This study aims to assess whether immunosuppression is beneficial in the treatment of idiopathic membranous nephropathy (IMN).

We reviewed randomized controlled trials (RCTs) addressing the effect of immunosuppression on histologically proven IMN in adults with nephrotic syndrome followed up for at least 6 months. The literature was searched according to Cochrane Collaboration guidelines. Four therapeutic classes were considered: (1) steroids (alone), (2) alkylating agents (alone or in combination with steroids), (3) calcineurin inhibitors (alone or in combination with steroids), and (4) antiproliferative agents (alone).

Eighteen RCTs were selected (1,025 patients). Overall, no differences were found between immunosuppressive treatment and placebo or no treatment. For oral glucocorticoid therapy, no beneficial effect was observed. For alkylating agents, a beneficial effect was observed on complete remission (relative risk [RR], 2.37; 95% confidence interval [CI], 1.32 to 4.25; P = 0.004). Excluding patients with particularly well-preserved renal function, there was no significant difference in complete remission. Cyclophosphamide therapy resulted in a lower rate of adverse-event discontinuations compared with chlorambucil (8 versus 21 discontinuations, respectively; RR, 2.34; 95% CI, 1.25 to 4.39; P = 0.008). For calcineurin inhibitors, no difference was observed. For antiproliferative agents, a paucity of data did not allow a conclusion.

The meta-analysis failed to show a long-term effect of treatment on patient and/or renal survival. There is weak evidence that the immunosuppressive regimen increased the remission rate. The review of safety showed a higher number of discontinuations for adverse events in immunosuppressive-treatment groups and that cyclophosphamide had fewer side effects than chlorambucil.