Statins can benefit patients with primary membranous nephropathy on venous thromboembolism.

OBJECTIVE: The aim of this study was to investigate the role of prophylactic use of statin in venous thromboembolism (VTE) in patients with primary membranous nephropathy (PMN). METHODS: A total of 734 patients with PMN were consecutively enrolled in this retrospective study. 564 patients had received statins prescription, while 170 patients did not. Kaplan-Meier methods were used for cumulative incidence plots of thromboembolic events and Cox proportional hazards regression models were used to assess risk factors. Finally, the effects of different potency of statins were evaluated. RESULTS: In the cohort, 37 patients (5.0%) experienced VTE. In a univariate Cox proportional hazard model, the hazard ratio (HR) for VTE in statin users versus statin non-users was 0.5 (95% CI 0.3-0.8, p = .03). Multivariable model proportional-hazards analysis corrected for co-medications and risk factors revealed that adjusted HR was 0.4 (95% CI 0.1-0.7, p = .03). According to the type and dose, statin users were assigned into 3 groups: high-intensity group (n = 278), moderate-intensity group (n = 186), and low-intensity group (n = 49). In comparison, incidences of VTEs in the three groups were similar (2.9% vs 4.8% vs 2.0%, p = .45). CONCLUSIONS: The prophylactic use of statins could effectively decrease the occurrence of VTE in patients with PMN, and the benefits have no difference in different potency of statins.

The role of prophylactic use of low molecular weight heparin or aspirin in thromboembolic events in primary membranous nephropathy.

Objective: The aim of this study is to investigate the role of prophylactic anticoagulation regimens based on low molecular weight heparin (LMWH) or aspirin in thromboembolic events in patients with primary membranous nephropathy (PMN). Methods: A total of 717 patients with PMN were consecutively enrolled in this retrospective study. The propensity score matching method was utilized to adjust for the selection bias inherent in an analysis of outcomes, which was stratified by the anticoagulation prophylaxis regimen. Results: According to the anticoagulation prophylaxis regimen, patients were assigned into three groups: only LMWH therapy (L + A-, n = 53), only aspirin therapy (L - A+, n = 97), and no therapy of LMWH or aspirin (L - A-, n = 567). After performing 1:1 match, 37 patients were selected in the L + A - group and the L - A- group, respectively, and 94 patients were selected in the L - A+ group and the L - A- group, respectively. It showed that the prophylactic use of LMWH had no protective effects on arterial thromboembolic events (ATEs) (10.8% vs. 21.6%, p = .21) or venous thromboembolic events (VTEs) (8.1% vs. 10.8%, p = .69). The incidence of VTEs in the L - A+ group was lower than the L - A- group (2.1% vs. 10.6%, p = .02), while there were no significant differences in the incidences of ATEs between the L - A+ group and the L - A- group (5.3% vs. 7.4%, p = .55). Conclusions: The prophylactic use of LMWH showed no benefits on the incidence of ATEs or VTEs in patients with PMN. Aspirin effectively decreased the incidence of VTEs, without effects on the occurrence of ATEs.

A Cohort Study of Incidences and Risk Factors for Thromboembolic Events in Patients with Idiopathic Membranous Nephropathy.

Objective The aims of this study were to assess incidences and characteristics of arterial thromboembolic events (ATEs) and venous thromboembolic events (VTEs) in Chinese patients with idiopathic membranous nephropathy (IMN), and to identify the predisposing risk factors of them.Methods A total of 766 consecutive Chinese patients with IMN were enrolled in this retrospective cohort study. The cumulative incidences of newly diagnosed ATEs and VTEs were calculated using Kaplan-Meier methods. Univariable risk prediction model analysis followed by multivariable survival analysis was used to evaluate the potential risk factors of ATE and VTE.Results At 0.5, 1, 2, 3, and 5 years after biopsy diagnosis of IMN, the cumulative incidence of newly diagnosed ATEs were 4.3%, 5.7%, 6.3%, 7.1%, and 8.0%, and of newly diagnosed VTEs were 5.9%, 6.8%, 6.9%, 7.0%, and 7.2%, respectively. In 78 ATEs events (71 patients), cardiovascular diseases, thrombotic ischemic stroke (IS) and peripheral artery disease accounted for 50%, 45% and 5% respectively; in 60 VTEs events(53 patients), the deep vein thrombosis, renal vein thrombosis and pulmonary embolism accounted for 60%, 13% and 27% respectively. At the time of event, 42.1% patients with ATEs and 81.5% patients with VTEs were at nephrotic syndrome(NS) status (χ 2=18.1, P<0.001). Severe proteinuria, aging, smoking, hypertension and prior ATE history were associated with ATEs. Aging was demonstrated as the independent risk factor for ATEs (P=0.001), and hypoalbuminemia was the dominant independent risk factor for VTEs (P=0.03). Conclusions Patients with IMN have increased incidences of ATEs and VTEs, and most of events occurred within the first 6 months of the disease. IS was very common in ATEs in our cohort. Severe proteinuria and classic risk factors for atherosclerosis were associated with onset of ATEs. Hypoalbuminemia independently predicted VTEs. Risks of both ATEs and VTEs were particularly high in the status of NS, particularly VTEs.

