Cause Of Renal Failure Research Articles

Low Insulin-Like Growth Factor-1 Level in Obesity Nephropathy: A New Risk Factor?

IntroductionIGF-1 (insulin-like growth factor-1) is a hormone involved in cell growth and other important processes. In the kidney, IGF-1 has a stimulating effect, increasing the blood flow and glomerular filtration rate. Although many experimental animal studies regarding the role of IGF-1 in the kidney have been conducted, few human studies are available in the literature. Obesity is a cause of renal failure, and several glomerular lesions associated with obesity have been described. However, no studies regarding the levels of IGF-1 in morbidly obese patients with renal injury associated with obesity have been conducted.AimTo determine the serum IGF-1 concentrations in morbidly obese patients with normal renal function but with different types of early obesity-related glomerular lesions and to evaluate the possible relationship between IGF-1 and the presence of renal lesions.MethodsEighty morbidly obese patients with renal biopsy, including 11 patients with no evidence of renal lesion, 17 patients with single glomerulomegaly, 21 patients with single podocyte hypertrophy, 10 patients with glomerulomegaly and podocyte hypertrophy, 5 patients with focal segmental hyalinosis, and 16 patients with increased mesangial matrix and/or mesangial proliferation, participated in this study. Biological parameters, including serum IGF-1 concentrations with the standard deviation score for age (SDS-IGF-1), were determined for all patients.ResultsEighty patients (50 women and 30 men) with a mean BMI of 52.63 ± 8.71 and a mean age of 42.40 ± 9.45 years were included in this study. IGF-1, IGF-1 SDS and IGF-1BP3 levels according to the renal injury were compared (normal glomeruli: IGF-1 = 190.17 ± 72.46; glomerulomegaly: IGF-1 = 122.3 ± 50.05; podocyte hypertrophy: IGF-1 = 119.81 ± 60.34; focal segmental hyalinosis: IGF-1 170.98 ± 100.83, increased mesangial matrix and/or mesangial proliferation: IGF-1 117.73 ± 63.87). Statistically significant differences were observed between serum levels of IGF-1 and between the levels of SDS-IGF-1 by comparing the group without glomerular lesion with the group formed by patients with any type of glomerular injury. Logistic regression analysis was performed, with the dependent variable defined as the glomerular injury. In the multivariate analysis, only SDS-IGF-1 was associated with glomerular injury, and low levels of IGF-1 SDS were a risk factor for kidney injury.ConclusionsOur study demonstrates that low IGF-1 serum levels are associated with renal lesions in morbidly obese patients without overt clinical renal manifestations.

Stromal β-catenin overexpression contributes to the pathogenesis of renal dysplasia.

Renal dysplasia, the leading cause of renal failure in children, is characterized by disrupted branching of the collecting ducts and primitive tubules, with an expansion of the stroma, yet a role for the renal stroma in the genesis of renal dysplasia is not known. Here, we demonstrate that expression of β-catenin, a key transcriptional co-activator in renal development, is markedly increased in the expanded stroma in human dysplastic tissue. To understand its contribution to the genesis of renal dysplasia, we generated a mouse model that overexpresses β-catenin specifically in stromal progenitors, termed β-cat(GOF-S) . Histopathological analysis of β-cat(GOF) (-S) mice revealed a marked expansion of fibroblast cells surrounding primitive ducts and tubules, similar to defects observed in human dysplastic kidneys. Characterization of the renal stroma in β-cat(GOF) (-S) mice revealed altered stromal cell differentiation in the expanded renal stroma demonstrating that this is not renal stroma but instead a population of stroma-like cells. These cells overexpress ectopic Wnt4 and Bmp4, factors necessary for endothelial cell migration and blood vessel formation. Characterization of the renal vasculature demonstrated disrupted endothelial cell migration, organization, and vascular morphogenesis in β-cat(GOF) (-S) mice. Analysis of human dysplastic tissue demonstrated a remarkably similar phenotype to that observed in our mouse model, including altered stromal cell differentiation, ectopic Wnt4 expression in the stroma-like cells, and disrupted endothelial cell migration and vessel formation. Our findings demonstrate that the overexpression of β-catenin in stromal cells is sufficient to cause renal dysplasia. Further, the pathogenesis of renal dysplasia is one of disrupted stromal differentiation and vascular morphogenesis. Taken together, this study demonstrates for the first time the contribution of stromal β-catenin overexpression to the genesis of renal dysplasia. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Serum glomerular albumin permeability activity: association with rapid progression to end-stage renal disease in focal segmental glomerulosclerosis.

