欢迎访问《中国循证儿科杂志》官方网站，今天是
English Version
中国循证儿科杂志

中国循证儿科杂志 ›› 2019, Vol. 14 ›› Issue (5): 327-331.DOI: 10.3969/j.issn.1673-5501.2019.05.002

• 论著 • 上一篇    下一篇

Ⅲ型或Ⅳ型狼疮性肾炎患儿环磷酰胺诱导治疗3和6个月后序贯吗替麦考酚酯的非随机对照试验

魏骐骄, 王长燕, 李冀, 王薇, 宋红梅   

  1. 中国医学科学院北京协和医学院北京协和医院儿科 北京,100730
  • 收稿日期:2019-09-19 出版日期:2019-10-25
  • 通讯作者: 宋红梅, E-mail:songhm1021@hotmail.com
  • 基金资助:
    中国医学科学院医学与健康科技创新工程项目:2016-I2M-1-008;北京市科协金桥工程种子资金C类项目:JQ17032

Non-randemized controlled trial of the efficacy and adverse effects if sequential mycophenolate mofetil after 3 months and 6 months of cyclophosphamide in children with type Ⅲ or Ⅳ lupus nephritis

WEI Qi-jiao, WANG Chang-yan, LI Ji, WANG Wei, SONG Hong-mei   

  1. Department of Pediatrics, Peking Union Medical College Hospital, Beijing 100730,China
  • Received:2019-09-19 Online:2019-10-25
  • Contact: SONG Hong-mei, E-mail: songhm1021@hotmail.com

PDF

603

摘要： 目的 对肾脏病理Ⅲ型或Ⅳ型的狼疮性肾炎(LN)患儿用环磷酰胺(CTX)诱导治疗3和6个月后序贯吗替麦考酚酯(MMF)的疗效和不良反应进行探讨。方法 非随机对照试验。Ⅲ型或Ⅳ型LN患儿,在患儿家长充分知晓CTX诱导治疗3个月(A组)和6个月(B组)后序贯MMF不同方案利弊的前提下,根据患儿家长意愿入A组或B组,考察两组疗效和随访12个月时药物不良反应事件。主要结局指标为有效率(完全缓解+部分缓解),完全缓解:血常规、肾功能、白蛋白、血沉正常,补体C3≥0.73 g·L-1,C4≥0.1 g·L-1,抗ds-DNA抗体免疫荧光法和ELISA法检测双阴性,且24 h尿蛋白定量<150 mg;部分缓解:达到以下任意1项,①24 h尿蛋白定量较治疗前降低50%,且总量<3.5 g·24 h-1,②血肌酐和尿蛋白/肌酐较治疗前改善50％,③血肌酐较治疗前改善50％,尿蛋白/肌酐<1.0,实验室检测均较治疗前有改善。结果 2012年1月至2018年1月符合本文纳入和排标准的33例患儿进入本文分析。A组和B组在发病年龄、肾活检年龄、性别、发病季节、居住环境、肾脏病理类型和自身免疫性疾病家族史差异均无统计学意义。两组治疗前、诱导治疗结束时(A组3个月、B组6个月)和治疗后12个月实验室检查指标(血常规、肾功能、补体、白蛋白、尿蛋白、抗ds-DNA抗体和ESR)差异均无统计学意义。诱导治疗3个月时两组患儿有效率差异无统计学意义,治疗3个月时A组和B组患儿CTX累积用量(mg·kg-1)分别为(94.0±20.5)和(104.1±34.8),差异无统计学意义(P=0.39),3个月及6个月时CTX平均累积量与治疗有效率不相关(r=0.95,P=0.051)。两组总的药物不良反应发生率差异无统计学意义,药物不良反应主要表现为WBC＜4×109·L-1、感染、胃肠道不适、月经不规律,均未出现因使用CTX所致的脱发及出血性膀胱炎。结论 Ⅲ型或Ⅳ型LN患儿CTX诱导治疗3和6个月后序贯MMF对治疗结局无影响。

关键词: 儿童增殖性狼疮性肾炎, 环磷酰胺, 吗替麦考酚酯, 诱导缓解治疗

Abstract: Objective To investigate the efficacy and adverse effects of sequential mycophenolate mafetil (MMF) after 3 months and 6 months of cyclophosphamide (CTX) in children with type Ⅲ or Ⅳ lupus nephritis (LN).Methods This is a non-randomized controlled trial. The objects were children with type Ⅲ or Ⅳ LN. Parents of these children were fully aware of the benefits and adverse effects of sequential MMF after 3 months (group A) and 6 months (group B) of CTX induction therapy. According to the parents' decision, these children were divided into group A and B. The efficacy and adverse events of the two groups were followed up for 1 year. The main outcome indicators of efficacy are as follows. Complete remission: blood routine, renal function, albumin, erythrocyte sedimentation rate are normal and C3≥0.73 g·L-1, C4≥0.1 g·L-1, anti-ds-DNA antibody is negative with two methods of immunofluorescence and ELISA. At the same time, 24 h urine protein should be lower than150 mg. Partial remission: Any one of the following is achieved:①24 h urine protein is 50% lower than that before treatment, and the total amount is <3.5 g·24 h-1.②Serum creatinine and urine protein/creatinine are improved by 50%.③Serum creatinine is improved by 50% and urinary protein/creatinine is <1.0. And laboratory tests are improved compared to before the treatment.Results Thirty three children were retrospectively analyzed. All the children were admitted to the Peking Union Medical College Hospital from January 2012 to January 2018. The age of onset, age of kidney biopsy, gender, season of onset, living environment, type of renal pathology, incidence of family history were similar in two groups. The efficacy and side effects have no significant difference between the two groups, at the end of treatment (3 months in group A, 6 months in group B) and 12 months after treatment. There was no significant difference in efficacy at 3 months between two groups. There was no significant difference in efficacy at 6 months and 1 year between two groups. At 3 months, the cumulative dose of CTX (mg·kg-1) were (94.0±20.5) and (104.1±34.8) respectively in group A and B. There was no significant difference (P=0.39). There was no correlation between the mean CTX cumulative amount and the efficacy at 3 months and 6 months(r= 0.95, P= 0.051). There was no significant difference in the incidence of adverse events between the two groups. The adverse events were mainly white blood cell reduction, infection, gastrointestinal discomfort and irregular menstruation. Hair loss and hemorrhagic cystitis did not happen because of CTX.Conclusions equencing of MMF after 3 months or 6 months of CTX treatment has no effect on efficacy and adverse effects for children with proliferative lupus nephritis.

Key words: Cyclophosphamide, Mycophenolate mofetil, Proliferative lupus nephritis in children, Remission induction therapy