Reduction In Glomerular Filtration Rate Research Articles

A Nomogram to Predict Significant Estimated Glomerular Filtration Rate Reduction After Robotic Partial Nephrectomy

BackgroundDecreased functional outcome after partial nephrectomy is associated with overall mortality. ObjectiveTo create a model that predicts ≥25% reduction from baseline estimated glomerular filtration rate (eGFR) in patients undergoing robot-assisted partial nephrectomy (RAPN) and to investigate the role of acute kidney injury (AKI) in this patient population. Design, setting, and participantsA total of 999 patients were identified from a multi-institutional database. Renal function was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for chronic kidney disease (CKD). AKI was defined as >25% reduction in eGFR from pre-RAPN period to discharge. Outcome measurements and statistical analysisA nomogram to predict significant eGFR reduction (≥25% from baseline) in the time-frame between 3 and 15mo after RAPN was built based on the coefficients of Cox survival function that ultimately included age, sex, Charlson comorbidity index, baseline eGFR, RENAL nephrometry score, AKI in patients with normal baseline renal function, and AKI on CKD. Such landmark analysis was chosen in order to account for eGFR fluctuations occurring within the first 3mo of RAPN. The proportional hazard assumption was evaluated through the Schönfeld test. Internal validation was performed using the leave-one-out cross validation. Calibration was graphically investigated. The decision curve analysis (DCA) was used to evaluate the net clinical benefit. Results and limitationsMedian (interquartile range [IQR]) age at surgery was 61yr (51, 68). Overall, 146 patients experienced significant eGFR reduction; median follow-up for survivors was 12.4mo. The 15-mo probability of significant eGFR reduction was 19%. All variables fitted into the model, including AKI in patients with normal renal function (hazard ratio [HR]: 4.51; 95% confidence interval [CI]: 3.12, 6.60; p<0.001) and AKI on CKD (HR: 4.90; 95% CI: 2.17, 11.1; p<0.001), emerged as predictors of significant eGFR reduction (all p≤0.048) and were considered to build a nomogram. The internally validated c index was 73%. The model demonstrated excellent calibration and a net benefit at the DCA with probabilities ≥4%. ConclusionsWe developed a nomogram that accurately predicts significant eGFR reduction after RAPN. This model may serve as a tool for early identification of patients at high risk for significant renal function decline after surgery. Patient summaryWe have developed a model for the prediction of renal function loss after partial nephrectomy for renal cancer.

An evidence-based systematic review of the off-label uses of lisinopril.

Lisinopril is an angiotensin-converting-enzyme inhibitor that is largely administered for off-label uses. This study aims to provide a comprehensive review of off-label uses of lisinopril to aid physicians to make evidence-based decisions. The following bibliographic databases were searched from inception up to 30 March 2017: PubMed, EMBASE, the Cochrane Library, Cochrane Central Register of Controlled Trials, Scopus, Ovid and Proquest. This systematic review sought all randomized trials conducted on adult individuals comparing lisinopril on its off-label uses with alternative drugs or placebos and reported direct or alternative clinical outcomes. Risk of bias assessment by using the Cochrane Collaboration risk-of-bias tool and quality evaluation took place. Included studies demonstrated significant positive effects of lisinopril on proteinuric kidney disease; however, lisinopril caused a slight reduction of glomerular filtration rate (GFR) especially for patients with GFR<90mlmin-1 . Lisinopril offered better outcomes in comparison to other standard treatments of diabetic nephropathy. Other studies showed positive effects of lisinopril for migraine, prevention of diabetes, myocardial fibrosis, mitral valve regurgitation, cardiomyopathy in patients with Duchenne muscular dystrophy, oligospermia and infertility, and diabetic retinopathy. Conversely, the studies reported that lisinopril was ineffective for five other off-label uses. The identified studies showed that lisinopril was highly effective for proteinuric kidney disease with a minor but inconsiderable decrease in GFR. Positive effects of lisinopril were demonstrated in seven other off-label uses; however, lisinopril cannot be recommended as the first choice for these until further clinical trials confirm these positive effects.

