Immunosuppression for membranous nephropathy: a systematic review and meta-analysis of 36 clinical trials

Abstract

Background and objectives: The efficacy and safety of immunosuppression for idiopathic membranous nephropathy (IMN) with nephrotic syndrome are still controversial. A systematic review and meta-analysis of randomized controlled trials (RCTs) was performed.

Design, setting, participants, & measurements: The Cochrane Library, PUBMED, EMBASE, Chinese Database, and Clinical Trial Registries (June 2012) were searched to identify RCTs investigating the effect of immunosuppression on adults with IMN and nephrotic syndrome.

Results: This review was an update (36 RCTs, 1762 participants) of the 2004 version (18 RCTs, 1025 participants). Immunosuppression significantly reduced all-cause mortality or ESRD (15 RCTs, 791 participants; risk ratio, 0.58 [95% confidence interval, 0.36-0.95]; P=0.03). However, the result was not consistent when prespecified subgroup analyses were undertaken. Immunosuppression increased complete or partial remission (CR + PR) (16 RCTs, 864 participants; 1.31 [1.01-1.70]; P=0.04) but resulted in more withdrawals or hospitalizations (16 RCTs, 880 participants; 5.35 [2.19-13.02]; P=0.002). Corticosteroids combined with alkylating agents significantly reduced all-cause mortality or ESRD (8 RCTs, 448 participants; 0.44 [0.26-0.75]; P=0.002) and increased CR + PR (7 RCTs, 422 participants; 1.46 [1.13-1.89]; P=0.004) but led to more adverse events (4 RCTs, 303 participants; 4.20 [1.15-15.32]; P=0.03). Cyclophosphamide was safer than chlorambucil (3 RCTs, 147 participants; 0.48 [0.26-0.90]; P=0.02). Cyclosporine and mycophenolate mofetil failed to show superiority over alkylating agents. Tacrolimus and adrenocorticotropic hormone significantly reduced proteinuria.

Conclusions: Alkylating agents plus corticosteroids had long-term and short-term benefits for adult IMN, but resulted in more withdrawals or hospitalizations.

Figure 1.

Study selection flow chart. RCT, randomized controlled trial.

Figure 2.

Immunosuppression significantly reduced all-cause mortality or risk of ESRD (A) and significantly increased complete or partial remission (B) at the end of follow-up compared with no treatment or ACEI. ACEI, angiotensin converting enzyme inhibitor; CI, confidence interval; IV, inverse variance method.

Figure 3.

Alkylating agents plus corticosteroids significantly reduced all-cause mortality or risk of ESRD (A) and significantly increased complete or partial remission (B) at the end of follow-up compared with no treatment or ACEI or corticosteroid monotherapy. ACEI, angiotensin converting enzyme inhibitor; CI, confidence interval; IV, inverse variance method.

Figure 4.

Cyclosporine ± corticosteroids failed to show superiority over no treatment, ACEI, or corticosteroids ± alkylating agents/azathioprine with regard to all-cause mortality or risk of ESRD (A) and complete or partial remission (B) at the end of follow-up. ACEI, angiotensin converting enzyme inhibitor; CI, confidence interval; IV, inverse variance method.