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)

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.

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.

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.

Effects of continuous and pulsatile flows generated by ventricular assist devices on renal function and pathology.

PubMed

Miyamoto, Takuma; Karimov, Jamshid H; Fukamachi, Kiyotaka

2018-03-01

Continuous-flow (CF) left ventricular assist devices (LVADs) are widely used to treat end-stage heart failure. Despite substantial improvement in clinical results, numerous complications remain associated with this technology. Worsening renal function is one, associated with morbidity and mortality in patients supported by CF LVADs. The effects of CF LVAD support on renal function have been investigated since the mid-1990s by many research groups. Area covered: We review the current status of LVAD therapy, experimental results regarding the effects of types of flow generated by LVADs on renal function and pathology, changes in renal function after LVAD implant, the influence of renal function on outcomes, and risk factors for renal dysfunction post implant. This information was obtained through online databases and direct extraction of single studies. Expert commentary: Immediately after CF LVAD implantation, renal function improves temporarily as patients recover from the kidneys' previously low perfusion and congestive state. However, many studies have shown that this initially recovered renal function gradually declines during long-term CF LVAD support. Although it is known that CF LVAD support adversely affects renal function over the long term, just how it does has not yet been clearly defined in terms of clinical symptoms or signs.

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

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.

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.

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.

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.

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.

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.

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

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.

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.

Cardiorenal Syndrome in Acute Heart Failure: Revisiting Paradigms.

PubMed

Núñez, Julio; Miñana, Gema; Santas, Enrique; Bertomeu-González, Vicente

2015-05-01

Cardiorenal syndrome has been defined as the simultaneous dysfunction of both the heart and the kidney. Worsening renal function that occurs in patients with acute heart failure has been classified as cardiorenal syndrome type 1. In this setting, worsening renal function is a common finding and is due to complex, multifactorial, and not fully understood processes involving hemodynamic (renal arterial hypoperfusion and renal venous congestion) and nonhemodynamic factors. Traditionally, worsening renal function has been associated with worse outcomes, but recent findings have revealed mixed and heterogeneous results, perhaps suggesting that the same phenotype represents a diversity of pathophysiological and clinical situations. Interpreting the magnitude and chronology of renal changes together with baseline renal function, fluid overload status, and clinical response to therapy might help clinicians to unravel the clinical meaning of renal function changes that occur during an episode of heart failure decompensation. In this article, we critically review the contemporary evidence on the pathophysiology and clinical aspects of worsening renal function in acute heart failure. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

High Prolactin Excretion in Patients with Diabetes Mellitus and Impaired Renal Function.

PubMed

Triebel, Jakob; Moreno-Vega, Aura Ileana; Vázquez-Membrillo, Miguel; Nava, Gabriel; García-Franco, Renata; López-Star, Ellery; Baldivieso-Hurtado, Olivia; Ochoa, Daniel; Macotela, Yazmín; Bertsch, Thomas; Martinez de la Escalera, Gonzalo; Clapp, Carmen

2015-01-01

The metabolic clearance of prolactin (PRL) is partially executed by the kidney. Here, we investigate the urine excretion of PRL in patients with Diabetes Mellitus and renal impairment. Serum and urine samples were collected from male, mestizo patients in central Mexico employing a cross-sectional study design. Ninety-eight individuals had either no diabetes and normal renal function (control), diabetes and normal renal function, or diabetes with impaired renal function. PRL was determined by a chemiluminescent immunometric assay; protein, albumin, and creatinine were evaluated using quantitative colorimetric assays. The results were analyzed using ANOVA-testing. Patients with Diabetes Mellitus and renal impairment had significantly higher urine PRL levels than patients with Diabetes Mellitus and normal renal function and control patients. Higher urine PRL levels were associated with lower glomerular filtration rates, higher serum creatinine, and higher urinary albumin-to-creatinine ratios (UACR). Urine PRL levels correlated positively with UACR. Serum PRL levels were similar among groups. Patients with Diabetes Mellitus and impaired renal function demonstrate a high urinary PRL excretion. Urinary PRL excretion in the context of proteinuria could contribute to PRL dysregulation in renal impairment.

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 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 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.

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.

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.

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.

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.

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.

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

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.

The Prognostic Importance of Changes in Renal Function during Treatment for Acute Heart Failure Depends on Admission Renal Function

PubMed Central

Reid, Ryan; Ezekowitz, Justin A.; Brown, Paul M.; McAlister, Finlay A.; Rowe, Brian H.; Braam, Branko

2015-01-01

Background Worsening and improving renal function during acute heart failure have been associated with adverse outcomes but few studies have considered the admission level of renal function upon which these changes are superimposed. Objectives The objective of this study was to evaluate definitions that incorporate both admission renal function and change in renal function. Methods 696 patients with acute heart failure with calculable eGFR were classified by admission renal function (Reduced [R, eGFR<45 ml/min] or Preserved [P, eGFR≥45 ml/min]) and change over hospital admission (worsening [WRF]: eGFR ≥20% decline; stable [SRF]; and improving [IRF]: eGFR ≥20% increase). The primary outcome was all-cause mortality. The prevalence of Pres and Red renal function was 47.8% and 52.2%. The frequency of R-WRF, R-SRF, and R-IRF was 11.4%, 28.7%, and 12.1%, respectively; the incidence of P-WRF, P-SRF, and P-IRF was 5.7%, 35.3%, and 6.8%, respectively. Survival was shorter for patients with R-WRF compared to R-IRF (median survival times 13.9 months (95%CI 7.7–24.9) and 32.5 months (95%CI 18.8–56.1), respectively), resulting in an acceleration factor of 2.3 (p = 0.016). Thus, an increase compared with a decrease in renal function was associated with greater than two times longer survival among patients with Reduced renal function. PMID:26380982

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.

Nephrotoxicity of ibandronate and zoledronate in Wistar rats with normal renal function and after unilateral nephrectomy.

PubMed

Bergner, R; Siegrist, B; Gretz, N; Pohlmeyer-Esch, G; Kränzlin, B

2015-09-01

A previous animal study compared the nephrotoxic effect of ibandronate (IBN) and zoledronate (ZOL), but interpretation of these study results was limited because of the model of minimal nephrotoxic dosage with a dosage ratio of 1:3. The present study investigated the nephrotoxicity of ibandronate and zoledronate in a 1.5:1 dose ratio, as used in clinical practice and compared the nephrotoxicity in rats with normal and with mildly to moderately impaired renal function. We compared rats with normal renal function (SHAM) and with impaired renal function after unilateral nephrectomy (UNX), treated either with ibandronate 1.5mg/kg, zoledronate 1mg/kg or placebo once (1×) or nine (9×) times. Renal function and markers of tubular toxicity were measured over a 27 week period. After last bisphosphonate treatment the rats were sacrificed and kidneys examined histologically. All bisphosphonate treated animals showed a significant tubular toxicity, which was temporary except in the ZOL-UNX-9×-group. Also the renal function was only transiently reduced except in the ZOL-UNX-9×-group. Histologically, bisphosphonate treatment led to cortical tubuloepithelial degeneration/necrosis and medullary tubuloepithelial swelling which were slightly more pronounced in ibandronate treated animals, when compared to zoledronate treated animals, especially with impaired renal function. In contrast to the previous study we found a similar nephrotoxicity of ibandronate and zoledronate in rats with normal renal function. In rats with impaired renal function the peak of toxicity had not even been fully reached until end of experiment in the zoledronate treated animals. The peak of toxicity seems to be more severe and delayed in rats with impaired renal function compared with rats with normal renal function. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

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.

Frequency response of the renal vasculature in congestive heart failure.

PubMed

DiBona, Gerald F; Sawin, Linda L

2003-04-29

The renal vasoconstrictor response to renal nerve stimulation is greater in congestive heart failure (CHF) rats than in control rats. This study tested the hypothesis that the enhanced renal vasoconstrictor response to renal nerve stimulation in CHF is a result of an impairment in the low-pass filter function of the renal vasculature. In response to conventional graded-frequency renal nerve stimulation, the reductions in renal blood flow at each stimulation frequency were greater in CHF rats than control rats. A pseudorandom binary sequence pattern of renal nerve stimulation was used to examine the frequency response of the renal vasculature. Although this did not affect the renal blood flow power spectrum in control rats, there was a 10-fold increase in renal blood flow power over the frequency range of 0.01 to 1.0 Hz in CHF rats. On analysis of transfer function gain, attenuation of the renal nerve stimulation input signal was similar in control and CHF rats over the frequency range of 0.001 to 0.1 Hz. However, over the frequency range of 0.1 to 1.0 Hz, although there was progressive attenuation of the input signal (-30 to -70 dB) in control rats, CHF rats exhibited a flat gain response (-20 dB) without progressive attenuation. The enhanced renal vasoconstrictor response to renal nerve stimulation in CHF rats is caused by an alteration in the low-pass filter function of the renal vasculature, resulting in a greater transfer of input signals into renal blood flow in the 0.1 to 1.0 Hz range.

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

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 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.

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.

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

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

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.

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.

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.

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.

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

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.

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

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.

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.

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.

WWSSF - a worldwide study on radioisotopic renal split function: reproducibility of renal split function assessment in children.

PubMed

Geist, Barbara Katharina; Dobrozemsky, Georg; Samal, Martin; Schaffarich, Michael P; Sinzinger, Helmut; Staudenherz, Anton

2015-12-01

The split or differential renal function is the most widely accepted quantitative parameter derived from radionuclide renography. To examine the intercenter variance of this parameter, we designed a worldwide round robin test. Five selected dynamic renal studies have been distributed all over the world by e-mail. Three of these studies are anonymized patient data acquired using the EANM standardized protocol and two studies are phantom studies. In a simple form, individual participants were asked to measure renal split function as well as to provide additional information such as data analysis software, positioning of background region of interest, or the method of calculation. We received the evaluation forms from 34 centers located in 21 countries. The analysis of the round robin test yielded an overall z-score of 0.3 (a z-score below 1 reflecting a good result). However, the z-scores from several centers were unacceptably high, with values greater than 3. In particular, the studies with impaired renal function showed a wide variance. A wide variance in the split renal function was found in patients with impaired kidney function. This study indicates the ultimate importance of quality control and standardization of the measurement of the split renal function. It is especially important with respect to the commonly accepted threshold for significant change in split renal function by 10%.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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

PubMed

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

2005-07-01

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

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: 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.

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.

Interaction between renal function and percutaneous edge-to-edge mitral valve repair using MitraClip.

PubMed

Kaneko, Hidehiro; Neuss, Michael; Schau, Thomas; Weissenborn, Jens; Butter, Christian

2017-02-01

MitraClip (MC; Abbott Vascular, Menlo Park, CA, USA) is a treatment option for mitral regurgitation. Renal dysfunction is closely associated with cardiovascular disease. However, the influence of renal function in MC remains not fully understood. In this study, we aimed to clarify the association between renal function and MC. We examined 206 consecutive patients who underwent MC and divided patients into 3 groups according to estimated glomerular filtration rate (eGFR), normal eGFR (≥60mL/min/1.73m 2 ) (n=70), mild chronic kidney disease (CKD) (30-59mL/min/1.73m 2 ) (n=106), and severe CKD (<30mL/min/1.73m 2 ) (n=30). N-terminal pro-B type natriuretic peptide (NT-pro BNP) levels increased with decreasing eGFR. Kaplan-Meier curves revealed that the long-term survival rate significantly decreased with eGFR. After adjustment with the covariates, severe CKD was still associated with mortality. Improved renal function was observed in 30% and associated with baseline lower NT-pro BNP levels. Patients with improved renal function had higher chronic phase survival rate. Renal dysfunction is common in MC patients and the survival rate decreased with eGFR in association with increased NT-pro BNP levels. MC may improve renal function in approximately 30% of MC patients. Improved renal function is associated with lower NT-pro BNP levels and results in satisfactory prognosis. These results implies a close association between renal function and MC treatment. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

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.

Clinical types and drug therapy of renal impairment in cirrhosis

PubMed Central

Rodés, J.; Bosch, J.; Arroyo, V.

1975-01-01

Four separate types of renal failure in cirrhosis are described: functional renal failure; diuretic induced uraemia; acute tubular necrosis; chronic intrinsic renal disease. Functional renal failure may arise spontaneously or be precipitated by such factors as haemorrhage, surgery, or infection. It carries a poor prognosis but preliminary results of treating this condition with plasma volume expansion in combination with high doses of furosemide are encouraging. PMID:1234328

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.

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 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.

Availability of information on renal function in Dutch community pharmacies.

PubMed

Koster, Ellen S; Philbert, Daphne; Noordam, Michelle; Winters, Nina A; Blom, Lyda; Bouvy, Marcel L

2016-08-01

Background Early detection and monitoring of impaired renal function may prevent drug related problems. Objective To assess the availability of information on patient's renal function in Dutch community pharmacies, for patients using medication that might need monitoring in case of renal impairment. Methods Per pharmacy, 25 patients aged ≥65 years using at least one drug that requires monitoring, were randomly selected from the pharmacy information system. For these patients, information on renal function [estimated glomerular filtration rate (eGFR)], was obtained from the pharmacy information system. When absent, this information was obtained from the general practitioner (GP). Results Data were collected for 1632 patients. For 1201 patients (74 %) eGFR values were not directly available in the pharmacy, for another 194 patients (12 %) the eGFR value was not up-to-date. For 1082 patients information could be obtained from the GP, resulting in 942 additional recent eGFR values. Finally, recent information on renal function was available for 72 % (n = 1179) of selected patients. Conclusion In patients using drugs that require renal monitoring, information on renal function is often unknown in the pharmacy. For the majority of patients this information can be retrieved from the GP.

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

AGXT2 rs37369 polymorphism predicts the renal function in patients with chronic heart failure.

PubMed

Hu, Xiao-Lei; Zeng, Wen-Jing; Li, Mu-Peng; Yang, Yong-Long; Kuang, Da-Bin; Li, He; Zhang, Yan-Jiao; Jiang, Chun; Peng, Li-Ming; Qi, Hong; Zhang, Ke; Chen, Xiao-Ping

2017-12-30

Patients with chronic heart failure (CHF) are often accompanied with varying degrees of renal diseases. The purpose of this study was to identify rs37369 polymorphism of AGXT2 specific to the renal function of CHF patients. A total of 1012 southern Chinese participants, including 487 CHF patients without history of renal diseases and 525 healthy volunteers, were recruited for this study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the genotypes of AGXT2 rs37369 polymorphism. Levels of blood urea nitrogen (BUN) and serum creatinine (SCr) were detected to indicate the renal function of the participants. BUN level was significantly higher in CHF patients without history of renal diseases compared with healthy volunteers (p=0.000). And the similar result was also obtained for SCr (p=0.000). Besides, our results indicated that the level of BUN correlated significantly with SCr in both the CHF patients without renal diseases (r=0.4533, p<0.0001) and volunteers (r=0.2489, p<0.0001). Furthermore, we found that the AGXT2 rs37369 polymorphism could significantly affect the level of BUN in CHF patients without history of renal diseases (p=0.036, AA+AG vs GG). Patients with rs37369 GG genotype showed a significantly reduced level of BUN compared to those with the AA genotype (p=0.024), and the significant difference was still observed in the smokers of CHF patients without renal diseases (p=0.023). In conclusion, we found that CHF might induce the impairment of kidney and cause deterioration of renal function. AGXT2 rs37369 polymorphism might affect the renal function of CHF patients free from renal diseases, especially in patients with cigarette smoking. Copyright © 2017. Published by Elsevier B.V.

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.

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

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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

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.

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

Reinnervation following catheter-based radio-frequency renal denervation.

PubMed

Booth, Lindsea C; Nishi, Erika E; Yao, Song T; Ramchandra, Rohit; Lambert, Gavin W; Schlaich, Markus P; May, Clive N

2015-04-20

What is the topic of this review? Does catheter-based renal denervation effectively denervate the afferent and efferent renal nerves and does reinnervation occur? What advances does it highlight? Following catheter-based renal denervation, the afferent and efferent responses to electrical stimulation were abolished, renal sympathetic nerve activity was absent, and levels of renal noradrenaline and immunohistochemistry for tyrosine hydroxylase and calcitonin gene-related peptide were significantly reduced. By 11 months after renal denervation, both the functional responses and anatomical markers of afferent and efferent renal nerves had returned to normal, indicating reinnervation. Renal denervation reduces blood pressure in animals with experimental hypertension and, recently, catheter-based renal denervation was shown to cause a prolonged decrease in blood pressure in patients with resistant hypertension. The randomized, sham-controlled Symplicity HTN-3 trial failed to meet its primary efficacy end-point, but there is evidence that renal denervation was incomplete in many patients. Currently, there is little information regarding the effectiveness of catheter-based renal denervation and the extent of reinnervation. We assessed the effectiveness of renal nerve denervation with the Symplicity Flex catheter and the functional and anatomical reinnervation at 5.5 and 11 months postdenervation. In anaesthetized, non-denervated sheep, there was a high level of renal sympathetic nerve activity, and electrical stimulation of the renal nerve increased blood pressure and reduced heart rate (afferent response) and caused renal vasoconstriction and reduced renal blood flow (efferent response). Immediately after renal denervation, renal sympathetic nerve activity and the responses to electrical stimulation were absent, indicating effective denervation. By 11 months after denervation, renal sympathetic nerve activity was present and the responses to electrical stimulation were normal, indicating reinnervation. Anatomical measures of renal innervation by sympathetic efferent nerves (tissue noradrenaline and tyrosine hydroxylase) and afferent sensory nerves (calcitonin gene-related peptide) demonstrated large decreases at 1 week postdenervation, but normal levels at 11 months postdenervation. In summary, catheter-based renal denervation is effective, but reinnervation occurs. Studies of central and renal changes postdenervation are required to understand the causes of the prolonged hypotensive response to catheter-based renal denervation in human hypertension. © 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.

[Renal decapsulation for the treatment of anuria : A "forgotten" treatment from the early 20th century].

PubMed

Dräger, D L; Protzel, C; Hakenberg, O W

2017-01-01

In the early 20th century, Harrison first performed renal decapsulation in anuric children with scarlet fever and observed improvement in renal function postoperatively. The pathophysiological explanation was seen in intraparenchymal renal pressure due to edema which was improved by surgical decapsulation. The technique of decapsulation was simple excision after incision and blunt dissection of the renal parenchyma. Renal decapsulation then became a procedure commonly used for many indications in inflammatory renal conditions; indications were renal angioneurosis, hydronephrosis, toxic, bacterial and chronic nephritis, renal abscess and even eclampsia. With the beginning of the antibiotic era, renal decapsulation became obsolete and has disappeared from the urological spectrum completely.

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.

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.

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.

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).

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

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.

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.

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.

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.

Renal hemodynamics in space.

PubMed

Kramer, H J; Heer, M; Cirillo, M; De Santo, N G

2001-09-01

Renal excretory function and hemodynamics are determined by the effective circulating plasma volume as well as by the interplay of systemic and local vasoconstrictors and vasodilators. Microgravity results in a headward shift of body fluid. Because the control conditions of astronauts were poorly defined in many studies, controversial results have been obtained regarding diuresis and natriuresis as well as renal hemodynamic changes in response to increased central blood volume, especially during the initial phase of space flight. Renal excretory function and renal hemodynamics in microgravity are affected in a complex fashion, because during the initial phase of space flight, variable mechanisms become operative to modulate the effects of increased central blood volume. They include interactions between vasodilators (dopamine, atrial natriuretic peptide, and prostaglandins) and vasoconstrictors (sympathetic nervous system and the renin-angiotensin system). The available data suggest a moderate rise in glomerular filtration rate during the first 2 days after launch without a significant increase in effective renal plasma flow. In contrast, too few data regarding the effects of space flight on renal function during the first 12 hours after launch are available and are, in addition, partly contradictory. Thus, detailed and well-controlled studies are required to shed more light on the role of the various factors besides microgravity that determine systemic and renal hemodynamics and renal excretory function during the different stages of space flight.

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 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

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.

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.

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.

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.

[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.

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.

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 Clinical Spectrum of Renal Insufficiency During Acute Glomerulonephritis in the Adult

PubMed Central

Lemieux, Guy; Cuvelier, Amedee A.; Lefebvre, Rene

1967-01-01

Twenty-seven adults with acute poststreptococcal glomerulonephritis were divided into two groups according to the severity of reduction in renal function: (1) 14 patients with mild depression of renal function, and (2) 13 patients with more severe renal insufficiency. In the first group the outcome was favourable, with complete clinical recovery in 11 patients. Only two patients in the second group have recovered. Five have died of renal failure and in six the chronic stage has developed. The most notable histopathological lesion observed in this group of patients was severe proliferative glomerulonephritis with a large number of epithelial crescents. According to the mode of development and time of onset of renal failure, these 13 patients could be divided into three sub-groups: (1) early renal failure without oliguria (three patients), (2) early renal failure with severe oliguria or anuria (three patients) and (3) delayed renal failure (seven patients). Although there are exceptions, the development of renal insufficiency in an adult patient suffering from acute glomerulonephritis is usually associated with a guarded prognosis. ImagesFig. 2 PMID:6021561

Three new renal simulators for use in nuclear medicine

NASA Astrophysics Data System (ADS)

Dullius, Marcos; Fonseca, Mateus; Botelho, Marcelo; Cunha, Clêdison; Souza, Divanízia

2014-03-01

Renal scintigraphy is useful to provide both functional and anatomic information of renal flow of cortical functions and evaluation of pathological collecting system. The objective of this study was develop and evaluate the performance of three renal phantoms: Two anthropomorphic static and another dynamic. The static images of the anthropomorphic phantoms were used for comparison with static renal scintigraphy with 99mTc-DMSA in different concentrations. These static phantoms were manufactured in two ways: one was made of acrylic using as mold a human kidney preserved in formaldehyde and the second was built with ABS (acrylonitrile butadiene styrene) in a 3D printer. The dynamic renal phantom was constructed of acrylic to simulate renal dynamics in scintigraphy with 99mTc-DTPA. These phantoms were scanned with static and dynamic protocols and compared with clinical data. Using these phantoms it is possible to acquire similar renal images as in the clinical scintigraphy. Therefore, these new renal phantoms can be very effective for use in the quality control of renal scintigraphy, and image processing systems.

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.

[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.

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.

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

[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.

The renal nerves in chronic heart failure: efferent and afferent mechanisms

PubMed Central

Schiller, Alicia M.; Pellegrino, Peter R.; Zucker, Irving H.

2015-01-01

The function of the renal nerves has been an area of scientific and medical interest for many years. The recent advent of a minimally invasive catheter-based method of renal denervation has renewed excitement in understanding the afferent and efferent actions of the renal nerves in multiple diseases. While hypertension has been the focus of much this work, less attention has been given to the role of the renal nerves in the development of chronic heart failure (CHF). Recent studies from our laboratory and those of others implicate an essential role for the renal nerves in the development and progression of CHF. Using a rabbit tachycardia model of CHF and surgical unilateral renal denervation, we provide evidence for both renal efferent and afferent mechanisms in the pathogenesis of CHF. Renal denervation prevented the decrease in renal blood flow observed in CHF while also preventing increases in Angiotensin-II receptor protein in the microvasculature of the renal cortex. Renal denervation in CHF also reduced physiological markers of autonomic dysfunction including an improvement in arterial baroreflex function, heart rate variability, and decreased resting cardiac sympathetic tone. Taken together, the renal sympathetic nerves are necessary in the pathogenesis of CHF via both efferent and afferent mechanisms. Additional investigation is warranted to fully understand the role of these nerves and their role as a therapeutic target in CHF. PMID:26300788

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.

Assessment of myocardial mechanics in patients with end-stage renal disease and renal transplant recipients using speckle tracking echocardiography.

PubMed

Pirat, Bahar; Bozbas, Huseyin; Simsek, Vahide; Sade, L Elif; Sayin, Burak; Muderrisoglu, Haldun; Haberal, Mehmet

2015-04-01

Velocity vector imaging allows quantitation of myocardial strain and strain rate from 2-dimensional images based on speckle tracking echocardiography. The aim of this study was to analyze the changes in myocardial strain and strain rate patterns in patients with end-stage renal disease and renal transplant recipients. We studied 33 patients with end-stage renal disease on hemodialysis (19 men; mean age, 36 ± 8 y), 24 renal transplant recipients with functional grafts (21 men; mean age, 36 ± 7 y) and 26 age- and sex-matched control subjects. Longitudinal peak systolic strain and strain rate for basal, mid, and apical segments of the left ventricular wall were determined by velocity vector imaging from apical 4- and 2-chamber views. The average longitudinal strain and strain rate for the left ventricle were noted. From short-axis views at the level of papillary muscles, average circumferential, and radial strain, and strain rate were assessed. Mean heart rate and systolic and diastolic blood pressure during imaging were similar between the groups. Longitudinal peak systolic strain and strain rate at basal and mid-segments of the lateral wall were significantly higher in renal transplant recipients and control groups than endstage renal disease patients. Average longitudinal systolic strain from the 4-chamber view was highest in control subjects (-14.5% ± 2.9%) and was higher in renal transplant recipients (-12.5% ± 3.0%) than end-stage renal disease patients (-10.2% ± 1.6%; P ≤ .001). Radial and circumferential strain and strain rate at the level of the papillary muscle were lower in patients with end-stage renal disease than other groups. Differences in myocardial function in patients with end-stage renal disease, renal transplant recipients, and normal controls can be quantified by strain imaging. Myocardial function is improved in renal transplant recipients compared with end-stage renal disease patients.

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.

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

Effect of renal impairment on the pharmacokinetics, pharmacodynamics, and safety of apixaban.

PubMed

Chang, Ming; Yu, Zhigang; Shenker, Andrew; Wang, Jessie; Pursley, Janice; Byon, Wonkyung; Boyd, Rebecca A; LaCreta, Frank; Frost, Charles E

2016-05-01

This open-label study evaluated apixaban pharmacokinetics, pharmacodynamics, and safety in subjects with mild, moderate, or severe renal impairment and in healthy subjects following a single 10-mg oral dose. The primary analysis determined the relationship between apixaban AUC∞ and 24-hour creatinine clearance (CLcr ) as a measure of renal function. The relationships between 24-hour CLcr and iohexol clearance, estimated CLcr (Cockcroft-Gault equation), and estimated glomerular filtration rate (modification of diet in renal disease [MDRD] equation) were also assessed. Secondary objectives included assessment of safety and tolerability as well as international normalized ratio (INR) and anti-factor Xa activity as pharmacodynamic endpoints. The regression analysis showed that decreasing renal function resulted in modestly increased apixaban exposure (AUC∞ increased by 44% in severe impairment with a 24-hour CLcr of 15 mL/min, compared with subjects with normal renal function), but it did not affect Cmax or the direct relationship between apixaban plasma concentration and anti-factor Xa activity or INR. The assessment of renal function measured by iohexol clearance, Cockcroft-Gault, and MDRD was consistent with that determined by 24-hour CLcr . Apixaban was well tolerated in this study. These results suggest that dose adjustment of apixaban is not required on the basis of renal function alone. © 2015, The American College of Clinical Pharmacology.

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.

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.

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.

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.

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.

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

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

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.

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.

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

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.

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.

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.

[Frequency, etiology, and outcomes of acute renal failure (data of Kaunas University of Medicine Hospital in 1995-2006)].

PubMed

Skarupskiene, Inga; Kuzminskis, Vytautas; Ziginskiene, Edita

2007-01-01

The aim of this study was to determine the frequency, etiology, and outcomes of acute renal failure. We retrospectively collected data on all patients (n=1653) who received renal replacement therapy for acute renal failure at the Kaunas University of Medicine Hospital during 1995-2006. The number of patients with acute renal failure increased nine times during the 11-year period. The mean age of patients was 59.76+/-17.52 years and increased from 44.97+/-17.1 years in 1995 to 62.84+/-16.49 years in 2006. The most common causes of acute renal failure were renal (n=646, 39%), prerenal (n=380, 23%), and obstructive (n=145, 9%). The renal replacement therapy was discontinued because of recovery of renal function in 49.9% of cases. The overall hospital mortality rate was 45.1%. Renal function did not recover in 6.7% of patients. The mortality rate over the 11-year period varied from 37.8 to 57.5%. The highest mortality rate was in the neurosurgical (62.3%) and cardiac surgical (61.8%) intensive care units. High mortality rate (more than 50%) was in the groups of patients with acute renal failure that was caused by hepatorenal syndrome, shock, sepsis, and reduced cardiac output.

Effect of endogenous angiotensin II on the frequency response of the renal vasculature.

PubMed

Dibona, Gerald F; Sawin, Linda L

2004-12-01

The renal vasculature functions as an efficient low-pass filter of the multiple frequencies contained within renal sympathetic nerve activity. This study examined the effect of angiotensin II on the frequency response of the renal vasculature. Physiological changes in the activity of the endogenous renin-angiotensin system were produced by alterations in dietary sodium intake. The frequency response of the renal vasculature was evaluated using pseudorandom binary sequence renal nerve stimulation, and the role of angiotensin II was evaluated by the administration of the angiotensin II AT(1)-receptor antagonist losartan. In low-sodium-diet rats with increased renin-angiotensin system activity, losartan steepened the renal vascular frequency response (i.e., greater attenuation); this was not seen in normal- or high-sodium-diet rats with normal or decreased renin-angiotensin system activity. Analysis of the transfer function from arterial pressure to renal blood flow, i.e., dynamic autoregulation, showed that the tubuloglomerular feedback but not the myogenic component was enhanced in low- and normal- but not in high-sodium-diet rats and that this was reversed by losartan administration. Thus physiological increases in endogenous renin-angiotensin activity inhibit the renal vascular frequency response to renal nerve stimulation while selectively enhancing the tubuloglomerular feedback component of dynamic autoregulation of renal blood flow.

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

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.

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.

Role of the Sympathetic Nervous System and Its Modulation in Renal Hypertension

PubMed Central

Sata, Yusuke; Head, Geoffrey A.; Denton, Kate; May, Clive N.; Schlaich, Markus P.

2018-01-01

The kidneys are densely innervated with renal efferent and afferent nerves to communicate with the central nervous system. Innervation of major structural components of the kidneys, such as blood vessels, tubules, the pelvis, and glomeruli, forms a bidirectional neural network to relay sensory and sympathetic signals to and from the brain. Renal efferent nerves regulate renal blood flow, glomerular filtration rate, tubular reabsorption of sodium and water, as well as release of renin and prostaglandins, all of which contribute to cardiovascular and renal regulation. Renal afferent nerves complete the feedback loop via central autonomic nuclei where the signals are integrated and modulate central sympathetic outflow; thus both types of nerves form integral parts of the self-regulated renorenal reflex loop. Renal sympathetic nerve activity (RSNA) is commonly increased in pathophysiological conditions such as hypertension and chronic- and end-stage renal disease. Increased RSNA raises blood pressure and can contribute to the deterioration of renal function. Attempts have been made to eliminate or interfere with this important link between the brain and the kidneys as a neuromodulatory treatment for these conditions. Catheter-based renal sympathetic denervation has been successfully applied in patients with resistant hypertension and was associated with significant falls in blood pressure and renal protection in most studies performed. The focus of this review is the neural contribution to the control of renal and cardiovascular hemodynamics and renal function in the setting of hypertension and chronic kidney disease, as well as the specific roles of renal efferent and afferent nerves in this scenario and their utility as a therapeutic target. PMID:29651418

Role of the Sympathetic Nervous System and Its Modulation in Renal Hypertension.