Serum Amylase in Patients of Chronic Kidney Disease Stage Three to Stage Five

Introduction: Chronic Kidney Disease (CKD) is a progressive loss in renal function over period of many months or years. As compared to the past decades, the number of kidney diseases leading to end CKD is increasing in Nepal. The disease is associated with the decreased glomerular filtration rate (GFR). There is decline in nephron function and number generally quantitated as reduction in glomerular filtration rate. As the GFR declines, there is accumulation of metabolic end products excreted by Kidney. Chronic kidney disease is identified by blood tests, creatinine and urea are two such substances routinely measured. Serum amylase is a pancreatic digestive enzyme that normally acts extracellular to cleave starch into smaller carbohydrate groups and, finally, into monosaccharide's. It is produced by 40-45% from the pancreas and (45%) reabsorbed by tubular cells. Elevations in serum total amylase among patients with CKD is due to impaired renal clearance and seen mostly when the creatinine clearance is below 50 ml/min. Several studies have been reported on this but there are no studies that have been done so far in Nepalese context.Objectives: This study is designed to correlate serum amylase with CKD stage three to stage five in patients of chronic renal disease irrespective of hemodialysis and prevalence of risk factors of CKD and different factors that may affect the level of serum amylase in patients presenting to Bir Hospital Nephrology department, Nepal.Methods: The study was a cross-sectional, observational, descriptive, hospital based carried out in Nephrology Unit of Bir hospital both inpatient or outpatient irrespective of hemodialysis from March 2014 to March 2015. Patients with increased serum amylase due to acute Pancreatitis, Mumps, Intestinal Obstruction, Peptic Ulcer, Cancer, other than renal cause were excluded. The results were analyzed using SPSS version 11 and Microsoft Excel by correlation coefficient. Result: Present study shows that among 126 patients, the prevalence of age group was from 15 years to 78 years with majority being male. The serum amylase levels were significantly higher in Chronic Kidney Disease Stage V with significant p-value. At 80-100 Serum Amylase level had strong correlation of 0.504 for CKD III stage and significant at 10 percent level. The correlation between CKD IV at 80-100 was significant at 10 percent but weak of 0.189. Whereas, CKD V was highly significant but negative at more than 161 Serum Amylase.Conclusion: From the study it was concluded that in Chronic Kidney Disease, Serum amylase was found to be higher as the eGFR decreases. BJHS 2018;3(2)6:403-407.

Abstract P265: Early Renal Hyperfiltration In Obese Dahl Salt-Sensitive Leptin Receptor Mutant Rats is Associated With Glomerular Leukocyte Extravasation and Renal Disease

Hypertension and diabetes are the major causes of chronic kidney disease (CKD). However, epidemiological studies within the last few decades have revealed obesity as an independent risk factor for CKD. Recently, we reported that the obese Dahl salt-sensitive leptin receptor mutant (SS LepR mutant) strain displays proteinuria and podocyte injury by 6 weeks of age independent of hyperglycemia and elevations in arterial pressure. The current study examined whether the development of renal injury in the SS LepR mutant strain is associated with elevations in glomerular filtration rate (GFR). During the study, the SS LepR mutant strain developed hyperinsulinemia and dyslipidemia but not hyperglycemia. Baseline MAP (via carotid catheter) at 6 weeks of age was similar between SS WT (n=8) and SS LepR mutant (n=8) rats and averaged 124 mmHg. However, by 18 weeks of age, MAP increased significantly in the SS LepR mutant strain compared to the values measured in SS WT rats (192±4 vs 149±6 mmHg, respectively). At baseline, protein excretion was 4-fold higher in the SS LepR mutant strain compared to SS WT rats and remained elevated over the course of the study (778±96 vs 137±25 mg/day, respectively). At 6 weeks of age, GFR was 34% higher in the SS LepR mutant strain compared to age-matched SS WT rats indicating renal hyperfiltration (2.92±0.23 vs 2.18±0.25 mL/min/kwt, respectively). While we observed only a 40% reduction in GFR in SS WT rats (1.30±0.07 mL/min/kwt), GFR markedly decreased by 70% in the SS LepR mutant strain (0.87±0.08 mL/min/kwt). Over time, kidneys from the SS LepR mutant strain displayed more glomerulosclerosis, mesangial expansion, and renal fibrosis in comparison to SS WT rats. Glomeruli were isolated from the renal cortex of both strains at 6 and 18 weeks of age and RNA sequencing was performed to identify genes and pathways driving glomerular injury. The major, most consistent signaling pathways that changed at 6 and 18 weeks of age were involved in leukocyte extravasation. In conclusion, these data provide evidence that renal hyperfiltration may contribute to glomerular capillary leukocyte extravasation leading to the early development of proteinuria during obesity in the absence of hypertension and hyperglycemia.

