JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
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Membranous nephropathy.

Membranous nephropathy (MN) is a glomerular disease that can occur at all ages. In adults, it is the most frequent cause of nephrotic syndrome. In ~80% of patients, there is no underlying cause of MN (primary MN) and the remaining cases are associated with medications or other diseases such as systemic lupus erythematosus, hepatitis virus infection or malignancies. MN is an autoimmune disease characterized by a thickening of the glomerular capillary walls due to immune complex deposition. Identification of the phospholipase A2 receptor (PLA2R) as the major antigen in adults in 2009 induced a paradigm shift in disease diagnosis and monitoring and several other antigens have since been characterized. Disease outcome is difficult to predict and around one-third of patients will undergo spontaneous remission. In those at high risk of progression, immunosuppressive therapy with cyclophosphamide plus corticosteroids has substantially reduced the need for kidney replacement therapy. Owing to carcinogenic risk, other treatments (calcineurin inhibitors and CD20-targeted B cell depletion therapy (rituximab)) have been developed. However, disease relapses are frequent when calcineurin inhibitors are stopped and the remission rate with rituximab is lower than with cyclophosphamide, particularly in patients with high PLA2R antibody titres. Other new drugs are already available and antigen-specific immunotherapies are being developed.

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