Pathogenic Variants in Complement Genes and Risk of Atypical Hemolytic Uremic Syndrome Relapse after Eculizumab Discontinuation
Pathogenic Variants in Complement Genes and Risk of Atypical Hemolytic Uremic Syndrome Relapse after Eculizumab Discontinuation
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DOI：
10.2215/cjn.06440616
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发表时间：
2017-01-01
影响因子：
9.8
通讯作者：
Fremeaux-Bacchi, Veronique
中科院分区：
文献类型：
--
作者：
Fakhouri, Fadi;Fila, Marc;Fremeaux-Bacchi, Veronique
背景和目的补体抑制剂eculizumab显著改善了非典型溶血性尿毒症综合征的预后。然而，Eulizumab治疗非典型溶血性尿毒症综合征的最佳持续时间仍存在争议。我们报告了法国非典型溶血性尿毒症综合征工作组首次在非典型溶血性尿毒症综合征患者中停用eculizumab的两年经验。设计、设置、参与者和测量使用法国非典型溶血性尿毒症综合征登记数据库，我们回顾了2010至2014年间所有停用eculizumab的非透析非典型溶血性尿毒症综合征患者，并回顾了他们的相关临床和生物学数据。停止使用eculizumab的决定是由负责患者的临床医生做出的。所有患者都通过定期尿检和血液测试进行密切监测。结果108例接受eculizumab治疗的患者中，38例(9例儿童，29例成人)停用eculizumab，中位疗程17.5个月。21名患者(55%)携带新的或罕见的补体基因变异。在检测到补体基因变异的患者和未检测到补体基因变异的患者中，使用eculizumab的肾脏恢复情况同样良好。中位随访22个月后，12名患者(31%)经历了非典型溶血性尿毒症综合征复发。11例有补体因子H变异的患者中有8例(72%)复发，8例膜辅因子蛋白变异的患者中有4例(50%)复发，16例无罕见变异的患者中没有发现复发。在复发患者中，早期重新引入(
Background and objectives The complement inhibitor eculizumab has dramatically improved the outcome of atypical hemolytic uremic syndrome. However, the optimal duration of eculizumab treatment in atypical hemolytic uremic syndrome remains debated. We report on the French atypical hemolytic uremic syndrome working group's first 2-year experience with eculizumab discontinuation in patients with atypical hemolytic uremic syndrome.Design, setting, participants & measurements Using the French atypical hemolytic uremic syndrome registry database, we retrospectively identified all dialysis free patients with atypical hemolytic uremic syndrome who discontinued eculizumab between 2010 and 2014 and reviewed their relevant clinical and biologic data. The decision to discontinue eculizumab was made by the clinician in charge of the patient. All patients were closely monitored by regular urine dipsticks and blood tests. Eculizumab was rapidly (24 48 hours) restarted in case of relapse.Results Among 108 patients treated with eculizumab, 38 patients (nine children and 29 adults) discontinued eculizumab (median treatment duration of 17.5 months). Twenty-one patients (55%) carried novel or rare complement genes variants. Renal recovery under eculizumab was equally good in patients with and those without complement gene variants detected. After a median follow-up of 22 months, 12 patients (31%) experienced atypical hemolytic uremic syndrome relapse. Eight of 11 patients (72%) with complement factor H variants, four of eight patients (50%) with membrane cofactor protein variants, and zero of 16 patients with no rare variant detected relapsed. In relapsing patients, early reintroduction (