Grape seed proanthocyanidins protect against streptozotocin­induced diabetic nephropathy by attenuating endoplasmic reticulum stress­induced apoptosis.

Diabetic nephropathy (DN) is by far the most common cause of end­stage renal disease (ESRD) in industrial countries, accounting for ~45% of all new ESRD cases in the United States. Grape seed proanthocyanidin extracts (GSPE) are powerful antioxidants, with an antioxidant ability 50­fold greater than that of vitamin E and 20­fold greater than that of vitamin C. The present study investigated whether GSPE can protect against streptozotocin (STZ)­induced DN and aimed to elucidate a possible mechanism. Male Sprague Dawley rats were randomly divided into three groups: Control group (N), diabetes mellitus group (DM) injected with 40 mg/kg STZ, and the GSPE treatment group (intragastric administration of 250 mg/kg/day GSPE for 16 weeks after diabetes was induced in the rats). Blood and kidney samples were collected after treatment. The renal pathological changes were determined with periodic acid­Schiff (PAS) staining, while the protein expression levels of glucose­regulated protein 78 (GRP78), phosphorylated­extracellular signal­regulated kinase (p­ERK) and Caspase­12 were determined by western blotting and immunohistochemical staining. Apoptosis was determined with a terminal deoxynucleotidyl transferase dUTP nick­end labeling (TUNEL) assay. Compared with the DM group, the GSPE group had no significant changes in the blood urea nitrogen (BUN) level and serum creatinine (Scr) level, but showed a significant decline in the renal index (RI) level and 24­h urinary albumin level (P<0.05). The histopathology results indicated very little pathological damage in the GSPE group. Compared with the DM group, the GSPE group had a significantly reduced number of TUNEL­positive cells (P<0.05), and the GSPE group had an obvious reduction in the protein expression of GRP78, p­ERK, and Caspase­12 (P<0.05). In this study, the results indicated that GSPE can protect renal function and attenuate endoplasmic reticulum stress­induced apoptosis via the Caspase­12 pathway in STZ­induced DN.

Therapy of Rituximab in Idiopathic Membranous Nephropathy with Nephrotic Syndrome: A Systematic Review and Meta-analysis.

Objective To investigate the efficacy and safety of rituximab (RTX) in the treatment of idiopathic membranous nephropathy (IMN) with nephrotic syndrome with a systematic review and meta-analysis. Methods PubMed, Embase, Cochrane Library and Clinical Trials (December 2016) were searched to identify researches investigating the treatment of RTX in adult patients with biopsy-proven IMN. Complete remission (CR) or partial remission was regarded as effective therapy, and the cumulated remission rate was calculated. Result Seven studies involved 120 patients (73% were men) were included in our systematic review and meta-analysis. All were prospective observation cohort studies or matched-cohort studies, mainly came from two medical centers, and one study was multi-centric (four nephrology units in northern Italy). The creatinine clearance was more than 20 ml/(min·1.73 m2) and persistent proteinuria higher than 3.5 g/d for at least 6 months. All patients received treatment previously [44 (36.7%) had immunosuppressive treatment]. In 12- and 24-month, 56% (95%CI, 0.47-0.65) and 68% (95%CI, 0.41-0.87) patients could reach remission, while 15% (95%CI, 0.09-0.23) and 20% (95%CI, 0.12-0.32) patients could reach CR. The reduction in proteinuria was gradual and obvious, paralleled with upward trend of serum albumin level and decreasing serum cholesterol level. Renal functions were stable. Relapses happened in 24 months were around 8%. RTX related adverse events were mild and were mostly infusion-related reactions. Conclusions RTX treatment in IMN was efficient, well tolerated and safe. More than 60% patients can reach partial remission or CR in 24 months, and relapse is rare. Adverse events of RTX are mostly infusion-related reactions and generally mild.

Efficacy and Safety of Tacrolimus versus Cyclosporine A for Idiopathic Membranous Nephropathy:A Network Meta-analysis.

