ISRN nephrology最新文献

Acute kidney injury (AKI) is a common complication in cirrhotic patients. Serum creatinine is a poor biomarker for detection of renal impairment in cirrhotic patients. This study aimed to evaluate urinary neutrophil gelatinase-associated lipocalin (NGAL) and urinary interleukin-18 (IL-18) as early biomarkers of acute kidney injury in cirrhotic patients. 160 patients with cirrhosis admitted to the Liver Units at Zagazig University Hospitals were classified into three groups: (I) nonascitic patients, (II) ascitic patients without renal impairment, and (III) ascitic patients with renal impairment. Patients with renal impairment were further divided into four subgroups: [A] prerenal azotemia, [B] chronic kidney disease (CKD), [C] hepatorenal syndrome (HRS), and [D] acute tubular necrosis (ATN). Significant elevation of both urinary NGAL and urinary IL-18 in cirrhotic patients with renal impairment especially in patients with ATN was observed. Urinary NGAL and urinary IL-18 have the ability to differentiate between AKI types in patients with cirrhosis. This could improve risk stratification for patients admitted to the hospital with cirrhosis, perhaps leading to early ICU admission, transplant evaluation, and prompt initiation of HRS therapy and early management of AKI.

Background. Cisplatin (CDDP) is an anticancer drug, which is accompanied with major side effects including nephrotoxicity. We tested two doses of losartan (10 and 20 mg/kg/day) against nephrotoxicity in a rat model treated with daily administration of CDDP (2.5 mg/kg/day). Methods. Five groups of rats were examined. Groups 1 and 2 received losartan 10 and 20 mg/kg/day, i.p, for a period of 10 days. Group 3 received saline for 10 days, but from day 3 the animals received CDDP (2.5 mg/kg/day, i.p) for the next seven days. Groups 4 and 5 received treatment regimen the same as groups 1 and 2, but from day 3 they also received CDDP for the next seven days. At the end of the experiment, blood samples were obtained and the kidneys were removed to undergo pathological investigation and to obtain supernatant from homogenized tissue. Results. CDDP induced nephrotoxicity, but the serum levels of creatinine and blood urea nitrogen were not attenuated by losartan. The pathological findings confirmed that losartan did not have nephroprotective effect in this experimental model. Conclusion. According to the findings, losartan could not improve renal function impaired by toxicity induced by continuous doses of CDDP, and also it worsened the renal failure.

Oxidative stress is associated with increased risk of cardiovascular disease in end-stage renal disease (ESRD) patients. Intravenous (IV) iron has been shown to increase oxidative stress. The aim of the study was to evaluate changes in oxidative stress markers following administration of IV sodium ferric gluconate (SFG) to ESRD patients with and without administration of the antioxidant, α -lipoic acid. This is an open-label, crossover study. 125 mg of IV SFG was administered during control (C) and intervention (I) visits. During the I visit, 600 mg of α -lipoic acid was given orally prior to IV SFG. Blood samples were collected at defined time periods for F2-isoprostane (FIP), lipid hydroperoxide (LHP), malondialdehyde (MDA), and iron indices. We recruited ten African-American ESRD subjects: 50% male; mean age 45 ± 9 years; mean hemoglobin 13 ± 1 g/dL; ferritin 449 ± 145 ng/mL; transferrin saturation 27 ± 4%. There were no significant differences in iron indices between the two visits after IV SFG. MDA, FIP, and LHP increased significantly for both C and I visits with a greater increase in the I group. Administration of IV SFG results in an acute rise in oxidative stress in ESRD patients. In contrast to previous studies, administration of α -lipoic acid was associated with a greater increase in oxidative stress.

