to be lower for patients with severe and extreme renal impairment than for patients with less severe renal impairment or normal renal function (P = 0.032). Repaglinide has a good safety and efficacy profile in type 2 diabetic patients complicated by renal impairment and is an appropriate treatment choice, even for individuals with more severe degrees of renal impairment.

Early impact of robot-assisted partial nephrectomy on renal function as assessed by renal scintigraphy.

PubMed

Luciani, Lorenzo G; Chiodini, Stefano; Donner, Davide; Cai, Tommaso; Vattovani, Valentino; Tiscione, Daniele; Giusti, Guido; Proietti, Silvia; Chierichetti, Franca; Malossini, Gianni

2016-06-01

To measure the early impact of robot-assisted partial nephrectomy (RAPN) on renal function as assessed by renal scan (Tc 99m-DTPA), addressing the issue of risk factors for ischemic damage to the kidney. All patients undergoing RAPN for cT1 renal masses between June 2013 and May 2014 were included in this prospective study. Renal function as expressed by glomerular filtration rate (GFR) was assessed by Technetium 99m-diethylenetriaminepentaacetic acid (Tc 99m-DTPA) renal scan preoperatively and postoperatively at 1 month in every patient. A multivariable analysis was used for the determination of independent factors predictive of GFR decrease of the operated kidney. Overall, 32 patients underwent RAPN in the time interval. Median tumor size, blood loss, and ischemia time were 4 cm, 200 mL, and 24 min, respectively. Two grade III complications occurred (postoperative bleeding in the renal fossa, urinoma). The GFR of the operated kidney decreased significantly from 51.7 ± 15.1 mL/min per 1.73 m(2) preoperatively to 40, 12 ± 12.4 mL/min per 1.73 m(2) 1 month postoperatively (p = 0.001) with a decrease of 22.4 %. On multivariable analysis, only tumor size (p = 0.05) was a predictor of GFR decrease of the operated kidney. Robotic-assisted partial nephrectomy had a detectable impact on early renal function in a series of relatively large tumors and prevailing intermediate nephrometric risk. A mean decrease of 22 % of GFR as assessed by renal scan in the operated kidney was found at 1 month postoperatively. In multivariable analysis, tumor size only was a significant predictor of renal function loss.

Reduced Renal Methylarginine Metabolism Protects against Progressive Kidney Damage

PubMed Central

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

2015-01-01

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

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

PubMed

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

2016-01-01

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

Mixed compared with single-source proteins in high-protein diets affect kidney structure and function differentially in obese fa/fa Zucker rats.

PubMed

Devassy, Jessay G; Wojcik, Jennifer L; Ibrahim, Naser H M; Zahradka, Peter; Taylor, Carla G; Aukema, Harold M

2017-02-01

Questions remain regarding the potential negative effects of dietary high protein (HP) on kidney health, particularly in the context of obesity in which the risk for renal disease is already increased. To examine whether some of the variability in HP effects on kidney health may be due to source of protein, obese fa/fa Zucker rats were given HP (35% of energy from protein) diets containing either casein, soy protein, or a mixed source of animal and plant proteins for 12 weeks. Control lean and obese rats were given diets containing casein at normal protein (15% of energy from protein) levels. Body weight and blood pressure were measured, and markers of renal structural changes, damage, and function were assessed. Obesity alone resulted in mild renal changes, as evidenced by higher kidney weights, proteinuria, and glomerular volumes. In obese rats, increasing the protein level using the single, but not mixed, protein sources resulted in higher renal fibrosis compared with the lean rats. The mixed-protein HP group also had lower levels of serum monocyte chemoattractant protein-1, even though this diet further increased kidney and glomerular size. Soy and mixed-protein HP diets also resulted in a small number of damaged glomeruli, while soy compared with mixed-protein HP diet delayed the increase in blood pressure over time. Since obesity itself confers added risk of renal disease, an HP diet from mixed-protein sources that enables weight loss but has fewer risks to renal health may be advantageous.

The role of myoglobin degradation in nephrotoxicity after rhabdomyolysis.

PubMed

Zorova, Ljubava D; Pevzner, Irina B; Chupyrkina, Anastasia A; Zorov, Savva D; Silachev, Denis N; Plotnikov, Egor Y; Zorov, Dmitry B

2016-08-25

The fate of myoglobin in renal cells was explored in an animal model of rhabdomyolysis known as the pathology highly related to oxidative stress resulting in impairment of renal functioning. The working hypothesis was that the proper degradation of myoglobin in rhabdomyolytic kidney can activate the reparative processes in the tissue. We found that incubation of myoglobin with kidney cells causes its accumulation in the cytoplasm. In rhabdomyolytic rats, the level of heme and free iron in cytoplasm and mitochondria of kidney cells is remarkably increased while inhibition of proteolysis results in further elevation of myoglobin content in the renal tissue. Heme oxygenase and ferritin levels were found to be increased in the kidney tissue at rhabdomyolysis and simulating conditions performed by i/v injection of myoglobin. In addition, the level of peroxidized lipids was high in rhabdomyolytic kidney and became even higher after inhibition of proteolysis by aprotinin. Elevated levels of carbonylated proteins were also observed after rhabdomyolysis, however, if prior to induction of rhabdomyolysis the injection of myoglobin was done, the level of carbonylated proteins dropped versus unprimed kidney tissue thus affording protection to the kidney against oxidative stress. Injection of myoglobin to the rat results in impairment of renal functioning and inhibition of myoglobin degradation in the rhabdomyolytic animal aggravates acute renal failure, demonstrating that degradation of myoglobin is somehow beneficial although it may result in undesired release of free iron which can participate in toxic redox cycling. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Comparison of Effects of Low-Flow Sevoflurane and Low-Flow Desflurane Anaesthesia on Renal Functions Using Cystatin C

PubMed Central

Duymaz, Gökçen; Yağar, Seyhan; Özgök, Ayşegül

2017-01-01

Objective Numerous studies have indicated nephrotoxic effects of sevoflurane because of its two bioproducts compound A and fluoride. Cystatin C (CyC) is a more sensitive biomarker than creatinine to show early and mild changes in kidney function. We designed this prospective randomised study to compare the effects of low-flow sevoflurane anaesthesia and low-flow desflurane anaesthesia on renal functions based on CyC levels. No studies have evaluated the effects of low-flow sevoflurane anaesthesia on renal functions based on CyC levels to date. Methods Thirty American Society of Anesthesiologists (ASA) physical status I–II patients who were scheduled for urological procedures were enrolled in this study. The patients were randomly assigned to 2 groups: low-flow sevoflurane anaesthesia or low-flow desflurane anaesthesia. Serum urea, creatinine and CyC levels were measured before the operation, just before extubation and 24 h after the operation. Creatinine clearance was calculated in the first 24-h urine sample. Results There were no significant differences in serum urea, creatinine and CyC levels or 24 h creatinine clearance between the groups. Conclusion Our study demonstrates with a more sensitive biomarker, CyC, that low-flow sevoflurane anaesthesia is safe in terms of the effects on renal function. PMID:28439441

Association of ABCB1 genetic variants with renal function in Africans and in Caucasians

PubMed Central

Bochud, Murielle; Eap, Chin B; Maillard, Marc; Johnson, Toby; Vollenweider, Peter; Bovet, Pascal; Elston, Robert C; Bergmann, Sven; Beckmann, Jacques S; Waterworth, Dawn M; Mooser, Vincent; Gabriel, Anne; Burnier, Michel

2008-01-01

Background The P-glycoprotein, encoded by the ABCB1 gene, is expressed in human endothelial and mesangial cells, which contribute to control renal plasma flow and glomerular filtration rate. We investigated the association of ABCB1 variants with renal function in African and Caucasian subjects. Methods In Africans (290 subjects from 62 pedigrees), we genotyped the 2677G>T and 3435 C>T ABCB1 polymorphisms. Glomerular filtration rate (GFR) was measured using inulin clearance and effective renal plasma flow (ERPF) using para-aminohippurate clearance. In Caucasians (5382 unrelated subjects), we analyzed 30 SNPs located within and around ABCB1, using data from the Affymetrix 500 K chip. GFR was estimated using the simplified Modification of the Diet in Renal Disease (MDRD) and Cockcroft-Gault equations. Results In Africans, compared to the reference genotype (GG or CC), each copy of the 2677T and 3435T allele was associated, respectively, with: GFR higher by 10.6 ± 2.9 (P < 0.001) and 4.4 ± 2.3 (P = 0.06) mL/min; ERPF higher by 47.5 ± 11.6 (P < 0.001) and 28.1 ± 10.5 (P = 0.007) mL/min; and renal resistances lower by 0.016 ± 0.004 (P < 0.001) and 0.011 ± 0.004 (P = 0.004) mm Hg/mL/min. In Caucasians, we identified 3 polymorphisms in the ABCB1 gene that were strongly associated with all estimates of GFR (smallest P value = 0.0006, overall P = 0.014 after multiple testing correction). Conclusion Variants of the ABCB1 gene were associated with renal function in both Africans and Caucasians and may therefore confer susceptibility to nephropathy in humans. If confirmed in other studies, these results point toward a new candidate gene for nephropathy in humans. PMID:18518969

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

PubMed Central

Maric-Bilkan, Christine; Flynn, Elizabeth R.

2012-01-01

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

Revascularization to preserve renal function in patients with atherosclerotic renovascular disease.

PubMed

Novick, A C; Textor, S C; Bodie, B; Khauli, R B

1984-08-01

There are a significant number of patients with advanced atherosclerotic renovascular disease whose blood pressure is well controlled with medical therapy but in whom such vascular disease poses a grave risk to overall renal function. This article reviews current concepts regarding screening, evaluation, and selection of patients with this disease for revascularization to preserve renal function. The underlying rationale for this approach is an increasing awareness that, in selected patients, atherosclerotic renovascular disease represents a surgically correctable cause of progressive renal failure.

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.

Points to consider in renal involvement in systemic sclerosis.

PubMed

Galluccio, Felice; Müller-Ladner, Ulf; Furst, Daniel E; Khanna, Dinesh; Matucci-Cerinic, Marco

2017-09-01

This article discusses points to consider when undertaking a clinical trial to test therapy for renal involvement in SSc, not including scleroderma renal crisis. Double-blind, randomized controlled trials vs placebo or standard background therapy should be strongly considered. Inclusion criteria should consider a pre-specified range of renal functions or stratification of renal function. Gender and age limitations are probably not necessary. Concomitant medications including vasodilators, immunosuppressants and endothelin receptor antagonists and confounding illnesses such as diabetes, kidney stones, hypertension and heart failure need to be considered. A measure of renal function should be strongly considered, while time to dialysis, mortality, prevention of scleroderma renal crisis and progression of renal disease can also be considered, although they remain to be validated. Detailed, pre-planned analysis should be strongly considered and should include accounting for missing data. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Influence of impairment in renal function on the accuracy of high-sensitivity cardiac troponin T for the diagnosis of perioperative myocardial infarction after heart valve surgery.

PubMed

Cubero-Gallego, Hector; Heredia-Rodriguez, Maria; Tamayo, Eduardo

2018-03-12

We aimed to assess the influence of impairment in renal function over the high-sensitivity cardiac troponin T (hs-cTnT) accuracy to diagnose perioperative myocardial infarction (MI) after heart valve surgery. Heart valve surgery was performed in 805 patients from June 2012 to January 2016. Patients with enzymatic curves of hs-cTnT suggestive of myocardial necrosis and electrocardiogram and/or transthoracic echocardiogram criteria were identified as patients with perioperative MI. Impairment in renal function was defined as a postoperative creatinine clearance <50 ml/min at 16 h after surgery and for at least 48 h. Patients included were divided into 2 groups at 16 h: (i) patients with normal renal function (creatinine clearance >50 ml/min) and (ii) patients with impairment in renal function (creatinine clearance <50 ml/min). From a total of 805 patients undergoing heart valve surgery, 88 patients developed perioperative MI. When comparing receiver operating characteristic curves in patients with perioperative MI according to renal function, the optimal threshold of hs-cTnT at 16 h differed in patients with impairment in renal function (1303 vs 1095 pg/ml, P < 0.001). The diagnostic accuracy of hs-cTnT at 16 h was 93.4% [95% confidence interval (CI) 89.98-96.86], with an area under receiver operating characteristic curve (0.993, 95% CI 0.988-0.999 vs 0.972, 95% CI 0.952-0.992; P < 0.001). Renal function might influence in hs-cTnT levels. However, a hs-cTnT threshold of 1303 pg/ml at 16 h may be applied according to renal function to diagnose perioperative MI after cardiac surgery.

[Asymptomatic Renal Stones: Do they really Exist?].

PubMed

Seseke, S; Rudolph, R; Rebmann, U

2011-11-01

Asymptomatic renal calculi without any history of colic, hematuria or infection can be found as an incidental finding during preven-tive check-ups. The aim of our study was to eval-uate whether these stones provoke symptoms with the need for further treatment during the follow-up and whether they cause cortical defects which may consecutively affect the renal func-tion. In a prospective study we evaluated 104  patients with renal calculi. The -medical history, radiological findings and functional imaging as well as urine and blood analyses were recorded and evaluated. The influence of stone size and localisation on the development of acute stone-related symptoms, renal function and renal scarring were evaluated. Furthermore, we analysed whether localised pathological findings in radiographic or functional imaging may influence the creatinine level. The follow-up was be-tween 12 and 48  months (median: 25  months). During the study period 27 / 104 of our patients (26 %) developed symptomatic events (renal colic, hematuria, infection) in which patients with middle pole calculi with a mean -cumulative stone diameter of 9.8  mm had the -highest risk. A localised renal scarring could be found in 36.6 %. These patients had a significantly higher risk in presenting an increased creatinine level. Increasing stone size was diagnosed in 39  cases (37.5 %). Asymptomatic renal stones have to be controlled regularly in order to prevent the -patient from loss of renal function and hypertension caused by increasing stones or urinary tract infection. © Georg Thieme Verlag KG Stuttgart ˙ New York.

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.

Predictors of post-hospitalization recovery of renal function among patients with acute kidney injury requiring dialysis.

PubMed

Pajewski, Russell; Gipson, Patrick; Heung, Michael

2018-01-01

Acute kidney injury (AKI) requiring dialysis complicates 1% of all hospital admissions, and up to 30% of survivors will still require dialysis at hospital discharge. There is a paucity of data to describe the postdischarge outcomes or to guide evidence-based dialysis management of this vulnerable population. Single-center, retrospective analysis of 100 consecutive patients with AKI who survived to hospital discharge and required outpatient dialysis. Data collection included baseline characteristics, hospitalization characteristics, and outpatient dialysis treatment variables. Primary outcome was dialysis independence 90 days after discharge. Overall, 43% of patients recovered adequate renal function to discontinue dialysis, with the majority recovering within 30 days post discharge. Worse baseline renal function was associated with lower likelihood of renal recovery. In the first week postdischarge, patients with subsequent nonrecovery of renal function had greater net fluid removal (5.3 vs. 4.1 L, P = 0.037), higher ultrafiltration rates (6.0 vs. 4.7 mL/kg/h, P = 0.041) and more frequent intradialytic hypotension (24.6% vs. 9.3% with 3 or more episodes, P = 0.049) compared to patients that later recovered. A significant proportion of AKI survivors will recover renal function following discharge. Outpatient intradialytic factors may influence subsequent renal function recovery. © 2017 International Society for Hemodialysis.

Metformin and/or Clomiphene Do Not Adversely Affect Liver or Renal Function in Women with Polycystic Ovary Syndrome

PubMed Central

Aubuchon, Mira; Kunselman, Allen R.; Schlaff, William D.; Diamond, Michael P.; Coutifaris, Christos; Carson, Sandra A.; Steinkampf, Michael P.; Carr, Bruce R.; McGovern, Peter G.; Cataldo, Nicholas A.; Gosman, Gabriella G.; Nestler, John E.; Myers, Evan R.

2011-01-01

Context: Nonalcoholic fatty liver disease is common to insulin-resistant states such as polycystic ovary syndrome (PCOS). Metformin (MET) is often used to treat PCOS but information is limited as to its effects on liver function. Objective: We sought to determine the effects of MET on serum hepatic parameters in PCOS patients. Design: This was a secondary analysis of a randomized, doubled-blind trial from 2002–2004. Setting: This multi-center clinical trial was conducted in academic centers. Patients: Six hundred twenty-six infertile women with PCOS with serum liver function parameters less than twice the upper limit of normal were included. Interventions: Clomiphene citrate (n = 209), MET (n = 208), or combined (n = 209) were given for up to 6 months. Main Outcome Measure: The percent change from baseline in renal and liver function between- and within-treatment arms was assessed. Results: Renal function improved in all treatment arms with significant decreases in serum blood urea nitrogen levels (range, −14.7 to −21.3%) as well as creatinine (−4.2 to −6.9%). There were similar decreases in liver transaminase levels in the clomiphene citrate and combined arms (−10% in bilirubin, −9 to −11% in transaminases) without significant changes in the MET arm. When categorizing baseline bilirubin, aspartate aminotransferase, and alanine aminotransferase into tertiles, there were significant within-treatment arm differences between the tertiles with the highest tertile having the largest decrease from baseline regardless of treatment arm. Conclusion: Women with PCOS can safely use metformin and clomiphene even in the setting of mildly abnormal liver function parameters, and both result in improved renal function. PMID:21832111

Serum Levels of the Adipokine Progranulin Depend on Renal Function

PubMed Central

Richter, Judit; Focke, Denise; Ebert, Thomas; Kovacs, Peter; Bachmann, Anette; Lössner, Ulrike; Kralisch, Susan; Kratzsch, Jürgen; Beige, Joachim; Anders, Matthias; Bast, Ingolf; Blüher, Matthias; Stumvoll, Michael; Fasshauer, Mathias

2013-01-01

OBJECTIVE Progranulin has recently been introduced as a novel adipokine inducing insulin resistance and obesity. In the current study, we investigated renal elimination, as well as association of the adipokine with markers of the metabolic syndrome. RESEARCH DESIGN AND METHODS Progranulin serum levels were quantified by enzyme-linked immunosorbent assay and correlated to anthropometric and biochemical parameters of renal function and glucose and lipid metabolism, as well as inflammation, in 532 patients with stages 1–5 of chronic kidney disease (CKD). RESULTS Median serum progranulin levels adjusted for age, sex, and BMI were significantly different between CKD stages with highest values detectable in stage 5 (stage 1, 58.3 µg/L; stage 2, 63.0 µg/L; stage 3, 65.4 µg/L; stage 4, 68.8 µg/L; and stage 5, 90.6 µg/L). Furthermore, CKD stage was the strongest independent predictor of circulating progranulin in our cohort. In addition, high-sensitivity interleukin-6 and adiponectin remained significantly and independently correlated with the adipokine. CONCLUSIONS We demonstrate that progranulin serum levels increase with deteriorating renal function. These findings are in accordance with the hypothesis that renal clearance is a major elimination route for circulating progranulin. Furthermore, the adipokine is positively and independently associated with markers of inflammation and adiponectin. PMID:23033238

Neural control of renal function.

PubMed

Johns, Edward J; Kopp, Ulla C; DiBona, Gerald F

2011-04-01

The kidney is innervated with efferent sympathetic nerve fibers that directly contact the vasculature, the renal tubules, and the juxtaglomerular granular cells. Via specific adrenoceptors, increased efferent renal sympathetic nerve activity decreases renal blood flow and glomerular filtration rate, increases renal tubular sodium and water reabsorption, and increases renin release. Decreased efferent renal sympathetic nerve activity produces opposite functional responses. This integrated system contributes importantly to homeostatic regulation of sodium and water balance under physiological conditions and to pathological alterations in sodium and water balance in disease. The kidney contains afferent sensory nerve fibers that are located primarily in the renal pelvic wall where they sense stretch. Stretch activation of these afferent sensory nerve fibers elicits an inhibitory renorenal reflex response wherein the contralateral kidney exhibits a compensatory natriuresis and diuresis due to diminished efferent renal sympathetic nerve activity. The renorenal reflex coordinates the excretory function of the two kidneys so as to facilitate homeostatic regulation of sodium and water balance. There is a negative feedback loop in which efferent renal sympathetic nerve activity facilitates increases in afferent renal nerve activity that in turn inhibit efferent renal sympathetic nerve activity so as to avoid excess renal sodium retention. In states of renal disease or injury, there is activation of afferent sensory nerve fibers that are excitatory, leading to increased peripheral sympathetic nerve activity, vasoconstriction, and increased arterial pressure. Proof of principle studies in essential hypertensive patients demonstrate that renal denervation produces sustained decreases in arterial pressure. © 2011 American Physiological Society. Compr Physiol 1:699-729, 2011.

Ipsilateral renal function preservation after robot-assisted partial nephrectomy (RAPN): an objective analysis using mercapto-acetyltriglycine (MAG3) renal scan data and volumetric assessment.

PubMed

Zargar, Homayoun; Akca, Oktay; Autorino, Riccardo; Brandao, Luis Felipe; Laydner, Humberto; Krishnan, Jayram; Samarasekera, Dinesh; Stein, Robert J; Kaouk, Jihad H

2015-05-01

To objectively assess ipsilateral renal function (IRF) preservation and factors influencing it after robot-assisted partial nephrectomy (RAPN). Our database was queried to identify patients who had undergone RAPN from 2007 to 2013 and had complete pre- and postoperative mercapto-acetyltriglycine (MAG3) renal scan assessment. The estimated glomerular filtration rate (eGFR) for the operated kidney was calculated by multiplying the percentage of contribution from the renal scan by the total eGFR. IRF preservation was defined as a ratio of the postoperative eGFR for the operated kidney to the preoperative eGFR for the operated kidney. The percentage of total eGFR preservation was calculated in the same manner (postoperative eGFR/preoperative eGFR × 100). The amount of healthy rim of renal parenchyma removed was assessed by deducting the volume of tumour from the volume of the PN specimen assessed on pathology. Multivariable linear regression was used for analysis. In all, 99 patients were included in the analysis. The overall median (interquartile range) total eGFR preservation and IRF preservation for the operated kidney was 83.83 (75.2-94.1)% and 72 (60.3-81)%, respectively (P < 0.01). On multivariable analysis, volume of healthy rim of renal parenchyma removed, warm ischaemia time (WIT) > 30 min, body mass index (BMI) and operated kidney preoperative eGFR were predictive of IRF preservation. Using total eGFR tends to overestimate the degree of renal function preservation after RAPN. This is particularly relevant when studying factors affecting functional outcomes after nephron-sparing surgery. IRF may be a more precise assessment method in this setting. Operated kidney baseline renal function, BMI, WIT >30 min, and amount of resected healthy renal parenchyma represent the factors with a significant impact on the IRF preservation. RAPN provides significant preservation of renal function as shown by objective assessment criteria. © 2014 The Authors. BJU International © 2014 BJU International.

Recovery of Na-glucose cotransport activity after renal ischemia is impaired in mice lacking vimentin.

PubMed

Runembert, Isabelle; Couette, Sylviane; Federici, Pierre; Colucci-Guyon, Emma; Babinet, Charles; Briand, Pascale; Friedlander, Gérard; Terzi, Fabiola

2004-11-01

Vimentin, an intermediate filament protein mainly expressed in mesenchyma-derived cells, is reexpressed in renal tubular epithelial cells under many pathological conditions, characterized by intense cell proliferation. Whether vimentin reexpression is only a marker of cell dedifferentiation or is instrumental in the maintenance of cell structure and/or function is still unknown. Here, we used vimentin knockout mice (Vim(-/-)) and an experimental model of acute renal injury (30-min bilateral renal ischemia) to explore the role of vimentin. Bilateral renal ischemia induced an initial phase of acute tubular necrosis that did not require vimentin and was similar, in terms of morphological and functional changes, in Vim(+/+) and Vim(-/-) mice. However, vimentin was essential to favor Na-glucose cotransporter 1 localization to brush-border membranes and to restore Na-glucose cotransport activity in regenerating tubular cells. We show that the effect of vimentin inactivation is specific and results in persistent glucosuria. We propose that vimentin is part of a structural network that favors carrier localization to plasma membranes to restore transport activity in injured kidneys.

Long-term results with renal autotransplantation for ureteral replacement.

PubMed

Bodie, B; Novick, A C; Rose, M; Straffon, R A

1986-12-01

From 1970 to 1984 renal autotransplantation was performed on 23 patients to replace all or a major portion of the ureter. The conditions necessitating ureteral replacement were postoperative ureteral injury in 16 cases, recurrent renal colic in 4, urinary undiversion in 2 and an atonic ureter in 1. Six patients presented with a solitary kidney and 1 underwent staged bilateral autotransplantation. After autotransplantation urinary continuity was restored by ureteroneocystostomy in 11 patients, pyelovesicostomy in 7, ureteroureterostomy in 2, pyeloureterostomy in 2 and ureterosigmoidostomy in 1. Postoperatively, there was no mortality and all but 1 of the autotransplanted kidneys functioned immediately. Two kidneys required removal postoperatively owing to bleeding. Currently, 20 patients are alive with functioning renal autotransplants at intervals of 1.5 to 14 years. The current serum creatinine level in these patients ranges from 1.1 to 2.2 mg. per dl., which in each case is improved or stable compared to the preoperative determination. Only 1 patient has experienced chronic bacteriuria. We conclude that renal autotransplantation provides excellent long-term treatment for patients who require ureteral replacement.

Successful renal transplantation from a brain-dead deceased donor with head injury, disseminated intravascular coagulation and deranged renal functions.

PubMed

Ghuge, P P; Kute, V B; Vanikar, A V; Gumber, M R; Gera, D N; Patel, H V; Shah, P R; Modi, P R; Shah, V R; Trivedi, H L

2013-11-01

Deceased donors (DDs) with the brain death due to head injury are the major source of organs for transplantation. The incidence of post-head injury disseminated intravascular coagulation (DIC) ranges from 24% to 50%. Many centers do not accept organs from donors with DIC due to increased risk of primary graft non-function and/or high chances of morbidity/mortality. We performed two successful renal transplants from a DD with head injury with DIC and deranged renal function. One of the recipients developed transient thrombocytopenia, but there was no evidence of DIC or delayed graft functions in either of the recipients. Over a follow-up of 1 month, both are doing well with stable graft function and hematological profile. Thus, a carefully selected DD with severe DIC even with deranged renal function is not a contraindication for organ donation if other risk factors for primary non-function are excluded. This approach will also help in overcoming organ shortage.

Renal function improvement in liver transplant recipients after early everolimus conversion: A clinical practice cohort study in Spain.

