Long-term outcomes of the Atypical Hemolytic Uremic Syndrome after kidney transplantation treated with eculizumab as first choice

IntroductionThe treatment of choice for Atypical Hemolytic Uremic Syndrome (aHUS) is the monoclonal antibody eculizumab. The objective of this study was to assess the efficacy and safety of eculizumab in a cohort of kidney transplant patients suffering from aHUS.MethodsDescription of the prospective cohort of all the patients primarily treated with eculizumab after transplantation and divided into the therapeutic (onset of aHUS after transplantation) and prophylactic use (patients with previous diagnosis of aHUS undergoing kidney transplantation).ResultsSeven cases were outlined: five of therapeutic use and two, prophylactic. From the five cases of therapeutic use, there was improvement of the thrombotic microangiopathy in the 48 hours following the start of the drug and no patient experienced relapse during an average follow-up of 21 months in the continuous use of eculizumab (minimum of 6 and maximum of 42 months). One patient died at 6 months, due to Aspergillus infection. From the two cases of prophylactic use, one patient experienced relapsed thrombotic microangiopathy after 4 months and another patient remained asymptomatic after 16 months of follow-up, both on chronic treatment.DiscussionThe therapeutic use of eculizumab showed to be effective, with improvement of the microangiopathy parameters and persisting up to the end of the follow-up, without relapses. The additional risk of immunosuppression, leading to opportunistic infections, was well tolerated. The prophylactic use showed to be effective and safe; however, the doses and intervals should be individualized in order to avoid relapsed microangiopathy, especially in patients with factor H mutation.

引言
非典型溶血性尿毒症综合征（aHUS）的首选治疗方案为单克隆抗体依库珠单抗（eculizumab）。本研究旨在评估依库珠单抗在合并aHUS的肾移植患者队列中的疗效与安全性。

方法
本研究对所有移植后主要接受依库珠单抗治疗的患者开展前瞻性队列分析，将其分为治疗组（移植后新发aHUS）与预防性给药组（术前已确诊aHUS并接受肾移植的患者）。

结果
共纳入7例病例：治疗组5例，预防性给药组2例。治疗组5例患者在启动依库珠单抗治疗后48小时内，血栓性微血管病（thrombotic microangiopathy）症状即得到改善；在平均21个月的持续治疗随访期内（最短随访6个月，最长42个月），无患者出现疾病复发。其中1例患者在治疗6个月时因曲霉感染死亡。预防性给药组2例患者中，1例在治疗4个月后出现血栓性微血管病复发，另1例经16个月随访仍无相关临床症状，二人均接受长期维持治疗。

讨论
治疗组应用依库珠单抗疗效确切，微血管病相关指标改善情况持续至随访结束，未出现疾病复发。免疫抑制带来的额外机会性感染风险整体耐受良好。预防性给药组同样展现出良好的疗效与安全性，但需个体化调整给药剂量与给药间隔，以避免血栓性微血管病复发，尤其针对存在补体因子H（factor H）突变的患者。