Predictors of Worsening Renal Function Over Time: A Population Based Study

Introduction Chronic kidney disease (CKD) is prevalent in 9–13% of the general population and is associated with increased cardiovascular morbidity, such as heart failure. The natural progression of the disease varies widely between individuals, but overall populations tend to have reduction in renal function over time. The aim of this study is to identify risk factors and characteristics of patients which may predict progression of CKD. Methods This study utilized a retrospective review of the Olmsted County Heart Function Study cohort. The population of this study is a random sample of 2042 Olmsted County residents aged ≥45 years. The current analysis only included 1328 participants who were evaluated at 2 visits, 4 years apart. At each visit, echocardiographic, laboratory and clinical outcome data was obtained. Glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease (MDRD) equation. The cohort was divided into 2 groups: reduction of GFR ≥20% and reduction in GFR Results Between visit 1 and 2 (mean 4.0±0.3 years), 424 (32%) individuals had a reduction of GFR by ≥20%. Individuals with reduction of GFR ≥20% were more significantly likely to be female (71% vs. 41%, p Conclusions In this community population, 32% had a reduction of GFR ≥20% over a 4 year period. Higher systolic BP and NT-proBNP together with EF

Guanylyl Cyclase A in Both Renal Proximal Tubular and Vascular Endothelial Cells Protects the Kidney against Acute Injury in Rodent Experimental Endotoxemia Models.

WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Natriuretic peptides are used, based on empirical observations, in intensive care units as antioliguric treatments. We hypothesized that natriuretic peptides prevent lipopolysaccharide-induced oliguria by activating guanylyl cyclase A, a receptor for natriuretic peptides, in proximal tubules and endothelial cells. Normal Sprague-Dawley rats and mice lacking guanylyl cyclase A in either endothelial cells or proximal tubular cells were challenged with lipopolysaccharide and assessed for oliguria and intratubular flow rate by intravital imaging with multiphoton microscopy. Recombinant atrial natriuretic peptide efficiently improved urine volume without changing blood pressure after lipopolysaccharide challenge in rats (urine volume at 4 h, lipopolysaccharide: 0.6 ± 0.3 ml · kg · h; lipopolysaccharide + fluid resuscitation: 4.6 ± 2.0 ml · kg · h; lipopolysaccharide + fluid resuscitation + atrial natriuretic peptide: 9.0 ± 4.8 ml · kg · h; mean ± SD; n = 5 per group). Lipopolysaccharide decreased glomerular filtration rate and slowed intraproximal tubular flow rate, as measured by in vivo imaging. Fluid resuscitation restored glomerular filtration rate but not tubular flow rate. Adding atrial natriuretic peptide to fluid resuscitation improved both glomerular filtration rate and tubular flow rate. Mice lacking guanylyl cyclase A in either proximal tubules or endothelium demonstrated less improvement of tubular flow rate when treated with atrial natriuretic peptide, compared with control mice. Deletion of endothelial, but not proximal tubular, guanylyl cyclase A augmented the reduction of glomerular filtration rate by lipopolysaccharide. Both endogenous and exogenous natriuretic peptides prevent lipopolysaccharide-induced oliguria by activating guanylyl cyclase A in proximal tubules and endothelial cells.