PubMed

Bilbao, Itxarone; Salcedo, Magdalena; Gómez, Miguel Angel; Jimenez, Carlos; Castroagudín, Javier; Fabregat, Joan; Almohalla, Carolina; Herrero, Ignacio; Cuervas-Mons, Valentín; Otero, Alejandra; Rubín, Angel; Miras, Manuel; Rodrigo, Juan; Serrano, Trinidad; Crespo, Gonzalo; De la Mata, Manuel; Bustamante, Javier; Gonzalez-Dieguez, M Luisa; Moreno, Antonia; Narvaez, Isidoro; Guilera, Magda

2015-08-01

A national, multicenter, retrospective study was conducted to assess the results obtained for liver transplant recipients with conversion to everolimus in daily practice. The study included 477 recipients (481 transplantations). Indications for conversion to everolimus were renal dysfunction (32.6% of cases), hepatocellular carcinoma (HCC; 30.2%; prophylactic treatment for 68.9%), and de novo malignancy (29.7%). The median time from transplantation to conversion to everolimus was 68.7 months for de novo malignancy, 23.8 months for renal dysfunction, and 7.1 months for HCC and other indications. During the first year of treatment, mean everolimus trough levels were 5.4 (standard deviation [SD], 2.7) ng/mL and doses remained stable (1.5 mg/day) from the first month after conversion. An everolimus monotherapy regimen was followed by 28.5% of patients at 12 months. Patients with renal dysfunction showed a glomerular filtration rate (4-variable Modification of Diet in Renal Disease) increase of 10.9 mL (baseline mean, 45.8 [SD, 25.3] versus 57.6 [SD, 27.6] mL/minute/1.73 m(2) ) at 3 months after everolimus initiation (P < 0.001), and 6.8 mL at 12 months. Improvement in renal function was higher in patients with early conversion (<1 year). Adverse events were the primary reason for discontinuation in 11.2% of cases. The probability of survival at 3 years after conversion to everolimus was 83.0%, 71.1%, and 59.5% for the renal dysfunction, de novo malignancy, and HCC groups, respectively. Everolimus is a viable option for the treatment of renal dysfunction, and earlier conversion is associated with better recovery of renal function. Prospective studies are needed to confirm advantages in patients with malignancy. © 2015 American Association for the Study of Liver Diseases.

Essentials of equine renal and urinary tract physiology.

PubMed

Toribio, Ramiro E

2007-12-01

Knowledge of urinary tract anatomy and the numerous functions of the kidney in regulating fluids, electrolytes, acid-base balance, and waste products improves the ability of the clinician to diagnose, treat, and make appropriate recommendations for the management of the horse with renal disease. Several conditions can directly or indirectly affect renal function on a temporary or permanent basis. Endogenous and exogenous compounds (eg, drugs, toxins, hemoglobin) alone or in combination with inappropriate renal blood flow can promote or exacerbate renal disease.

Multiple Low-Dose Radiation Prevents Type 2 Diabetes-Induced Renal Damage through Attenuation of Dyslipidemia and Insulin Resistance and Subsequent Renal Inflammation and Oxidative Stress

PubMed Central

Shao, Minglong; Lu, Xuemian; Cong, Weitao; Xing, Xiao; Tan, Yi; Li, Yunqian; Li, Xiaokun; Jin, Litai; Wang, Xiaojie; Dong, Juancong; Jin, Shunzi; Zhang, Chi; Cai, Lu

2014-01-01

Background Dyslipidemia and lipotoxicity-induced insulin resistance, inflammation and oxidative stress are the key pathogeneses of renal damage in type 2 diabetes. Increasing evidence shows that whole-body low dose radiation (LDR) plays a critical role in attenuating insulin resistance, inflammation and oxidative stress. Objective The aims of the present study were to investigate whether LDR can prevent type 2 diabetes-induced renal damage and the underlying mechanisms. Methods Mice were fed with a high-fat diet (HFD, 40% of calories from fat) for 12 weeks to induce obesity followed by a single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg) to develop a type 2 diabetic mouse model. The mice were exposed to LDR at different doses (25, 50 and 75 mGy) for 4 or 8 weeks along with HFD treatment. At each time-point, the kidney weight, renal function, blood glucose level and insulin resistance were examined. The pathological changes, renal lipid profiles, inflammation, oxidative stress and fibrosis were also measured. Results HFD/STZ-induced type 2 diabetic mice exhibited severe pathological changes in the kidney and renal dysfunction. Exposure of the mice to LDR for 4 weeks, especially at 50 and 75 mGy, significantly improved lipid profiles, insulin sensitivity and protein kinase B activation, meanwhile, attenuated inflammation and oxidative stress in the diabetic kidney. The LDR-induced anti-oxidative effect was associated with up-regulation of renal nuclear factor E2-related factor-2 (Nrf-2) expression and function. However, the above beneficial effects were weakened once LDR treatment was extended to 8 weeks. Conclusion These results suggest that LDR exposure significantly prevented type 2 diabetes-induced kidney injury characterized by renal dysfunction and pathological changes. The protective mechanisms of LDR are complicated but may be mainly attributed to the attenuation of dyslipidemia and the subsequent lipotoxicity-induced insulin resistance, inflammation and oxidative stress. PMID:24651118

A unified pathogenesis for kidney diseases, including genetic diseases and cancers, by the protein-homeostasis-system hypothesis.

PubMed

Lee, Kyung-Yil

2017-06-01

Every cell of an organism is separated and protected by a cell membrane. It is proposed that harmony between intercellular communication and the health of an organism is controlled by a system, designated the protein-homeostasis-system (PHS). Kidneys consist of a variety of types of renal cells, each with its own characteristic cell-receptor interactions and producing characteristic proteins. A functional union of these renal cells can be determined by various renal function tests, and harmonious intercellular communication is essential for the healthy state of the host. Injury to a kind of renal cells can impair renal function and induce an imbalance in total body health. Every acute or chronic renal disease has unknown etiologic substances that are responsible for renal cell injury at the molecular level. The immune/repair system of the host should control the etiologic substances acting against renal cells; if this system fails, the disease progresses to end stage renal disease. Each renal disease has its characteristic pathologic lesions where immune cells and immune proteins, such as immunoglobulins and complements, are infiltrated. These immune cells and immune proteins may control the etiologic substances involved in renal pathologic lesions. Also, genetic renal diseases and cancers may originate from a protein deficiency or malfunctioning protein under the PHS. A unified pathogenesis for renal diseases, including acute glomerulonephritis, idiopathic nephrotic syndrome, immunoglobulin A nephropathy, genetic renal diseases such as Alport syndrome, and malignancies such as Wilms tumor and renal cell carcinoma, is proposed using the PHS hypothesis.

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

PubMed

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

2017-01-01

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

Kidney injury after sodium phosphate solution beyond the acute renal failure.

PubMed

Fernández-Juárez, Gema; Parejo, Leticia; Villacorta, Javier; Tato, Ana; Cazar, Ramiro; Guerrero, Carmen; Marin, Isabel Martinez; Ocaña, Javier; Mendez-Abreu, Angel; López, Katia; Gruss, Enrique; Gallego, Eduardo

2016-01-01

Screening colonoscopy with polipectomy reduces colonorectal cancer incidence and mortality. An adequate bowel cleansing is one of the keys to achieving best results with this technique. Oral sodium phosphate solution (OSP) had a widespread use in the 90s decade. Its efficacy was similar to polyethylene glycol (PEG) solution, but with less cost and convenient administration. Series of patients with acute renal failure due to OSP use have been reported. However, large cohorts of patients found no difference in the incidence of renal damage between these two solutions. From 2006 to 2009 we identified twelve cases of phosphate nephropathy after colonoscopy prepared with OSP. All patients were followed up to six months. All patients had received just a single dose. We analyzed 12 cases with phosphate nephropathy; three patients debuted with AKI and nine patients had chronic renal injury. Four cases were confirmed with renal biopsy. One patient with AKI needed hemodialysis at diagnosis without subsequent recovery. Two patients (both with chronic damage) fully recovered their previous renal function. The remaining patients (nine) had an average loss of estimated glomerular filtration rate of 24ml/min/1.73m(2). The use of OSP can lead to both acute and chronic renal damage. However, chronic injury was the most common pattern. Both forms of presentation imply a significant and irreversible loss of renal function. Further studies analyzing renal damage secondary to bowel cleaning should consider these two different patterns of injury. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

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

PubMed

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

2015-10-01

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

The use of fibrous, supramolecular membranes and human tubular cells for renal epithelial tissue engineering: towards a suitable membrane for a bioartificial kidney.

PubMed

Dankers, Patricia Y W; Boomker, Jasper M; Huizinga-van der Vlag, Ali; Smedts, Frank M M; Harmsen, Martin C; van Luyn, Marja J A

2010-11-10

A bioartificial kidney, which is composed of a membrane cartridge with renal epithelial cells, can substitute important kidney functions in patients with renal failure. A particular challenge is the maintenance of monolayer integrity and specialized renal epithelial cell functions ex vivo. We hypothesized that this can be improved by electro-spun, supramolecular polymer membranes which show clear benefits in ease of processability. We found that after 7 d, in comparison to conventional microporous membranes, renal tubular cells cultured on top of our fibrous supramolecular membranes formed polarized monolayers, which is prerequisite for a well-functioning bioartificial kidney. In future, these supramolecular membranes allow for incorporation of peptides that may increase cell function even further.

Diagnostic value and biological significance of antibody-coated bacteria in urine

PubMed Central

Mengoli, C; Arosio, E; Bonato, D; Spiazzi, G; Pancera, P; Montesi, G; Lechi, A; Scuro, LA

1980-01-01

The incidence of antibody-coated bacteria (ACB) in the urinary sediments as an indication of the site of urinary tract infections (UTI) was investigated in 103 adult subjects with persistent bacteriuria by means of a direct immunofluorescence technique. ACB were found in 49 of 58 (84·5%) subjects with long-standing upper urinary tract obstruction and in 5 of 45 (11·1%) with lower UTI; this difference was statistically significant (X2 = 51·79; P<0·001). The group with upper UTI was further subdivided according to renal function (patients with renal insufficiency had both bilateral obstruction and bilateral renal damage); 21 positive results were obtained in 27 (77·8%) patients with normal renal function, whereas 28 positive cases were observed among 31 (90·3%) patients with chronic renal insufficiency. Thus the degree of renal involvement also seemed to influence the outcome of the test. Within the group of lower UTI, a higher rate of `false-positive' results was obtained in 14 patients with symptomatic long-standing infection (21·4%) than in 31 subjects with asymptomatic bacteriuria (6·4%). The three major immunoglobulin classes and the secretory component were studied in 42 cases. Of these, 29 were found to be positive for ACB. The constant presence of IgA and secretory component on the surface of ACB suggests that the secretory immune system plays an important role in UTI. ImagesFig. 1 PMID:6988464

Diabetic rats present higher urinary loss of proteins and lower renal expression of megalin, cubilin, ClC-5, and CFTR.

PubMed

Figueira, Miriam F; Castiglione, Raquel C; de Lemos Barbosa, Carolina M; Ornellas, Felipe M; da Silva Feltran, Geórgia; Morales, Marcelo M; da Fonseca, Rodrigo N; de Souza-Menezes, Jackson

2017-07-01

Diabetic nephropathy (DN) occurs in around 40% of those with diabetes. Proteinuria is the main characteristic of DN and develops as a result of increased permeability of the glomerulus capillary wall and/or decreased proximal tubule endocytosis. The goal of this work was to evaluate renal function and the expression of megalin, cubilin, CFTR (cystic fibrosis transmembrane conductance regulator), and ClC-5 in the proximal tubule and renal cortex of rats with type 1 diabetes. Male Wistar rats were randomly assigned to control (CTRL) and diabetic (DM) groups for 4 weeks. Renal function was assessed in 24-h urine sample by calculating clearance and fractional excretion of solutes. The RNA and protein contents of ClC-5, CFTR, megalin, and cubilin were determined in the renal proximal tubule and cortex using real-time polymerase chain reaction and western blotting techniques, respectively. The results showed higher creatinine clearance and higher urinary excretion of proteins, albumin, and transferrin in the DM group than in the CTRL group. Furthermore, the renal cortex and proximal tubule of diabetic animals showed downregulation of megalin, cubilin, ClC-5, and CFTR, critical components of the endocytic apparatus. These data suggest dysfunction in proximal tubule low-molecular-weight endocytosis and protein glomerulus filtration in the kidney of diabetic rats. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

[Position paper on the results of Symplicity HTN-3 trial. Grupo de estudio de la hipertensión arterial resistente].

PubMed

Azpiri-López, José Ramón; Assad-Morell, José Luis; Ponce de León-Martínez, Enrique; Monreal-Puente, Rogelio; Dávila-Bortoni, Adrián; Vázquez-Díaz, Luis Alberto; Treviño-Frutos, Ramón Javier; Barrera-Oranday, Félix; Del Angel-Soto, Juan Gustavo; Martínez, José Guadalupe; Arellano-Torres, Marcelo

2015-01-01

Renal artery denervation has shown to be an effective treatment for resistant hypertension. Symplicity HTN 1 and 2 trials showed in small and uncontrolled groups, significant systolic blood pressure reductions down to 30 mm Hg. Symplicity HTN-3, a double blind, randomized, placebo controlled clinical trial shaded this initial enthusiasm. Surprisingly, their results showed that renal denervation has a similar effect to placebo. Pre-specified subgroup analysis showed that non-black race individuals, younger than 65 years and with normal renal function, had a statistically significant systolic blood pressure decrease. This manuscript critically appraises the Symplicity HTN-3 trial, proposing possible explanations for the results. Also declares our group position and future actions regarding renal denervation. Copyright © 2014 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

Pharmacokinetic/Pharmacodynamic Modeling and Simulation of Cefiderocol, a Parenteral Siderophore Cephalosporin, for Dose Adjustment Based on Renal Function.

PubMed

Katsube, Takayuki; Wajima, Toshihiro; Ishibashi, Toru; Arjona Ferreira, Juan Camilo; Echols, Roger

2017-01-01

Cefiderocol, a novel parenteral siderophore cephalosporin, exhibits potent efficacy against most Gram-negative bacteria, including carbapenem-resistant strains. Since cefiderocol is excreted primarily via the kidneys, this study was conducted to develop a population pharmacokinetics (PK) model to determine dose adjustment based on renal function. Population PK models were developed based on data for cefiderocol concentrations in plasma, urine, and dialysate with a nonlinear mixed-effects model approach. Monte-Carlo simulations were conducted to calculate the probability of target attainment (PTA) of fraction of time during the dosing interval where the free drug concentration in plasma exceeds the MIC (T f >MIC ) for an MIC range of 0.25 to 16 μg/ml. For the simulations, dose regimens were selected to compare cefiderocol exposure among groups with different levels of renal function. The developed models well described the PK of cefiderocol for each renal function group. A dose of 2 g every 8 h with 3-h infusions provided >90% PTA for 75% T f >MIC for an MIC of ≤4 μg/ml for patients with normal renal function, while a more frequent dose (every 6 h) could be used for patients with augmented renal function. A reduced dose and/or extended dosing interval was selected for patients with impaired renal function. A supplemental dose immediately after intermittent hemodialysis was proposed for patients requiring intermittent hemodialysis. The PK of cefiderocol could be adequately modeled, and the modeling-and-simulation approach suggested dose regimens based on renal function, ensuring drug exposure with adequate bactericidal effect. Copyright © 2016 American Society for Microbiology.

Effect of renal function status on the prognostic value of heart rate in acute ischemic stroke patients.

PubMed

Zhu, Zhengbao; Zhong, Chongke; Xu, Tian; Wang, Aili; Peng, Yanbo; Xu, Tan; Peng, Hao; Chen, Chung-Shiuan; Wang, Jinchao; Ju, Zhong; Li, Qunwei; Geng, Deqin; Sun, Yingxian; Du, Qingjuan; Li, Yongqiu; Chen, Jing; Zhang, Yonghong; He, Jiang

2017-08-01

The association between heart rate and prognosis of ischemic stroke remains debatable, and whether renal function status influences the relationship between them is still not elucidated. A total of 3923 ischemic stroke patients were included in this prospective multicenter study from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). The primary outcome was a combination of death and major disability (modified Rankin Scale score ≥3) at 3 months after stroke. Secondary outcomes were, separately, death and major disability. The association between heart rate tertiles and primary outcome was appreciably modified by renal function status (p interaction  = 0.037). After multivariate adjustment, high heart rate was associated with increased risk of primary outcome in patients with abnormal renal function (odds ratio, 1.61; 95% confidence interval, 1.02-2.54; p trend  = 0.039) but not in patients with normal renal function (odds ratio, 0.96; 95% confidence interval, 0.75-1.23; p trend  = 0.741), when two extreme tertiles were compared. Each 10 bpm increase of heart rate was associated with 21% (95% CI: 1%-44%) increased risk of primary outcome, and a linear association between heart rate and risk of primary outcome was observed among patients with abnormal renal function (p for linearity = 0.002). High heart rate may be merely a strong predictor of poor prognosis in acute ischemic stroke patients with abnormal renal function, suggesting that heart rate reduction should be applied to ischemic stroke patients with abnormal renal function to improve their prognosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Meta-analysis of safety and efficacy for direct oral anticoagulation treatment of non-valvular atrial fibrillation in relation to renal function.

PubMed

Zou, Rongjun; Tao, Jun; Shi, Wanting; Yang, Minglei; Li, Hongmu; Lin, Xifeng; Yang, Songran; Hua, Ping

2017-12-01

We performed a meta-analysis of the safety and efficacy of anticoagulation treatment for atrial fibrillation (AF) in relation to renal function. We also examined the change in estimated glomerular filtration rate (eGFR) from baseline and compared the outcomes for patients with stable and worsening renal function. We selected studies that used randomized controlled trials in which outcomes for direct oral anticoagulants (DOACs) (dabigatran, rivaroxaban, apixaban, or edoxaban) were compared with those for warfarin in AF patients with normal, mild or moderate renal function, except the severe one (creatinine clearance<30). We assessed five clinical trials, involving 72,608 patients. Pooled analysis indicated that the risk of stroke was lower for DOACs than for warfarin among patients with mild renal impairment (Risk ratio, 0.79; 95% confidence interval, 0.68-0.91) and moderate renal impairment (0.80, 0.69-0.92). No major differences were found in patients with normal renal function. Additionally, DOACs were associated with fewer major bleeds among patients with normal (0.77, 0.70-0.84), mild (0.86, 0.77-0.95), and moderate renal impairment (0.73, 0.65-0.82). Among those treated with DOACs, a lower dosage was associated with lower risk of major bleeding (0.75, 0.68-0.83) and higher risk of stroke or systemic embolism (1.28, 1.12-1.47). Further, DOACs tended to be associated with a lower estimated glomerular filtration rate (eGFR) than warfarin even after 30months. Finally, we found significant differences in the risk of stroke (2.09, 1.64-2.68) and major bleeding (2.01, 1.66-2.42) between patients with stable and worsening renal function. DOACs have a greater clinical benefit than warfarin with respect to renal function. They are associated with a comparatively lower risk of stroke and major bleeding, as well lower eGFR. This suggests these agents are a better choice in patients with renal disease. Copyright © 2017. Published by Elsevier Ltd.

Biomarkers of Renal Tumor Burden and Progression in TSC

DTIC Science & Technology

2012-09-01

code) Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 Biomarkers of Renal Tumor Burden and Progression in TSC Dr. Elahna Paul 1...appearance and growth rates) and renal function parameters (e.g. blood pressure, serum chemistries, urinalysis and urine chemistries). (2) Measure...and renal function parameters (e.g. blood pressure, serum chemistries, urinalysis and urine chemistries). (2) Measure soluble growth factors

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

PubMed

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

2017-01-01

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

Association between renal function and cardiovascular structure and function in heart failure with preserved ejection fraction.

PubMed

Gori, Mauro; Senni, Michele; Gupta, Deepak K; Charytan, David M; Kraigher-Krainer, Elisabeth; Pieske, Burkert; Claggett, Brian; Shah, Amil M; Santos, Angela B S; Zile, Michael R; Voors, Adriaan A; McMurray, John J V; Packer, Milton; Bransford, Toni; Lefkowitz, Martin; Solomon, Scott D

2014-12-21

Renal dysfunction is a common comorbidity in patients with heart failure and preserved ejection fraction (HFpEF). We sought to determine whether renal dysfunction was associated with measures of cardiovascular structure/function in patients with HFpEF. We studied 217 participants from the PARAMOUNT study with HFpEF who had echocardiography and measures of kidney function. We evaluated the relationships between renal dysfunction [estimated glomerular filtration rate (eGFR) >30 and <60 mL/min/1.73 m(2) and/or albuminuria] and cardiovascular structure/function. The mean age of the study population was 71 years, 55% were women, 94% hypertensive, and 40% diabetic. Impairment of at least one parameter of kidney function was present in 62% of patients (16% only albuminuria, 23% only low eGFR, 23% both). Renal dysfunction was associated with abnormal LV geometry (defined as concentric hypertrophy, or eccentric hypertrophy, or concentric remodelling) (adjusted P = 0.048), lower midwall fractional shortening (MWFS) (P = 0.009), and higher NT-proBNP (P = 0.006). Compared with patients without renal dysfunction, those with low eGFR and no albuminuria had a higher prevalence of abnormal LV geometry (P = 0.032) and lower MWFS (P < 0.01), as opposed to those with only albuminuria. Conversely, albuminuria alone was associated with greater LV dimensions (P < 0.05). Patients with combined renal impairment had mixed abnormalities (higher LV wall thicknesses, NT-proBNP; lower MWFS). Renal dysfunction, as determined by both eGFR and albuminuria, is highly prevalent in HFpEF, and associated with cardiac remodelling and subtle systolic dysfunction. The observed differences in cardiac structure/function between each type of renal damage suggest that both parameters of kidney function might play a distinct role in HFpEF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Niacin improves renal lipid metabolism and slows progression in chronic kidney disease.

PubMed

Cho, Kyu-hyang; Kim, Hyun-ju; Kamanna, Vaijinath S; Vaziri, Nosratola D

2010-01-01

Mounting evidence points to lipid accumulation in the diseased kidney and its contribution to progression of nephropathy. We recently found heavy lipid accumulation and marked dysregulation of lipid metabolism in the remnant kidneys of rats with chronic renal failure (CRF). Present study sought to determine efficacy of niacin supplementation on renal tissue lipid metabolism in CRF. Kidney function, lipid content, and expression of molecules involved in cholesterol and fatty acid metabolism were determined in untreated CRF (5/6 nephrectomized), niacin-treated CRF (50 mg/kg/day in drinking water for 12 weeks) and control rats. CRF resulted in hypertension, proteinuria, renal tissue lipid accumulation, up-regulation of scavenger receptor A1 (SR-A1), acyl-CoA cholesterol acyltransferase-1 (ACAT1), carbohydrate-responsive element binding protein (ChREBP), fatty acid synthase (FAS), acyl-CoA carboxylase (ACC), liver X receptor (LXR), ATP binding cassette (ABC) A-1, ABCG-1, and SR-B1 and down-regulation of sterol responsive element binding protein-1 (SREBP-1), SREBP-2, HMG-CoA reductase, PPAR-alpha, fatty acid binding protein (L-FABP), and CPT1A. Niacin therapy attenuated hypertension, proteinuria, and tubulo-interstitial injury, reduced renal tissue lipids, CD36, ChREBP, LXR, ABCA-1, ABCG-1, and SR-B1 abundance and raised PPAR-alpha and L-FABP. Niacin administration improves renal tissue lipid metabolism and renal function and structure in experimental CRF.

Acute and chronic effects of the insecticide endrin on renal function and renal hemodynamics.

DOT National Transportation Integrated Search

1963-10-01

Chronic and acute effects of the insecticide endrin on renal function were studied in dogs. Animals were exposed to endrin chronically by intramuscular injection and acutely by intravenous infusion. In acute studies dogs developed systemic hypertensi...

Reduced Renal Methylarginine Metabolism Protects against Progressive Kidney Damage.

PubMed

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

2015-12-01

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

Tracing the evolutionary origins of insect renal function.

PubMed

Halberg, Kenneth A; Terhzaz, Selim; Cabrero, Pablo; Davies, Shireen A; Dow, Julian A T

2015-04-21

Knowledge on neuropeptide receptor systems is integral to understanding animal physiology. Yet, obtaining general insight into neuropeptide signalling in a clade as biodiverse as the insects is problematic. Here we apply fluorescent analogues of three key insect neuropeptides to map renal tissue architecture across systematically chosen representatives of the major insect Orders, to provide an unprecedented overview of insect renal function and control. In endopterygote insects, such as Drosophila, two distinct transporting cell types receive separate neuropeptide signals, whereas in the ancestral exopterygotes, a single, general cell type mediates all signals. Intriguingly, the largest insect Order Coleoptera (beetles) has evolved a unique approach, in which only a small fraction of cells are targets for neuropeptide action. In addition to demonstrating a universal utility of this technology, our results reveal not only a generality of signalling by the evolutionarily ancient neuropeptide families but also a clear functional separation of the types of cells that mediate the signal.

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

PubMed

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

2018-04-14

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

Both in- and out-hospital worsening of renal function predict outcome in patients with heart failure: results from the Coordinating Study Evaluating Outcome of Advising and Counseling in Heart Failure (COACH).

PubMed

Damman, Kevin; Jaarsma, Tiny; Voors, Adriaan A; Navis, Gerjan; Hillege, Hans L; van Veldhuisen, Dirk J

2009-09-01

The effect of worsening renal function (WRF) after discharge on outcome in patients with heart failure is unknown. We assessed estimated glomerular filtration rate (eGFR) and serum creatinine at admission, discharge, and 6 and 12 months after discharge, in 1023 heart failure patients. Worsening renal function was defined as an increase in serum creatinine of >26.5 micromol/L and >25%. The primary endpoint was a composite of all-cause mortality and heart failure admissions. The mean age of patients was 71 +/- 11 years, and 62% was male. Mean eGFR at admission was 55 +/- 21 mL/min/1.73 m(2). In-hospital WRF occurred in 11% of patients, while 16 and 9% experienced WRF from 0 to 6, and 6 to 12 months after discharge, respectively. In multivariate landmark analysis, WRF at any point in time was associated with a higher incidence of the primary endpoint: hazard ratio (HR) 1.63 (1.10-2.40), P = 0.014 for in-hospital WRF, HR 2.06 (1.13-3.74), P = 0.018 for WRF between 0-6 months, and HR 5.03 (2.13-11.88), P < 0.001 for WRF between 6-12 months. Both in- and out-hospital worsening of renal function are independently related to poor prognosis in patients with heart failure, suggesting that renal function in heart failure patients should be monitored long after discharge.

A new contrast media for functional MR urography: Gd-MAG3.