BackgroundFocal segmental glomerulosclerosis (FSGS) is a major cause of renal failure. Sera of some FSGS patients increase glomerular albumin permeability (Palb) during in vitro testing and cause proteinuria in experimental animals.ObjectivesTo determine whether permeability activity of FSGS serum (Palb activity) is associated with rate of progression to renal replacement therapy (RRT).DesignThis is an observational study based on medical and demographic information and Palb activity testing.SettingStudies were performed at Medical College of Wisconsin.PatientsSerum was submitted by patients’ nephrologists for measurement of Palb activity. Each patient had had a biopsy diagnosis of FSGS, had reached ESRD and was on dialysis or had a functioning transplant.MeasurementsPalb activity, clinical characteristics and time between biopsy diagnosis and RRT (T-RRT) were recorded for each patient.MethodsPalb activity was measured using established in vitro techniques.ResultsPalb and T-RRT were inversely correlated. Neither Palb nor T-RRT varied with demographics or medications. Kaplan–Meier survival curves showed that patients with Palb ≥ 0.5 progressed to RRT more rapidly than others.LimitationsOnly patients who had reached RRT were included. Limited clinical information was available for each patient. Central verification of biopsy characteristics was not performed and detailed descriptions of renal histology were not available.ConclusionsPalb activity is associated with the rate of progression to RRT in patients with FSGS. Additional observations will be needed to verify that Palb activity predicts prognosis and is useful in stratifying patients for clinical decision making or treatment trials.

Inpp5e suppresses polycystic kidney disease via inhibition of PI3K/Akt-dependent mTORC1 signaling.

Polycystic kidney disease (PKD) is a common cause of renal failure with few effective treatments. INPP5E is an inositol polyphosphate 5-phosphatase that dephosphorylates phosphoinositide 3-kinase (PI3K)-generated PI(3,4,5)P3 and is mutated in ciliopathy syndromes. Germline Inpp5e deletion is embryonically lethal, attributed to cilia stability defects, and is associated with polycystic kidneys. However, the molecular mechanisms responsible for PKD development upon Inpp5e loss remain unknown. Here, we show conditional inactivation of Inpp5e in mouse kidney epithelium results in severe PKD and renal failure, associated with a partial reduction in cilia number and hyperactivation of PI3K/Akt and downstream mammalian target of rapamycin complex 1 (mTORC1) signaling. Treatment with an mTORC1 inhibitor improved kidney morphology and function, but did not affect cilia number or length. Therefore, we identify Inpp5e as an essential inhibitor of the PI3K/Akt/mTORC1 signaling axis in renal epithelial cells, and demonstrate a critical role for Inpp5e-dependent mTORC1 regulation in PKD suppression.

Neonatal vascularization and oxygen tension regulate appropriate perinatal renal medulla/papilla maturation.

Congenital medullary dysplasia with obstructive nephropathy is a common congenital disorder observed in paediatric patients and represents the foremost cause of renal failure. However, the molecular processes regulating normal papillary outgrowth during the postnatal period are unclear. In this study, transcriptional profiling of the renal medulla across postnatal development revealed enrichment of non-canonical Wnt signalling, vascular development, and planar cell polarity genes, all of which may contribute to perinatal medulla/papilla maturation. These pathways were investigated in a model of papillary hypoplasia with functional obstruction, the Crim1(KST264/KST264) transgenic mouse. Postnatal elongation of the renal papilla via convergent extension was unaffected in the Crim1(KST264/KST264) hypoplastic renal papilla. In contrast, these mice displayed a disorganized papillary vascular network, tissue hypoxia, and elevated Vegfa expression. In addition, we demonstrate the involvement of accompanying systemic hypoxia arising from placental insufficiency, in appropriate papillary maturation. In conclusion, this study highlights the requirement for normal vascular development in collecting duct patterning, development of appropriate nephron architecture, and perinatal papillary maturation, such that disturbances contribute to obstructive nephropathy.