PubMed

Sata, Yusuke; Head, Geoffrey A; Denton, Kate; May, Clive N; Schlaich, Markus P

2018-01-01

The kidneys are densely innervated with renal efferent and afferent nerves to communicate with the central nervous system. Innervation of major structural components of the kidneys, such as blood vessels, tubules, the pelvis, and glomeruli, forms a bidirectional neural network to relay sensory and sympathetic signals to and from the brain. Renal efferent nerves regulate renal blood flow, glomerular filtration rate, tubular reabsorption of sodium and water, as well as release of renin and prostaglandins, all of which contribute to cardiovascular and renal regulation. Renal afferent nerves complete the feedback loop via central autonomic nuclei where the signals are integrated and modulate central sympathetic outflow; thus both types of nerves form integral parts of the self-regulated renorenal reflex loop. Renal sympathetic nerve activity (RSNA) is commonly increased in pathophysiological conditions such as hypertension and chronic- and end-stage renal disease. Increased RSNA raises blood pressure and can contribute to the deterioration of renal function. Attempts have been made to eliminate or interfere with this important link between the brain and the kidneys as a neuromodulatory treatment for these conditions. Catheter-based renal sympathetic denervation has been successfully applied in patients with resistant hypertension and was associated with significant falls in blood pressure and renal protection in most studies performed. The focus of this review is the neural contribution to the control of renal and cardiovascular hemodynamics and renal function in the setting of hypertension and chronic kidney disease, as well as the specific roles of renal efferent and afferent nerves in this scenario and their utility as a therapeutic target.

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

Eppur Si Muove: The Dynamic Nature of Physiological Control of Renal Blood Flow by the Renal Sympathetic Nerves

PubMed Central

Schiller, Alicia M.; Pellegrino, Peter Ricci; Zucker, Irving H.

2016-01-01

Tubuloglomerular feedback and the myogenic response are widely appreciated as important regulators of renal blood flow, but the role of the sympathetic nervous system in physiological renal blood flow control remains controversial. Where classic studies using static measures of renal blood flow failed, dynamic approaches have succeeded in demonstrating sympathetic control of renal blood flow under normal physiological conditions. This review focuses on transfer function analysis of renal pressure-flow, which leverages the physical relationship between blood pressure and flow to assess the underlying vascular control mechanisms. Studies using this approach indicate that the renal nerves are important in the rapid regulation of the renal vasculature. Animals with intact renal innervation show a sympathetic signature in the frequency range associated with sympathetic vasomotion that is eliminated by renal denervation. In conscious rabbits, this sympathetic signature exerts vasoconstrictive, baroreflex control of renal vascular conductance, matching well with the rhythmic, baroreflex-influenced control of renal sympathetic nerve activity and complementing findings from other studies employing dynamic approaches to study renal sympathetic vascular control. In this light, classic studies reporting that nerve stimulation and renal denervation do not affect static measures of renal blood flow provide evidence for the strength of renal autoregulation rather than evidence against physiological renal sympathetic control of renal blood flow. Thus, alongside tubuloglomerular feedback and the myogenic response, renal sympathetic outflow should be considered an important physiological regulator of renal blood flow. Clinically, renal sympathetic vasomotion may be important for solving the problems facing the field of therapeutic renal denervation. PMID:27514571

Eppur Si Muove: The dynamic nature of physiological control of renal blood flow by the renal sympathetic nerves.

PubMed

Schiller, Alicia M; Pellegrino, Peter Ricci; Zucker, Irving H

2017-05-01

Tubuloglomerular feedback and the myogenic response are widely appreciated as important regulators of renal blood flow, but the role of the sympathetic nervous system in physiological renal blood flow control remains controversial. Where classic studies using static measures of renal blood flow failed, dynamic approaches have succeeded in demonstrating sympathetic control of renal blood flow under normal physiological conditions. This review focuses on transfer function analysis of renal pressure-flow, which leverages the physical relationship between blood pressure and flow to assess the underlying vascular control mechanisms. Studies using this approach indicate that the renal nerves are important in the rapid regulation of the renal vasculature. Animals with intact renal innervation show a sympathetic signature in the frequency range associated with sympathetic vasomotion that is eliminated by renal denervation. In conscious rabbits, this sympathetic signature exerts vasoconstrictive, baroreflex control of renal vascular conductance, matching well with the rhythmic, baroreflex-influenced control of renal sympathetic nerve activity and complementing findings from other studies employing dynamic approaches to study renal sympathetic vascular control. In this light, classic studies reporting that nerve stimulation and renal denervation do not affect static measures of renal blood flow provide evidence for the strength of renal autoregulation rather than evidence against physiological renal sympathetic control of renal blood flow. Thus, alongside tubuloglomerular feedback and the myogenic response, renal sympathetic outflow should be considered an important physiological regulator of renal blood flow. Clinically, renal sympathetic vasomotion may be important for solving the problems facing the field of therapeutic renal denervation. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

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

[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.

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.

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.

Renal and adrenal tumors: Pathology, radiology, ultrasonography, therapy, immunology

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

Lohr, E.; Leder, L.D.

1987-01-01

Aspects as diverse as radiology, pathology, urology, pediatrics and immunology have been brought together in one book. The most up-do-date methods of tumor diagnosis by CT, NMR, and ultrasound are covered, as are methods of catheter embolization and radiation techniques in case of primarily inoperable tumors. Contents: Pathology of Renal and Adrenal Neoplasms; Ultrasound Diagnosis of Renal and Pararenal Tumors; Computed-Body-Tomography of Renal Carcinoma and Perirenal Masses; Magnetic Resonance Imaging of Renal Mass Lesions; I-125 Embolotherapy of Renal Tumors; Adrenal Mass Lesions in Infants and Children; Computed Tomography of the Adrenal Glands; Scintigraphic Studies of Renal and Adrenal Function; Surgicalmore » Management of Renal Cell Carcinoma; Operative Therapy of Nephroblastoma; Nonoperative Treatment of Renal Cell Carcinoma; Prenatal Wilms' Tumor; Congenital Neuroblastoma; Nonsurgical Management of Wilms' Tumor; Immunologic Aspects of Malignant Renal Disease.« less

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.

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.

The relationship between renal volume and histology in obese and nonobese kidney donors.

PubMed

Tatar, Erhan; Sen, Sait; Harman, Mustafa; Kircelli, Fatih; Gungor, Ozkan; Sarsik, Banu; Asci, Gulay; Hoscoskun, Cuneyt; Basci, Ali; Toz, Huseyin

2015-06-01

Obesity and related kidney diseases have become a global epidemic problem. However, the underlying pathogenesis of obesity-related renal diseases has not been clearly understood. In this study, we explored the link between renal volume (RV) determined by computed tomography (CT) and renal histology together with functional parameters in an obese population. Eighty-two kidney donors who underwent CT for the measurement of kidney volume and zero-hour renal biopsy for renal histology were included in this cross-sectional study. Protein creatinine clearance and eGFR were evaluated in 24-h urine specimens as indicators of renal function. Mean body mass index (BMI) was 28 ± 4.2 kg/m(2); 32.9% (n = 27) were obese. Mean RV was 196 ± 36 cm(3). RV was positively correlated with BMI, body surface area and creatinine clearance and negatively with HDL-cholesterol in the whole population. Renal function parameters of obese subjects were better, and their renal volumes were higher compared with the nonobese subjects. In obese subjects, corrected RV was positively correlated with glomerular filtration rate (r = 0.46, P = 0.01) and negatively with sclerotic glomeruli (r = -0.38, P = 0.04) and chronicity index (r = -0.43, P = 0.02). In adjusted ordinal logistic regression analysis, corrected RV was significantly associated with chronicity index (OR: 0.96; P = 0.01). In obese cases, decreased RV determined by CT is associated with worse renal histology. In this population, kidney imaging techniques may provide important clues about renal survival. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

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.

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...

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.

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.

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

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.

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)

Oral Manifestations in a Renal Osteodystrophy Patient - A Case Report with Review of Literature

PubMed Central

Nisha V, Aarthi; GS, Asokan; CA, Prakash; MM, Varadharaja

2014-01-01

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. PMID:25302278

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.

[Fetal urology].

PubMed

Jakobovits, Akos; Jakobovits, Antal

2009-06-14

Although it becomes vitally important only after birth, renal function already plays significant role in maintaining fetal metabolic equilibrium. The kidneys significantly contribute to production of amniotic fluid. Adequate amount of amniotic fluid is needed to stimulate the intrauterine fetal respiratory activity. Intrauterine breathing is essential for lung development. As a result, oligohydramnion is conducive to pulmonary hypoplasia. The latter may lead to neonatal demise soon after birth. In extrauterine life kidneys eliminate nitrogen containing metabolic byproducts. Inadequate renal function results therefore lethal uremia. Integrity of ureters and the urethra is essential for the maintenance of renal function. Retention of urine causes degeneration of the functional units of the kidneys and ensuing deterioration of renal function. Intrauterine kidney puncture or shunt procedure may delay this process in some cases. On the other hand, once renal function has been damaged, no therapy can restart it. Certain anomalies of renal excretory pathways may also be associated with other congenital abnormalities, making the therapeutic efforts pointless. Presence of these associated intrauterine defects makes early pregnancy termination a management alternative, as well as it affects favorably perinatal mortality rates.

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

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.

Morphological and functional renovascular changes as cause of resistant arterial hypertension - case report and literature review.

PubMed

Costache, Irina Iuliana; Costea, Claudia Florida; Fotea, Vasile; Rusu, Victor Laurian; Aursulesei, Viviana; Al Namat, Razan; Costache, Dan Alexandru; Dumitrescu, Nicoleta; Buzdugă, Cătălin Mihai; Dumitrescu, Gabriela Florenţa; Sava, Anca; Bogdănici, Camelia Margareta

2018-01-01

Resistant hypertension is defined by the inability to maintain within normal limits the blood pressure values of an individual, while he is under treatment with maximal tolerated doses of three antihypertensive agents. One of the most common types of resistant hypertension is renovascular hypertension (RVH), which is caused by the narrowing of the renal arteries, in the context of existing atherosclerotic plaques at that level. We are presenting the case of a hypertensive 56-year-old man admitted in the Clinic of Cardiology for a sudden rise of his blood pressure values, despite undergoing the scheduled treatment. The abdominal bruit discovered at the clinical examination and the hypokalemia, together with the mild impairment of the renal function raised the suspicion of an existing stenosis of the main renal blood vessels. Simple grey scale kidney ultrasound, Doppler ultrasound of the renal arteries, abdominal computed tomography and magnetic resonance angiography of the renal arteries, along with invasive renal angiography demonstrated a smaller right kidney, adrenal incidentalomas, reduced vascular diameter of renal arteries due to atheromatous lesions, thrombosis of the infrarenal segment of the abdominal aorta, and reduced vascular hemodynamics in the same territories. After the renal arteries revascularization and with minimal antihypertensive treatment, the patient had a favorable outcome, with normalization of blood pressure and renal function. Atherosclerotic disease causing renal artery stenosis is essential to be taken into consideration in the etiopathogenesis of resistant hypertension especially because RVH is a potentially curable disease.

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.

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.

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.

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.

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.

A Literature Review of Renal Surgical Anatomy and Surgical Strategies for Partial Nephrectomy

PubMed Central

Klatte, Tobias; Ficarra, Vincenzo; Gratzke, Christian; Kaouk, Jihad; Kutikov, Alexander; Macchi, Veronica; Mottrie, Alexandre; Porpiglia, Francesco; Porter, James; Rogers, Craig G.; Russo, Paul; Thompson, R. Houston; Uzzo, Robert G.; Wood, Christopher G.; Gill, Inderbir S.

2016-01-01

Context A detailed understanding of renal surgical anatomy is necessary to optimize preoperative planning and operative technique and provide a basis for improved outcomes. Objective To evaluate the literature regarding pertinent surgical anatomy of the kidney and related structures, nephrometry scoring systems, and current surgical strategies for partial nephrectomy (PN). Evidence acquisition A literature review was conducted. Evidence synthesis Surgical renal anatomy fundamentally impacts PN surgery. The renal artery divides into anterior and posterior divisions, from which approximately five segmental terminal arteries originate. The renal veins are not terminal. Variations in the vascular and lymphatic channels are common; thus, concurrent lymphadenectomy is not routinely indicated during PN for cT1 renal masses in the setting of clinically negative lymph nodes. Renal-protocol contrast-enhanced computed tomography or magnetic resonance imaging is used for standard imaging. Anatomy-based nephrometry scoring systems allow standardized academic reporting of tumor characteristics and predict PN outcomes (complications, remnant function, possibly histology). Anatomy-based novel surgical approaches may reduce ischemic time during PN; these include early unclamping, segmental clamping, tumor-specific clamping (zero ischemia), and unclamped PN. Cancer cure after PN relies on complete resection, which can be achieved by thin margins. Post-PN renal function is impacted by kidney quality, remnant quantity, and ischemia type and duration. Conclusions Surgical renal anatomy underpins imaging, nephrometry scoring systems, and vascular control techniques that reduce global renal ischemia and may impact post-PN function. A contemporary ideal PN excises the tumor with a thin negative margin, delicately secures the tumor bed to maximize vascularized remnant parenchyma, and minimizes global ischemia to the renal remnant with minimal complications. Patient summary In this report we review renal surgical anatomy. Renal mass imaging allows detailed delineation of the anatomy and vasculature and permits nephrometry scoring, and thus precise, patient-specific surgical planning. Novel off-clamp techniques have been developed that may lead to improved outcomes. PMID:25911061

A Literature Review of Renal Surgical Anatomy and Surgical Strategies for Partial Nephrectomy.

PubMed

Klatte, Tobias; Ficarra, Vincenzo; Gratzke, Christian; Kaouk, Jihad; Kutikov, Alexander; Macchi, Veronica; Mottrie, Alexandre; Porpiglia, Francesco; Porter, James; Rogers, Craig G; Russo, Paul; Thompson, R Houston; Uzzo, Robert G; Wood, Christopher G; Gill, Inderbir S

2015-12-01

A detailed understanding of renal surgical anatomy is necessary to optimize preoperative planning and operative technique and provide a basis for improved outcomes. To evaluate the literature regarding pertinent surgical anatomy of the kidney and related structures, nephrometry scoring systems, and current surgical strategies for partial nephrectomy (PN). A literature review was conducted. Surgical renal anatomy fundamentally impacts PN surgery. The renal artery divides into anterior and posterior divisions, from which approximately five segmental terminal arteries originate. The renal veins are not terminal. Variations in the vascular and lymphatic channels are common; thus, concurrent lymphadenectomy is not routinely indicated during PN for cT1 renal masses in the setting of clinically negative lymph nodes. Renal-protocol contrast-enhanced computed tomography or magnetic resonance imaging is used for standard imaging. Anatomy-based nephrometry scoring systems allow standardized academic reporting of tumor characteristics and predict PN outcomes (complications, remnant function, possibly histology). Anatomy-based novel surgical approaches may reduce ischemic time during PN; these include early unclamping, segmental clamping, tumor-specific clamping (zero ischemia), and unclamped PN. Cancer cure after PN relies on complete resection, which can be achieved by thin margins. Post-PN renal function is impacted by kidney quality, remnant quantity, and ischemia type and duration. Surgical renal anatomy underpins imaging, nephrometry scoring systems, and vascular control techniques that reduce global renal ischemia and may impact post-PN function. A contemporary ideal PN excises the tumor with a thin negative margin, delicately secures the tumor bed to maximize vascularized remnant parenchyma, and minimizes global ischemia to the renal remnant with minimal complications. In this report we review renal surgical anatomy. Renal mass imaging allows detailed delineation of the anatomy and vasculature and permits nephrometry scoring, and thus precise, patient-specific surgical planning. Novel off-clamp techniques have been developed that may lead to improved outcomes. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

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

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

Renal manifestations in children with Alagille syndrome.

PubMed

Di Pinto, Diana; Adragna, Marta

2018-04-01

Alagille syndrome (AS) is a cholestatic disease secondary to scarcity of interlobular bile ducts. It is associated with extrahepatic manifestations, and renal involvement is frequent. To describe the prevalence, type and outcome of renal pathology in children with AS. The presence and outcome of renal pathology was retrospectively studied in 21 children who met AS criteria. Renal pathology was observed in 18 patients (85.7%): (1) ultrasound variations in 7 patients (6 cases of bilateral renal dysplasia and 1 case of renal agenesis); (2) distal renal tubular acidosis in 2 patients; (3) a drop in glomerular filtration and/or proteinuria in 16 patients. The frequency of a drop in glomerular filtration was similar between patients with and without pathological kidney ultrasound findings. Our study confirms a high prevalence of renal involvement, which enhances the importance of diagnosis and renal function follow-up in children with AS. Sociedad Argentina de Pediatría.

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.

Delafloxacin Pharmacokinetics in Subjects With Varying Degrees of Renal Function.

PubMed

Hoover, Randall K; Alcorn, Harry; Lawrence, Laura; Paulson, Susan K; Quintas, Megan; Cammarata, Sue K

2018-04-01

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 AUC 0-∞ . After intravenous administration, mean total clearance was 13.7 and 7.07 L/h, and mean AUC 0-∞ 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 CL CR . 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). © 2017, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

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

PubMed

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

2009-05-01

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

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.

Robot-assisted laparoscopic partial nephrectomy versus laparoscopic partial nephrectomy: A propensity score-matched comparative analysis of surgical outcomes and preserved renal parenchymal volume.

PubMed

Tachibana, Hidekazu; Takagi, Toshio; Kondo, Tsunenori; Ishida, Hideki; Tanabe, Kazunari

2018-04-01

To compare surgical outcomes, including renal function and the preserved renal parenchymal volume, between robot-assisted laparoscopic partial nephrectomy and laparoscopic partial nephrectomy using propensity score-matched analyses. In total, 253 patients, with a normal contralateral kidney, who underwent laparoscopic partial nephrectomy (n = 131) or robot-assisted laparoscopic partial nephrectomy (n = 122) with renal arterial clamping between 2010 and 2015, were included. Patients' background and tumor factors were adjusted by propensity score matching. Surgical outcomes, including postoperative renal function, complications, warm ischemia time and preserved renal parenchymal volume, evaluated by volumetric analysis, were compared between the surgical procedures. After matching, 64 patients were assigned to each group. The mean age was 56-57 years, and the mean tumor size was 22 mm. Approximately 50% of patients had low complexity tumors (RENAL nephrometry score 4-7). The incidence rate of acute kidney failure was significantly lower in the robot-assisted laparoscopic partial nephrectomy (11%) than laparoscopic partial nephrectomy (23%) group (P = 0.049), and warm ischemia time shorter in the robot-assisted laparoscopic partial nephrectomy (17 min) than laparoscopic partial nephrectomy (25 min) group (P < 0.0001). The preservation rate of renal function, measured by the estimated glomerular filtration rate, at 6 months post-surgery was 96% for robot-assisted laparoscopic partial nephrectomy and 90% for laparoscopic partial nephrectomy (P < 0.0001). The preserved renal parenchymal volume was higher for robot-assisted laparoscopic partial nephrectomy (89%) than laparoscopic partial nephrectomy (77%; P < 0.0001). The rate of perioperative complications, surgical margin status and length of hospital stay were equivalent for both techniques. Robot-assisted laparoscopic partial nephrectomy allows to achieve better preservation of renal function and parenchymal volume than laparoscopic partial nephrectomy. © 2018 The Japanese Urological Association.

[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.

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

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

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.

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.

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.

Renal involvement in juvenile rheumatoid arthritis: report of two cases.

PubMed

Gedalia, A; Mendez, E A; Craver, R; Vehaskari, M; Espinoza, L R

2001-01-01

Renal involvement is a rare occurrence in juvenile rheumatoid arthritis (JRA). We report on two JRA patients with kidney disease. The first was a 14-year-old African-American female with a 12-month history of polyarthritis. On presentation she was found to have an ESR of 127 mm/h and a positive ANA, rheumatoid factor (RF), perinuclear antineutrophil cytoplasmic antibodies (pANCA), haematuria, proteinuria with normal BUN and creatinine. Renal biopsy showed focal segmental glomerulosclerosis. Her renal function deteriorated to end-stage renal failure requiring dialysis within a few months, despite aggressive treatment with steorids and monthly i.v. pulses of cyclophosphamide. The second patient presented with a 6-week history of polyarthritis and intermittent fever, and had a salmon-coloured evanescent rash. On presentation his laboratory evaluation was significant for elevated ESR and negative ANA, RF and ANCA tests. Within 8 months the patient had developed a persistent microscopic haematuria. Renal biopsy showed mild mesangial glomerulonephritis. On low-dose methotrexate therapy his JRA went into remission and his renal function remained normal. The haematuria persisted for 1 year and then resolved spontaneously. This is the first time that focal segmental glomerulosclerosis and mesangial glomerulonephritis have been described in JRA. Although the association may be just coincidental, further studies are needed to define the role of JRA in these renal conditions. In patients with JRA, urinalysis and renal function should be routinely monitored.

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.

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.

Tributyltin chloride induces renal dysfunction by inflammation and oxidative stress in female rats.

PubMed

Coutinho, João V S; Freitas-Lima, Leandro C; Freitas, Frederico F C T; Freitas, Flávia P S; Podratz, Priscila L; Magnago, Rafaella P L; Porto, Marcella L; Meyrelles, Silvana S; Vasquez, Elisardo C; Brandão, Poliane A A; Carneiro, Maria T W D; Paiva-Melo, Francisca D; Miranda-Alves, Leandro; Silva, Ian V; Gava, Agata L; Graceli, Jones B

2016-10-17

Tributyltin chloride (TBT) is an organometallic pollutant that is used as a biocide in antifouling paints. TBT induces several toxic and endocrine-disrupting effects. However, studies evaluating the effects of TBT on renal function are rare. This study demonstrates that TBT exposure is responsible for improper renal function as well as the development of abnormal morphophysiology in mammalian kidneys. Female rats were treated with TBT, and their renal morphophysiology was assessed. Morphophysiological abnormalities such as decreased glomerular filtration rate and increased proteinuria levels were observed in TBT rats. In addition, increases in inflammation, collagen deposition and α-smooth muscle actin (α-SMA) protein expression were observed in TBT kidneys. A disrupted cellular redox balance and apoptosis in kidney tissue were also observed in TBT rats. TBT rats demonstrated reduced serum estrogen levels and estrogen receptor-α (ERα) protein expression in renal cortex. Together, these data provide in vivo evidence that TBT is toxic to normal renal function and that these effects may be associated with renal histopathology complications, such as inflammation and fibrosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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.

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.

Clinical Pharmacokinetics of Sulfobutylether-β-Cyclodextrin in Patients With Varying Degrees of Renal Impairment.

PubMed

Hoover, Randall K; Alcorn, Harry; Lawrence, Laura; Paulson, Susan K; Quintas, Megan; Luke, David R; Cammarata, Sue K

2018-03-26

Delafloxacin, a fluoroquinolone, has activity against Gram-positive organisms including methicillin-resistant S aureus and fluoroquinolone-susceptible and -resistant Gram-negative organisms. The intravenous formulation of delafloxacin contains the excipient sulfobutylether-β-cyclodextrin (SBECD), which is eliminated by renal filtration. This study examined the pharmacokinetics and safety of SBECD after single intravenous (IV) infusions in subjects with renal impairment. The study was an open-label, parallel-group, crossover study in subjects with normal renal function or mild, moderate, or severe renal impairment, and those with end-stage renal disease undergoing hemodialysis. Subjects received 300 mg delafloxacin IV or placebo IV, containing 2400 mg SBECD, in 2 periods separated by ≥14-day washouts. SBECD total clearance decreased with decreasing renal function, with a corresponding increase in area under the concentration-time curve (AUC 0-∞ ). After IV delafloxacin 300 mg administration, SBECD mean total clearance was 6.28 and 1.24 L/h, mean AUC 0-∞ was 387 and 2130 h·μg/mL, and mean renal clearance was 5.36 and 1.14 L/h in normal and severe renal subjects, respectively. Similar values were obtained after IV placebo administration. In subjects with end-stage renal disease, delafloxacin 300 mg IV produced mean SBECD AUC 0-48 values of 2715 and 7861 h·μg/mL when dosed before and after hemodialysis, respectively. Total SBECD clearance exhibited linear relationships to estimated glomerular filtration rate and creatinine clearance. Single doses of IV delafloxacin 300 mg and IV placebo were well tolerated in all groups. In conclusion, decreasing renal function causes reduced SBECD clearance and increased exposures, but SBECD continues to exhibit a good safety and tolerability profile in IV formulations. © 2018, The American College of Clinical Pharmacology.

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.

Influence of renal insufficiency on the pharmacokinetics of cicletanine and its effects on the urinary excretion of electrolytes and prostanoids.

PubMed Central

Ferry, N; Geoffroy, J; Pozet, N; Cuisinaud, G; Benzoni, D; Zech, P Y; Sassard, J

1988-01-01

1. The kinetics of a single oral dose (300 mg) of cicletanine a new antihypertensive drug with diuretic properties, and its effects on the urinary excretion of electrolytes and of the major stable metabolites of prostacyclin and thromboxane A2 were studied in patients with normal renal function (n = 6), mild (n = 9) and severe (n = 10) renal insufficiency. 2. In normotensive subjects with normal renal function, cicletanine was rapidly and regularly absorbed, its apparent elimination half-life established around 7 h, and both its renal clearance (0.4 ml min-1) and its cumulative renal excretion (0.85% of the administered dose), were low. Mild renal insufficiency did not significantly alter these parameters, while severe renal impairment reduced the renal clearance and the cumulative urinary excretion of cicletanine and increased its apparent elimination half-life (31 h). However the area under the plasma curve was not changed due to reduced plasma concentrations in these patients. 3. Cicletanine induced a rapid and marked (four fold as a mean) increase in the urinary excretion of water, sodium and potassium which lasted for 6 to 10 h, in subjects with normal renal function. Renal insufficiency did not alter the slope of the calculated plasma concentration-effects curves but reduced the maximum effect observed for water, sodium and potassium. 4. A single oral dose of cicletanine did not change the urinary excretion of 6-keto-prostaglandin F1 alpha and thromboxane B2 in the three groups of patients studied, the basal values of which being found to be closely related to the creatinine clearance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3358898

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.

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

PubMed

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

2015-12-01

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

Renal and blood pressure effects from environmental cadmium exposure in Thai children

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

Swaddiwudhipong, Witaya, E-mail: swaddi@hotmail.com; Mahasakpan, Pranee; Jeekeeree, Wanpen

Very few studies have shown renal and blood pressure effects from environmental cadmium exposure in children. This population study examined associations between urinary cadmium excretion, a good biomarker of long-term cadmium exposure, and renal dysfunctions and blood pressure in environmentally exposed Thai children. Renal functions including urinary excretion of β{sub 2}-microglobulin, calcium (early renal effects), and total protein (late renal effect), and blood pressure were measured in 594 primary school children. Of the children studied, 19.0% had urinary cadmium ≥1 μg/g creatinine. The prevalence of urinary cadmium ≥1 μg/g creatinine was significantly higher in girls and in those consuming ricemore » grown in cadmium-contaminated areas. The geometric mean levels of urinary β{sub 2}-microglobulin, calcium, and total protein significantly increased with increasing tertiles of urinary cadmium. The analysis did not show increased blood pressure with increasing tertiles of urinary cadmium. After adjusting for age, sex, and blood lead levels, the analysis showed significant positive associations between urinary cadmium and urinary β{sub 2}-microglobulin and urinary calcium, but not urinary total protein nor blood pressure. Our findings provide evidence that environmental cadmium exposure can affect renal functions in children. A follow-up study is essential to assess the clinical significance and progress of renal effects in these children. - Highlights: • Few studies show renal effects from environmental cadmium exposure in children. • We report renal and blood pressure effects from cadmium exposure in Thai children. • Urinary β{sub 2}-microglobulin and calcium increased with increasing urinary cadmium. • The study found no association between urinary cadmium levels and blood pressure. • Environmental cadmium exposure can affect renal functions in children.« less

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.

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.

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

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.

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.

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.

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.

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.

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.

Renal function and size at young adult age after intrauterine growth restriction and very premature birth.

PubMed

Keijzer-Veen, Mandy G; Kleinveld, Hilda A; Lequin, Maarten H; Dekker, Friedo W; Nauta, Jeroen; de Rijke, Yolanda B; van der Heijden, Bert J

2007-10-01

Premature birth and intrauterine growth restriction may increase the risk of developing renal disease at adult age. Renal function may already be impaired at young adult age. Cross-sectional study. Very premature individuals (gestational age < 32 weeks) recruited from Project on Premature and Small for Gestational Age Infants and full-term-born controls (37 to 42 weeks) recruited from a children's hospital in Rotterdam, The Netherlands. All individuals were 20 years of age at the time of study. Gestational age and birth weight: premature and small for gestational age (SGA; n = 23), premature and appropriate for gestational age (n = 29), and controls (n = 30). Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and filtration fraction before and after renal stimulation with low-dose dopamine infusion and oral amino-acid intake. Urine albumin and renal ultrasound. Height, weight, kidney length and volume, GFR, and ERPF were significantly lower in the SGA group than in controls. After adjustment for body surface area, GFR did not differ significantly among groups. Mean ERPF was 71 mL/min/1.73 m(2) (95% confidence interval [CI], 3 to 139) less, but filtration fraction was only 1.3% (95% CI, -0.3 to 3.0) greater, in the SGA group than controls. Renal stimulation significantly increased GFR and ERPF and decreased filtration fraction in all groups. After renal stimulation, ERPF was 130 mL/min/1.73 m(2) (95% CI, 21 to 238) greater in the SGA group than controls, but GFR and filtration fraction did not differ significantly among groups. Microalbuminuria was present in 2 patients (8.7%) in the SGA group, but none in the appropriate-for-gestational-age group or controls. Renal function correlated with renal size. Small sample size. Our findings do not fully support the hypothesis that preterm birth in combination with intrauterine growth restriction contributes to renal function alterations at young adult age. Larger studies are needed to evaluate this hypothesis.

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).

SGLT2 inhibitors and renal outcomes in type 2 diabetes with or without renal impairment: A systematic review and meta-analysis.

