Ri-bao Wei

L-Carnitine supplementation for adults with end-stage kidney disease requiring maintenance hemodialysis: a systematic review and meta-analysis.

BACKGROUND A previous meta-analysis indicated that l-carnitine significantly increased hemoglobin and decreased the required erythropoietin dose in maintenance hemodialysis patients. OBJECTIVE An updated systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to reevaluate effects of l-carnitine. DESIGN The Cochrane Library, PubMed, and EMBASE databases (31 December 2012) were searched to identify RCTs that investigated effects of l-carnitine in adults with end-stage kidney disease that required maintenance hemodialysis. RESULTS Forty-nine RCTs (1734 participants) were included. l-Carnitine significantly decreased serum low-density lipoprotein (LDL) (mean difference: -5.82 mg/dL; 95% CI: -11.61, -0.04 mg/dL) and C-reactive protein (CRP) (-3.65 mg/L; -6.19, -1.12 mg/L). There were no significant differences in triglycerides (-0.89 mg/dL; -29.32, 27.53 mg/dL), cholesterol (0.14 mg/dL; -6.15, 6.42 mg/dL), high-density lipoprotein (1.13 mg/dL; -2.44, 4.70 mg/dL), hemoglobin (0.68 g/dL; 0.14, 1.50 g/dL), hematocrit (2.04%; -1.39, 5.48%), albumin (1.65 g/L; -0.22, 3.51 g/L), or the required erythropoietin dose (-0.76 KU/wk; -1.75, 0.23 KU/wk). No adverse effects were reported. CONCLUSIONS This meta-analysis failed to confirm the previous findings regarding the effects of l-carnitine on hemoglobin and the erythropoietin dose but showed that l-carnitine significantly decreased serum LDL and CRP. The extent of the decrease in LDL was not clinically relevant, whereas the significant decrease in CRP was both statistically and clinically relevant. However, the relevance of decrease in CRP with hard endpoints such as all-cause mortality and cardiovascular complications still remains to be clarified.

NAD Blocks High Glucose Induced Mesangial Hypertrophy via Activation of the Sirtuins-AMPK- mTOR Pathway

Background/aims-Since the discovery of NAD-dependent deacetylases, Sirtuins, it has been recognized that maintaining intracellular levels of NAD is crucial for the management of stress-response of cells. Here we show that high glucose(HG)-induced mesangial hypertrophy is associated with loss of intracellular levels of NAD. This study was designed to investigate the effect of NAD on HG-induced mesangial hypertrophy. Methods-The rat glomerular mesangial cells (MCs) were incubated in HG medium with or without NAD. Afterwards, NAD+/NADH ratio and enzyme activity of Sirtuins was determined. In addition, the expression analyses of AMPK-mTOR signaling were evaluated by Western blot analysis. Results-We showed that HG induced the NAD+/NADH ratio and the levels of SIRT1 and SIRT3 activity decreased as well as mesangial hypertrophy, but NAD was capable of maintaining intracellular NAD+/NADH ratio and levels of SIRT1 and SIRT3 activity as well as of blocking the HG-induced mesangial hypertrophy in vitro. Activating Sirtuins by NAD blocked the activation of pro-hypertrophic Akt signaling, and augmented the activity of the antihypertrophic AMPK signaling in MCs, which prevented the subsequent induction of mTOR-mediated protein synthesis. By AMPK knockdown, we showed it upregulated phosphorylation of mTOR. In such, the NAD inhibited HG-induced mesangial hypertrophy whereas NAD lost its inhibitory effect in the presence of AMPK siRNA. Conclusion-These results reveal a novel role of NAD as an inhibitor of mesangial hypertrophic signaling, and suggest that prevention of NAD depletion may be critical in the treatment of mesangial hypertrophy.

Meta-analysis of combined therapy for adult hepatitis B virus-associated glomerulonephritis