Impaired fasting glucose is associated with lower glomerular filtration rate decline among men but not women –a large cohort study from Israel

ObjectivesEarly stages of diabetes are associated with an increased glomerular filtration rate (GFR). Little is known, however, about the change in GFR among patients with impaired fasting glucose (IFG). We aimed to evaluate the yearly decline rate of GFR among IFG patients. MethodsA retrospective analysis of a large cohort of subjects attending a medical screening center in Israel. Patients with diabetes mellitus and patients with decreased estimated GFR (eGFR) were excluded. We divided the cohort into 2 subgroups; Healthy controls and impaired fasting control subjects. For each group, we calculated the average yearly estimated GFR decline (ΔeGFR). The results were adjusted for age, BMI, hypertension and smoking status. Results8176 subjects met the inclusion criteria. The median follow up time was 4.8 years (range 2.0 to 13.4). For the whole cohort (men and women), yearly ΔeGFR was −0.68 among healthy controls, and − 0.47 among IFG patients (p = .003). Among men, average yearly ΔeGFR in healthy controls and IFG patients was −0.7 and − 0.4, respectively (p = .0002). All results remained significant after adjusting for age, BMI, hypertension, smoking status and level of HDL and triglycerides. In contrast, among IFG women there was no significant difference in ΔeGFR in comparison with healthy women. ConclusionsImpaired fasting glucose is associated with a decreased rate of GFR reduction compared with healthy subjects. This effect is gender dependent - observed in men but not in women. A mechanism of glomerular hyperfiltration might be involved.

Prolonged Intravenous Colistin Use Associated with Acquired Bartter-Like Syndrome in an Adult Patient: A Case Report

Colistin-induced nephrotoxicity has widely been identified through the elevation of serum creatinine level or a reduction of glomerular filtration rate, but tubulopathy associated with colistin use is poorly understood. Herein, the authors describe a unique case of a 32-year-old quadriplegic male who developed persistent hypomagnesaemia, hypokalaemia, and metabolic alkalosis &gt;4 weeks into therapy with intravenous colistimethate sodium for the treatment of decubitus sacral osteomyelitis by extensively drug-resistant Klebsiella pneumoniae. This required daily aggressive intravenous repletion of electrolytes and fluids while on the treatment, but it was only after 6 days of finishing the treatment with the antibiotic that metabolic changes resembling acquired Bartter-like syndrome started resolving.

High serum levels of p,p’-DDE are associated with an accelerated decline in GFR during 10 years follow-up

Over the past 20 years, the global incidence of chronic kidney disease (CKD) has been increasing and organochlorine pesticides (such as DDT) is a suspected etiological factor. The present study examines the associations between low level background exposure to p,p’-DDE (1-dichloro-2,2-bis (p-chlorophenyl) ethylene), the main DDT metabolite, and kidney function during a 10-year follow-up. Data was analysed from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (n = 1016, 50% women, all aged 70 years). Serum levels of p,p’-DDE was measured by gas chromatography coupled to high-resolution mass spectrometry (GC/HRMS) at baseline (i.e. age of 70 years). Glomerular filtration rate (GFR) was estimated using serum creatinine and cystatin C at 70, 75 and 80 years of age. A significant decline in GFR was seen during the 10-year follow-up (−24 ml/min/1.73 m2, p < 0.0001). A significant negative interaction was seen between baseline p,p’-DDE levels and change in GFR over time (p < 0.0001) following adjustment for sex, systolic blood pressure, diabetes, BMI, smoking and education level at age 70. Subjects with the lowest levels of p,p’-DDE levels at age 70 showed the lowest decline in GFR over 10 years, while subjects with the highest p,p’-DDE levels showed the greatest decline.Baseline levels of p,p’-DDE were related to an accelerated reduction in GFR over 10 years suggesting a nephrotoxic effect of DDT/p,p’-DDE. These findings support a potential role for DDT in the epidemic of CKD of unknown etiology (CKDu) in agricultural communities of Sri Lanka and Central America where DDT was previously used.

9 THE CORRELATION AMONG HYPERTENSION, REDUCTION OF GLOMERULAR FILTRATION RATE AND HYPERURICEMIA IN BATU CITY'S POPULATION OF FARMER

