Membranous nephropathy in systemic lupus erythematosus: a therapeutic enigma

Renal disease is a major cause of mortality and morbidity in systemic lupus erythematosus. Among the histological classes of lupus nephritis, membranous nephropathy comprises only one-fifth of all cases. Reported survival and rates of end-stage renal disease in membranous lupus nephropathy (MLN) vary considerably, because of substantial heterogeneity among the published studies. The risk of progression from MLN to renal failure is generally reduced in the absence of proliferative lesions, but patients are, nevertheless, at risk of thromboembolic complications. The optimal therapy for MLN remains elusive because of a lack of controlled trials; however, cardiovascular protection and blockade of the renin-angiotensin system should be instituted early in all patients. Mixed membranous and proliferative lupus nephritis should be treated in the same way as pure proliferative lupus nephritis. If MLN is not accompanied by proliferative lesions but is associated with clinically relevant proteinuria, renal insufficiency or failure to respond to supportive therapies, immunosuppressive treatment is indicated. Treatment options include glucocorticoids combined with azathioprine, calcineurin inhibitors or alkylating agents. The efficacy of mycophenolate mofetil in MLN remains to be confirmed. Controlled trials to compare existing immunosuppressive agents and experimental modalities such as sirolimus, rituximab and infliximab should be undertaken in the future.