PubMed

Seidu, Samuel; Kunutsor, Setor K; Cos, Xavier; Gillani, Syed; Khunti, Kamlesh

2018-06-01

Sodium-glucose co-transporter 2 (SGLT2) inhibitors may have renal protective effects in people with impaired kidney function. We assessed the use of SGLT2 inhibitors in people with type 2 diabetes with or without renal impairment [defined as estimated glomerular filtration rate (eGFR) of ≥30 and <60ml/min/1.73m 2 and/or UACR>300 and ≤5000mg/g] by conducting a systematic review and meta-analysis of available studies. Randomised controlled trials (RCTs) were identified from MEDLINE, EMABASE, Web of Science, the Cochrane Library, and search of bibliographies to March 2017. No relevant observational study was identified. Summary measures were presented as mean differences and narrative synthesis performed for studies that could not be pooled. 42 articles which included 40 RCTs comprising 29,954 patients were included. In populations with renal impairment, SGLT2 inhibition compared with placebo was consistently associated with an initial decrease in eGFR followed by an increase and return to baseline levels. In pooled analysis of 17 studies in populations without renal impairment, there was no significant change in eGFR comparing SGLT2 inhibitors with placebo (mean difference, 0.51ml/min/1.73m 2 ; 95% CI: -0.69, 1.72; p=403). SGLT2 inhibition relative to placebo was associated with preservation in serum creatinine levels or initial increases followed by return to baseline levels in patients with renal impairment, but levels were preserved in patients without renal impairment. In populations with or without renal impairment, SGLT2 inhibitors (particularly canagliflozin and empagliflozin) compared with placebo were associated with decreased urine albumin, improved albuminiuria, slowed progression to macroalbuminuria, and reduced the risk of worsening renal impairment, the initiation of kidney transplant, and death from renal disease. Emerging data suggests that with SGLT2 inhibition, renal function seems to be preserved in people with diabetes with or without renal impairment. Furthermore, SGLT2 inhibition prevents further renal function deterioration and death from kidney disease in these patients. Copyright © 2018 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

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.

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.

New magnetic resonance imaging methods in nephrology

PubMed Central

Zhang, Jeff L.; Morrell, Glen; Rusinek, Henry; Sigmund, Eric; Chandarana, Hersh; Lerman, Lilach O.; Prasad, Pottumarthi Vara; Niles, David; Artz, Nathan; Fain, Sean; Vivier, Pierre H.; Cheung, Alfred K.; Lee, Vivian S.

2013-01-01

Established as a method to study anatomic changes, such as renal tumors or atherosclerotic vascular disease, magnetic resonance imaging (MRI) to interrogate renal function has only recently begun to come of age. In this review, we briefly introduce some of the most important MRI techniques for renal functional imaging, and then review current findings on their use for diagnosis and monitoring of major kidney diseases. Specific applications include renovascular disease, diabetic nephropathy, renal transplants, renal masses, acute kidney injury and pediatric anomalies. With this review, we hope to encourage more collaboration between nephrologists and radiologists to accelerate the development and application of modern MRI tools in nephrology clinics. PMID:24067433

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.

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

Application of Onyx for Renal Arteriovenous Malformation With First Case Report of a Renal Hyperdense Striation Sign

PubMed Central

Juan, Yu-Hsiang; Lin, Yu-Ching; Sheng, Ting-Wen; Cheung, Yun-Chung; Ng, Shu-Hang; Yu, Chin-Wei; Wong, Ho-Fai

2015-01-01

Abstract Onyx is an emerging treatment modality for visceral vascular malformations, especially in cases in which delicate nidal penetration of the arteriovenous malformation (AVM) is desired. A computed tomography (CT) image presentation of hyperdense striations along the renal medulla secondary to the tantalum powder has not been previously reported. A 65-year-old woman presented to our institution with intermittent gross hematuria and left flank pain for 10 days. Both CT and conventional angiographies confirmed cirsoid-type renal AVM, which was successfully treated with Onyx. Follow-up CT after treatment revealed presence of hyperdense striations along the renal medulla, which resolved during later image follow-up. Despite its frequent usage in neural intervention, the application of Onyx in visceral AVM is gradually gaining interest, especially in cases in which delicate nidal penetration of the AVM is desired. Renal hyperdense striation sign should be recognized to avoid confusion with embolizer migration, and further studies in patients with renal function impairment may be helpful in understanding its influence of renal function. PMID:26426661

Acute kidney injury as the presenting manifestation of sarcoidosis: A case series and review of literature.

PubMed

Rajkumar, Theepika; Lea-Henry, Tom; Chacko, Bobby

2018-06-01

Acute kidney injury is rarely the presenting feature of sarcoidosis. We present a case series of patients whose diagnosis of sarcoidosis was only brought to light by the development of renal impairment. Concurrent hypercalcaemia was noted, prompting further investigation. The patients discussed experienced a significant and rapid improvement in both renal function and hypercalcaemia in response to therapy with prednisolone. This is out of keeping with previous reports of sarcoidosis-induced renal impairment. Our case series highlights the importance of testing for hypercalcaemia in the context of acute kidney injury. Sarcoidosis is primarily a disease of the lungs and reticuloendothelial system; however, the prevalence of renal involvement with sarcoidosis may be under-recognized. The renal manifestations of sarcoidosis are discussed in the context of the current literature. Furthermore, from our experience, we postulate that in the context of sarcoidosis-induced renal injury, concurrent hypercalcaemia may present prior to the development of chronic renal injury and therefore these patients may be more likely to recover renal function. © 2017 Asian Pacific Society of Nephrology.

Late-onset renal vein thrombosis: A case report and review of the literature

PubMed Central

Hogan, Jessica L.; Rosenthal, Stanton J.; Yarlagadda, Sri G.; Jones, Jill A.; Schmitt, Timothy M.; Kumer, Sean C.; Kaplan, Bruce; Deas, Shenequa L.; Nawabi, Atta M.

2014-01-01

INTRODUCTION Renal vein thrombosis, a rare complication of renal transplantation, often causes graft loss. Diagnosis includes ultrasound with Doppler, and it is often treated with anticoagulation or mechanical thrombectomy. Success is improved with early diagnosis and institution of treatment. PRESENTATION OF CASE We report here the case of a 29 year-old female with sudden development of very late-onset renal vein thrombosis after simultaneous kidney pancreas transplant. This resolved initially with thrombectomy, stenting and anticoagulation, but thrombosis recurred, necessitating operative intervention. Intraoperatively the renal vein was discovered to be compressed by a large ovarian cyst. DISCUSSION Compression of the renal vein by a lymphocele or hematoma is a known cause of thrombosis, but this is the first documented case of compression and thrombosis due to an ovarian cyst. CONCLUSION Early detection and treatment of renal vein thrombosis is paramount to restoring renal allograft function. Any woman of childbearing age may have thrombosis due to compression by an ovarian cyst, and screening for this possibility may improve long-term graft function in this population. PMID:25528029

Late-onset renal vein thrombosis: A case report and review of the literature.

PubMed

Hogan, Jessica L; Rosenthal, Stanton J; Yarlagadda, Sri G; Jones, Jill A; Schmitt, Timothy M; Kumer, Sean C; Kaplan, Bruce; Deas, Shenequa L; Nawabi, Atta M

2015-01-01

Renal vein thrombosis, a rare complication of renal transplantation, often causes graft loss. Diagnosis includes ultrasound with Doppler, and it is often treated with anticoagulation or mechanical thrombectomy. Success is improved with early diagnosis and institution of treatment. We report here the case of a 29 year-old female with sudden development of very late-onset renal vein thrombosis after simultaneous kidney pancreas transplant. This resolved initially with thrombectomy, stenting and anticoagulation, but thrombosis recurred, necessitating operative intervention. Intraoperatively the renal vein was discovered to be compressed by a large ovarian cyst. Compression of the renal vein by a lymphocele or hematoma is a known cause of thrombosis, but this is the first documented case of compression and thrombosis due to an ovarian cyst. Early detection and treatment of renal vein thrombosis is paramount to restoring renal allograft function. Any woman of childbearing age may have thrombosis due to compression by an ovarian cyst, and screening for this possibility may improve long-term graft function in this population. Published by Elsevier Ltd.

Zinc deficiency during growth: influence on renal function and morphology.

PubMed

Tomat, Analía Lorena; Costa, María Angeles; Girgulsky, Luciana Carolina; Veiras, Luciana; Weisstaub, Adriana Ruth; Inserra, Felipe; Balaszczuk, Ana María; Arranz, Cristina Teresa

2007-03-13

This study was designed to investigate the effects of moderate zinc deficiency during growth on renal morphology and function in adult life. Weaned male Wistar rats were divided into two groups and fed either a moderately zinc-deficient diet (zinc: 8 mg/kg, n=12) or a control diet (zinc: 30 mg/kg, n=12) for 60 days. We evaluated: renal parameters, NADPH-diaphorase and nitric oxide synthase activity in kidney, renal morphology and apoptotic cells in renal cortex. Zinc-deficient rats showed a decrease in glomerular filtration rate and no changes in sodium and potassium urinary excretion. Zinc deficiency decreased NADPH diaphorase activity in glomeruli and tubular segment of nephrons, and reduced activity of nitric oxide synthase in the renal medulla and cortex, showing that zinc plays an important role in preservation of the renal nitric oxide system. A reduction in nephron number, glomerular capillary area and number of glomerular nuclei in cortical and juxtamedullary areas was observed in zinc deficient kidneys. Sirius red staining and immunostaining for alpha-smooth muscle-actin and collagen III showed no signs of fibrosis in the renal cortex and medulla. An increase in the number of apoptotic cells in distal tubules and cortical collecting ducts neighboring glomeruli and, to a lesser extent, in the glomeruli was observed in zinc deficient rats. The major finding of our study is the emergence of moderate zinc deficiency during growth as a potential nutritional factor related to abnormalities in renal morphology and function that facilitates the development of cardiovascular and renal diseases in adult life.

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

Homer W. Smith's contribution to renal physiology.

PubMed

Giebisch, Gerhard

2004-01-01

Homer Smith was, for three decades, from the 1930s until his death in 1962, one of the leaders in the field of renal physiology. His contributions were many: he played a major role in introducing and popularizing renal clearance methods, introduced non-invasive methods for the measurement of glomerular filtration rate, of renal blood flow and tubular transport capacity, and provided novel insights into the mechanisms of excretion of water and electrolytes. Homer Smith's contributions went far beyond his personal investigations. He was a superb writer of several inspiring textbooks of renal physiology that exerted great and lasting influence on the development of renal physiology. Smith's intellectual insights and ability for critical analysis of data allowed him to create broad concepts that defined the functional properties of glomeruli, tubules and the renal circulation. A distinguishing feature of Homer Smith's career was his close contact and collaboration, over many years, with several clinicians of his alma mater, New York University. For initiating these pathophysiological investigations, he is justly credited to have advanced, in a major way, our understanding of altered renal function in disease. Smith's lasting scientific impact is also reflected by a whole school of investigators that trained with him and who applied his methods, analyses and concepts to the study of renal function all over the world. So great was his influence and preeminence that Robert Pitts, in his excellent tribute to Homer Smith in the Memoirs of the National Academy of Science states that his death brought an end to what might be aptly called the Smithian Era of renal physiology.

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.

Protective Role for Antioxidants in Acute Kidney Disease

PubMed Central

Dennis, Joanne M.; Witting, Paul K.

2017-01-01

Acute kidney injury causes significant morbidity and mortality in the community and clinic. Various pathologies, including renal and cardiovascular disease, traumatic injury/rhabdomyolysis, sepsis, and nephrotoxicity, that cause acute kidney injury (AKI), induce general or regional decreases in renal blood flow. The ensuing renal hypoxia and ischemia promotes the formation of reactive oxygen species (ROS) such as superoxide radical anions, peroxides, and hydroxyl radicals, that can oxidatively damage biomolecules and membranes, and affect organelle function and induce renal tubule cell injury, inflammation, and vascular dysfunction. Acute kidney injury is associated with increased oxidative damage, and various endogenous and synthetic antioxidants that mitigate source and derived oxidants are beneficial in cell-based and animal studies. However, the benefit of synthetic antioxidant supplementation in human acute kidney injury and renal disease remains to be realized. The endogenous low-molecular weight, non-proteinaceous antioxidant, ascorbate (vitamin C), is a promising therapeutic in human renal injury in critical illness and nephrotoxicity. Ascorbate may exert significant protection by reducing reactive oxygen species and renal oxidative damage via its antioxidant activity, and/or by its non-antioxidant functions in maintaining hydroxylase and monooxygenase enzymes, and endothelium and vascular function. Ascorbate supplementation may be particularly important in renal injury patients with low vitamin C status. PMID:28686196

Association Between the Use of Proton Pump Inhibitors and the Risk of ESRD in Renal Diseases: A Population-Based, Case-Control Study

PubMed Central

Peng, Yen-Chun; Lin, Cheng-Li; Yeh, Hong-Zen; Chang, Chi-Sen; Wu, Yu-Lin; Kao, Chia-Hung

2016-01-01

Abstract Proton pump inhibitors (PPIs) use may be associated with nephritis and acute renal injury. The risk of PPIs and deterioration of renal function, in patients with renal diseases, needs to be investigated. A case-control study was conducted in a nation-wide data setting from the Taiwan National Health Insurance Research Database (NHIRD). This case-control study used data extracted from NHIRD between the years 2006 and 2011. We used propensity scores to match 3808 patients suffering from renal diseases (ICD-9-CM codes 580–589), with patients (aged ≥20 years) who had had a recent diagnosis of end-stage renal diseases (ESRDs) and had undertaken renal replacement therapy during the period of 2006 to 2011. The 3808 control subjects were selected from people who had a history of renal diseases, but no ESRD. The risk of ESRD in patients with renal diseases and PPIs use was estimated by using odds ratios (ORs) and 95% confidence intervals (CI). The use of a PPIs was associated with a significantly higher risk of ESRD (adjusted OR = 1.88, 95% CI = 1.71–2.06) in renal disease patients. Of all the types of PPI combined, the adjusted OR was 1.92 (95% CI = 1.74–2.13) for those on <100 cumulative DDD and was 1.74-fold (95% CI = 1.52–2.00) for those on ≥100 cumulative DDD. PPIs use is associated with the risk of ESRD in patients with renal diseases. It is necessary that appropriate prescription of PPIs coordinated with the close monitoring renal function of patients diagnosed with renal disease. PMID:27082596

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

Effect of Renal Impairment on the Pharmacokinetics and Pharmacodynamics of Verinurad, a Selective Uric Acid Reabsorption Inhibitor.

PubMed

Smith, William B; Hall, Jesse; Berg, Jolene K; Kazimir, Michal; Yamamoto, Amy; Walker, Susan; Lee, Caroline A; Shen, Zancong; Wilson, David M; Zhou, Dongmei; Gillen, Michael; Marbury, Thomas C

2018-06-11

BACKGROUND AND OBJECTIVE: Verinurad (RDEA3170) is a high-affinity, selective URAT1 transporter inhibitor in development for treating gout and asymptomatic hyperuricemia. This Phase I, single-dose study investigated the pharmacokinetics, pharmacodynamics, and safety of verinurad in adults with renal impairment and controls with normal renal function. Males aged 18-85 years were enrolled with serum urate (sUA) 4.5-10 mg/dl and creatinine clearance 60- < 90, 30- < 60, 15- < 30, or ≥ 90 ml/min (mild, moderate, severe renal impairment and controls, respectively; n = 7/8). Verinurad 15 mg was administered orally under fasted conditions. Serial plasma/serum and urine samplings were 30 min pre-dose to 72 h post-dose. Compared to controls, verinurad maximum observed plasma concentration increased by 53, 73, and 128% and area under the concentration-time curve increased by 24, 148, and 130%, in subjects with mild, moderate, and severe renal impairment, respectively; renal clearance decreased by 5, 42, and 79%. Exposures of major verinurad metabolites also increased with increasing renal impairment. Verinurad decreased sUA in all groups, with greater maximal changes in control and mild renal impairment than moderate and severe impairment groups (- 38.3, - 36.9, - 20.5, - 12.6%, respectively). There were no adverse event-related withdrawals or clinically meaningful changes in laboratory values. Exposures of verinurad and metabolites increased with decreasing renal function. Consistent with the renal-dependent mechanism of action of verinurad, increasing severity of renal impairment was associated with decreased sUA lowering. Verinurad safety assessments were similar regardless of renal impairment. Continued investigation of verinurad is warranted in patients with gout and renal impairment. CLINICALTRIALS. NCT02219516.

Noncontrast-enhanced magnetic resonance renal angiography using a repetitive artery and venous labelling technique at 3 T: comparison with contrast-enhanced magnetic resonance angiography in subjects with normal renal function.

PubMed

Park, Sung Yoon; Kim, Chan Kyo; Kim, EunJu; Park, Byung Kwan

2015-02-01

To investigate the feasibility of noncontrast-enhanced MR angiography (NC-MRA) using the repetitive artery and venous labelling (RAVEL) technique to evaluate renal arteries compared to contrast-enhanced MR angiography (CE-MRA). Twenty-five subjects with normal renal function underwent NC-MRA using a RAVEL technique and CE-MRA at 3 T. Two independent readers analysed the MRA images. Image quality, number of renal arteries, presence or absence of an early branching vessel, and diameter of the main renal arteries were evaluated. The overall image quality of NC-MRA was fair or greater in 88% of right and 92% of left renal arteries, while it was 96% in both sides with CE-MRA. On NC-MRA, the number of renal arteries in all subjects was perfectly predicted by both readers. Sensitivity and specificity for predicting early branching vessels were 82% and 100% for reader 1 and 82% and 95% for reader 2. Inter-modality agreement for comparing the diameters of main renal arteries was good or excellent at all segments for both readers. Inter-reader agreement was moderate or good at all segments except at the right distal segment on NC-MRA. NC-MRA with the RAVEL technique at 3 T may have comparable diagnostic feasibility for evaluating renal arteries compared to CE-MRA. • Accurate pre-treatment evaluation of renal artery anatomy helps clinical decision-making. • NC-MRA using RAVEL offers acceptable imaging quality for renal artery evaluation. • The 3 T RAVEL technique provides excellent diagnostic performance for renal artery evaluation. • The 3 T RAVEL technique may be an alternative to contrast-enhanced MRA.

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.

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.

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.

[Anatomy character of renal artery and treatment of living-donor renal transplantation].

PubMed

Zhang, Lei; Fei, Ji-guang; Chen, Li-zhong; Wang, Chang-xi; Deng, Su-xiong; Qiu, Jiang; Li, Jun; Chen, Guo-dong; Huang, Gang

2009-12-15

To study the anatomy characters of renal artery and the treatment of multiple arteries in living donor renal grafts. Records of 142 living donors were analyzed in our center. We analyzed the anatomic structure of renal arteries by DSA and CTA pre-transplantation. Thirty-one kidneys with multiple arteries were transplanted after reconstruction. Then clinical effects were compared between multiple-renal-arteries group (n=31) and single-renal-artery group (n=111). The incidence of multiple renal artery was 30.99%, and there was no difference between both sides (left kidney 22.54%, right kidney 22.13%). If the multiple artery occurred in left or right kidney, the incidence of the multiple artery occurred in the other side was 56.25% and 60.00%, respectively. The diameter of left main renal artery was more magnanimous (P=0.001) and the first branch was more closed to abdominal aorta (P=0.004). Operation time and warm/cool ischemia time were longer in the multiple-renal-arteries group. However, estimated blood loss, delayed graft function, acute rejection and flow rate of arcuate artery were similar in both groups, the same as serum creatinine and serum creatinine clearance rate on day 7, 1 month and 3 month post-operation. It was shown by repeated measures ANOVA that graft with multiple arteries didn't affect the tendency of renal function at early time post-operation. Comprehending the character of renal artery and accurate treatment of multiple artery anastomosis are critical for the effect of the living kidney transplantation.

GDF11 induces kidney fibrosis, renal cell epithelial-to-mesenchymal transition, and kidney dysfunction and failure.

PubMed

Pons, Marianne; Koniaris, Leonidas G; Moe, Sharon M; Gutierrez, Juan C; Esquela-Kerscher, Aurora; Zimmers, Teresa A

2018-05-03

GDF11 modulates embryonic patterning and kidney organogenesis. Herein, we sought to define GDF11 function in the adult kidney and in renal diseases. In vitro renal cell lines, genetic, and murine in vivo renal injury models were examined. Among tissues tested, Gdf11 was highest in normal adult mouse kidney. Expression was increased acutely after 5/6 nephrectomy, ischemia-reperfusion injury, kanamycin toxicity, or unilateral ureteric obstruction. Systemic, high-dose GDF11 administration in adult mice led to renal failure, with accompanying kidney atrophy, interstitial fibrosis, epithelial-to-mesenchymal transition of renal tubular cells, and eventually death. These effects were associated with phosphorylation of SMAD2 and could be blocked by follistatin. In contrast, Gdf11 heterozygous mice showed reduced renal Gdf11 expression, renal fibrosis, and expression of fibrosis-associated genes both at baseline and after unilateral ureteric obstruction compared with wild-type littermates. The kidney-specific consequences of GDF11 dose modulation are direct effects on kidney cells. GDF11 induced proliferation and activation of NRK49f renal fibroblasts and also promoted epithelial-to-mesenchymal transition of IMCD-3 tubular epithelial cells in a SMAD3-dependent manner. Taken together, these data suggest that GDF11 and its downstream signals are critical in vivo mediators of renal injury. These effects are through direct actions of GDF11 on renal tubular cells and fibroblasts. Thus, regulation of GDF11 presents a therapeutic target for diseases involving renal fibrosis and impaired tubular function. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

[Current role of color Doppler ultrasound in acute renal failure].

PubMed

Bertolotto, M; Quaia, E; Rimondini, A; Lubin, E; Pozzi Mucelli, R

2001-01-01

Acute Renal Failure (ARF) is characterized by a rapid decline of the glomerular filtration rate, due to hypotension (prerenal ARF), obstruction of the urinary tract (post-renal ARF) or renal parenchymal disease (renal ARF). The differential diagnosis among different causes of ARF is based on anamnesis, clinical symptoms and laboratory data. Usually ultrasound (US) is the only imaging examination performed in these patients, because it is safe and readily available. In patients with ARF gray scale US is usually performed to rule out obstruction since it is highly sensitive to recognize hydronephrosis. Patients with renal ARF have no specific changes in renal morphology. The size of the kidneys is usually normal or increased, with smooth margins. Detection of small kidneys suggests underlying chronic renal pathology and worse prognosis. Echogenicity and parenchymal thickness are usually normal, but in some cases there are hyperechogenic kidneys, increased parenchymal thickness and increased cortico-medullary differentiation. Evaluation of renal vasculature with pulsed Doppler US is useful in the differential diagnosis between prerenal ARF and acute tubular necrosis (ATN), and in the diagnosis of renal obstruction. Latest generation US apparatus allow color Doppler and power Doppler evaluation of renal vasculature up to the interlobular vessels. A significant, but non specific, reduction in renal perfusion is usually appreciable in the patients with ARF. There are renal pathologic conditions presenting with ARF in which color Doppler US provides more specific morphologic and functional information. In particular, color Doppler US often provides direct or indirect signs which can lead to the right diagnosis in old patients with chronic renal insufficiency complicated with ARF, in patients with acute pyelonephritis, hepatic disease, vasculitis, thrombotic microangiopathies, and in patients with acute thrombosis of the renal artery and vein. Contrast enhanced US is another useful diagnostic tool in patients with ARF which has been recently introduced in clinical practice. Microbubble administration may reduce technical failure in the evaluation of the renal artery. Moreover, perfusion defects due to stenosis or thrombosis of the renal segmentary vessels are better recognized. New diagnostic possibilities of enhanced US include evaluation of both cortical and medullar vessels, and functional evaluation of renal perfusion. Measuring the transit time of the microbubbles is useful for the diagnosis of renal artery stenosis and, in transplanted kidneys, for differential diagnosis between ATN and acute rejection.

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.

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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Concealed renal failure and adverse drug reactions in older patients with type 2 diabetes mellitus.

PubMed

Corsonello, Andrea; Pedone, Claudio; Corica, Francesco; Mazzei, Bruno; Di Iorio, Angelo; Carbonin, Pierugo; Incalzi, Raffaele Antonelli

2005-09-01

In elderly patients serum creatinine may be normal despite decreased glomerular filtration rate (GFR). The aim of this study was to evaluate the prevalence of this "concealed" renal failure, i.e., renal failure with normal serum creatinine levels, in elderly diabetic patients, and to verify whether it is a risk factor for adverse drug reactions (ADR) to hydrosoluble drugs. We used data on 2257 hospitalized patients with type 2 diabetes mellitus enrolled in the Gruppo Italiano di Farmacovigilanza nell'Anziano study. On the basis of serum creatinine and calculated GFR, patients were grouped as follows: normal renal function (normal serum creatinine levels and normal GFR), concealed (normal serum creatinine levels and reduced GFR), or overt (increased creatinine levels and reduced GFR) renal failure. GFR was calculated using the Modification of Diet in Renal Disease (MDRD) equation. The outcome of the study was the incidence of ADR to hydrosoluble drugs during the hospital stay. The relationship between renal function and ADR was evaluated using Cox regression analysis including potential confounders. Concealed renal failure was observed in 363 (16.1%) of patients studied. Patients with concealed or overt renal failure were older, had more frequently cognitive impairment and polypharmacy, and had lower serum albumin levels than did those with normal renal function. Both concealed (hazard ratio = 1.90; 95% confidence interval, 1.04-3.48; p =.036) and overt (hazard ratio = 2.23; 95% confidence interval, 1.40-3.55; p =.001) renal failure were significantly associated with ADR to hydrosoluble drugs. The use of more than four drugs also qualified as an independent risk factor for ADRs to hydrosoluble drugs during hospital stay. Older diabetic patients should be systematically screened to ascertain the presence of concealed renal failure in an attempt to optimize the pharmacological treatment and reduce the risk of ADRs.

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.

[Renal failure in patients with liver transplant: incidence and predisposing factors].

PubMed

Gerona, S; Laudano, O; Macías, S; San Román, E; Galdame, O; Torres, O; Sorkin, E; Ciardullo, M; de Santibañes, E; Mastai, R

1997-01-01

Renal failure is a common finding in patients undergoing orthotopic liver transplantation. The aim of the present study was to evaluate the incidence, prognostic value of pre, intra and postoperative factors and severity of renal dysfunction in patients who undergo liver transplantation. Therefore, the records of 38 consecutive adult patients were reviewed. Renal failure was defined arbitrarily as an increase in creatinine (> 1.5 mg/dl) and/or blood urea (> 80 mg/dl). Three patients were excluded of the final analysis (1 acute liver failure and 2 with a survival lower than 72 hs.) Twenty one of the 35 patients has renal failure after orthotopic liver transplantation. Six of these episodes developed early, having occurred within the first 6 days. Late renal impairment occurred in 15 patients within the hospitalization (40 +/- 10 days) (Mean +/- SD). In he overall series, liver function, evaluated by Child-Pugh classification, a higher blood-related requirements and cyclosporine levels were observed more in those who experienced renal failure than those who did not (p < 0.05). Early renal failure was related with preoperative (liver function) and intraoperative (blood requirements) factors and several causes (nephrotoxic drugs and graft failure) other than cyclosporine were present in patients who developed late renal impairment. No mortality. No mortality was associated with renal failure. We conclude that renal failure a) is a common finding after liver transplantation, b) the pathogenesis of this complication is multifactorial and, c) in not related with a poor outcome.

Prevalence and predictors of renal artery stenosis in patients undergoing peripheral and coronary angiography.

PubMed

Shukla, Anand N; Madan, Tarun H; Jayaram, Ashwal A; Kute, Vivek B; Rawal, Jayesh R; Manjunath, A P; Udhreja, Satyam

2013-12-01

Renal artery stenosis is a potential cause of secondary hypertension, ischemic nephropathy and end-stage renal disease. Atherosclerosis is by far the most common etiology of renal artery stenosis in elderly. We investigated whether the presence of significant atherosclerotic renal artery stenosis (ARAS) with luminal diameter narrowing ≥50 % could be predicted in patients undergoing peripheral and coronary angiography. The records of 3,500 consecutive patients undergoing simultaneous renal angiography along with peripheral and coronary angiography were reviewed. The patients with known renal artery disease were excluded. Prevalence of ARAS was 5.7 %. Significant ARAS (luminal diameter narrowing ≥50 %) was present in 139 patients (3.9 %). Hypertension with altered serum creatinine and triple-vessel CAD were associated with significant renal artery stenosis in multivariate analysis. No significant relationship between the involved coronary arteries like left anterior descending, left circumflex, right coronary artery and ARAS was found. Only hypertension and altered serum creatinine were associated with bilateral ARAS. Extent of CAD or risk factors like diabetes, hyperlipidemia or smoking did not predict the unilateral or bilateral ARAS. Prevalence of ARAS among the patients in routine cardiac catheterization was 5.7 %. Hypertension is closely associated with significant ARAS. Significant CAD in the form of triple-vessel disease and altered renal function tests are closely associated with ARAS. They predict the presence of significant renal artery stenosis in patients undergoing routine peripheral and coronary angiography. Moreover, hypertension and altered renal functions predict bilateral ARAS.

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

Increased renal sympathetic nerve activity leads to hypertension and renal dysfunction in offspring from diabetic mothers.

PubMed

de Almeida Chaves Rodrigues, Aline Fernanda; de Lima, Ingrid Lauren Brites; Bergamaschi, Cássia Toledo; Campos, Ruy Ribeiro; Hirata, Aparecida Emiko; Schoorlemmer, Guus Hermanus Maria; Gomes, Guiomar Nascimento

2013-01-15

The exposure of the fetus to a hyperglycemic environment promotes the development of hypertension and renal dysfunction in the offspring at adult age. We evaluated the role of renal nerves in the hypertension and renal changes seen in offspring of diabetic rats. Diabetes was induced in female Wistar rats (streptozotocin, 60 mg/kg ip) before mating. Male offspring from control and diabetic dams were studied at an age of 3 mo. Systolic blood pressure measured by tail cuff was increased in offspring of diabetic dams (146 ± 1.6 mmHg, n = 19, compared with 117 ± 1.4 mmHg, n = 18, in controls). Renal function, baseline renal sympathetic nerve activity (rSNA), and arterial baroreceptor control of rSNA were analyzed in anesthetized animals. Glomerular filtration rate, fractional sodium excretion, and urine flow were significantly reduced in offspring of diabetic dams. Two weeks after renal denervation, blood pressure and renal function in offspring from diabetic dams were similar to control, suggesting that renal nerves contribute to sodium retention in offspring from diabetic dams. Moreover, basal rSNA was increased in offspring from diabetic dams, and baroreceptor control of rSNA was impaired, with blunted responses to infusion of nitroprusside and phenylephrine. Thus, data from this study indicate that in offspring from diabetic mothers, renal nerves have a clear role in the etiology of hypertension; however, other factors may also contribute to this condition.

Acute kidney injury: not just acute renal failure anymore?

PubMed

Dirkes, Susan

2011-02-01

Until recently, no uniform standard existed for diagnosing and classifying acute renal failure. To clarify diagnosis, the Acute Dialysis Quality Initiative group stated its consensus on the need for a clear definition and classification system of renal dysfunction with measurable criteria. Today the term acute kidney injury has replaced the term acute renal failure, with an understanding that such injury is a common clinical problem in critically ill patients and typically is predictive of an increase in morbidity and mortality. A classification system, known as RIFLE (risk of injury, injury, failure, loss of function, and end-stage renal failure), includes specific goals for preventing acute kidney injury: adequate hydration, maintenance of renal perfusion, limiting exposure to nephrotoxins, drug protective strategies, and the use of renal replacement therapies that reduce renal injury.

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.