Background: Many studies were found correlation between hypertension, hyperuricemia and reduction of glomerular filtration rate in general population but little or no information was found correlation in farmer's population. Objective: To explore the correlation between systolic blood pressure (SBP), diastolic blood pressure (DBP) and Glomerular Filtration Rate (GFR) with serum uric acid levels in specific population (Batu City's Farmer). Method: It was observational analytic among specific population with cross sectional method. A total of 102 subjects from farmer in Bumi Aji Village, Batu City. All participants were individually interviewed with a structured questionnaire and measured according to standard protocol Fasting blood samples were then collected for the measurement of uric acid, glucose, lipids and creatinine. The levels of correlation between variables were determined by calculating Pearson's correlation coefficients (r). Result: There were 82 subjects (77%) female, mean age 46,7 ± 10,4, mean uric acid 5,6 ± 1,54, prevalence of hyperuricemia 30,4%, mean Systolic Blood Pressure 124 ± 19,4, mean diastolic blood pressure 80,5 ± 13,2 Mean GFR 90,5 ± 29,06. In subject with hyperuricemia display significantly higher SBP (p = 0,016), higher DBP (p = 0,008), higher triglyceride (p = 0,01) lower HDL (p = 0,026). Pearson correlation showed that hyperuricemia correlate with increase systolic blood pressure (r = 0,41, p = 0,000), increase diastolic blood pressure (r = 0,43, p = 0,000), Increase Triglycerides (r = 0,39, p = 0,000), low HDL level (r = −0,244, p = 0,007,). Conclusions: In this study, we suggest that serum uric acid has significant correlation with levels of blood pressure and weak correlation with GFR reduction. Further investigation is required to establish the treatment for hyperuricemia in hypertensive patients.

CT Based Visceral Fat Measures Predict Complexity, Complications and Low Clearance in Living Donor Nephrectomy

Donor nephrectomy operative complexity and postoperative outcomes remain subject to large degrees of unexplained heterogeneity. This study assess the clinical correlation of CT based intrabdominal and perinephric fat content using 3 different fat calculation methods (1. % visceral fat at the umbilicus, 2. 3D visceral fat content of the whole abdomen and donated kidney and 3. perinephric fat in anterior, posterior, medial and lateral planes at the level of the renal vein) producing 15 separate data points for each donor. The study was performed in a single centre in 500 patients undergoing hand assisted laparoscopic donor nephrectomy between 2005 - 2014 who had CT angiography performed as part of their routine preoperative work up. Analysis of each fat measure was carried out with spearman correlations, test and ANOVA. Multivariate regression models of the predictors of a low post donation clearance state at one year (GFR <45mls/min) and operating time (as a marker of operative complexity) were also developed. The mean age of the cohort was 44.1 yrs, 17% were obese and 51% female. Abdominal visceral fat content (r2=0.12 coefficient 0.36 p=0.001) and perinephric fat content (r2=0.14, coefficient 0.07 p<0.001) were strong independent predictors of operating time when adjusted for operating surgeon, arterial multiplicity. Total abdominal visceral fat measures were also greater in those developing postoperative infection (1692cm2 v 1489cm2 p=0.04). Greater perinephric fat content was associated with incisional hernia development (235cm2 v 163cm2 p=0.04). The mean reduction in glomerular filtration rate (GFR) post renal donation at one year was 30.5mls/min (SD 9.6). Spearman rank correlation statistics demonstrated significant positive associations between GFR reduction at one year post donation and visceral fat content at the umbilicus (spearman rho=0.14, p=0.03) and total abdominal visceral fat content (spearman rho 0.13, p=0.04). There was no association with BMI (spearman rho 0.02, p=0.69). Similarly subcutaneous and perinephric fat measures demonstrated no relationship. 7% of the kidney donors studied had a one year post donation "low" GFR clearance state (<45mls/min). A logistic regression model adjusted for preoperative GFR and age demonstrated abdominal visceral fat content measured at the umbilicus to be an independent predictor of a low GFR state at one year (OR 1.1 p=0.001, LR chi2 = 68, p=0.001 r2 = 0.48). |In this the largest CT based anthropometric study of kidney donors to date; visceral and perinephric CT based fat measurements appear to be superior predictors of short and long term outcomes (when compared to BMI). In marginal cases of donation particulary where there is concern over residual renal function post donation, these measures may facilitate perioperative decision making.