Prognostic value of kidney biopsy in myeloma cast nephropathy: a retrospective study of 70 patients.

BACKGROUND Light chain myeloma cast nephropathy (MCN) is the major cause of renal failure in multiple myeloma and strongly impacts patient survival. The role of kidney biopsy in the management of MCN is unclear. METHODS Renal pathological findings were retrospectively studied in 70 patients with multiple myeloma and MCN. Patients were categorized according to the achievement or not of renal response, as defined by estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m(2) and/or dialysis independence at 3 months. RESULTS Thirty-two patients (46%) achieved a renal response. In the whole study population, the following parameters differed significantly between patients with and without renal response, respectively: baseline median eGFR (13.3 versus 9.3 mL/min/1.73 m(2), P = 0.017), Acute Kidney Injury Network Stage 3 (68.8 versus 92.1%, P = 0.019), haematological response rate (94 versus 34%, P < 0.0001), median percentage of free light chain (FLC) reduction at Day 21 (92 versus 24%, P = 0.006) and median number of casts/10 fields (14 versus 25, P = 0.005). The extent of interstitial fibrosis and tubular atrophy was similar. In multivariate analysis, only FLC reduction at Day 21 was significantly associated with renal response. However, when considering only the subgroup of haematological responders, both median number of casts [odds ratio (OR) = 0.93, 95% confidence interval (95% CI): 0.88-0.98, P = 0.01] and extent of tubular atrophy (OR = 0.03, 95% CI: 0.00-0.52, P = 0.02) were independent predictors of renal response. CONCLUSIONS In MCN, the presence of numerous casts and diffuse tubular atrophy is associated with poor renal prognosis. These data suggest that additional strategies to reduce FLC burden should be considered in patients with extensive cast formation.

Is overhydration in peritoneal dialysis patients associated with cardiac mortality that might be reversible?

To study the relationship between overhydration (OH) in peritoneal dialysis (PD) patients and cardiac mortality. OH, as measured by body composition monitor (BCM), is associated with increased mortality in dialysis patients. BCM has been used to guide treatment on the assumption that correcting OH will improve cardiac morbidity and mortality although data demonstrating causality that is reversible is limited. We wished to determine if OH in PD patients predicted cardiac mortality, and if there was a correlation between OH and cardiac troponin-T (cTnT) levels. Finally, we wished to determine if improving OH values would lead to a decrement in cTnT. All prevalent PD patients over the study period of 57 mo who had contemporaneous BCM and cTnT measurements were followed irrespective of transplantation or PD technique failure. We also studied a cohort of patients with who had severe OH (> +2L). The Fresenius Body Composition Monitor was used to obtain hydration parameters. cTnT levels were done as part of routine clinical care. Data was analysed using SPSS version 20.0. There were 48 deaths in the 336 patients. The patients that died from cardiac or non-cardiac causes were similar with respect to their age, incidence of diabetes mellitus, gender, ethnicity and cause of renal failure. However, the patients with cardiac causes of death had significantly shorter dialysis vintage (10.3 mo vs 37.0 mo, P < 0.0001) and were significantly more overhydrated by BCM measurement (2.95 L vs 1.35 L, P < 0.05). The mean (standard error of the means) hydration status of the 336 patients was +1.15 (0.12) L and the median [interquartile range (IQR)] cTnT level was 43.5 (20-90) ng/L. The cTnT results were not normally distributed and were therefore transformed logarithmically. There was a statistically significant correlation between Log (cTnT) with the OH value (Spearman r value 0.425, P < 0.0001). We identified a sub-group of patients that were severely overhydrated; median (IQR) hydration at baseline was +2.7 (2.3 to 3.7) L. They were followed up for a minimum of 6 mo. Reduction in OH values in these patients over 6 mo correlated with lowering of cTnT levels (Spearman r value 0.29, P < 0.02). Patients that were overhydrated had higher cTnT, and had deaths that were more likely to be cardiac related. Reduction in OH correlated with lowering of cTnT.

