依库珠单抗治疗与儿童中高突变相关非典型溶血尿毒综合征的肾脏改善恢复：一项回顾性队列研究。

Improved Renal Recovery with Eculizumab Therapy among Children with High Prevalence of Mutation-Associated Atypical Hemolytic Uremic Syndrome: A Retrospective Cohort Study.

机构信息

Division of Pediatric Nephrology, Children's Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia,

Division of Pediatric Nephrology, Department of Pediatrics, McMaster Children's Hospital, McMaster University, Hamilton, Ontario, Canada,

出版信息

Kidney Blood Press Res. 2020;45(6):939-954. doi: 10.1159/000510612. Epub 2020 Nov 25.

DOI:10.1159/000510612

PMID:33238263

Abstract

INTRODUCTION

Genetic defects that determine uncontrolled activation of the alternative complement pathway have been well documented, which account for approximately 40-60% of atypical hemolytic uremic syndrome (aHUS) cases worldwide. In Saudi Arabia, nearly half of the marriages are consanguineous, resulting in a high prevalence of such genetic diseases. Recent studies have demonstrated the effectiveness of eculizumab against aHUS.

OBJECTIVE

We report our experience of using plasma therapy or/and eculizumab to treat children with aHUS in a tertiary care center in Saudi Arabia and to compare their clinical characteristics, genetic mutations, and treatment outcomes.

METHODS

A retrospective cohort study was conducted between January 2010 and May 2017. Data, including demographic parameters, clinical presentation, hospital stay duration, need for dialysis, renal recovery, genetic mutations, and outcomes, were obtained from electronic medical records of all eligible patients.

RESULTS

Overall, 21 children with aHUS were included, of which 12 (57.1%) received eculizumab therapy and 9 (42.9%) received only plasma therapy. End-stage renal disease occurred in 7 children (33.3%), of which 4 (57.1%) received only plasma therapy and 3 (42.9%) received eculizumab therapy whose genetic mutations were not related to the complement dysregulation system. No child who received eculizumab therapy showed recurrence; however, 3 children (33.3%) who received plasma therapy alone showed recurrence. Genetic mutations were detected in 12/20 (60%) of those who underwent genetic screening.

CONCLUSIONS

Children who received eculizumab therapy showed good renal recovery and maintained remission compared with children who received plasma therapy alone. Genetic mutations were detected in 60% of the patients, which was associated with a high prevalence of consanguineous marriages.

摘要

简介

已充分记录了决定替代补体途径不受控制激活的遗传缺陷，这些缺陷约占全球 40-60%的非典型溶血尿毒综合征 (aHUS) 病例。在沙特阿拉伯，近一半的婚姻是近亲结婚，导致此类遗传疾病的高发。最近的研究表明依库珠单抗对 aHUS 有效。

目的

我们报告了在沙特阿拉伯的一家三级护理中心使用血浆疗法或/和依库珠单抗治疗 aHUS 儿童的经验，并比较了他们的临床特征、遗传突变和治疗结果。

方法

对 2010 年 1 月至 2017 年 5 月期间进行的回顾性队列研究。从所有符合条件的患者的电子病历中获取数据，包括人口统计学参数、临床表现、住院时间、是否需要透析、肾功能恢复、遗传突变和结局。

结果

总体而言，共纳入 21 例 aHUS 患儿，其中 12 例（57.1%）接受依库珠单抗治疗，9 例（42.9%）仅接受血浆治疗。7 例（33.3%）患儿发生终末期肾病，其中 4 例（57.1%）仅接受血浆治疗，3 例（42.9%）接受依库珠单抗治疗，且其遗传突变与补体失调系统无关。接受依库珠单抗治疗的患儿均未复发；然而，仅接受血浆治疗的 3 例患儿（33.3%）出现复发。接受基因筛查的 20 例患儿中有 12 例（60%）检测到遗传突变。