激素、钙调磷酸酶抑制剂和吗替麦考酚酯三联用药治疗激素耐药型肾病综合征患儿的疗效和安全性

doi:10.3969/j.issn.1673-5501.2021.01.004

摘要/Abstract

摘要： 背景少数病初即表现为激素耐药型的儿童原发性肾病综合征,临床治疗较困难,对于无明确遗传因素证据患儿,临床多采用激素联合一种或多种免疫抑制剂进行治疗,但目前尚无统一的药物添加原则或规范的治疗方案。目的观察激素联合钙调磷酸酶抑制剂、吗替麦考酚酯对初治激素耐药型肾病综合征患儿的治疗效果和安全性。设计回顾性非随机对照研究。方法纳入2014年1月至2020年12月北京大学第一医院儿科收治的初治激素耐药型肾病综合征患儿,除外遗传因素后,分为A组(激素+钙调磷酸酶抑制剂+吗替麦考酚酯三联治疗,三种药按先后顺序依次添加)、B组(激素+钙调磷酸酶抑制剂+吗替麦考酚酯三联治疗,激素联合钙调磷酸酶抑制剂治疗3个月以上无效,改为激素联合吗替麦考酚酯治疗3个月以上仍无效,最后三者联用)、C组(钙调磷酸酶抑制剂+吗替麦考酚酯治疗,因类固醇性糖尿病或青光眼停用激素)和D组(激素+钙调磷酸酶抑制剂+美罗华),比较各组的治疗效果。主要观察指标 尿蛋白转阴时间、尿蛋白阴性时间百分比、平均复发次数。结果 39例患儿纳入分析,A、B、C、D组分别为16、8、3、12例。A、B、C、D组尿蛋白转阴率分别为75.0%(12/16)、75.0%(6/8)、100%(3/3)和75.0%(9/12),组间比较差异无统计学意义(P>0.05)。A、D组平均尿蛋白转阴时间低于B、C组,尿蛋白阴性时间百分比高于B、C组,差异均有统计学意义(P<0.05)。A和D组间平均尿蛋白转阴时间和尿蛋白阴性时间百分比差异均无统计学意义(P>0.05)。各组患儿用药期间未报告药物相关不良反应。结论对于少数原发性激素耐药型肾病综合征患儿,激素联合钙调磷酸酶抑制剂、吗替麦考酚酯三联治疗有较好的效果。

关键词: 肾病综合征, 激素耐药型, 钙调磷酸酶抑制剂, 吗替麦考酚酯

Abstract: Background A few cases of childhood primary nephrotic syndrome showed steroid-resistant nephrotic syndrome (SRNS) which was difficult to treat. For these cases of SRNS, after excluding genetic factors other agents were added such as calcineurin inhibitor and mycophenolate mofetil. However, there were no regular principles or unified therapeutic schedules. Objective To observe the therapeutic effects and safety of steroid combined with calcineurin inhibitors and mycophenolate mofetil on pediatric cases of steroid-resistant nephrotic syndrome. Design Retrospective non-randomized controlled study. Methods Data were collected from children with steroid-resistant nephrotic syndrome treated in the department of pediatrics of Peking University First Hospital from January 2014 to December 2020. After excluding genetic factors, they were divided into four groups as A (steroid + calcineurin inhibitor + mycophenolate mofetil, added sequentially), B (if steroid combined calcineurin inhibitor for over 3 months is ineffective, it will be replaced by steroid combined with mycophenolate mofetil for over 3 months. If there is still no effect, the triple therapy of steroid, calcineurin inhibitor and mycophenolate mofetil will be used.), C (calcineurin inhibitor + mycophenolate mofetil, withdrawal of steroid because of glucocorticoid diabetes or glaucoma) and D (steroid + calcineurin inhibitor + rituximab). Main observation parameters The time of urine protein changed negative, the time percentage of urine protein remained negative and average numbers of relapse. Results There were 39 pediatric cases of steroid-resistant nephrotic syndrome in this study, including 16, 8, 3 and 12 cases in group A, B, C and D, respectively. The urine protein negative rates of group A, B, C and D were 75.0% (12/16), 75.0% (6/8), 100% (3/3) and 75.0% (9/12), respectively. There was no difference on urine protein negative rate between four groups (P>0.05). However, the average time of urine protein conversed to negative was much less while the percentage of urine protein conversed to negative was much higher in groups A and D as compared to group B and C (P<0.05). There was no significant difference in the average time of urine protein conversed to negative and the percentage of urine protein conversed to negative between group A and group D (P>0.05). Conclusion Steroid combined with calcineurin inhibitors and mycophenolate mofetil showed better effects on some idiopathic steroid-resistant nephrotic syndrome in children.

Key words: Nephrotic syndrome, Steroid-resistant, Calcineurin inhibitors, Mycophenolate mofetil

苏白鸽, 张宏文, 刘晓宇, 肖慧捷, 姚勇. 激素、钙调磷酸酶抑制剂和吗替麦考酚酯三联用药治疗激素耐药型肾病综合征患儿的疗效和安全性[J]. 中国循证儿科杂志, 2021, 16(1): 56-60.

SU Baige, ZHANG Hongwen, LIU Xiaoyu, XIAO Huijie, YAO Yong. The effects of steroid combined with calcineurin inhibitors and mycophenolate mofetil on pediatric cases of steroid-resistant nephrotic syndrome[J]. Chinese Journal of Evidence-Based Pediatrics, 2021, 16(1): 56-60.

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