How to manage hypertension with atherosclerotic renal artery stenosis?

PubMed

Ricco, Jean-Baptiste; Belmonte, Romain; Illuminati, Guilio; Barral, Xavier; Schneider, Fabrice; Chavent, Bertrand

2017-04-01

The management of atherosclerotic renal artery stenosis (ARAS) in patients with hypertension has been the topic of great controversy. Major contemporary clinical trials such as the Cardiovascular Outcomes for Renal Artery lesions (CORAL) and Angioplasty and Stenting for Renal Atherosclerotic lesions (ASTRAL) have failed to show significant benefit of revascularization over medical management in controlling blood pressure and preserving renal function. We present here the implications and limitations of these trials and formulate recommendations for management of ARAS.

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.

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.

Nephron sparing by partial median nephrectomy for treatment of renal hemangioma in a dog.

PubMed

Mott, J C; McAnulty, J F; Darien, D L; Steinberg, H

1996-04-15

A 6-year-old neutered male Golden Retriever was admitted for evaluation of intermittent hematuria of 2 months' duration. A 3-cm heterogeneous mass causing distortion of the caudomedial aspect of the left kidney was detected via ultrasonography. Histologic examination of a renal tissue sample obtained by ultrasound-guided biopsy revealed a telangiectatic vascular plexus of unknown origin. Low glomerular filtration rate was identified by a modified exogenous creatinine clearance test. Excretory urography revealed a filling defect in the medial aspect of the caudal pole of the kidney, near the hilus. Because total renal function was low, a decision was made to perform nephron-sparing surgery involving resection of centrally located renal parenchymal and pelvic tissue by en bloc resection in the median plane, instead of radical nephrectomy. After surgery, the hematuria resolved and further decrease in renal function was not evident. Nephron-sparing surgery is a viable option for dogs with compromised renal function when there is concern that radical nephrectomy may precipitate uremia.

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.

Neural regulation of renal tubular sodium reabsorption and renin secretion: integrative aspects.

PubMed

DiBona, G F

1987-01-01

Efferent renal sympathetic nerve activity plays an important role in the regulation of renal function. Via its direct influence on renal tubular sodium reabsorption throughout the entire mammalian nephron, alterations in efferent renal sympathetic nerve activity represent an important physiological contribution to the overall role of the kidney in the regulation of external sodium balance and the defense against sodium deficit and surfeit. Abnormalities of this mechanism can lead to inappropriate renal sodium retention and augmentation of renin secretion, two factors which are capable of contributing to the development and maintenance of hypertension.

Dissecting the roles of aquaporins in renal pathophysiology using transgenic mice

PubMed Central

Verkman, A. S.

2008-01-01

Transgenic mice lacking renal aquaporins (AQPs), or containing mutated AQPs, have been useful in confirming anticipated AQP functions in renal physiology and in discovering new functions. Mice lacking AQPs 1–4 manifest defects in urinary concentrating ability to different extents. Mechanistic studies have confirmed the involvement of AQP1 in near-isosmolar fluid absorption in proximal tubule, and in countercurrent multiplication and exchange mechanisms that produce medullary hypertonicity in the antidiuretic kidney. Deletion of AQPs 2–4 impairs urinary concentrating ability by reduction of transcellular water permeability in collecting duct. Recently created transgenic mouse models of nephrogenic diabetes insipidus produced by AQP2 gene mutation offer exciting possibilities to test new drug therapies. Several unanticipated AQP functions in kidney have been discovered recently that are unrelated to their role in transcellular water transport. There is evidence for involvement of AQP1 in kidney cell migration following renal injury, of AQP7 in renal glycerol clearance, of AQP11 in prevention of renal cystic disease, and possibly of AQP3 in regulation of collecting duct cell proliferation. Future work in renal AQPs will focus on mechanisms responsible for these non-fluid-transporting functions, and on the development of small-molecule AQP inhibitors for use as aquaretic-type diuretics. PMID:18519083

Bioengineering in renal transplantation: technological advances and novel options.

PubMed

Yeo, Wee-Song; Zhang, Yao-Chun

2017-06-06

End-stage kidney disease (ESKD) is one of the most prevalent diseases in the world with significant morbidity and mortality. Current modes of renal replacement therapy include dialysis and renal transplantation. Although dialysis is an acceptable mode of renal replacement therapy, it does have its shortcomings, which include poorer life expectancy compared with renal transplantation, risk of infections and vascular thrombosis, lack of vascular access and absence of biosynthetic functions of the kidney. Renal transplantation, in contrast, is the preferred option of renal replacement therapy, with improved morbidity and mortality rates and quality of life, compared with dialysis. Renal transplantation, however, may not be available to all patients with ESKD. Some of the key factors limiting the availability and efficiency of renal transplantation include shortage of donor organs and the constant risk of rejection with complications associated with over-immunosuppression respectively. This review focuses chiefly on the potential roles of bioengineering in overcoming limitations in renal transplantation via the development of cell-based bioartificial dialysis devices as bridging options before renal transplantation, and the development of new sources of organs utilizing cell and organ engineering.

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.

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 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.

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.

High anion gap metabolic acidosis induced by cumulation of ketones, L- and D-lactate, 5-oxoproline and acute renal failure.

PubMed

Heireman, Laura; Mahieu, Boris; Helbert, Mark; Uyttenbroeck, Wim; Stroobants, Jan; Piqueur, Marian

2017-07-27

Frequent causes of high anion gap metabolic acidosis (HAGMA) are lactic acidosis, ketoacidosis and impaired renal function. In this case report, a HAGMA caused by ketones, L- and D-lactate, acute renal failure as well as 5-oxoproline is discussed. A 69-year-old woman was admitted to the emergency department with lowered consciousness, hyperventilation, diarrhoea and vomiting. The patient had suffered uncontrolled type 2 diabetes mellitus, underwent gastric bypass surgery in the past and was chronically treated with high doses of paracetamol and fosfomycin. Urosepsis was diagnosed, whilst laboratory analysis of serum bicarbonate concentration and calculation of the anion gap indicated a  HAGMA. L-lactate, D-lactate, β-hydroxybutyric acid, acetone and 5-oxoproline serum levels were markedly elevated and renal function was impaired. We concluded that this case of HAGMA was induced by a variety of underlying conditions: sepsis, hyperglycaemia, prior gastric bypass surgery, decreased renal perfusion and paracetamol intake. Risk factors for 5-oxoproline intoxication present in this case are female gender, sepsis, impaired renal function and uncontrolled type 2 diabetes mellitus. Furthermore, chronic antibiotic treatment with fosfomycin might have played a role in the increased production of 5-oxoproline. Paracetamol-induced 5-oxoproline intoxication should be considered as a cause of HAGMA in patients with female gender, sepsis, impaired renal function or uncontrolled type 2 diabetes mellitus, even when other more obvious causes of HAGMA such as lactate, ketones or renal failure can be identified.

Significant impact of R.E.N.A.L. nephrometry score on changes in postoperative renal function early after robot-assisted partial nephrectomy.

PubMed

Miyake, Hideaki; Furukawa, Junya; Hinata, Nobuyuki; Muramaki, Mototsugu; Tanaka, Kazushi; Fujisawa, Masato

2015-06-01

Our objective was to evaluate the significance of the R.E.N.A.L. nephrometry score (RNS)--developed to quantitatively evaluate the complexity of renal tumors in a reproducible manner--in perioperative and renal functional outcomes following robot-assisted partial nephrectomy (RAPN). This study assessed 48 consecutive patients with renal tumors who underwent RAPN. Preoperative RNS for each patient was calculated, and its impact on several parameters associated with perioperative outcomes, including postoperative renal function, was investigated with Spearman's rank correlation test. Mean RNS in the 48 patients was 6.8; of these 48 patients, 21 (43.7%), 24 (50.0%), and three (6.3%) were classified into low-, moderate-, and high-complexity groups, respectively. The RNS was significantly correlated with resected tumor weight and postoperative changes in estimated glomerular filtration rate (eGFR) at both 1 and 4 weeks--but not age, body mass index (BMI), preoperative eGFR, operative time, warm ischemia time, estimated blood loss, postoperative complications, or eGFR-- after RAPN. No component of the RNS (R: radius; E: exophytic/endophytic properties; N: nearness of tumor to the collecting system or sinus; A: anterior/posterior; L: location relative to polar lines) alone had a significant impact on postoperative changes in eGFR at 1 and 4 weeks, whereas resected tumor weight was significantly associated with the R and E subcategories. Measurement of total RNS is useful for predicting renal functional outcomes early after RAPN.

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.

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

PubMed

Cao, Xia; Wu, Liuxin; Chen, Zhiheng

2018-03-01

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

Comparison of computer tomographic volumetry versus nuclear split renal function to determine residual renal function after living kidney donation.

PubMed

Patankar, Khalil; Low, Ronny Su-Tong; Blakeway, Darryn; Ferrari, Paolo

2014-07-01

Living-donor kidney transplantation is an established practice. Traditionally a combination of renal scintigram and computed tomography (CT) is used to select the kidney that is to be harvested in each donor. To evaluate the ability of split renal volume (SRV) calculated from volumetric examination of CT images compared to nuclear split renal function (nSRF) derived from gamma camera scintigram to predict donor residual single kidney function after donor nephrectomy. This pilot study comprised a retrospective analysis of CT images and renal scintigrams from 12 subsequent live kidney donors who had at least 12 months post-donation renal function follow-up. nSRF derived from the renal scintigram, expressed as the right kidney's function in percent of the total, was 50.2 ± 3.3 (range, 44.1-54.0%) and SRV estimated following analysis of CT imaging was 49.0 ± 2.9 (range, 46.4-52.3%). Although the correlation between nSRF and SRV was moderate (R = 0.46), there was 92% agreement on the dominant kidney if a difference of <2% in nSRF versus SRV was considered. Post-donation glomerular filtration rate (GFR) by CKD-EPI formula was 92 ± 10 mL/min/1.73m2 at 1 year and the correlation between estimated GFR (eGFR) at 1 year and extrapolated single kidney eGFR adjusted by nSRF (R(2 )= 0.69, P = 0.0007) or SRV (R(2 )= 0.74, P = 0.0003) was similar. Calculation of SRV from pre-donation CT examination is a valid method to estimate nSRF with good concordance with nSRF determined by renal scintigram and could replace the latter in the assessment of potential kidney donors. © The Foundation Acta Radiologica 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Influence of renal function on the association between homocysteine level and risk of ischemic stroke.

PubMed

Cheng, Yao; Kong, Fan-Zhen; Dong, Xiao-Feng; Xu, Qin-Rong; Gui, Qian; Wang, Wei; Feng, Hong-Xuan; Luo, Wei-Feng; Gao, Zong-En; Wu, Guan-Hui

2017-01-01

We examined whether the association between total homocysteine (tHCY) and risk of ischemic stroke (IS) varies depending on renal function to gain insight into why tHCY-lowering vitamins do not reduce the incidence of cardiovascular disease in clinical trials. We analyzed data from 542 IS patients with large artery atherosclerosis (LAA) or small artery occlusion (SAO) after stratification by estimated glomerular filtration rate (eGFR) to evaluate renal function. We found that tHCY level was positively associated with the occurrence of IS in both LAA (OR: 1.159, 95% CI: 1.074-1.252, P <0.001) and SAO (OR: 1.143, 95% CI: 1.064-1.228, P <0.001) patients and in LAA (OR: 1.135, 95% CI: 1.047-1.230, P =0.002) and SAO (OR: 1.159, 95% CI: 1.060-1.268, P =0.001) subgroups with normal renal function but not in LAA or SAO subgroups with renal insufficiency. eGFR level was positively associated with IS in LAA (OR: 1.022, 95% CI: 1.010-1.034, P <0.001) and SAO (OR: 1.024, 1.012-1.037, P <0.001) subgroups with normal renal function but was negatively associated with IS in LAA (OR: 0.875, 95% CI: 0.829-0.925, P <0.001) and SAO (OR: 0.890, 95% CI: 0.850-0.932, P <0.001) subgroups with renal insufficiency. Folic acid level was negatively associated with IS in LAA (OR: 0.734, 95% CI: 0.606-0.889, P =0.002) and SAO (OR: 0.861, 95% CI: 0.767-0.967, P =0.012) subgroups with renal insufficiency. Therefore, renal function as evaluated by eGFR exerts a significant influence on the association between tHCY and risk of IS.

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

Early diagnosis of diabetic vascular complications: impairment of red blood cell deformability

NASA Astrophysics Data System (ADS)

Shin, Sehyun; Ku, Yunhee; Park, Cheol-Woo; Suh, Jang-Soo

2006-02-01

Reduced deformability of red blood cells (RBCs) may play an important role on the pathogenesis of chronic vascular complications of diabetes mellitus. However, available techniques for measuring RBC deformability often require washing process after each measurement, which is not optimal for day-to-day clinical use at point of care. The objectives of the present study are to develop a device and to delineate the correlation of impaired RBC deformability with diabetic nephropathy. We developed a disposable ektacytometry to measure RBC deformability, which adopted a laser diffraction technique and slit rheometry. The essential features of this design are its simplicity (ease of operation and no moving parts) and a disposable element which is in contact with the blood sample. We studied adult diabetic patients divided into three groups according to diabetic complications. Group I comprised 57 diabetic patients with normal renal function. Group II comprised 26 diabetic patients with chronic renal failure (CRF). Group III consisted of 30 diabetic subjects with end-stage renal disease (ESRD) on hemodialysis. According to the renal function for the diabetic groups, matched non-diabetic groups were served as control. We found substantially impaired red blood cell deformability in those with normal renal function (group I) compared to non-diabetic control (P = 0.0005). As renal function decreases, an increased impairment in RBC deformability was found. Diabetic patients with chronic renal failure (group II) when compared to non-diabetic controls (CRF) had an apparently greater impairment in RBC deformability (P = 0.07). The non-diabetic cohort (CRF), on the other hand, manifested significant impairment in red blood cell deformability compared to healthy control (P = 0.0001). The newly developed slit ektacytometer can measure the RBC deformability with ease and accuracy. In addition, progressive impairment in cell deformability is associated with renal function loss in all patients regardless of the presence or absence of diabetes. In diabetic patients, early impairment in RBC deformability appears in patients with normal renal function.

The arginine-creatine pathway is disturbed in children and adolescents with renal transplants.

PubMed

Andrade, Fernando; Rodríguez-Soriano, Juan; Prieto, José Angel; Elorz, Javier; Aguirre, Mireia; Ariceta, Gema; Martin, Sergio; Sanjurjo, Pablo; Aldámiz-Echevarría, Luis

2008-08-01

Cardiovascular disease is an important cause of morbidity in recipients of renal transplants. The aim of the present study was to analyze the status of the arginine-creatine pathway in such patients, given the relationship between the arginine metabolism and both renal function and the methionine-homocysteine cycle. Twenty-nine children and adolescents (median age 13, range 6-18 years), who had received a renal allograft 14.5-82.0 months before, were recruited for the study. On immunosuppressive therapy, all patients evidenced an adequate level of renal function. Plasma concentrations of homocysteine and glycine were significantly higher, whereas urinary excretions of guanidinoacetate and creatine were significantly lower than controls. Urinary excretions of guanidinoacetate and creatine correlated positively with creatinine clearance. Urinary excretion of creatine was negatively correlated with plasma concentration of homocysteine. The demonstration of disturbances in the arginine-creatine pathway in patients with well-functioning renal transplants and in absence of chronic renal failure represents a novel finding. We speculate that the low urinary excretion of guanidinoacetate and creatine is probably related to the nephrotoxic effect of immunosuppressive therapy and to defective methylation associated with the presence of hyperhomocysteinemia.

Study on the effect of black cumin (Nigella sativa Linn.) on experimental renal ischemia-reperfusion injury in rats.

PubMed

Mousavi, Ghafour

2015-08-01

To evaluate the effect of Black cumin (Nigella sativa Linn.) pre-treatment on renal ischemia/reperfusion (I/R) induced injury in the rats. A total of 40 male Wistar rats were randomly allocated into five equal groups including Sham, I/R model and three I/R+ Black cumin (0.5, 1 and 2%)-treated groups. I/R groups' kidneys were subjected to 60 min of global ischemia at 37°C followed by 24 h of reperfusion. At the end of reperfusion period, the rats were euthanized. Superoxide dismutase, catalase and glutathione peroxidase activities as well as reduced glutathione and renal malondialdehyde contents were determined in renal tissues. Kidney function tests and histopathological examination were also performed. High serum creatinine, blood urea nitrogen and uric acid as well as malondialhehyde (MDA) levels, and low antioxidant enzyme activities were observed in I/R rats compared to the sham rats. Pre-treatment with Black cumin for three weeks prior to IR operation improved renal function and reduced I/R induced renal inflammation and oxidative injury. These biochemical observations were supported by histopathological test of kidney sections. Black cumin significantly prevented renal ischemia/reperfusion induced functional and histological injuries.

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 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

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.

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.

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

IGF-1, IGFBP-3 and ALS in adult patients with chronic kidney disease.

PubMed

Lepenies, Julia; Wu, Zida; Stewart, Paul M; Strasburger, Christian J; Quinkler, Marcus

2010-04-01

Insulin-like growth factor I (IGF-1) is for the most part bound in a ternary complex with IGF-binding protein-3 (IGFBP-3) and acid-labile subunit (ALS). This ternary complex is a storage form of IGF-1 in blood and passes not through the renal glomerulus. Little information is available in regard to the components of the ternary complex in adult renal disease. To investigate levels of serum IGF-1, IGFBP-3 and ALS in relation to renal function and extent of proteinuria. We measured IGF-1, IGFBP-3 and ALS concentrations in 137 patients who were investigated due to proteinuria and/or haematuria and/or renal impairment. The patients received renal biopsies and the histological diagnosis was documented. Urinary albumin excretion and relevant clinical parameter were evaluated. IGF-1 showed a highly positive correlation to IGFBP-3 and ALS, and the latter to IGFBP-3. IGF-1, IGFBP-3 and ALS decreased with increasing age. IGF-1 and IGFBP-3 showed no significant change depending on the creatinine clearance. However, ALS decreased with decreasing renal function. In patients with heavy proteinuria ALS levels, but not IGF-1 and IGFBP-3 levels, decreased significantly. Patients with chronic ischaemic renal damage and diabetic glomerulopathy showed higher IGF-1 and IGFBP-3 levels compared to patients with thin glomerular basement membrane disease despite their older age. IGF-1 and IGFBP-3 levels seem to be independent of renal function and severity of proteinuria. However, ALS levels are altered in renal failure and nephrotic syndrome, which may be due to increased renal loss or diminished hepatic production or both. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

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.

Renal cortical involvement in children with first UTI: does it differ in the presence of primary VUR?

PubMed

Aktaş, Gül Ege; Inanir, Sabahat; Turoğlu, Halil Turgut

2008-12-01

The aim of this study was to investigate the influence of vesicoureteral reflux (VUR) on dimercaptosuccinic acid (DMSA) scintigraphic patterns in children with first symptomatic urinary tract infection (UTI). A total of 45 children with the diagnosis of first symptomatic UTI (28 girls, 17 boys, mean age 18 months, range 1 month-11 years) were reviewed. All DMSA scans were obtained within 2 months of bacteriologically proven UTI (median 21 days, mean 26 +/- 21, 14). After the exclusion of the patients with bilateral cortical lesions, 82 renal units were analyzed. The scintigraphic patterns included regional and global description of renal cortical abnormality (normal or decreased differential renal function, regional renal function (RRF), and the number and severity of cortical lesions). Vesicoureteral reflux was detected in 26 (32%) renal units (15 with grade 1-2, 11 with grade 3-4). Renal cortical abnormality was observed in 10 renal units without VUR (10/56, 17%) and 13 renal units with VUR (13/26: 50%). Of the 15 renal units, 5 with grade 1-2 VUR (5/15) and 8 of the 11 renal units with grade 3-4 VUR (8/11) had renal cortical involvement. The most common scintigraphic pattern in the patients without VUR was the preserved RRF (>or=45%) and two or fewer photon-deficient areas. On the other hand, a decreased RRF (<45) associated with cortical lesions was the most frequent finding in patients with refluxing kidneys (8/26, 30%), especially in those with grade 3-4 disease. This investigation showed that the presence of VUR affects DMSA patterns in children with first symptomatic UTI.

Pregnancy in women with renal disease. Yes or no?

PubMed Central

Edipidis, K

2011-01-01

Women with renal disease who conceive and continue pregnancy, are at significant risk for adverse maternal and fetal outcomes. Although advances in antenatal and neonatal care continue to improve these outcomes, the risks remain proportionate to the degree of underlying renal dysfunction. The aim of this article, is to examine the impact of varying degrees of renal insufficiency on pregnancy outcome, in women with chronic renal disease and to provide if possible, useful conclusions whether and when, a woman with Chronic Kidney Disease (CKD), should decide to get pregnant. This article, reviews briefly the normal physiological changes of renal function during pregnancy, and make an attempt to clarify the nature and severity of the risks, in the settings of chronic renal insufficiency and end stage renal disease, including dialysis patients and transplant recipients. PMID:21897751

Losartan corrects abnormal frequency response of renal vasculature in congestive heart failure.

PubMed

DiBona, Gerald F; Sawin, Linda L

2003-11-01

In congestive heart failure, renal blood flow is decreased and renal vascular resistance is increased in a setting of increased activity of both the sympathetic nervous and renin-angiotensin systems. The renal vasoconstrictor response to renal nerve stimulation is enhanced. This is associated with an abnormality in the low-pass filter function of the renal vasculature wherein higher frequencies (> or =0.01 Hz) within renal sympathetic nerve activity are not normally attenuated and are passed into the renal blood flow signal. This study tested the hypothesis that excess angiotensin II action mediates the abnormal frequency response characteristics of the renal vasculature in congestive heart failure. In anesthetized rats, the renal vasoconstrictor response to graded frequency renal nerve stimulation was significantly greater in congestive heart failure than in control rats. Losartan attenuated the renal vasoconstrictor response to a significantly greater degree in congestive heart failure than in control rats. In control rats, the frequency response of the renal vasculature was that of a first order (-20 dB/frequency decade) low-pass filter with a corner frequency (-3 dB, 30% attenuation) of 0.002 Hz and 97% attenuation (-30 dB) at > or =0.1 Hz. In congestive heart failure rats, attenuation did not exceed 45% (-5 dB) over the frequency range of 0.001-0.6 Hz. The frequency response of the renal vasculature was not affected by losartan treatment in control rats but was completely restored to normal by losartan treatment in congestive heart failure rats. The enhanced renal vasoconstrictor response to renal nerve stimulation and the associated abnormality in the frequency response characteristics of the renal vasculature seen in congestive heart failure are mediated by the action of angiotensin II on renal angiotensin II AT1 receptors.

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

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.

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

Myoglobinuric acute renal failure in phencyclidine overdose: report of observations in eight cases.

PubMed

Patel, R; Das, M; Palazzolo, M; Ansari, A; Balasubramaniam, S

1980-11-01

Eight cases of myoglobinuric acute renal failure that developed following exposure to phencyclidine were seen in the emergency department of the Martin Luther King Jr. General Hospital during a period of 36 months. All eight survived with complete recovery of renal function. Dialysis was necessary in three patients. Acute renal failure is an uncommon complication of phencyclidine abuse.

Renal embolic protection devices improve blood flow after stenting for atherosclerotic renal artery stenosis.

PubMed

Paul, Timir K; Lee, John H; White, Christopher J

2012-11-15

We sought to measure angiographic renal frame counts (RFC), as a quantitative angiographic assessment of renal blood flow, to evaluate microvascular compromise due to atheroembolism associated with RAS. Atheroembolism associated with renal artery stenting (RAS) has been implicated as a cause for worsening renal function following successful intervention. Use of a distal embolic protection device (EPD) during RAS has been shown to be safe with debris capture in a high percentage of cases. However, objective benefit for renal function with EPD has been difficult to demonstrate. A control group of 30 consecutive patients (33 kidneys) who underwent RAS without EPD were compared with 33 consecutive patients (33 kidneys) who underwent RAS with EPD using RFC measurement. The prestent and poststent mean RFC for the control group was 30.4 ± 12.1 vs. 23.7 ± 9.9 (P = 0.002) and for the EPD group it was 42.6 ± 12.6 vs. 28.3 ± 9.2 (P < 0.0001). The EPD group had a greater improvement in renal blood flow, manifested by a greater reduction of the RFC (Δ RFC) 14.2 ± 15.2 vs. 6.7 ± 11.7 (P = 0.03) compared with the control group. The use of an EPD was associated with a much larger improvement in renal blood flow (lower RFC) following RAS. This suggests that EPD's may be effective in preventing renal atheroembolic injury and that a controlled trial measuring the impact of EPD's on renal blood flow following RAS should be performed. Copyright © 2012 Wiley Periodicals, Inc.

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.

[Executive summary of the recommendations on the evaluation and management of renal disease in human immunodeficiency virus-infected patients].

PubMed

Gorriz, José L; Gutiérrez, Félix; Trullàs, Joan C; Arazo, Piedad; Arribas, Jose R; Barril, Guillermina; Cervero, Miguel; Cofán, Frederic; Domingo, Pere; Estrada, Vicente; Fulladosa, Xavier; Galindo, María J; Gràcia, Sílvia; Iribarren, José A; Knobel, Hernando; López-Aldeguer, José; Lozano, Fernando; Martínez-Castelao, Alberto; Martínez, Esteban; Mazuecos, Maria A; Miralles, Celia; Montañés, Rosario; Negredo, Eugenia; Palacios, Rosario; Pérez-Elías, María J; Portilla, Joaquín; Praga, Manuel; Quereda, Carlos; Rivero, Antonio; Santamaría, Juan M; Sanz, José; Sanz, Jesús; Miró, José M

2014-11-01

The aim of this article is to update the 2010 recommendations on the evaluation and management of renal disease in human immunodeficiency virus (HIV)-infected patients. Renal function should be monitored in all HIV-infected patients. The basic renal work-up should include measurements of serum creatinine, estimated glomerular filtration rate by CKD-EPI, urine protein-to-creatinine ratio, and urinary sediment. Tubular function tests should include determination of serum phosphate levels and urine dipstick for glycosuria. In the absence of abnormal values, renal screening should be performed annually. In patients treated with tenofovir, or with risk factors for chronic kidney disease (CKD), more frequent renal screening is recommended. In order to prevent disease progression, potentially nephrotoxic antiretroviral drugs are not recommended in patients with CKD or risk factors for CKD. The document provides indications for renal biopsy and advises on the optimal time for referral of a patient to the nephrologist. The indications for and evaluation and management of dialysis and renal transplantation are also addressed. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Family clustering of secondary chronic kidney disease with hypertension or diabetes mellitus. A case-control study.

PubMed

de Almeida, Fernando Antonio; Ciambelli, Giuliano Serafino; Bertoco, André Luz; Jurado, Marcelo Mai; Siqueira, Guilherme Vasconcelos; Bernardo, Eder Augusto; Pavan, Maria Valeria; Gianini, Reinaldo José

2015-02-01

In Brazil hypertension and type 2 diabetes mellitus are responsible for 60% of cases of end-stage renal disease in renal replacement therapy. In the United States studies have identified family clustering of chronic kidney disease, predominantly in African-Americans. A single Brazilian study observed family clustering among patients with chronic kidney disease when compared with hospitalized patients with normal renal function. This article aims to assess whether there is family clustering of chronic kidney disease in relatives of individuals in renal replacement therapy caused by hypertension and/or diabetes mellitus. A case-control study with 336 patients in renal replacement therapy with diabetes mellitus or hypertension for at least 5 years (cases) and a control matched sample group of individuals with hypertension or diabetes mellitus and normal renal function (n = 389). Individuals in renal replacement therapy (cases) had a ratio of 2.35 (95% CI 1.42-3.89, p < 0.001) versus the control group in having relatives with chronic renal disease, irrespective of race or causative illness. There is family clustering of chronic kidney disease in the sample studied, and this predisposition is irrespective of race and underlying disease (hypertension or diabetes mellitus).

Does renal ageing affect survival?

PubMed

Razzaque, M Shawkat

2007-10-01

The effects of ageing on progressive deterioration of renal function, both in human and experimental animals, are described elsewhere, but the effect of renal damage on overall survival and longevity is not yet clearly established. The wild-type animals of various genetic backgrounds, fed with regular diet, overtime develop severe age-associated nephropathy, that include but not limited to inflammatory cell infiltration, glomerulosclerosis, and tubulointerstitial fibrosis. Such renal damage significantly reduces their survival. Reducing renal damage, either by caloric restriction or by suppressing growth hormone (GH)/insulin-like growth factor-1 (IGF-1) activity could significantly enhance the longevity of these animals. Available survival studies using experimental animals clearly suggest that kidney pathology is one of the important non-neoplastic lesions that could affect overall survival, and that restoration of renal function by preventing kidney damage could significantly extend longevity. Careful long-term studies are needed to determine the human relevance of these experimental studies.

[Quality assurance of the renal applications software].

PubMed

del Real Núñez, R; Contreras Puertas, P I; Moreno Ortega, E; Mena Bares, L M; Maza Muret, F R; Latre Romero, J M

2007-01-01

The need for quality assurance of all technical aspects of nuclear medicine studies is widely recognised. However, little attention has been paid to the quality assurance of the applications software. Our work reported here aims at verifying the analysis software for processing of renal nuclear medicine studies (renograms). The software tools were used to build a synthetic dynamic model of renal system. The model consists of two phases: perfusion and function. The organs of interest (kidneys, bladder and aortic artery) were simple geometric forms. The uptake of the renal structures was described by mathematic functions. Curves corresponding to normal or pathological conditions were simulated for kidneys, bladder and aortic artery by appropriate selection of parameters. There was no difference between the parameters of the mathematic curves and the quantitative data produced by the renal analysis program. Our test procedure is simple to apply, reliable, reproducible and rapid to verify the renal applications software.

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.

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.

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.

Changes of renal sinus fat and renal parenchymal fat during an 18-month randomized weight loss trial.

