Idiopathic membranous nephropathy: diagnosis and treatment.

Idiopathic membranous nephropathy is still the most common glomerular disease associated with nephrotic syndrome. The greater the proteinuria, the greater the long-term risk for renal failure. In addition, patients who have membranous nephropathy with nephrotic syndrome have significant morbidity and mortality, in particular related to thromboembolic and cardiovascular complications. There is no specific treatment for membranous nephropathy. Supportive care with the use of diuretics and angiotensin-converting enzyme inhibitors in combination with angiotensin II receptor blocker is recommended, but these agents have only a limited effect. Immunosuppressive treatment options include the use of corticosteroids, alkylating agents, cyclosporin A, tacrolimus, and mycophenolate mofetil, but their use is controversial, not all have been shown to be effective, and their use can be associated with significant adverse effects. This has resulted in relatively small improvement in the prognosis of membranous nephropathy in the past 30 yr, with up to 40% of patients eventually reaching end-stage renal failure. Agents that offer more complete response rates with lower adverse effects are truly needed. Recent data suggest that B cells play a key role in the pathogenesis of a number of autoimmune diseases including membranous nephropathy and that selective depletion of B cells in humans may be beneficial in preventing the production of pathogenic immunoglobulins and subsequent renal injury.