Primary membranous nephropathy: an endless story.

Primary membranous nephropathy (PMN) is an autoimmune disease caused by the attack of autoantibodies against podocyte antigens leading to the in situ production of immune complexes. However, the etiology is unknown and the pathogenesis is still far from being completely elucidated. MN is prevalently idiopathic or primary, but in about 20-30% of cases it is secondary to chronic infections, systemic diseases, exposure to drugs, or malignancy. The differentiation between primary and secondary MN may be difficult, particularly when MN precedes signs and symptoms of the original disease, as in some cases of cancer or systemic lupus erythematosus. The natural course of PMN is variable, but in the long term 40-60% of patients with nephrotic syndrome progress to end-stage renal disease (ESRD) or die from thrombotic or cardiovascular events. PMN is a treatable disease. Patients with asymptomatic proteinuria should receive supportive care. Immunosuppressive treatments should be given to patients with nephrotic syndrome or risk of progression. The most frequently adopted treatments rely on cyclical therapy alternating steroids with a cytotoxic agent every other month, i.e., rituximab at different doses, or calcineurin inhibitors plus low-dose steroids. A good rate of response may be obtained but relapses can occur. Randomized controlled trials, with adequate size, long-term follow-up, and fair definition of endpoints are needed to identify treatment with the best therapeutic index.