IGA NEPHROPATHY WITH GLOMERULAR EXTRACAPILLARY PROLIFERATION IN ADULTS

Glomerular extracapillary proliferation in IgA nephropathy is one of the unfavorable prognostic signs that in some cases, contributes to a rapid progression of the renal failure. The aim of the study was to assess the effect of extracapillary proliferation and its degree on clinical and morphological parameters and the prognosis of IgA nephropathy. Two hundred and six cases of IgA nephropathy diagnosed on kidney biopsy with light and luminescence microscopy using the Oxford classification were analyzed. Quantitative evaluation of the crescents was done by calculating their percentage and crescent score. Extracapillary proliferation was detected in 64 cases (31.1 %) and was associated with more frequent deposits of IgA and C3 in the glomerular basal membranes. In most cases (59.4 %), extracapillary proliferation affects less than a quarter of the glomeruli, while more than half of the glomerulus lesions develops only in single cases (6.3 %). Clinical manifestations of cases of IgA nephropathy with crescents were overwhelmingly characterized by nephritic syndrome (71.9 %) in single cases (3.1 %) there was a rapidly progressive lesion, not associated with the presence of more than half of crescentic glomeruli in the biopsy. Glomerular extracapillary proliferation in every fourth patient was accompanied by isolated urinary abnormalities. The crescent score of 0.75 and more, associated with impaired renal function, revealed more frequently hypertension and more pronounced sclerotic glomerular and interstitial changes. The progression of IgA nephropathy with extracapillary proliferation in the form of reduction in glomerular filtration rate by 50 % or the onset of dialysis (12.5 %) was combined with a high level of proteinuria and marked interstitial fibrosis in the biopsy. The kidney function survival analysis revealed a one-year survival in 87 %, 3 years – in 84 and 5 years – in 67 % of cases.

DOES HYPERURICEMIA INFLUENCE ON EFFICACY OF RADIOFREQUENCY SYMPATHETIC DENERVATION OF THE RENAL ARTERY?

Objective: Hyperuricemia is a risk factor for chronic renal insufficiency and is frequently encountered in patients with arterial hypertension (AH). However the impact of hyperuricemia on efficacy of radiofrequency sympathetic denervation (RFD) of the renal artery in patients with resistant AH (RAH) has not been fully appreciated. The objective of the study was to assess the efficacy of RFD of the renal artery in patients with RAH and hyperuricemia one year after the procedure. Design and method: 15 patients with RAH and hyperuricemia were examined while a comparison group consisted of 12 patients with RAH and without hyperuricemia. All patients received five antihypertensive drugs including diuretics. At baseline and one year after RFD of the renal artery the following parameters were assessed: 24-hour blood pressure monitoring, glomerular filtration rate (GFR) based on Modification of Diet in Renal Disease (MDRD) equation, 24-hour microalbuminuria and left-ventricular myocardial mass index (LVMMI). Results: In one year after RFD of the renal artery the significant decrease in mean 24-hour systolic and diastolic BP was detected in both groups according to 24-hour blood pressure monitoring. GFR level significantly decreased in main group of patients. No changes in microalbuminuria were found. LVMMI did not reach significant differences in patients with RAH and hyperuricemia while significant decrease was observed in a comparison group. Conclusions: In patients with RAH and hyperuricemia one year after RFD of the renal artery along with identical hypotensive effect the significant reduction in GFR was observed. Moreover, no decrease in LVMMI was detected that might be caused by a latent kidney disease providing additional factors for maintenance of AH.

Effects of δ-tocotrienol on ochratoxin A-induced nephrotoxicity in rats.

Ochratoxin A (OTA), is a natural contaminant of the food chain worldwide involved in the development of different type of cancers in animals and humans. Several studies suggested that oxidative damage might contribute to increase the cytotoxicity and carcinogenicity capabilities of OTA. The aim of this study was to evaluate the possible protective effect of δ-tocotrienol (Delta), a natural form of vitamin E, against OTA-induced nephrotoxicity. Male Sprague-Dawley rats were treated with OTA and/or Delta by gavage for 14 days. Our results shown that OTA treatment induced the increase of reactive oxigen species production correlated to a strong reduction of Glomerular Filtration Rate (GFR) and absoluted fluid reabsorption (Jv) with conseguent significant increase in blood pressure. Consistent, we noted in the kidney of rats treated with OTA, an increase in malondialdheyde and dihydroethidium production and a reduction of the activity of the catalase, superoxide dismutase, and glutathione peroxidase. Conversly, in the rat group subjected to the concomitant treatment OTA plus Delta, we observed the restored effect, compared the OTA treatment group, on blood pressure, GFR, Jv, and all activities of renal antioxidant enzymes. Finally, as far as concern the tissue damage induced by OTA and measured evaluating fibronectin protein levels, we observed that in OTA plus Delta group this effect is not restored. Our findings releval that a mechanism underlying the renal toxicity induced by OTA is the oxidative stress and provide a new rationale to use a Delta in order to protect, at least in part, against OTA-induced nephrotoxicity.