Prevention Strategies of Contrast Medium Induced Nephropathy (CIN): A Review of the Current Literature

Contrast medium induced nephropathy is the third most common cause of renal failure for inpatients and represents the 10% of all acute kidney injury occurring during hospital-stay. It is associated with prolonged hospitalization, cost increase and, above all, an unfavourable short- and long-term prognosis. Here, the authors discuss about the contrast medium induced nephropathy prevention strategies, from the identification of patients at risk and drugs potentially nephrotoxic, to the hydration with possible administration of drugs that appeared to be, in some contexts, nephron-protective, and finally we analyze the radiological procedure aimed at the correct choice of type and administration modality of the contrast medium according to current literature.

Crystal-induced nephrotoxicity associated with acyclovir use in paediatric patient

Drug-induced nephrotoxicity has evolved as one of the significant causes of renal failure in the contemporary setting accounting up to 20%. Acyclovir is an antiviral agent, which has the potential for precipitating transient crystal-induced nephrotoxicity, especially in elderly, euvolemic or renal patients when given as rapid intravenous bolus. The current case depicts evolution and management of transient nephropathy in a paediatric patient treated with acyclovir for viral encephalopathy. The case presents a contrasting scenario to the conventional milieu of risk factors and surmises the possibility of genetic factor predisposition.

An Overview of Regular Dialysis Treatment in Japan (As of 31 December 2013).

A nationwide survey of 4325 dialysis facilities was conducted at the end of 2013, among which 4268 (98.7%) responded. The number of new dialysis patients was 38,095 in 2013. Since 2008, the number of new dialysis patients has remained almost the same without any marked increase or decrease. The number of dialysis patients who died in 2013 was 30,751. The dialysis patient population has been growing every year in Japan; it was 314,438 at the end of 2013. The number of dialysis patients per million at the end of 2013 was 2470. The crude death rate of dialysis patients in 2013 was 9.8%. The mean age of new dialysis patients was 68.7 years and the mean age of the entire dialysis patient population was 67.2 years. The most common primary cause of renal failure among new dialysis patients was diabetic nephropathy (43.8%). The actual number of new dialysis patients with diabetic nephropathy has almost been unchanged for the last few years. Diabetic nephropathy was also the most common primary disease among the entire dialysis patient population (37.6%), followed by chronic glomerulonephritis (32.4%). The percentage of dialysis patients with diabetic nephropathy has been increasing continuously, whereas the percentage of dialysis patients with chronic glomerulonephritis has been decreasing. The number of patients who underwent hemodiafiltration (HDF) at the end of 2013 was 31,371, a marked increase from that in 2012. This number is more than twice that at the end of 2011 and approximately 1.5 times the number at the end of 2012. In particular, the number of patients who underwent online HDF increased approximately fivefold over the last 2 years. Among 151,426 dialysis patients with primary causes of renal failure other than diabetic nephropathy, 10.8% had a history of diabetes. Among those with a history of diabetes, 26.8% used glycoalbumin as an indicator of blood glucose level; and 33.0 and 27.6% were administered insulin and dipeptidyl peptidase (DPP)-4 inhibitor, respectively, as a medication of diabetes. The facility survey showed that 9392 patients underwent peritoneal dialysis (PD). The patient survey revealed that 1920 of these PD patients also underwent another dialysis method using extracorporeal circulation, such as hemodialysis (HD) or HDF. The number of patients who underwent HD at home at the end of 2013 was 461, a marked increase from that at the end of 2012 (393).