Objective To compare the efficacy and safety of tacrolimus with those of cyclosporine in treating idiopathic membranous nephropathy (IMN) via network meta-analysis. Methods Databases including PubMed,Embase,CENTRAL (Cochrane),Wanfang Database,CNKI,and VIP citation database were searched for relevant studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Package Meta 4.5.0 and Gemtc 0.8.1 in R 3.3.1 were used to analyze the included studies. Results In this network meta-analysis,the complete remission rate (RR=0.98,95% CI:0.70-1.40)and the total remission rate (RR=1.00,95% CI:0.90-1.20)of idiopathic membranous nephropathy did not differ significantly between IMN patients treated with cyclosporine A or tacrolimusand,nor did the incidences of hepatic dysfunction(RR=1.40,95% CI:0.52-4.00),infection(RR=0.75,95% CI:0.18-3.10),or gastrointestinal syndrome(RR=2.1,95% CI:0.36-28.00). Conclusion Cyclosporine A seems to have similar effectiveness and safety to tacrolimus in treating IMN.

The Neglected Significance of Glomerular Density as a 5-year Progression Indicator for IgA Nephropathy△.

Objective To investigate whether glomerular density (GD) could be an independent prognostic factor for patients of IgA nephropathy with estimated glomerular filtration rate (eGFR) of 30 to 60 ml/min per 1.73 m2, or for patients with time-average proteinuria < 0.5 g/d. Methods A total of 173 patients with biopsy-confirmed IgA nephropathy diagnosed from January 2000 to December 2010 were included. All of these patients were followed up for more than 5 years. The endpoint was a > 30% of decline in eGFR from baseline after 5-year follow-up. The optimal cut-off value of GD was calculated by ROC curve. Kaplan-Meier method and Cox regression analysis was used for survival analysis. Results A 30% of decline in eGFR occurred in 14.5% of all patients. The optimal diagnostic cut-off value of GD was 1.99/mm2 (AUC = 0.90, sensitivity = 84.0%, specificity = 81.8%) determined by ROC curve. The low GD group (GD < 1.99 per mm2) experienced a significant increase in renal endpoint for patients with eGFR of 30 to 60 ml/min per 1.73 m2 (six patients in lower GD group, while one patient in the other group). For patients with time-average proteinuria < 0.5 g/d, the lower GD group showed a higher eGFR decline from baseline (4.5±16.7 ml/min per 1.73 m2 vs. -8.1±21.4 ml/min per 1.73 m2, P = 0.038); two patients in this group reached the endpoint, while no patients in the higher GD group did. Conclusion GD could be an independent prognostic factor for patients of IgA nephropathy with eGFR at 30 to 60 ml/min per 1.73 m2 of body surface, particularly for those with time-averaged amount of urine protein less than 0.5 g per day.

Epigallocatechin-3-gallate protects against cisplatin-induced nephrotoxicity by inhibiting endoplasmic reticulum stress-induced apoptosis.

Cisplatin (CP)-induced nephrotoxicity hampers its application in clinic. Green tea, particularly its predominant polyphenolic constituent epigallocatechin-3-gallate (EGCG), possesses anti-inflammatory, antioxidant, and anti-apoptotic properties. The present study was designed to investigate the protective effects of EGCG against CP-induced nephrotoxicity in mice. Male C57/BL6 mice in different groups received single injection of CP (20 mg/kg) and EGCG (100 mg/kg) in various sets and kidney tissues and blood were collected after killing. Then, samples were used for biochemical and immunohistochemical assay. Our results showed EGCG decreased biochemical factors and immunohistochemical damage induced by CP. Besides, expression of phosphorylated-extracellular signal-regulated kinase (p-ERK), glucose-regulated protein 78 (GRP78), caspase-12, and apoptosis of kidney were decreased by EGCG via inhibition of endoplasmic reticulum (ER) stress-induced apoptosis.

Epigallocatechin-3-gallate protects against cisplatin nephrotoxicity by inhibiting the apoptosis in mouse.

Cisplatin (CP) is a commonly used anticancer drug, but its notable side effect of nephrotoxicity limits its use in clinic. Epigallocatechin-3-gallate (EGCG), an anti-oxidant, anti-inflammatory, and anti-tumorigenic green tea polyphenol, has been available on the market for its beneficial effects. The aim of this study was to investigate whether EGCG can prevent the nephrotoxic effect of CP and the involved mechanisms. Male C57/BL6 mice were randomly divided into four groups: control group, EGCG group, CP group, and CP+EGCG group. On day 5, mice were sacrificed. Our results showed that EGCG treatment significantly ameliorated the histopathological changes and the increased serum creatinine and blood urea nitrogen (BUN) induced by CP. TUNEL-positive cells significantly reduced in the CP+EGCG group compared with CP group. EGCG also inhibited the expression of the ligand of death receptor Fas (Fas-L), apoptosis regulator BAX (Bax) and tumor-suppressor protein p53, and increased the expression of B-cell lymphoma 2 (Bcl-2). These findings suggest that EGCG can ameliorate CP-induced apoptosis in the kidney by regulating death receptor Fas conducted extrinsic pathway, and the expression of Bax and Bcl-2.