Vancomycin-Associated Acute Kidney Injury with a Steep Rise in Serum Creatinine

Background: Vancomycin-associated (VA) acute kidney injury (AKI) is being increasingly recognized. A distinct pattern of rapid rise in serum creatinine (sCr) during VA-AKI has occasionally been observed. However, such scenarios remain underreported. Methods: We conducted an online survey at the American Society of Nephrology Communities forum and reviewed publications of VA-AKI via PubMed or Google searching for cases of precipitous AKI (those with rise in sCr ≥1.5 mg/dL/day) attributable to vancomycin. Results: We identified 12 original cases compiled from 6 different hospitals and 4 published cases (n = 16; 38% women, age 43.5 ± 16 years, weight 108 ± 23 kg, body mass index 35 ± 7 kg/m²) of precipitous AKI observed shortly after large cumulative doses of VA (8.8 ± 5 g). The median steepest 24-h rise in sCr was 2.6 mg/dL (range 1.5–3.5 mg/dL) and the slope of the initial 48-h sCr rise was greater than that of a control AKI (non-VA, n = 48) group (2.03 ± 0.1 vs. 0.62 ± 0.0 mg/dL/day; p < 0.0001). The steep rise in sCr in the VA-AKI was not accompanied by anuria. Overt rhabdomyolysis was absent in all cases. Further, in 3 precipitous VA-AKI cases, simultaneous serum cystatin C values did not rise precipitously, suggesting that the reductions in glomerular filtration rate were overestimated by the sCr increase. Conclusions: VA-AKI can manifest with a precipitous rise in sCr shortly after a high cumulative dose of vancomycin. True toxic tubular injury overrepresented by the sCr rise is postulated.

Endothelial factors in the pathogenesis and treatment of chronic kidney disease Part I: General mechanisms: a joint consensus statement from the European Society of Hypertension Working Group on Endothelin and Endothelial Factors and The Japanese Society of Hypertension.

: Kidney damage is a common consequence of arterial hypertension, but is also a cause of atherogenesis. Dysfunction and/or harm of the endothelium in glomeruli and tubular interstitium damage the function of these structures and translates into dynamic changes of filtration fraction, with progressive reduction in glomerular filtration rate, expansion of extracellular fluid volume, abnormal ion balance, and hypoxia, ultimately leading to chronic kidney disease. Considering the key role played by endothelial dysfunction in chronic kidney disease, the Working Group on Endothelin and Endothelial Factors of the European Society of Hypertension and the Japanese Society of Hypertension have critically reviewed available knowledge on the mechanisms underlying endothelial cell injury. This resulted into two articles: in the first, we herein examine the mechanisms by which endothelial factors induce vascular remodeling and the role of different players, including endothelin-1, the renin-angiotensin-aldosterone system and their interactions, and of oxidative stress; in the second, we discuss the role of endothelial dysfunction in the major disease conditions that affect the kidney.

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

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

The dark side of the kidney in cardio-renal syndrome: renal venous hypertension and congestive kidney failure.

Renal involvement in some forms of acute or chronic diseases, such as heart failure or sepsis, presents with a complex pathophysiological basis that is not always clearly distinguishable. In these clinical settings, kidney failure is traditionally and almost exclusively attributed to renal hypoperfusion and it is commonly accepted that causal elements are pre-renal, such as a reduction in the ejection fraction or absolute or relative hypovolemia acting directly on oxygen transport mechanisms and renal autoregulation systems, causing a reduction of glomerular filtration rate. Nevertheless, the concept emerging from accumulating clinical and experimental evidence is that in complex clinical pictures, kidney failure is strongly linked to the hemodynamic alterations occurring in the renal venous micro and macrocirculation. Accordingly, the transmission of the increased venous pressure to the renal venous compartment and the consequent increasing renal afterload has a pivotal role in determining and sustaining the kidney damage. The aim of this review was to clarify the physiopathological aspects of the link between worsening renal function and renal venous hypertension, analyzing the prognostic and therapeutic implications of the so-called congestive kidney failure in cardio-renal syndrome and in other clinical contexts of its possible onset.