Mapping murine diabetic kidney disease using chemical exchange saturation transfer MRI

Diabetic nephropathy (DN) is the leading cause of renal failure; however, current clinical tests are insufficient for assessing this disease. DN is associated with changes in renal metabolites, so we evaluated the utility of chemical exchange saturation transfer (CEST) imaging to detect changes characteristic of this disease. Sensitivity of CEST imaging at 7 Tesla to DN was evaluated by imaging diabetic mice [db/db, db/db endothelial nitric oxide synthase (eNOS)-/-] that show different levels of nephropathy as well as by longitudinal imaging (8 to 24 weeks). Nondiabetic (db/m) mice were used as controls. Compared with nondiabetic mice, the CEST contrasts of hydroxyl metabolites that correspond to glucose and glycogen were significantly increased in papilla (P), inner medulla (IM), and outer medulla (OM) in db/db and db/db eNOS-/- kidneys at 16 weeks. The db/db eNOS-/- mice that showed advanced nephropathy exhibited greater CEST effects in OM and significant CEST contrasts were also observed in cortex. Longitudinally, db/db mice exhibited progressive increases in hydroxyl signals in IM+P and OM from 12 to 24 weeks and an increase was also observed in cortex at 24 weeks. CEST MRI can be used to measure changes of hydroxyl metabolites in kidney during progression of DN. Magn Reson Med 76:1531-1541, 2016. © 2015 International Society for Magnetic Resonance in Medicine.

The risk for end-stage renal disease is increased after burn

ObjectiveAcute kidney injury (AKI) commonly complicates burn. Recently, AKI has been suggested to be causally related to chronic end-stage renal disease (ESRD), but controversial data also exist. Our aim was to study the risk of ESRD after burn in a nationwide analysis. MethodsAll burn patients undergoing hospitalization between 1998 and 2011 were identified from the National Hospital Discharge Register, and the data were linked with the Finnish Registry for Kidney Diseases, which includes all individuals receiving chronic renal replacement therapy (RRT) in Finland. ResultsAltogether 41,179 adults were treated at hospitals for burns in Finland between 1998 and 2011. Of these, 86 had a diagnosis of AKI related to the burn. Forty-three burn survivors had ESRD and RRT initiated related to or after the burn. The overall risk for ESRD after burn was increased (standardized incidence ratio, SIR, 2.40, 95% CI 1.73–3.23) compared with the Finnish population. Standardized incidence ratio was 3.11 (95% CI 1.66–5.32) in women and 1.89 (95% CI 1.27–2.69) in men. Of these 43 patients, 38 had a specific non-burn-related diagnosis of ESRD identified in the registry, and ESRD was deemed unlikely to be directly related to the burn. In five patients, the diagnosis of ESRD was unknown cause of renal failure, and causality of the burn with ESRD was evaluated as plausible. ConclusionIn conclusion, a significantly increased risk of ESRD was recorded after a severe burn. Our results do not support increased incidence of ESRD solely as a consequence of AKI due to burn, but burn may increase the risk of ESRD in patients with pre-existing chronic kidney disease.

Abstract 12014: Modified HASBLED Bleeding Risk Score in Dialysis Patients With Atrial Fibrillation

Introduction: Hemodialysis patients (HD pts) with atrial fibrillation (AF) have increased risk of stroke. The HASBLED (Hypertension (HTN), Abnl Renal/Liver Function, Stroke, Bleeding Hx, Labile INR, Elderly, Drugs/Alcohol) risk score predicts bleeding in the general AF population. It is unknown whether the HASBLED score can be applied to HD pts who are at additional bleeding risk due to uremic platelet dysfunction and the regular use of heparin. Hypothesis: To address this question, we queried the United States Renal Data System (USRDS) for bleeding events in HD pts with AF, and correlated those events with a modified HASBLED (mHASBLED) score. Methods: All incident HD pts with AF from the USRDS for 2006-2010 were queried for major bleeding events and mHASBLED parameters using ICD-9 diagnosis codes and data from CMS form 2728. For mHASBLED, the HTN parameter was defined as "HTN as the cause of renal failure", and labile INR as &gt; 16 INRs/yr, but all other parameters could be derived from the dataset. Logistic regression (LR) analysis was used to estimate the odds ratio (OR) for the mHASBLED score to predict major bleeding events. Results: 74,631 HD pts had AF, and 9.8% had a major bleeding event (GI bleeding and hemorrhagic stroke). By univariate analysis, those who bled were more likely to be elderly, have an underlying cause of renal disease due to HTN, prior bleeding event, hepatitis C, labile INR, and be on oral anticoagulants. By LR, variables with the greatest impact on bleeding were HTN as a cause of underlying renal disease, prior bleeding history, and labile INR (OR of 1.10, 2.20 and 2.24, respectively). The OR for bleeding events increased by 1.28 for each unit increase in mHASBLED. Older age, prior stroke, abnormal renal or liver function, and drug use had the least effect. Note that the lowest possible score in this cohort is 1, given that all patients had renal failure. Conclusions: In HD pts with AF, the mHASBLED predicts major bleeding events. The universal presence of renal disease, and the lack of specific clinical data from the USRDS may limit the clinical precision of a given score, however mHASBLED may remain a useful indicator of bleeding risk in this population.

