Glibenclamide Effects on Renal Function and Histology after Acute Hemorrhage in Rats under Sevoflurane Anesthesia

Introduction. Hypovolemia from hemorrhage evokes protective compensatory reactions, such as the renin-angiotensin system, which interferes in the clearance function and can lead to ischemia. This study was designed to evaluate the effects of glibenclamide, a K⁺_ATP channel blocker, on renal function and histology in rats in a state of hemorrhagic shock under sevoflurane anesthesia. Material and Methods. Twenty Wistar rats were randomized into two groups of 10 animals each (G1 and G2), only one of which (G2) received intravenous glibenclamide (1 μg.g^?1), 60 min before bleeding was begun. Both groups were anesthetized with sevoflurane and kept on spontaneous respiration with oxygen-air, while being bled of 30% of volemia in three stages with 10 min intervals. There was an evaluation of renal function—sodium para-aminohippurate and iothalamate clearances, filtration fraction, renal blood flow, renal vascular resistance—and renal histology. Renal function attributes were evaluated at three moments: M1 and M2, coinciding with the first and third stages of bleeding; and M3, 30 min after M2, when the animals were subjected to bilateral nephrectomy before being sacrificed. Results. Significant differences were found in para-aminohippurate clearance, G1 < G2, and higher renal vascular resistance values were observed in G1. Histological examination showed the greater vulnerability of kidneys exposed to sevoflurane alone (G1) with higher scores of vascular and tubular dilatation. There were vascular congestion and tubular vacuolization only in G1. Necrosis and signs of tubular regeneration did not differ in both groups. Conclusion. Treatment with glibenclamide attenuated acutely the renal histological changes after hemorrhage in rats under sevoflurane anesthesia.     

Analysis of gene mutations in PKD1/PKD2 by multiplex ligation-dependent probe amplification: some new findings

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is a serious genetic disorder that can lead to chronic renal disease. Protein dysfunction caused by mutations in the genes polycystic kidney disease 1 (PKD1) and polycystic kidney disease 2 (PKD2) is an important factor in the pathogenesis of ADPKD. In the present study, 30 Chinese patients with confirmed diagnosis of ADPKD, based on ultrasound or computerized tomography (CT) findings were selected, and the exon copy numbers of PKD1 and PKD2 were determined using multiplex ligation-dependent probe amplification (MLPA). MLPA identified exon deletion in 1 case, suspected exon deletion in 4 cases, and suspected duplications in 3 cases. One case of suspected exon deletion was confirmed using quantitative real-time polymerase chain reaction (q-PCR) and sequencing (PKD2 exon 8). A missense mutation was observed in 1 case of exon deletion using q-PCR and sequencing (PKD1 exon 40, c.11333 C>A). The cases of suspected duplications were verified by q-PCR, and the copy number of exon 6 of PKD1 in 1 case of suspected duplication was 3.8 times greater than that in normal controls. Our findings provide new insights into ADPKD screening and mark a possibly meaningful step toward improved diagnosis and treatment of patients with ADPKD.     

Clinical Spectrum of Renal Disorders in Patients with Cirrhosis of Liver

Background: There are limited studies describing various renal disorders and their prognostic impact in patients with cirrhosis of liver. The aim of this work was to study the clinical spectrum of renal disorders in patients with cirrhosis of liver and their prognostic impact. Methods: Patients with diagnosis of cirrhosis of liver were included in this study. Cirrhosis was diagnosed using standard clinical criteria. The cirrhotic patients were prospectively analyzed for the presence of renal diseases during the study period from January 2008 to April 2009. Results: Four hundred and four patients were included in this study and renal diseases were present in 44% (n = 178) patients. The spectrum of renal diseases were acute kidney injury (AKI; 24.5%), chronic kidney disease (CKD; 15.6%), acute on chronic renal failure (1.5%), nephritic syndrome (1.5%), and nephrotic syndrome (1%). The types of AKI were acute tubular necrosis (ATN; 44.4%), prerenal failure (36.4%), and hepatorenal syndrome (19.2%). The incidence of renal diseases was 15.7% in class A, 50% in class B, and 54.8% in class C cirrhosis. There was significant increase in mortality in patients with class C cirrhosis versus without renal disease (78.1% vs. 53.2%; p < 0.001). Conclusions: Renal diseases were present in a significant proportion (44%) of cirrhotic patients. ATN was the commonest form of AKI and we noted that the prevalence of CKD was 15.6% in our cirrhotic patients. The incidence of renal disease increased with increase in severity of cirrhosis of liver. The presence of renal disease seems to have adverse prognostic impact on class C cirrhosis.     