ASSESSMENT OF CARDIOVASCULAR RISK AND COMORBIDITY IN PATIENTS WITH CHRONIC KIDNEY DISEASE

High rates of morbidity and mortality in patients with chronic diseases of the kidney are for the most part caused by the high prevalence of cardiovascular diseases and high rates of fatal cardiovascular events. The aim of the study was to establish the prevalence and distribution of cardiovascular risk factors in patients with chronic kidney diseases, in various stages of chronic renal failure. The examinees were classified into three groups based on the level of glomerular filtration rate: over 60 ml/min/1.73m2; 30-59 ml/min/1.73m2; and 15-29 ml/ min/1.73m2. Traditional risk factors of age, hypertension, systolic blood pressure, glycemia, diabetes, serum level of total cholesterol and triglycerides, triglyceridemia, and hypertrophy of the left ventricle showed a significantly positive rising trend of their mean values or prevalence, inversely dependent upon the level of declining glomerular filtration rates. Mean values of serum HDL cholesterol level demonstrated a significant declining trend, concomitant with decreasing glomerular filtration rate. The prevalence of hypercholesterolemy, smoking and obesity, as well as the mean value of body mass index, showed significant intergroup variations, but without any continuing trend related to glomerular filtration rate. Non-traditional risk factors of anemia, proteinuria, and hypoalbuminemia showed a significant rising trend of prevalence inversely dependent upon the degree of reduction of glomerular filtration rate. The levels of hematocrit and serum albumins showed a positive correlation with the reduction of glomerular filtration rate. In pre-dialysis patients with chronic kidney diseases, a high prevalence of the studied cardiovascular risk factors was found. Cardiovascular risk progressively rises with decreasing glomerular filtration rate, being significantly elevated as early as the initial stages of renal failure.

Urinary N-acetyl-β-glucosaminidase and estimated Glomerular filtration rate may identify patients to be treated with immuno-suppression at diagnosis in idiopathic membranous nephropathy.

The clinical course of idiopathic membranous nephropathy (IMN) varies from spontaneous remission of nephrotic syndrome (NS) to end-stage renal disease (ESRD). The aim of the study was baseline identification of patients with high risk of progression for which immunosuppressive therapy is mandatory. Eighty-six IMN subjects were followed for a median of 69months (range 6-253). Receiver operating characteristic curve and Cox proportional hazards model were used to evaluate prognostic factors for progression, defined as ESRD or estimated glomerular filtration rate (eGFR) reduction ≥50% of baseline. Among all, 24 subjects had progression. Area under the ROC curve of N-acetyl-β-glucosaminidase/creatinine ratio (NAG/C) were significantly higher than proteinuria/24h (0.770 and 0.637 respectively, P = 0.018). In Cox proportional hazards regression analysis, NAG/C and eGFR were independent predictors of progression. Compared to lowest tertile of NAG/C (<9.4 UI/gC) or highest tertile of eGFR (≥88mL/min per 1.73m2 ), the multivariable-adjusted hazard ratio of highest tertile of NAG/C (≥19.2) was 18.97 (95%CI, 1.70-211.86) and lowest tertile of eGFR (<59) was 11.58 (95%CI, 2.02-66.29). Subjects with high NAG/C or low eGFR (high-risk, n=43) had greater progression rate compared to moderate to low NAG/C and high eGFR (low-risk, n=43) with or without NS at baseline (Log-rank test P = 0.001 and 0.006, respectively). In NS subjects (n=65), high-risk group progression rate was significantly higher (91% vs. 29%, P = 0.003) and remission rate significantly lower (0% vs. 42%, p<0.001) in non-immunosuppressed compared to steroids and cyclophosphamide treated patients; no significant differences were observed in low-risk group. Idiopathic membranous nephropathy subjects with high NAG/C and low eGFR have greater risk of progression, and immunosuppressive treatment is suggested at diagnosis.