利妥昔单抗治疗儿童激素敏感型肾病综合征后B细胞重建时间的影响因素  

The variables affecting the time of B-cell reconstruction in children with steroid-sensitive nephrotic syndrome treated with rituximab

作　　者：芦盼 李纪同 张书锋[1] 刘玉洁[1] 赵公平 刘翠华[1] Lu Pan;Li Jitong;Zhang Shufeng;Liu Yujie;Zhao Gongping;Liu Cuihua(Department of Nephrology and Rheumatology,Children′s Hospital Affiliated to Zhengzhou University,Henan Children′s Hospital,Zhengzhou Children′s Hospital,Zhengzhou Key Laboratory of Children′s Kidney Disease Research,Zhengzhou 450018,China)

机构地区：[1]郑州大学附属儿童医院,河南省儿童医院郑州儿童医院肾脏风湿科,郑州市儿童肾脏病研究重点实验室,郑州450018

出　　处：《中华儿科杂志》2024年第9期841-846,共6页Chinese Journal of Pediatrics

基　　金：河南省医学科技攻关计划省部共建重点项目(SBGJ202002124)。

摘　　要：目的探讨利妥昔单抗(RTX)治疗儿童激素敏感型肾病综合征(SSNS)后外周血CD19+B细胞重建时间的影响因素。方法回顾性队列研究。选择2019年12月至2023年5月于郑州大学附属儿童医院肾脏风湿免疫科就诊且接受RTX治疗的42例SSNS患儿为研究对象,收集其一般资料、免疫抑制剂应用情况及实验室指标如CD19+B细胞计数、尿蛋白定量等。根据B细胞重建时间将研究对象分为早期重建组和晚期重建组。采用Logistic回归分析RTX治疗SSNS后B细胞重建时间的影响因素,并采用受试者工作特征(ROC)曲线分析其预测价值。结果42例患儿中男35例、女7例,起病年龄3.5(2.2,5.9)岁,应用RTX年龄(8.4±3.3)岁,B细胞重建时间为(152±53)d,早期重建组20例,晚期重建组22例。两组患儿在应用RTX前1年内激素累积剂量[0.29(0.16,0.50)比0.29(0.19,0.46)mg/(kg·d)]、应用他克莫司比例[65%(13/20)比45%(10/22)]、累积剂量[0.04(0.03,0.05)比0.03(0.03,0.06)mg/(kg·d)]和应用RTX时激素剂量[0.73(0.49,0.90)比0.71(0.58,0.89)mg/(kg·d)]、应用他克莫司比例[50%(10/20)比41%(9/22)]、剂量[0.03(0.02,0.04)比0.02(0.01,0.04)mg/(kg·d)]及应用RTX后他克莫司停用时间[71(42,91)比64(42,91)d]差异均无统计学意义(均P>0.05)。多因素回归分析显示,第2剂RTX应用后B细胞计数与重建时间相关(OR=0.26,95%CI 0.10~0.68,P=0.006),其预测重建时间ROC曲线下面积为0.89(95%CI 0.78~0.99,P<0.001),最佳截断值为0.925×106/L。结论既往和伴随应用他克莫司及其应用时长、RTX应用前1年内激素和他克莫司累积剂量及应用时的剂量不影响SSNS患儿B细胞的重建;第2剂RTX治疗SSNS后外周血B细胞计数(0.925×106/L)是重建时间的独立预测因素,可以较好预测重建时间并进行早期干预,维持疾病缓解。Objective To investigate the factors affecting the time taken for B cell reconstitution after rituximab(RTX)treatment in children with steroid-sensitive nephrotic syndrome.Methods This was a retrospective cohort study.The clinical data of 42 children with SSNS who received treatment with RTX in Department of Nephrology,Rheumatology and Immunology,Children′s Hospital Affiliated to Zhengzhou University between December 2019 and May 2023 were analyzed retrospectively.The data of demographics,immunosuppressant treatment and laboratory tests such as CD19+B cell count,urinary protein quantification were collected.The patients were divided into 2 groups,the early B cell reconstruction group and the late reconstruction group based on the average time of B cell reconstruction.A multivariate logistic regression model was used to analyze the factors impacting the timing of B cell reconstruction,and the predictive value of these factors was assessed by plotting the receiver operating characteristic(ROC)curve.Results There were 42 children,with 35 males and 7 females.They were aged 3.5(2.2,5.9)years at the onset of PNS and(8.4±3.3)years at their first RTX treatment.The time for B cell reconstitution was(152±53)d.There were 20 children in the early reconstruction group and 22 children in the late reconstruction group.There were no statistically significant differences(all P>0.05)between the 2 groups in terms of the cumulative dose of steroids within 1 year before receiving RTX infusion(0.29(0.16,0.50)vs.0.29(0.19,0.46)mg/(kg·d)),the percentage of children using tacrolimus before RTX(65%(13/20)vs.45%(10/22))and cumulative doses(0.04(0.03,0.05)vs.0.03(0.03,0.06)mg/(kg·d)),the steroid doses at the time of RTX infusion(0.73(0.49,0.90)vs.0.71(0.58,0.89)mg/(kg·d)),the percentage of children using tacrolimus at the initial RTX infusion(50%(10/20)vs.41%(9/22))and the doses(0.03(0.02,0.04)vs.0.02(0.01,0.04)mg/(kg·d)),the discontinuation time of tacrolimus post-RTX infusion(71(42,91)vs.64(42,91)d).A multivariate analysis reveale

关 键 词：儿童 利妥昔单抗 肾病综合征 B细胞 危险因素 

分 类 号：R726.9[医药卫生—儿科]