Levi Charlène, Frémeaux-Bacchi Véronique, Zuber Julien, Rabant Marion, Devriese Magali, Snanoudj Renaud, Scemla Anne, Amrouche Lucile, Mejean Arnaud, Legendre Christophe, Sberro-Soussan Rebecca
Service de Néphrologie, Transplantation Adulte, Hôpital Necker-Enfants Malades, Université Paris Descartes, Assistance Publique-Hôpitaux de Paris, Paris, France.
Service d'immunobiologie Hôpital Européen Georges Pompidou, Université Paris Descartes, Assistance Publique-Hôpitaux de Paris, Paris, France.
Transplantation. 2017 Dec;101(12):2924-2930. doi: 10.1097/TP.0000000000001909.
Atypical hemolytic uremic syndrome (aHUS) is an orphan disease with a high rate of recurrence after kidney transplantation. However, reports of successful prevention of posttransplant aHUS recurrence with eculizumab emerged a few years ago. To further delineate its optimal use, we describe the largest series of kidney transplant recipients treated with prophylactic eculizumab.
Twelve renal transplant recipients with aHUS-related end-stage renal disease received eculizumab: 10 from day 0 and 2 at the time of recurrence (days 6 and 25). Clinical and histological features, complement assessment, and free eculizumab measurements were analyzed. The median follow-up was 24.6 months.
Five patients had failed at least 1 previous renal transplant from aHUS. A genetic mutation was identified in 9 patients, anti-H antibodies were found in 2. No patient demonstrated biological recurrence of thrombotic microangiopathy under treatment. Three antibody-mediated rejections (AMRs) occurred without detectable C5 residual activity. AMR was associated with subclinical thrombotic microangiopathy in 2 patients. One patient lost his graft after several complications, including AMR. One patient experienced posttransplant C3 glomerulonephritis. The last median serum creatinine was 128.2 ± 40.8 μmol/L.
These data confirm that eculizumab is highly effective in preventing posttransplantation aHUS recurrence, yet may not fully block AMR pathogenesis.
非典型溶血尿毒综合征（aHUS）是一种罕见病，肾移植后复发率很高。然而，几年前出现了使用依库珠单抗成功预防移植后aHUS复发的报道。为了进一步明确其最佳使用方法，我们描述了接受预防性依库珠单抗治疗的最大系列肾移植受者。
12例患有aHUS相关终末期肾病的肾移植受者接受了依库珠单抗治疗：10例从第0天开始治疗，2例在复发时（第6天和第25天）开始治疗。分析了临床和组织学特征、补体评估以及游离依库珠单抗测量结果。中位随访时间为24.6个月。
5例患者之前至少有1次因aHUS导致肾移植失败。9例患者检测到基因突变，2例发现抗H抗体。治疗期间没有患者出现血栓性微血管病的生物学复发。发生了3次抗体介导的排斥反应（AMR），且未检测到C5残余活性。2例患者的AMR与亚临床血栓性微血管病有关。1例患者在出现包括AMR在内的多种并发症后失去了移植肾。1例患者发生了移植后C3肾小球肾炎。最后一次血清肌酐中位数为128.2±40.8μmol/L。
这些数据证实依库珠单抗在预防移植后aHUS复发方面非常有效，但可能无法完全阻断AMR的发病机制。