PubMed

Zelicha, Hila; Schwarzfuchs, Dan; Shelef, Ilan; Gepner, Yftach; Tsaban, Gal; Tene, Lilac; Yaskolka Meir, Anat; Bilitzky, Avital; Komy, Oded; Cohen, Noa; Bril, Nitzan; Rein, Michal; Serfaty, Dana; Kenigsbuch, Shira; Chassidim, Yoash; Sarusi, Benjamin; Thiery, Joachim; Ceglarek, Uta; Stumvoll, Michael; Blüher, Matthias; Haviv, Yosef S; Stampfer, Meir J; Rudich, Assaf; Shai, Iris

2018-08-01

Data regarding the role of kidney adiposity, its clinical implications, and its dynamics during weight-loss are sparse. We investigated the effect of long-term weight-loss induced intervention diets on dynamics of renal-sinus-fat, an ectopic fat depot, and %renal-parenchymal-fat, lipid accumulation within the renal parenchyma. We randomized 278 participants with abdominal obesity/dyslipidemia to low-fat or Mediterranean/low-carbohydrate diets, with or without exercise. We quantified renal-sinus-fat and %renal-parenchymal-fat by whole body magnetic-resonance-imaging. Participants (age = 48 years; 89% men; body-mass-index = 31 kg/m 2 ) had 86% retention to the trial after 18 months. Both increased renal-sinus-fat and %renal-parenchymal-fat were directly associated with hypertension, and with higher abdominal deep-subcutaneous-adipose-tissue and visceral-adipose-tissue (p of trend < 0.05 for all) after adjustment for body weight. Higher renal-sinus-fat was associated with lower estimated-glomerular-filtration-rate and with higher microalbuminuria and %HbA1C beyond body weight. After 18 months of intervention, overall renal-sinus-fat (-9%; p < 0.05 vs. baseline) but not %renal-parenchymal-fat (-1.7%; p = 0.13 vs. baseline) significantly decreased, and similarly across the intervention groups. Renal-sinus-fat and %renal-parenchymal-fat changes were correlated with weight-loss per-se (p < 0.05). In a model adjusted for age, sex, and visceral-adipose-tissue changes, 18 months reduction in renal-sinus-fat associated with decreased pancreatic, hepatic and cardiac fats (p < 0.05 for all) and with decreased cholesterol/high-density lipoprotein-cholesterol (HDL-c) (β = 0.13; p = 0.05), triglycerides/HDL-c (β = 0.13; p = 0.05), insulin (β = 0.12; p = 0.05) and gamma glutamyl transpeptidase (β = 0.24; p = 0.001), but not with improved renal function parameters or blood pressure. Decreased intake of sodium was associated with a reduction in %renal-parenchymal-fat, after adjustment for 18 months weight-loss (β = 0.15; p = 0.026) and hypertension (β = 0.14; p = 0.04). Renal-sinus-fat and renal-parenchymal-fat are fairly related to weight-loss. Decreased renal-sinus-fat is associated with improved hepatic parameters, independent of changes in weight or hepatic fat, rather than with improved renal function or blood pressure parameters. CLINICALTRIALS. NCT01530724. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Enteral nutrition in patients with acute renal failure.

PubMed

Fiaccadori, Enrico; Maggiore, Umberto; Giacosa, Roberto; Rotelli, Carlo; Picetti, Edoardo; Sagripanti, Sibilla; Melfa, Luigi; Meschi, Tiziana; Borghi, Loris; Cabassi, Aderville

2004-03-01

Systematic studies on safety and efficacy of enteral nutrition in patients with acute renal failure (ARF) are lacking. We studied enteral nutrition-related complications and adequacy of nutrient administration during 2525 days of artificial nutrition in 247 consecutive patients fed exclusively by the enteral route: 65 had normal renal function, 68 had ARF not requiring renal replacement therapy, and 114 required renal replacement therapy. No difference was found in gastrointestinal or mechanical complications between ARF patients and patients with normal renal function, except for high gastric residual volumes, which occurred in 3.1% of patients with normal renal function, 7.3% of patients with ARF not requiring renal replacement therapy, 13.2% of patients with ARF on renal replacement therapy (P= 0.02 for trend), and for nasogastric tube obstruction: 0.0%, 5.9%, 14%, respectively (P < 0.001). Gastrointestinal complications were the most frequent cause of suboptimal delivery; the ratio of administered to prescribed daily volume was well above 90% in all the three groups. Definitive withdrawal of enteral nutrition due to complications was documented in 6.1%, 13.2%. and 14.9% of patients, respectively (P= 0.09 for trend). At regimen, mean delivered nonprotein calories were 19.8 kcal/kg (SD 4.6), 22.6 kcal/kg (8.4), 23.4 kcal/kg (6.5); protein intake was 0.92 g/kg (0.21), 0.87 g/kg (0.25), and 0.92 g/kg (0.21), the latter value being below that currently recommended for ARF patients on renal replacement therapy. Median fluid intake with enteral nutrition was 1440 mL (range 720 to 1960), 1200 (720 to 2400), and 960 (360 to 1920). Enteral nutrition is a safe and effective nutritional technique to deliver artificial nutrition in ARF patients. Parenteral amino acid supplementation may be required, especially in patients with ARF needing renal replacement therapy.

Progressive kidney failure as the sole manifestation of extrapulmonary sarcoidosis.

PubMed

Sethi, Supreet; Relia, Nitin; Syal, Gaurav; Kaushik, Chhavi; Gokden, Neriman; Malik, Ahmad B

2013-09-01

Sarcoidosis is a chronic multisystem disorder characterized by an accumulation of T lymphocytes and mononuclear phagocytes, non-caseating epitheliod granulomas and derangement of normal tissue architecture in affected organs. Sarcoidosis can affect any organ system, however approximately 90% of patients with sarcoidosis have pulmonary, lymph node, cutaneous or ocular manifestations. Renal involvement in sarcoidosis is rare and clinically significant renal dysfunction even less common. We present a case of isolated renal sarcoidosis which manifested with progressively worsening renal function and hypercalcemia. A systematic diagnostic approach with pertinent laboratory studies, imaging and renal biopsy elucidated the diagnosis of renal sarcoidosis without any evidence of systemic involvement.

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

Ramadan fasting and patients with renal diseases: A mini review of the literature.

PubMed

Emami-Naini, Afsoon; Roomizadeh, Peyman; Baradaran, Azar; Abedini, Amin; Abtahi, Mohammad

2013-08-01

Fasting during the month of Ramadan is one of the five pillars of Islam. During this month, adult Muslims are obligated to refrain from eating and drinking from dawn to dusk. Although based on Islamic principles patients are exempted from fasting, each year, many Muslim patients express their willingness to observe the fast in Ramadan month to respect the cultural customs. There are concerns about the impact of fluid restriction and dehydration during Ramadan fasting for patients with renal diseases. In this study, we reviewed the PubMed, Google Scholar, EBSCO, SCIRUS, Embase, and DOAJ data sources to identify the published studies on the impact of Ramadan fasting on patients with renal diseases. Our review on published reports on renal transplant recipients revealed no injurious effect of Ramadan fasting for the renal graft function. Nearly all studies on this topic suggest that Ramadan fasting is safe when the function of the renal graft is acceptable and stable. Regarding the impact of Ramadan fasting on patients with chronic kidney disease, there is concern about the role of renal hypoperfusion in developing tubular cell injury. Finally, there is controversy between studies about the risk of dehydration in Ramadan in developing renal stones. There are uncertainties about the change in the incidence of renal colic in Ramadan month compared with the other periods of the year. Despite such discrepancies, nearly all studies are in agreement on consuming adequate amounts of water from dusk to dawn to reduce the risk of renal stone formation.

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.

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.

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.

Acquired perforating dermatosis: a report of 8 cases.

PubMed

González-Lara, L; Gómez-Bernal, S; Vázquez-López, F; Vivanco-Allende, B

2014-01-01

Acquired perforating dermatosis (APD) is an uncommon disease characterized by lesions exhibiting transepidermal elimination of collagen or elastic fibers. APD affects adults and is associated with systemic diseases, mainly diabetes mellitus and renal failure. We present 8 cases of APD. Seven patients had concomitant diabetes mellitus with or without chronic renal failure, and 1 had alcoholic cirrhosis. In the patients with chronic renal failure, the onset of APD coincided with transient worsening of renal function. The mean increase in creatinine concentrations above baseline was 1.14mg/dL. Acute deterioration of renal function may be involved in APD. Further studies are needed to investigate this association. Copyright © 2013 Elsevier España, S.L. y AEDV. All rights reserved.

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.

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.

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.

Effect of renal function on serum concentration of 1,5-anhydroglucitol in type 2 diabetic patients in chronic kidney disease stages I-III: A comparative study with HbA1c and glycated albumin.

PubMed

Hasslacher, Christoph; Kulozik, Felix

2016-09-01

1,5-Anhydroglucitol (1,5-AG) is a new blood glucose control marker reflecting temporary glucose elevations. However, 1,5-AG is of limited value in patients with advanced renal insufficiency. The aim of the present study was to assess the correlation between 1,5-AG levels and renal function in patients with earlier stages of nephropathy compared with another two markers of diabetes control, namely HbA1c and glycated albumin (GA). The following parameters were measured in 377 patients with type 2 diabetes: HbA1c, serum concentrations of 1,5-AG, GA and creatinine, hemoglobin, urinary albumin/creatinine ratio, and urinary excretion of α1 -microglobulin (A1M). Estimated glomerular filtration rate (eGFR) was calculated according to the Cockgroft-Gault formula. There was a negative correlation between 1,5-AG and renal function (r = -0.18; P < 0.001). Concentrations of 1,5-AG were, on average, 27.2% lower in patients with glomerular hyperfiltration (eGFR >120 mL/min) compared with patients with moderate renal impairment (eGFR 30-59 mL/min; P = 0.016). In contrast, HbA1c, GA levels and urinary A1M excretion did not differ between the two patient groups. The mean age of patients with eGFR 30-59 mL/min was substantially higher than that of patients with glomerular hyperfiltration (P < 0.001). Thus, an age-related change in the renal glucose threshold could be the reason for the observed correlation between 1,5-AG and renal function. In clinical practice, age and renal function must be taken into consideration when interpreting 1,5-AG levels, even in the absence of advanced renal impairment. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

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.

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

Vascular Augmentation in Renal Transplantation: Supercharging and Turbocharging.

PubMed

Jeong, Euicheol C; Hwang, Seung Hwan; Eo, Su Rak

2017-05-01

The most common anatomic variant seen in donor kidneys for renal transplantation is the presence of multiple renal arteries, which can cause an increased risk of complications. Accessory renal arteries should be anastomosed to the proper source arteries to improve renal perfusion via the appropriate vascular reconstruction techniques. In microsurgery, 2 kinds of vascular augmentation methods, known as 'supercharging' and 'turbocharging,' have been introduced to ensure vascular perfusion in the transferred flap. Supercharging uses a distant source of the vessels, while turbocharging uses vascular sources within the same flap territory. These technical concepts can also be applied in renal transplantation, and in this report, we describe 2 patients who underwent procedures using supercharging and turbocharging. In one case, the ipsilateral deep inferior epigastric artery was transposed to the accessory renal artery (supercharging), and in the other case, the accessory renal artery was anastomosed to the corresponding main renal artery with a vascular graft (turbocharging). The transplanted kidneys showed good perfusion and proper function. No cases of renal failure, hypertension, rejection, or urologic complications were observed. These microsurgical techniques can be safely utilized for renal transplantation with donor kidneys that have multiple arteries with a lower complication rate and better outcome.

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.

Association of renal function and symptoms with mortality in star fruit (Averrhoa carambola) intoxication.

PubMed

Chua, Choon-Bing; Sun, Cheuk-Kwan; Tsui, Huan-Wen; Yang, Po-Jen; Lee, Kuo-Hsin; Hsu, Chih-Wei; Tsai, I-Ting

2017-08-01

Star fruit (SF) is a commonly available fruit produced and eaten in tropical and subtropical countries. Since 1993, various reports have described neurotoxicity after eating SF, but this clinical condition remains unfamiliar. We aimed to describe this clinical entity, the role of renal dysfunction in this disorder, treatment strategies, and prognosis of patients with SF intoxication. We conducted a search of PubMed and Google Scholar databases from 1993 to 2016. We included reports describing patients with a clear history of SF ingestion with acute symptoms. We described the demographic characteristics, reported SF intake, treatments used, and outcomes. We reviewed totally 126 patients (male:female = 1.5:1) from 33 articles with mean age 54.4 ± 11 (range: 30-84). The most common symptom was hiccups (65%), whereas confusion and seizure were the most common symptoms associated with mortality (42% and 61%, respectively). Pre-intoxication renal function also affected mortality. While there was no mortality in patients with normal renal function (NRF), the mortality of patients among reported cases with chronic renal insufficiency and end-stage renal disease undergoing dialysis were 36% and 27%, respectively. With the inclusion of patients reported to have NRF, the overall mortality was 24%. Consistently, the number of SF consumed was substantially higher in the patients with NRF than those with renal functional impairment. The most common treatment strategy was hemodialysis (59%). Patients with impaired renal function were at higher risks of SF intoxication. Severe neurologic symptoms mandate immediate medical intervention because of the association between their occurrence and high mortalities. Toxin removal through dialysis, rather than symptomatic relief, seems to be beneficial to patient survival. Early and continuous dialysis appears to alleviate severe symptoms and prevent symptom rebounds.

Detection of early changes in renal function using 99mTc-MAG3 imaging in a murine model of ischemia-reperfusion injury

PubMed Central

Roberts, John; Chen, Bo; Curtis, Lisa M.; Agarwal, Anupam; Sanders, Paul W.; Zinn, Kurt R.

2012-01-01

Accurate determination of renal function in mice is a major impediment to the use of murine models in acute kidney injury. The purpose of this study was to determine whether early changes in renal function could be detected using dynamic gamma camera imaging in a mouse model of ischemia-reperfusion (I/R) injury. C57BL/6 mice (n = 5/group) underwent a right nephrectomy, followed by either 30 min of I/R injury or sham surgery of the remaining kidney. Dynamic renal studies (21 min, 10 s/frame) were conducted before surgery (baseline) and at 5, 24, and 48 h by injection of 99mTc-mercaptoacetyltriglycine (MAG3; ~1.0 mCi/mouse) via the tail vein. The percentage of injected dose (%ID) in the kidney was calculated for each 10-s interval after MAG3 injection, using standard region of interest analyses. A defect in renal function in I/R-treated mice was detected as early as 5 h after surgery compared with sham-treated mice, identified by the increased %ID (at peak) in the I/R-treated kidneys at 100 s (P < 0.01) that remained significantly higher than sham-treated mice for the duration of the scan until 600 s (P < 0.05). At 48 h, the renal scan demonstrated functional renal recovery of the I/R mice and was comparable to sham-treated mice. Our study shows that using dynamic imaging, renal dysfunction can be detected and quantified reliably as early as 5 h after I/R insult, allowing for evaluation of early treatment interventions. PMID:17634403

Randomized trial of single-dose versus divided-dose rabbit anti-thymocyte globulin induction in renal transplantation: an interim report.

PubMed

Stevens, R Brian; Mercer, David F; Grant, Wendy J; Freifeld, Alison G; Lane, James T; Groggel, Gerald C; Rigley, Theodore H; Nielsen, Kathleen J; Henning, Megan E; Skorupa, Jill Y; Skorupa, Anna J; Christensen, Kecia A; Sandoz, John P; Kellogg, Anna M; Langnas, Alan N; Wrenshall, Lucile E

2008-05-27

The optimal dosing protocol for rabbit anti-thymocyte globulin (rATG) induction in renal transplantation has not been determined, but evidence exists that rATG infusion before renal allograft reperfusion improves early graft function. Infusing a large rATG dose over a short interval has not previously been evaluated for its effect on renal function and allograft nephropathy in a prospective, randomized comparison against conventional rATG induction. Between April 20, 2004 and December 26, 2007 we enrolled renal transplant patients into a prospective, randomized, nonblinded 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=160) followed after 6 months by calcineurin-inhibitor withdrawal. Primary endpoints are renal function by calculated glomerular filtration rate (GFR) and chronic allograft nephropathy at protocol biopsy. We now present the early GFR data of all 160 patients and safety and efficacy data of the first 142 patients with 6 months follow up and before calcineurin inhibitor withdrawal (average follow up=23.3+/-11.6 months). There were no differences between groups in rATG-related adverse events, patient and graft survival, acute rejection, or chronic allograft nephropathy rate at 6 months. Calculated DeltaGFR (POD 1-4) was significantly better in the single-dose group (P=0.02), with a trend toward improved renal function from months 2 to 6 in recipients of deceased donor kidneys (P=0.08). This study demonstrates that administering 6 mg/kg of rATG over 24 hr is safe and is associated with improved early renal function compared with administering rATG in alternate-day doses.

Impact of parenchymal loss on renal function after laparoscopic partial nephrectomy under warm ischemia.

PubMed

Bagheri, Fariborz; Pusztai, Csaba; Farkas, László; Kallidonis, Panagiotis; Buzogány, István; Szabó, Zsuzsanna; Lantos, János; Imre, Marianna; Farkas, Nelli; Szántó, Árpád

2016-12-01

To elucidate the impact of renal parenchymal loss and the ischemic reperfusion injury (RI) on the renal function after laparoscopic partial nephrectomy (LPN) under warm ischemia (WI). Thirty-five patients with a single polar renal mass ≤4 cm and normal contralateral kidney underwent LPN. Transperitoneal LPN with WI using en bloc hilar occlusion was performed. The total differential renal function (T-DRF) using 99m Tc-dimercaptosuccinic acid was evaluated preoperatively and postoperatively over a period of 1 year. A special region of interest (ROI) was selected on the non-tumorous pole of the involved kidney, and was compared with the same ROI in the contralateral kidney. The latter comparison was defined as partial differential renal function (P-DRF). Any postoperative decline in the P-DRF of the operated kidney was attributed to the RI. Subtraction of the P-DRF decline from the T-DRF decline was attributed to the parenchymal loss caused by the resection of the tumor and suturing of the normal parenchyma. The mean WI time was 22 min, and the mean weight of resected specimen was 18 g. The mean postoperative eGFR declined to 87 ml/min/1.73 m 2 from its baseline mean value of 97 ml/min/1.73 m 2 (p value = 0.075). Mean postoperative T-DRF and P-DRF of the operated kidney declined by 7 and 3 %, respectively. After LPN of small renal mass, decline in renal function is primarily attributed to parenchymal loss caused by tumor resection and suturing of the normal parenchyma rather than the RI.

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.

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

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

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.

The renin-angiotensin-aldosterone system blockade in patients with advanced diabetic kidney disease.

PubMed

Bermejo, Sheila; García, Carles Oriol; Rodríguez, Eva; Barrios, Clara; Otero, Sol; Mojal, Sergi; Pascual, Julio; Soler, María José

Diabetic kidney disease is the leading cause of end-stage chronic kidney disease. The renin-angiotensin-aldosterone system (RAAS) blockade has been shown to slow the progression of diabetic kidney disease. Our objectives were: to study the percentage of patients with diabetic kidney disease treated with RAAS blockade, to determine its renal function, safety profile and assess whether its administration is associated with increased progression of CKD after 3 years of follow-up. Retrospective study. 197 diabetic kidney disease patients were included and divided into three groups according to the treatment: patients who had never received RAAS blockade (non-RAAS blockade), patients who at some point had received RAAS blockade (inconstant-RAAS blockade) and patients who received RAAS blockade (constant-RAAS blockade). Clinical characteristics and analytical variables such as renal function, electrolytes, glycosylated haemoglobin and glomerular filtration rate according to chronic kidney disease -EPI and MDRD formulas were assessed. We also studied their clinical course (baseline, 1 and 3 years follow-up) in terms of treatment group, survival, risk factors and renal prognosis. Non-RAAS blockade patients had worse renal function and older age (p<0.05) at baseline compared to RAAS blockade patients. Patients who received RAAS blockade were not found to have greater toxicity or chronic kidney disease progression and no differences in renal prognosis were identified. Mortality was higher in non-RAAS blockade patients, older patients and patients with worse renal function (p<0.05). In the multivariate analysis, older age and worse renal function were risk factors for mortality. Treatment with RAAS blockade is more common in diabetic kidney disease patients with eGFR≥30ml/min/1.73m 2 . In our study, there were no differences in the evolution of renal function between the three groups. Older age and worse renal function were associated with higher mortality in patients who did not receive RAAS blockade. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Evaluation of coronary microvascular function in patients with end-stage renal disease, and renal allograft recipients.

PubMed

Bozbas, Huseyin; Pirat, Bahar; Demirtas, Saadet; Simşek, Vahide; Yildirir, Aylin; Sade, Elif; Sayin, Burak; Sezer, Siren; Karakayali, Hamdi; Muderrisoglu, Haldun

2009-02-01

Approximately half of all deaths in patients with end-stage renal disease (ESRD) are due to cardiovascular diseases. Although renal transplant improves survival and quality of life in these patients, cardiovascular events significantly affect survival. We sought to evaluate coronary flow reserve (CFR), an indicator of coronary microvascular function, in patients with ESRD and in patients with a functioning kidney graft. Eighty-six patients (30 with ESRD, 30 with a functioning renal allograft, and 26 controls) free of coronary artery disease or diabetes mellitus were included. Transthoracic Doppler echocardiography was used to measure coronary peak flow velocities at baseline and after dipyridamole infusion. CFR was calculated as the ratio of hyperemic to baseline diastolic peak flow velocities and was compared among the groups. The mean age of the study population was 36.1+/-7.3 years. No between-group differences were found regarding age, sex, or prevalences of traditional coronary risk factors other than hypertension. Compared with the renal transplant and control groups, the ESRD group had significantly lower mean CFR values. On multivariate regression analysis, serum levels of creatinine, age, and diastolic dysfunction were independent predictors of CFR. CFR is impaired in patients with ESRD suggesting that coronary microvascular dysfunction, an early finding of atherosclerosis, is evident in these patients. Although associated with a decreased CFR compared with controls, renal transplant on the other hand seems to have a favorable effect on coronary microvascular function.

Experimental drug-induced changes in renal function and biodistribution of /sup 99m/Tc-MDP

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

McAfee, J.G.; Singh, A.; Roskopf, M.

Increased renal uptake of /sup 99m/Tc methylene diphosphonate (MDP) was observed irregularly in rats after methotrexate, vincristine or gentamicin, administered separately. Cisplatin regularly induced a dose-related increased MDP uptake which correlated with the degree of tubular damage histologically. The augmented MDP renal uptake was not consistently accompanied by a decreased clearance of simultaneously injected I-131 Hippuran, particularly at lower drug dose levels. This observation agreed with previous evidence that the mechanisms of tubular transport of diphosphonates and organic acids like Hippuran are different. At higher dose levels, the augmented MDP uptake was accompanied by increased renal calcium, hypophosphatemia, elevated serummore » urea nitrogen and creatinine, and only occasional, mild hypercalcemia. The magnitude of the increased renal uptake of MDP observed could not be explained by alterations in iron metabolism or by dehydration. Drug-induced renal retention of MDP by a factor of 2 or more above normal appears to be a useful indicator of tubular damage when other parameters of renal function are sometimes normal.« less

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.

[Early detection, prevention and management of renal failure in liver transplantation].

PubMed

Castells, Lluís; Baliellas, Carme; Bilbao, Itxarone; Cantarell, Carme; Cruzado, Josep Maria; Esforzado, Núria; García-Valdecasas, Juan Carlos; Lladó, Laura; Rimola, Antoni; Serón, Daniel; Oppenheimer, Federico

2014-10-01

Renal failure is a frequent complication in liver transplant recipients and is associated with increased morbidity and mortality. A variety of risk factors for the development of renal failure in the pre- and post-transplantation periods have been described, as well as at the time of surgery. To reduce the negative impact of renal failure in this population, an active approach is required for the identification of those patients with risk factors, the implementation of preventive strategies, and the early detection of progressive deterioration of renal function. Based on published evidence and on clinical experience, this document presents a series of recommendations on monitoring RF in LT recipients, as well as on the prevention and management of acute and chronic renal failure after LT and referral of these patients to the nephrologist. In addition, this document also provides an update of the various immunosuppressive regimens tested in this population for the prevention and control of post-transplantation deterioration of renal function. Copyright © 2013 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

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.

The role of sympathetic nervous system in the progression of chronic kidney disease in the era of catheter based sympathetic renal denervation.

PubMed

Petras, Dimitrios; Koutroutsos, Konstantinos; Kordalis, Athanasios; Tsioufis, Costas; Stefanadis, Christodoulos

2013-08-01

The kidney has been shown to be critically involved as both trigger and target of sympathetic nervous system overactivity in both experimental and clinical studies. Renal injury and ischemia, activation of renin angiotensin system and dysfunction of nitric oxide system have been implicated in adrenergic activation from kidney. Conversely, several lines of evidence suggest that sympathetic overactivity, through functional and morphological alterations in renal physiology and structure, may contribute to kidney injury and chronic kidney disease progression. Pharmacologic modulation of sympathetic nervous system activity has been found to have a blood pressure independent renoprotective effect. The inadequate normalization of sympathoexcitation by pharmacologic treatment asks for novel treatment options. Catheter based renal denervation targets selectively both efferent and afferent renal nerves and functionally denervates the kidney providing blood pressure reduction in clinical trials and renoprotection in experimental models by ameliorating the effects of excessive renal sympathetic drive. This review will focus on the role of sympathetic overactivity in the pathogenesis of kidney injury and CKD progression and will speculate on the effect of renal denervation to these conditions.

Accelerated recovery from nephrotic syndrome with acute renal failure by double filtration plasmapheresis in a patient with lupus podocytopathy.

PubMed

Iwazu, Yoshitaka; Akimoto, Tetsu; Izawa, Sayoko; Inoue, Makoto; Muto, Shigeaki; Ando, Yasuhiro; Iwazu, Kana; Fukushima, Noriyoshi; Yumura, Wako; Kusano, Eiji

2012-06-01

We describe a case of an adult female who presented with nephrotic syndrome. She was diagnosed with systemic lupus erythematosus with serum antinuclear antibodies, leucopenia with lymphopenia, butterfly erythema, and nephrotic syndrome. Renal biopsy revealed normal glomeruli with diffuse effacement of the foot processes, consistent with lupus podocytopathy. Although human albumin replacement was performed initially, acute renal failure developed rapidly. Therefore, she was treated with double filtration plasmapheresis (DFPP) in addition to oral steroid. After steroid therapy combined with DFPP, the renal function and proteinuria improved rapidly. Although the impact of DFPP on the treatment of lupus nephritis remains to be delineated, our observations suggest that DFPP in lupus podocytopathy played a pivotal role in facilitating the early recovery from renal injuries. Because of the rapid improvement of renal function without any change in body weight by DFPP, acute renal failure in the setting of lupus podocytopathy might contribute to an alternative pathophysiological factor for the diminished glomerular filtration rate, similar to that observed in the setting of idiopathic minimal change glomerulopathy.

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

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

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.

Hemodynamic Measurements for the Selection of Patients With Renal Artery Stenosis: A Systematic Review.

PubMed

van Brussel, Peter M; van de Hoef, Tim P; de Winter, Robbert J; Vogt, Liffert; van den Born, Bert-Jan

2017-05-22

Interventions targeting renal artery stenoses have been shown to lower blood pressure and preserve renal function. In recent studies, the efficacy of catheter-based percutaneous transluminal renal angioplasty with stent placement has been called into question. In the identification of functional coronary lesions, hyperemic measurements have earned a place in daily practice for clinical decision making, allowing discrimination between solitary coronary lesions and diffuse microvascular disease. Next to differences in clinical characteristics, the selection of renal arteries suitable for intervention is currently on the basis of anatomic grading of the stenosis by angiography rather than functional assessment under hyperemia. It is conceivable that, like the coronary circulation, functional measurements may better predict therapeutic efficacy of percutaneous transluminal renal angioplasty with stent placement. In this systematic review, the authors evaluate the available clinical evidence on the optimal hyperemic agents to induce intrarenal hyperemia, their association with anatomic grading, and their predictive value for treatment effects. In addition, the potential value of combined pressure and flow measurements to discriminate macrovascular from microvascular disease is discussed. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Imaging techniques in the management of chronic kidney disease: current developments and future perspectives.

PubMed

Herget-Rosenthal, Stefan

2011-05-01

The measurement of both renal function and structure is critical in clinical nephrology to detect, stage, and monitor chronic kidney disease (CKD). Current imaging modalities especially ultrasound (US), computed tomography, and magnetic resonance imaging (MRI) provide adequate information on structural changes but little on functional impairment in CKD. Although not yet considered first-line procedures for evaluating patients with renal disease, new US and MR imaging techniques may permit the assessment of renal function in the near future. Combined with established imaging techniques, contrast-enhanced US, dynamic contrast-enhanced MRI, blood oxygen level dependency MRI, or diffusion-weighted imaging may provide rapid, accurate, simultaneous, and noninvasive imaging of the structure of kidneys, macrovascular and microvascular renal perfusion, oxygenation, and glomerular filtration rate. Recent developments in molecular imaging indicate that pathophysiological pathways of renal diseases such as apoptosis, coagulation, fibrosis, and ischemia will be visualized at the tissue level. These major advances in imaging and developments in hardware and software could enable comprehensive imaging of renal structure and function in four dimensions (three dimensions plus time), and imaging is expected to play an increasing role in the management of CKD. Copyright © 2011 Elsevier Inc. All rights reserved.

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.

Experience with extracorporeal renal operations and autotransplantation in the management of complicated urologic disorders.

PubMed

Novick, A C; Straffon, R A; Stewart, B H

1981-07-01

Renal autotransplantation with or without an extracorporeal renal operation was performed 45 times upon 43 patients. Twenty-one patients underwent renal autotransplantation as surgical treatment for renovascular hypertension, all of whom are cured or have improved postoperatively. Sixteen renal autotransplants were performed upon 14 patients with extensive ureteral disease, 14 of which were successful. Six patients with carcinoma centrally located in a solitary kidney underwent extracorporeal partial nephrectomy and autotransplantation. Three of these patients are alive with functioning autografts and are tumor-free from one to five years postoperatively. Two patients with multiple recurrent renal calculi were successfully treated by extracorporeal pyelolithotomy and autotransplantation with pyelovesicostomy. An extracorporeal renal operation and autotransplantation can provide the best solution for selected urologic problems not correctable by conventional methods.

The kidney in the pathogenesis of hypertension: the role of renal nerves.

PubMed

DiBona, G F

1985-04-01

The intrinsic efferent innervation of the kidney consists of exclusively noradrenergic fibers that innervate the preglomerular and postgomerular vasculature, all elements of the juxtagomerular apparatus and virtually all segments of the nephron in both cortical and medullo-papillary regions. Increases in efferent renal sympathetic nerve activity produce renal vasoconstriction, release of renin, catecholamines, prostaglandins and other vasoactive substances, and increases in renal tubular sodium reabsorption; these responses are graded and differentiated. The intrinsic afferent innervation of the kidney consists of mechanoreceptors and chemoreceptors which participate in reno-renal and reno-systemic reflexes that modulate sympathetic neural outflow in an organ-specific differentiated pattern. Therefore, alterations in efferent and afferent renal nerve activity produce changes in several important renal functions known to contribute to the development and maintenance of hypertension.

Renal Vascular Structure and Rarefaction

PubMed Central

Chade, Alejandro R.

2014-01-01

An intact microcirculation is vital for diffusion of oxygen and nutrients and for removal of toxins of every organ and system in the human body. The functional and/or anatomical loss of microvessels is known as rarefaction, which can compromise the normal organ function and have been suggested as a possible starting point of several diseases. The purpose of this overview is to discuss the potential underlying mechanisms leading to renal microvascular rarefaction, and the potential consequences on renal function and on the progression of renal damage. Although the kidney is a special organ that receives much more blood than its metabolic needs, experimental and clinical evidence indicates that renal microvascular rarefaction is associated to prevalent cardiovascular diseases such as diabetes, hypertension, and atherosclerosis, either as cause or consequence. On the other hand, emerging experimental evidence using progenitor cells or angiogenic cytokines supports the feasibility of therapeutic interventions capable of modifying the progressive nature of microvascular rarefaction in the kidney. This overview will also attempt to discuss the potential renoprotective mechanisms of the therapeutic targeting of the renal microcirculation. PMID:23720331

Fatal bilateral dioctophymatosis.