PubMed

Algin, Oktay

2011-07-01

Tc-99m-MAG3 (tubular agent) provides high imaging quality and extraction efficiency; and has become one of the most widely used agent for scintigraphic examinations of urinary system pathologies and renal transplants. Recently, it was reported that functional magnetic resonance urography (FMRU) can be sufficient in detection of urinary tract obstruction, renal artery stenosis, calculation of kidney functions and evaluation of renal transplants. However the pharmacokinetics of magnetic resonance (MR) contrast-media used in FMRU and Tc-99m-MAG3 differs from each other. This may cause discordant results between the FMRU and most of the scintigraphic studies. To our knowledge, there is no contrast-media which is specific for FMRU. A kidney specific contrast material can be developed for FMRU studies as well. MAG3 is a good candidate for this chelation. In conclusion, MR imaging (MRI) will be the most useful and important technique for morphologic-functional evaluation of urinary system. FMRU examinations performed with MAG3 chelated gadolinium can be sufficient for the complete evaluation of urinary tract even in patients with impaired renal functions ("all in one MRI"). MRI has some important advantages including no risk for radiation exposure, high temporal and spatial resolution, no need for nephrotoxic contrast agent; besides being a fast and feasible technique. Gadolinium-containing contrast agents may cause a life-threatening adverse reaction known as nephrogenic systemic fibrosis in patients with severe renal impairment, but Gd-MAG3 may reduce the risk of nephrogenic systemic fibrosis due to its higher extraction capacity and other features. Copyright © 2011 Elsevier Ltd. All rights reserved.

Transjugular intrahepatic portosystemic shunt: impact on systemic hemodynamics and renal and cardiac function in patients with cirrhosis.

PubMed

Busk, Troels M; Bendtsen, Flemming; Poulsen, Jørgen H; Clemmesen, Jens O; Larsen, Fin S; Goetze, Jens P; Iversen, Jens S; Jensen, Magnus T; Møgelvang, Rasmus; Pedersen, Erling B; Bech, Jesper N; Møller, Søren

2018-02-01

Transjugular intrahepatic portosystemic shunt (TIPS) alleviates portal hypertension and possibly increases central blood volume (CBV). Moreover, renal function often improves; however, its effects on cardiac function are unclear. The aims of our study were to examine the effects of TIPS on hemodynamics and renal and cardiac function in patients with cirrhosis. In 25 cirrhotic patients, we analyzed systemic, cardiac, and splanchnic hemodynamics by catheterization of the liver veins and right heart chambers before and 1 wk after TIPS. Additionally, we measured renal and cardiac markers and performed advanced echocardiography before, 1 wk after, and 4 mo after TIPS. CBV increased significantly after TIPS (+4.6%, P < 0.05). Cardiac output (CO) increased (+15.3%, P < 0.005) due to an increase in stroke volume (SV) (+11.1%, P < 0.005), whereas heart rate (HR) was initially unchanged. Cardiopulmonary pressures increased after TIPS, whereas copeptin, a marker of vasopressin, decreased (-18%, P < 0.005) and proatrial natriuretic peptide increased (+52%, P < 0.0005) 1 wk after TIPS and returned to baseline 4 mo after TIPS. Plasma neutrophil gelatinase-associated lipocalin, renin, aldosterone, and serum creatinine decreased after TIPS (-36%, P < 0.005; -65%, P < 0.05; -90%, P < 0.005; and -13%, P < 0.005, respectively). Echocardiography revealed subtle changes in cardiac function after TIPS, although these were within the normal range. TIPS increases CBV by increasing CO and SV, whereas HR is initially unaltered. These results indicate an inability to increase the heart rate in response to a hemodynamic challenge that only partially increases CBV after TIPS. These changes, however, are sufficient for improving renal function. NEW & NOTEWORTHY For the first time, we have combined advanced techniques to study the integrated effects of transjugular intrahepatic portosystemic shunt (TIPS) in cirrhosis. We showed that TIPS increases central blood volume (CBV) through improved cardiac inotropy. Advanced echocardiography demonstrated that myocardial function was unaffected by the dramatic increase in preload after TIPS. Finally, renal function improved due to the increase in CBV. Recognition of these physiological changes significantly contributes to our clinical understanding of TIPS.

Evaluation of renal function change during first-line tyrosine kinase inhibitor therapy for metastatic renal cell carcinoma.

PubMed

Ishihara, Hiroki; Kondo, Tsunenori; Fukuda, Hironori; Yoshida, Kazuhiko; Omae, Kenji; Takagi, Toshio; Iizuka, Junpei; Kobayashi, Hirohito; Tanabe, Kazunari

2017-12-01

The change in renal function induced by first-line tyrosine kinase inhibitor therapy for metastatic renal cell carcinoma remains unclear. One hundred and thirty-four patients were evaluated. Sunitinib (SU) and sorafenib (SO) were administered to 91 (67.9%) and 43 (32.1%) patients, respectively. The change in estimated glomerular filtration rate (ΔeGFR) was calculated as [(eGFR at each time point - pre-treatment eGFR)/pre-treatment eGFR] × 100. ΔeGFR was compared between SU- and SO users using a mixed-effects model for repeated measures data with two or greater. Additionally, predictors for ΔeGFR ≤ -10% at 6 months after therapy initiation were evaluated using multivariate logistic regression analysis. Throughout the 24 months after therapy initiation, ΔeGFR was negatively greater in SU users, compared with that in SO users (P < 0.0001). In SU users, renal dysfunction was observed regardless of pre-treatment chronic kidney disease (CKD) status, whereas the magnitude of renal dysfunction was milder in SO users. In SO users without pre-treatment CKD, renal function did not significantly deteriorate. Moreover, ΔeGFR ≤ -10% was more frequently observed in SU users after 3 months (P = 0.0121) and 6 months (P = 0.0009). Finally, SU usage was an independent predictor for ΔeGFR ≤ -10% at 6 months (odds ratio 8.87, P = 0.0053), along with pre-treatment hypertension (odds ratio 4.69, P = 00072). Deterioration of renal function was stronger with SU than SO. During SU therapy, renal function should be monitored and pre-treatment kidney function should be taken into consideration for therapy selection. © The Author 2017. Published by Oxford University Press.

Histological findings in two renal transplants accomplishing operational tolerance criteria

PubMed Central

Azancot, M.A.; Cantarell, C.; Torres, I.B.; Serón, D.R.

2011-01-01

Operational tolerance is defined as stable renal function in transplants without immunosuppression for at least 1 year. We present histological assessments of two patients with operational tolerance. The first withdrew immunosuppression in 2005 and presents stable renal function (creatinine 1.5 mg/dL) without proteinuria. The biopsy showed mild chronic tubulointerstitial changes without inflammation. The second withdrew immunosuppression in 2009 and maintains stable renal function (creatinine 1.6 mg/dL) with mild proteinuria. Histology showed chronic humoural rejection and Class II anti-human leukocyte antigen antibodies were detected. These cases suggest that a renal biopsy may be useful to rule out subclinical pathology in patients with operational tolerance. PMID:25984157

Histological findings in two renal transplants accomplishing operational tolerance criteria.

PubMed

Azancot, M A; Moreso, F; Cantarell, C; Torres, I B; Serón, D R

2011-06-01

Operational tolerance is defined as stable renal function in transplants without immunosuppression for at least 1 year. We present histological assessments of two patients with operational tolerance. The first withdrew immunosuppression in 2005 and presents stable renal function (creatinine 1.5 mg/dL) without proteinuria. The biopsy showed mild chronic tubulointerstitial changes without inflammation. The second withdrew immunosuppression in 2009 and maintains stable renal function (creatinine 1.6 mg/dL) with mild proteinuria. Histology showed chronic humoural rejection and Class II anti-human leukocyte antigen antibodies were detected. These cases suggest that a renal biopsy may be useful to rule out subclinical pathology in patients with operational tolerance.

Renal Heme Oxygenase-1 Induction with Hemin Augments Renal Hemodynamics, Renal Autoregulation, and Excretory Function

PubMed Central

Botros, Fady T.; Dobrowolski, Leszek; Navar, L. Gabriel

2012-01-01

Heme oxygenases (HO-1; HO-2) catalyze conversion of heme to free iron, carbon monoxide, and biliverdin/bilirubin. To determine the effects of renal HO-1 induction on blood pressure and renal function, normal control rats (n = 7) and hemin-treated rats (n = 6) were studied. Renal clearance studies were performed on anesthetized rats to assess renal function; renal blood flow (RBF) was measured using a transonic flow probe placed around the left renal artery. Hemin treatment significantly induced renal HO-1. Mean arterial pressure and heart rate were not different (115 ± 5 mmHg versus 112 ± 4 mmHg and 331 ± 16 versus 346 ± 10 bpm). However, RBF was significantly higher (9.1 ± 0.8 versus 7.0 ± 0.5 mL/min/g, P < 0.05), and renal vascular resistance was significantly lower (13.0 ± 0.9 versus 16.6 ± 1.4 [mmHg/(mL/min/g)], P < 0.05). Likewise, glomerular filtration rate was significantly elevated (1.4 ± 0.2 versus 1.0 ± 0.1 mL/min/g, P < 0.05), and urine flow and sodium excretion were also higher (18.9 ± 3.9 versus 8.2 ± 1.0 μL/min/g, P < 0.05 and 1.9 ± 0.6 versus 0.2 ± 0.1 μmol/min/g, P < 0.05, resp.). The plateau of the autoregulation relationship was elevated, and renal vascular responses to acute angiotensin II infusion were attenuated in hemin-treated rats reflecting the vasodilatory effect of HO-1 induction. We conclude that renal HO-1 induction augments renal function which may contribute to the antihypertensive effects of HO-1 induction observed in hypertension models. PMID:22518281

Effect of selective inhibition of renal inducible nitric oxide synthase on renal blood flow and function in experimental hyperdynamic sepsis.

PubMed

Ishikawa, Ken; Calzavacca, Paolo; Bellomo, Rinaldo; Bailey, Michael; May, Clive N

2012-08-01

Nitric oxide plays an important role in the control of renal blood flow and renal function. In sepsis, increased levels of inducible nitric oxide synthase produce excessive nitric oxide, which may contribute to the development of acute kidney injury. We, therefore, examined the effects of intrarenal infusion of selective inducible nitric oxide synthase inhibitors in a large animal model of hyperdynamic sepsis in which acute kidney injury occurs in the presence of increased renal blood flow. Prospective crossover randomized controlled interventional studies. University-affiliated research institute. Twelve unilaterally nephrectomized Merino ewes. Infusion of a selective (1400W) and a partially selective inducible nitric oxide synthase inhibitor (aminoguanidine) into the renal artery for 2 hrs after the induction of sepsis, and comparison with a nonselective inhibitor (Nω-nitro-L-arginine methyl ester). In sheep with nonhypotensive hyperdynamic sepsis, creatinine clearance halved (32 to 16 mL/min, ratio [95% confidence interval] 0.51 [0.28-0.92]) despite increased renal blood flow (241 to 343 mL/min, difference [95% confidence interval] 102 [78-126]). Infusion of 1400W did not change renal blood flow, urine output, or creatinine clearance, whereas infusion of Nω-nitro-L-arginine methyl ester and a high dose of aminoguanidine normalized renal blood flow, but did not alter creatinine clearance. In hyperdynamic sepsis, intrarenal infusion of a highly selective inducible nitric oxide synthase inhibitor did not reduce the elevated renal blood flow or improve renal function. In contrast, renal blood flow was reduced by infusion of a nonselective NOS inhibitor or a high dose of a partially selective inducible nitric oxide synthase inhibitor. The renal vasodilatation in septic acute kidney injury may be due to nitric oxide derived from the endothelial and neural isoforms of nitric oxide synthase, but their blockade did not restore renal function.

A Novel Therapy to Attenuate Acute Kidney Injury and Ischemic Allograft Damage after Allogenic Kidney Transplantation in Mice

PubMed Central

Gueler, Faikah; Shushakova, Nelli; Mengel, Michael; Hueper, Katja; Chen, Rongjun; Liu, Xiaokun; Park, Joon-Keun; Haller, Hermann

2015-01-01

Ischemia followed by reperfusion contributes to the initial damage to allografts after kidney transplantation (ktx). In this study we tested the hypothesis that a tetrapeptide EA-230 (AQGV), might improve survival and attenuate loss of kidney function in a mouse model of renal ischemia/reperfusion injury (IRI) and ischemia-induced delayed graft function after allogenic kidney transplantation. IRI was induced in male C57Bl/6N mice by transient bilateral renal pedicle clamping for 35 min. Treatment with EA-230 (20–50mg/kg twice daily i.p. for four consecutive days) was initiated 24 hours after IRI when acute kidney injury (AKI) was already established. The treatment resulted in markedly improved survival in a dose dependent manner. Acute tubular injury two days after IRI was diminished and tubular epithelial cell proliferation was significantly enhanced by EA-230 treatment. Furthermore, CTGF up-regulation, a marker of post-ischemic fibrosis, at four weeks after IRI was significantly less in EA-230 treated renal tissue. To learn more about these effects, we measured renal blood flow (RBF) and glomerular filtration rate (GFR) at 28 hours after IRI. EA-230 improved both GFR and RBF significantly. Next, EA-230 treatment was tested in a model of ischemia-induced delayed graft function after allogenic kidney transplantation. The recipients were treated with EA-230 (50 mg/kg) twice daily i.p. which improved renal function and allograft survival by attenuating ischemic allograft damage. In conclusion, EA-230 is a novel and promising therapeutic agent for treating acute kidney injury and preventing IRI-induced post-transplant ischemic allograft injury. Its beneficial effect is associated with improved renal perfusion after IRI and enhanced regeneration of tubular epithelial cells. PMID:25617900

A novel therapy to attenuate acute kidney injury and ischemic allograft damage after allogenic kidney transplantation in mice.

PubMed

Gueler, Faikah; Shushakova, Nelli; Mengel, Michael; Hueper, Katja; Chen, Rongjun; Liu, Xiaokun; Park, Joon-Keun; Haller, Hermann; Wensvoort, Gert; Rong, Song

2015-01-01

Ischemia followed by reperfusion contributes to the initial damage to allografts after kidney transplantation (ktx). In this study we tested the hypothesis that a tetrapeptide EA-230 (AQGV), might improve survival and attenuate loss of kidney function in a mouse model of renal ischemia/reperfusion injury (IRI) and ischemia-induced delayed graft function after allogenic kidney transplantation. IRI was induced in male C57Bl/6N mice by transient bilateral renal pedicle clamping for 35 min. Treatment with EA-230 (20-50mg/kg twice daily i.p. for four consecutive days) was initiated 24 hours after IRI when acute kidney injury (AKI) was already established. The treatment resulted in markedly improved survival in a dose dependent manner. Acute tubular injury two days after IRI was diminished and tubular epithelial cell proliferation was significantly enhanced by EA-230 treatment. Furthermore, CTGF up-regulation, a marker of post-ischemic fibrosis, at four weeks after IRI was significantly less in EA-230 treated renal tissue. To learn more about these effects, we measured renal blood flow (RBF) and glomerular filtration rate (GFR) at 28 hours after IRI. EA-230 improved both GFR and RBF significantly. Next, EA-230 treatment was tested in a model of ischemia-induced delayed graft function after allogenic kidney transplantation. The recipients were treated with EA-230 (50 mg/kg) twice daily i.p. which improved renal function and allograft survival by attenuating ischemic allograft damage. In conclusion, EA-230 is a novel and promising therapeutic agent for treating acute kidney injury and preventing IRI-induced post-transplant ischemic allograft injury. Its beneficial effect is associated with improved renal perfusion after IRI and enhanced regeneration of tubular epithelial cells.

Effects of creatine supplementation on renal function: a randomized, double-blind, placebo-controlled clinical trial.

PubMed

Gualano, Bruno; Ugrinowitsch, Carlos; Novaes, Rafael Batista; Artioli, Guilherme Gianini; Shimizu, Maria Heloisa; Seguro, Antonio Carlos; Harris, Roger Charles; Lancha, Antonio Herbert

2008-05-01

Creatine (CR) supplementation is commonly used by athletes. However, its effects on renal function remain controversial. The aim of this study was to evaluate the effects of creatine supplementation on renal function in healthy sedentary males (18-35 years old) submitted to exercise training. A randomized, double-blind, placebo-controlled trial was performed. Subjects (n = 18) were randomly allocated to receive treatment with either creatine (CR) ( approximately 10 g day(-1) over 3 months) or placebo (PL) (dextrose). All subjects undertook moderate intensity aerobic training, in three 40-min sessions per week, during 3 months. Serum creatinine, serum and urinary sodium and potassium were determined at baseline and at the end of the study. Cystatin C was assessed prior to training (PRE), after 4 (POST 4) and 12 weeks (POST 12). Cystatin C levels (mg L(-1)) (PRE CR: 0.82 +/- 0.09; PL: 0.88 +/- 0.07 vs. POST 12 CR: 0.71 +/- 0.06; PL: 0.75 +/- 0.09, P = 0.0001) were decreased over time, suggesting an increase in glomerular filtration rate. Serum creatinine decreased with training in PL but was unchanged with training in CR. No significant differences were observed within or between groups in other parameters investigated. The decrease in cystatin C indicates that high-dose creatine supplementation over 3 months does not provoke any renal dysfunction in healthy males undergoing aerobic training. In addition, the results suggest that moderate aerobic training per se may improve renal function.

Thyroid function modifies the association between ratio of triglyceride to high-density lipoprotein cholesterol and renal function: a multicenter cross-sectional study

PubMed Central

Yuan, Zhongshang; Zhao, Meng; Zhang, Bingchang; Zhang, Haiqing; Zhang, Xu; Guan, Qingbo; Ning, Guang; Gao, Ling; Xue, Fuzhong; Zhao, Jiajun

2015-01-01

Hypothyroidism was confirmed to be associated with both dyslipidemia and renal dysfunction. However, the impact of thyroid function on the relationship between serum lipid levels and renal function has never been given sufficient attention. In this large-scale multicenter cross-sectional study, the ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL) and the prevalence of hypothyroidism in CKD subjects were significantly higher than those in non-CKD ones (P < 0.001). After adjustment for potential confounding factors, TG/HDL was shown to be significantly associated with serum Cr levels (β = 0.551; 95%CI, 0.394–0.708), and eGFR (β = −0.481; 95%CI, −0.731–−0.230). The risk for CKD was significantly increased as TG/HDL ratio was elevated (adjusted odds ratio = 1.20; 95%CI, 1.11–1.27). These significant associations were found among subjects with euthyroidism and hypothyroidism rather than hyperthyroidism. Furthermore, the associations between TG/HDL and Cr or CKD status were significantly greater in hypothyroidism than those in euthyroidism (P < 0.05). These results suggested that elevated TG/HDL ratio was associated with renal dysfunction; it exhibited a significantly stronger association with Cr and CKD in hypothyroidism than in euthyroidism. Therefore, more attention should be paid on lipid profile to prevent or delay the occurrence and progression of renal dysfunction, especially for those with hypothyroidism. PMID:26179571

Thyroid function modifies the association between ratio of triglyceride to high-density lipoprotein cholesterol and renal function: a multicenter cross-sectional study.

PubMed

Yuan, Zhongshang; Zhao, Meng; Zhang, Bingchang; Zhang, Haiqing; Zhang, Xu; Guan, Qingbo; Ning, Guang; Gao, Ling; Xue, Fuzhong; Zhao, Jiajun

2015-07-16

Hypothyroidism was confirmed to be associated with both dyslipidemia and renal dysfunction. However, the impact of thyroid function on the relationship between serum lipid levels and renal function has never been given sufficient attention. In this large-scale multicenter cross-sectional study, the ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL) and the prevalence of hypothyroidism in CKD subjects were significantly higher than those in non-CKD ones (P < 0.001). After adjustment for potential confounding factors, TG/HDL was shown to be significantly associated with serum Cr levels (β = 0.551; 95%CI, 0.394-0.708), and eGFR (β = -0.481; 95%CI, -0.731--0.230). The risk for CKD was significantly increased as TG/HDL ratio was elevated (adjusted odds ratio = 1.20; 95%CI, 1.11-1.27). These significant associations were found among subjects with euthyroidism and hypothyroidism rather than hyperthyroidism. Furthermore, the associations between TG/HDL and Cr or CKD status were significantly greater in hypothyroidism than those in euthyroidism (P < 0.05). These results suggested that elevated TG/HDL ratio was associated with renal dysfunction; it exhibited a significantly stronger association with Cr and CKD in hypothyroidism than in euthyroidism. Therefore, more attention should be paid on lipid profile to prevent or delay the occurrence and progression of renal dysfunction, especially for those with hypothyroidism.

Alport syndrome and pregnancy: a case series and literature review.

PubMed

Brunini, Francesca; Zaina, Barbara; Gianfreda, Davide; Ossola, Wally; Giani, Marisa; Fedele, Luigi; Messa, Piergiorgio; Moroni, Gabriella

2018-06-01

To assess pregnancy outcome in women with Alport syndrome and the impact of pregnancy on the disease progression. We describe one of the largest series of pregnancies in Alport syndrome. Seven pregnancies of six women were monitored by a multidisciplinary team of nephrologists and gynecologists. After delivery, patients were followed for at least 3 years. We compare our results with those in the literature. Pregnancy course was uneventful in the patient with isolated microscopic hematuria. In the other cases, all presenting mild proteinuria at conception, some complications occurred. Proteinuria worsened during the last trimester, reaching nephrotic ranges in five out of six pregnancies and was associated with fluid overload leading to hospitalizations and early delivery. The majority of the newborns had a low birth weight. The two patients with arterial hypertension at conception and twin pregnancy developed pre-eclampsia and renal function deterioration persisted after delivery. The one with pre-pregnancy renal dysfunction reached end-stage renal disease. In the other patients, in which renal function and blood pressure were and remained normal, proteinuria improved after delivery and no signs of disease progression were recorded at last observation. Our observations suggest that Alport syndrome should be considered a potential risk factor for pregnancy in proteinuric patients due to the development of pre-eclampsia, renal function deterioration, and/or full-blown nephrotic syndrome that results in anasarca, slowing of fetal growth and pre-term delivery. Thus, all women with Alport syndrome should receive pre-conceptional counseling and be kept in close follow-up during pregnancy.

Factor H autoantibody is associated with atypical hemolytic uremic syndrome in children in the United Kingdom and Ireland.

PubMed

Brocklebank, Vicky; Johnson, Sally; Sheerin, Thomas P; Marks, Stephen D; Gilbert, Rodney D; Tyerman, Kay; Kinoshita, Meredith; Awan, Atif; Kaur, Amrit; Webb, Nicholas; Hegde, Shivaram; Finlay, Eric; Fitzpatrick, Maggie; Walsh, Patrick R; Wong, Edwin K S; Booth, Caroline; Kerecuk, Larissa; Salama, Alan D; Almond, Mike; Inward, Carol; Goodship, Timothy H; Sheerin, Neil S; Marchbank, Kevin J; Kavanagh, David

2017-11-01

Factor H autoantibodies can impair complement regulation, resulting in atypical hemolytic uremic syndrome, predominantly in childhood. There are no trials investigating treatment, and clinical practice is only informed by retrospective cohort analysis. Here we examined 175 children presenting with atypical hemolytic uremic syndrome in the United Kingdom and Ireland for factor H autoantibodies that included 17 children with titers above the international standard. Of the 17, seven had a concomitant rare genetic variant in a gene encoding a complement pathway component or regulator. Two children received supportive treatment; both developed established renal failure. Plasma exchange was associated with a poor rate of renal recovery in seven of 11 treated. Six patients treated with eculizumab recovered renal function. Contrary to global practice, immunosuppressive therapy to prevent relapse in plasma exchange-treated patients was not adopted due to concerns over treatment-associated complications. Without immunosuppression, the relapse rate was high (five of seven). However, reintroduction of treatment resulted in recovery of renal function. All patients treated with eculizumab achieved sustained remission. Five patients received renal transplants without specific factor H autoantibody-targeted treatment with recurrence in one who also had a functionally significant CFI mutation. Thus, our current practice is to initiate eculizumab therapy for treatment of factor H autoantibody-mediated atypical hemolytic uremic syndrome rather than plasma exchange with or without immunosuppression. Based on this retrospective analysis we see no suggestion of inferior treatment, albeit the strength of our conclusions is limited by the small sample size. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Antiurolithiatic Effect of Sirupeelai Samoola Kudineer: A Polyherbal Siddha Decoction on Ethylene Glycol-induced Renal Calculus in Experimental Rats

PubMed Central

Vasanthi, A. Hannah Rachel; Muthulakshmi, V.; Gayathri, V.; Manikandan, R.; Ananthi, S.; Kuruvilla, Sarah

2017-01-01

Background: Sirupeelai Samoola Kudineer (SK), a polyherbal decoction containing four medicinal plants has been used in Siddha system of medicine, practiced in Southern parts of India for the management of urolithiasis. Objective: The present study is carried out to scientifically validate the traditional claim and to study the mechanism of action of the drug. Materials and Methods: In the present study, anti-urolithiatic effect of SK was evaluated in Sprague-Dawley rats using ethylene glycol through drinking water and intraperitoneal injection of sodium oxalate. Renal damage was confirmed by the increased production of thiobarbituric acid reactive substance (TBARS). Results: Co-treatment with SK to urolithiatic rats for 21 days significantly prevented the elevation of renal and urinary stone biomarkers in plasma and renal tissue thereby preventing renal damage and the formation of renal calculi. Administration of SK at all doses and cystone restored the antioxidant (glutathione) levels by preventing the elevation of TBARS in the kidney tissue, which was further confirmed by histological sections. Conclusions: SK treatment promotes diuresis which leads to flushing of the renal stones and maintains the alkaline environment in the urinary system which probably mediates the antilithiatic activity. SK provides structural and functional protection to the kidneys by enhancing its physiological function against stone formation and validates its clinical use. SUMMARY SK exhibited antilithiatic and diuretic potential in ethylene glycol and sodium oxalate induced urolithiasis in ratsElevated urinary stone markers (Calcium, oxalate, uric acid, magnesium and phosphates) in plasma and renal tubular enzymes (LDH, GGT, ALP, AST ALT) in urolithiatic rats were reversed by SK treatmentSK administration significantly reduced the level of renal stress markers like Urea, Creatinine, LPO and elevated SOD, GPx, GSH levels aiding in nephroprotectionSK also provides structural and functional protection against ethylene glycol- induced renal calculus in rats as evidenced by histopathological studies. Abbreviations used: SK: Sirupeelai Samoola Kudineer; TBARS: ThioBarbituric Acid Reactive Substances; SOD: SuperOxide Dismutase; GPx: Gluthathione peroxidase; GSH- Glutathione; LPO: Lipid peroxidation as measured as TBARS; AST: Aspartate AminoTransferase; ALT: Alanine Amino transferase; GGT: Gamma Glutamyl Transferase; LDH: Lactate Dehydrogenase. PMID:28808392

Improvement of renal function after human umbilical cord mesenchymal stem cell treatment on chronic renal failure and thoracic spinal cord entrapment: a case report.