Comparison of Intravenous and Oral Hydration in the Prevention of Contrast-Induced Acute Kidney Injury in Low-Risk Patients: A Randomized Trial

Aims: Contrast-induced acute kidney injury (CI-AKI) is a common cause of renal failure. We evaluated the effectiveness of oral sodium citrate versus intravenous (IV) sodium bicarbonate for CI-AKI prophylaxis as well as their influence on kidney injury biomarkers. Material and Methods: A randomized, controlled, single-center study including 130 hospitalized patients (62.3% men), who were randomized to receive sodium bicarbonate (1/6 men, 3 ml/kg/h for 1 h; n = 43), oral sodium citrate (75 ml/10 kg divided into 4 doses; n = 43) or nonspecific hydration (n = 44) before contrast administration, was conducted. Serum creatinine and kidney injury biomarkers (cystatin C, neutrophil gelatinase-associated lipocalin, interleukin-8, F2-isoprostanes and cardiotrophin-1 [CT-1]) were assessed. Results: Incidence of CI-AKI was 9.2% with no differences found between hydration groups: 7.0% in sodium bicarbonate group, 11.6% in oral sodium citrate group and 9.1% in the nonspecific hydration group. Urinary creatinine and urinary CT-1/creatinine ratio decreased 4 h after contrast infusion (p < 0.001), but none of the biomarkers assessed were affected by the treatments. Conclusions: There were no differences in hydration with oral sodium citrate and IV sodium bicarbonate for the prophylaxis of CI-AKI. Therefore, oral hydration represents a safe, inexpensive and practical method for preventing CI-AKI in low-risk patients. No effect on biomarkers for kidney injury could be demonstrated.

Prognostic value of kidney biopsy in myeloma cast nephropathy: a retrospective study of 70 patients.

Light chain myeloma cast nephropathy (MCN) is the major cause of renal failure in multiple myeloma and strongly impacts patient survival. The role of kidney biopsy in the management of MCN is unclear. Renal pathological findings were retrospectively studied in 70 patients with multiple myeloma and MCN. Patients were categorized according to the achievement or not of renal response, as defined by estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m(2) and/or dialysis independence at 3 months. Thirty-two patients (46%) achieved a renal response. In the whole study population, the following parameters differed significantly between patients with and without renal response, respectively: baseline median eGFR (13.3 versus 9.3 mL/min/1.73 m(2), P = 0.017), Acute Kidney Injury Network Stage 3 (68.8 versus 92.1%, P = 0.019), haematological response rate (94 versus 34%, P < 0.0001), median percentage of free light chain (FLC) reduction at Day 21 (92 versus 24%, P = 0.006) and median number of casts/10 fields (14 versus 25, P = 0.005). The extent of interstitial fibrosis and tubular atrophy was similar. In multivariate analysis, only FLC reduction at Day 21 was significantly associated with renal response. However, when considering only the subgroup of haematological responders, both median number of casts [odds ratio (OR) = 0.93, 95% confidence interval (95% CI): 0.88-0.98, P = 0.01] and extent of tubular atrophy (OR = 0.03, 95% CI: 0.00-0.52, P = 0.02) were independent predictors of renal response. In MCN, the presence of numerous casts and diffuse tubular atrophy is associated with poor renal prognosis. These data suggest that additional strategies to reduce FLC burden should be considered in patients with extensive cast formation.

Magnetic resonance microscopy of renal and biliary abnormalities in excised tissues from a mouse model of autosomal recessive polycystic kidney disease.

