Treatment of nephrotic syndrome in children and controlled trials

Aim. To determine the sequential therapy of childhood nephrotic syndrome (NS) with presumed minimal change nephropathy using the evidence from clinical trials. Methods. Meta-analysis of 22 randomized controlled trials was performed, using frequency of relapse and side effects of therapeutic regimes. Results. A meta-analysis of seven trials comparing duration of therapy for initial onset showed that duration of at least 3 months significantly reduced the risk of relapse at 12-24 months (relative risk 0.73; 95% confidence interval 0.60-0.89) without an increase in adverse events. Five trials were performed for steroid treatment of relapse. Deflazacort reduced relapses during therapy, but is not generally available. No difference was observed when comparing single and divided dosing of prednisone. Frequency of relapses could not be influenced by duration of relapse therapy. Alternate day therapy was more effective than intermittent use of prednisone. Two studies out of five on cyclophosphamide or chlorambucil showed consistently that alkylating agents should be used before cyclosporine as alternative therapy to steroids. Conclusions. Children with initial onset of NS should be treated with prednisone at a dose of 60 mg/m(2) /day for 6 weeks, followed by a dose of 40 mg/m(2) /48 h for at least another 6 weeks. If steroid toxicity for treatment of relapsing NS requires alternative treatment, cyclophosphamide (2 mg/kg/day for at least 8 weeks) remains the drug of choice with a curative potential. If children still relapse after alkylating agents, levamisole may serve as an alternative only for frequent relapsing NS, whereas steroid-dependent NS should be treated with cyclosporine.