PubMed

Rahyussalim, Ahmad Jabir; Saleh, Ifran; Kurniawati, Tri; Lutfi, Andi Praja Wira Yudha

2017-11-30

Chronic renal failure is an important clinical problem with significant socioeconomic impact worldwide. Thoracic spinal cord entrapment induced by a metabolic yield deposit in patients with renal failure results in intrusion of nervous tissue and consequently loss of motor and sensory function. Human umbilical cord mesenchymal stem cells are immune naïve and they are able to differentiate into other phenotypes, including the neural lineage. Over the past decade, advances in the field of regenerative medicine allowed development of cell therapies suitable for kidney repair. Mesenchymal stem cell studies in animal models of chronic renal failure have uncovered a unique potential of these cells for improving function and regenerating the damaged kidney. We report a case of a 62-year-old ethnic Indonesian woman previously diagnosed as having thoracic spinal cord entrapment with paraplegic condition and chronic renal failure on hemodialysis. She had diabetes mellitus that affected her kidneys and had chronic renal failure for 2 years, with creatinine level of 11 mg/dl, and no urinating since then. She was treated with human umbilical cord mesenchymal stem cell implantation protocol. This protocol consists of implantation of 16 million human umbilical cord mesenchymal stem cells intrathecally and 16 million human umbilical cord mesenchymal stem cells intravenously. Three weeks after first intrathecal and intravenous implantation she could move her toes and her kidney improved. Her creatinine level decreased to 9 mg/dl. Now after 8 months she can raise her legs and her creatinine level is 2 mg/dl with normal urinating. Human umbilical cord mesenchymal stem cell implantations led to significant improvement for spinal cord entrapment and kidney failure. The major histocompatibility in allogeneic implantation is an important issue to be addressed in the future.

Fluid and electrolyte disturbances in cirrhosis.

PubMed

Papper, S

1976-01-01

Glomerular filtration rate and renal plasma flow may be normal, reduced or increased in cirrhosis. The mechanism of departures from normal is not known. Other renal functional changes in cirrhosis include avid sodium reabsorption, impaired concentrating and diluting abilities, and partial renal tubular acidosis. Fluid and electrolyte disorders are common. Sodium retention with edema and ascites should generally be treated conservatively because they tend to disappear as the liver heals and because forced diuresis has hazards. The indications for diuretics are (1) incipient or overt atelectasis; (2) abdominal distress; and (3) possibility of skin breakdown. Hyponatremia is common and its mechanism and treatment must be assessed in each patient. Hypokalemia occurs and requires treatment. Respiratory alkalosis and renal tubular acidosis seldom need therapy. The hepatorenal syndrome is defined as functional renal failure in the absence of other known causes of renal functional impairment. The prognosis is terrible and therapy is unsatisfactory. The best approach is not to equate the occurrence of renal failure in cirrhosis with the hepatorenal syndrome. Rather the physician should first explore all treatable causes of renal failure, eg, dehydration, obstruction, infection, heart failure, potassium depletion, and others.

Design and Methodological Considerations of the Centers for Disease Control and Prevention Urologic and Renal Protocol for the Newborn and Young Child with Spina Bifida.

PubMed

Routh, Jonathan C; Cheng, Earl Y; Austin, J Christopher; Baum, Michelle A; Gargollo, Patricio C; Grady, Richard W; Herron, Adrienne R; Kim, Steven S; King, Shelly J; Koh, Chester J; Paramsothy, Pangaja; Raman, Lisa; Schechter, Michael S; Smith, Kathryn A; Tanaka, Stacy T; Thibadeau, Judy K; Walker, William O; Wallis, M Chad; Wiener, John S; Joseph, David B

2016-12-01

Care of children with spina bifida has significantly advanced in the last half century, resulting in gains in longevity and quality of life for affected children and caregivers. Bladder dysfunction is the norm in patients with spina bifida and may result in infection, renal scarring and chronic kidney disease. However, the optimal urological management for spina bifida related bladder dysfunction is unknown. In 2012 the Centers for Disease Control and Prevention convened a working group composed of pediatric urologists, nephrologists, epidemiologists, methodologists, community advocates and Centers for Disease Control and Prevention personnel to develop a protocol to optimize urological care of children with spina bifida from the newborn period through age 5 years. An iterative quality improvement protocol was selected. In this model participating institutions agree to prospectively treat all newborns with spina bifida using a single consensus based protocol. During the 5-year study period outcomes will be routinely assessed and the protocol adjusted as needed to optimize patient and process outcomes. Primary study outcomes include urinary tract infections, renal scarring, renal function and bladder characteristics. The protocol specifies the timing and use of testing (eg ultrasonography, urodynamics) and interventions (eg intermittent catheterization, prophylactic antibiotics, antimuscarinic medications). Starting in 2014 the Centers for Disease Control and Prevention began funding 9 study sites to implement and evaluate the protocol. The Centers for Disease Control and Prevention Urologic and Renal Protocol for the Newborn and Young Child with Spina Bifida began accruing patients in 2015. Assessment in the first 5 years will focus on urinary tract infections, renal function, renal scarring and clinical process improvements. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

[Contribution of X-ray computed tomography in the evaluation of kidney performance].

PubMed

Lemoine, Sandrine; Rognant, Nicolas; Collet-Benzaquen, Diane; Juillard, Laurent

2012-07-01

X-ray computer assisted tomography scanner is an imaging method based on the use of X-ray attenuation in tissue. This attenuation is proportional to the density of the tissue (without or after contrast media injection) in each pixel image of the image. Spiral scanner, the electron beam computed tomography (EBCT) scanner and multidetector computed tomography scanner allow renal anatomical measurements, such as cortical and medullary volume, but also the measurement of renal functional parameters, such as regional renal perfusion, renal blood flow and glomerular filtration rate. These functional parameters are extracted from the modeling of the kinetics of the contrast media concentration in the vascular space and the renal tissue, using two main mathematical models (the gamma variate model and the Patlak model). Renal functional imaging allows measuring quantitative parameters on each kidney separately, in a non-invasive manner, providing significant opportunities in nephrology, both for experimental and clinical studies. However, this method uses contrast media that may alter renal function, thus limiting its use in patients with chronic renal failure. Moreover, the increase irradiation delivered to the patient with multi detector computed tomography (MDCT) should be considered. Copyright © 2011 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Non-invasive evaluation of stable renal allograft function using point shear-wave elastography.

PubMed

Kim, Bom Jun; Kim, Chan Kyo; Park, Jung Jae

2018-01-01

To investigate the feasibility of point shear-wave elastography (SWE) in evaluating patients with stable renal allograft function who underwent protocol biopsies. 95 patients with stable renal allograft function that underwent ultrasound-guided biopsies at predefined time points (10 days or 1 year after transplantation) were enrolled. Ultrasound and point SWE examinations were performed immediately before protocol biopsies. Patients were categorized into two groups: subclinical rejection (SCR) and non-SCR. Tissue elasticity (kPa) on SWE was measured in the cortex of all renal allografts. SCR was pathologically confirmed in 34 patients. Tissue elasticity of the SCR group (31.0 kPa) was significantly greater than that of the non-SCR group (24.5 kPa) (=0.016), while resistive index value did not show a significant difference between the two groups (p = 0.112). Tissue elasticity in renal allografts demonstrated significantly moderate negative correlation with estimated glomerular filtration rate (correlation coefficient = -0.604, p < 0.001). Tissue elasticity was not independent factor for SCR prediction on multivariate analysis. As a non-invasive tool, point SWE appears feasible in distinguishing between patients with SCR and without SCR in stable functioning renal allografts. Moreover, it may demonstrate the functional state of renal allografts. Advances in knowledge: On point SWE, SCR has greater tissue elasticity than non-SCR.

Effect of first myocardial ischemic event on renal function.

PubMed

Eijkelkamp, Wouter B A; de Graeff, Pieter A; van Veldhuisen, Dirk J; van Dokkum, Richard P E; Gansevoort, Ronald T; de Jong, Paul E; de Zeeuw, Dick; Hillege, Hans L

2007-07-01

Effects of cardiovascular dysfunction on renal function have been poorly characterized. Therefore, we investigated the relation between a first ischemic cardiac event and long-term renal function changes in the general population from the PREVEND study. We studied 6,360 subjects with a total follow-up duration of 27.017 subject-years. The estimated mean proportional increase in serum creatinine after a first ischemic cardiac event was 3.1% compared with 0.4% per year of follow-up in subjects without such an event (p = 0.005). This represented a significantly larger decrease in estimated glomerular filtration rate after the event in subjects with an event versus the decrease in subjects without a first ischemic cardiac event (2.2 vs 0.5 ml/min/1.73 m(2)/year of follow-up, p = 0.006). In multivariate analysis with adjustment for renal risk factors, this event showed an independent association with serum creatinine change. In conclusion, a first ischemic cardiac event appears to enhance the natural decrease in renal function. Because even mild renal dysfunction should be considered a major cardiovascular risk factor after myocardial infarction, increased renal function loss after an ischemic cardiac event could add to the risk for subsequent cardiovascular morbidity, thus closing a vicious circle.

Validation of cystatin C-based equations for evaluating residual renal function in patients on continuous ambulatory peritoneal dialysis.

PubMed

Zhong, Hui; Zhang, Wei; Qin, Min; Gou, ZhongPing; Feng, Ping

2017-06-01

Residual renal function needs to be assessed frequently in patients on continuous ambulatory peritoneal dialysis (CAPD). A commonly used method is to measure creatinine (Cr) and urea clearance in urine collected over 24 h, but collection can be cumbersome and difficult to manage. A faster, simpler alternative is to measure levels of cystatin C (CysC) in serum, but the accuracy and reliability of this method is controversial. Our study aims to validate published CysC-based equations for estimating residual renal function in patients on CAPD. Residual renal function was measured by calculating average clearance of urea and Cr in 24-h urine as well as by applying CysC- or Cr-based equations published by Hoek and Yang. We then compared the performance of the equations against the 24-h urine results. In our sample of 255 patients ages 47.9 ± 15.6 years, the serum CysC level was 6.43 ± 1.13 mg/L. Serum CysC level was not significantly associated with age, gender, height, weight, body mass index, hemoglobin, intact parathyroid hormone, normalized protein catabolic rate or the presence of diabetes. In contrast, serum CysC levels did correlate with peritoneal clearance of CysC and with levels of prealbumin and high-sensitivity C-reactive protein. Residual renal function was 2.56 ± 2.07 mL/min/1.73 m 2 based on 24-h urine sampling, compared with estimates (mL/min/1.73 m 2 ) of 2.98 ± 0.66 for Hoek's equation, 2.03 ± 0.97 for Yang's CysC-based equation and 2.70 ± 1.30 for Yang's Cr-based equation. Accuracies within 30%/50% of measured residual renal function for the three equations were 29.02/48.24, 34.90/56.86 and 31.37/54.90. The three equations for estimating residual renal function showed similar limits of agreement and differed significantly from the measured value. Published CysC-based equations do not appear to be particularly reliable for patients on CAPD. Further development and validation of CysC-based equations should take into account peritoneal clearance of CysC and other relevant factors. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Differentiation of Solid Renal Tumors with Multiparametric MR Imaging.

PubMed

Lopes Vendrami, Camila; Parada Villavicencio, Carolina; DeJulio, Todd J; Chatterjee, Argha; Casalino, David D; Horowitz, Jeanne M; Oberlin, Daniel T; Yang, Guang-Yu; Nikolaidis, Paul; Miller, Frank H

2017-01-01

Characterization of renal tumors is critical to determine the best therapeutic approach and improve overall patient survival. Because of increased use of high-resolution cross-sectional imaging in clinical practice, renal masses are being discovered with increased frequency. As a result, accurate imaging characterization of these lesions is more important than ever. However, because of the wide array of imaging features encountered as well as overlapping characteristics, identifying reliable imaging criteria for differentiating malignant from benign renal masses remains a challenge. Multiparametric magnetic resonance (MR) imaging based on various anatomic and functional parameters has an important role and adds diagnostic value in detection and characterization of renal masses. MR imaging may allow distinction of benign solid renal masses from several renal cell carcinoma (RCC) subtypes, potentially suggest the histologic grade of a neoplasm, and play an important role in ensuring appropriate patient management to avoid unnecessary surgery or other interventions. It is also a useful noninvasive imaging tool for patients who undergo active surveillance of renal masses and for follow-up after treatment of a renal mass. The purpose of this article is to review the characteristic MR imaging features of RCC and common benign renal masses and propose a diagnostic imaging approach to evaluation of solid renal masses using multiparametric MR imaging. © RSNA, 2017.

Evidence of uncoupling between renal dysfunction and injury in cardiorenal syndrome: insights from the BIONICS study.

PubMed

Legrand, Matthieu; De Berardinis, Benedetta; Gaggin, Hanna K; Magrini, Laura; Belcher, Arianna; Zancla, Benedetta; Femia, Alexandra; Simon, Mandy; Motiwala, Shweta; Sambhare, Rasika; Di Somma, Salvatore; Mebazaa, Alexandre; Vaidya, Vishal S; Januzzi, James L

2014-01-01

The objective of the study was to assess urinary biomarkers of renal injury for their individual or collective ability to predict Worsening renal function (WRF) in patients with acutely decompensated heart failure (ADHF). In a prospective, blinded international study, 87 emergency department (ED) patients with ADHF were evaluated with biomarkers of cardiac stretch (B type natriuretic peptide [BNP] and its amino terminal equivalent [NT-proBNP], ST2), biomarkers of renal function (creatinine, estimated glomerular filtration rate [eGFR]) and biomarkers of renal injury (plasma neutrophil gelatinase associated lipocalin [pNGAL], urine kidney injury molecule-1 [KIM-1], urine N-acetyl-beta-D-glucosaminidase [NAG], urine Cystatin C, urine fibrinogen). The primary endpoint was WRF. 26% developed WRF; baseline characteristics of subjects who developed WRF were generally comparable to those who did not. Biomarkers of renal function and urine biomarkers of renal injury were not correlated, while urine biomarkers of renal injury correlated between each other. Biomarker concentrations were similar between patients with and without WRF except for baseline BNP. Although plasma NGAL was associated with the combined endpoint, none of the biomarker showed predictive accuracy for WRF. In ED patients with ADHF, urine biomarkers of renal injury did not predict WRF. Our data suggest that a weak association exists between renal dysfunction and renal injury in this setting (Clinicaltrials.gov NCT#0150153).

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.

Efficacy and safety of lipid lowering by alirocumab in chronic kidney disease.

PubMed

Toth, Peter P; Dwyer, Jamie P; Cannon, Christopher P; Colhoun, Helen M; Rader, Daniel J; Upadhyay, Ashish; Louie, Michael J; Koren, Andrew; Letierce, Alexia; Mandel, Jonas; Banach, Maciej

2018-06-01

Individuals with chronic kidney disease are at increased risk of premature cardiovascular disease. Among them, many with elevated low-density lipoprotein cholesterol (LDL-C) are unable to achieve optimal LDL-C on statins and require additional lipid-lowering therapy. To study this, we compared the LDL-C-lowering efficacy and safety of alirocumab in individuals with hypercholesterolemia with impaired renal function, defined as eGFR 30-59 ml/min/1.73 m 2 , to those without impaired renal function eGFR ≥60 ml/min/1.73 m 2 . A total of 4629 hypercholesterolemic individuals without or with impaired renal function, pooled from eight phase 3 ODYSSEY trials (double-blind treatments of 24-104 weeks), were on alirocumab 150 mg or 75/150 mg every two weeks vs. placebo or ezetimibe. Overall, 10.1% had impaired renal function and over 99% were receiving statin treatment. Baseline LDL-C in alirocumab and control groups was comparable in subgroups analyzed. LDL-C reductions at week 24 ranged from 46.1 to 62.2% or 48.3 to 60.1% with alirocumab among individuals with or without impaired renal function, respectively. Similar reductions were observed for lipoprotein (a), non-high-density lipoprotein cholesterol, apolipoprotein B, and triglycerides. Safety data were similar in both treatment subgroups, regardless of the degree of CKD. Renal function did not change over time in response to alirocumab. This post hoc efficacy analysis is limited by evaluation of alirocumab treatment effects on renal and lipid parameters by serum biochemistry. Thus, alirocumab consistently lowered LDL-C regardless of impaired renal function, with safety comparable to control, among individuals with hypercholesterolemia who nearly all were on statin treatment. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Metabolic and hemodynamic effects of sodium-dependent glucose cotransporter 2 inhibitors on cardio-renal protection in the treatment of patients with type 2 diabetes mellitus.

PubMed

Kashiwagi, Atsunori; Maegawa, Hiroshi

2017-07-01

The specific sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) inhibit glucose reabsorption in proximal renal tubular cells, and both fasting and postprandial glucose significantly decrease because of urinary glucose loss. As a result, pancreatic β-cell function and peripheral insulin action significantly improve with relief from glucose toxicity. Furthermore, whole-body energy metabolism changes to relative glucose deficiency and triggers increased lipolysis in fat cells, and fatty acid oxidation and then ketone body production in the liver during treatment with SGLT2 inhibitors. In addition, SGLT2 inhibitors have profound hemodynamic effects including diuresis, dehydration, weight loss and lowering blood pressure. The most recent findings on SGLT2 inhibitors come from results of the Empagliflozin, Cardiovascular Outcomes and Mortality in Type 2 Diabetes trial. SGLT2 inhibitors exert extremely unique and cardio-renal protection through metabolic and hemodynamic effects, with long-term durability on the reduction of blood glucose, bodyweight and blood pressure. Although a site of action of SGLT2 inhibitors is highly specific to inhibit renal glucose reabsorption, whole-body energy metabolism, and hemodynamic and renal functions are profoundly modulated during the treatment of SGLT2 inhibitors. Previous studies suggest multifactorial clinical benefits and safety concerns of SGLT2 inhibitors. Although ambivalent clinical results of this drug are still under active discussion, the present review summarizes promising recent evidence on the cardio-renal and metabolic benefits of SGLT2 inhibitors in the treatment of type 2 diabetes. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Case discussion: impaired renal function and tolerance to high altitude.

PubMed

2002-01-01

A 58-year-old woman who plans a trek in the Himalayas at altitudes from 4500 to 5000 m is known to have the loss of about 50% of renal function based on glomerular filtration studies and renal biopsy. Possible risks and management are discussed.

The effect of non-diabetic chronic renal failure on olfactory function.

PubMed

Koseoglu, S; Derin, S; Huddam, B; Sahan, M

2017-05-01

In chronic renal failure (CRF), deterioration of glomerular filtration results in accumulation of metabolites in the body which affect all organs. This study was performed to investigate the olfactory functions, and determine if hemodialysis or peritoneal dialysis improves olfactory function in non-diabetic CRF patients. The olfactory functions were analyzed in CRF patients not on a dialysis program and had a creatinine level≥2mg/dL, in CRF patients on hemodialysis or peritoneal dialysis, and in healthy controls. Diabetic patients were excluded since diabetes alone is a cause of olfactory dysfunction. The study group consisted of a total of 107 individuals including 38CRF patients on a hemodialysis program, 15 CRF patients on peritoneal dialysis, 30 patients with a creatinine level ≥ 2mg/dL without any need for dialysis, and 24 healthy controls with normal renal functions. Olfactory functions were analyzed with "Sniffin' sticks" test, and the groups were compared for the test results. All test parameters were impaired in patients with CRF. The median TDI scores of the patients with CRF and the healthy subjects were 24.75 (13-36) and 32.5 (27.75-37.75), respectively, with a statistically significant difference in between (P<0.001). The olfactory functions for the dialysis patients were better than those for the CRF patients not on a dialysis program (P=0.020). Non-diabetic CRF affects olfactory functions negatively. Dialysis improves olfactory functions in those patients. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

The role of renal function loss on circadian misalignment of cytokines EPO, IGF-1, IL-6 and TNF-alfa in chronic renal disease.

PubMed

van der Putten, Karien; Koch, Birgit; van Someren, Eus; Wielders, Jos; Ter Wee, Piet; Nagtegaal, Elsbeth; Gaillard, Carlo

2011-01-01

Chronic inflammation plays a pivotal role in the development of renal disease. Circadian sleep-wake rhythm is disturbed in renal disease. Awareness of other disturbed rhythms, such as inflammation processes, can affect the treatment of patients with renal disease. Knowledge of possibly related circadian misalignment of the cytokines erythropoietin (EPO), Insulin Growth Factor-1 (IGF-1) and interleukins (IL) however is limited. We therefore performed an observational study. The objective of this study was to characterize levels of EPO, IGF-1 and inflammation markers IL-6 and TNF-α, related to renal function. The study population consisted of patients with various degrees of renal function, admitted to our hospital. During 24 hours, blood of 28 subjects with various degrees of renal function was collected every 2 hours. The patients were stable, not acutely ill and they were waiting for a procedure, such as elective surgery. Circadian parameters of EPO, IGF-1, IL-6 and TNF-α were measured in serum and were correlated with glomerular filtration rate (GFR) and Hb, using Pearson correlations. Although diurnal variations in EPO level were found in 15 out of 28 patients, the curves did not show a consistent phase. The presence of an EPO rhythm was not related to GFR. No diurnal rhythm could be detected for IGF-1, IL-6 and TNF-α. Mean levels of IGF-1 were correlated inversely to mean levels of EPO (p=0.03). When divided based on GFR and Hb subjects with GFR 10-30 ml/min and lower Hb had the highest IGF-1 levels (p=0.02). A relationship between Il-6, TNF-α and EPO or GFR was not found. The existence of a circadian (mis)alignment of EPO, IGF-1, IL-6 and TNF-α was not found. The association between high IGF-1 and low Hb suggests that EPO and IGF-1 have an alternating role, dependent on GFR, in stimulating erythropoiesis. These results could have consequences for the treatment of anemia.

Renal Salvage with Renal Artery Stenting Improves Long-term Survival.

PubMed

Modrall, J Gregory; Trimmer, Clayton; Tsai, Shirling; Kirkwood, Melissa L; Ali, Mujtaba; Rectenwald, John E; Timaran, Carlos H; Rosero, Eric B

2017-11-01

The Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) Trial cast doubt on the benefits of renal artery stenting (RAS). However, the outcomes for patients with chronic kidney disease (CKD) were not analyzed separately in the CORAL Trial. We hypothesized that patients who experienced a significant improvement in renal function after RAS would have improved long-term survival, compared with patients whose renal function was not improved by stenting. This single-center retrospective study included 60 patients with stage 3 or worse CKD and renal artery occlusive disease who were treated with RAS for renal salvage. Patients were categorized as "responders" or "nonresponders" based on postoperative changes in estimated glomerular filtration rate (eGFR) after RAS. "Responders" were those patients with an improvement of at least 20% in eGFR over baseline; all others were categorized as "nonresponders." Survival was analyzed using the Kaplan-Meier method. Cox proportional hazards regression was used to identify predictors of long-term survival. The median age of the cohort was 66 years (interquartile range [IQR], 60-73). Median preoperative eGFR was 34 mL/min/1.73 m 2 (IQR, 24-45). At late follow-up (median 35 months, IQR, 22-97 months), 16 of 60 patients (26.7%) were categorized as "responders" with a median increase in postoperative eGFR of 40% (IQR, 21-67). Long-term survival was superior for responders, compared with nonresponders (P = 0.046 by log-rank test). Cox proportional hazards regression identified improved renal function after RAS as the only significant predictor of increased long-term survival (hazard ratio = 0.235, 95% confidence interval = 0.075-0.733; P = 0.0126 for improved versus worsened renal function after RAS). Successful salvage of renal function by RAS is associated with improved long-term survival. These data provide an important counter argument to the prior negative clinical trials that found no benefit to RAS. Published by Elsevier Inc.

Peripheral and central interactions between the renin-angiotensin system and the renal sympathetic nerves in control of renal function.

PubMed

DiBona, G F

2001-06-01

Increases in renal sympathetic nerve activity (RSNA) regulate the functions of the nephron, the vasculature, and the renin-containing juxtaglomerular granular cells. As increased activity of the renin-angiotensin system can also influence nephron and vascular function, it is important to understand the interactions between RSNA and the renin-angiotensin system in the control of renal function. These interactions can be intrarenal, that is, the direct (via specific innervation) and indirect (via angiotensin II) contributions of increased RSNA to the regulation of renal function. The effects of increased RSNA on renal function are attenuated when the activity of the renin-angiotensin system is suppressed or antagonized with angiotensin-converting enzyme inhibitors or angiotensin II-type AT1 receptor antagonists. The effects of intrarenal administration of angiotensin II are attenuated following renal denervation. These interactions can also be extrarenal, that is, in the central nervous system, wherein RSNA and its arterial baroreflex control are modulated by changes in activity of the renin-angiotensin system. In addition to the circumventricular organs, the permeable blood-brain barrier of which permits interactions with circulating angiotensin II, there are interactions at sites behind the blood-brain barrier that depend on the influence of local angiotensin II. The responses to central administration of angiotensin II type AT1 receptor antagonists, into the ventricular system or microinjected into the rostral ventrolateral medulla, are modulated by changes in activity of the renin-angiotensin system produced by physiological changes in dietary sodium intake. Similar modulation is observed in pathophysiological models wherein activity of both the renin-angiotensin and sympathetic nervous systems is increased (e.g., congestive heart failure). Thus, both renal and extrarenal sites of interaction between the renin-angiotensin system and RSNA are involved in influencing the neural control of renal function.

[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.

Protective effects of efonidipine, a T- and L-type calcium channel blocker, on renal function and arterial stiffness in type 2 diabetic patients with hypertension and nephropathy.

PubMed

Sasaki, Hidehisa; Saiki, Atsuhito; Endo, Kei; Ban, Noriko; Yamaguchi, Takashi; Kawana, Hidetoshi; Nagayama, Daizi; Ohhira, Masahiro; Oyama, Tomokazu; Miyashita, Yoh; Shirai, Kohji

2009-10-01

The three types of calcium channel blocker (CCB), L-, T- and N-type, possess heterogeneous actions on endothelial function and renal microvascular function. In the present study, we evaluated the effects of two CCBs, efonidipine and amlodipine, on renal function and arterial stiffness. Forty type 2 diabetic patients with hypertension and nephropathy receiving angiotensin receptor II blockers were enrolled and randomly divided into two groups: the efonidipine group was administered efonidipine hydrochloride ethanolate 40 mg/day and the amlodipine group was admin-istered amlodipine besilate 5 mg/day for 12 months. Arterial stiffness was evaluated by the cardio-ankle vascular index (CAVI). Changes in blood pressure during the study were almost the same in the two groups. Sig-nificant increases in serum creatinine and urinary albumin and a significant decrease in the esti-mated glomerular filtration rate were observed in the amlodipine group, but not in the efonidipine group. On the other hand, significant decreases in plasma aldosterone, urinary 8-hydroxy-2'-deoxy-guanosine and CAVI were observed after 12 months in the efonidipine group, but not in the amlo-dipine group. These results suggest that efonidipine, which is both a T-type and L-type calcium chan-nel blocker, has more favorable effects on renal function, oxidative stress and arterial stiffness than amlodipine, an L-type calcium channel blocker.