PubMed

Li, Gang; Liu, Caigang; Li, Fang; Zhou, Maoyi; Liu, Xiangyong; Niu, Yuanjie

2010-12-01

Dioctophyma renale is a parasite that frequently occurs in animals but rarely in humans. The present report describes the clinical observations of a D. renale infection in a 51-yr-old woman. Its clinical signs and diagnostic findings were unspecific until giant worms were observed in the urine and histological findings confirmed it was a D. renale infection. She refused treatment and died of bilateral renal function failure. This is the first confirmed report to follow the natural progression of D. renale infection in a human. Here, we discuss a conservative therapeutic approach and features associated with this parasitic infection.

Diagnosis of hydronephrosis: comparison of radionuclide scanning and sonography

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

Malave, S.R.; Neiman, H.L.; Spies, S.M.

1980-12-01

Diagnostic sonographic and radioisotope scanning techniques have been shown to be useful in the diagnosis of obstructive uropathy. The accuracy of both methods was compared and sonography was found to provide the more accurate data (sensitivity, 90%, specificity, 98%; accuracy, 97%). Sonography provides excellent anatomic information and enables one to grade the degree of dilatation. Renal radionuclide studies were less sensitive in detecting obstruction, particularly in the presence of chronic renal disease, but offered additional information regarding relative renal blood flow, total effective renal plasma flow, and interval change in renal parenchymal function.

[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.

Dialysis in rats with acute renal failure: evaluation of three different dialyzer membranes.

PubMed

Kränzlin, B; Gretz, N; Kirschfink, M; Mujais, S K

1996-11-01

Exposure to complement-activating cellulosic dialysis membranes has been claimed to adversely affect the course of acute renal failure (ARF). To test this hypothesis, male Sprague-Dawley rats were allocated to 2 groups: in Group 1, ARF was induced by bilateral renal artery clamping whereas in Group 2, animals underwent a sham procedure. In each group, rats were further allocated to undergo hemodialysis with either a Cuprophan, a Hemophan, or a polyacrylonitrile minidialyzer on Days 4 and 8 after surgery, or no dialysis. Renal function was measured by inulin clearance on the days after dialysis. Additionally, total complement activity (CH50) was estimated on Days 1, 2, 4, and 8, and complement factor C3 was detected immunohistochemically. The degree of renal failure and the rate of recovery of renal function were similar in all the ARF groups irrespective of whether they had undergone dialysis or not, or of the type of the dialysis membrane. Furthermore, there were no significant differences in the course of CH50 or in the amount and distribution of complement factor C3 in the kidney tissue between the rats of Groups 1 and 2. Our findings refute the hypothesis that in ischemic ARF exposure to complement-activating cellulosic dialysis membranes impairs the recovery of renal function in rats.

Supplementation with chromium picolinate recovers renal Cr concentration and improves carbohydrate metabolism and renal function in type 2 diabetic mice.

PubMed

Mita, Yukiko; Ishihara, Kengo; Fukuchi, Yoshiko; Fukuya, Yoko; Yasumoto, Kyoden

2005-01-01

To study the preventive effect of supplemented chromium picolinate (CrPic) on the development of diabetic nephropathy in mice, we analyzed the effects of CrPic supplementation on renal function and concentrations of serum glucose and tissue chromium (Cr). In experiment 1, male KK-Ay obese diabetic mice were fed either a control diet (control) or a diet supplemented with 2 mg/kg diet (Cr2) or 10 mg/kg diet (Cr10) of Cr for 12 wk. Cr10 significantly ameliorated hyperglycemia after a glucose load, creatinine clearance rates, and urinary microalbumin levels (p<0.05). In experiment 2, the Cr10 diet was fed to male KK-Ay obese diabetic mice and C57BL nondiabetic mice for 4 wk. The CrPic diet reduced urinary albumin excretion in the diabetic mice (p<0.05). Inductively coupled plasma-mass spectrometry analysis revealed that the renal Cr content and the recovery of renal Cr concentration after Cr supplementation were significantly lower in the diabetic mice than in the nondiabetic mice (p<0.01). These observations suggest that Cr supplementation of type 2 diabetic mice reduces the symptoms of hyperglycemia and improves the renal function by recovering renal Cr concentration.

Renal blood flow, fractional excretion of sodium and acute kidney injury: time for a new paradigm?

PubMed

Prowle, John; Bagshaw, Sean M; Bellomo, Rinaldo

2012-12-01

Global renal blood flow is considered pivotal to renal function. Decreased global renal blood flow (decreased perfusion) is further considered the major mechanism of reduced glomerular filtration rate responsible for the development of acute kidney injury (AKI) in critically ill patients. Additionally, urinary biochemical tests are widely taught to allow the differential diagnosis of prerenal (functional) AKI and intrinsic [structural AKI (so-called acute tubular necrosis)]. In this review we will examine recent evidence regarding these two key clinical paradigms. Recent animal experiments and clinical studies in humans using cine-phase contrast magnetic resonance technology are not consistent with the decreased perfusion paradigm. They suggest instead that changes in the intra-renal circulation including modification in efferent arteriolar function and intra-renal shunting are much more likely to be responsible for AKI, especially in sepsis. Similarly, recent human studies indicate the urinary biochemistry has limited diagnostic or prognostic ability and is dissociated form biomarker and microscopic evidence of tubular injury. Intra-renal microcirculatory changes are likely more important than changes in global blood flow in the development of AKI. Urinary biochemistry is not a clinically useful diagnostic or prognostic tool in critically ill patients at risk of or with AKI.

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.

Effect of whole soy and purified isoflavone daidzein on renal function--a 6-month randomized controlled trial in equol-producing postmenopausal women with prehypertension.

PubMed

Liu, Zhao-min; Ho, Suzanne C; Chen, Yu-ming; Tang, Nelson; Woo, Jean

2014-09-01

The aim of the study was to examine the long-term effect of commonly used whole soy foods (soy flour) and purified daidzein (one major isoflavone and the precursor of equol) on renal function among prehypertensive postmenopausal women who are also equol producers, a population most likely to benefit from soy intervention. This was a 6-month double-blind, randomized, placebo-controlled trial. Two hundred seventy eligible Chinese women were randomized to either one of the three treatments: 40 g soy flour (whole soy group), 40 g low-fat milk powder + 63 mg daidzein (daidzein group) or 40 g low-fat milk powder (placebo group) daily each for 6 months. Fasting blood and 24-h urine samples were collected at the beginning and end of trial. Serum creatinine, cystatin C, urea, angiotensin-converting enzyme, minerals and 24-h urinary creatinine and minerals were analyzed. Estimated glomerular filtration rate (eGFR) was calculated with the Cockcroft-Gault and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. Two hundred fifty-three subjects completed the study according to the protocol. Urinary isoflavones indicated good compliance of participants. No significant changes were observed in most of renal parameters, however, there was a less decrease in eGFRcockcroft in 6-month change (p=0.044) and %change (p=0.031) with whole soy intake relative to milk placebo. Subgroup analysis among women with lowered renal function suggested whole soy consumption tended to improve markers of renal function relative to control. Six-month consumption of whole soy tended to have a modest improvement of renal function in prehypertensive postmenopausal women with lowered renal function. Future trials in subjects with more declined renal function are necessary. The trial was registered in ClinicalTrials.gov with identifier of NCT01270737. (URL: http://clinicaltrials.gov/ct2/show/NCT01270737). Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Salt loading produces severe renal hemodynamic dysfunction independent of arterial pressure in spontaneously hypertensive rats.

PubMed

Matavelli, Luis C; Zhou, Xiaoyan; Varagic, Jasmina; Susic, Dinko; Frohlich, Edward D

2007-02-01

We have previously shown that salt excess has adverse cardiac effects in spontaneously hypertensive rats (SHR), independent of its increased arterial pressure; however, the renal effects have not been reported. In the present study we evaluated the role of three levels of salt loading in SHR on renal function, systemic and renal hemodynamics, and glomerular dynamics. At 8 wk of age, rats were given a 4% (n = 11), 6% (n = 9), or 8% (n = 11) salt-load diet for the ensuing 8 wk; control rats (n = 11) received standard chow (0.6% NaCl). Rats had weekly 24-h proteinuria and albuminuria quantified. At the end of salt loading, all rats had systemic and renal hemodynamics measured; glomerular dynamics were specially studied by renal micropuncture in the control, 4% and 6% salt-loaded rats. Proteinuria and albuminuria progressively increased by the second week of salt loading in the 6% and 8% salt-loaded rats. Mean arterial pressure increased minimally, and glomerular filtration rate decreased in all salt-loaded rats. The 6% and 8% salt-loaded rats demonstrated decreased renal plasma flow and increased renal vascular resistance and serum creatinine concentration. Furthermore, 4% and 6% salt-loaded rats had diminished single-nephron plasma flow and increased afferent and efferent arteriolar resistances; glomerular hydrostatic pressure also increased in the 6% salt-loaded rats. In conclusion, dietary salt loading as low as 4% dramatically deteriorated renal function, renal hemodynamics, and glomerular dynamics in SHR independent of a minimal further increase in arterial pressure. These findings support the concept of a strong independent causal relationship between salt excess and cardiovascular and renal injury.

Diabetes mellitus with normal renal function is associated with anaemia.

PubMed

Grossman, Chagai; Dovrish, Zamir; Koren-Morag, Nira; Bornstein, Gil; Leibowitz, Avshalom

2014-05-01

Anaemia is a common complication of diabetes mellitus (DM), usually related to renal failure. There is scarce information as to the levels of haemoglobin (Hb) and the rate of anaemia in diabetic patients with normal renal function. We, therefore, evaluated haemoglobin levels and the rate of anaemia in diabetic subjects with normal renal functions [estimated glomerular filtration rate (eGFR) > 60 mL/min]. The charts of 9250 subjects who attended the Institute of Periodic Medical Examinations at the Chaim Sheba Medical Center for a routine yearly check-up were reviewed. Four hundred and forty-five subjects with type 2 DM and normal renal function were indentified and compared with those without DM who were routinely examined at the same time. Subjects' electronic records were used to build a biochemical and clinical database. Mean haemoglobin levels were lower in subjects with DM than in those without (14.2 vs. 14.7 g/dL, respectively; p < 0.001). Anaemia was observed in 48 (10.8%) subjects in the diabetic group and in only 12 (2.7%) in the nondiabetic group (p < 0.001). Multivariate analysis revealed that age, gender, history of gastrointestinal disease, use of beta blockers, renal function and DM were independent determinants of haemoglobin levels. After adjustment for age, gender, history of gastrointestinal tract diseases and renal function, DM remained a significant determinant of anaemia with an odds ratio of 2.15 (confidence interval: 1.07-4.31). Anaemia is more common in diabetic patients even when eGFR > 60 mL/min. Copyright © 2013 John Wiley & Sons, Ltd.

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

Cardiac and renal function in a large cohort of amateur marathon runners.

PubMed

Hewing, Bernd; Schattke, Sebastian; Spethmann, Sebastian; Sanad, Wasiem; Schroeckh, Sabrina; Schimke, Ingolf; Halleck, Fabian; Peters, Harm; Brechtel, Lars; Lock, Jürgen; Baumann, Gert; Dreger, Henryk; Borges, Adrian C; Knebel, Fabian

2015-03-21

Participation of amateur runners in endurance races continues to increase. Previous studies of marathon runners have raised concerns about exercise-induced myocardial and renal dysfunction and damage. In our pooled analysis, we aimed to characterize changes of cardiac and renal function after marathon running in a large cohort of mostly elderly amateur marathon runners. A total of 167 participants of the Berlin-Marathon (female n = 89, male n = 78; age = 50.3 ± 11.4 years) were included and cardiac and renal function was analyzed prior to, immediately after and 2 weeks following the race by echocardiography and blood tests (including cardiac troponin T, NT-proBNP and cystatin C). Among the runners, 58% exhibited a significant increase in cardiac biomarkers after completion of the marathon. Overall, the changes in echocardiographic parameters for systolic or diastolic left and right ventricular function did not indicate relevant myocardial dysfunction. Notably, 30% of all participants showed >25% decrease in cystatin C-estimated glomerular filtration rate (GFR) from baseline directly after the marathon; in 8%, we observed a decline of more than 50%. All cardiac and renal parameters returned to baseline ranges within 2 weeks after the marathon. The increase in cardiac biomarkers after completing a marathon was not accompanied by relevant cardiac dysfunction as assessed by echocardiography. After the race, a high proportion of runners experienced a decrease in cystatin C-estimated GFR, which is suggestive of transient, exercise-related alteration of renal function. However, we did not observe persistent detrimental effects on 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.

Vesicoureteral Reflux in Kidney Transplantation.

PubMed

Molenaar, Nina M; Minnee, Robert C; Bemelman, Frederike J; Idu, Mirza M

2017-06-01

Vesicoureteral reflux (VUR) is frequently found after transplantation, but its impact on graft function, urine tract infection, and graft loss remains uncertain. Therefore our objective was to evaluate the effects of VUR on the outcome of renal transplantation. We included 1008 adult renal transplant recipients of whom a 1-week posttransplant voiding cystourethrogram was available. Study end points included occurrence of bacteriuria, renal function, and graft survival. In total, 106 (10.5%) of 1008 graft recipients had a diagnosis of VUR on voiding cystography. The incidence of bacteriuria was comparable in the reflux and nonreflux group (17% vs 17.4%, P = .91). There was no significant difference in renal function at 3 months and 1 year in patients with and without VUR. One- and 5-year graft survival in patients with VUR was 85.8% and 82.1% compared to 87.3% and 83.0% in patients without VUR ( P = .68 and P = .80). Posttransplant VUR has no correlations with early bacteriuria, renal function, and graft survival.

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.

Focal segmental necrotizing glomerulonephritis in rheumatoid arthritis.

PubMed

Harper, L; Cockwell, P; Howie, A J; Michael, J; Richards, N T; Savage, C O; Wheeler, D C; Bacon, P A; Adu, D

1997-02-01

We report ten patients with rheumatoid arthritis (RA) who developed a focal segmental necrotizing glomerulonephritis (FSNGN) and extracapillary proliferation typical of vasculitic glomerulonephritis. Five patients also had extrarenal vasculitis. Renal presentation was with renal impairment (n = 9) (median creatinine 726 mumol/l, range 230-1592 mumol/l), microscopic haematuria (n = 8) and proteinuria (n = 10). Nine patients were seropositive for rheumatoid factor and nine had bone erosions. Serum from four of five patients tested by indirect immunofluorescence was positive for antineutrophil cytoplasmic antibody (ANCA) with perinuclear staining. Only three patients had penicillamine or gold therapy. Treatment was with prednisolone and cyclophosphamide (six patients, two of whom were also plasma-exchanged), prednisolone and azathioprine (two patients) and prednisolone alone (two patients). There was a marked improvement in renal function in eight patients. Two patients with dialysis-dependent renal failure recovered renal function, although in one patient this was transient and she required further dialysis 4 months later. Two other patients progressed to dialysis at 3 months and 1 year respectively. Four patients died, one remains dialysis-dependent, and four continue to have good renal function at 5 year follow-up (median creatinine 148.5 mumol/l, range 120-193 mumol/l). One patient was lost to follow-up at 5 years. FSNGN should be considered in all patients with RA and renal impairment, proteinuria and/or microscopic haematuria. This diagnosis appears to be more likely in patients with clinical extrarenal vasculitis, bone erosions or who are seropositive. In these cases, an urgent renal biopsy is indicated.

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.

Pharmacokinetic profile of nifedipine GITS in hypertensive patients with chronic renal impairment.

PubMed

Schneider, R; Stolero, D; Griffel, L; Kobelt, R; Brendel, E; Iaina, A

1994-01-01

25 hypertensive patients with normal or impaired renal function underwent pharmacokinetic and safety studies after single and multiple dose administration of nifedipine GITS (Gastro-Intestinal Therapeutic System) 60mg tablets. Complete pharmacokinetic data were obtained from 23 of these patients. Blood pressure and heart rate changes were compatible with the known properties of the drug. Impaired renal function did not affect the maximum plasma concentrations or bioavailability of nifedipine after single or multiple dose administration of nifedipine GITS, nor was there any evidence of excessive drug accumulation in the presence of renal impairment.

[Diuretics in acute kidney failure: useful or harmful?].

PubMed

Tataw, J; Saudan, P

2011-03-02

Loop diuretics are commonly prescribed within different clinical settings to prevent and or to treat acute renal failure. In most cases they facilitate fluid management following an increased urine output. Experimental models in animals revealed protective effects of loop diuretics in acute renal failure. Several clinical trials have failed to outline better outcomes associated with the use of diuretics in acute renal failure as there was no recovery in renal function nor a reduction in the number of dialysis sessions required. Glomerular filtration rate did not improve with the administration of loop diuretics after continuous renal replacement therapy. The administration of loop diuretics in the management of acute renal failure should be mainly restricted to patients with hypervolemia.

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

Pharmacokinetics of brotizolam in renal failure

PubMed Central

Evers, J.; Renner, E.; Bechtel, W. D.

1983-01-01

1 Kinetics of brotizolam (0.25 mg) were studied in patients with different degrees of renal failure after single and repeated oral ingestion. Serum levels were analysed by radio-immunoassay. 2 Patients were divided into three groups according to their renal function, i.e. creatinine clearance values of 45-80, 15-45, or less than 15 ml/min. 3 The mean elimination half-life was 6.9-8.15 h, with a considerable variation of the peak concentration and elimination half-life in slight to moderate renal failure. There was no delay in elimination in severe renal failure and there was no drug accumulation. 4 No dose adjustment is necessary for brotizolam in renal failure. PMID:6661376

Translational medicine: the antihypertensive effect of renal denervation.

PubMed

DiBona, Gerald F; Esler, Murray

2010-02-01

Translational medicine is concerned with the translation of research discoveries into clinical applications for the prevention, diagnosis, and treatment of human diseases. Here we briefly review the research concerning the role of the renal sympathetic nerves (efferent and afferent) in the control of renal function, with particular reference to hypertension. The accumulated evidence is compelling for a primary role of the renal innervation in the pathogenesis of hypertension. These research discoveries led to the development of a catheter-based procedure for renal denervation in human subjects. A proof-of-principle study in patients with hypertension resistant to conventional therapy has demonstrated that the procedure is safe and produces renal denervation with sustained lowering of arterial pressure.

[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.

Improvement in Renal Hemodynamics following Combined Angiotensin II Infusion and AT1R Blockade in Aged Female Sheep following Fetal Unilateral Nephrectomy

PubMed Central

Singh, Reetu R.; Lankadeva, Yugeesh R.

2013-01-01

Renin-angiotensin system (RAS) is a powerful modulator of renal hemodynamic and fluid homeostasis. Up-regulation in components of intra-renal RAS occurs with ageing. Recently we reported that 2 year old uninephrectomised (uni-x) female sheep have low renin hypertension and reduced renal function. By 5 years of age, these uni-x sheep had augmented decrease in renal blood flow (RBF) compared to sham. We hypothesised that this decrease in RBF in 5 year old uni-x sheep was due to an up-regulation in components of the intra-renal RAS. In this study, renal responses to angiotensin II (AngII) infusion and AngII type 1 receptor (AT1R) blockade were examined in the same 5 year old sheep. We also administered AngII in the presence of losartan to increase AngII bioavailability to the AT2R in order to understand AT2R contribution to renal function in this model. Uni-x animals had significantly lower renal cortical content of renin, AngII (∼40%) and Ang 1–7 (∼60%) and reduced cortical expression of AT1R gene than sham animals. In response to both AngII infusion and AT1R blockade via losartan, renal hemodynamic responses and tubular sodium excretion were significantly attenuated in uni-x animals compared to sham. However, AngII infusion in the presence of losartan caused ∼33% increase in RBF in uni-x sheep compared to ∼14% in sham (P<0.05). This was associated with a significant decrease in renal vascular resistance in the uni-x animals (22% vs 15%, P<0.05) without any changes in systemic blood pressure. The present study shows that majority of the intra-renal RAS components are suppressed in this model of low renin hypertension. However, increasing the availability of AngII to AT2R by AT1R blockade improved renal blood flow in uni-x sheep. This suggests that manipulation of the AT2R maybe a potential therapeutic target for treatment of renal dysfunction associated with a congenital nephron deficit. PMID:23840884

Impact of renal function deterioration on adverse events during anticoagulation therapy using non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation.

PubMed

Miyamoto, Koji; Aiba, Takeshi; Arihiro, Shoji; Watanabe, Makoto; Kokubo, Yoshihiro; Ishibashi, Kohei; Hirose, Sayako; Wada, Mitsuru; Nakajima, Ikutaro; Okamura, Hideo; Noda, Takashi; Nagatsuka, Kazuyuki; Noguchi, Teruo; Anzai, Toshihisa; Yasuda, Satoshi; Ogawa, Hisao; Kamakura, Shiro; Shimizu, Wataru; Miyamoto, Yoshihiro; Toyoda, Kazunori; Kusano, Kengo

2016-08-01

Renal function is crucial for patients with non-valvular atrial fibrillation (NVAF) using non-vitamin K antagonist oral anticoagulants (NOAC). The incidence of renal function deterioration during anticoagulation therapy and its impact of adverse events are unknown. In 807 consecutive NVAF patients treated with NOAC and with estimated creatinine clearance (eCCr) ≥ 50 ml/min (mean age 68 ± 11 years, mean CHADS2 score = 1.8 ± 1.4, CHA2DS2-VASc score = 2.8 ± 1.8, HAS-BLED score = 1.7 ± 1.1), we analyzed the time course of renal function and clinical outcomes, and compared these with the data of general Japanese inhabitants from the Suita Study (n = 2140). Of the 807 patients, 751 (93 %) maintained eCCr ≥ 50 ml/min (group A) whereas the remaining 56 (7 %) fell into the eCCr < 50 ml/min (group B) during the 382 ± 288 days of follow-up. Multivariate logistic regression analysis revealed that advanced age, lower body weight, and congestive heart failure were independent predictors for renal function deterioration in patients with eCCr ≥ 50 ml/min at baseline. Major and/or minor bleedings were more commonly observed in group B than in group A (21 vs. 8 %; P = 0.0004). The CHADS2, CHA2DS2-VASc, and HAS-BLED scores were also significant predictors of renal function deterioration (P < 0.0001). The incidences of renal function deterioration were 1.4, 3.4, 10.5 and 11.7 % in patients with CHADS2 score of 0, 1, 2 and ≥3, respectively. As to CHA2DS2-VASc score, renal function deterioration occurred in 0, 1.7, 9.8 and 15.0 % with a score of 0, 1-2, 3-4 and ≥5, respectively. In the Suita Study of the general population, on the other hand, 122 of 2140 participants with eCCr ≥ 50 ml/min at baseline (5.7 %) fell into the eCCr < 50 ml/min during about 2 years. The incidence of renal function deterioration increased with the CHADS2 score in the general population as well as in our patients. Renal function deterioration was not uncommon and was associated with more frequent adverse events including major bleeding in NVAF patients with anticoagulation therapy. CHADS2, CHA2DS2-VASc, and HAS-BLED scores may be useful as an index of predicting renal function deterioration.

Congestive renal failure: the pathophysiology and treatment of renal venous hypertension.

PubMed

Ross, Edward A

2012-12-01

Longstanding experimental evidence supports the role of renal venous hypertension in causing kidney dysfunction and "congestive renal failure." A focus has been heart failure, in which the cardiorenal syndrome may partly be due to high venous pressure, rather than traditional mechanisms involving low cardiac output. Analogous diseases are intra-abdominal hypertension and renal vein thrombosis. Proposed pathophysiologic mechanisms include reduced transglomerular pressure, elevated renal interstitial pressure, myogenic and neural reflexes, baroreceptor stimulation, activation of sympathetic nervous and renin angiotensin aldosterone systems, and enhanced proinflammatory pathways. Most clinical trials have addressed the underlying condition rather than venous hypertension per se. Interpreting the effects of therapeutic interventions on renal venous congestion are therefore problematic because of such confounders as changes in left ventricular function, cardiac output, and blood pressure. Nevertheless, there is preliminary evidence from small studies of intense medical therapy or extracorporeal ultrafiltration for heart failure that there can be changes to central venous pressure that correlate inversely with renal function, independently from the cardiac index. Larger more rigorous trials are needed to definitively establish under what circumstances conventional pharmacologic or ultrafiltration goals might best be directed toward central venous pressures rather than left ventricular or cardiac output parameters. Copyright © 2012 Elsevier Inc. 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

Postoperative chronic renal failure: a new syndrome?

PubMed Central

Merino, G E; Buselmeier, T J; Kjellstrand, C M

1975-01-01

Of 125 patients with postsurgical acute tubular necrosis, 87 died, 34 regained clinical normal renal function, and 4 survivors (9.5%) were left with severe permanent renal failure, two of whom required chronic dialysis and transplantation. Preoperatively these 4 patients had normal renal function. The 4 patients were above age 60, two had undergone methoxyflurane anesthesia, and nephrotoxic antibiotics were used in all. The incidence of permanent renal failure is much higher than ever reported and may reflect the survival of patients who previously died because of less ideal dialysis. We believe that the cause of this permanent lesion is multifactorial, including age (over 60 years), nephrotoxic antibiotics (particularly cephalothin and gentamicin sulfate), and nephrotoxic anesthetic (methoxyflurane) agents. This combination of factors should be avoided whenever possible. Images Fig. 2. PMID:1147707

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.

Ramadan fasting and patients with renal diseases: A mini review of the literature

PubMed Central

Emami-Naini, Afsoon; Roomizadeh, Peyman; Baradaran, Azar; Abedini, Amin; Abtahi, Mohammad

2013-01-01

Fasting during the month of Ramadan is one of the five pillars of Islam. During this month, adult Muslims are obligated to refrain from eating and drinking from dawn to dusk. Although based on Islamic principles patients are exempted from fasting, each year, many Muslim patients express their willingness to observe the fast in Ramadan month to respect the cultural customs. There are concerns about the impact of fluid restriction and dehydration during Ramadan fasting for patients with renal diseases. In this study, we reviewed the PubMed, Google Scholar, EBSCO, SCIRUS, Embase, and DOAJ data sources to identify the published studies on the impact of Ramadan fasting on patients with renal diseases. Our review on published reports on renal transplant recipients revealed no injurious effect of Ramadan fasting for the renal graft function. Nearly all studies on this topic suggest that Ramadan fasting is safe when the function of the renal graft is acceptable and stable. Regarding the impact of Ramadan fasting on patients with chronic kidney disease, there is concern about the role of renal hypoperfusion in developing tubular cell injury. Finally, there is controversy between studies about the risk of dehydration in Ramadan in developing renal stones. There are uncertainties about the change in the incidence of renal colic in Ramadan month compared with the other periods of the year. Despite such discrepancies, nearly all studies are in agreement on consuming adequate amounts of water from dusk to dawn to reduce the risk of renal stone formation. PMID:24379850

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.

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

Antithrombotic drug therapy for IgA nephropathy: a meta analysis of randomized controlled trials.

PubMed

Liu, Xiu-Juan; Geng, Yan-Qiu; Xin, Shao-Nan; Huang, Guo-Ming; Tu, Xiao-Wen; Ding, Zhong-Ru; Chen, Xiang-Mei

2011-01-01

Antithrombotic agents, including antiplatelet agents, anticoagulants and thrombolysis agents, have been widely used in the management of immunoglobulin A (IgA) nephropathy in Chinese and Japanese populations. To systematically evaluate the effects of antithrombotic agents for IgA nephropathy. Data sources consisted of MEDLINE, EMBASE, the Cochrane Library, Chinese Biomedical Literature Database (CBM), Chinese Science and Technology Periodicals Databases (CNKI) and Japana Centra Revuo Medicina (http://www.jamas.gr.jp) up to April 5, 2011. The quality of the studies was evaluated from the intention to treat analysis and allocation concealment, as well as by the Jadad method. Meta-analyses were performed on the outcomes of proteinuria and renal function. Six articles met the predetermined inclusion criteria. Antithrombotic agents showed statistically significant effects on proteinuria (p<0.0001) but not on the protection of renal function (p=0.07). The pooled risk ratio for proteinuria was 0.53, [95% confidence intervals (CI): 0.41-0.68; I(2)=0%] and for renal function it was 0.42 (95% CI 0.17-1.06; I(2)=72%). Subgroup analysis showed that dipyridamole was beneficial for proteinuria (p=0.0003) but had no significant effects on protecting renal function. Urokinase had statistically significant effects both on the reduction of proteinuria (p=0.0005) and protecting renal function (p<0.00001) when compared with the control group. Antithrombotic agents had statistically significant effects on the reduction of proteinuria but not on the protection of renal function in patients with IgAN. Urokinase had statistically significant effects both on the reduction of proteinuria and on protecting renal function. Urokinase was shown to be a promising medication and should be investigated further.

Intra-renal delivery of mesenchymal stem cells attenuates myocardial injury after reversal of hypertension in porcine renovascular disease.

PubMed

Eirin, Alfonso; Zhu, Xiang-Yang; Ferguson, Christopher M; Riester, Scott M; van Wijnen, Andre J; Lerman, Amir; Lerman, Lilach O

2015-01-19

Percutaneous transluminal renal angioplasty (PTRA) fails to fully improve cardiac injury and dysfunction in patients with renovascular hypertension (RVH). Mesenchymal stem cells (MSCs) restore renal function, but their potential for attenuating cardiac injury after reversal of RVH has not been explored. We hypothesized that replenishment of MSCs during PTRA would improve cardiac function and oxygenation, and decrease myocardial injury in porcine RVH. Pigs were studied after 16 weeks of RVH, RVH treated 4 weeks earlier with PTRA with or without adjunct intra-renal delivery of MSC (10^6 cells), and controls. Cardiac structure, function (fast-computed tomography (CT)), and myocardial oxygenation (Blood-Oxygen-Level-Dependent- magnetic resonance imaging) were assessed in-vivo. Myocardial microvascular density (micro-CT) and myocardial injury were evaluated ex-vivo. Kidney venous and systemic blood levels of inflammatory markers were measured and their renal release calculated. PTRA normalized blood pressure, yet stenotic-kidney glomerular filtration rate, similarly blunted in RVH and RVH + PTRA, normalized only in PTRA + MSC-treated pigs. PTRA attenuated left ventricular remodeling, whereas myocardial oxygenation, subendocardial microvascular density, and diastolic function remained decreased in RVH + PTRA, but normalized in RVH + PTRA-MSC. Circulating isoprostane levels and renal release of inflammatory cytokines increased in RVH and RVH + PTRA, but normalized in RVH + PTRA-MSC, as did myocardial oxidative stress, inflammation, collagen deposition, and fibrosis. Intra-renal MSC delivery during PTRA preserved stenotic-kidney function, reduced systemic oxidative stress and inflammation, and thereby improved cardiac function, oxygenation, and myocardial injury four weeks after revascularization, suggesting a therapeutic potential for adjunctive MSC delivery to preserve cardiac function and structure after reversal of experimental RVH.

