In patients with membranous nephropathy, alkylating agents (cyclophosphamide or chlorambucil) alone or in combination with steroids achieve remission of nephrotic syndrome more effectively than conservative treatment or steroids alone, but can cause myelotoxicity, infections, and cancer. Calcineurin inhibitors can improve proteinuria, but are nephrotoxic. Most patients relapse after treatment withdrawal and can become treatment dependent, which increases the risk of nephrotoxicity. The discovery of nephritogenic autoantibodies against podocyte M-type phospholipase A2 receptor (PLA₂R) and thrombospondin type-1 domain- containing protein 7A (THSD7A) antigens provides a clear pathophysiological rationale for interventions that specifically target B-cell lineages to prevent antibody production and subepithelial deposition. The anti-CD20 monoclonal antibody rituximab is safe and achieves remission of proteinuria in approximately two-thirds of patients with membranous nephropathy. In those with PLA₂R-related disease, remission can be predicted by anti-PLA₂R antibody depletion and relapse by antibody re-emergence into the circulation. Thus, integrated evaluation of serology and proteinuria could guide identification of affected patients and treatment with individually tailored protocols. Nonspecific and toxic immunosuppressive regimens will fall out of use. B-cell modulation by rituximab and second-generation anti-CD20 antibodies (or plasma cell-targeted therapy in anti-CD20 resistant forms of disease) will lead to a novel therapeutic paradigm for patients with membranous nephropathy.

在膜性肾病患者中，单独使用烷化剂（环磷酰胺或苯丁酸氮芥）或与类固醇合用比单独使用类固醇或类固醇能更有效地缓解肾病综合征，但会引起骨髓毒性，感染和癌症。钙调神经磷酸酶抑制剂可以改善蛋白尿，但具有肾毒性。大多数患者在停药后会复发，并可能变得依赖于治疗，这增加了肾毒性的风险。针对足细胞M型磷脂酶A2受体（PLA ₂R）和含血小板反应蛋白1型域的蛋白7A（THSD7A）抗原为专门针对B细胞谱系以防止抗体产生和上皮下沉积的干预措施提供了明确的病理生理原理。抗CD20单克隆抗体利妥昔单抗是安全的，可在约三分之二的膜性肾病患者中实现蛋白尿的缓解。在患有PLA ₂ R相关疾病的患者中，可以通过抗PLA ₂预测缓解R抗体的耗竭和复发是通过抗体重新出现进入循环而实现的。因此，对血清学和蛋白尿的综合评估可以指导确定受影响的患者以及采用个性化方案进行治疗。非特异性和毒性的免疫抑制方案将不再使用。利妥昔单抗和第二代抗CD20抗体（或抗CD20耐药形式的浆细胞靶向治疗）对B细胞的调节将导致膜性肾病患者的新型治疗范例。