Renal injury in Seipin-deficient lipodystrophic mice and its reversal by adipose tissue transplantation or leptin administration alone: adipose tissue-kidney crosstalk.

PubMed

Liu, Xue-Jing; Wu, Xiao-Yue; Wang, Huan; Wang, Su-Xia; Kong, Wei; Zhang, Ling; Liu, George; Huang, Wei

2018-05-08

Seipin deficiency is responsible for type 2 congenital generalized lipodystrophy with severe loss of adipose tissue (AT) and could lead to renal failure in humans. However, the effect of Seipin on renal function is poorly understood. Here we report that Seipin knockout (SKO) mice exhibited impaired renal function, enlarged glomerular and mesangial surface areas, renal depositions of lipid, and advanced glycation end products. Elevated glycosuria and increased electrolyte excretion were also detected. Relative renal gene expression in fatty acid oxidation and reabsorption pathways were impaired in SKO mice. Elevated glycosuria might be associated with reduced renal glucose transporter 2 levels. To improve renal function, AT transplantation or leptin administration alone was performed. Both treatments effectively ameliorated renal injury by improving all of the parameters that were measured in the kidney. The treatments also rescued insulin resistance and low plasma leptin levels in SKO mice. Our findings demonstrate for the first time that Seipin deficiency induces renal injury, which is closely related to glucolipotoxicity and impaired renal reabsorption in SKO mice, and is primarily caused by the loss of AT and especially the lack of leptin. AT transplantation and leptin administration are two effective treatments for renal injury in Seipin-deficient mice.-Liu, X.-J., Wu, X.-Y., Wang, H., Wang, S.-X., Kong, W., Zhang, L., Liu, G., Huang, W. Renal injury in Seipin-deficient lipodystrophic mice and its reversal by adipose tissue transplantation or leptin administration alone: adipose tissue-kidney crosstalk.

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

Effect of Cuscuta chinensis on renal function in ischemia/reperfusion-induced acute renal failure rats.

PubMed

Shin, Sun; Lee, Yun Jung; Kim, Eun Ju; Lee, An Sook; Kang, Dae Gill; Lee, Ho Sub

2011-01-01

The kidneys play a central role in regulating water, ion composition and excretion of metabolic waste products in the urine. Cuscuta chinensis has been known as an important traditional Oriental medicine for the treatment of liver and kidney disorders. Thus, we studied whether an aqueous extract of Cuscuta chinensis (ACC) seeds has an effect on renal function parameters in ischemia/reperfusion-induced acute renal failure (ARF) rats. Administration of 250 mg/kg/day ACC showed that renal functional parameters including urinary excretion rate, osmolality, Na(+), K(+), Cl(-), creatinine clearance, solute-free water reabsorption were significantly recovered in ischemia/reperfusion-induced ARF. Periodic acid Schiff staining showed that administration of ACC improved tubular damage in ischemia/reperfusion-induced ARF. In immunoblot and immunohistological examinations, ischemia/reperfusion-induced ARF decreased the expressions of water channel AQP 2, 3 and sodium potassium pump Na,K-ATPase in the renal medulla. However, administration of ACC markedly incremented AQP 2, 3 and Na,K-ATPase expressions. Therefore, these data indicate that administration of ACC ameliorates regulation of the urine concentration and renal functions in rats with ischemia/reperfusion-induced ARF.

Using OCT to predict post-transplant renal function

NASA Astrophysics Data System (ADS)

Andrews, Peter M.; Chen, Yu; Wierwille, Jeremiah; Joh, Daniel; Alexandrov, Peter; Rogalsky, Derek; Moody, Patrick; Chen, Allen; Cooper, Matthew; Verbesey, Jennifer E.; Gong, Wei; Wang, Hsing-Wen

2013-03-01

The treatment of choice for patients with end-stage renal disease is kidney transplantation. However, acute tubular necrosis (ATN) induced by an ischemic insult (e.g., from prolonged ex vivo storage times, or non-heart beating cadavers) is a major factor limiting the availability of donor kidneys. In addition, ischemic induced ATN is a significant risk factor for eventual graft survival and can be difficult to discern from rejection. Currently, there are no rapid and reliable tests to determine ATN suffered by donor kidneys and whether or not donor kidneys might exhibit delayed graft function. OCT (optical coherence tomography) is a rapidly emerging imaging modality that can function as a type of "optical biopsy", providing cross-sectional images of tissue morphology in situ and in real-time. In a series of recent clinical trials, we evaluated the ability of OCT to image those features of the renal microstructure that are predictive of ATN. Specifically, we found that OCT could effectively image through the intact human renal capsule and determine the extent of acute tubular necrosis. We also found that Doppler based OCT (i.e., DOCT) revealed renal blood flow dynamics that is also reported to be a determiner of post-transplant renal function. This kind of information will allow transplant surgeons to make the most efficient use of available donor kidneys, eliminate the possible use of bad donor kidneys, provide a measure of expected post-transplant renal function, and allow better distinction between post-transplant immunological rejection and ischemic-induced acute renal failure.

Population pharmacokinetics and pharmacodynamics of rivaroxaban in patients with non-valvular atrial fibrillation: results from ROCKET AF.

PubMed

Girgis, I G; Patel, M R; Peters, G R; Moore, K T; Mahaffey, K W; Nessel, C C; Halperin, J L; Califf, R M; Fox, K A A; Becker, R C

2014-08-01

Two once-daily rivaroxaban dosing regimens were compared with warfarin for stroke prevention in patients with non-valvular atrial fibrillation in ROCKET AF: 20 mg for patients with normal/mildly impaired renal function and 15 mg for patients with moderate renal impairment. Rivaroxaban population pharmacokinetic (PK)/pharmacodynamic (PD) modeling data from ROCKET AF patients (n = 161) are reported and are used to confirm established rivaroxaban PK and PK/PD models and to re-estimate values of the models' parameters for the current AF population. An oral one-compartment model with first-order absorption adequately described rivaroxaban PK. Age, renal function, and lean body mass influenced the PK model. Prothrombin time and prothrombinase-induced clotting time exhibited a near-linear relationship with rivaroxaban plasma concentration; inhibitory effects were observed through to 24 hours post-dose. Rivaroxaban plasma concentration and factor Xa activity had an inhibitory maximum-effect (Emax ) relationship. Renal function (on prothrombin time; prothrombinase-induced clotting time) and age (on factor Xa activity) had moderate effects on PK/PD models. PK and PK/PD models were shown to be adequate for describing the current dataset. These findings confirm the modeling and empirical results that led to the selection of doses tested against warfarin in ROCKET AF. © 2014, The American College of Clinical Pharmacology.

Renal Effects and Underlying Molecular Mechanisms of Long-Term Salt Content Diets in Spontaneously Hypertensive Rats

PubMed Central

Berger, Rebeca Caldeira Machado; Vassallo, Paula Frizera; Crajoinas, Renato de Oliveira; Oliveira, Marilene Luzia; Martins, Flávia Letícia; Nogueira, Breno Valentim; Motta-Santos, Daisy; Araújo, Isabella Binotti; Forechi, Ludimila; Girardi, Adriana Castello Costa; Santos, Robson Augusto Souza; Mill, José Geraldo

2015-01-01

Several evidences have shown that salt excess is an important determinant of cardiovascular and renal derangement in hypertension. The present study aimed to investigate the renal effects of chronic high or low salt intake in the context of hypertension and to elucidate the molecular mechanisms underlying such effects. To this end, newly weaned male SHR were fed with diets only differing in NaCl content: normal salt (NS: 0.3%), low salt (LS: 0.03%), and high salt diet (HS: 3%) until 7 months of age. Analysis of renal function, morphology, and evaluation of the expression of the main molecular components involved in the renal handling of albumin, including podocyte slit-diaphragm proteins and proximal tubule endocytic receptors were performed. The relationship between diets and the balance of the renal angiotensin-converting enzyme (ACE) and ACE2 enzymes was also examined. HS produced glomerular hypertrophy and decreased ACE2 and nephrin expressions, loss of morphological integrity of the podocyte processes, and increased proteinuria, characterized by loss of albumin and high molecular weight proteins. Conversely, severe hypertension was attenuated and renal dysfunction was prevented by LS since proteinuria was much lower than in the NS SHRs. This was associated with a decrease in kidney ACE/ACE2 protein and activity ratio and increased cubilin renal expression. Taken together, these results suggest that LS attenuates hypertension progression in SHRs and preserves renal function. The mechanisms partially explaining these findings include modulation of the intrarenal ACE/ACE2 balance and the increased cubilin expression. Importantly, HS worsens hypertensive kidney injury and decreases the expression nephrin, a key component of the slit diaphragm. PMID:26495970

Delafloxacin Pharmacokinetics in Subjects With Varying Degrees of Renal Function

PubMed Central

Hoover, Randall K.; Alcorn, Harry; Lawrence, Laura; Paulson, Susan K.; Quintas, Megan

2017-01-01

Abstract Delafloxacin, a fluoroquinolone, has activity against gram‐positive organisms including methicillin‐resistant Staphylococcus aureus and fluoroquinolone‐susceptible and –resistant gram‐negative organisms. This study was conducted to determine delafloxacin pharmacokinetics after a single intravenous infusion or oral dose administration in subjects with varying degrees of renal function. The study was an open‐label, parallel‐group crossover study in subjects with normal renal function or with mild, moderate, or severe renal impairment. Subjects received 300 mg delafloxacin intravenously, placebo intravenously, and 400 mg delafloxacin orally in 3 periods separated by ≥14‐day washouts. Blood and urine pharmacokinetic parameters were calculated using noncompartmental methods. Delafloxacin total clearance decreased with decreasing renal function, with a corresponding increase in AUC0–∞. After intravenous administration, mean total clearance was 13.7 and 7.07 L/h, and mean AUC0–∞ was 22.6 and 45.0 μg·h/mL in normal and severe renal subjects, respectively. Mean renal clearance as determined by urinary excretion was 6.03 and 0.44 L/h in normal and severe renal impairment subjects, respectively. Total clearance exhibited linear relationships to eGFR and CLCR. Similar observations were found after oral administration of delafloxacin. Single doses of delafloxacin 300 mg intravenously and 400 mg orally were well tolerated in all groups. In conclusion, renal insufficiency has an effect on delafloxacin clearance; a dosing adjustment for intravenous dosing is warranted for patients with severe renal impairment (eGFR < 30 mL/min). PMID:29251785

Differentiation of vasoactive renal sympathetic nerve fibres.

PubMed

Dibona, G F

2000-01-01

Activation of renal sympathetic nerves produces marked changes in renal haemodynamics, tubular ion and water transport and renin secretion. This review examines information indicating that these effects are mediated by functionally specific groups of renal sympathetic nerve fibres separately innervating the renal vessels, tubules and juxtaglomerular granular cells.

Renal impairment in HIV-infected patients initiating tenofovir-containing antiretroviral therapy regimens in a Primary Healthcare Setting in South Africa.

PubMed

Kamkuemah, Monika; Kaplan, Richard; Bekker, Linda-Gail; Little, Francesca; Myer, Landon

2015-04-01

Long-term use of tenofovir disoproxil fumarate is associated with declines in glomerular function and chronic kidney disease in HIV-infected patients. We aimed to assess the prevalence and incidence of renal impairment in a primary care setting in sub-Saharan Africa. We analysed data from 1092 HIV-infected patients initiating tenofovir at a primary care clinic in Cape Town, South Africa. Renal function was assessed for the first 12 months on ART by estimating glomerular filtration rate (eGFR) calculated using the Cockroft-Gault equation categorised into normal, mild, moderate and severe reduction in renal function based on values >90, 60-89, 30-59 and <30 ml/min/1.73 m(2) , respectively. Associations were assessed using logistic regression, and average GFR trajectory over time was modelled using linear mixed-effects models. The cohort consisted of 62% women; median age was 34 years (IQR 29; 41 years). The majority had normal renal function pre-ART (79%), 19% had mildly reduced GFR, and 2% had moderate renal impairment. Older age, more advanced WHO stage and anaemia were independently associated with prevalent renal impairment. On average, estimated glomerular function improved over the first year on tenofovir [1.10 ml/min/1.73 m(2) average increase over 12 months (95% CI: 0.80; 1.40)]. Male gender, anaemia and immunosuppression (WHO Stage III/IV and CD4 cell counts <100 cells/mm(3) ) were associated with lower average eGFR levels over time. Overall, 3% developed eGFR <50 ml/min/1.73 m(2) during this period. Serum creatinine tests conducted before 4 months on ART had low predictive value for predicting change in eGFR after a year on ART. Generally, renal function improved in HIV-infected adults initiating ART in this primary healthcare setting during the first year on ART. While monitoring of renal function is recommended in the first 4 months on ART, renal impairment appears uncommon during the first 12 months of tenofovir-containing ART in primary care populations. © 2014 John Wiley & Sons Ltd.

Cystatin C a marker for renal function after exercise.

PubMed

Mingels, A; Jacobs, L; Kleijnen, V; Wodzig, W; Dieijen-Visser, M van

2009-09-01

Renal impairment is common during and after severe exercise. In clinical practice, renal function is evaluated using serum creatinine, urine parameters, and equations to estimate the Glomular Filtration Rate (GFR). However, creatinine levels may be biased by skeletal muscle damage and the GFR equations, requiring age, gender and body weight, are shown to be inadequate in normals. In the present study, we show that serum cystatin C and creatinine concentrations were elevated after marathon running in 26% and 46% of the 70 recreational male runners, respectively, possibly because of reduction in renal blood flow. The mean cystatin C increase was twice as low as compared to creatinine (21% and 41%, respectively), suggesting that cystatin C is indeed less biased by muscle damage. Future research has to reveal whether training diminishes the elevation in renal markers. Overall, cystatin C seems a more reliable method to establish renal function during and after extensive exercise. Georg Thieme Verlag KG Stuttgart.

FXYD8, a Novel Regulator of Renal Na+/K+-ATPase in the Euryhaline Teleost, Tetraodon nigroviridis

PubMed Central

Wang, Pei-Jen; Yang, Wen-Kai; Lin, Chia-Hao; Hwang, Hau-Hsuan; Lee, Tsung-Han

2017-01-01

FXYD proteins are important regulators of Na+/K+-ATPase (NKA) activity in mammals. As an inhabitant of estuaries, the pufferfish (Tetraodon nigroviridis) responds to ambient salinity changes with efficient osmoregulation, including alterations in branchial, and renal NKA activities. Previous studies on teleostean FXYDs have mainly focused on the expression and potential functions of FXYD proteins in gills. The goal of the present study was to elucidate the potential role of FXYD8, a member of the fish FXYD protein family, in the modulation of NKA activity in the kidneys of this euryhaline pufferfish by using molecular, biochemical, and physiological approaches. The results demonstrate that T. nigroviridis FXYD8 (TnFXYD8) interacts with NKA in renal tubules. Meanwhile, the protein expression of renal TnFXYD8 was found to be significantly upregulated in hyperosmotic seawater-acclimated pufferfish. Moreover, overexpression of TnFXYD8 in Xenopus oocytes decreased NKA activity. Our results suggest the FXYD8 is able to modulate NKA activity through inhibitory effects upon salinity challenge. The present study further extends our understanding of the functions of FXYD proteins, the regulators of NKA, in vertebrates. PMID:28848450

The use of renal replacement therapy in acute decompensated heart failure.

PubMed

Udani, Suneel M; Murray, Patrick T

2009-01-01

The worsening of renal function in the context of decompensated heart failure is an increasingly common clinical scenario, dubbed the cardiorenal syndrome. Its development is not completely understood; however, it results from the hemodynamic and neurohumoral alterations that occur in the setting of left ventricular pressure and volume overload with poor cardiac output. Diuretics have been the mainstay of treatment; however, they are often unsuccessful in reversing the vicious cycle of volume overload, worsening cardiac function, and azotemia. Renal replacement therapy (RRT) in the form of isolated or continuous ultrafiltration (UF) with or without a component of solute clearance (hemofiltration or hemodialysis) has been increasingly utilized as a therapeutic tool in this setting. Initial clinical trial data on the use of UF have demonstrated promising cardiac outcomes with regard to fluid removal and symptom relief without worsening renal function. The addition of a component of solute clearance may provide additional benefits in these patients with varying degrees of renal impairment. The exact clinical setting in which the various forms of RRT should be applied as initial or early therapy for acute decompensated heart failure (ADHF) remains unknown. More research examining the use of RRT in ADHF is necessary; however, it appears that the patients with the most severe clinical presentations have the best chance of benefiting from the early application of RRT.

Maternal determinants of renal mass and function in the fetus and neonate.

PubMed

Brophy, Patrick

2017-04-01

The impact of adverse maternal and early gestational issues, ranging from maternal-fetal interactions all the way through to premature birth, are recognized as having influence on the subsequent development of chronic diseases later in life. The development of chronic kidney disease (CKD) as a direct result of early life renal injury or a sequela of diseases such as hypertension or diabetes is a good model example of the potential impact that early life events may have on renal development and lifelong function. The global monetary and human resource cost of CKD is exorbitant. Socio-economic factors, along with other factors (genetic and environmental) may significantly influence the timing and display of phenotypic expression in fetuses and neonates at risk for developing CKD, yet very few of these factors are studied or well understood. In general our focus has been directed at treatment once CKD is established. This strategy has been and remains short-sighted and costly. Earlier understanding of the intrauterine determinants of renal mass development (i.e. environmental "biomes", poor maternal-fetal health, socio-economic factors impacting early life events, diet, access to value based health care and educational opportunities on disease evolution) may allow us an opportunity for earlier intervention. This article aims to provide some foundation for improved understanding of the maternal determinants of renal mass and function in the fetus and neonate. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

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

2002-01-01

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

Single dose pharmacokinetics of the transdermal rotigotine patch in patients with impaired renal function.

PubMed

Cawello, Willi; Ahrweiler, Sascha; Sulowicz, Wladyslaw; Szymczakiewicz-Multanowska, Agnieszka; Braun, Marina

2012-01-01

To evaluate the influence of different stages of chronic renal insufficiency on the pharmacokinetics and safety/tolerability of the transdermally applied dopamine agonist rotigotine in an open label group comparison including 32 subjects (healthy, mild, moderate or severe impairment of renal function and patients with end-stage renal insufficiency requiring haemodialysis). METHODS All subjects received a single transdermal 10 cm² patch (24 h patch-on period) containing 4.5 mg rotigotine (nominal drug release 2 mg 24 h⁻¹). Main evaluations included relative bioavailability and renal elimination of rotigotine and its metabolites. Point estimates for the ratios between the groups with moderate to severe renal impairment and healthy subjects for the pharmacokinetic parameters AUC(0,t(last) ) and C(max) for the active substance unconjugated rotigotine were near 1:0.88 for AUC and 0.93 for C(max) for moderate renal impairment, 1.14 and 1.18 for severe renal impairment and 1.05 and 1.25 for end-stage renal insufficiency requiring haemodialysis. There was no correlation of these parameters with creatinine clearance. The amount of unconjugated rotigotine excreted into urine and renal clearance decreased with increasing severity of renal insufficiency but had no observable effect on total clearance as the amounts excreted were below 1% of the administered dose. Occurrence of adverse events did not increase with the degree of renal insufficiency. The pharmacokinetic profiles of unconjugated rotigotine were similar in healthy subjects and subjects with impaired renal function indicating that no dose adjustments are required for transdermal rotigotine in patients with different stages of chronic renal insufficiency including patients on haemodialysis. © 2011 UCB Biosciences GmbH. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

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

PubMed

Jagannathan, Ram; Patzer, Rachel E

2017-08-29

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

The Mitochondria-Targeted Antioxidant Mitoquinone Protects against Cold Storage Injury of Renal Tubular Cells and Rat Kidneys

PubMed Central

Mitchell, Tanecia; Rotaru, Dumitru; Saba, Hamida; Smith, Robin A. J.; Murphy, Michael P.

2011-01-01

The majority of kidneys used for transplantation are obtained from deceased donors. These kidneys must undergo cold preservation/storage before transplantation to preserve tissue quality and allow time for recipient selection and transport. However, cold storage (CS) can result in tissue injury, kidney discardment, or long-term renal dysfunction after transplantation. We have previously determined mitochondrial superoxide and other downstream oxidants to be important signaling molecules that contribute to CS plus rewarming (RW) injury of rat renal proximal tubular cells. Thus, this study's purpose was to determine whether adding mitoquinone (MitoQ), a mitochondria-targeted antioxidant, to University of Wisconsin (UW) preservation solution could offer protection against CS injury. CS was initiated by placing renal cells or isolated rat kidneys in UW solution alone (4 h at 4°C) or UW solution containing MitoQ or its control compound, decyltriphenylphosphonium bromide (DecylTPP) (1 μM in vitro; 100 μM ex vivo). Oxidant production, mitochondrial function, cell viability, and alterations in renal morphology were assessed after CS exposure. CS induced a 2- to 3-fold increase in mitochondrial superoxide generation and tyrosine nitration, partial inactivation of mitochondrial complexes, and a significant increase in cell death and/or renal damage. MitoQ treatment decreased oxidant production ∼2-fold, completely prevented mitochondrial dysfunction, and significantly improved cell viability and/or renal morphology, whereas DecylTPP treatment did not offer any protection. These findings implicate that MitoQ could potentially be of therapeutic use for reducing organ preservation damage and kidney discardment and/or possibly improving renal function after transplantation. PMID:21159749

The mitochondria-targeted antioxidant mitoquinone protects against cold storage injury of renal tubular cells and rat kidneys.

PubMed

Mitchell, Tanecia; Rotaru, Dumitru; Saba, Hamida; Smith, Robin A J; Murphy, Michael P; MacMillan-Crow, Lee Ann

2011-03-01

The majority of kidneys used for transplantation are obtained from deceased donors. These kidneys must undergo cold preservation/storage before transplantation to preserve tissue quality and allow time for recipient selection and transport. However, cold storage (CS) can result in tissue injury, kidney discardment, or long-term renal dysfunction after transplantation. We have previously determined mitochondrial superoxide and other downstream oxidants to be important signaling molecules that contribute to CS plus rewarming (RW) injury of rat renal proximal tubular cells. Thus, this study's purpose was to determine whether adding mitoquinone (MitoQ), a mitochondria-targeted antioxidant, to University of Wisconsin (UW) preservation solution could offer protection against CS injury. CS was initiated by placing renal cells or isolated rat kidneys in UW solution alone (4 h at 4°C) or UW solution containing MitoQ or its control compound, decyltriphenylphosphonium bromide (DecylTPP) (1 μM in vitro; 100 μM ex vivo). Oxidant production, mitochondrial function, cell viability, and alterations in renal morphology were assessed after CS exposure. CS induced a 2- to 3-fold increase in mitochondrial superoxide generation and tyrosine nitration, partial inactivation of mitochondrial complexes, and a significant increase in cell death and/or renal damage. MitoQ treatment decreased oxidant production ~2-fold, completely prevented mitochondrial dysfunction, and significantly improved cell viability and/or renal morphology, whereas DecylTPP treatment did not offer any protection. These findings implicate that MitoQ could potentially be of therapeutic use for reducing organ preservation damage and kidney discardment and/or possibly improving renal function after transplantation.

Chronic Renal Failure Secondary to Unrecognized Neurogenic Bladder in A Child with Myelodysplasia.

PubMed

Ahmed, Shameem; Paul, Siba Prosad

2017-01-01

Myelodysplasia includes a group of developmental anomalies resulting from defects that occur during neural tube closure. Urological morbidity in patients with myelodysplasia is significant and if not treated appropriately in a timely manner can potentially lead to progressive renal failure, requiring dialysis or transplantation. We report the case of a 13-year old girl with neurogenic bladder who presented chronic renal failure secondary to lipomyelomeningocele with retethering of cord. She was managed with urinary indwelling catheterization until optimization of renal function and then underwent detethering of cord with excision and repair of residual lipomeningomyelocele. Her renal parameters improved gradually over weeks and then were managed on self clean intermittent catheterization. The case emphasizes the need for considering retethering of spinal cord in children with myelodysplasia where symptoms of neurogenic bladder and recurrent urinary tract infections occur.

Nonsteroidal Anti-Inflammatory Drugs and the Kidney

PubMed Central

Hörl, Walter H.

2010-01-01

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the isoenzymes COX-1 and COX-2 of cyclooxygenase (COX). Renal side effects (e.g., kidney function, fluid and urinary electrolyte excretion) vary with the extent of COX-2-COX-1 selectivity and the administered dose of these compounds. While young healthy subjects will rarely experience adverse renal effects with the use of NSAIDs, elderly patients and those with co-morbibity (e.g., congestive heart failure, liver cirrhosis or chronic kidney disease) and drug combinations (e.g., renin-angiotensin blockers, diuretics plus NSAIDs) may develop acute renal failure. This review summarizes our present knowledge how traditional NSAIDs and selective COX-2 inhibitors may affect the kidney under various experimental and clinical conditions, and how these drugs may influence renal inflammation, water transport, sodium and potassium balance and how renal dysfunction or hypertension may result. PMID:27713354

Longitudinal assessment of renal size and function in extremely low birth weight children at 7 and 11 years of age.

