利妥昔单抗治疗激素依赖肾病综合征患儿五例

Treatment of children with steroid-dependent nephrotic syndrome with rituximab

目的 探讨利妥昔单抗（RTX）治疗激素依赖肾病综合征患儿的疗效.方法 2012年5月至2013年2月选取我院收治的激素依赖且仅对加用钙调神经磷酸酶抑制剂有效、但减量后仍然复发的患儿5例（男3例,女2例）为研究对象.停用钙调神经磷酸酶抑制剂,激素改为足量应用,一般状况改善后,给予RTX 375 mg/m2,每周1次,共3次为一疗程;尿蛋白转阴后5d,激素改为隔日2 mg/kg,以后每2周减5 mg,直至停药.用药期间定期监测,当外周血CD19^＋B细胞≥3％时再补充1次RTX,用法同前.观察患儿尿蛋白转阴情况、维持缓解时间、激素及环孢素副作用改善的情况、循环CD19^＋B细胞水平变化及RTX不良反应情况.结果 5例患儿于开始第1次RTX治疗后2～7d尿蛋白转阴.治疗前外周血CD19^＋B淋巴细胞比例为7.8％ ～13.0％,第1疗程RTX治疗后均下降至0,随访第6～8月时开始回升,当第7～10个月上升至3.3％ ～6.1％时,再次给予1次RTX,CD19^＋B淋巴细胞再次降为0,其中2例（例3、例1）患儿于第16、17个月时CD19^＋B淋巴细胞再次回升,并于第17、18个月回升至4.16％、4.17％时分别再次给予1次RTX,后CD19^＋B淋巴细胞再次降至0.目前5例患儿尿蛋白持续阴性,维持缓解12 ～20个月.RTX输注过程中与随访中均未见明显不良反应,激素和钙调神经磷酸酶抑制剂的副作用如柯兴貌、齿龈增生等基本消失.结论 对于激素依赖且仅对钙调神经磷酸酶抑制剂有效、但减量后仍然复发的肾病综合征患儿,在首次RTX治疗后,通过定期监测CD19^＋B淋巴细胞水平补充RTX,可以使患儿摆脱激素和免疫抑制剂,维持缓解状态.

Objective To investigate the effects of rituximab （RTX） in children with steroiddependent nephrotic syndrome.Method Five cases of children with steroid-dependent nephrotic syndrome seen from May 2012 to February 2013 in whom only steroid plus calcineurin inhibitor was effective and the disease recurred on reduction of dose were enrolled into this study,including 3 males and 2 females.Calcineurin inhibitors were stopped and steroids was changed to full dose.After the general condition improved,RTX was given at a dose of 375 mg/m2,once a week for a total of three times for one course.After urine protein became negative for five days,the dose of steroid was changed to 2 mg/kg every other day,thereafter the dose was reduced by 5 mg per every 2 weeks,until discontinuation.After regular monitoring,when peripheral blood B cells were ≥ 3%,a second RTX was added.Result Urine protein was negative in 2-7 days in 5 patients after the first RTX treatment.Before treatment B lymphocytes in peripheral blood was 7.8% to 13.0% and after the first course of RTX treatment decreased to 0 in the first 6 to 8 months at the beginning of recovery,while in the first 7 to 10 months to 3.3%-6.1%,after a second RTX was given,B lymphocytes were reduced to 0,but in two cases （cases 1 and 3） B lymphocytes rose again at 16 and 17 months,in the first 17 and 18 months rose to 4.16% and 4.17%,RTX was given once again respectively.B lymphocytes were reduced to 0 again.Currently the 5 patients continued to be negative for urine protein,maintaining remission for 12 to 20 months.RTX infusion had no significant side effects,and side effects of steroid and calcineurin inhibitor disappeared.Conclusion In children with steroiddependent and only calcineurin inhibitor effective nephritic syndrome,relapse may still occur after improvement of nephrotic syndrome,after the first RTX treatment,regular monitoring of B lymphocytes,RTX supplementary treatment in advance can help discontinuation of steroids and immunosuppressive agents and maintain remission.