上海交通大学学报（医学版）

上海交通大学学报（医学版） ›› 2018, Vol. 38 ›› Issue (3): 333-.doi: 10.3969/j.issn.1674-8115.2018.03.017

• 综述 • 上一篇    下一篇

利妥昔单克隆抗体治疗原发性肾小球肾炎的应用进展

杨小茜 1 ，谢静远 1, 2，牟姗 2, 3   

  1. 上海交通大学 医学院 1. 附属瑞金医院肾脏内科，上海 200025；2. 附属肾脏病研究所，上海 200025；3. 附属仁济医院肾脏科，上海 200127
  • 出版日期:2018-03-28 发布日期:2018-05-03
  • 通讯作者: 谢静远，电子信箱：nephroxie@163.com。
  • 作者简介:?杨小茜（1994—），女，博士生；电子信箱：qdyangxiaoqian@163.com。
  • 基金资助:
     上海市教育委员会高峰高原学科建设计划（20152207）；上海市科学技术委员会国际合作交流项目（14430721000)；上海交通大学医学院多中心临床研究项目（DLY201510）；国家自然科学基金（81373865，81573748）；上海市优秀学术带头人计划（16XD1401900）

Advances in application of rituximab in treatment of primary glomerulonephritis

YANG Xiao-qian1 , XIE Jing-yuan1, 2, MOU Shan2, 3   

  1. 1. Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; 2. Institute of Nephrology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China ; 3. Renal Division, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
  • Online:2018-03-28 Published:2018-05-03
  • Supported by:
    Shanghai Municipal Education Commission— Gaofeng Clinical Medicine Grant Support, 20152207; International Cooperation and Exchange Program of Science and Technology Committee of Shanghai Municipality, 14430721000; Multicenter Clinical Research Project of Shanghai Jiao Tong University School of Medicine, DLY201510; National Natural Science Foundation of China, 81373865, 81573748; Program of Shanghai Excellent Academic Leader, 16XD1401900

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摘要： 原发性肾小球肾炎（primary glomerulonephritis，PGN）是我国终末期肾病的最主要病因。PGN 的病理类型主要包括 IgA 肾病、膜性肾病、微小病变型肾病、局灶节段性肾小球硬化和膜增生性肾小球肾炎等。PGN 致病机制与肾脏局部免疫复合物沉积、足细胞损伤、感染、补体系统调控异常等相关。目前，PGN 缺乏特异性治疗方法，主要治疗方法包括肾素血管紧张素系统抑制剂、激素、细胞毒药物治疗，降脂，抗凝及抗血小板黏附等；如患者对现有治疗药物不敏感或不耐受其不良反应，则预后较差。利妥昔单克隆抗体（rituximab，RTX）是一种人鼠嵌合抗 CD20 的单克隆抗体，RTX 与 B 淋巴细胞表面 CD20 抗原结合后可通过清除循环中 B 淋巴细胞而发挥免疫抑制作用。RTX 最早用于治疗血液系统肿瘤，越来越多的证据显示 RTX 亦对部分自身免疫性疾病有效，如系统性红斑狼疮、抗中性粒细胞胞质抗体相关性血管炎等，因此该药是否可用于治疗 PGN 受到广泛关注。近年来，陆续有 RTX 治疗 PGN 的临床试验结果发表。该文主要就 RTX 治疗特发性膜性肾病、微小病变型肾病、局灶节段性肾小球硬化和 IgA 肾病方面的研究进展作一综述。

关键词: 利妥昔单克隆抗体, 原发性肾小球肾炎, 治疗, B 淋巴细胞

Abstract:

 Primary glomerulonephritis (PGN) remains the major cause of end-stage renal disease (ESRD) in our country. The histologic entity of PGN mainly includes immunoglobulin A nephropathy (IgAN), idiopathic membranous nephropathy (IMN), minimal change disease (MCD), focal and segmental glomerulosclerosis (FSGS) and membranoproliferative glomerulonephritis (MPGN). The pathogenesis of PGN is correlated with renal immune complex deposition, podocyte injury, infection and abnormal regulation of complement system. Nowadays PGN is short of specific treatments, the main therapeutic methods of PGN consists of renin angiotensin aldosterone system (RAAS) inhibitor, corticosteroids, cytotoxic drugs, lipid-lowering agents, anticoagulant therapy and antiplatelet adhesion. Patients who are drug-resistant or intolerance of the side effects will have a poor prognosis. Rituximab (RTX) is a chimeric monoclonal anti-CD20 antibody. The binding of RTX to CD20 on the cell membrane of B lymphocytes leads to significant depletion of peripheral B lymphocytes, which plays an immunosuppressive role. Rituximab is originally approved for the treatment of lymphoma, after that there was growing evidence showed RTX was effective in part of immunological diseases, including systemic lupus erythematosus and anitneutrophil cytoplasmic antibody associated vasculitis. As a result, whether RTX will act as an effective treatment modality in PGN has aroused extensive attention. In recently years, clinical researches concerning RTX used for the treatment of PGN have been published in succession. This paper reviewed clinical studies focused on the use of rituximab in the treatment of IMN, MCD, FSGS and IgAN.

Key words: rituximab (RTX), primary glomerulonephritis (PGN), treatments, B lymphocytes