Membranous nephropathy (MN) is a glomerular disease characterized by proteinuria, usually in a nephrotic range, and variable natural course. The etiology is unknown in many cases, while in some patients, MN may be secondary to infection, to other diseases, or to exposure to drugs and toxic substances. In idiopathic MN, the antigens are probably located at the base of podocytes, and the glomerular lesions occur by the local formation of immune complexes, with consequent activation of complement and inflammation triggered by the membrane attack complex C5b-9. Patients with severe proteinuria, those with advanced tubulointerstitial changes at renal biopsy and those with increased serum creatinine at presentation have a poorer prognosis, while patients showing complete or even partial remission of proteinuria have a favorable prognosis. The indications for and types of treatment are controversial. There is no good evidence in favor of therapies based on corticosteroids alone. Cyclophosphamide and chlorambucil may increase the probability of remission, but the prolonged use of these agents may cause disquieting adverse effects. Good results have been obtained by alternating corticosteroids and a cytotoxic agent every other month for 6 months. Other potential treatments are represented by cyclosporine, synthetic adrenocorticotropic hormone (ACTH), mycophenolate mofetil, rituximab and intravenous immunoglobulins. Further studies addressed to recognizing the responsible antigen(s), and interventions directed to interfere with the specific antibodies, with regulators of glomerular permeability, and/or with factors regulating the complement activity might allow us to better understand the physiopathology of MN and to organize more specific and effective treatments in the near future.
