The treatment of idiopathic membranous nephropathy

Membranous nephropathy remains the most common cause of the nephrotic syndrome in adults. Most patients do well with long-term natural history studies reporting a 10-year renal survival of 70% to 90% but the remainder progress to end stage renal failure. This plus the associated morbidity of those with persistent high grade proteinuria makes the decision about the timing and type of treatment difficult. Models have been developed to help predict at an early stage of the disease those at the highest risk of progression and their use is encouraged. The use of nonspecific, nontoxic therapy, ie, angiotensin-converting enzyme inhibitor (ACEI), for both hypertension control and their renoprotective effect is supported by evidence from high-quality studies. Modest dietary protein restriction may be of use but its effect is more controversial. If subnephrotic proteinuria plus normal renal function is present or inducible, conservative therapy and ongoing observation is probably all that is warranted. If high-grade proteinuria (>3.5 g/d) persists then the Italian regime consisting of cytotoxic therapy alternating monthly with prednisone treatment for three cycles has shown the best evidence of long-term induction of remission of proteinuria and preservation of renal function. If this fails or is judged too toxic then a 6- to 12-month course of cyclosporine seems warranted, especially if renal function is deteriorating. Introduction of treatment for risk reduction of both secondary effects of the disease and for modification of the adverse effects of immunosuppressive drugs should be considered in cases with high-grade persistent proteinuria.