PubMed

Starzec, Katarzyna; Klimek, Małgorzata; Grudzień, Andrzej; Jagła, Mateusz; Kwinta, Przemko

2016-11-01

There are a lack of studies describing a longitudinal association between preterm delivery and renal complications later in life. We assessed renal size and function in preterm infants born with extremely low birth weight (ELBW) during 4 years of follow-up, comparing these parameters to age-matched children born full term (term controls). The results of selected renal laboratory tests [levels of cystatin C, creatinine, blood urea nitrogen (BUN)] and of renal ultrasound evaluations were compared between the ELBW group and the term control group at age 7 and 11 years. The study population consisted of 64 children born with ELBW (ELBW children) who had been recruited at birth and 36 children born at term (term children) who took part in both follow-up assessments. Renal ultrasound examination revealed a significantly smaller renal volume in the 7- and 11-year-old ELBW children compared to the term controls [right kidney volume: 50.8 vs. 61.2 ml/m(2), respectively, at 7 years (p <0.01) and 51.4 vs. 58.2 ml/m(2), respectively, at 11 years (p <0.01); left kidney volume: 51.4 vs. 60.3 ml/m(2), respectively, at 7 years (p <0.01) and 55.2 vs. 60.7 ml/m(2), respectively, at 11 years (p = 0.02)]. Renal function in ELBW children was also affected. Serum cystatin C levels were significantly higher in ELBW children than in the controls at 7 years of age, and this difference remained statistically significant at 11 years of age [0.63 vs. 0.59 mg/l, respectively, at 7 years (p = 0.02) and 0.72 vs. 0.61 mg/l, respectively, at 11 years (p = 0.01)]. Six ELBW children also had elevated cystatin C levels (0.97-1.11 mg/l) at 11 years of age. Cystatin C levels were within normal range in the ELBW children at age 7 years and in term children in both follow-up studies. BUN levels were higher in ELBW children at the age of 11 years (4.49 vs. 4.15 mmol/l; p = 0.028). Continued follow-up of these patients will reveal whether the observed worsening in renal function will persist into adulthood.

Screening for Albuminuria Identifies Individuals at Increased Renal Risk

PubMed Central

van der Velde, Marije; Halbesma, Nynke; de Charro, Frank T.; Bakker, Stephan J.L.; de Zeeuw, Dick; de Jong, Paul E.; Gansevoort, Ronald T.

2009-01-01

It is unknown whether screening for albuminuria in the general population identifies individuals at increased risk for renal replacement therapy (RRT) or accelerated loss of renal function. Here, in a general population-based cohort of 40,854 individuals aged 28 to 75 yr, we collected a first morning void for measurement of urinary albumin. In a subset of 6879 individuals, we measured 24-h urinary albumin excretion and estimated GFR at baseline and during 6 yr of follow-up. Linkage with the national RRT registry identified 45 individuals who started RRT during 9 yr of follow-up. The quantity of albuminuria was associated with increased renal risk: the higher the level of albuminuria, the higher the risk of need for renal replacement therapy and the more rapid renal function decline. A urinary albumin concentration of ≥20 mg/L identified individuals who started RRT during follow-up with 58% sensitivity and 92% specificity. Of the identified individuals, 39% were previously unknown to have impaired renal function, and 50% were not being medically treated. Restricting screening to high-risk groups (e.g., known hypertension, diabetes, cardiovascular disease [CVD], older age) reduced the sensitivity of the test only marginally but failed to identify 45% of individuals with micro- and macroalbuminuria. In conclusion, individuals with elevated levels of urinary albumin are at increased risk for RRT and accelerated loss of renal function. Screening for albuminuria identifies patients at increased risk for progressive renal disease, 40 to 50% of whom were previously undiagnosed or untreated. PMID:19211710

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

PubMed

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

2018-06-01

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

The Role of mTOR Inhibitors in Liver Transplantation: Reviewing the Evidence

PubMed Central

Klintmalm, Goran B.; Nashan, Björn

2014-01-01

Despite the success of liver transplantation, long-term complications remain, including de novo malignancies, metabolic syndrome, and the recurrence of hepatitis C virus (HCV) and hepatocellular carcinoma (HCC). The current mainstay of treatment, calcineurin inhibitors (CNIs), can also worsen posttransplant renal dysfunction, neurotoxicity, and diabetes. Clearly there is a need for better immunosuppressive agents that maintain similar rates of efficacy and renal function whilst minimizing adverse effects. The mammalian target of rapamycin (mTOR) inhibitors with a mechanism of action that is different from other immunosuppressive agents has the potential to address some of these issues. In this review we surveyed the literature for reports of the use of mTOR inhibitors in adult liver transplantation with respect to renal function, efficacy, safety, neurological symptoms, de novo tumors, and the recurrence of HCC and HCV. The results of our review indicate that mTOR inhibitors are associated with efficacy comparable to CNIs while having benefits on renal function in liver transplantation. We also consider newer dosing schedules that may limit side effects. Finally, we discuss evidence that mTOR inhibitors may have benefits in the oncology setting and in relation to HCV-related allograft fibrosis, metabolic syndrome, and neurotoxicity. PMID:24719752

From anatomy to function: diagnosis of atherosclerotic renal artery stenosis.

PubMed

Odudu, Aghogho; Vassallo, Diana; Kalra, Philip A

2015-12-01

Atherosclerotic renal artery stenosis (ARAS) affects 7% of the over 65 s and will be increasingly common with an ageing population. ARAS obstructs normal renal perfusion with adverse renal and cardiovascular consequences. Drug therapy is directed at reducing atherosclerotic risk. Two recent major trials of revascularization for ARAS showed that clinical outcomes were not improved beyond those offered by optimal drug therapy in most patients. This reflects experimental data showing that restoration of blood flow alone may not attenuate a cascade of tissue injury. A shift from anatomic to functional imaging of ARAS coupled to novel therapies might improve clinical outcomes in selected patients. This review outlines the case for separately assessing hemodynamic significance of arterial stenosis and functional reserve of renal parenchymal tissue. The authors consider current and emerging diagnostic techniques for ARAS and their potential to allow individualized and functionally directed treatments.

Oral manifestations in a renal osteodystrophy patient - a case report with review of literature.

PubMed

J, Parthiban; Nisha V, Aarthi; Gs, Asokan; Ca, Prakash; Mm, Varadharaja

2014-08-01

Renal Osteodystrophy (ROD) is a common complication of chronic renal disease (CRD) and is the part of a broad spectrum of disorders of mineral metabolism that occurs in the clinical setting. It occurs early in the course of chronic renal failure and progresses as the kidney function deteriorates. It is an osseous alteration believed to arise from increased parathyroid function associated with inappropriate calcium, phosphorus and vitamin D metabolism. Involvement of the jaws is common and radiographic alterations are often one of the earliest signs of chronic renal failure. Herein, reporting a case of Chronic Renal Failure (Bilateral Grade I Neuropathy) with ROD presenting oral manifestations in an 11-year -old male child.

Reversal deterioration of renal function accompanied with primary hypothyrodism.

PubMed

Dragović, Tamara

2012-02-01

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

Obstetric acute renal failure 1956-1987.

PubMed

Turney, J H; Ellis, C M; Parsons, F M

1989-06-01

A total of 142 women with severe acute renal failure (ARF) resulting from obstetric causes was treated by dialysis at a single centre from 1956 to 1987. One-year survival was 78.6%, which compares favourably with other causes of ARF. Abortion, haemorrhage and preclampsia comprised 95% of cases, with survival being best (82.9%) with abortion. Survival was adversely affected by increasing age. Acute cortical necrosis (12.7% of patients) carried 100% mortality after 6 years. Follow-up of survivors showed normal renal function up to 31 years following ARF; 25-year patient survival was 71.6%. Improvements in obstetric care and the disappearance of illegal abortions have resulted in a dramatic decline in the incidence of obstetric ARF.

Aging and the Disposition and Toxicity of Mercury in Rats

PubMed Central

Bridges, Christy C.; Joshee, Lucy; Zalups, Rudolfs K.

2014-01-01

Progressive loss of functioning nephrons, secondary to age-related glomerular disease, can impair the ability of the kidneys to effectively clear metabolic wastes and toxicants from blood. Additionally, as renal mass is diminished, cellular hypertrophy occurs in functional nephrons that remain. We hypothesize that these nephrons are exposed to greater levels of nephrotoxicants, such as inorganic mercury (Hg2+), and thus are at an increased risk of becoming intoxicated by these compounds. The purpose of the present study was to characterize the effects of aging on the disposition and renal toxicity of Hg2+ in young adult and aged Wistar rats. Paired groups of animals were injected (i.v.) with either a 0.5 μmol • kg−1 non-nephrotoxic or a 2.5 μmol • kg−1 nephrotoxic dose of mercuric chloride (HgCl2). Plasma creatinine and renal biomarkers of proximal tubular injury were greater in both groups of aged rats than in the corresponding groups of young adult rats. Histologically, evidence of glomerular sclerosis, tubular atrophy, interstitial inflammation and fibrosis were significant features of kidneys from aged animals. In addition, proximal tubular necrosis, especially along the straight segments in the inner cortex and outer stripe of the outer medulla was a prominent feature in the renal sections from both aged and young rats treated with the nephrotoxic dose of HgCl2. Our findings indicate 1) that overall renal function is significantly impaired in aged rats, resulting in chronic renal insufficiency and 2) the disposition of HgCl2 in aging rats is significantly altered compared to that of young rats. PMID:24548775

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

Renal hypodysplasia associates with a WNT4 variant that causes aberrant canonical WNT signaling.

PubMed

Vivante, Asaf; Mark-Danieli, Michal; Davidovits, Miriam; Harari-Steinberg, Orit; Omer, Dorit; Gnatek, Yehudit; Cleper, Roxana; Landau, Daniel; Kovalski, Yael; Weissman, Irit; Eisenstein, Israel; Soudack, Michalle; Wolf, Haike Reznik; Issler, Naomi; Lotan, Danny; Anikster, Yair; Dekel, Benjamin

2013-03-01

Abnormal differentiation of the renal stem/progenitor pool into kidney tissue can lead to renal hypodysplasia (RHD), but the underlying causes of RHD are not well understood. In this multicenter study, we identified 20 Israeli pedigrees with isolated familial, nonsyndromic RHD and screened for mutations in candidate genes involved in kidney development, including PAX2, HNF1B, EYA1, SIX1, SIX2, SALL1, GDNF, WNT4, and WT1. In addition to previously reported RHD-causing genes, we found that two affected brothers were heterozygous for a missense variant in the WNT4 gene. Functional analysis of this variant revealed both antagonistic and agonistic canonical WNT stimuli, dependent on cell type. In HEK293 cells, WNT4 inhibited WNT3A induced canonical activation, and the WNT4 variant significantly enhanced this inhibition of the canonical WNT pathway. In contrast, in primary cultures of human fetal kidney cells, which maintain WNT activation and more closely represent WNT signaling in renal progenitors during nephrogenesis, this mutation caused significant loss of function, resulting in diminished canonical WNT/β-catenin signaling. In conclusion, heterozygous WNT4 variants are likely to play a causative role in renal hypodysplasia.

Renal Hypodysplasia Associates with a Wnt4 Variant that Causes Aberrant Canonical Wnt Signaling

PubMed Central

Vivante, Asaf; Mark-Danieli, Michal; Davidovits, Miriam; Harari-Steinberg, Orit; Omer, Dorit; Gnatek, Yehudit; Cleper, Roxana; Landau, Daniel; Kovalski, Yael; Weissman, Irit; Eisenstein, Israel; Soudack, Michalle; Wolf, Haike Reznik; Issler, Naomi; Lotan, Danny; Anikster, Yair

2013-01-01

Abnormal differentiation of the renal stem/progenitor pool into kidney tissue can lead to renal hypodysplasia (RHD), but the underlying causes of RHD are not well understood. In this multicenter study, we identified 20 Israeli pedigrees with isolated familial, nonsyndromic RHD and screened for mutations in candidate genes involved in kidney development, including PAX2, HNF1B, EYA1, SIX1, SIX2, SALL1, GDNF, WNT4, and WT1. In addition to previously reported RHD-causing genes, we found that two affected brothers were heterozygous for a missense variant in the WNT4 gene. Functional analysis of this variant revealed both antagonistic and agonistic canonical WNT stimuli, dependent on cell type. In HEK293 cells, WNT4 inhibited WNT3A induced canonical activation, and the WNT4 variant significantly enhanced this inhibition of the canonical WNT pathway. In contrast, in primary cultures of human fetal kidney cells, which maintain WNT activation and more closely represent WNT signaling in renal progenitors during nephrogenesis, this mutation caused significant loss of function, resulting in diminished canonical WNT/β-catenin signaling. In conclusion, heterozygous WNT4 variants are likely to play a causative role in renal hypodysplasia. PMID:23520208

Downregulated microRNA-510-5p acts as a tumor suppressor in renal cell carcinoma.

PubMed

Chen, Duqun; Li, Yuchi; Yu, Zuhu; Li, Yifan; Su, Zhengming; Ni, Liangchao; Yang, Shangqi; Gui, Yaoting; Lai, Yongqing

2015-08-01

MicroRNA (miR)-510-5p has been demonstrated to be involved in a number of types of malignancy; however, the function of miR-510-5p in renal cancer remains unclear. The present study aimed to determine the expression of miR-510-5p in renal cell carcinoma (RCC) specimens and analyzed the impact of miR-510-5p on renal cancer by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, wound scratch and apoptosis assays. The results showed that miR-510-5p was significantly downregulated in RCC specimens compared with normal renal specimens. Overexpression of miR-510-5p by synthetic mature mimics reduced cell proliferation and migration and induced an increase in cell apoptosis, indicating that miR-510-5p may act as a tumor suppressor in RCC. The present study firstly revealed that downregulated miR-510-5p functioned as a tumor suppressor by reducing cellular proliferation and migration, and inducing apoptosis in RCC. Further research is required to define target genes of miR-510-5p to determine the cellular mechanism of miR-510-5p in the carcinogenesis of RCC.

Differential effects of grape juice on gastric emptying and renal function from cisplatin-induced acute adverse toxicity.

PubMed

Ko, J-L; Tsai, C-H; Liu, T-C; Lin, M-Y; Lin, H-L; Ou, C-C

2016-08-01

Grape skin and seeds contain large amounts of phytochemicals such as polyphenols, resveratrol, and proanthocyanidins, which possess antioxidant activities. Cisplatin is widely used in the treatment of cancer. High doses of cisplatin have also been known to produce acute adverse effects. The aim of this study was to investigate the protective effects of antioxidant properties of whole grape juice (with skin and seeds) on cisplatin-induced acute gastrointestinal tract disorders and nephrotoxicity in Wistar rats. Gastric emptying is significantly increased in whole grape juice-pretreated rats when compared to cisplatin treatment alone. The expression of ghrelin mRNA of stomach is increased in rats with whole grape juice. However, pretreatment with whole grape juice did not reduce renal function markers in acute renal toxicity. No significant changes were recorded in the oxidative stress/antioxidant status parameters of any study group. In contrast, pretreatment with whole grape juice slightly improved tubular cell vacuolization, tubular dilatation, and cast formation in renal tubules. These results show that consumption of whole grape juice induces somewhat beneficial effects in preventing cisplatin-mediated dyspepsia but does not offer protection against cisplatin-induced acute renal toxicity. © The Author(s) 2015.

Risk factors associated with the deterioration of renal function after kidney transplantation.

PubMed

Serón, Daniel; Fulladosa, Xavier; Moreso, Francesc

2005-12-01

Renal function early after transplantation is associated with a large number of risk factors, including donor age and acute rejection. During the 1990s, donor age increased and the incidence of acute rejection decreased. Renal function between the third and sixth month improved slightly, while renal function deterioration between the third or sixth month and the 12th month improved significantly. This modification coincides with the introduction of mycophenolate mofetil and tacrolimus. The tendency for sustained renal improvement early after transplantation became more evident after the introduction of anti-calcineurin-free regimens. Studies of protocol biopsies have shown that there is an increase of glomerular volume after transplantation and that a larger glomerular volume at 4 months is associated with a better glomerular filtration rate. This adaptation mechanism is impaired in patients with chronic allograft nephropathy or in patients with high cyclosporin levels. Taken together, these data suggest that the steady improvement of renal allograft function may be partly explained by a better glomerular adaptation after transplantation because of the avoidance of the vasoconstrictive effect of anti-calcineurinic agents, and a significant decrease in the prevalence of chronic allograft nephropathy early after transplantation.

Copeptin Associates with Cause-Specific Mortality in Patients with Impaired Renal Function: Results from the LURIC and the 4D Study.

PubMed

Krane, Vera; Genser, Bernd; Kleber, Marcus E; Drechsler, Christiane; März, Winfried; Delgado, Graciela; Allolio, Bruno; Wanner, Christoph; Fenske, Wiebke

2017-05-01

In chronic kidney disease (CKD) arginine vasopressin (AVP) cannot efficiently act via renal V2-receptors. AVP is upregulated leading to augmented activation of V1a- and V1b-receptors, which might contribute to the increase in cardiovascular and infectious complications in CKD. Here, we evaluate copeptin, a surrogate of AVP, and its association with cause specific mortality among patients within the whole spectrum of renal function. Copeptin was measured in baseline samples from the LURIC (n = 3131 patients with coronary angiograms) and the 4D-Study (n = 1241 type 2 diabetic hemodialysis patients). Patients were stratified into 4 groups: estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m 2 , 60-89 mL/min/1.73 m 2 , <60 mL/min/1.73 m 2 , and hemodialysis. The association of copeptin with mortality was assessed by Cox proportional hazards regression during 9.9 years of median follow-up in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study and 4 years of median follow-up in the German Diabetes Dialysis Study (4D-Study). Median copeptin increased with decreasing eGFR: 5.6 [interquartile range (IQR), 3.1-8.1] pmol/L (eGFR ≥90 mL/min/1.73 m 2 ), 6.7 (2.9-10.5) pmol/L (eGFR 60-89 mL/min/1.73 m 2 ), 15.3 (6.7-23.9) pmol/L (eGFR <60 mL/min/1.73 m 2 ), and 80.8 (51.2-122) pmol/L (hemodialysis), respectively. Per SD increase in copeptin, the risk of coronary, infectious, and all-cause mortality increased by 25, 30, and 15% [hazard ratios (HR), 1.25; 95% CI, 1.13-1.39; HR, 1.30; 95% CI, 0.98-1.71; and HR, 1.15; 95% CI, 1.05-1.25], respectively, in patients with eGFR 60-89 mL/min/1.73 m 2 . Except for coronary death, results were similar among patients with more advanced renal disease. No significant association was found in patients with normal renal function. Copeptin concentrations were independently associated with coronary, infectious, and all-cause mortality in patients with renal impairment. In patients with normal renal function no significant association was found. © 2017 American Association for Clinical Chemistry.

The impact of intrarenal nitric oxide synthase inhibition on renal blood flow and function in mild and severe hyperdynamic sepsis.

PubMed

Ishikawa, Ken; Bellomo, Rinaldo; May, Clive N

2011-04-01

In experimental hyperdynamic sepsis, renal function deteriorates despite renal vasodilatation and increased renal blood flow. Because nitric oxide is increased in sepsis and participates in renal blood flow control, we investigated the effects of intrarenal Nω-nitro-L-arginine methyl ester, a nonspecific nitric oxide synthase inhibitor, in mild and severe sepsis. Prospective crossover and randomized control interventional studies. University-affiliated research institute. Thirty-two merino ewes. Examination of responses to intrarenal infusion of Nω-nitro-L-arginine methyl ester for 8 hrs in unilaterally nephrectomized normal sheep and in sheep administered Escherichia coli. : In normal sheep, Nω-nitro-L-arginine methyl ester decreased renal blood flow (301 ± 30 to 228 ± 26 mL/min) and creatinine clearance (40.0 ± 5.8 to 31.1 ± 2.8 mL/min), whereas plasma creatinine increased, but fractional excretion of sodium was unchanged. In sheep with nonhypotensive hyperdynamic sepsis, plasma creatinine increased and there were decreases in creatinine clearance (34.5 ± 4.6 to 20.1 ± 3.7 mL/min) and fractional excretion of sodium despite increased renal blood flow. Infusion of Nω-nitro-L-arginine methyl ester normalized renal blood flow and increased urine output, but creatinine clearance did not improve and plasma creatinine and fractional excretion of sodium increased. In sheep with severe hypotensive sepsis, creatinine clearance decreased further (31.1 ± 5.4 to 16.0 ± 1.7 mL/min) despite increased renal blood flow. Infusion of Nω-nitro-L-arginine methyl ester restored mean arterial pressure and reduced renal blood flow but did not improve plasma creatinine or creatinine clearance. In hyperdynamic sepsis, with or without hypotension, creatinine clearance decreased despite increasing renal blood flow. Intrarenal Nω-nitro-L-arginine methyl ester infusion reduced renal blood flow but did not improve creatinine clearance. These data indicate that septic acute kidney injury is not the result of decreased renal blood flow nor is it improved by nonspecific nitric oxide synthase inhibition.

Impact of Polymyxin B Associated Acute Kidney Injury in 1-Year Mortality and Renal Function Recovery.

PubMed

Gomes, Eduardo C; Falci, Diego R; Bergo, Pedro; Zavascki, Alexandre P; Rigatto, Maria Helena

2018-03-01

To evaluate the impact of polymyxin B (PMB)- associated Acute Kidney Injury (AKI) in 1-year mortality and renal function recovery. Patients >18 years old who survived the first 30-days after PMB therapy were followed for 1-year. The impact of AKI and Renal Failure (using RIFLE score) in 1-year mortality was analyzed, along with other confounding variables. Variables with a P value ≤0.2 were included in a forward stepwise Cox regression model. In the subgroup of patients who developed AKI, we evaluated renal function recovery. A total of 234 patients were included for analyses. Of these, 108 (46.1%) died, in a median time of 63 (38.3-102.5) days. The use of other nephrotoxic drugs along with PMB (P=0.05), renal failure (P=0.03), dialysis (P<0.01) and re-exposure to PMB (P<0.01), were all significantly related to 1-year mortality, while male gender had a protective effect (P=0.01). Independent factors related to death were age (aHR 1.02, 95%CI 1.00-1.03, P=0.02), re-exposure to PMB (aHR 2.69, 95%CI 1.82-3.95, P<0.01), and male gender (aHR0.6, 95%CI 0.41-0.87, P=0.01), when controlled for renal failure (aHR 1.28, 95%CI 0.78-2.10, P=0.34).Thirty one of 94 (33%) patients who developed AKI had renal function recovery within one-year. Mortality rates were high in the first year after PMB use and only one third of patients who develop AKI return to baseline renal function. Strategies to reduce renal toxicity are urgently needed in these patients. Copyright © 2018. Published by Elsevier B.V.

Hemodynamic and neurochemical determinates of renal function in chronic heart failure.

PubMed

Gilbert, Cameron; Cherney, David Z I; Parker, Andrea B; Mak, Susanna; Floras, John S; Al-Hesayen, Abdul; Parker, John D

2016-01-15

Abnormal renal function is common in acute and chronic congestive heart failure (CHF) and is related to the severity of congestion. However, treatment of congestion often leads to worsening renal function. Our objective was to explore basal determinants of renal function and their response to hemodynamic interventions. Thirty-seven patients without CHF and 59 patients with chronic CHF (ejection fraction; 23 ± 8%) underwent right heart catheterization, measurements of glomerular filtration rate (GFR; inulin) and renal plasma flow (RPF; para-aminohippurate), and radiotracer estimates of renal sympathetic activity. A subset (26 without, 36 with CHF) underwent acute pharmacological intervention with dobutamine or nitroprusside. We explored the relationship between baseline and drug-induced hemodynamic changes and changes in renal function. In CHF, there was an inverse relationship among right atrial mean pressure (RAM) pressure, RPF, and GFR. By contrast, mean arterial pressure (MAP), cardiac index (CI), and measures of renal sympathetic activity were not significant predictors. In those with CHF there was also an inverse relationship among the drug-induced changes in RAM as well as pulmonary artery mean pressure and the change in GFR. Changes in MAP and CI did not predict the change in GFR in those with CHF. Baseline values and changes in RAM pressure did not correlate with GFR in those without CHF. In the CHF group there was a positive correlation between RAM pressure and renal sympathetic activity. There was also an inverse relationship among RAM pressure, GFR, and RPF in patients with chronic CHF. The observation that acute reductions in RAM pressure is associated with an increase in GFR in patients with CHF has important clinical implications. Copyright © 2016 the American Physiological Society.

The role of the immune system in kidney disease.

PubMed

Tecklenborg, J; Clayton, D; Siebert, S; Coley, S M

2018-05-01

The immune system and the kidneys are closely linked. In health the kidneys contribute to immune homeostasis, while components of the immune system mediate many acute forms of renal disease and play a central role in progression of chronic kidney disease. A dysregulated immune system can have either direct or indirect renal effects. Direct immune-mediated kidney diseases are usually a consequence of autoantibodies directed against a constituent renal antigen, such as collagen IV in anti-glomerular basement membrane disease. Indirect immune-mediated renal disease often follows systemic autoimmunity with immune complex formation, but can also be due to uncontrolled activation of the complement pathways. Although the range of mechanisms of immune dysregulation leading to renal disease is broad, the pathways leading to injury are similar. Loss of immune homeostasis in renal disease results in perpetual immune cell recruitment and worsening damage to the kidney. Uncoordinated attempts at tissue repair, after immune-mediated disease or non-immune mediated injury, result in fibrosis of structures important for renal function, leading eventually to kidney failure. As renal disease often manifests clinically only when substantial damage has already occurred, new diagnostic methods and indeed treatments must be identified to inhibit further progression and promote appropriate tissue repair. Studying cases in which immune homeostasis is re-established may reveal new treatment possibilities. © 2018 British Society for Immunology.

Role of the intrarenal renin-angiotensin system in the progression of renal disease.

PubMed

Urushihara, Maki; Kagami, Shoji

2017-09-01

The intrarenal renin-angiotensin system (RAS) has many well-documented pathophysiologic functions in both blood pressure regulation and renal disease development. Angiotensin II (Ang II) is the major bioactive product of the RAS. It induces inflammation, renal cell growth, mitogenesis, apoptosis, migration, and differentiation. In addition, Ang II regulates the gene expression of bioactive substances and activates multiple intracellular signaling pathways that are involved in renal damage. Activation of the Ang II type 1 (AT1) receptor pathway results in the production of proinflammatory mediators, intracellular formation of reactive oxygen species, cell proliferation, and extracellular matrix synthesis, which in turn facilities renal injury. Involvement of angiotensinogen (AGT) in intrarenal RAS activation and development of renal disease has previously been reported. Moreover, studies have demonstrated that the urinary excretion rates of AGT provide a specific index of the intrarenal RAS status. Enhanced intrarenal AGT levels have been observed in experimental models of renal disease, supporting the concept that AGT plays an important role in the development and progression of renal disease. In this review, we focus on the role of intrarenal RAS activation in the pathophysiology of renal disease. Additionally, we explored the potential of urinary AGT as a novel biomarker of intrarenal RAS status in renal disease.