Determination of Rituximab Dose According to Immunologic Risk in ABO-Incompatible Kidney Transplantation

The adequate rituximab (RTX) dosage in ABO-incompatible transplantation (ABO-IKT) remains undetermined. We used two kinds of RTX dosage groups [low RTX (100 mg/m²) and typical RTX (375 mg/m²) dosage groups] according to immunologic risks and investigated the change of B-cell, anti-ABO antibodies, and the clinical outcome in ABO-IKT according to the RTX dose. Fifteen patients with high immunologic risk [panel reactive antibody (PRA) > 50%, retransplant, AB to O transplant] were assigned to typical RTX group and 17 patients without risk were assigned to low RTX group. We compared the changes of B-cell, anti-ABO antibody titer, required number of plasmapheresis (PP), and the clinical outcome after transplantation between the two groups. After infusion of RTX, peripheral blood B-cell counts were successfully depleted to <1% in both groups. Before kidney transplantation (KT), the minimal number of PP to achieve the target titer (1:16) (2.6 ± 2.7 vs. 2.2 ± 2.5; p = 0.66) and the titer reduction rate of anti-ABO antibodies did not differ between the two groups (low RTX: 1.52 ± 1.21 vs. typical RTX: 1.53 ± 1.20, p = 0.94). After KT, anti-ABO antibody titer was suppressed less than 1:32 in both groups up to posttransplant 1 year. The allograft function and infectious complication did not differ between the two groups as well. In ABO-IKT, low RTX is comparable with typical RTX dosing with respect to B-cell depletion, antibody rebound suppression, the effect on clinical outcome in patients with low immunologic risk.     

Effect of Dexmedetomidine on Ischemia-Reperfusion Injury in Rat Kidney: A Histopathologic Study

Ischemia-reperfusion (I-R) injury remains the leading cause of acute renal failure. The purpose of this experimental study was to determine the role of dexmedetomidine on histologic alterations induced by renal I-R in rats. In the present study, thirty male Sprague-Dawley rats weighing 200–220 g were randomly assigned into three groups: the sham-control group (group 1, n?=?10), the R/untreated group (group 2, n?=?10), and the I-R/dexmedetomidine-treated group (group 3, n?=?10). For group one, we performed a sham operation. The abdomen was dissected, the right kidney was harvested, and then the left renal pedicle exposed. Renal clamping was not applied. For group 2, rats underwent left renal ischemia for 60 minutes followed by reperfusion for 45 minutes. For group 3, the same surgical procedure as in group 2 was performed, and dexmedetomidine (100 μg/kg, intraperitoneal) was administrated at the starting time of reperfusion. The rats were sacrificed after reperfusion, and the kidney tissue was harvested. The histopathological score in the kidney of the I-R/dexmedetomidine-treated group rats was significantly lower than that of I-R/untreated group rats. This score in I-R/untreated group rats was higher than the other two groups, which was statistically significant. In the I-R/untreated group rats, kidneys of untreated ischemia rats showed tubular cell swelling, cellular vacuolization, pyknotic nuclei, medullary congestion, and moderate to severe necrosis. Treatment with dexmedetomidine shows normal glomeruli and slight edema of the tubular cells. These findings provide the first evidence that dexmedetomidine can reduce the renal injury caused by I-R of the kidney, and may be useful in enhancing the tolerance of the kidney against renal injury.     

