Department of Medicine, Division of Nephrology, Columbia University, New York, New York, USA.
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA.
Am J Nephrol. 2018;47 Suppl 1:30-42. doi: 10.1159/000481635. Epub 2018 May 31.
Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults. This review focuses on mechanisms involved in the pathogenesis of MN and approaches to treatment of this disease.
Our understanding of the pathogenesis of primary MN has advanced greatly with the identification of M-type phospholipase A2 receptor and thrombospondin type-1 domain-containing 7A as target antigens whose antibodies serve as biomarkers of this disease. Additional research, including investigations into the roles of complement and melanocortin receptors on the podocyte, may further improve our understanding of how best to treat this condition. Immunosuppressive therapies, including corticosteroids alternating with alkylating agents, and calcineurin inhibitors are partially successful in reducing proteinuria in MN, but their use may be associated with significant adverse effects and a high relapse rate. Novel interventions, including targeting B cells with rituximab as well as treatment with adrenocorticotropic hormone (ACTH), are being investigated. Key Messages: The understanding of treatment targets and availability of new biomarkers has facilitated diagnosis and improved risk stratification for MN and may also be useful for individualizing treatment with a wider range of therapeutic options for patients with MN. Considerable evidence supports the use of B-cell depletion as initial therapy in nephrotic patients with MN. ACTH should be considered for patients who do not respond to traditional therapies such as alkylating agents and calcineurin inhibitors.
膜性肾病（MN）是成人肾病综合征的常见病因。本篇综述重点关注 MN 发病机制中的相关机制以及该疾病的治疗方法。
随着 M 型磷脂酶 A2 受体和血栓反应蛋白 1 型结构域包含 7A 被确定为靶抗原，以及其抗体作为该疾病的生物标志物，我们对原发性 MN 的发病机制的认识有了很大的提高。其他研究，包括对足细胞中补体和黑色素皮质素受体作用的研究，可能进一步提高我们对如何最好地治疗这种疾病的认识。免疫抑制疗法，包括皮质类固醇与烷化剂的交替使用以及钙调神经磷酸酶抑制剂，在减少 MN 中的蛋白尿方面部分有效，但它们的使用可能与严重不良反应和高复发率有关。目前正在研究新型干预措施，包括用利妥昔单抗靶向 B 细胞以及使用促肾上腺皮质激素（ACTH）治疗。
对治疗靶点的认识和新生物标志物的出现促进了 MN 的诊断和风险分层的改善，并且对于使用更广泛的治疗选择对 MN 患者进行个体化治疗也可能是有用的。大量证据支持在患有 MN 的肾病患者中首先使用 B 细胞耗竭作为初始治疗。对于那些对传统疗法（如烷化剂和钙调神经磷酸酶抑制剂）无反应的患者，应考虑使用 ACTH。
