Abstract:

Objective

To assess the efficacy and safety of novel immunosuppressants in the treatment of adult idiopathic membranous nephropathy (IMN) with nephrotic syndrome.

Methods

The Cochrane library, PubMed, and Embase were searched (December 2013) to identify randomized controlled trials ( RCTs) that compared novel immunosuppressants with corticosteroid plus alkylating agents(chlorambucil or cyclophosphamide). The Cochrane-recommended bias risk tool was used to assess the quality of studies. The inverse-variance random-effects method was used to assess all-cause mortality or the risk of progression to end-stage renal disease (ESRD), the rate of decline in renal function, complete or partial remission, proteinuria, and adverse events leading to discontinuation or hospitalization. Data were synthesized with the RevMan software version 5. 2. The effect of treatment was presented with risk ratio(RR) and 95% confidence interval (95% CI), and the publication bias was analyzed with funnel plot.

Results

Nine RCTs with 383 patients were included. The novel immunosuppressants included were cyclosporine, tacrolimus, mycophenolate mofetil, and adrenocorticotropic hormone (ACTH). Compared to classical therapy of corticosteroid plus alkylating agents, novel immunosuppressants did not significantly reduce the all-cause mortality or the risk of progression to ESRD [3 RCTs,104 patients,RR=1.37 (0.52,3.61),P=0.53],did not decrease the rate of decline in renal function [3 RCTs,104 patients, RR=1.19 (0.78,1.81),P=0.42],did not improve complete or partial remission [8 RCTs,349 patients,RR=1.01 (0.79,1.30),P=0.93],or did not reduce proteinuria [5 RCTs,175 patients,MD= -0.45 ( -1.56,0.66) g/day, P=0.43].There was no difference between the two groups in the risk of adverse events leading to discontinuation or hospitalization [5 RCTs, 80 patients, RR =0.80 (0.49, 1.32), P =0.39]. However, subgroup analyses indicated that the novel immunosuppressants significantly increased complete or partial remission [6 RCTs,240 patients,RR=1.21 (1.03, 1.42), P =0.02] and decreased proteinuria [3 RCTs, 147 patients, MD =-1.35 ( -1.94, -0.76) g/day, P ＜0.00001].

Conclusions

This meta-analysis did not indicate that the efficacy of novel immunosuppressants was superior to that of corticosteroid plus alkylating agents in treating adult IMN with nephrotic syndrome. More RCTs are needed to confirm the results from subgroup analyses.

Key words: Immunosuppression, Idiopathic membranous nephropathy, Meta-analysis