Polycystic kidney disease (PKD) is transmitted as either an autosomal dominant or recessive trait and is a major cause of renal failure and liver fibrosis. The cpk mouse model of autosomal recessive PKD (ARPKD) has been extensively characterized using standard histopathological techniques after euthanasia. In the current study, we sought to validate magnetic resonance microscopy (MRM) as a robust tool for assessing the ARPKD phenotype. We used MRM to evaluate the liver and kidney of wild-type and cpk animals at resolutions <100 μm and generated three-dimensional (3D) renderings for pathological evaluation. Our study demonstrates that MRM is an excellent method for evaluating the complex, 3D structural defects in this ARPKD mouse model. We found that MRM was equivalent to water displacement in assessing kidney volume. Additionally, using MRM we demonstrated for the first time that the cpk liver exhibits less extensive ductal arborization, that it was reduced in volume, and that the ductal volume was disproportionately smaller. Histopathology indicates that this is a consequence of bile duct malformation. With its reduced processing time, volumetric information, and 3D capabilities, MRM will be a useful tool for future in vivo and longitudinal studies of disease progression in ARPKD. In addition, MRM will provide a unique tool to determine whether the human disease shares the newly appreciated features of the murine biliary phenotype.

Diagnostik und Therapie des hepatorenalen Syndroms

Portal hypertension occurs frequently in advanced liver cirrhosis and accounts for the majority of lethal complications. Compensatory splanchnic vasodilation and counter regulatory mechanisms (e.g. activation of the renin-angiotensin-aldosterone system) increase renal vascular resistance, which may facilitate acute kidney injury and the development of hepatorenal syndrome (HRS). HRS represents a functional, yet reversible renal impairment with elevated serum creatinine levels. Establishing the diagnosis, fluid challenge test and several investigations are needed to exclude acute kidney injury and other causes of renal failure. Early treatment with albumin and vasoconstrictors improves the prognosis of HRS patients. The only curative treatment of HRS so far is improvement of liver function implying liver transplantation in many cases. TIPS placement may be useful as a bridging tool to transplantation unless hepatic encephalopathy is present. Spontaneous bacterial peritonitis (SBP) is a relevant, independent risk factor for HRS. In patients with liver cirrhosis and SBP in addition to antibiotics, preventive albumin treatment is recommended.

Profiling and initial validation of urinary microRNAs as biomarkers in IgA nephropathy.

Background. MicroRNAs (miRNAs) have been found in virtually all body fluids and used successfully as biomarkers for various diseases. Evidence indicates that miRNAs have important roles in IgA nephropathy (IgAN), a major cause of renal failure. In this study, we looked for differentially expressed miRNAs in IgAN and further evaluated the correlations between candidate miRNAs and the severity of IgAN.Methods. Microarray and RT-qRCR (real-time quantitative polymerase chain reaction) were sequentially used to screen and further verify miRNA expression profiles in urinary sediments of IgAN patients in two independent cohorts. The screening cohort consisted of 32 urine samples from 18 patients with IgAN, 4 patients with MN (membranous nephropathy), 4 patients with MCD (minimal changes disease) and 6 healthy subjects; the validation cohort consisted of 102 IgAN patients, 41 MN patients, 27 MCD patients and 34 healthy subjects. The renal pathological lesions of patients with IgAN were evaluated according to Lee’s grading system and Oxford classification.Results. At the screening phase, significance analysis of microarrays analysis showed that no miRNA was differentially expressed in the IgAN group compared to all control groups. But IgAN grade I–II and III subgroups (according to Lee’s grading system) shared dysregulation of two miRNAs (miR-3613-3p and miR-4668-5p). At the validation phase, RT-qPCR results showed that urinary level of miR-3613-3p was significantly lower in IgAN than that in MN, MCD and healthy controls (0.47, 0.44 and 0.24 folds, respectively, all P < 0.01 by Mann–Whitney U test); urinary level of miR-4668-5p was also significantly lower in IgAN than that in healthy controls (0.49 fold, P < 0.01). Significant correlations were found between urinary levels of miR-3613-3p with 24-hour urinary protein excretion (Spearman r = 0.50, P = 0.034), eGFR (estimated glomerular filtration rate) (r = − 0.48, P = 0.043) and Lee’s grades (r = 0.57, P = 0.014). Similarly, miR-4668-5p was significantly correlated with eGFR (r = − 0.50, P = 0.034) and Lee’s grades (r = 0.57, P = 0.013). For segmental glomerulosclerosis according to Oxford classification, patients scored as S0 had significantly lower levels of urinary miR-3613-3p and miR-4668-5p than those scored as S1 (0.41 and 0.43 folds, respectively, all P < 0.05).Conclusions. The expression profile of miRNAs was significantly altered in urinary sediments from patients with IgAN. Urinary expression of miR-3613-3p was down-regulated in patients with IgAN. Moreover, urinary levels of both miR-3613-3p and miR-4668-5p were correlated with disease severity. Further studies are needed to explore the roles of miR-3613-3p and miR-4668-5p in the pathogenesis and progression of IgA nephropathy.

