Service des Maladies du Rein et du Métabolisme, Transplantation et Immunologie Clinique, Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants maladies, Université Paris Cité, Paris, France.
Laboratoire d'Anatomie et Cytologie Pathologiques, Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants maladies, Université Paris Cité, Paris, France; Laboratory of Clinical and Experimental Pathology, Hospital-Integrated Biobank (BB-0033-00025), Team 4, Institute of Research on Cancer and Aging of Nice, InsermU1081, CNRS UMR7284, FHU OncoAge, Institut Hospitalo-Universitaire RespirERA, Université Côte d'Azur, Hôpital Pasteur, CHU de Nice, CEDEX 1, Nice, France.
Am J Transplant. 2024 Jul;24(7):1205-1217. doi: 10.1016/j.ajt.2024.01.029. Epub 2024 Feb 5.
De novo thrombotic microangiopathy (dnTMA), after renal transplantation may significantly alter graft outcomes. However, its pathogenesis and the role of complement alternative pathway dysregulation remain elusive. We studied all consecutive adult patients with a kidney allograft biopsy performed between January 2004 and March 2016 displaying dnTMA. Ninety-two patients were included. The median time of occurrence was 166 (IQR 25-811) days. The majority (82.6 %) had TMA localized only in the graft. Calcineurin inhibitor toxicity and antibody-mediated rejection (ABMR) were the 2 most frequent causes (54.3% and 37.0%, respectively). However, etiological factors were multiple in 37% patients. Interestingly, pathogenic variants in the genes of complement alternative pathway were significantly more frequent in the 42 tested patients than in healthy controls (16.7% vs 3.7% respectively, P < .008). The overall graft survival after biopsy was 66.0% at 5 years and 23.4% at 10 years, significantly worse than a matched cohort without TMA. Moreover, graft survival of patients with TMA and ABMR was worse than a matched cohort with ABMR without TMA. The 2 main prognostic factors were a positive C4d staining and a lower estimated glomerular filtration rate at diagnosis. DnTMA is a severe and multifactorial disease, induced by 1 or several endothelium-insulting conditions, mostly calcineurin inhibitor toxicity and ABMR.
肾移植后新发血栓性微血管病（dnTMA）可能显著改变移植物的预后。然而，其发病机制和补体替代途径失调的作用仍不清楚。我们研究了 2004 年 1 月至 2016 年 3 月期间所有连续进行的、表现为 dnTMA 的成人肾移植活检患者。共纳入 92 例患者。发生时间中位数为 166（IQR 25-811）天。大多数（82.6%）患者的 TMA 仅局限于移植物。钙调神经磷酸酶抑制剂毒性和抗体介导的排斥反应（ABMR）是最常见的两种原因（分别为 54.3%和 37.0%）。然而，37%的患者存在多种病因。有趣的是，在 42 例接受检测的患者中，补体替代途径基因的致病性变异明显比健康对照组更常见（分别为 16.7%和 3.7%，P<.008）。活检后 5 年总体移植物存活率为 66.0%，10 年为 23.4%，明显低于无 TMA 的匹配队列。此外，有 TMA 和 ABMR 的患者的移植物存活率比无 TMA 的 ABMR 患者更差。2 个主要预后因素是 C4d 染色阳性和诊断时肾小球滤过率估计值较低。dnTMA 是一种严重的、多因素疾病，由 1 种或多种内皮细胞损伤条件引起，主要是钙调神经磷酸酶抑制剂毒性和 ABMR。