AIM To investigate the efficacy and safety of combined antiviral and immunosuppressant therapy in adult hepatitis B virus-associated glomerulonephritis (HBV-GN) patients. METHODS A computerized literature search was carried out in the PubMed database, Embase, the Cochrane Library, Chinese BioMedical Literature on disc, Chinese Medical Current Contents, Chinese National Knowledge Infrastructure, Wanfang and VIP (Chinese Technological Journal of Database) to collect articles between June 1980 and December 2010 on therapy with immunosuppressants, e.g., glucorticosteroids, mycophenolate mofetil and leflunomide, combined with antivirals, e.g., interferon, lamivudine, entecavir and adefovir dipivoxil, in adult HBV-GN patients. The primary outcomes were remission of proteinuria, clearance of HBV e-antigen, and elevation of serum albumin. The secondary outcomes were blood levels of alanine aminotransferase, serum creatinine, and HBV-DNA titer. Meta-analysis was performed using Review Manager 5.1. Fixed or random effect models were employed to combine the results after a heterogeneity test. The effects of the combined therapy were analyzed for different doses of glucorticosteroid and different types of HBV-GN. RESULTS Twelve clinical trials with 317 patients were included. A significantly higher incidence of HBV-GN was found in male patients (relative risk = 2.40, 95% CI: 1.98-2.93). Combined therapy reduced the proteinuria significantly with a mean difference of 4.19 (95% CI: 3.86-4.53) and increased the serum albumin concentration significantly with a mean difference of -11.95 (95% CI: -12.97-10.93) without significant alterations of liver function (mean difference: 4.62, 95% CI: -2.55-11.79) and renal function (mean difference: 10.29, 95% CI: 0.14-20.45). No significant activation of HBV-DNA replication occurred (mean difference: 0.12, 95% CI: -0.37-0.62). There was no significant difference between the high dose glucorticosteroid group and the low dose glucorticosteroid group in terms of proteinuria remission (P = 0.76) and between different pathological types of HBV-GN [membranous glomerulonephritis (MN) vs. mesangial proliferative glomerulonephritis, P = 0.68; MN vs membranoproliferative glomerulonephritis, P = 0.27]. CONCLUSION Combined antiviral and immunosuppressant therapy can improve the proteinuria in HBV-GN patients without altering HBV replication or damaging liver and renal functions.

Treatment of 5/6 nephrectomy rats with sulodexide： a novel therapy for chronic renal failure

AbstractAim:Sulodexide, a glycosaminoglycan, could reduce albuminuria in diabetic patients. The aim of this study was to determine whether sulodexide could be used to treat chronic kidney failure in rats.Methods:Sixty Wistar rats undergone 5/6 nephrectomy, then were randomly divided into 4 groups: the model group, sulodexide group (sulodexide 5 mg/kg per day, im), irbesartan group irbesartan (20 mg/kg per day, ig) and sulodexide plus irbesartan group. Another 12 rats were enrolled into the sham operation group. After the treatments for 4, 8 and 12 weeks, urinary protein and serum creatinine levels were measured. After 12 weeks, serum cholesterin and triglycerides levels were measured, and the degrees of glomerular sclerosis and renal tubulointerstitial fibrosis were scored. The expression of aminopeptidase P (JG-12) in the renal tissue was examined using immunohistochemical staining. The renal expressions of endothelial nitric oxide synthase (eNOS) and tissue type plasminogen activator (tPA) were detected with RT-PCR and Western blot.Results:Proteinuria was markedly attenuated in the sulodexide-treated groups. After 4 and 8 weeks only the sulodexide-treated groups showed significant reduction in serum creatinine; while after 12 weeks all the three treatment groups showed significant reduction in serum creatinine. Furthermore, all the three treatment groups showed significant reduction in the scores of glomerular sclerosis and tubulointerstitial fibrosis. The glomerular expression of JG-12 was increased in both the sulodexide group and the sulodexide plus irbesartan group, but not in the irbesartan group. The eNOS mRNA and protein expression was decreased and the tPA mRNA and protein expression was significantly increased in the model group compared with Sham group. Sulodexide, irbesartan, and their combination reversed the decrease of eNOS expression but increased the tPA expression much more compared with model group.Conclusion:Sulodexide was similar to irbesartan that can decrease proteinuria and attenuate renal lesions in 5/6 nephrectomy rats. The renal protection by sulodexide might be achieved via its impact on renal vascular endothelial cells.

Grape Seed Proanthocyanidin Extract Reduces Renal Ischemia/Reperfusion Injuries in Rats

Abstract: Activation of reactive oxygen species and inflammation are implicated in renal ischemia/reperfusion (I/R) injuries. This study investigated whether grape seed proanthocyanidin extract (GSPE) protects against renal I/R injury by its effect on reactive oxygen species and the inflammation pathway. Wistar rats were administered GSPE before renal ischemia, followed by reperfusion for 24 hours. Plasma concentrations of urea, creatinine and cystatin C were measured for renal dysfunction. Serum and tissue superoxide dismutase activity and glutathione peroxidase and malondialdehyde levels were measured. Renal sections were analyzed for histological grading of renal injury, and nuclear factor-ĸB activity was determined. GSPE significantly reduced increases in urea, creatinine and cystatin C; increased kidney superoxide dismutase activity and glutathione peroxidase levels and reduced malondialdehyde levels. GSPE reduced histological renal damage and nuclear factor-ĸB activity. These results suggest that GSPE reduces renal dysfunction and injury caused by renal I/R.