Chemopreventive role of Coriandrum sativum against gentamicin-induced renal histopathological damage in rats.

Drug induced nephrotoxicity is one of the most common causes of renal failure. Gentamicin belongs to aminoglycosides, which elicit nephrotoxic potential. Natural antioxidants from plants demonstrate a number of biotherapeutic activities. Coriander is an important medicinal plant known for its hepatoprotective, diuretic, carminative, digestive and antihelminthic potential. This study was designed to investigate whether the extract of Coriandrum sativum ameliorates the nephrotoxicity induced by gentamicin in rats. Dried coriander powder was coarsely grinded and subjected to defatting by petroleum ether and further with ethyl acetate. The extract was filtered and subjected to phytochemical and phytoanalytical studies.Acute toxicity in Wistar rats was determined by the OECD Guideline (423). Animals were divided into four groups. The first group served as positive control, while the second group was toxic control (gentamicin treated). The third and fourth group were treated with the extract (200 and 400 mg/kg gentamicin). After 8 days, the animals were sacrificed and biochemical and histopathological studies were carried out. Phytochemical screening of the extract demonstrated Coriandrum sativum to be rich in flavonoids, polyphenolics and alkaloids. Results of acute toxicity suggested the use of 200 mg/kg and 400 mg/kg for Coriandrum sativum in the study. Coriandrum sativum extract at the dose of 400 mg/kg significantly (p<0.01) decreased creatinine levels in the animals, along with a decrease in serum urea and blood urea nitrogen. Treatment with Coriandrum sativum extract ameliorated renal histological lesions. It is concluded that Coriandrum sativum is a potential source of nephroprotective phytochemical activity, with flavonoids and polyphenols as the major components.

Late initiation of dialysis in diabetic Egyptian patients

The number of chronic kidney disease (CKD) patients has been increasing over the past two decades, both globally and in Egypt. In our current study we tried to identify the pattern of end-stage renal patients [chronic kidney disease stage 5 (CKD5)], who presented at a tertiary referral center (Cairo University Hospital, Kasr-Alainy School of Medicine), to identify the epidemiological characteristics, clinical presentation, hospital course, and outcome. This is a prospective analysis of all medical admissions through the emergency department (Department 6) of Kasr-Alainy School of Medicine, Cairo University, in 1 year from July 2010 to July 2011. We included patients with proven CKD 5 who needed to be started on renal replacement therapy. A total of 571 patients were identified, of whom 82 patients (36 males and 46 females) proved to have CKD5 and needed to be started on renal replacement therapy. The mean age of the included patients was 51.63 ± 14.7 years. Oliguria and vomiting were the most frequent symptoms, as seen in 52 cases (63.4%), followed by symptoms of volume overload in 24 patients (29.3%) and disturbed level of consciousness and fever in six patients (7.3%). Diabetic nephropathy was the most common cause of renal failure in our studied cohort (51.2%), followed by hypertension (22%); the cause was unknown in 25% of patients. Four patients (4.9%) died during their hospital stay. In conclusion, our study showed that there is delayed referral for nephrology care and delayed initiation of dialysis when patients presented through the emergency department. Of particular interest was the fact that diabetic patients were most often subjected to this practice.