Delayed graft function (DGF) of kidney transplants increases risk of rejection. We aimed to assess the utility of weekly biopsies during DGF in the setting of currently used immunosuppression and identify variables associated with rejection during DGF. We reviewed all kidney transplants at our institution between January 2008 and December 2011. All patients received rabbit antithymocyte globulin/Thymoglobulin (ATG) or Basiliximab/Simulect induction with maintenance tacrolimus + mycophenolate + corticosteroid therapy. Patients undergoing at least one weekly biopsy during DGF comprised the study group. Eighty-three/420 (19.8%) recipients during this period experienced DGF lasting ≥1 week and underwent weekly biopsies until DGF resolved. Biopsy revealed significant rejection only in 4/83 patients (4.8%) (one Banff 1-A and two Banff 2-A cellular rejections, and one acute humoral rejection). Six other/83 patients (7.2%) had Banff-borderline rejection of uncertain clinical significance. Four variables (ATG versus Basiliximab induction, patient age, panel reactive anti-HLA antibody level at transplantation, and living versus deceased donor transplants) were statistically significantly different between patients with and without rejection, though the clinical significance of these differences is questionable given the low incidence of rejection. Conclusions. Under current immunosuppression regimens, rejection during DGF is uncommon and the utility of serial biopsies during DGF is limited.

Background. Precise estimation of the glomerular filtration rate (GFR) and the identification of markers of progression are important. We compared creatinine, cystatin, and combined CKD-EPI equations with (99m)Tc-DTPA scintigraphy to measure GFR and proteinuria as markers of progression. Methods. Cross-sectional, observational study including 300 subjects. CKD was classified by (99m)Tc-DTPA scintigraphy. Determinations. Creatinine, 24-hour creatinine clearance, cystatin, Hoek formula, and creatinine, cystatin, and combined CKD-EPI equations. Results. In the global assessment, creatinine CKD-EPI and combined CKD-EPI equations yielded the highest correlations with (99m)Tc-DTPA: ρ = 0.839, P < 0.0001 and ρ = 0.831, P < 0.0001. Intergroup analysis versus (99m)Tc-DTPA: control G, creatinine clearance ρ = 0.414, P = 0.013; G3, combined CKD-EPI ρ = 0.5317, P < 0.0001; G4, Hoek ρ = 0.618, P < 0.0001, combined CKD-EPI ρ = 0.4638, P < 0.0001; and G5, creatinine clearance ρ = 0.5414, P < 0.0001, combined CKD-EPI ρ = 0.5288, P < 0.0001. In the global assessment, proteinuria displayed the highest significant correlations with cystatin ( ρ = 0.5433, P < 0.0001) and cystatin-based equations (Hoek: ρ = -0.5309, P < 0.0001). When GFR < 60 mL/min: in stage 3, proteinuria-cystatin ( ρ = 0.4341, P < 0.0001); proteinuria-Hoek ( ρ = -0.4105, P < 0.0001); in stage 4, proteinuria-cystatin ( ρ = 0.4877, P < 0.0001); proteinuria-Hoek ( ρ = -0.4877, P = 0.0026). Conclusions. At every stage of GFR < 60 mL/min, cystatin-based equations displayed better correlations with (99m)Tc-DTPA. Proteinuria and cystatin-based equations showed strong associations and high degrees of correlation.

Virtually, all studies reporting the outcomes of living kidney donation beyond the first year from donation were retrospective. In this prospective study, the outcome of 81 consecutive living kidney donors was thoroughly evaluated. Clinical, laboratory, and radiological assessments were carried out at predonation (basal), 3, 6, 12, and 24 months after donation. The mean age at time of donation was 37.8 ± 9.8 years and the majority was females (75.3%). The mean BMI increased significantly after donation (P < 0.04). The mean serum creatinine levels (mg/dl) were 0.75 ± 0.14, 1.01 ± 0.22, 0.99 ± 0.21, 0.98 ± 0.20, and 0.94 ± 0.20 (P < 0.0001). Likewise, the mean levels of measured creatinine clearance (mL/min) were 148.8 ± 35.7, 94.7 ± 26.6, 95.5 ± 24.6, 96.7 ± 20.2, and 101.6 ± 26.2 (P < 0.0001). The mean 24 hours urinary protein excretion (gm/dL) were 0.09 ± 0.03, 0.19 ± 0.18, 0.16 ± 0.09, 0.18 ± 0.25, and 0.17 ± 0.12 (P < 0.0001). There were significant increases in the means of the longitudinal and transverse diameters of the remaining kidney over time (P < 0.001). Out of 42 female donors, eleven female donors have got successful postdonation pregnancies. There were no reported surgical complications, either intra- or postoperative. Long-term follow-up is necessary for all living kidney donors through local institutional and world registries. This trial is registered with ClinicalTrials.gov NCT00813579.

