ARE CYTOTOXIC AGENTS BENEFICIAL IN IDIOPATHIC MEMBRANOUS NEPHROPATHY - A METAANALYSIS OF THE CONTROLLED TRIALS

The use of cytotoxic agents for the treatment of idiopathic membranous nephropathy is controversial. Although several controlled trials have been published, both the comparison groups and the study findings hav e varied, resulting in clinical uncertainty. To explore this uncertain ty, a meta-analysis of controlled trials of treatment with cyclophosph amide or chlorambucil was performed in patients with idiopathic membra nous nephropathy and nephrotic-range proteinuria. Patients in the cont rol groups received only symptomatic treatment or corticosteroids. Des criptive and quantitative data from each trial were abstracted indepen dently. Outcomes included effects of treatment on renal function and p roteinuria, with a complete remission (CR) or partial remission (PR) d efined as the complete or partial resolution of proteinuria without de terioration of renal function. For patients having either any response (CR or PR) or only a CR, both the relative risk (RR) and the number n eeded to be treated were calculated. The five trials that satisfied cr iteria for inclusion in the analysis were clinically and statistically homogeneous. There were no placebo-controlled trials that met the cri teria for inclusion. Among the 228 patients in these studies, the RR o f achieving any response with cytotoxic agents was 2.3 (95% confidence interval, 1.7 to 3.2) and the RR for a CR was 4.6 (95% confidence int erval, 2.2 to 9.3), with respective numbers needed to be treated of 2. 9 and 4.7, meaning that between three and five patients would need to be treated with cytotoxic agents to achieve one response. Exclusion of the only nonrandomized trial had no significant effect on the results . Both chlorambucil and cyclo-phosphamide showed similar beneficial ef fects. This meta-analysis demonstrates that treatment with cytotoxic a gents benefits patients with idiopathic nephrotic syndrome due to memb ranous nephropathy by bringing about the resolution of nephrotic-range proteinuria. The published results of these five trials do not allow a conclusion to be drawn regarding the effects of cytotoxic drug thera py on renal function, highlighting the need for studies of the long-te rm benefits and risks of therapies for idiopathic membranous nephropat hy.