多靶点免疫抑制剂治疗儿童激素耐药型肾病综合征前瞻性研究

A prospective study of multi-target immunosuppressive therapy for children with steroid-resistant nephritic syndrome

目的探讨多靶点免疫抑制剂治疗儿童激素耐药型肾病综合征(SRNS)疗效及安全性。方法选择2013年9月至2015年10月安徽省儿童医院等5家医疗机构的SRNS患儿48例,在综合治疗基础上随机分为两组:(1)观察组:给予环孢素(CSA)[3~4 mg/(kg·d)]联合霉酚酸酯(MMF)[20 mg/(kg·d)]多靶点治疗;(2)对照组:给予CSA[4~6 mg/(kg·d)]。治疗期间严密监测各组不良反应,分别于治疗后2周、1个月、3个月、6个月测定患儿CSA浓度、尿蛋白/尿肌酐、肝肾功能、血常规、尿常规等。结果治疗期间观察组CSA平均血药浓度为(88.76±16.94)μg/L,对照组为(152.96±19.20)μg/L(P<0.001)。治疗1、3个月,观察组尿蛋白/尿肌酐与对照组同时间尿蛋白/尿肌酐相比下降(P<0.05)。治疗1、3个月,观察组血浆白蛋白与对照组同时间血浆白蛋白相比升高(P<0.05)。治疗期间两组尿β2-微球蛋白相比差异无统计学意义(P>0.05)。观察组总缓解率为88%,对照组总缓解率为87%。观察组在治疗2周、1个月时缓解率优于对照组(P<0.05)。治疗期间主要的副反应有感染、胃肠道反应、多毛、高血压、白细胞下降。观察组在治疗期间不良反应发生率明显低于对照组(P<0.05)。结论 CSA联合MMF可以使SRNS患儿早期即可得到缓解,也可与单用CSA一样维持长期缓解,但副反应更小。

Objective To observe the efficacy and safety of muhi-target immunosuppressive therapy in treatment of children with steroid-resistant nephritic syndrome （SRNS）. Methods A total of 48 children with SRNS were enrolled in this muhicenter prospective study. Based on the same comprehensive treatment, the children were randomly divided into two groups ： （ 1 ） observation group ： they were orally given CSA [ 3 -4 mg/（kg· d ） ] and MMF 120 mg/（kg· d） ] multi- target immunosuppressive therapy; （2）control group：they were orally given CSA I4- 6 mg/（kg· d） ]. The side effects were closely observed. The plasma concentrations of CSA, urine protein to creatinine ratios, liver and kidney function, blood routine and urine β2-microglobulin were respectively compared between the two groups after 2 weeks, 1 month, 3 months and 6 months of treatment. Results The average plasma concentrations of CSA in the observation group was （88.86±16.94） μg/L, and in the control group it was （152.96±19.20） μg/L（P 〈0.001）. The urine protein to creatinine ratios in the observation group after 1 month and 3 months of treatment were lower than the control group in the same time period （P 〈 0.05）. The serum albumin in the observation group after 1 month and 3 months of treatment was higher than the control group in the same time period （P 〈 0.05 ）. The urine β2-microglobulin in these two groups bad no differ-ences during the treatment （P 〉 0.05）. The overall remis- sion rate of the observation group was 88%, and in the control group it was 87%. The remission rate of the obser- vation group after 2 weeks and 1 month of treatment was better than the control group（P 〈 0.05）. The main side ef- fect during therapy was infection, gastrointestinal reac-tion, crinosity, hypertension and leukocyte decrease. The side effect of the observation group was less than the control group （P 〈 0.05）. Conclusion The multi-target therapy in children with SRNS by CSA and MMF results in early remis- sion and can keep long-term remission with mild side effect.