目的 探讨利妥昔单抗联合环磷酰胺对特发性膜性肾病（IMN）患者的临床疗效。方法 选取2018年8月—2020年8月石家庄市人民医院129例IMN患者作为研究对象，根据纳入患者的治疗方案将患者分为环磷酰胺组、利妥昔单抗组和利妥昔单抗与环磷酰胺联用组（简称联用组），环磷酰胺组予以注射用环磷酰胺治疗，静脉滴注，每次0.8～1.0 g，每月1次；治疗6个月后达到临床完全缓解或部分缓解，继续治疗3个月（累积剂量＜10 g），治疗6个月无效者停用。利妥昔单抗组予以利妥昔单抗注射液，静脉滴注，375 mg·m^-2，每周1次。联用组予以利妥昔单抗注射液及注射用环磷酰胺治疗，用法用量分别同单用组。3组均持续治疗6个月。比较3组疾病缓解率、IMN相关指标［24 h尿蛋白定量、抗磷脂酶A2受体（PLA2R）抗体、血肌酐］、T淋巴细胞亚群分布、尿中攻膜复合物（C5b-9）、免疫球蛋白G4（IgG4）、复发率及感染并发症发生率。结果 联用组总有效率（81.40%）较环磷酰胺组、利妥昔单抗组（53.49%、60.47%）显著升高（P＜0.05）。治疗后，3组24 h尿蛋白定量、抗PLA2R抗体、尿C5b-9、IgG4水平均较本组治疗前显著下降（P＜0.05）；且治疗后联用组24 h尿蛋白定量、抗PLA2R抗体、尿C5b-9、IgG4水平较环磷酰胺组、利妥昔单抗组显著降低（P＜0.05）。治疗后，3组CD4⁺、CD4⁺/CD8⁺均较本组治疗前显著下降（P＜0.05），CD8⁺显著升高（P＜0.05），且治疗后联用组CD4⁺、CD4⁺/CD8⁺较环磷酰胺组、利妥昔单抗组显著降低（P＜0.05），CD8⁺较环磷酰胺组、利妥昔单抗组显著升高（P＜0.05）。联用组12个月复发率（2.33%）较环磷酰胺组、利妥昔单抗组（20.93%、18.60%）显著降低（P＜0.05）；3组感染并发症比较，差异无统计学意义（P＞0.05）。结论 利妥昔单抗联合环磷酰胺可有效缓解IMN病情，并改善患者肾功能、免疫功能，且安全可靠。

Objective To investigate the clinical efficacy of rituximab in combination with cyclophosphamide in treatmeng of patients with idiopathic membranous nephropathy (IMN). Methods 129 patients with IMN in Shijiazhuang People's Hospital from August 2018 to August 2020 were selected as study subjects. According to the treatment plan of the included patients, they were divided into a cyclophosphamide group, a rituximab group, and a combination of rituximab and cyclophosphamide group (referred to as the combination group). The cyclophosphamide group was treated with Cyclophosphamide Injection, intravenous drip, 0.8— 1.0 g each time, once a month. After six months of treatment, complete or partial clinical remission was achieved. Treatment continued for three months (cumulative dose < 10 g), and those who failed after six months were discontinued. The rituximab group received Rituximab Injection, intravenous drip, 375 mg·m^-2, once a week. The combination group was treated with Rituximab Injection and Cyclophosphamide Injection, with the same usage and dosage as the single use group. All three groups were treated continuously for six months. The remission rate, nephropathy-related indicators [24 h urine protein quantification, phospholipase A2 receptor antibody (PLA2R), blood creatinine], T lymphocyte subsets, urinary tapping membrane complex (C5b-9), immunoglobulin G4 (IgG4), relapse rate and complication rate of infection were also compared among the three groups. Results The disease remission rate was higher in the combination group (81.40%) compared with cyclophosphamide group and rituximab group (53.49%, 60.47%) (P < 0.05). After treatment, the 24 h urinary protein quantification, anti PLA2R antibody, urinary C5b-9, and IgG4 levels in three groups significantly decreased before treatment of same group (P < 0.05), 24 h urine protein quantification, PLA2R, urine C5b-9 and IgG4 were lower in the combination group compared with cyclophosphamide group and rituximab group after treatment (P < 0.05). After treatment, the CD4⁺and CD4⁺/CD8⁺ levels in three groups significantly decreased compared to before treatment of same group (P < 0.05), while the CD8⁺ levels significantly increased (P < 0.05). CD4⁺, CD4⁺/CD8⁺ were lower in the combination group compared with cyclophosphamide group and rituximab group after treatment, and CD8⁺ was higher in the combination group compared with cyclophosphamide group and rituximab group (P < 0.05). The 12-month recurrence rate was lower in the combination group (2.33%) compared with cyclophosphamide group and rituximab group (20.93% and 18.60%) (P < 0.05). The differences were not statistically significant when comparing the complications of infection in the three groups (P > 0.05). Conclusion Rituximab combined with immunosuppressants-cyclophosphamide can effectively alleviate IMN disease and improve renal and immune function, and the treatment is safe and reliable.

R983

河北省2023年度医学科学研究课题计划项目（20231601）