AlZabali Saeed, AlBatati Sawsan, Rahim Khawla, Faqeehi Hassan, Osman Abubaker, Bamhraz Abdulaziz, Saleh Mohammed A, Kari Jameela A, Aloufi Majed, Eid Loai, Nasser Haydar, Imam Abubakr, AlHammadi Entesar, Alkandari Omar, Al Riyami Mohammed, Sethi Sidharth, Licht Christoph, Alhasan Khalid A, AlAnazi Abdulkarim
Pediatric Nephrology Department, King Fahad Medical City, Riyadh 11525, Saudi Arabia.
Division of Pediatric Nephrology, Children's Hospital-McMaster University, Hamilton, ON L8N 3Z5, Canada.
Children (Basel). 2022 Nov 11;9(11):1734. doi: 10.3390/children9111734.
Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening thrombotic microangiopathy (TMA), which has been treated successfully with eculizumab. The optimal duration of eculizumab in treating patients with aHUS remains poorly defined.
We conducted a multicenter retrospective study in the Arabian Gulf region for children of less than 18 years of age who were diagnosed with aHUS and who discontinued eculizumab between June 2013 and June 2021 to assess the rate and risk factors of aHUS recurrence.
We analyzed 28 patients with a clinical diagnosis of aHUS who had discontinued eculizumab. The most common reason for the discontinuation of eculizumab was renal and hematological remission (71.4%), followed by negative genetic testing (28.6%). During a median follow-up period of 24 months after discontinuation, 8 patients (28.5%) experienced HUS relapse. The risk factors of recurrence were positive genetic mutations ( = 0.020). On the other hand, there was no significant relationship between the relapse and age of presentation, the need for acute dialysis, the duration of eculizumab therapy before discontinuation, or the timing of eculizumab after the presentation. Regarding the renal outcomes after discontinuation, 23 patients were in remission with normal renal function, while 4 patients had chronic kidney disease (CKD) (three of them had pre-existing chronic kidney disease (CKD) before discontinuation, and one case developed a new CKD after discontinuation) and one patient underwent transplantation.
The discontinuation of eculizumab in patients with aHUS is not without risk; it can result in HUS recurrence. Eculizumab discontinuation can be performed with close monitoring of the patients. It is essential to assess risk the factors for relapse before eculizumab discontinuation, in particular in children with a positive complement variant and any degree of residual CKD, as HUS relapse may lead to additional loss of kidney function. Resuming eculizumab promptly after relapse is effective in most patients.
非典型溶血尿毒综合征（aHUS）是一种罕见的、危及生命的血栓性微血管病（TMA），已通过依库珠单抗成功治疗。依库珠单抗治疗aHUS患者的最佳疗程仍不明确。
我们在阿拉伯海湾地区对2013年6月至2021年6月期间诊断为aHUS且停用依库珠单抗的18岁以下儿童进行了一项多中心回顾性研究，以评估aHUS复发的发生率和危险因素。
我们分析了28例临床诊断为aHUS且已停用依库珠单抗的患者。停用依库珠单抗最常见的原因是肾脏和血液学缓解（71.4%），其次是基因检测阴性（28.6%）。在停药后的中位随访期24个月内，8例患者（28.5%）出现HUS复发。复发的危险因素是基因突变阳性（P = 0.020）。另一方面，复发与发病年龄、急性透析需求、停药前依库珠单抗治疗时间或发病后依库珠单抗使用时间之间无显著关系。关于停药后的肾脏结局，23例患者肾功能正常且病情缓解，4例患者患有慢性肾脏病（CKD）（其中3例在停药前已有慢性肾脏病，1例在停药后出现新的CKD），1例患者接受了移植。
aHUS患者停用依库珠单抗并非没有风险；可能导致HUS复发。停用依库珠单抗时可对患者进行密切监测。在停用依库珠单抗前评估复发的危险因素至关重要，尤其是对于补体变异阳性且有任何程度残余CKD的儿童，因为HUS复发可能导致肾功能进一步丧失。复发后及时恢复使用依库珠单抗对大多数患者有效。