Glomerular mesangial cells (MC), like most cell types secrete hyaluronan (HA), which attached to the cell surface via CD44, is the backbone of a hydrophilic gel matrix around these cells. Reduced extracellular matrix thickness and viscosity result from HA cleavage during inflammation. HA fragments were reported to trigger innate immunity via Toll-like receptor-(TLR-) 2 and/or TLR4 in immune cells. We questioned whether HA fragments also regulate the immunostimulatory capacity of smooth muscle cell-like MC. LPS (TLR4-ligand) and PAM3CysSK4 (TLR2-ligand) induced IL-6 secretion in MC; highly purified endotoxin-free HA < 3000 Da up to 50  μ g/mL did not. Bovine-testis-hyaluronidase from was used to digest MC-HA into HA fragments of different size directly in the cell culture. Resultant HA fragments did not activate TLR4-deficient MC, while TLR2-deficient MC responded to LPS-contamination of hyaluronidase, not to produced HA fragments. Hyaluronidase increased the stimulatory effect of TLR2-/-3/-5 ligands on their TLR-receptors in TLR4-deficient MC, excluding any effect by LPS-contamination. Supplemented heparin suppressed every stimulatory effect in a dose-dependent manner. We conclude that the glycosaminoglycan HA creates a pericellular jelly barrier, which covers surface receptors like the TLRs. Barrier-thickness and viscosity balanced by HA-synthesis and degradation and the amount of HA-receptors on the cell surface regulate innate immunity via the accessibility of the receptors.

Introduction. Cystatin C has been used in the critical care setting to evaluate renal function. Nevertheless, it has also been found to correlate with mortality, but it is not clear whether this association is due to acute kidney injury (AKI) or to other mechanism. Objective. To evaluate whether serum cystatin C at intensive care unit (ICU) entry predicts AKI and mortality in elderly patients. Materials and Methods. It was a prospective study of ICU elderly patients without AKI at admission. We evaluated 400 patients based on normality for serum cystatin C at ICU entry, of whom 234 (58%) were selected and 45 (19%) developed AKI. Results. We observed that higher serum levels of cystatin C did not predict AKI (1.05 ± 0.48 versus 0.94 ± 0.36 mg/L; P = 0.1). However, it was an independent predictor of mortality, H.R. = 6.16 (95% CI 1.46-26.00; P = 0.01), in contrast with AKI, which was not associated with death. In the ROC curves, cystatin C also provided a moderate and significant area (0.67; P = 0.03) compared to AKI (0.47; P = 0.6) to detect death. Conclusion. We demonstrated that higher cystatin C levels are an independent predictor of mortality in ICU elderly patients and may be used as a marker of poor prognosis.

The aim of this study was to assess removal dynamics of paracetamol (PAR), as an extraordinary chromophore in spent dialysate, upon the optical monitoring of dialysis of end-stage renal disease patients with inflammation complications. Seven dialysis sessions of different patients were followed to whom PAR was used as a pain reliever or antipyretic. Spent dialysate was sampled hourly and analyzed using HPLC with MS/MS and UV detection. Quantitative calculations were made on the basis of the peak areas on the chromatograms at 280 nm for uric acid (UA) and 254 nm for PAR and its metabolites (PAR-M). Peaks of UA, PAR, PAR-glucuronide, and PAR-sulphate were identified on the basis of specific mass spectra. Removal of PAR was found to be proportional to that of uric acid if intake of the drug by patient occurred half a day before dialysis. But disturbances of the UV-absorbance curves at 280 nm were observed related to rise of UA concentration in spent dialysate when PAR was taken by patients in the course of dialysis. The mechanism of such relation remains unknown. It was concluded that possible benefits and risks of treatment of uremic patients with paracetamol-containing drugs may need to be reassessed.

The novel roles of vitamin D were discovered and valued in this century. In addition to the maintenance of calcium and phosphorus balance, vitamin D regulates the function of the kidneys, heart, and immune system. Moreover, its anti-inflammatory, antiapoptotic, and antifibrotic roles have gained considerable attention. Vitamin D is also important for the maintenance of homeostasis by regulation of hormone secretion, cell proliferation, and differentiation. This paper will review these pleiotropic functions of vitamin D.