小剂量利妥昔单抗治疗特发性膜性肾病的疗效及其影响因素

doi:10.3969/j.issn.1006-7795.2022.05.003

摘要/Abstract

摘要： 目的探讨小剂量利妥昔单抗(rituximab,RTX)对特发性膜性肾病(idiopathic membranous nephropathy,IMN)的治疗效果及其影响治疗效果的因素。方法收集2019年1月1日至2021年7月31日经首都医科大学附属北京安贞医院肾内科肾活体组织检查(以下简称活检)确诊为IMN,并使用小剂量RTX治疗且有随访资料的35例患者的临床资料,初步探讨RTX的临床疗效。结果 35例患者中10例(28.6%)初始治疗药物为RTX;所有患者RTX单次剂量为0.2~1.0 g,累积剂量为1.0(0.6,1.3)g;中位随访时间6(4.0,12.0)个月。①所有患者应用RTX治疗后尿蛋白减少,血清白蛋白均较前上升,治疗缓解率51.4%,完全缓解率20.0%。按性别、年龄、治疗前血抗磷脂酶A2受体(phospholipase A2 receptor,PLA2R)抗体是否阳性,用SPSS统计软件倾向性评分方法以1∶1随机匹配同期治疗方案为非RTX的免疫抑制治疗患者作为对照组,治疗后2组间缓解率差异无统计学意义, RTX治疗组血白蛋白及肌酐升高幅度低于对照组(P<0.05)。②初始就使用RTX的治疗组与既往接受过免疫抑制的治疗组临床基线资料相比较,初始治疗组血白蛋白浓度更低、治疗后达到B细胞<5 μL的RTX剂量较低(P均<0.05)、病理合并缺血性肾损伤比例更高(P<0.05);而2组治疗缓解率相比较差异无统计学意义。③治疗缓解组与未缓解组相比,治疗后未缓解组基线血肌酐浓度更高(P<0.05)。多因素Cox风险比例回归分析提示RTX作为初始治疗是治疗缓解的独立因素HR=3.025 (95% CI: 1.024~8.932)。结论 RTX无论作为初始治疗抑或免疫抑制治疗效果欠佳时的治疗药物,对IMN均能获得较好疗效,初始就选择使用RTX更有利于疾病缓解。

关键词: 特发性膜性肾病, 利妥昔单抗, 初始治疗

Abstract: Objective To investigate the therapeutic effect of low-dose rituximab (RTX) in idiopathic membranous nephropathy (IMN)and its influence factors.Methods Data of 35 patients with idiopathic membranous nephropathy diagnosed by renal biopsy in Beijing Anzhen Hospital Capital Medical University and treated with low-dose RTX January 1, 2019 to July 31, 2021 with follow-up were collected retrospectively to explore the clinical efficacy of low-dose rituximab therapy. Results A total of 35 patients were enrolled in this study, of which 10 cases (28.6%) were treated with RTX as initial treatment. The single dose of RTX in all patients was 0.2-1.0 g, and the cumulative dose was 1.0 (0.6, 1.3) g. The median follow-up time was 6 (4.0, 12.0) months. ① After RTX treatment, the urine protein decreased, and the serum albumin increased. The treatment remission rate was 51.4% and the complete remission rate was 20.0%.According to sex, age, and serum anti-idiopathic membranous nephropathy(PLA2R)-antibody before treatment, patients with non RTX immunosuppressive treatment were randomly matched 1∶1 as the control group. There was no difference in remission rate between two groups after treatment. The range of increase of serum albumin and creatinine in RTX group was lower than that in control group (P<0.05). ② Compared to the previous immunosuppressive treatment group, the level of serum albumin before treatment and dose of RTX achieving B cell <5 μL were lower (all P<0.05)in the initial group, and the proportion of pathological changes of renal ischemia was higher (P < 0.05). There was no significant difference in the remission rate between the two groups. ③ Compared with the non remission group, the serum creatinine level before treatment was lower in the remission group (P < 0.05). Multivariate Cox regression analysis showed that RTX as initial treatment was an independent influencing factor of treatment remission (HR=3.025, 95% CI: 1.024-8.932). Conclusion RTX had satisfactory curative effect on IMN, whether it was used as the initial treatment or as the follow up treatment when the previous treatment effect is poor. The initial use of RTX in IMN is more conducive to disease remission.

Key words: idiopathic membranous nephropathy, rituximab, initial treatment

中图分类号:

徐潇漪, 王国勤, 程虹, 赵智睿, 董鸿瑞, 孙丽君. 小剂量利妥昔单抗治疗特发性膜性肾病的疗效及其影响因素[J]. 首都医科大学学报, 2022, 43(5): 680-686.

Xu Xiaoyi, Wang Guoqin, Cheng Hong, Zhao Zhirui, Dong Hongrui, Sun Lijun. Efficacy and influence factors of low-dose rituximab therapy in idiopathic membranous nephropathy[J]. Journal of Capital Medical University, 2022, 43(5): 680-686.

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