中国实用儿科杂志

中国实用儿科杂志 ›› 2025, Vol. 40 ›› Issue (11): 909-917.DOI: 10.19538/j.ek2025110608

• 论著 • 上一篇    下一篇

利妥昔单抗联合霉酚酸酯或他克莫司在治疗儿童激素依赖型肾病综合征的有效性和安全性评估——单中心回顾性队列研究

  

  1. 重庆医科大学附属儿童医院肾脏内科  国家儿童健康与疾病临床医学研究中心  儿童发育疾病研究教育部重点实验室  儿童代谢与炎症性疾病重庆市重点实验室，重庆  401122
  • 出版日期:2025-11-06 发布日期:2025-12-11
  • 通讯作者: 李秋，电子信箱：liqiu_21@126.com；阳海平，电子信箱：oyhp 0708@163.com
  • 基金资助:
    重庆市科卫联合攻关项目（2023GGXM001）

Evaluation of the efficacy and safety of rituximab combined with mycophenolate mofetil or tacrolimus in the treatment of pediatric steroid-dependent nephrotic syndrome：a single-center retrospective study

  1. Department of Nephrology Children’s Hospital of Chongqing Medical University，National Clinical Research Center for Child Health and Disorders，Ministry of Education Key；Laboratory of Child Development and Disorders，Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases，Chongqing  401122，China
  • Online:2025-11-06 Published:2025-12-11

摘要： 目的　探讨利妥昔单抗（rituximab，RTX）联合霉酚酸酯（mycophenolate mofetil，MMF）或他克莫司（tacrolimus，TAC）治疗儿童激素依赖型肾病综合征（steroid-dependent nephrotic syndrome，SDNS）的有效性和安全性。方法　回顾性队列研究。选择2016年10月至2023年8月于重庆医科大学附属儿童医院就诊并首次输注RTX的59例SDNS患儿作为研究对象，收集其一般资料、激素使用情况、实验室指标等。根据输注RTX后选用的免疫抑制剂类型分为MMF组和TAC组。采用重叠加权平衡基线水平，采用加权后Kaplan-Meier法分析RTX治疗后两组患儿复发情况的差异、加权后Cox回归法分析两组患儿激素使用情况的差异。通过使用Cox回归多因素分析探究在首次输注RTX后影响疾病复发的因素。结果　59例患儿中男46例，女13例，发病年龄3.9（2.5，5.9）岁、RTX治疗年龄10.5（7.6，12.6）岁，MMF组23例，TAC组36例。重叠加权后，基线特征得到平衡。在首次输注RTX后，MMF组年复发率比TAC组更低［（0.175±0.582）vs（0.672±1.186），P=0.033］；两组患儿的无复发时间、激素依赖程度、维持缓解时激素剂量、最低激素剂量、最低激素维持时间、免疫抑制剂减量情况、不良事件发生率差异均无统计学意义（均P>0.05）。多因素回归分析显示，对于SDNS患儿，体重是首次输注RTX后影响疾病复发的危险因素（HR=1.154，95%CI 1.051~1.266，P=0.003）。结论　对于首次输注RTX的SDNS患儿，使用MMF进行维持治疗时疾病复发率比使用TAC更低，两种药物在降低激素用量及安全性方面无明显差异。

关键词:

Abstract: Objective　To investigate the efficacy and safety of rituximab（RTX）combined with mycophenolate mofetil（MMF）or tacrolimus（TAC）in the treatment of pediatric steroid-dependent nephrotic syndrome（SDNS）. Methods　This retrospective cohort study enrolled 59 pediatric patients with steroid-dependent nephrotic syndrome（SDNS）who received their first rituximab（RTX）infusion at the Children’s Hospital of Chongqing Medical University between October 2016 and August 2023.Demographic characteristics，corticosteroid usage，and laboratory parameters were collected.Participants were categorized into two groups based on post-RTX immunosuppressant regimens：mycophenolate mofetil（MMF）or 
tacrolimus（TAC）.Overlap weighting was applied to balance baseline characteristics.Weighted Kaplan-Meier analysis was used to compare relapse rates between the two groups，while weighted Cox regression models were employed to evaluate differences in corticosteroid use.Multivariable Cox regression analysis was used to identify the factors affecting disease relapse following initial RTX treatment. Results　The cohort comprised 59 patients（46 male，13 female）with a median age of 3.9 years（IQR 2.5，5.9）at disease onset and a median age of 10.5 years（IQR 7.6，12.6）at RTX initiation.Participants were divided into MMF group（n=23）and TAC（n=36）group.After overlap weighting，baseline characteristics were balanced.The MMF group demonstrated a significantly lower annualized relapse rate compared to the TAC group ［（0.175±0.582）vs.（0.672±1.186）episodes/year，P=0.033］ after the first RTX infusion.No statistically significant differences were observed between groups in relapse-free survival，corticosteroid dependency ，steroid dose at maintaining relief， minimal steroid dose ，minimal steroid maintenance duration，immunosuppressant tapering ，or incidence of adverse events（all P>0.05）. Multivariable Cox regression identified body weight as a risk factor for relapse after initial RTX therapy（HR=1.154，95% CI 1.051~1.266，P=0.003）in SDNS children. Conclusion In pediatric patients with steroid-dependent nephrotic syndrome（SDNS）receiving initial rituximab（RTX）therapy，maintenance treatment with mycophenolate mofetil（MMF）is associated with a significantly lower relapse rate compared to tacrolimus（TAC）.No statistically significant differences are observed between MMF and TAC in reducing corticosteroid dosage or safety profiles.

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