Supplementation of Eurycoma longifolia Jack Extract for 6 Weeks Does Not Affect Urinary Testosterone: Epitestosterone Ratio, Liver and Renal Functions in Male Recreational Athletes

PubMed Central

Chen, Chee Keong; Mohamad, Wan Mohd Zahiruddin Wan; Ooi, Foong Kiew; Ismail, Shaiful Bahari; Abdullah, Mohamad Rusli; George, Annie

2014-01-01

Background: Eurycoma longifolia Jack (ElJ) has been shown to elevate serum testosterone and increased muscle strength in humans. This study investigated the effects of Physta® a standardized water extract of ElJ (400 mg/day for 6 weeks) on testosterone: epitestosterone (T:E) ratio, liver and renal functions in male recreational athletes. Methods: A total of 13 healthy male recreational athletes were recruited in this double blind, placebo-controlled, cross-over study. The participants were required to consume either 400 mg of ElJ or placebo daily for 6 weeks in the first supplementation regimen. Following a 3 week wash-out period, the participants were requested to consume the other supplement for another 6 weeks. Mid-stream urine samples and blood samples were collected prior to and after 6 weeks of supplementation with either ElJ or placebo. The urine samples were subsequently analyzed for T:E ratio while the blood samples were analyzed for liver and renal functions. Results: T:E ratio was not significantly different following 6 weeks supplementation of either ElJ or placebo compared with their respective baseline values. Similarly, there were no significant changes in both the liver and renal functions tests following the supplementation of ElJ. Conclusions: Supplementation of ElJ i.e. Physta® at a dosage of 400 mg/day for 6 weeks did not affect the urinary T:E ratio and hence will not breach any doping policies of the International Olympic Committee for administration of exogenous testosterone or its precursor. In addition, the supplementation of ElJ at this dosage and duration was safe as it did adversely affect the liver and renal functions. PMID:25013692

Preoperative determinant of early postoperative renal function following radical cystectomy and intestinal urinary diversion.

PubMed

Gondo, Tatsuo; Ohno, Yoshio; Nakashima, Jun; Hashimoto, Takeshi; Nakagami, Yoshihiro; Tachibana, Masaaki

2017-02-01

To identify preoperative factors correlated with postoperative early renal function in patients who had undergone radical cystectomy (RC) and intestinal urinary diversion. We retrospectively identified 201 consecutive bladder cancer patients without distant metastasis who had undergone RC at our institution between 2003 and 2012. The estimated glomerular filtration rate (eGFR) was calculated using the modified Chronic Kidney Disease Epidemiology equation before RC and 3 months following RC. Univariate and stepwise multiple linear regression analyses were applied to estimate postoperative renal function and to identify significant preoperative predictors of postoperative renal function. Patients who had undergone intestinal urinary diversion and were available for the collection of follow-up data (n = 164) were eligible for the present study. Median preoperative and postoperative eGFRs were 69.7 (interquartile range [IQR] 56.3-78.0) and 70.7 (IQR 57.3-78.1), respectively. In univariate analyses, age, preoperative proteinuria, thickness of abdominal subcutaneous fat tissue (TSF), preoperative serum creatinine level, preoperative eGFR, and urinary diversion type were significantly associated with postoperative eGFR. In a stepwise multiple linear regression analysis, preoperative eGFR, age, and TSF were significant factors for predicting postoperative eGFR (p < 0.001, p = 0.02, and p = 0.046, respectively). The estimated postoperative eGFRs correlated well with the actual postoperative eGFRs (r = 0.65, p < 0.001). Preoperative eGFR, age, and TSF were independent preoperative factors for determining postoperative renal function in patients who had undergone RC and intestinal urinary diversion. These results may be used for patient counseling before surgery, including the planning of perioperative chemotherapy administration.

Long-term health and work outcomes of renal transplantation and patterns of work status during the end-stage renal disease trajectory.

PubMed

van der Mei, Sijrike F; Kuiper, Daphne; Groothoff, Johan W; van den Heuvel, Wim J A; van Son, Willem J; Brouwer, Sandra

2011-09-01

The aim of this study was to examine the health- and work outcomes of renal transplant recipients long-term after transplantation as well as the pattern of work status, work ability and disability benefits during the end-stage renal disease (ESRD) trajectory that precedes transplantation. 34 transplant recipients completed interviews 3, 13 months and >6 years posttransplantation. Health status (SF-36), work ability (WAI), and fatigue (CIS) were assessed by questionnaires, clinical data were derived from medical charts, and data on functional limitations were extracted from the social security system database. The work status trajectory preceding transplantation was examined retrospectively. Of the 34 third wave transplant recipients, 29% were severely fatigued. Compared with the general working population, recipients experienced worse general health and less vitality. Non-working recipients had worse renal function and general health, and more limitations in physical functioning compared to working recipients. The WAI score indicated moderate work ability for 60% of the employed recipients. Although 67% were employed (45% parttime), 30% of those working still received some disability benefits. Social insurance physicians found variable levels of functional limitations. The mean work status trajectory showed more sickness absence and less work ability during dialysis, but after transplantation, both work status and work ability generally improved. Transplant recipients have a compromised health status which leads to functional limitations and disability. Although work status improved after transplantation, a substantial number of the transplant recipients received disability benefits. The negative health consequences of anti-rejection medications may play an important role in long-term work ability. These results indicate that a 'new' kidney has advantages over dialysis with respect to work, but does not necessarily leads to 'normal' work outcomes.

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

PubMed

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

2018-06-01

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

Green Tea Polyphenols Ameliorate the Early Renal Damage Induced by a High-Fat Diet via Ketogenesis/SIRT3 Pathway

PubMed Central

Yi, Weijie; Xie, Xiao; Du, Miying; Bu, Yongjun; Wu, Nannan; Yang, Hui; Tian, Chong; Xu, Fangyi; Xiang, Siyun; Zhang, Piwei; Chen, Zhuo

2017-01-01

Scope Several reports in the literature have suggested the renoprotective effects of ketone bodies and green tea polyphenols (GTPs). Our previous study found that GTP consumption could elevate the renal expression of the ketogenic rate-limiting enzyme, which was decreased by a high-fat diet (HFD) in rats. Here, we investigated whether ketogenesis can mediate renoprotection by GTPs against an HFD. Methods and Results Wistar rats were fed a standard or HFD with or without GTPs for 18 weeks. The renal oxidative stress level, kidney function, renal expression, and activity levels of mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase 2 (HMGCS2) and sirtuin 3(SIRT3) were detected. The increased renal oxidative stress and the loss of renal function induced by the HFD were ameliorated by GTPs. Renal ketogenesis and SIRT3 expression and activity levels, which were reduced by the HFD, were restored by GTPs. In vitro, HEK293 cells were transfected with the eukaryotic expression plasmid pcDNA HMGCS2. GTP treatment could upregulate HMGCS2 and SIRT3 expression. Although SIRT3 expression was not affected by HMGCS2 transfection, the 4-hydroxy-2-nonenal (4-HNE) level and the acetyl-MnSOD (K122)/MnSOD ratio were reduced in HMGCS2-transfected cells in the context of H2O2. Conclusion The ketogenesis/SIRT3 pathway mediates the renoprotection of GTPs against the oxidative stress induced by an HFD. PMID:28814987

Population Pharmacokinetics and Therapeutic Efficacy of Febuxostat in Patients with Severe Renal Impairment.

PubMed

Hira, Daiki; Chisaki, Yugo; Noda, Satoshi; Araki, Hisazumi; Uzu, Takashi; Maegawa, Hiroshi; Yano, Yoshitaka; Morita, Shin-Ya; Terada, Tomohiro

2015-01-01

The aim of the present study was to determine the influence of severe renal dysfunction (estimated glomerular filtration rate <30 ml/min/1.73 m(2), including hemodialysis) on the pharmacokinetics and therapeutic effects of febuxostat using a population pharmacokinetic analysis. This study recruited patients with hyperuricemia who were initially treated with allopurinol, but were switched to febuxostat, and it consists of 2 sub-studies: a pharmacokinetic study (26 patients) and retrospective efficacy evaluation study (51 patients). The demographic and clinical data of patients were collected from electronic medical records. Plasma febuxostat concentrations were obtained at each hospital visit. Population pharmacokinetic modeling was performed with NONMEM version 7.2. A total of 128 plasma febuxostat concentrations from 26 patients were used in the population pharmacokinetic analysis. The data were best described by a 1-compartment model with first order absorption. Covariate analysis revealed that renal function did not influence the pharmacokinetics of febuxostat, whereas actual body weight significantly influenced apparent clearance and apparent volume of distribution. The retrospective efficacy analysis showed the favorable therapeutic response of febuxostat switched from allopurinol in patients with moderate to severe renal impairment. No serious adverse event associated with febuxostat was observed irrespective of renal function. The population pharmacokinetic analysis and therapeutic analysis of febuxostat revealed that severe renal dysfunction had no influence on the pharmacokinetic parameters of febuxostat. These results suggest that febuxostat is tolerated well by patients with severe renal impairment. © 2015 S. Karger AG, Basel.

Impact of Stone Removal on Renal Function: A Review

PubMed Central

Wood, Kyle; Keys, Tristan; Mufarrij, Patrick; Assimos, Dean G

2011-01-01

Stone removal can improve renal function by eradicating obstruction and, in certain cases, an underlying infection. Stone-removing procedures, however, may negatively impact functional integrity. Many things may impact the latter, including the procedures used, the methods of assessing function, the time when these assessments are made, the occurrence of complications, the baseline condition of the kidney, and patient-related factors. In the majority of cases, little significant functional impairment occurs. However, there are gaps in our knowledge of this subject, including the cumulative effects of multiple procedures violating the renal parenchyma and long-term functional outcomes. PMID:21935339

Pharmacokinetics of the Novel Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone (BAY 94-8862) in Individuals With Renal Impairment.

PubMed

Heinig, Roland; Kimmeskamp-Kirschbaum, Nina; Halabi, Atef; Lentini, Silvia

2016-11-01

Finerenone (BAY 94-8862) is a nonsteroidal mineralocorticoid receptor antagonist in development for the treatment of diabetic kidney disease. This observational trial compared the pharmacokinetics of a single oral dose of finerenone 10 mg (immediate-release tablet) in adults with mild (creatinine clearance [CL CR ] 50-80 mL/min; n = 8), moderate (CL CR 30 to < 50 mL/min; n = 8), or severe (CL CR < 30 mL/min; n  =  9) renal impairment with those in adults with normal renal function (CL CR > 80 mL/min; n  = 8) over 96 hours postdose. Exposure to finerenone was not affected by mild renal impairment. In participants with moderate or severe renal impairment, exposure to finerenone was increased compared with those with normal renal function (increase in area under the curve for unbound finerenone, 57.1% [outlier excluded] and 46.5%, respectively), with moderate to high interindividual variability. Renal impairment had no consistent effect on the maximum plasma concentration, C max (differences in C max for unbound finerenone of +12% and -7% with moderate [outlier excluded] and severe impairment vs normal renal function, respectively). Renal elimination of finerenone is minimal. However, changes in exposure may occur because of the effects of renal impairment on nonrenal routes of elimination. © 2016, The American College of Clinical Pharmacology.

Hyperammonemia associated with distal renal tubular acidosis or urinary tract infection: a systematic review.

PubMed

Clericetti, Caterina M; Milani, Gregorio P; Lava, Sebastiano A G; Bianchetti, Mario G; Simonetti, Giacomo D; Giannini, Olivier

2018-03-01

Hyperammonemia usually results from an inborn error of metabolism or from an advanced liver disease. Individual case reports suggest that both distal renal tubular acidosis and urinary tract infection may also result in hyperammonemia. A systematic review of the literature on hyperammonemia secondary to distal renal tubular acidosis and urinary tract infection was conducted. We identified 39 reports on distal renal tubular acidosis or urinary tract infections in association with hyperammonemia published between 1980 and 2017. Hyperammonemia was detected in 13 children with distal renal tubular acidosis and in one adult patient with distal renal tubular acidosis secondary to primary hyperparathyroidism. In these patients a negative relationship was observed between circulating ammonia and bicarbonate levels (P < 0.05). In 31 patients (19 children, 12 adults), an acute urinary tract infection was complicated by acute hyperammonemia and symptoms and signs of acute neuronal dysfunction, such as an altered level of consciousness, convulsions and asterixis, often associated with signs of brain edema, such as anorexia and vomiting. Urea-splitting bacteria were isolated in 28 of the 31 cases. The urinary tract was anatomically or functionally abnormal in 30 of these patients. This study reveals that both altered distal renal tubular acidification and urinary tract infection may be associated with relevant hyperammonemia in both children and adults.

The correlation between effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) with renal scintigraphy 99mTc-DTPA study

NASA Astrophysics Data System (ADS)

Ratnasari, D.; Nazir, F.; Toresano, L. O. H. Z.; Pawiro, S. A.; Soejoko, D. S.

2016-03-01

The prevalence of chronic renal diseases in Indonesia has an increasing annual trend, because it is frequently unrecognized and often co-exists with other disease. GFR and ERPF are parameters currently utilized to estimate renal function at routine renal scintigraphy 99m-Tc DTPA study. This study used 99m-Tc DTPA to measure GFR and ERPF. The purpose of this study was to find the correlation between ERPF and GFR, for ERPF analysis with Schlegel's method, and GFR analysis with Gate's method, as well as to find correction factor between both variables. Analysis of renal scintigraphy has been performed at Department of Nuclear Medicine Pertamina Center Hospital to thirty patient images acquired from 2014 to 2015 which were analyzed retrospectively data, using gamma camera dual head with counting method from renal scintigraphy 99m-Tc DTPA study. The calculation was executed by means of both display and manual calculation. Pearson's statistical analysis resulted on Positive Correlation for all data, with ERPF and GFR (display) showing Strongly Positive Correlation (r = 0.82; p- value < 0.05). Standard deviation was found to be 27.58 and 107.64 for GFR and ERPF (display), respectively. Our result indicated that the use of 99mTc-DTPA measure ERPF was not recommended.

Wavelet-based segmentation of renal compartments in DCE-MRI of human kidney: initial results in patients and healthy volunteers.

PubMed

Li, Sheng; Zöllner, Frank G; Merrem, Andreas D; Peng, Yinghong; Roervik, Jarle; Lundervold, Arvid; Schad, Lothar R

2012-03-01

Renal diseases can lead to kidney failure that requires life-long dialysis or renal transplantation. Early detection and treatment can prevent progression towards end stage renal disease. MRI has evolved into a standard examination for the assessment of the renal morphology and function. We propose a wavelet-based clustering to group the voxel time courses and thereby, to segment the renal compartments. This approach comprises (1) a nonparametric, discrete wavelet transform of the voxel time course, (2) thresholding of the wavelet coefficients using Stein's Unbiased Risk estimator, and (3) k-means clustering of the wavelet coefficients to segment the kidneys. Our method was applied to 3D dynamic contrast enhanced (DCE-) MRI data sets of human kidney in four healthy volunteers and three patients. On average, the renal cortex in the healthy volunteers could be segmented at 88%, the medulla at 91%, and the pelvis at 98% accuracy. In the patient data, with aberrant voxel time courses, the segmentation was also feasible with good results for the kidney compartments. In conclusion wavelet based clustering of DCE-MRI of kidney is feasible and a valuable tool towards automated perfusion and glomerular filtration rate quantification. Copyright © 2011 Elsevier Ltd. All rights reserved.

Hypertension and Hyperglycemia Synergize to Cause Incipient Renal Tubular Alterations Resulting in Increased NGAL Urinary Excretion in Rats

PubMed Central

Blázquez-Medela, Ana M.; García-Sánchez, Omar; Blanco-Gozalo, Víctor; Quiros, Yaremi; Montero, María J.; Martínez-Salgado, Carlos; López-Novoa, José M.; López-Hernández, Francisco J.

2014-01-01

Background Hypertension and diabetes are the two leading causes of chronic kidney disease (CKD) eventually leading to end stage renal disease (ESRD) and the need of renal replacement therapy. Mortality among CKD and ESRD patients is high, mostly due to cardiovascular events. New early markers of risk are necessary to better anticipate the course of the disease, to detect the renal affection of additive risk factors, and to appropriately handle patients in a pre-emptive and personalized manner. Methods Renal function and NGAL urinary excretion was monitored in rats with spontaneous (SHR) or L-NAME induced hypertension rendered hyperglycemic (or not as controls). Results Combination of hypertension and hyperglycemia (but not each of these factors independently) causes an increased urinary excretion of neutrophil gelatinase-associated lipocalin (NGAL) in the rat, in the absence of signs of renal damage. Increased NGAL excretion is observed in diabetic animals with two independent models of hypertension. Elevated urinary NGAL results from a specific alteration in its tubular handling, rather than from an increase in its renal expression. In fact, when kidneys of hyperglycaemic-hypertensive rats are perfused in situ with Krebs-dextran solution containing exogenous NGAL, they excrete more NGAL in the urine than hypertensive rats. We also show that albuminuria is not capable of detecting the additive effect posed by the coexistence of these two risk factors. Conclusions Our results suggest that accumulation of hypertension and hyperglycemia induces an incipient and quite specific alteration in the tubular handling of NGAL resulting in its increased urinary excretion. PMID:25148248

Parathyroidectomy Halts the Deterioration of Renal Function in Primary Hyperparathyroidism.

PubMed

Tassone, Francesco; Guarnieri, Andrea; Castellano, Elena; Baffoni, Claudia; Attanasio, Roberto; Borretta, Giorgio

2015-08-01

Decreased renal function has been consistently included among factors prompting recommendation for surgery in primary hyperparathyroidism (PHPT). However, most retrospective studies addressing this issue did not show an improvement in renal function after parathyroidectomy (PTX). The aim of this study was to investigate changes in renal function after PTX in PHPT patients subdivided according to renal function at diagnosis. This was a retrospective cross-sectional study. We studied 109 consecutive PHPT patients before and after PTX. Biochemical evaluation included fasting total and ionized serum calcium, phosphate, creatinine, immunoreactive intact PTH, and 25-hydroxyvitamin D3 levels. Glomerular filtration rate (GFR) was assessed with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Mean (± SD) CKD-EPI estimated GFR (eGFR) at diagnosis was 82.4 ± 19.3 mL/min/1.73 m(2) (median, 84.8 mL/min/1.73 m(2); interquartile range, 68.5-94.2 mL/min/1.73 m(2)). Patients with eGFR equal to or higher than 60 mL/min/1.73 m(2) (group 1, n = 95) were significantly younger than patients with eGFR lower than 60 mL/min/1.73 m(2) (group 2, n = 14; P < .0003). After PTX, eGFR did not change in patients of group 2 (P = .509), whereas it was significantly reduced in patients of group 1 (P < .0002). The difference in eGFR between baseline and post-PTX values was correlated negatively with baseline serum creatinine (R = -0.27; P = .0052) and positively with baseline CKD-EPI eGFR (R = 0.32; P = .00062). At multiple regression analysis, only systolic blood pressure and baseline CKD-EPI eGFR were independent predictors of GFR variation. Surgical cure of PHPT halts renal function deterioration in patients with coexisting renal disease. Our study thus supports the indication for surgery in patients with eGFR less than 60 mL/min/1.73 m(2), as recommended by current guidelines. Moreover, our data show that presurgical renal function is a relevant predictor of renal function after PTX.

Treatment options for renal cell carcinoma in renal allografts: a case series from a single institution.

PubMed

Swords, Darden C; Al-Geizawi, Samer M; Farney, Alan C; Rogers, Jeffrey; Burkart, John M; Assimos, Dean G; Stratta, Robert J

2013-01-01

Renal cell carcinoma (RCC) is more common in renal transplant and dialysis patients than the general population. However, RCC in transplanted kidneys is rare, and treatment has previously consisted of nephrectomy with a return to dialysis. There has been recent interest in nephron-sparing procedures as a treatment option for RCC in allograft kidneys in an effort to retain allograft function. Four patients with RCC in allograft kidneys were treated with nephrectomy, partial nephrectomy, or radiofrequency ablation. All of the patients are without evidence of recurrence of RCC after treatment. We found nephron-sparing procedures to be reasonable initial options in managing incidental RCCs diagnosed in functioning allografts to maintain an improved quality of life and avoid immediate dialysis compared with radical nephrectomy of a functioning allograft. However, in non-functioning renal allografts, radical nephrectomy may allow for a higher chance of cure without the loss of transplant function. Consequently, radical nephrectomy should be utilized whenever the allograft is non-functioning and the patient's surgical risk is not prohibitive. © 2013 John Wiley & Sons A/S.

Implementation of Get with the Guideline Acute Myocardial Infarction Program at Johns Hopkins Hospital and Its Effect on Core Measures

DTIC Science & Technology

2007-05-25

allergy E Patient is discharged on hydralazine/nitrate therapy* E Hypotension* El Moderate or severe aortic stenosis El Worsening renal function* E...Hypotension* E Moderate or severe aortic stenosis El Worsening renal function* E Hyperkalemia* E Bilateral renal artery stenosis * E Pregnancy* E Other...Hyperkalemia* El Bilateral renal artery stenosis * E Pregnancy* El Other - must be documented in medical record Angiotension Receptor Blocker (ARB

[Hereditary cerebro-oculo-renal syndromes].

PubMed

Sessa, Galina; Hjortshøj, Tina Duelund; Egfjord, Martin

2014-02-17

Although many congenital diseases present disturbances of the central nervous system, eyes and renal function, only few of these have a defined genetic basis. The first clinical features of cerebro-oculo-renal diseases usually develop in early childhood and deterioration of kidney function and even end-stage kidney disease may occur in a young age. The syndromes should be considered in patients with retarded growth and development, central nervous system abnormalities, impaired vision or blindness and progressive renal failure.

[A case report of simultaneous liver, pancreas-duodenum, and kidney transplantation in a patient with post-hepatitic cirrhosis combined with uremia and insulin-dependent diabetes related to chronic pancreatitis].

PubMed

Wang, He; Dou, Ke-feng; Yang, Xiao-jian; Qin, Wei-jun; Zhang, Geng; Yu, Lei; Kang, Fu-xia; Chen, Shao-yang; Xiong, Li-ze; Song, Zhen-shun; Liu, Zheng-cai

2006-09-12

To study the effect of triple organ transplantation (liver, kidney, and pancreas) in patient of end-stage liver disease with renal failure and diabetes, and to explore the optimal surgical procedure. Simultaneous piggyback orthotopic heterotopic liver, pancreas-duodenum, and kidney transplantation was performed on a 43-year-old male patient with exocrine pancreatic insufficiency and insulin-dependent diabetes related to chronic pancreatitis (CP) who developed hepatic and renal failure. The pancreatic exocrine secretions were drained enterically to the jejunum. Prednisone, tacrolimus, mycophenolate mofetil, and ATG were used as immunosuppression therapy. Good liver and pancreas allograft function recovery was achieved within 7 days after the operation. And the recovery of renal allograft function was delayed. The renal allograft was removed because of break-down of renal blood flow 16 days after the transplantation. A new renal transplantation was performed at the same position. The second kidney graft recovered its normal function 3 days later. Up to the writing of this paper no acute rejection of organs and such complications as pancreatitis, thrombosis, and localized infection occurred. The patient became insulin independent with normal liver and renal function. Simultaneous piggyback orthotopic heterotopic liver, pancreas-duodenum, and kidney transplantation can be a good method for the patients with exocrine pancreatic insufficiency and insulin-dependent diabetes combined with hepatic and renal failure.

Clinical Correlates and Prognostic Value of Proenkephalin in Acute and Chronic Heart Failure.

PubMed

Matsue, Yuya; Ter Maaten, Jozine M; Struck, Joachim; Metra, Marco; O'Connor, Christopher M; Ponikowski, Piotr; Teerlink, John R; Cotter, Gad; Davison, Beth; Cleland, John G; Givertz, Michael M; Bloomfield, Daniel M; Dittrich, Howard C; van Veldhuisen, Dirk J; van der Meer, Peter; Damman, Kevin; Voors, Adriaan A

2017-03-01

Proenkephalin (pro-ENK) has emerged as a novel biomarker associated with both renal function and cardiac function. However, its clinical and prognostic value have not been well evaluated in symptomatic patients with heart failure. The association between pro-ENK and markers of renal function was evaluated in 95 patients with chronic heart failure who underwent renal hemodynamic measurements, including renal blood flow (RBF) and glomerular filtration rate (GFR) with the use of 131 I-Hippuran and 125 I-iothalamate clearances, respectively. The association between pro-ENK and clinical outcome in acute heart failure was assessed in another 1589 patients. Pro-ENK was strongly correlated with both RBF (P < .001) and GFR (P < .001), but not with renal tubular markers. In the acute heart failure cohort, pro-ENK was a predictor of death through 180 days, heart failure rehospitalization through 60 days, and death or cardiovascular or renal rehospitalization through day 60 in univariable analyses, but its predictive value was lost in a multivariable model when other renal markers were entered in the model. In patients with chronic and acute heart failure, pro-ENK is strongly associated with glomerular function, but not with tubular damage. Pro-ENK provides limited prognostic information in patients with acute heart failure on top of established renal markers. Copyright © 2016 Elsevier Inc. All rights reserved.

Single-dose rATG induction at renal transplantation: superior renal function and glucoregulation with less hypomagnesemia.

PubMed

Stevens, R Brian; Lane, James T; Boerner, Brian P; Miles, Clifford D; Rigley, Theodore H; Sandoz, John P; Nielsen, Kathleen J; Skorupa, Jill Y; Skorupa, Anna J; Kaplan, Bruce; Wrenshall, Lucile E

2012-01-01

Rabbit anti-thymocyte globulin (rATG) induction reduces reperfusion injury and improves renal function in kidney recipients by means of properties unrelated to T-cell lysis. Here, we analyze intensive rATG induction (single dose, rATG(S) , vs. divided dose, rATG(D) ) for improved renal function and protection against hyperglycemia. Patients without diabetes (n = 98 of 180) in a prospective randomized trial of intensive rATG induction were followed for six months for the major secondary composite end point of impaired glucose regulation (hyperglycemia and new-onset diabetes after transplantation, NODAT). Prospectively collected data included fasting blood glucose and HbA(1c). Serum Mg(++) was routinely collected and retrospectively analyzed. Induction with rATG(S) produced less impaired glucose regulation (p = 0.05), delayed NODAT development (p = 0.02), less hyperglycemia (p = 0.02), better renal function (p = 0.04), and less hypomagnesemia (p = 0.02), a factor associated with a lower incidence of NODAT. Generalized linear modeling confirmed that rATG(S) protects against a synergistic interaction between tacrolimus and sirolimus that otherwise increased hypomagnesemia (p = 0.008) and hyperglycemia (p = 0.03). rATG(S) initiated before renal reperfusion improved early renal function and reduced impaired glucose regulation, an injury by diabetogenic maintenance agents (tacrolimus and sirolimus). © 2011 John Wiley & Sons A/S.

Renal function and plasma volume following ultramarathon cycling.