Clinical evaluation of serum cystatin C and creatinine in patients with chronic kidney disease: A meta-analysis

Objective Glomerular filtration rate (GFR) is an important indicator of renal function. This meta-analysis aimed to evaluate the diagnostic value of serum cystatin C (CysC) and serum creatinine (SCr) for estimating GFR in patients with chronic kidney disease. Methods Google Scholar, PubMed®, Cochrane Library and China National Knowledge Infrastructure databases were searched, to identify randomized controlled trials that determined the diagnostic value of CysC and SCr, for estimating GFR in patients with chronic kidney disease. Results The inclusion criteria were met by 17 studies (total number of patients with chronic kidney disease, 2521). Meta-analysis showed that when the diagnostic cut-off value of GFR was 80–90 ml/min/1.73 m2, the heterogeneity was modest for CysC (I2 = 48%, summary sensitivity [SEN] = 0.803, summary specificity [SPE] = 0.821), but there was no heterogeneity for SCr (I2 = 0.0%, SEN = 0.697, SPE = 0.787). Meta-analysis of the studies demonstrated a significant difference between patients with chronic kidney disease and controls, for CysC and SCr. Conclusions This meta-analysis demonstrated significant correlations between CysC, SCr and GFR. CysC was more sensitive, but less specific, than SCr for the estimation of GFR.

Clinical and pathological analysis of hepatitis B virus-related membranous nephropathy and idiopathic membranous nephropathy.

OBJECTIVE The Hepatitis B virus infection rate is high in the Chinese population. The implications of HBV infection are widely recognized, and membranous glomerulonephritis is the most common renal lesion associated with HBV infection. We compared the clinicopathologic features of 119 HBV-related membranous nephropathy (HBV-MN) and 143 idiopathic membranous nephropathy (IMN) patients to identify those factors that facilitate their discrimination. METHODS Cohort analysis of demographic information, clinical manifestations, laboratory parameters, renal pathology and prognostic features of the two groups. RESULTS Most HBV-MN patients were young or middle-aged; the onset age in the HBVMN group was younger than the IMN group (p < 0.05). A male predominance was found in both groups. And the two groups both presented with heavy proteinuria or nephrotic syndrome. In contrast to IMN patients, the HBV-MN group was presented with a high occurrence of microscopic hematuria (73.95 vs. 35.66%) and renal insufficiency (47.06 vs. 24.48%). Plasma complement C3 and C4 in HBV-MN patients were significantly lower than in IMN patients (p < 0.05). The hyperlipidemia was more severe in IMN patients (p < 0.05). The occurrences of segmental glomerular damage, mesangial cell proliferation and tubulointerstitial damage were more common in the HBV-MN group (p < 0.05). Immunofluorescence staining of polyclonal immunoglobulin and polytypic complement immunoglobulin were more frequent in the HBV-MN group. The followup data showed there were no statistic differences in the prognosis between HBV-MN and IMN. CONCLUSION HBV-MN patients commonly showed nephrotic syndrome accompanied with renal and hepatic dysfunction which was different from IMN patients. The primary pathological feature of HBVMN was atypical membranous nephropathy, which is usually associated with the inflammatory changes in HBV infection. The renal survival rates did not differ between HBVMN patients and IMN patients.

Grape seed extract enhances eNOS expression and NO production through regulating calcium-mediated AKT phosphorylation in H2O2-treated endothelium.

GSE (grape seed extract) has been shown to exhibit protective effects against cardiovascular events and atherosclerosis, although the underlying molecular mechanisms of action are unknown. Herein, we assessed the ability of GSE to enhance eNOS (endothelial nitric oxide synthase) expression and NO (nitric oxide) production in H2O2 (hydrogen peroxide)‐treated HUVECs (human umbilical vein endothelial cells). GSE enhanced eNOS expression and NO release in H2O2‐treated cells in a dose‐dependent manner. GSE inhibited intracellular ROS (reactive oxygen species) and reduced intracellular calcium in a dose‐dependent manner in H2O2‐treated cells, as shown by confocal microscopy. ROS was inhibited in cells pretreated with 5.0 μM GSE, 2.0 μM TG (thapsigargin) and 20.0 μM 2‐APB (2‐aminoethoxydiphenyl borate) instead of 0.25 μM extracellular calcium. In addition, GSE enhanced eNOS expression and reduced ROS production via increasing p‐AKT (AKT phosphorylation) with high extracellular calcium (13 mM). In conclusion, GSE protected against endothelial injury by up‐regulation of eNOS and NO expression via inhibiting InsP3Rs (inositol 1,4,5‐trisphosphate receptors)‐mediated intracellular excessive calcium release and by activating p‐AKT in endothelial cells.

Validation of a differential diagnostic model of diabetic nephropathy and non-diabetic renal diseases and the establishment of a new diagnostic model.

The aims of the present study were to validate the differential diagnostic model of diabetic nephropathy (DN) and non‐diabetic renal diseases (NDRD) established in 2003 and to establish a new diagnostic model suitable for the current clinical characteristics of DN.

Validation of a differential diagnostic model of diabetic nephropathy and non-diabetic renal diseases and the establishment of a new diagnostic model 糖尿病肾病和非糖尿病性肾脏疾病的鉴别诊断模型的验证及新模型的建立

The aims of the present study were to validate the differential diagnostic model of diabetic nephropathy (DN) and non‐diabetic renal diseases (NDRD) established in 2003 and to establish a new diagnostic model suitable for the current clinical characteristics of DN.