Immunosuppressive treatment of idiopathic membranous nephropathy: the dilemma continues

Idiopathic membranous nephropathy (IMN) is one of the most common causes of nephrotic syndrome (NS) in adults and may progress to end-stage renal disease (ESRD). Given the variable course, it remains unclear who to treat with immunosuppression (IS) and with what regimen. Corticosteroids, alkylating agents, calcineurin inhibitors (CNIs), and antimetabolites have all been used in randomized controlled trials (RCTs). Previous meta-analyses of these trials were unable to demonstrate a benefit on death or progression to ESRD compared to no treatment or placebo. Since the last round of these analyses (in 2004) additional RCTs have been published. The Cochrane Central Register of Controlled Trials and Medline were searched from 2003 until February, 2012 for new RCTs in the treatment of IMN to update the database. Twelve trials were found. Due to significant heterogeneity of patients and regimens, they are discussed qualitatively only and are integrated with prior RCTs and relevant observational data. In conclusion, patients with non-nephrotic proteinuria should not be offered IS therapy. Those with NS and declining renal function should be treated. The best evidence supports a combined steroid and alkylating agent regimen. Calcineurin inhibitors clearly produce short-term benefit (proteinuria reduction and remission) but their ability to favorably affect death or ESRD remains unproven. There is little support for antimetabolite use. Other agents (rituximab and adrenocorticotropin) require further study. For the large group of patients with NS but normal renal function it remains a dilemma who to treat and with what regimen.