儿童抗H因子抗体相关非典型溶血尿毒综合征的临床特征和预后分析  

Clinical characteristics and prognosis of anti-factor H antibody associated-atypical hemolytic uremic syndrome in children

作　　者：吴丹[1] 刘小荣[1] 陈植[1] 凌晨[1] 孟群[1] Wu Dan;Liu Xiaorong;Chen Zhi;Ling Chen;Meng Qun(Department of Nephrology,Beijing Children′s Hospital,Capital Medical University,National Center for Children′s Health,Beijing 100045,China)

机构地区：[1]国家儿童医学中心,首都医科大学附属北京儿童医院肾脏科,北京100045

出　　处：《中华实用儿科临床杂志》2023年第6期431-437,共7页Chinese Journal of Applied Clinical Pediatrics

基　　金：北京市科学技术委员会首都临床特色应用研究(Z161100000516106);首都卫生发展科研专项项目(2016-2-2094);北京市科学技术委员会重点项目(D181100000118006)。

摘　　要：目的总结儿童抗H因子抗体相关非典型溶血尿毒综合征(aHUS)的临床特点,分析疾病复发和不良预后的相关危险因素。方法对2011年11月至2021年11月首都医科大学附属北京儿童医院确诊的52例抗H因子抗体相关aHUS患儿进行前瞻性队列研究,描述其遗传背景、临床和肾脏病理特征以及治疗和预后,采用生存曲线和Cox回归模型对疾病复发和预后进行分析。结果52例患儿中男33例,女19例;起病年龄为2.4~12.8岁,92.3%(48/52)的患儿起病年龄集中在4~12岁。42例患儿评估了H因子相关蛋白1(CFHR1)和H因子相关蛋白3(CFHR3)基因拷贝数,42.9%(18/42)的患儿携带CFHR1纯合缺失,CFHR1纯合缺失患儿有83.3%(15/18)合并CFHR3纯合缺失。在血浆治疗的基础上,首次起病时免疫抑制治疗(激素和/或免疫抑制剂)的使用率为76.9%(40/52),总病程的使用率为86.5%(45/52),免疫抑制治疗总疗程为6~20个月。中位随访时间为58(28,91)个月,仅23.1%(12/52)的患儿出现复发。CFHR1纯合缺失患儿较非纯合缺失患儿无复发生存率显著降低(χ^(2)=4.700,P=0.030)。CFHR1合并CFHR3纯合缺失患儿较其他患儿无复发生存率也显著下降(χ^(2)=4.181,P=0.041)。随访结束时,73.1%(38/52)的患儿肾功能正常,且无持续蛋白尿和高血压,23.1%(12/52)的患儿有持续蛋白尿和/或高血压,仅1例患儿处于慢性肾脏病3~4期,1例患儿为透析依赖。结论抗H因子抗体相关aHUS患儿发病年龄集中在4~12岁,对血浆疗法联合免疫抑制治疗反应良好。抗H因子抗体相关aHUS患儿合并CFHR1、CFHR3纯合缺失患儿复发率高,早期使用免疫抑制治疗和完善CFHR1、CFHR3基因拷贝数评估,对于预防疾病复发及改善预后具有重要意义。Objective To summarize the clinical data of anti-factor H antibody-associated atypical hemolytic uremic syndrome(aHUS)in children,and analyze the risk factors for disease recurrence and poor prognosis.Methods A prospective cohort study was conducted on 52 children with anti-factor H antibody-associated aHUS in Beijing Children′s Hospital,Capital Medical University from November 2011 to November 2021.Patient information about the genetic background,clinical and renal pathological characteristics,treatment,and prognosis were collected.Then,the disease recurrence and prognosis were analyzed using the survival curve and Cox regression model.Results In 52 children,there were 33 males and 19 females.The average age of onset for aHUS was 2.4-12.8 years,and 92.3%(48/52)of the children developed symptoms at the age of 4-12 years.The copy numbers of complement factor-H-related 1(CFHR1)and complement factor-H-related 3(CFHR3)genes were calculated in 42 children.Among the 42 cases,18 cases(42.9%)had CFHR1 homozygous deletion,and 83.3%(15/18)of them also had CFHR3 homozygous deletion.All the patients were given plasma therapy.Besides,76.9%(40/52)of the children were treated with immunosuppressive therapy(steroid and/or immunosuppressant)at the first onset of the disease.About 86.5%(45/52 cases)of the patients received immunosuppressive therapy in the course of disease,and the immunosuppressive treatment lasted for 6-20 months in total.The median follow-up time was 58(28,91)months.Among 52 patients,only 12 patients(23.1%)suffered disease recurrence.The relapse-free survival rate in children with CFHR1 homozygous deletion was significantly lower than that in children with non-homozygous deletion(χ^(2)=4.700,P=0.030).The relapse-free survival rate in children with CFHR1 and CFHR3 homozygous deletions was also significantly lower than that in other children(χ^(2)=4.181,P=0.041).At the end of the follow-up,73.1%(38/52)of the children had normal renal function and no persistent proteinuria or hypertension.23.1%(12/52 cases)of t

关 键 词：非典型溶血尿毒综合征 补体因子H 预后 血栓性微血管病 儿童 

分 类 号：R726.9[医药卫生—儿科]