Combining new tools to assess renal function and morphology: a holistic approach to study the effects of aging and a congenital nephron deficit.

PubMed

Geraci, Stefania; Chacon-Caldera, Jorge; Cullen-McEwen, Luise; Schad, Lothar R; Sticht, Carsten; Puelles, Victor G; Bertram, John F; Gretz, Norbert

2017-09-01

Recently, new methods for assessing renal function in conscious mice (transcutaneous assessment) and for counting and sizing all glomeruli in whole kidneys (MRI) have been described. In the present study, these methods were used to assess renal structure and function in aging mice, and in mice born with a congenital low-nephron endowment. Age-related nephron loss was analyzed in adult C57BL/6 mice (10-50 wk of age), and congenital nephron deficit was assessed in glial cell line-derived neurotrophic factor heterozygous (GDNF HET)-null mutant mice. Renal function was measured through the transcutaneous quantitation of fluorescein isothiocyanate-sinistrin half-life ( t 1/2 ) in conscious mice. MRI was used to image, count, and size cationic-ferritin labeled glomeruli in whole kidneys ex vivo. Design-based stereology was used to validate the MRI measurements of glomerular number and mean volume. In adult C57BL/6 mice, older age was associated with fewer and larger glomeruli, and a rightward shift in the glomerular size distribution. These changes coincided with a decrease in renal function. GNDF HET mice had a congenital nephron deficit that was associated with glomerular hypertrophy and exacerbated by aging. These findings suggest that glomerular hypertrophy and hyperfiltration are compensatory processes that can occur in conjunction with both age-related nephron loss and congenital nephron deficiency. The combination of measurement of renal function in conscious animals and quantitation of glomerular number, volume, and volume distribution provides a powerful new tool for investigating aspects of renal aging and functional changes. Copyright © 2017 the American Physiological Society.

Renal Function Changes Following Left Ventricular Assist Device Implantation.

PubMed

Daimee, Usama A; Wang, Meng; Papernov, Anna; Sherazi, Saadia; McNitt, Scott; Vidula, Himabindu; Chen, Leway; Alexis, Jeffrey D; Kutyifa, Valentina

2017-12-15

Limited data assessing the clinical significance of post-left ventricular assist device (LVAD) in renal function are available. We aimed to investigate the impact of changes in renal function after LVAD implantation on subsequent long-term outcomes. We followed 184 patients with HeartMate II LVADs implanted between May 2008 and November 2014. Serial assessment of renal function, was performed at baseline and at day 1, day 7, 1 month, 3 months, 6 months, 1 year, and 2 years after implantation. Effects of 1-month GFR and changes in GFR from baseline to 1 month on long-term mortality and hospital re-admission were evaluated. There were 30 patients with GFR <45 (low), 44 with GFR 45 to 59 (intermediate), and 110 with GFR ≥60 (normal) at baseline. Only patients with baseline GFR <45 experienced significant improvement in GFR after 2 years of follow-up (p = 0.012). At 1 month, a higher GFR category was significantly associated with a 31% reduction in mortality (hazard ratio [HR] 0.69, CI 0.49 to 0.98, p = 0.036), but not re-admission. Patients with baseline low and intermediate GFR who had no improvement in renal function category at 1 month experienced significantly greater risk of mortality (HR 1.95, CI 1.10 to 3.43, p = 0.022) and re-admission (HR 1.75, CI 1.07 to 2.84, p = 0.025), relative to patients whose GFR was normal at baseline and 1 month. In conclusion, renal function after LVAD implantation improves in patients with GFR <45. Change in renal function from baseline to 1 month after implantation is a powerful marker of long-term outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Education for patients with chronic kidney disease in Taiwan: a prospective repeated measures study.

PubMed

Yen, Miaofen; Huang, Jeng-Jong; Teng, Hsiu-Lan

2008-11-01

To investigate the physical, knowledge and quality of life outcomes of an educational intervention for patients with early stage chronic kidney disease. A comprehensive predialysis education care team can be effective in slowing the progression of chronic kidney disease. A single group repeated measures design was used to evaluate the effects of the intervention. Participants were recruited through health department community health screen data banks. A predialysis, team-delivered educational intervention covering renal function health care, dietary management of renal function and the effects of Chinese herb medication on renal function was designed and implemented. Data were collected at baseline, six and 12 months. Study outcomes included physical indicators, knowledge (renal function protection, use of Chinese herbs and renal function and diet) and quality of life. Data were analysed using repeated measure anova to test for change over time in outcome variables. Sixty-six persons participated in this study. The predialysis educational intervention showed significant differences at the three time points in overall knowledge scores, waist-hip ratio, body mass index and global health status. Knowledge measures increased at month 6 and decreased at month 12. The primary indicator of renal function, glomerular filtration rate, remained stable throughout the 12 months of follow-up, despite the relatively older mean age of study participants. A predialysis education care team can provide effective disease-specific knowledge and may help retard deterioration of renal function in persons with early-stage chronic kidney disease. The intervention dose may need to be repeated every six months to maintain knowledge effects. A predialysis educational program with disease-specific knowledge and information is feasible and may provide positive outcomes for patients. Topics on the uses of Chinese herbs should be included for people who are likely to use alternative therapies.

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

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

PubMed

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

2017-06-06

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

Sunitinib-Induced Acute Interstitial Nephritis in a Thrombocytopenic Renal Cell Cancer Patient.

PubMed

Azar, Ibrahim; Esfandiarifard, Saghi; Sinai, Pedram; Wazir, Ali; Foulke, Llewellyn; Mehdi, Syed

2017-01-01

Sunitinib, a multitargeted tyrosine kinase inhibitor (TKI), is currently the standard of care for patients with metastatic renal cell carcinoma. Renal adverse events associated with sunitinib include proteinuria, renal insufficiency secondary to focal segmental glomerulosclerosis (FSGS), and thrombotic microangiopathy. We describe the second reported instance of biopsy-proven sunitinib-induced acute interstitial nephritis (AIN), in a challenging case complicated by thrombocytopenia. The case illustrates the importance of early diagnosis and intervention in ensuring long-term recovery from renal complications. Four other cases of AIN reported along with inhibition of the vascular endothelial growth factor (VEGF) by either TKI (sunitinib and sorafenib) or antibodies (bevacizumab) suggest a possible class effect. Given our experience, we recommend monitoring renal function with VEGF inhibition, and in the case of renal failure in the setting of an unclear diagnosis, we recommend prompt biopsy.

[CHRONIC RENAL FAILURE AND PREGNANCY--A CASE REPORT].

PubMed

Amaliev, G M; Uchikova, E; Malinova, M

2015-01-01

Pregnancy in women with chronic renal failure is a complex therapeutic problem requiring a multidisciplinary approach. It is associated with a higher risk of many perinatal complications. The most common abnormalities are related to: progression of renal failure, development of preeclampsia development of nephrotic syndrome, anemic syndrome, IUGR and fetal death. The prognosis depends on the values of serum creatinine prior to pregnancy, the degree of deterioration of renal function, development of additional obstetric complications and the specific etiological reasons that have led to the occurrence of renal failure. Determining the optimum time for authorization birth depends on the condition of the mother, the condition of the fetus and the rate of progression of renal failure, and the deadline the pregnancy should be terminated is 35 weeks. We present a case of a patient with chronic renal failure, with favorable perinatal outcome.

Peri-operative kidney injury and long-term chronic kidney disease following orthotopic heart transplantation in children.

PubMed

Hoskote, Aparna; Burch, Michael

2015-06-01

Significant advances in cardiac intensive care including extracorporeal life support have enabled children with complex congenital heart disease and end-stage heart failure to be supported while awaiting transplantation. With an increasing number of survivors after heart transplantation in children, the complications from long-term immunosuppression, including renal insufficiency, are becoming more apparent. Severe renal dysfunction after heart transplant is defined by a serum creatinine level >2.5 mg/dL (221 μmol/L), and/or need for dialysis or renal transplant. The degree of renal dysfunction is variable and is progressive over time. About 3-10 % of heart transplant recipients will go on to develop severe renal dysfunction within the first 10 years post-transplantation. Multiple risk factors for chronic kidney disease post-transplant have been identified, which include pre-transplant worsening renal function, recipient demographics and morbidity, peri-transplant haemodynamics and long-term exposure to calcineurin inhibitors. Renal insufficiency increases the risk of post-transplant morbidity and mortality. Hence, screening for renal dysfunction pre-, peri- and post-transplantation is important. Early and timely detection of renal insufficiency may help minimize renal insults, and allow prompt implementation of renoprotective strategies. Close monitoring and pre-emptive management of renal dysfunction is an integral aspect of peri-transplant and subsequent post-transplant long-term care.

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.

Dual Gas Treatment With Hydrogen and Carbon Monoxide Attenuates Oxidative Stress and Protects From Renal Ischemia-Reperfusion Injury.

PubMed

Nishida, T; Hayashi, T; Inamoto, T; Kato, R; Ibuki, N; Takahara, K; Takai, T; Yoshikawa, Y; Uchimoto, T; Saito, K; Tanda, N; Kouno, J; Minami, K; Uehara, H; Hirano, H; Nomi, H; Okada, Y; Azuma, H

Hydrogen (H 2 ) and carbon monoxide (CO) gas are both reported to reduce reactive oxygen species and alleviate tissue ischemia-reperfusion (I-R) injury. The present study was conducted to evaluate the effects of a mixture of H 2 gas and CO gas (dual gas) in comparison with hydrogen gas (H 2 : 2%) alone on I-R renal injury (composition of dual gas; N 2 : 77.8%; O 2 : 20.9%; H 2 : 1.30%; CO: 250 parts per million). Adult male Sprague-Dawley rats (body weight 250-280 g) were divided into 5 groups: (1) sham operation control, (2) dual gas inhalation (dual treatment) without I-R treatment, (3) I-R renal injury, (4) H 2 gas alone inhalation (H 2 treatment) with I-R renal injury, and (5) dual treatment with I-R renal injury. I-R renal injury was induced by clamping the left renal artery and vein for 45 minutes followed by reperfusion, and then contralateral nephrectomy was performed 2 weeks later. Renal function was markedly decreased at 24 hours after reperfusion, and thereafter the effects of dual gas were assessed by histologic examination and determination of the superoxide radical, together with functional and molecular analyses. Pathologic examination of the kidney of I-R rats revealed severe renal damage. Importantly, cytoprotective effects of the dual treatment in comparison with H 2 treatment and I-R renal injury were observed in terms of superoxide radical scavenging activity and histochemical features. Rats given dual treatment and I-R renal injury showed significant decreases in blood urea nitrogen. Increased expression of several inflammatory cytokines (tumor necrosis factor-α, interleukin-6, intracellular adhesion molecule-1, nuclear factor-κB, hypoxia inducible factor-1α, and heme oxygenase-1) was attenuated by the dual treatment. Dual gas inhalation decreases oxidative stress and markedly improves I-R-induced renal injury. Copyright © 2017 Elsevier Inc. All rights reserved.

75 FR 70933 - Cardiovascular and Renal Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-19

...] Cardiovascular and Renal Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug Administration, HHS... of Committee: Cardiovascular and Renal Drugs Advisory Committee. General Function of the Committees... appropriate clinical study design for thromboxane receptor antagonists for prevention of cardiovascular events...

First documented case of successful kidney transplantation from a donor with acute renal failure treated with dialysis.

PubMed

Bacak-Kocman, Iva; Peric, Mladen; Kastelan, Zeljko; Kes, Petar; Mesar, Ines; Basic-Jukic, Nikolina

2013-10-01

There is a widening gap between the needs and possibilities of kidney transplantation. In order to solve the problem of organ shortage, the selection criteria for kidney donors have been less stringent over the last years. Favorable outcome of renal transplantation from deceased donors with acute renal failure requiring dialysis may have an important role in expanding the pool of donors. We present the case of two renal transplantations from a polytraumatized 20-years old donor with acute renal failure requiring dialysis. One recipient established good diuresis from the first post-transplant day and did not require hemodialysis. The second recipient had delayed graft function and was treated with 8 hemodialysis sessions. The patient was discharged with good diuresis and normal serum creatinine. After two years of follow-up, both recipients have normal graft function. According to our experience, kidneys from deceased young donors with acute renal failure requiring dialysis may be transplanted, in order to decrease the number of patients on transplantation waiting lists.

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.

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

Achievement of trifecta in minimally invasive partial nephrectomy correlates with functional preservation of operated kidney: a multi-institutional assessment using MAG3 renal scan.

PubMed

Zargar, Homayoun; Porpiglia, Francesco; Porter, James; Quarto, Giuseppe; Perdona, Sisto; Bertolo, Riccardo; Autorino, Riccardo; Kaouk, Jihad H

2016-07-01

To validate and compare the values of "MIC" and "trifecta" as predictors of operated kidney functional preservation in a multi-institutional cohort of patients undergoing minimally invasive PN. We retrospectively reviewed records of consecutive cases of minimally invasive PN performed for cT1 renal masses in 4 centers from 2009 to 2013. Inclusion criteria consisted of availability of a renal scan obtained within 2 weeks prior to surgery and follow-up renal scan 3-6 months after the surgery. The primary endpoint of the study was to compare the degree of ipsilateral renal function preservation assessed by MAG3 renal scan in relation to achievement of MIC and trifecta. Total of 351 patients met our inclusion criteria. The rates of trifecta achievement for cT1a and cT1b tumors were 78.9 and 60.6 %, respectively. The rate of MIC achievement for cT1a tumors and cT1b tumors was 60.3 and 31.7 %, respectively. On multivariable linear regression model, only the degree of tumor complexity assessed by R.E.N.A.L nephrometry score [coefficient B -1.8 (-2.7, -0.9); p < 0.0001] and the achievement of trifecta [coefficient B 6.1 (2.4,9.8); p = 0.014] or MIC (coefficient B 7.2 (3.8,0.6); p < 0.0001) were significant clinical factors predicting ipsilateral split function preservation. Achievement of both MIC and "trifecta" is associated with higher proportion of split renal function preservation for cT1 tumors after minimally invasive PN. Thus, these outcome measures can be regarded not only as markers of surgical quality, but also as reliable surrogates for predicting functional outcome in the operated kidney.

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

Roux-en-Y Esophagojejunostomy Ameliorates Renal Function Through Reduction of Renal Inflammatory and Fibrotic Markers in Diabetic Nephropathy.

PubMed

Wang, Cuifang; He, Bing; Piao, Dongxu; Han, Ping

2016-07-01

Roux-en-Y bariatric surgery has been shown to have a remarkable and sustainable improvement in type 2 diabetes. Recent clinical studies have shown that bariatric surgery can improve or halt the development of diabetic microvascular complications such as nephropathy. However, the exact underlying mechanisms of surgical procedures are unknown. Here, we have investigated the effects of Roux-en-Y esophagojejunostomy (RYEJ) on renal function and inflammation and fibrosis biomarkers for renal injury in type 2 diabetic rats. Sprague-Dawley rats with high fat diet and streptozotocin (STZ)-induced diabetes were randomly assigned into four groups: diabetic nephropathy (DN), DN treated with food restriction (DN-FR), DN treated with RYEJ surgery (DN-RYEJ), and DN-RYEJ sham (n = 6/group). Age-matched normal rats were assigned as control group. RYEJ and sham surgeries were performed. Hyperinsulinemic-euglycemic clamps with tracer infusion were completed to assess insulin sensitivity. Twenty-four hour urine albumin excretion rate (UAER) and glomerular filtration rate (GFR) were measured. The renal pathological injury was assessed by hematoxylin and eosin (HE) staining. Kidney messenger RNA (mRNA) and/or protein content/distribution of phospho-c-Jun NH2-terminal kinase (JNK), monocyte chemoattractant protein (MCP)-1, transforming growth factor (TGF)-β1, and mitogen-activated protein kinase phosphatase 5 (MKP5) were evaluated by real-time PCR and/or Western blotting/immunohistochemistry. Roux-en-Y esophagojejunostomy improved insulin sensitivity. RYEJ ameliorated renal function by improving UAER and GFR and attenuated glomerular hypertrophy after surgery. RYEJ also significantly downregulated the levels of JNK-mediated inflammatory response and upregulated the level of the anti-inflammatory mediator MKP5. Roux-en-Y esophagojejunostomy alleviates insulin resistance. RYEJ surgery ameliorated renal function and attenuated glomerular hypertrophy in a DN rat model. The considerable nephroprotective function may be mainly attributed to the reduced inflammatory and fibrotic biomarkers after RYEJ. The improvements in renal function and inflammation are not wholly dependent on the magnitude of weight loss.

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

Relationship between age, renal function and bone mineral density in the US population.

PubMed

Klawansky, Sidney; Komaroff, Eugene; Cavanaugh, Paul F; Mitchell, David Y; Gordon, Matthew J; Connelly, Janet E; Ross, Susan D

2003-07-01

Bisphosphonate drugs for treating osteoporosis are excreted by the kidney. However, many of the major trials on efficacy and safety of the bisphophonates for treating osteoporosis excluded patients with significant renal compromise. Since both osteoporosis and renal insufficiency become more prevalent with age, it seems prudent for physicians to be aware of the prevalence of renal dysfunction in patients with osteoporosis who are candidates for treatment with bisphosphonates. Data on 13,831 men and women aged 20+ from the Third National Health and Nutrition Examination Survey, 1988-1994 (NHANES III) were used to study the occurrence of compromise in renal clearance function in men and women with osteopenia and osteoporosis. To estimate creatinine clearance (CCr), a measure of renal function, serum creatinine (sCr), weight and age were inserted into the Cockcoft-Gault (C-G) formula. The World Health Organization gender specific bone mineral density (BMD) cut-offs were used to define the populations with osteopenia and osteoporosis. For women ages 20-80+ with osteoporosis, the percent prevalence (95% CI) for mild to moderate compromise of CCr

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.

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.

Clinical features, course and prognosis of idiopathic membranous nephropathy depending on the presence of antibodies against M-type phospholipase A2 receptor.

PubMed

Jatem Escalante, Elías; Segarra Medrano, Alfons; Carnicer Cáceres, Clara; Martín-Gómez, M Adoración; Salcedo Allende, María Teresa; Ostos Roldan, Helena; Agraz Pamplona, Irene

2015-01-01

In membranous nephropathy, the presence of antibodies against M-type phospholipase A2 receptor is considered highly specific for idiopathic forms. However, no specific association to a particular clinical profile has been found for such antibodies. To assess potential differences in initial clinical profile, course and prognosis of idiopathic membranous nephropathy depending on the presence of anti-PLA2R antibodies. Eighty-five patients with idiopathic membranous nephropathy were included (55 anti-PLA2R-positive and 30 anti-PLA2R-negative). Clinical, biochemical and pathological variables were recorded at the time of diagnosis. Frequency of spontaneous remission, incidence of response to first-line therapy, frequency and number of recurrences, survival of renal function free from renal replacement therapy, survival of renal function free from chronic renal insufficiency and frequency of occurrence of malignant, infectious or autoimmune diseases during follow-up were recorded. At the time of diagnosis, anti-PLA2R-negative patients were significantly older and had a higher frequency of spontaneous remission. No differences were noted in the response to first-line treatment, frequency and number of recurrences, survival of renal function free from renal replacement therapy, or survival of renal function free from chronic renal insufficiency. Anti-PLA2R-negative patients with idiopathic membranous nephropathy were older and experienced spontaneous remission more often than anti-PLA2R-positive patients. No differences in terms of treatment response, recurrences, and final prognosis were observed between both groups of patients. Copyright © 2015 The Authors. Published by Elsevier España, S.L.U. All rights reserved.

Impaired endogenous nighttime melatonin secretion relates to intrarenal renin-angiotensin system activation and renal damage in patients with chronic kidney disease.

PubMed

Ishigaki, Sayaka; Ohashi, Naro; Isobe, Shinsuke; Tsuji, Naoko; Iwakura, Takamasa; Ono, Masafumi; Sakao, Yukitoshi; Tsuji, Takayuki; Kato, Akihiko; Miyajima, Hiroaki; Yasuda, Hideo

2016-12-01

Activation of the intrarenal renin-angiotensin system (RAS) plays a critical role in the pathophysiology of chronic kidney disease (CKD) and hypertension. The circadian rhythm of intrarenal RAS activation leads to renal damage and hypertension, which are associated with diurnal blood pressure (BP) variation. The activation of intrarenal RAS following reactive oxygen species (ROS) activation, sympathetic hyperactivity and nitric oxide (NO) inhibition leads to the development of renal damage. Melatonin is a hormone regulating the circadian rhythm, and has multiple functions such as anti-oxidant and anti-adrenergic effects and enhancement of NO bioavailability. Nocturnal melatonin concentrations are lower in CKD patients. However, it is not known if impaired endogenous melatonin secretion is related to BP, intrarenal RAS, or renal damage in CKD patients. We recruited 53 CKD patients and conducted 24-h ambulatory BP monitoring. urine was collected during the daytime and nighttime. We investigated the relationship among the melatonin metabolite urinary 6-sulphatoxymelatonin (U-aMT6s), BP, renal function, urinary angiotensinogen (U-AGT), and urinary albumin (U-Alb). Patients' U-aMT6s levels were significantly and negatively correlated with clinical parameters such as renal function, systolic BP, U-AGT, and U-Alb, during both day and night. Multiple regression analyses for U-aMT6s levels were performed using age, gender, renal function, and each parameter (BPs, U-AGT or U-Alb), at daytime and nighttime. U-aMT6s levels were significantly associated with U-AGT (β = -0.31, p = 0.044) and U-Alb (β = -0.25, p = 0.025) only at night. Impaired nighttime melatonin secretion may be associated with nighttime intrarenal RAS activation and renal damage in CKD patients.

Urinary peptidomics in a rodent model of diabetic nephropathy highlights epidermal growth factor as a biomarker for renal deterioration in patients with type 2 diabetes.

PubMed

Betz, Boris B; Jenks, Sara J; Cronshaw, Andrew D; Lamont, Douglas J; Cairns, Carolynn; Manning, Jonathan R; Goddard, Jane; Webb, David J; Mullins, John J; Hughes, Jeremy; McLachlan, Stela; Strachan, Mark W J; Price, Jackie F; Conway, Bryan R

2016-05-01

Many diabetic patients suffer from declining renal function without developing albuminuria. To identify alternative biomarkers for diabetic nephropathy (DN) we performed urinary peptidomic analysis in a rodent model in which hyperglycemia and hypertension synergize to promote renal pathologic changes consistent with human DN. We identified 297 increased and 15 decreased peptides in the urine of rats with DN compared with controls, including peptides derived from proteins associated with DN and novel candidate biomarkers. We confirmed by ELISA that one of the parent proteins, urinary epidermal growth factor (uEGF), was more than 2-fold reduced in rats with DN in comparison with controls. To assess the clinical utility of uEGF we examined renal outcomes in 642 participants from the Edinburgh Type 2 Diabetes Study who were normoalbuminuric and had preserved renal function at baseline. After adjustment for established renal risk factors, a lower uEGF to creatinine ratio was associated with new-onset estimated glomerular filtration rate less than 60 ml/min per 1.73m(2) (odds ratio 0.48; 95% confidence interval, 0.26-0.90), rapid (over 5% per annum) decline in renal function (odds ratio 0.44; 95% confidence interval, 0.27-0.72) or the composite of both outcomes (odds ratio 0.38; 95% confidence interval, 0.24-0.62). Thus, the utility of a low uEGF to creatinine ratio as a biomarker of progressive decline in renal function in normoalbuminuric patients should be assessed in additional populations. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Novel prediction model of renal function after nephrectomy from automated renal volumetry with preoperative multidetector computed tomography (MDCT).

PubMed

Isotani, Shuji; Shimoyama, Hirofumi; Yokota, Isao; Noma, Yasuhiro; Kitamura, Kousuke; China, Toshiyuki; Saito, Keisuke; Hisasue, Shin-ichi; Ide, Hisamitsu; Muto, Satoru; Yamaguchi, Raizo; Ukimura, Osamu; Gill, Inderbir S; Horie, Shigeo

2015-10-01

The predictive model of postoperative renal function may impact on planning nephrectomy. To develop the novel predictive model using combination of clinical indices with computer volumetry to measure the preserved renal cortex volume (RCV) using multidetector computed tomography (MDCT), and to prospectively validate performance of the model. Total 60 patients undergoing radical nephrectomy from 2011 to 2013 participated, including a development cohort of 39 patients and an external validation cohort of 21 patients. RCV was calculated by voxel count using software (Vincent, FUJIFILM). Renal function before and after radical nephrectomy was assessed via the estimated glomerular filtration rate (eGFR). Factors affecting postoperative eGFR were examined by regression analysis to develop the novel model for predicting postoperative eGFR with a backward elimination method. The predictive model was externally validated and the performance of the model was compared with that of the previously reported models. The postoperative eGFR value was associated with age, preoperative eGFR, preserved renal parenchymal volume (RPV), preserved RCV, % of RPV alteration, and % of RCV alteration (p < 0.01). The significant correlated variables for %eGFR alteration were %RCV preservation (r = 0.58, p < 0.01) and %RPV preservation (r = 0.54, p < 0.01). We developed our regression model as follows: postoperative eGFR = 57.87 - 0.55(age) - 15.01(body surface area) + 0.30(preoperative eGFR) + 52.92(%RCV preservation). Strong correlation was seen between postoperative eGFR and the calculated estimation model (r = 0.83; p < 0.001). The external validation cohort (n = 21) showed our model outperformed previously reported models. Combining MDCT renal volumetry and clinical indices might yield an important tool for predicting postoperative renal function.

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.

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

PubMed

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

2016-07-01

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

Sinomenine attenuates renal fibrosis through Nrf2-mediated inhibition of oxidative stress and TGFβ signaling

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

Qin, Tian

Renal fibrosis is the common feature of chronic kidney disease and mainly mediated by TGFβ-associated pro-fibrogenic signaling, which causes excessive extracellular matrix accumulation and successive loss of kidney functions. Sinomenine (SIN), an alkaloid derived from medicinal herb extensively used in treatment of rheumatoid arthritis and various inflammatory disorders, displays renal protective properties in experimental animals; however its pharmacological potency against renal fibrosis is not explored. In this study we report that SIN possesses strong anti-renal fibrosis functions in kidney cell and in mouse fibrotic kidney. SIN beneficially modulated the pro-fibrogenic protein expression in TGFβ-treated kidney cells and attenuated the renalmore » fibrotic pathogenesis incurred by unilateral ureteral obstruction (UUO), which correlated with its activation of Nrf2 signaling - the key defender against oxidative stress with anti-fibrotic potentials. Further investigation on its regulation of Nrf2 downstream events revealed that SIN significantly balanced oxidative stress via improving the expression and activity of anti-oxidant and detoxifying enzymes, and interrupted the pro-fibrogenic signaling of TGFβ/Smad and Wnt/β-catenin. Even more impressively SIN achieved its anti-fibrotic activities in an Nrf2-dependent manner, suggesting that SIN regulation of Nrf2-associated anti-fibrotic activities constitutes a critical component of SIN's renoprotective functions. Collectively our studies have demonstrated a novel anti-fibrotic property of SIN and its upstream events and provided a molecular basis for SIN's potential applications in treatment of renal fibrosis-associated kidney disorders. - Highlights: • Sinomenine has strong potency of inhibiting renal fibrosis in UUO mouse kidney. • Sinomenine attenuates the expression of profibrogenic proteins. • Sinomenine balances renal fibrosis-associated oxidative stress. • Sinomenine mitigates profibrogenic signaling of TGBβ/Smad and Wnt/β-catenin. • Sinomenine exerts anti-renal fibrotic functions mainly via activating Nrf2 pathways.« less

Renal mechanoreceptor dysfunction: an intermediate phenotype in spontaneously hypertensive rats.

PubMed

DiBona, G F; Jones, S Y; Kopp, U C

1999-01-01

This study tested the hypothesis that decreased responsiveness of renal mechanosensitive neurons constitutes an intermediate phenotype in spontaneously hypertensive rats (SHR). Decreased responsiveness of these sensory neurons would contribute to increased renal sympathetic nerve activity and sodium retention, characteristic findings in hypertension. A backcross population, developed by mating borderline hypertensive rats with Wistar-Kyoto rats (WKY) (the F1 of a cross between an SHR and a normotensive WKY), was fed 8% NaCl food for 12 weeks from age 4 to 16 weeks. Responses to increases in ureteral pressure to 20 and 40 mm Hg in 80 backcross rats instrumented for measurement of mean arterial pressure and afferent renal nerve activity were determined. Mean arterial pressure ranged from 110 to 212 mm Hg and was inversely correlated with the magnitude of the increase in afferent renal nerve activity during increased ureteral pressure. Thus, decreased responsiveness of renal mechanosensitive neurons cosegregated with hypertension in this backcross population. This aspect of the complex quantitative trait of altered renal sympathetic neural control of renal function, ie, decreased renal mechanoreceptor responsiveness, is part of an intermediate phenotype in SHR.

Temporary renal ischemia during nephron sparing surgery is associated with short-term but not long-term impairment in renal function.

PubMed

Yossepowitch, Ofer; Eggener, Scott E; Serio, Angel; Huang, William C; Snyder, Mark E; Vickers, Andrew J; Russo, Paul

2006-10-01

The emergence of laparoscopic nephron sparing surgery has rekindled interest in the impact of warm renal ischemia on renal function. To provide data with which warm renal ischemia can be compared we analyzed short-term and long-term changes in the glomerular filtration rate after temporary cold renal ischemia. In patients undergoing open nephron sparing surgery the estimated glomerular filtration rate was assessed preoperatively, early in the postoperative hospital stay, and 1 and 12 months after surgery using the abbreviated Modification of Diet in Renal Disease Study equation. We separately analyzed 70 patients with a solitary kidney and 592 with 2 functioning kidneys. The end point was the percent change from the baseline glomerular filtration rate. A linear regression model was used to test the association between the glomerular filtration rate change, and ischemia time, patient age, tumor size, estimated blood loss and intraoperative fluid administration. Median cold ischemia time was 31 minutes in patients with a solitary kidney and 35 minutes in those with 2 kidneys. Compared to patients with 2 kidneys those with a solitary kidney had a significantly lower preoperative estimated glomerular filtration rate (p < 0.001), which decreased a median of 30% during the early postoperative period, and 15% and 32% 1 and 12 months after surgery, respectively. In patients with 2 kidneys the corresponding glomerular filtration rate decreases were 16%, 13% and 14%, respectively. On multivariate analyses in each group cold ischemia duration and intraoperative blood loss were significantly associated with early glomerular filtration rate changes. However, 12 months after surgery age was the only independent predictor of a glomerular filtration rate decrease in patients with 2 kidneys. Cold renal ischemia during nephron sparing surgery is a significant determinant of the short-term postoperative glomerular filtration rate. Longer clamping time is particularly detrimental in patients with a solitary kidney but it does not appear to influence long-term renal function. Patients of advanced age may be less likely to recover from acute ischemic renal injury.

Morbidity, mortality and economic burden of renal impairment in cardiac intensive care.

