Immunosuppressive agents in childhood nephrotic syndrome: a meta-analysis of randomized controlled trials

Abstract

Background: Many children with steroid-sensitive nephrotic syndrome (SSNS) relapse frequently and receive immunosuppressive agents. In this systematic review of randomized controlled trials (RCTs), the benefits and harms of these immunosuppressive agents are evaluated.

Methods: RCTs with outcome data at six months or more that evaluated noncorticosteroid agents in relapsing SSNS were included. A summary relative risk for relapse at 6 to 12 months was calculated using a random effects model.

Results: Seventeen trials involving 631 children were identified. Cyclophosphamide [3 trials; relative risk (RR) 0.44, 95% confidence interval (CI), 0.26 to 0.73] and chlorambucil (2 trials; RR 0.13, 95% CI, 0.03 to 0.57) significantly reduced the relapse risk at 6 to 12 months compared with prednisone alone. In the single chlorambucil versus cyclophosphamide trial, there was no observed difference in relapse risk at two years (RR 1.31, 95% CI, 0.80 to 2.13). Cyclosporine was as effective as cyclophosphamide (1 trial; RR 1.07, 95% CI, 0.48 to 2.35) and chlorambucil (1 trial; RR 0.82, 95% CI, 0.44 to 1.53), but the effect was not sustained when cyclosporine was ceased. During treatment, levamisole (3 trials; RR 0.60, 95% CI, 0.45 to 0.79) was more effective than steroids alone, but the effect was not sustained.

Conclusions: Cyclophosphamide, chorambucil, cyclosporine, and levamisole reduce the risk of relapse in children with relapsing SSNS compared with prednisone alone. Clinically important differences in efficacy among these agents are possible, and further comparative trials are still needed. Meanwhile, the choice between these agents depends on physician and patient preferences related to therapy duration and complication type and frequency.