Cytotoxics, cyclosporine and membranous nephropathy

Membranous nephropathy remains the most common underlying cause of adult-onset nephrotic syndrome. Most patients with the idiopathic variant do well, with 10-year renal survival in a quite tight range of 70-90%. This indolence in the disease process and the spontaneous remission rate of 15-30% are the major factors that have prevented a uniform opinion from developing regarding therapy. The best long-term results come from the studies of an Italian group which used a regimen of chlorambucil and prednisone. Their most recent publication showed an impressive improvement in renal survival at 10 years from 62% in their untreated group to 90% in their treated group. The perceived risk: benefit ratio in the asymptomatic patient, however, has prevented the application of this approach to the average patient with idiopathic membranous nephropathy. The only randomized controlled study to use pulsed cyclophosphamide plus prednisone showed no benefit compared with the use of steroids alone. In contrast to the best cytotoxic trials, the application of cyclosporine treatment has been largely limited to patients at high risk of progression. Cyclosporine's efficacy in the short term is unquestioned, and a recent randomized controlled trial suggests an improved long-term preservation of renal function. Its costs, risks and long-term benefits require continuing assessment.