PubMed

Chew, D P; Astley, C; Molloy, D; Vaile, J; De Pasquale, C G; Aylward, P

2006-03-01

Moderate to severe impairment of renal function has emerged as a potent risk factor for adverse short- and long-term outcomes among patients presenting with cardiac disease. We sought to define the clinical, late mortality and economic burden of this risk factor among patients presenting to cardiac intensive care. A clinical audit of patients presenting to cardiac intensive care was undertaken between July 2002 and June 2003. All patients presenting with cardiac diagnoses were included in the study. Baseline creatinine levels were assessed in all patients. Late mortality was assessed by the interrogation of the National Death Register. Renal impairment was defined as estimated glomerular filtration rate <60 mL/min per 1.73 m2, as calculated by the Modified Diet in Renal Disease formula. In-hospital and late outcomes were compared by Cox proportional hazards modelling, adjusting for known confounders. A matched analysis and attributable risk calculation were undertaken to assess the proportion of late mortality accounted for by impairment of renal function and other known negative prognostic factors. The in-hospital total cost associated with renal impairment was assessed by linear regression. Glomerular filtration rate <60 mL/min per 1.73 m2 was evident in 33.0% of this population. Among these patients, in-hospital and late mortality were substantially increased: risk ratio 13.2; 95% CI 3.0-58.1; P < 0.001 and hazard ratio 6.2; 95% CI 3.6-10.7; P < 0.001, respectively. In matched analysis, renal impairment to this level was associated with 42.1% of all the late deaths observed. Paradoxically, patients with renal impairment were more conservatively managed, but their hospitalizations were associated with an excess adjusted in-hospital cost of $A1676. Impaired renal function is associated with a striking clinical and economic burden among patients presenting to cardiac intensive care. As a marker for future risk, renal function accounts for a substantial proportion of the burden of late mortality. The burden of risk suggests a greater potential opportunity for improvement of outcomes through optimisation of therapeutic strategies.

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

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

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

Midi-maxi computer interaction in the interpretation of nuclear medicine procedures

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

Schlapper, G.A.

1977-01-01

A study of renal function with an Anger Gamma Camera coupled with a Digital Equipment Corporation Gamma-11 System and an IBM System 370 demonstrates the potential of quantitative determinations of physiological function through the application of midi-maxi computer interaction in the interpretation of nuclear medicine procedures. It is shown that radiotracers can provide an opportunity to assess physiological processes of renal function by noninvasively following the path of a tracer as a function of time. Time-activity relationships obtained over seven anatomically defined regions are related to parameters of a seven compartment model employed to describe the renal clearance process. Themore » values obtained for clinically significant parameters agree with known renal pathophysiology. Differentiation of failure of acute, chronic, and obstructive forms is indicated.« less

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

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.

Clinical value of natriuretic peptides in chronic kidney disease.

PubMed

Santos-Araújo, Carla; Leite-Moreira, Adelino; Pestana, Manuel

2015-01-01

According to several lines of evidence, natriuretic peptides (NP) are the main components of a cardiac-renal axis that operate in clinical conditions of decreased cardiac hemodynamic tolerance to regulate sodium homeostasis, blood pressure and vascular function. Even though it is reasonable to assume that NP may exert a relevant role in the adaptive response to renal mass ablation, evidence gathered so far suggest that this contribution is probably complex and dependent on the type and degree of the functional mass loss. In the last years NP have been increasingly used to diagnose, monitor treatment and define the prognosis of several cardiovascular (CV) diseases. However, in many clinical settings, like chronic kidney disease (CKD), the predictive value of these biomarkers has been questioned. In fact, it is now well established that renal function significantly affects the plasmatic levels of NP and that renal failure is the clinical condition associated with the highest plasmatic levels of these peptides. The complexity of the relation between NP plasmatic levels and CV and renal functions has obvious consequences, as it may limit the predictive value of NP in CV assessment of CKD patients and be a demanding exercise for clinicians involved in the daily management of these patients. This review describes the role of NP in the regulatory response to renal function loss and addresses the main factors involved in the clinical valorization of the peptides in the context of significant renal failure. Copyright © 2015 The Authors. Published by Elsevier España, S.L.U. All rights reserved.

GPER Mediates Functional Endothelial Aging in Renal Arteries.

PubMed

Meyer, Matthias R; Rosemann, Thomas; Barton, Matthias; Prossnitz, Eric R

2017-01-01

Aging is associated with impaired renal artery function, which is partly characterized by arterial stiffening and a reduced vasodilatory capacity due to excessive generation of reactive oxygen species by NADPH oxidases (Nox). The abundance and activity of Nox depends on basal activity of the heptahelical transmembrane receptor GPER; however, whether GPER contributes to age-dependent functional changes in renal arteries is unknown. This study investigated the effect of aging and Nox activity on renal artery tone in wild-type and GPER-deficient (Gper-/-) mice (4 and 24 months old). In wild-type mice, aging markedly impaired endothelium-dependent, nitric oxide (NO)-mediated relaxations to acetylcholine, which were largely preserved in renal arteries of aged Gper-/- mice. The Nox inhibitor gp91ds-tat abolished this difference by greatly enhancing relaxations in wild-type mice, while having no effect in Gper-/- mice. Contractions to angiotensin II and phenylephrine in wild-type mice were partly sensitive to gp91ds-tat but unaffected by aging. Again, deletion of GPER abolished effects of Nox inhibition on contractile responses. In conclusion, basal activity of GPER is required for the age-dependent impairment of endothelium-dependent, NO-mediated relaxation in the renal artery. Restoration of relaxation by a Nox inhibitor in aged wild-type but not Gper-/- mice strongly supports a role for Nox-derived reactive oxygen species as the underlying cause. Pharmacological blockers of GPER signaling may thus be suitable to inhibit functional endothelial aging of renal arteries by reducing Nox-derived oxidative stress and, possibly, the associated age-dependent deterioration of kidney function. © 2017 S. Karger AG, Basel.

Remission of proteinuria and preservation of renal function in patients with renal AA amyloidosis secondary to rheumatoid arthritis.

PubMed

Ueno, Toshiharu; Takeda, Kazuhito; Nagata, Michio

2012-02-01

Renal AA amyloidosis presents as a life-threatening disease in patients with rheumatoid arthritis (RA). Although several newly developed immunosuppressive drugs have been tried, patients often progress to end-stage renal failure with unsatisfactory survival rate. A total of nine consecutive cases of severe nephrotic renal AA amyloidosis presented to us. Complete remission of proteinuria was observed in four cases (responders), and the remaining five reached the end point of haemodialysis or death (non-responders); these groups were retrospectively compared. The patients were treated with immunosuppressants, biological drugs and anti-hypertensive drugs. Levels of serum creatinine (S-Cr), urinary protein-creatinine ratio (UP/UCr), blood pressure (BP) and C-reactive protein (CRP) were measured. Histological characteristics of renal amyloid deposition and extent of kidney injury were also scored. Prior to treatment, clinical data (S-Cr, UP/UCr, BP and CRP) and histological severity (glomerular sclerosis, tubulointerstitial injury and extent of amyloid deposition) observed in the renal biopsy specimen were not significantly different between the groups. Following therapeutic intervention, proteinuria disappeared (UP/UCr <0.3) in responders within 12 ± 5.4 months but persisted in non-responders. Consequently, renal function stabilized in responders, but it deteriorated in all non-responders. Strict inflammatory control along with optimal control of hypertension was achieved in responders during the treatment. Regardless of histological severity, intensive therapeutic intervention that includes strict inflammatory control and optimal control of hypertension may change the histology-predicted prognosis of RA-associated renal AA amyloidosis.

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.

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

PubMed Central

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

2018-01-01

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

Oxidative Stress in Hypertension: Role of the Kidney

PubMed Central

Araujo, Magali

2014-01-01

Abstract Significance: Renal oxidative stress can be a cause, a consequence, or more often a potentiating factor for hypertension. Increased reactive oxygen species (ROS) in the kidney have been reported in multiple models of hypertension and related to renal vasoconstriction and alterations of renal function. Nicotinamide adenine dinucleotide phosphate oxidase is the central source of ROS in the hypertensive kidney, but a defective antioxidant system also can contribute. Recent Advances: Superoxide has been identified as the principal ROS implicated for vascular and tubular dysfunction, but hydrogen peroxide (H2O2) has been implicated in diminishing preglomerular vascular reactivity, and promoting medullary blood flow and pressure natriuresis in hypertensive animals. Critical Issues and Future Directions: Increased renal ROS have been implicated in renal vasoconstriction, renin release, activation of renal afferent nerves, augmented contraction, and myogenic responses of afferent arterioles, enhanced tubuloglomerular feedback, dysfunction of glomerular cells, and proteinuria. Inhibition of ROS with antioxidants, superoxide dismutase mimetics, or blockers of the renin-angiotensin-aldosterone system or genetic deletion of one of the components of the signaling cascade often attenuates or delays the onset of hypertension and preserves the renal structure and function. Novel approaches are required to dampen the renal oxidative stress pathways to reduced O2−• rather than H2O2 selectivity and/or to enhance the endogenous antioxidant pathways to susceptible subjects to prevent the development and renal-damaging effects of hypertension. Antioxid. Redox Signal. 20, 74–101. PMID:23472618

[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.

A Rare Case of Renal Impairment Caused by Primary Hypothyroidism.

PubMed

Choy, Joleen; Yaxley, Julian; Yaxley, William

2018-05-01

An association between hypothyroidism and renal impairment has rarely been reported in the literature. We describe a case of hypothyroidism that was associated with otherwise unexplained acute kidney impairment, which was reversed with treatment. A 21-year-old female patient presented to her family physician with myalgia, and preliminary investigations revealed an elevated level of creatine kinase and poor renal function. Primary hypothyroidism was diagnosed and no other apparent etiology for renal failure could be identified despite extensive investigations by the Nephrology Department. Notably, the patient's renal impairment showed prompt resolution following thyroid hormone replacement.

[Renal denervation as treatment option for hypertension].

PubMed

Blankestijn, P J; Bots, M L

2016-01-01

The rationale behind catheter-based renal denervation is that afferent and efferent renal nerves play a role in the pathogenesis and maintenance of high blood pressure, and that this can be prevented by blocking the function of the renal nerves. Since the introduction of catheter-based renal denervation, several observational and a small number of randomised controlled trials have been conducted. The available evidence does not allow for a definitive conclusion regarding its efficacy. There have been no serious side-effects reported. The development of this treatment concept has not been finalised; new trials have just commenced or will start in the near future.

Renal function changes after fenestrated endovascular aneurysm repair.

PubMed

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

2016-08-01

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

Prevalence and Factors Associated with Renal Dysfunction Among HIV-Infected Patients

DTIC Science & Technology

2010-01-01

cross-sectional study at two military clinics with open access to care to determine the impact of HIV factors, including antiretroviral therap¥, on...clinics with open access to care to determine the impact of HIV factors, including antiretroviral therapi, on renal function. Renal dysfunction was...measurement for determination of renal dysfunction rather than measurements over a 3-month or greater period used to establish chronic kidney disease.21

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.

78 FR 76307 - Cardiovascular and Renal Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-17

...] Cardiovascular and Renal Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug Administration, HHS...: Cardiovascular and Renal Drugs Advisory Committee. General Function of the Committee: To provide advice and... combined endpoint of cardiovascular death, MI, stroke, and urgent coronary revascularization. FDA intends...

Abdominal aortic aneurysm associated with congenital solitary pelvic kidney treated with novel hybrid technique.

PubMed

Malinowski, Michael J; Al-Nouri, Omar; Hershberger, Richard; Halandras, Pegge M; Aulivola, Bernadette; Cho, Jae S

2014-08-01

Renal ectopia in the rare condition of associated abdominal aortic aneurysm presents a difficult clinical challenge with respect to access to the aorto-iliac segment and preservation of renal function because of its anomalous renal arterial anatomy and inevitable renal ischemia at the time of open repair. Multiple operative techniques are described throughout the literature to cope with both problems. We report a case of a 57-year-old male with an aorto-iliac aneurysm and a congenital solitary pelvic kidney successfully treated by hybrid total renal revascularization using iliorenal bypass followed by unilateral internal iliac artery coil embolization and conventional endovascular aortic aneurysm repair without any clinical evidence of renal impairment. Copyright © 2014 Elsevier Inc. All rights reserved.

[Comparison of validity and safety between holmium: YAG laser and traditional surgery in partial nephrectomy].

PubMed

Bi, Sheng; Xia, Ming

2015-08-11

To compare the validity and safety between holmium: YAG laser and traditional surgery in partial nephrectomy. A total of 28 patients were divided into two groups (holmium: YAG laser group without renal artery clamping and traditional surgery group with renal artery clamping). The intraoperative blood loss, total operative time, renal artery clamping time, postoperative hospital stay, separated renal function, postoperative complications and depth of tissue injury were recorded. The intraoperative blood loss, total operative time, renal artery clamping time, postoperative hospital stay, separated renal function, postoperative complications and depth of tissue injury were 80 ml, 77 min, 0 min, 7.4 days, 35 ml/min, 0, 0.9 cm, respectively, in holmium: YAG laser group. And in traditional surgery group were 69 ml, 111 min, 25.5 min, 7.3 days, 34 ml/min, 0, 2.0 cm, respectively. The differences of total operative time, renal artery clamping time and depth of tissue injury between two groups were statistically significant. The others were not statistically significant. Holmium: YAG laser is effective and safe in partial nephrectomy. It can decrease the total operative time, minimize the warm ischemia time and enlarge the extent of surgical excision.

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

Periodontitis associated with chronic renal failure: a case report.

PubMed

Khocht, A

1996-11-01

Chronic renal disease is associated with well-documented impairments in polymorphonuclear leucocyte (PMN) function. PMNs are important in defending the periodontium against plaque infections. This report discusses a case of periodontitis in a patient with chronic renal failure. It presents treatment provided and 1-year follow up. It shows that periodontal infections in patients with depressed PMN function could still be managed successfully with standard periodontal treatment emphasizing plaque control.

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.

Xenon treatment attenuates early renal allograft injury associated with prolonged hypothermic storage in rats.

PubMed

Zhao, Hailin; Yoshida, Akira; Xiao, Wei; Ologunde, Rele; O'Dea, Kieran P; Takata, Masao; Tralau-Stewart, Catherine; George, Andrew J T; Ma, Daqing

2013-10-01

Prolonged hypothermic storage elicits severe ischemia-reperfusion injury (IRI) to renal grafts, contributing to delayed graft function (DGF) and episodes of acute immune rejection and shortened graft survival. Organoprotective strategies are therefore needed for improving long-term transplant outcome. The aim of this study is to investigate the renoprotective effect of xenon on early allograft injury associated with prolonged hypothermic storage. Xenon exposure enhanced the expression of heat-shock protein 70 (HSP-70) and heme oxygenase 1 (HO-1) and promoted cell survival after hypothermia-hypoxia insult in human proximal tubular (HK-2) cells, which was abolished by HSP-70 or HO-1 siRNA. In the brown Norway to Lewis rat renal transplantation, xenon administered to donor or recipient decreased the renal tubular cell death, inflammation, and MHC II expression, while delayed graft function (DGF) was therefore reduced. Pathological changes associated with acute rejection, including T-cell, macrophage, and fibroblast infiltration, were also decreased with xenon treatment. Donors or recipients treated with xenon in combination with cyclosporin A had prolonged renal allograft survival. Xenon protects allografts against delayed graft function, attenuates acute immune rejection, and enhances graft survival after prolonged hypothermic storage. Furthermore, xenon works additively with cyclosporin A to preserve post-transplant renal function.

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

Does bariatric surgery really prevent deterioration of renal function?

PubMed

Kim, Eun Young; Kim, Yong Jin

2016-05-01

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

LDL-oxidation, serum uric acid, kidney function and pulse-wave velocity: Data from the Brisighella Heart Study cohort.

PubMed

Cicero, Arrigo F G; Kuwabara, Masanari; Johnson, Richard; Bove, Marilisa; Fogacci, Federica; Rosticci, Martina; Giovannini, Marina; D'Addato, Sergio; Borghi, Claudio

2018-06-15

Serum uric acid (SUA) and oxidized LDL (oxLDL) may be associated with arterial aging. The aim of our study was to evaluate the relationship between SUA, oxLDL and arterial stiffness in subjects with normal renal function and in patients with mild or moderate renal impairment. From the database of the 2012 Brisighella Heart Study, we compared age-matched adult, non-smoker subjects without cardiovascular disease and with normal renal function (n = 205), subjects with stage II chronic kidney disease (CKD) (n = 118) and subjects with stage III CKD (n = 94). All subjects underwent a determination of the LDL oxidative susceptibility, oxLDL levels, SUA and Pulse Wave Velocity (PWV). By univariate analysis, PWV correlated with a large number of clinical, haemodynamic and metabolic parameters, including estimated glomerular filtration rate (eGFR) in subjects with normal renal function and in those with stage II or III CKD. Stepwise multiple regression analyses showed that in the presence of normal renal function or stage II CKD, the main predictors of PWV were age, systolic blood pressure (SBP), ox-LDL, apolipoprotein B and SUA (p < 0.05), while in the presence of stage III CKD only age, SBP and apolipoprotein B remained significant (p < 0.05). Both ox-LDL and SUA independently predicts PWV only in subjects with normal or mildly reduced renal function, but not in the subjects with more compromised eGFR. This study confirms the complex relationship of SUA with cardiovascular and metabolic disease in the patient with established renal disease. Copyright © 2018 Elsevier B.V. All rights reserved.

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

PubMed

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

2015-12-01

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

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.

Capsulotomy for treatment of compartment syndrome in patients with post extracorporeal shock wave lithotripsy renal hematomas: safe and effective, but also advisable?

PubMed

Al Ghazal, Andreas; Schnoeller, Thomas J; Baechle, Christian; Steinestel, Julie; Jentzmik, Florian; Steffens, Sandra; Hirning, Christian; Schrader, Mark; Schrader, Andres J

2014-07-08

To examine whether surgical decompression of hematomas by capsulotomy can help to improve long-term renal function following extracorporeal shock wave lithotripsy (SWL). This study retrospectively identified 7 patients who underwent capsulotomy for post SWL renal hematomas between 2008 and 2012. The control group comprised 8 conservatively treated patients. The median follow-up time was 22 months. The two groups were comparable in age, gender, body mass index, risk factors for developing hematomas (renal failure, urinary flow impairment, indwelling ureteral stent and diabetes mellitus) and the selected SWL modalities. Hematoma size was also similar. However, significantly more patients in the surgical group had purely intracapsular hematomas (85.7% vs. 37.5%) without a potentially pressure-relieving capsular rupture. There were no significant differences in the post-interventional drop in hemoglobin, rise in retention parameters or drop in glomerular filtration rate (GFR). No capsulotomy-related complications were observed, but surgery required a significantly longer hospital stay than conservative management (median, 9 days vs. 5 days). The two groups also showed comparable recovery of renal function at long-term follow-up (median change in GFR from baseline, 97.1% and 97.8%, respectively). Since renal function did not differ between the two treatment groups, the conservative management remains the standard treatment for post-SWL renal hematoma.

Disparate effects of single endothelin A and B receptor blocker therapy on the progression of renal injury in advanced renovascular disease

PubMed Central

Chade, Alejandro R.; Stewart, Nicholas J.; Peavy, Patrick R.

2013-01-01

We hypothesized that chronic specific endothelin (ET)-A receptor blockade therapy would reverse renal dysfunction and injury in advanced experimental renovascular disease. To test this, unilateral renovascular disease was induced in 19 pigs and after 6 weeks, single-kidney hemodynamics and function was quantified in vivo using computed-tomography. All pigs with renovascular disease were divided such that 7 were untreated, 7 were treated with ET-A blockers, and 5 were treated with ET-B blockers. Four weeks later, all pigs were re-studied in vivo, then euthanized and ex vivo studies performed on the stenotic kidney to quantify microvascular density, remodeling, renal oxidative stress, inflammation, and fibrosis. RBF, GFR, and redox status were significantly improved in the stenotic kidney after ET-A but not ET-B blockade. Furthermore, only ET-A blockade therapy reversed renal microvascular rarefaction and diminished remodeling, which was accompanied by a marked decreased in renal inflammatory and fibrogenic activity. Thus, ET-A but not ET-B blockade ameliorated renal injury in pigs with advanced renovascular disease by stimulating microvascular proliferation and decreasing the progression of microvascular remodeling, renal inflammation and fibrosis in the stenotic kidney. These effects were functionally consequential since ET-A blockade improved single kidney microvascular endothelial function, RBF, and GFR, and decreased albuminuria. PMID:24352153

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.

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.

Randomized prospective study of the evolution of renal function depending on the anticalcineurin used.

PubMed

Moro, J A; Almenar Bonet, L; Martínez-Dolz, L; Raso, R; Sánchez-Lázaro, I; Agüero, J; Salvador, Antonio

2008-11-01

Renal failure is one of the primary medium- to long-term morbidities in heart transplant (HT) recipients. To a great extent, this renal deterioration is associated with calcineurin inhibitors, primarily cyclosporine A (CsA). It has been suggested that tacrolimus provides better renal function in these patients. We assessed the medium-term evolution of renal function depending on the calcineurin inhibitor used after HT. We assessed 40 consecutive HT recipients over one year. Patients were randomized to receive CsA (n = 20) or tacrolimus (n = 20) in combination with mycophenolate mofetil (1 g/12 h) and deflazacort in decreasing dosages. We analyzed demographic variables before HT, creatinine values before and six months after HT and incidence of acute rejection. No demographic, clinical, or analytical differences were observed were between the two groups before HT. Repeated measures analysis of variance of creatinine values showed no significant differences between the two groups (P = .98). Furthermore, no differences were observed in either the incidence of rejection (P = .02) or rejection-free survival (P = .14). There seems to be no difference in efficacy profile and renal tolerability between CsA and tacrolimus therapy during the first months after HT.

The Putative Role of the Antiageing Protein Klotho in Cardiovascular and Renal Disease

PubMed Central

Maltese, Giuseppe; Karalliedde, Janaka

2012-01-01

Ageing is a multifactorial process often characterized by a progressive decline in physiological function(s). Ageing can and is often associated with an increased incidence of cardiovascular and renal disease. Klotho is a novel antiageing gene that encodes a protein with multiple pleiotropic functions including an emerging role in cardiorenal disease. Mice deficient for this gene display a phenotype of premature human ageing characterized by diffuse vascular calcification, altered calcium/phosphate metabolism, and shortened lifespan. Klotho is mainly expressed in the renal tubules but it also exists as circulating soluble form detectable in the blood, with systemic effects. Reduction in soluble Klotho has been associated with renal disease, hyperphosphataemia, increased oxidative stress, endothelial dysfunction, and diffuse vascular calcification. Conversely, overexpression of Klotho promotes cardiovascular-renal protection. The majority of the research on Klotho has been conducted in vitro and in animal studies but there is emerging data from human studies which suggest that Klotho may be a modifiable factor involved in the pathogenesis of cardiovascular and renal disease in at-risk populations. Further data is required to confirm if this novel protein can emerge as therapeutic tool that may be used to prevent or slow progression of cardiorenal disease. PMID:22121479

Renal Safety Pharmacology in Drug Discovery and Development.

PubMed

Benjamin, Amanda; Nogueira da Costa, Andre; Delaunois, Annie; Rosseels, Marie-Luce; Valentin, Jean-Pierre

2015-01-01

The kidney is a complex excretory organ playing a crucial role in various physiological processes such as fluid and electrolyte balance, control of blood pressure, removal of waste products, and drug disposition. Drug-induced kidney injury (DIKI) remains a significant cause of candidate drug attrition during drug development. However, the incidence of renal toxicities in preclinical studies is low, and the mechanisms by which drugs induce kidney injury are still poorly understood. Although some in vitro investigational tools have been developed, the in vivo assessment of renal function remains the most widely used methodology to identify DIKI. Stand-alone safety pharmacology studies usually include assessment of glomerular and hemodynamic function, coupled with urine and plasma analyses. However, as renal function is not part of the ICH S7A core battery, such studies are not routinely conducted by pharmaceutical companies. The most common approach consists in integrating renal/urinary measurements in repeat-dose toxicity studies. In addition to the standard analyses and histopathological examination of kidneys, novel promising urinary biomarkers have emerged over the last decade, offering greater sensitivity and specificity than traditional renal parameters. Seven of these biomarkers have been qualified by regulatory agencies for use in rat toxicity studies.

Serum uric acid and renal function in patients with type 1 diabetes: a nationwide study in Brazil.

PubMed

Pizarro, Marcela Haas; Santos, Deborah Conte; Barros, Bianca Senger Vasconcelos; de Melo, Laura Gomes Nunes; Gomes, Marilia Brito

2018-01-01

Diabetes nephropathy is a microvascular complication associated with high morbidity and mortality in patients with type 1 diabetes, and its pathogenesis is not fully understood. Our aim was to evaluate the association between levels of serum uric acid and renal function assessed by glomerular filtration rate (GFR) and albuminuria in patients with type 1 diabetes. This is a multicenter, cross-sectional, observational study with 1686 patients, conducted between August 2011 and August 2014 in 14 public clinics from ten Brazilian cities. Renal function was estimated by CKD-EPI (adults) and by Schwartz (adolescents). We analyzed 1686 patients, aged 30.1 ± 12.0, with 15.4 ± 9.3 years of duration of diabetes; 55.8% were female and 54.0% were Caucasians. Serum uric acid was related to renal function, with a mean of 4.8 ± 1.4 (in the normal renal function group) vs 5.2 ± 2.0 (GFR ≥ 60 ml/min and albuminuria) vs 6.5 ± 2.6 mg/dl (GFR < 60 ml/min). In the pooled group, multivariate analysis showed an inverse correlation between serum uric acid and GFR (r = - 0.316, p < 0.001) with a decrease of 4.11 ml/min in the GFR for every increase of 1 mg/dl in serum uric acid. Considering only patients with normal renal function (n = 1170), a decrease of 2.04 ml/min in the GFR for every increase of 1 mg/dl in Serum uric acid was noted using multivariate analysis. Patients with higher levels of serum uric acid have worse renal function, independently of HbA1c or duration of diabetes, which persisted even in patients with normal renal function. Further prospective studies are necessary to establish if patients with higher serum uric acid may have an elevated risk for developing chronic kidney disease.

Analysis on influencing factors of abnormal renal function in elderly patients with type 2 diabetes mellitus.

PubMed

Chai, Tao; Zhang, Dawei; Li, Zhongxin

2018-04-12

To investigate the related influencing factors of abnormal renal function in elderly in patients with type 2 diabetes mellitus (T2DM) and their clinical significance. The clinical data of elderly T2DM patients hospitalized in Beijing Luhe Hospital from January 2013 to June2016 were retrospectively analyzed. According to their glomerular filtration rate (GFR) levels, these patients were divided into GFR ≥90 mL/min/1.73m2 group (Group A), GFR =60-90 mL/min/1.73m2 group (Group B), and GFR <60 mL/min/1.73m2 group (Group C, i.e., abnormal renal function group). Clinical and laboratory indicators were compared among each group. A total of 614 elderly T2DM patients were collected and divided into Group A (n=186), Group B (n=280) and Group C (n=148, 24.10%). Among them, patients clinically diagnosed with diabetic nephropathy (DN) accounted for 13.68%, and those complicated with high blood pressure (HBP) accounted for 61.40%. In Group C, DN accounted for only 29.73%. In elderly T2DM patients, HBP course, systolic blood pressure (SBP), diastolic blood pressure (DBP), 2h postprandial blood glucose (2hPBG), serum total cholesterol (TC) and blood uric acid (BUA) were independent influencing factors associated with abnormal renal function, among which HBP had a more significant impact on abnormal renal function. With the increase of blood pressure (BP) level, the extension in the course of DM, the increase in urinary albumin/creatinine (Alb/Cr) and the decrease in GFR, the incidence rate of abnormal renal function was increased. HBP course, SBP, DBP, 2hPBG, TC and BUA are independent risk factors for abnormal renal function in elderly patients with T2DM. Well-controlled BP and blood glucose are protective factors, and a comprehensive treatment targeting to the above influencing factors has important clinical significance in preventing and delaying the occurrence and development of abnormal renal function.

Changes in renal function after discontinuation of vitamin D analogues in advanced chronic kidney disease.

PubMed

Caravaca, Francisco; Caravaca-Fontán, Fernando; Azevedo, Lilia; Luna, Enrique

In routine clinical practice, the prescription of vitamin D analogues (VDA) in patients with chronic kidney disease (CKD) is often associated with a decline of the estimated renal function. The reason for this is not fully understood. To analyse the effects of VDA discontinuation in advanced CKD and to determine the factors associated with changes in renal function. Retrospective cohort study of adult patients with advanced CKD. The case subgroup was treated with VDA and this medication was discontinued at baseline (the first visit). The control subgroup was not treated with VDA and they were selected according to comparability principles for CKD progression by propensity score matching. The primary outcome measure was a change to both the estimated glomerular filtration rate (MDRD-GFR) and the measured glomerular filtration rate (mGFR by combined creatinine and urea clearances). Baseline parameters related to mineral metabolism and creatinine generation were analysed as potential determinants of renal function changes. The study sample consisted of 67 cases and 67 controls. Renal function improved in 67% of cases and worsened in 72% of controls (p<0.0001). Changes in MDRD-GFR for the case subgroup and the control subgroup were +0.455±0.997 vs. -0.436±1.103ml/min/1.73 m 2 /month (p<0.0001), respectively. Total creatinine excretion was slightly higher in cases than in controls but the difference was not significant. According to multivariate logistic and linear regression analyses, baseline total serum calcium was one of the best determinants of both renal function recovery (Odds ratio=3.49; p=0.001), and of the extent of renal function recovery (beta=0.276; p=0.001). Discontinuation of VDA treatment in CKD patients is associated with significant recovery of estimated renal function. The extent of these changes is mainly associated with baseline total serum calcium. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

[A comparative study of the renal damage produced after the extracorporeal shock wave lithotripsy according to the lithiasis location].

PubMed

Cancho Gil, Ma J; Díz Rodríguez, R; Vírseda Chamorro, M; Alpuente Román, C; Cabrera Cabrera, J A; Paños Lozano, P

2005-04-01

The Extracorporeal shock waves lithotripsy (ESWL) is fundamental in the treatment of lithiasis. However, there are evidences that it can produce renal damage. The objective of our study is to determine the degree of affectation of the glomerular and tubular function after ESWL, and the influence of the lithiasis location on the type of renal damage. A prospective longitudinal study was carried out in 14 patients with normal renal function subjected to ESWL. We determined the basal level, and the levels at the 24 hours, at the 4th and the 10th day post ESWL of: microalbuminuria (MA) (that values the glomerular function), and N-acetyl glucosamide (NAG) and alanine aminopeptidase (AAP), (that value the tubular function). The basal levels of of MA, NAG and AAP didn't show significant differences in connection with the localization of the stones. A significant increase was observed of the three parameters only 24 hours post ESWL. No significant differences were observed between the variation of the microalbuminuria levels, AAP and NAG and the treatment in relation to the localization of the stones. It exists a glomerular and tubular damage after ESWL. This damage is not related with the pelvic or calicial location of the stones. In patient with previous normal renal function, the renal damage recovers at the 4th day post ESWL.

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.