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

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 t hese immunosuppressive agents are evaluated. Methods. RCTs with, outcome data at sis months or more that evaluated nonco rticosteroid agents in relapsing SSNS were included. A summary relative ris k for relapse at 6 to 12 months was calculated using a random effects model . Results. Seventeen trials involving 631 children were identified. Cyclaphos phamide [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) sig nificantly reduced the relapse risk at 6 to 12 months compared with prednis one 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 cycle: phosphamide (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 cea sed. 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 re duce the risk of relapse in children with relapsing SSNS compared with pred nisone alone. Clinically; important differences in efficacy among these age nts are possible, and further comparative trials are still needed. Meanwhil e, the choice between these agents depends on physician and patient prefere nces related to therapy duration and complication type and frequency.