利妥昔单克隆抗体治疗原发性肾小球肾炎的应用进展

Advances in application of rituximab in treatment of primary glomerulonephritis

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。

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.