利妥昔单抗抵抗性膜性肾病的诊治进展  

Research progress on rituximab-refractory membranous nephropathy

作　　者：姚盛华 王慧 韩宗阳 马坤岭 Yao Shenghua;Wang Hui;Han Zongyang;Ma Kunling(Department of Nephrology,Yuyao People's Hospital of Zhejiang Province,Yuyao 315400,China;Department of Nephrology,the Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310009,China)

机构地区：[1]浙江省余姚市人民医院肾内科,余姚315400 [2]浙江大学医学院附属第二医院肾内科,杭州310009

出　　处：《中华肾脏病杂志》2024年第10期827-833,共7页Chinese Journal of Nephrology

基　　金：国家自然科学基金(82370716、82170736)。

摘　　要：近年来,利妥昔单抗逐渐应用于特发性膜性肾病(idiopathic membranous nephropathy,IMN)的治疗。相较于传统的治疗方案,利妥昔单抗治疗IMN的安全性和有效性已得到证实,可使60%~80%的患者获得缓解。其余20%~40%的患者可能存在利妥昔单抗抵抗性,其可能的机制包括:利妥昔单抗生物利用度降低;利妥昔单抗被靶向B细胞内化;抗利妥昔单抗抗体的产生;慢性、不可逆性的肾小球损伤;无法有效清除次级淋巴器官中的自身反应性B细胞克隆。存在利妥昔单抗抵抗性的IMN患者的治疗仍然存在争议和挑战。IMN作为一种自身抗体驱动的疾病,使得B细胞靶向药、浆细胞靶向药、补体抑制剂等使用合理化,也真正实现了对IMN患者的个体化管理。本文主要综述了利妥昔单抗抵抗性膜性肾病的机制及药物治疗进展,旨在为IMN的临床诊疗提供帮助。In recent years,rituximab has been gradually used in the treatment of idiopathic membranous nephropathy(IMN).Compared with traditional treatments,the safety and effectiveness of rituximab in the treatment of IMN have been confirmed,which induces remission in 60%-80%of patients.For the remaining 20%-40%patients,several mechanisms can explain rituximab resistance:decreased rituximab bioavailability;internalized by targeted B cells;the generation of anti-rituximab antibody;chronic and irreversible damage to the glomerular filtration barrier;autoreactive B-cell clones in secondary lymphoid organs that cannot be effectively eliminated.The treatment of patients with rituximab-refractory IMN remains controversial and challenging.The recognition of IMN as an antibody-mediated autoimmune disease has rationalized the use of immunosuppressive drugs such as B cell-targeted therapies,plasma cell-targeted therapies,and complement inhibitors.This review mainly summarizes recent advances in the understanding of the physiological mechanisms of rituximab resistance,and in the management of rituximab-refractory IMN,aiming to aid in the clinical management of IMN.

关 键 词：肾小球肾炎 膜性 利妥昔单抗 B淋巴细胞刺激因子 抗原 CD20 蛋白酶体抑制剂 补体灭活剂 

分 类 号：R692[医药卫生—泌尿科学]