PubMed

Neumayr, G; Pfister, R; Hoertnagl, H; Mitterbauer, G; Prokop, W; Joannidis, M

2005-01-01

In recreational cyclists marathon cycling influences renal function only on a minimal scale. Respective information on extreme ultramarathon cycling in better trained athletes is not available. The objective was to evaluate the renal and haematological effects of ultraendurance cycling in the world's best ultramarathon cyclists. Creatinine (CR), urea, haemoglobin (Hb), haematocrit (Hct) and plasma volume (PV) were investigated in 16 male ultramarathon cyclists during the 1st Race Across the Alps in 2001 (distance: 525 km; cumulative altitude difference: 12,600 m). All renal functional parameters were normal pre-exercise. During the race serum CR, urea and uric acid rose significantly by 33, 97 % and 18 % (p <0.001 respectively) and nearly normalised again on the following day. The decline in calculated CR clearance was 25 %. There was a negative correlation (r=- 0.575, p=0.02) between the rise in serum CR and the athlete's training kilometers. The serum urea/CR ratio rose above 40 in 12 athletes (75 %). Mean fractional sodium excretion and fractional uric acid excretion fell below 0.5 % (p <0.001) and 7 %, indicating reduced renal perfusion. The deflection of the renal functional parameters was temporary and nearly gone after 24 hours of recovery. Hct declined during the race from 0.44 to 0.42, and continued falling on the next day (0.42 --> 0.40; p <0.001). The corresponding rises in calculated PV were + 8 % and + 22 %. The study affirms that in world class cyclists the enormous strains of ultramarathon cycling influence renal function only on a minimal scale. The impact on the PV, however, is pronounced leading to marked haemodilution post-exercise. This very temporary "impairment of renal function" seems to be the physiological response to ultramarathon cycling and may be attenuated to some extent by preceding high-volume training.

Pharmacokinetics and Tolerability of Lorcaserin in Special Populations: Elderly Patients and Patients with Renal or Hepatic Impairment.

PubMed

Christopher, Ronald J; Morgan, Michael E; Tang, Yong; Anderson, Christen; Sanchez, Matilde; Shanahan, William

2017-04-01

To determine whether dosage adjustment is likely to be necessary for effective and well-tolerated use of a pharmaceutical agent, guidance documents from the US Food and Drug Administration recommend pharmacokinetics studies in patients with impaired renal or impaired hepatic function and in the elderly population. Three studies were conducted to evaluate the pharmacokinetic properties and tolerability of lorcaserin in these populations. Lorcaserin was evaluated in single-dose pharmacokinetics studies of 3 overweight/obese populations: (1) elderly (aged >65 years) patients; (2) patients with impaired renal function; and (3) those with impaired hepatic function. In elderly patients, C max was lower (geometric mean ratio [GMR], 0.83; 90% CI, 0.71-0.97), but AUC was unchanged versus adult patients. In patients with renal impairment, C max was reduced versus that in patients with normal renal function (GMR: mild impairment, 0.99 [90% CI, 0.76-1.29]; moderate, 0.70 [90% CI, 0.54-0.90]; and severe, 0.69 [90% CI, 0.53-0.89]); no trend in AUC was observed in this group versus renal impairment. In patients with hepatic impairment, C max was decreased (GMR: mild impairment, 0.92 [90% CI, 0.76-1.11]; moderate, 0.86 [90% CI, 0.71-1.04]), and AUC was increased versus patients with normal hepatic function. Based on these findings, no lorcaserin dose adjustments are necessary in elderly patients with normal renal function or in patients with mild/moderate renal or hepatic impairment. ClinicalTrials.gov identifiers: NCT00828581, NCT00828438, and NCT00828932. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Renal uptake and tolerability of a 2'-O-methoxyethyl modified antisense oligonucleotide (ISIS 113715) in monkey.

PubMed

Henry, Scott P; Johnson, Mark; Zanardi, Thomas A; Fey, Robert; Auyeung, Diana; Lappin, Patrick B; Levin, Arthur A

2012-11-15

The primary target organ for uptake of systemically administered phosphorothioate oligonucleotides is the kidney cortex and the proximal tubular epithelium in particular. To determine the effect of oligonucleotide uptake on renal function, a detailed renal physiology study was performed in cynomolgus monkeys treated with 10-40 mg/kg/week ISIS 113715 for 4 weeks. The concentrations of oligonucleotide in the kidney cortex ranged from 1400 to 2600 μg/g. These concentrations were associated with histologic changes in proximal tubular epithelial cells that ranged from the appearance of cytoplasmic basophilic granules to atrophic and degenerative changes at higher concentrations. However, there were no renal functional abnormalities as determined by the typical measurements of blood urea nitrogen, serum creatinine, creatinine clearance, or urine specific gravity. Nor were there changes in glomerular filtration rate, or renal blood flow. Specific urinary markers of tubular epithelial cell damage, such as N-acetyl-glucosaminidase, and α-glutathione-s-transferase were not affected. Tubular function was further evaluated by monitoring the urinary excretion of amino acids, β(2)-microglobulin, or glucose. Renal function was challenged by administering a glucose load and by examining concentrating ability after a 4-h water deprivation. Neither challenge produced any evidence of change in renal function. The only change observed was a low incidence of increased urine protein/creatinine ratio in monkeys treated with ≥40 mg/kg/week which was rapidly reversible. Collectively, these data indicate that ISIS 113715-uptake by the proximal tubular epithelium has little or no effect on renal function at concentrations of 2600 μg/g. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Renal neural mechanisms in salt-sensitive hypertension.

PubMed

DiBona, G F

1995-01-01

Genetic forms of salt (NaCl)-sensitive hypertension are characterized by increased renal sympathetic nerve activity responses to environmental stimuli. The increases in renal sympathetic nerve activity produce marked changes in renal function with renal vasoconstriction and sodium and water retention which can contribute to the initiation, development and maintenance of hypertension. In genetic forms of NaCl-sensitive hypertension, increased dietary NaCl intake produces alterations in norepinephrine kinetics with decreased concentrations of norepinephrine in regions of the anterior hypothalamus which are critical for the regulation of peripheral sympathetic nerve activity. This local central decrease in tonic alpha 2 adrenoceptor sympathoinhibitory input leads to increased peripheral (renal) sympathetic nerve activity and hypertension. Similarly, with increased dietary NaCl intake, patients with NaCl-sensitive hypertension develop increased arterial pressure, renal vasoconstriction, increased glomerular capillary pressure and increased urinary albumin excretion. Thus, increased dietary NaCl intake can, via central nervous system actions, produce increases in renal sympathetic nerve activity whose renal functional effects contribute to the pathophysiology of hypertension.

Diuretic 99mTc DTPA renography in assessment of renal function and drainage in infants with antenatally detected hydronephrosis.

PubMed

Radulović, Marija; Pucar, Dragan; Jauković, Ljiljana; Sisić, Marija; Krstić, Zoran; Ajdinović, Boris

2015-12-01

The controversy over the postnatal management of infants with antenataly detected hydronephrosis (ANH) still exists. We presented the results of diuretic 99mTc diethylenetriamine pentaacetic acid (DTPA) renography in 30 infants with the antenatal diagnosis of unilateral renal pelvic dilatation. The aim of this study was to assess the renal function determined by the pattern of drainage and split renal function (SRF) on diuretic renography and to correlate these findings with anteroposterior pelvic diameter (APD) estimated by ultrasonography. A total of 30 infants with 60 renal units (RU) (25 boys and 5 girls, median age 6.0 months, range 2-24) presented with unilateral hydronephrosis on ultrasound in the newborn period, underwent DTPA diuretic renal scintigraphy (F+15 protocol). The median APD evaluated on perinatal ultrasound was 15 mm (range 5-30). The postnatal associated clinical diagnosis were pelviureteric junction obstruction (PUJ), simple hydronephrosis, megaureter, vesicoureteral reflux (VUR) and posterior urethral valves in 11, 10, 6, 2 and 1 infant, respectively. Images and Tmax/2 after diuretic stimulation on the background subtracted renographic curves were used as the criteria for classifying the drainage as good, partial, and poor or no drainage. The SRF was calculated with the integral method. Good drainage was shown in 36/60, partial drainage in 13/60 and poor or no drainage in 11/60 RU. The SRF > 40% was observed in 55/60 RU, with no RU showing SRF lower than 23.5%. In infants with severe ANH the obstruction was not excluded in 94.1%. Diuretic renography in antenatally detected hydronephrosis should be a useful tool in postnatal follow up, especially in differentiating nonobstructive hydronephrosis from obstructive. It is also importanat to assess and monitor the SRF. Our results suggest that even in the presence of partial or no drainage, SRF may not be significantly impaired.

Polyuria due to vasopressin V2 receptor antagonism is not associated with increased ureter diameter in ADPKD patients

PubMed Central

Casteleijn, Niek F.; Messchendorp, A. Lianne; Bae, Kyong T.; Higashihara, Eiji; Kappert, Peter; Torres, Vicente; Meijer, Esther; Leliveld, Anna M.

2017-01-01

Background Tolvaptan, a vasopressin V2 receptor antagonist, has been shown to reduce the rates of growth in total kidney volume (TKV) and renal function loss in ADPKD patients, but also leads to polyuria because of its aquaretic effect. Prolonged polyuria can result in ureter dilatation with consequently renal function loss. Therefore, we aimed to investigate the effect of tolvaptan-induced polyuria on ureter diameter in ADPKD patients. Methods 70 ADPKD patients were included (51 were randomized to tolvaptan and 19 to placebo). At baseline and after 3 years of treatment renal function was measured (mGFR) and MRI was performed to measure TKV and ureter diameter at the levels of renal pelvis and fifth lumbar vertebral body (L5). Results In these patients [65.7 % male, age 41 ± 9 years, mGFR 74 ± 27 mL/min/1.73 m2 and TKV 1.92 (1.27–2.67) L], no differences were found between tolvaptan and placebo-treated patients in 24-h urine volume at baseline (2.5 vs. 2.5 L, p = 0.8), nor in ureter diameter at renal pelvis and L5 (4.0 vs. 4.2 mm, p = 0.4 and 3.0 vs. 3.1 mm, p = 0.3). After 3 years of treatment 24-h urine volume was higher in tolvaptan-treated patients when compared to placebo (4.7 vs. 2.3 L, p < 0.001), but no differences were found in ureter diameter between both groups (renal pelvis: 4.2 vs. 4.4 mm, p = 0.4 and L5: 3.1 vs. 3.3 mm, p = 0.4). Conclusions Tolvaptan-induced polyuria did not lead to an increase in ureter diameter, suggesting that tolvaptan is a safe therapy from a urological point of view. PMID:27339446

Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model

PubMed Central

Wang, Xuexiang; Johnson, Ashley C.; Williams, Jan M.; White, Tiffani; Chade, Alejandro R.; Zhang, Jie; Liu, Ruisheng; Roman, Richard J.; Lee, Jonathan W.; Kyle, Patrick B.; Solberg-Woods, Leah

2015-01-01

Some studies have reported up to 40% of patients born with a single kidney develop hypertension, proteinuria, and in some cases renal failure. The increased susceptibility to renal injury may be due, in part, to reduced nephron numbers. Notably, children who undergo nephrectomy or adults who serve as kidney donors exhibit little difference in renal function compared with persons who have two kidneys. However, the difference in risk between being born with a single kidney versus being born with two kidneys and then undergoing nephrectomy are unclear. Animal models used previously to investigate this question are not ideal because they require invasive methods to model congenital solitary kidney. In this study, we describe a new genetic animal model, the heterogeneous stock-derived model of unilateral renal agenesis (HSRA) rat, which demonstrates 50%–75% spontaneous incidence of a single kidney. The HSRA model is characterized by reduced nephron number (more than would be expected by loss of one kidney), early kidney/glomerular hypertrophy, and progressive renal injury, which culminates in reduced renal function. Long-term studies of temporal relationships among BP, renal hemodynamics, and renal function demonstrate that spontaneous single-kidney HSRA rats are more likely than uninephrectomized normal littermates to exhibit renal impairment because of the combination of reduced nephron numbers and prolonged exposure to renal compensatory mechanisms (i.e., hyperfiltration). Future studies with this novel animal model may provide additional insight into the genetic contributions to kidney development and agenesis and the factors influencing susceptibility to renal injury in individuals with congenital solitary kidney. PMID:25349207

Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model.

PubMed

Wang, Xuexiang; Johnson, Ashley C; Williams, Jan M; White, Tiffani; Chade, Alejandro R; Zhang, Jie; Liu, Ruisheng; Roman, Richard J; Lee, Jonathan W; Kyle, Patrick B; Solberg-Woods, Leah; Garrett, Michael R

2015-07-01

Some studies have reported up to 40% of patients born with a single kidney develop hypertension, proteinuria, and in some cases renal failure. The increased susceptibility to renal injury may be due, in part, to reduced nephron numbers. Notably, children who undergo nephrectomy or adults who serve as kidney donors exhibit little difference in renal function compared with persons who have two kidneys. However, the difference in risk between being born with a single kidney versus being born with two kidneys and then undergoing nephrectomy are unclear. Animal models used previously to investigate this question are not ideal because they require invasive methods to model congenital solitary kidney. In this study, we describe a new genetic animal model, the heterogeneous stock-derived model of unilateral renal agenesis (HSRA) rat, which demonstrates 50%-75% spontaneous incidence of a single kidney. The HSRA model is characterized by reduced nephron number (more than would be expected by loss of one kidney), early kidney/glomerular hypertrophy, and progressive renal injury, which culminates in reduced renal function. Long-term studies of temporal relationships among BP, renal hemodynamics, and renal function demonstrate that spontaneous single-kidney HSRA rats are more likely than uninephrectomized normal littermates to exhibit renal impairment because of the combination of reduced nephron numbers and prolonged exposure to renal compensatory mechanisms (i.e., hyperfiltration). Future studies with this novel animal model may provide additional insight into the genetic contributions to kidney development and agenesis and the factors influencing susceptibility to renal injury in individuals with congenital solitary kidney. Copyright © 2015 by the American Society of Nephrology.

Treatment of multiple synchronous misdiagnosed renal cell cancers in a young patient affected by a "de novo" Von Hippel-Lindau syndrome.

PubMed

Allasia, Marco; Battaglia, Antonino; Pasini, Barbara; Gazzera, Carlo; Calandri, Marco; Bosio, Andrea; Gontero, Paolo; Destefanis, Paolo

2017-02-28

Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited syndrome occurring in one out of 36,000 live births. Diagnosis could be a challenge in patients with no familial VHL history. Renal cancer (RCC) represents one of the most important manifestations. RCC is usually recurrent and multifocal. Actually treating RCC in VHL patients represent a clinical dilemma: the oncological outcomes must be balanced against renal function preservation. A young man with a negative familial history was referred to our department with seven misdiagnosed renal masses. VHL disease was determined through genetic test. The multiple RCCs were treated by surgery and percutaneous thermal ablation by radiofrequency ablation (RFA) with complete control of RCC and no impairment of renal function. This case history confirms that VHL disease has to be suspected in young patients with evidence of synchronous multiple renal masses and in presence of specific clinical criteria.RFA appears to be safe in terms of oncological radicalism and in renal function preservation.In hereditary RCC, we should purpose, whenever it is possible, minimally invasive treatment in terms of low hospital stay and a minimal loss of renal tissue.

Germanium in ginseng is low and causes no sodium and water retention or renal toxicity in the diuretic-resistant rats

PubMed Central

Tan, Chunjiang; Xiao, Lu; Chen, Wenlie

2015-01-01

Ginseng preparations contain high concentrations of germanium (Ge), which was reported to contribute to diuretic resistance or renal failure. However, Ge content in ginseng and the influence on renal functions remain unclear. Forty rats were randomly divided into control group, low, moderate, and high Ge ginseng-treated group and observed for 25 days. Daily urine, renal functions, and serum and urine electrolytics were measured. Ge retention in the organs and renal histological changes were also evaluated. Ge content ranged from 0.007 to 0.450 µg/g in various ginseng samples. Four groups showed no difference in the daily urine output, glomerular filtration rate, urinary electrolytes excretions, 24 h-urine protein, as well as plasma and urine urea nitrogen, creatinine, osmotic pressure, and pH values. Ge did not cause any renal pathological effects in this study. No Na and water retention was detected in the ginseng-treated groups. Ge retention in various organs was found highest in spleen, followed by the kidney, liver, lung, stomach, heart, and pancreas. The total Ge contents in various ginsengs were low, and ginseng treatment did not affect renal functions or cause renal histological changes. PMID:25711879

Renal electrolyte circadian rhythms - Independence from feeding and activity patterns

NASA Technical Reports Server (NTRS)

Moore-Ede, M. C.; Herd, J. A.

1977-01-01

Experiments were conducted on six unanesthetized chair-acclimatized adult male squirrel monkeys (Saimiri sciureus) weighing 600-900 g to determine whether internal synchronization is the result of simple passive dependence of renal excretory rhythms on endogenous rhythms of those variable that influence electrolyte excretion such as dietary intake and muscular activity. Independence of the urinary rhythms from diurnal variations in feeding, drinking, and activity was secured by depriving the animals of food, water, and training them to perform a two-hourly schedule of feeding, drinking, and activity throughout day and night. Results indicate that the internal synchronization which is normally observed between the behavioral and urinary rhythms cannot be explained by any direct dependence of renal function on behavioral patterns. The most probable mechanism for circadian internal synchronization is that the various behavioral and renal rhythms are controlled by potentially independent separate oscillators which are normally kept in synchrony with one another.

Alkaline phosphatase for treatment of sepsis-induced acute kidney injury: a prospective randomized double-blind placebo-controlled trial

PubMed Central

2012-01-01

Introduction To evaluate whether alkaline phosphatase (AP) treatment improves renal function in sepsis-induced acute kidney injury (AKI), a prospective, double-blind, randomized, placebo-controlled study in critically ill patients with severe sepsis or septic shock with evidence of AKI was performed. Methods Thirty-six adult patients with severe sepsis or septic shock according to Systemic Inflammatory Response Syndrome criteria and renal injury defined according to the AKI Network criteria were included. Dialysis intervention was standardized according to Acute Dialysis Quality Initiative consensus. Intravenous infusion of alkaline phosphatase (bolus injection of 67.5 U/kg body weight followed by continuous infusion of 132.5 U/kg/24 h for 48 hours, or placebo) starting within 48 hours of AKI onset and followed up to 28 days post-treatment. The primary outcome variable was progress in renal function variables (endogenous creatinine clearance, requirement and duration of renal replacement therapy, RRT) after 28 days. The secondary outcome variables included changes in circulating inflammatory mediators, urinary excretion of biomarkers of tubular injury, and safety. Results There was a significant (P = 0.02) difference in favor of AP treatment relative to controls for the primary outcome variable. Individual renal parameters showed that endogenous creatinine clearance (baseline to Day 28) was significantly higher in the treated group relative to placebo (from 50 ± 27 to 108 ± 73 mL/minute (mean ± SEM) for the AP group; and from 40 ± 37 to 65 ± 30 mL/minute for placebo; P = 0.01). Reductions in RRT requirement and duration did not reach significance. The results in renal parameters were supported by significantly more pronounced reductions in the systemic markers C-reactive protein, Interleukin-6, LPS-binding protein and in the urinary excretion of Kidney Injury Molecule-1 and Interleukin-18 in AP-treated patients relative to placebo. The Drug Safety Monitoring Board did not raise any issues throughout the trial. Conclusions The improvements in renal function suggest alkaline phosphatase is a promising new treatment for patients with severe sepsis or septic shock with AKI. Trial Registration www.clinicaltrials.gov: NCTNCT00511186 PMID:22269279

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

PubMed Central

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

2014-01-01

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

Population pharmacokinetic–pharmacodynamic analysis for sugammadex-mediated reversal of rocuronium-induced neuromuscular blockade

PubMed Central

Kleijn, Huub J; Zollinger, Daniel P; van den Heuvel, Michiel W; Kerbusch, Thomas

2011-01-01

AIMS An integrated population pharmacokinetic–pharmacodynamic model was developed with the following aims: to simultaneously describe pharmacokinetic behaviour of sugammadex and rocuronium; to establish the pharmacokinetic–pharmacodynamic model for rocuronium-induced neuromuscular blockade and reversal by sugammadex; to evaluate covariate effects; and to explore, by simulation, typical covariate effects on reversal time. METHODS Data (n = 446) from eight sugammadex clinical studies covering men, women, non-Asians, Asians, paediatrics, adults and the elderly, with various degrees of renal impairment, were used. Modelling and simulation techniques based on physiological principles were applied to capture rocuronium and sugammadex pharmacokinetics and pharmacodynamics and to identify and quantify covariate effects. RESULTS Sugammadex pharmacokinetics were affected by renal function, bodyweight and race, and rocuronium pharmacokinetics were affected by age, renal function and race. Sevoflurane potentiated rocuronium-induced neuromuscular blockade. Posterior predictive checks and bootstrapping illustrated the accuracy and robustness of the model. External validation showed concordance between observed and predicted reversal times, but interindividual variability in reversal time was pronounced. Simulated reversal times in typical adults were 0.8, 1.5 and 1.4 min upon reversal with sugammadex 16 mg kg−1 3 min after rocuronium, sugammadex 4 mg kg−1 during deep neuromuscular blockade and sugammadex 2 mg kg−1 during moderate blockade, respectively. Simulations indicated that reversal times were faster in paediatric patients and slightly slower in elderly patients compared with adults. Renal function did not affect reversal time. CONCLUSIONS Simulations of the therapeutic dosing regimens demonstrated limited impact of age, renal function and sevoflurane use, as predicted reversal time in typical subjects was always <2 min. PMID:21535448

Effects of alpha-2 agonists on renal function in hypertensive humans.

PubMed

Goldberg, M; Gehr, M

1985-01-01

Centrally acting adrenergic agonists, by decreasing peripheral adrenergic activity, are effective antihypertensive agents. The older agents, however, especially methyldopa, have been associated with weight gain, clinical edema, and antihypertensive tolerance when used as monotherapy. While acute studies in humans have demonstrated weight gain and sodium retention with clonidine and guanabenz, chronic administration results in a decrease in weight and plasma volume. The absence of chronic weight gain and of sodium retention could be the result of a counterbalance between hypotension-related antinatriuresis, secondary to a decrease in glomerular filtration rate and renal blood flow, and natriuretic activity, as a result of a decrease in renal sympathetic tone. Whereas natriuresis and water diuresis have been demonstrated in animals with acute clonidine or guanabenz administration, this has not been demonstrated in humans. Recent studies in which saline administration was used to precondition humans to a subsequent natriuretic stimulus (i.e., guanabenz-induced decreased renal adrenergic activity) resulted in stabilization of renal blood flow and natriuresis. Selective reduction renal sympathetic activity affecting salt and water transport may explain why guanabenz and probably also clonidine seem to be devoid of the sodium/fluid-retaining properties that are common with other antihypertensive agents. Because agents of this class have effects other than pure central alpha-2 agonism (such as alpha-1 activity), they might have confounding and counterbalancing side effects leading to sodium and water retention.

Long-term changes of renal function in relation to ace inhibitor/angiotensin receptor blocker dosing in patients with heart failure and chronic kidney disease.

PubMed

Fröhlich, Hanna; Nelges, Christoph; Täger, Tobias; Schwenger, Vedat; Cebola, Rita; Schnorbach, Johannes; Goode, Kevin M; Kazmi, Syed; Katus, Hugo A; Cleland, John G F; Clark, Andrew L; Frankenstein, Lutz

2016-08-01

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have become cornerstones of therapy for chronic heart failure (CHF). Guidelines advise high target doses for ACEIs/ARBs, but fear of worsening renal function may limit dose titration in patients with concomitant chronic kidney disease (CKD). In this retrospective observational study, we identified 722 consecutive patients with systolic CHF, stable CKD stage III/IV (estimated glomerular filtration rate [eGFR] 15-60 mL min(-1) 1.73 m(-2)) and chronic ACEI/ARB treatment from the outpatient heart failure clinics at the Universities of Hull, UK, and Heidelberg, Germany. Change of renal function, worsening CHF, and hyperkalemia at 12-month follow-up were analyzed as a function of both baseline ACEI/ARB dose and dose change from baseline. ΔeGFR was not related to baseline dose of ACEI/ARB (P = .58), or to relative (P = .18) or absolute change of ACEI/ARB dose (P = .21) during follow-up. Expressing change of renal function as a categorical variable (improved/stable/decreased) as well as subgroup analyses with respect to age, sex, New York Heart Association functional class, left ventricular ejection fraction, diabetes, concomitant aldosterone antagonists, CKD stage, hypertension, ACEI vs ARB, and congestion status yielded similar results. There was no association of dose/dose change with incidence of either worsening CHF or hyperkalemia. In patients with systolic CHF and stable CKD stage III/IV, neither continuation of high doses of ACEI/ARB nor up-titration was related to adverse changes in longer-term renal function. Conversely, down-titration was not associated with improvement in eGFR. Use of high doses of ACEI/ARB and their up-titration in patients with CHF and CKD III/IV may be appropriate provided that the patient is adequately monitored. Copyright © 2016 Elsevier Inc. All rights reserved.

Metformin and/or clomiphene do not adversely affect liver or renal function in women with polycystic ovary syndrome.

PubMed

Aubuchon, Mira; Kunselman, Allen R; Schlaff, William D; Diamond, Michael P; Coutifaris, Christos; Carson, Sandra A; Steinkampf, Michael P; Carr, Bruce R; McGovern, Peter G; Cataldo, Nicholas A; Gosman, Gabriella G; Nestler, John E; Myers, Evan R; Legro, Richard S

2011-10-01

Nonalcoholic fatty liver disease is common to insulin-resistant states such as polycystic ovary syndrome (PCOS). Metformin (MET) is often used to treat PCOS but information is limited as to its effects on liver function. We sought to determine the effects of MET on serum hepatic parameters in PCOS patients. This was a secondary analysis of a randomized, doubled-blind trial from 2002-2004. This multi-center clinical trial was conducted in academic centers. Six hundred twenty-six infertile women with PCOS with serum liver function parameters less than twice the upper limit of normal were included. Clomiphene citrate (n = 209), MET (n = 208), or combined (n = 209) were given for up to 6 months. The percent change from baseline in renal and liver function between- and within-treatment arms was assessed. Renal function improved in all treatment arms with significant decreases in serum blood urea nitrogen levels (range, -14.7 to -21.3%) as well as creatinine (-4.2 to -6.9%). There were similar decreases in liver transaminase levels in the clomiphene citrate and combined arms (-10% in bilirubin, -9 to -11% in transaminases) without significant changes in the MET arm. When categorizing baseline bilirubin, aspartate aminotransferase, and alanine aminotransferase into tertiles, there were significant within-treatment arm differences between the tertiles with the highest tertile having the largest decrease from baseline regardless of treatment arm. Women with PCOS can safely use metformin and clomiphene even in the setting of mildly abnormal liver function parameters, and both result in improved renal function.