中国实用儿科杂志

中国实用儿科杂志 ›› 2022, Vol. 37 ›› Issue (8): 625-631.DOI: 10.19538/j.ek2022080612

• 论著 • 上一篇    下一篇

环孢霉素A与他克莫司治疗儿童难治性肾病综合征疗效及安全性对照研究

  

  1. 上海市儿童医院 上海交通大学学院附属儿童医院肾脏风湿科，上海  200062
  • 出版日期:2022-08-06 发布日期:2022-08-31
  • 通讯作者: 黄文彦，电子信箱：hwy65@hotmail.com
  • 基金资助:
    上海市自然科学基金面上项目（19ZR1442300）；上海市卫生和计划生育委员会科研课题青年项目（20164Y0192）

Efficacy and safety of cyclosporine A versus tacrolimus in children with refractory nephrotic syndrome

  1. Department of Nephrology and Rheumatology，Shanghai Children’s Hospital of Shanghai，Children’s Hospital Affiliated to Shanghai Jiaotong University School of Medicine，Shanghai  200062，China
  • Online:2022-08-06 Published:2022-08-31

摘要： 目的    评估环孢霉素A与他克莫司治疗儿童难治性肾病综合征的疗效及安全性。方法    回顾性分析2012年6月至2018年6月在上海市儿童医院接受环孢霉素A与他克莫司治疗的118例难治性肾病综合征患儿信息，包含患儿一般情况、实验室检查、肾组织病理、治疗后转归及不良反应等，并进行统计分析。采用Kaplan-Meier生存分析绘制生存曲线，行相关比较分析。结果    一般临床资料：纳入环孢霉素A治疗病例总计66例，其中18例为激素耐药型肾病综合征，45例为激素依赖型肾病综合征，3例为频反复型肾病综合征，其中56例行肾穿刺活检。52例他克莫司组中12例为激素耐药型肾病综合征，40例为激素依赖型肾病综合征，其中47例行肾穿刺活检；疗效及安全性分析：环孢霉素A与他克莫司对难治性肾病综合征维持远期完全缓解无组间差异。但治疗第6个月，难治性肾病综合征他克莫司组完全缓解率（86.5%）明显高于环孢霉素A组（68.2%），差异有统计学意义（P<0.05），其中以激素依赖型/频反复型肾病综合征疗效差异有统计学意义（P<0.05），激素耐药型肾病综合征组间疗效无统计学差异。此外，在微小病变组及非微小病变组内，环孢霉素A与他克莫司无疗效差异；副反应方面，他克莫司组多毛症发生率、牙龈增生发生率均明显低于环孢霉素A组，且有显著性差异（P<0.01），但在使用他克莫司第16个月及18个月后出现2例急性胰腺炎患儿。环孢霉素A组急性肾损伤（5/66）及慢性肾毒性改变（2/66）发生率高于他克莫司组。结论    环孢霉素A与他克莫司对难治性肾病综合征远期疗效无差异。对于激素依赖型/频反复型肾病综合征患儿，他克莫司短期疗效较环孢霉素A更好，但需警惕急性胰腺炎发生。对环孢霉素A累计治疗时间超过30个月患儿需高度警惕钙调神经磷酸酶抑制剂肾毒性发生。

关键词: 儿童, 肾病综合征, 环孢霉素A, 他克莫司

Abstract: Objective    To evaluate the efficacy and safety of cyclosporine A（CsA）and tacrolimus（TAC）in children with refractory primary nephrotic syndrome（PNS）. Methods    One hundred and eighteen children with refractory PNS， who were treated with TAC or CsA from June 2012 to June 2018，were included in the study. Patient’s clinical and pathological information were gathered for retrospective analysis，including general informatioin，laboratory tests，renal pathology，prognosis and side effects. Kaplan-Meier was used to draw survival curves and comparative analysis was made. Results    In the CsA group（66 cases），patients with frequent relapses（FRNS），steroid dependency （SDNS），or resistance to steroid therapy（SRNS）were 3，45 and 18，respectively. In the TAC group（52 cases），patients with SDNS or SRNS were 40 and 12，respectively. Fifty-six of the 66 patients（84.8%）in the CsA group and 47 of the 52 patients （90.4%） in the TAC group received percutaneous renal biopsy. There was no difference between the two groups in the long-term complete remission of NS. At the end of 6 months of therapy，complete remission was seen in 68.2%（45/66）and 86.5% （45/52）of refractory PNS patients treated with CsA and TAC，respectively（P?< 0.05）. The efficacy of CsA and TAC in FRNS and SDNS was significant difference，but there was no significantly different in SRNS. There was no difference in the effects between CsA and TAC in the minimal change diseace（MCD） group and non-MCD group. The side effects of gum hyperplasia and hypertrichosis were significantly less in TAC group as compared to CsA group（P< 0.01）. But two patients had acute pancreatitis after 16 and 18 months of treatment with TAC. The incidence rate of acute kidney injury（5/66）and chronic nephrotoxicity（2/66）in CsA group was higher than that in TAC group. Conclusion    In the long term，the efficacy of CsA and TAC in refractory PNS has no significant difference. But the treatment for FRNS and SDNS with TAC is associated with higher efficacy in comparison with CsA at 6 months of therapy，but it is necessary to be alert to the presence of acute pancreatitis. The patient with CsA treatment over 30 months should be alert to the CNI nephrotoxicity.

Key words: child, nephrotic syndrome, cyclosporine A, tacrolimus