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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 m) 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.
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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.
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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 =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.
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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 m, 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/mm(AUC = 0.90, sensitivity = 84.0%, specificity = 81.8%) determined by ROC curve. The low GD group (GD < 1.99 per mm) experienced a significant increase in renal endpoint for patients with eGFR of 30 to 60 ml/min per 1.73 m(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 mvs. -8.1±21.4 ml/min per 1.73 m, 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 mof body surface, particularly for those with time-averaged amount of urine protein less than 0.5 g per day.