A Mildly Altered Vascular Homeostasis in Early Stage of CKD

Background. A continuous increase in number of CKD patients entering ESRD is a growing public health threat, which reflects the present therapeutic failure usually initiating at the late stage of CKD. Objective. To study the mechanism of vascular repair in CKD patients associated with mildly impaired renal function, which included angiogenic factors such as VEFG, angiopoietin-1, and flt-1 (VEGFR1); and antiangiogenic factors such as angiopoietin-2 and KDR (VEGFR2). Results. A mild defect in angiogenic factor—namely, angiopoietin-1—was observed, whereas VEGF and flt-1 (VEGFR1) were within normal limit. Also, antiangiogenic factor—namely, angiopoietin-2—was mildly elevated, whereas KDR (VEGFR2) remained within normal limit. Conclusion. The mechanism of vascular repair appears to be adequately functional in the early stage of CKD. Therapeutic intervention at this stage can improve renal perfusion and restore renal function as indicated in normoalbuminuric, type 2 diabetic nephropathy. The authors encourage changing the conceptual view of treatment under common treatment at late stage of CKD to treatment at early stage of CKD under an environment favorable for renal regeneration.     

Progression of Kidney Damage in Balkan Endemic Nephropathy: A 15-Year Follow-Up of Patients with Kidney Biopsy Examination

Progression of kidney damage was studied in 18 patients with Balkan endemic nephropathy (BEN), with a mean 15-year follow-up after renal biopsy. According to kidney function, estimated by ^99mTc-DTPA clearance, patients were divided into three groups: with apparently normal kidney function (clearance 103.5 ± 21.3 mL/min/1.73 m²), with incipient renal failure (clearance 65.5 ± 11.3), and with advanced renal failure (clearance 28.0 ± 6.2). The mean yearly decrease of glomerular filtration rate was 2.74 mL/min. In two patients, an increase of kidney function was recorded. Six patients become dialysis dependent, two from the group with incipient renal failure, but all four from the group with advanced renal failure. Three patients died after 8 to 12 years of follow-up, one from causes unrelated to kidney disease and two from end-stage renal failure. This study has shown that BEN is characterized by a slow course and prolonged evolution, modified by medical supervision and treatment.     

Health-Related Quality of Life and Dialysis Dependence in Critically Ill Patient Survivors of Acute Kidney Injury

Background: Acute kidney injury is a common disorder in critical ill patients and it is associated with high mortality. Few studies focus on long-term perspectives such as health-related quality of life (HRQOL) and dialysis dependence. Methods: Prospective cohort study at the intensive care unit (ICU) of a Brazilian tertiary hospital. All patients requiring dialysis over a 2-year enrollment period were included. The Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) assessed the HRQOL along with patient status and dialysis dependence. Results: 408 patients (11%) required dialysis. ICU, hospital, and after-hospital cumulative fatality rates were 70%, 74%, and 80%, respectively. A total of 68 of 82 eligible patients were interviewed in an average of 256 days after hospital discharge, while 8 patients (11.8%) were in regular dialysis. There was no association between Acute Physiology and Chronic Health Evaluation II score, use of vasopressors, mechanical ventilation, creatinine, number of dialysis, and SF-36 scores. Better HRQOL was associated with previous conditions, as younger age and no chronic kidney disease; condition related to severity of acute illness, as have not had sepsis, short period at ICU, and hospital; and conditions after discharge, considered working currently. Conclusions: Previous chronic kidney disease was strongly associated with permanence in dialysis and lower further HRQOL. Younger survivors who have not had sepsis or long stays at hospitals, able to return to their jobs, had better HRQOL.     

An unusual case of reversible acute kidney injury due to chlorine dioxide poisoning

Abstract

Chlorine dioxide is a commonly used water disinfectant. Toxicity of chlorine dioxide and its metabolites is rare. In experimental studies, it was shown that acute and chronic toxicity were associated with insignificant hematological changes. Acute kidney injury due to chlorine dioxide was not reported. Two cases of renal toxicity due to its metabolites, chlorate and chlorite were reported. Herein, we report a case of chlorine dioxide poisoning presenting with acute kidney injury.