Autophagy in the Pathogenesis of Membranous Nephropathy.

Membranous nephropathy (MN) is a leading cause of nephrotic syndrome in adults. In most cases, its etiology is unknown (idiopathic), while ∼30% of cases are secondary to other diseases, infections, or exposure to drugs and toxic agents. Up to 70% of patients with idiopathic MN have circulating antibodies against the M-type phospholipase A2 receptor, a podocyte surface protein. The formation of immune complexes on podocytes triggers complement activation, leading to the activation of both the C5b-C9 complex and C5a. Recently, several novel podocyte antigens have been identified in both idiopathic and secondary MN. Autophagy, a cellular mechanism that removes and recycles damaged cytoplasmic material, may have a dual role in MN pathogenesis. It can regulate innate and adaptive immune responses, promoting the production of autoantibodies against podocyte antigens. However, autophagy also protects podocytes from apoptosis and injury. In addition, it plays a role in the progression of tubular atrophy and interstitial fibrosis, which can lead to chronic kidney disease and kidney failure. This article explores the mechanisms that activate and regulate macroautophagy and examines its role in MN. The potential therapeutic implications of autophagy regulation in MN, based on preliminary studies, are also discussed.