Department of Clinical Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden.
Department of Histopathology, Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Histopathology. 2019 Jul;75(1):88-103. doi: 10.1111/his.13855.
Post-transplant thrombotic microangiopathy (TMA) is a rare and clinically challenging finding in renal transplant biopsies. In addition to recurrent atypical haemolytic uraemic syndrome, TMA in renal transplants is associated with various conditions, such as calcineurin inhibitor (CNI) treatment, antibody-mediated rejection (ABMR), viral infections, sepsis, pregnancy, malignancies, and surgery. The therapeutic implications of this diagnosis are considerable. In order to better understand post-transplant TMA and to identify histological or clinical differences between associated causes, we conducted a multicentre retrospective study.
Clinical parameters and transplant renal biopsy findings from 81 patients with TMA were analysed. Biopsies from 38 patients were also analysed with electron microscopy. On the basis of clinical-pathological correlation, TMA was attributed to a main aetiology, whenever possible. TMA occurred at a median of 30 days post-transplantation. Systemic features of TMA were present in only 18% of cases. Twenty-two per cent of cases were attributed to CNI and 11% to ABMR. Although other potentially contributing factors were found in 56% of patients, in most cases (63%) no clearly attributable cause of TMA was identified. Histological differences between groups were minimal. The detection of ultrastructural features that are usually associated with ABMR may help to establish ABMR as the cause of TMA.
Although CNI and ABMR appear to be the main contributors to post-transplant TMA, the aetiology of most cases is probably multifactorial, and TMA cannot be unequivocally attributed to a single underlying aetiology. Morphological features of TMA are not discriminating, but electron microscopy may help to identify ABMR-associated TMA.
移植后血栓性微血管病（TMA）是肾移植活检中罕见且具有挑战性的临床发现。除了复发性非典型溶血尿毒综合征外，肾移植中的 TMA 还与各种情况相关，如钙调神经磷酸酶抑制剂（CNI）治疗、抗体介导的排斥反应（ABMR）、病毒感染、脓毒症、妊娠、恶性肿瘤和手术。该诊断的治疗意义相当大。为了更好地理解移植后 TMA 并确定相关病因的组织学或临床差异，我们进行了一项多中心回顾性研究。
分析了 81 例 TMA 患者的临床参数和移植肾活检结果。对 38 例患者的活检标本还进行了电子显微镜分析。根据临床病理相关性，尽可能将 TMA 归因于主要病因。TMA 发生在移植后中位数为 30 天。只有 18%的病例存在 TMA 的全身特征。22%的病例归因于 CNI，11%归因于 ABMR。尽管在 56%的患者中发现了其他潜在的促成因素，但在大多数情况下（63%），无法明确确定 TMA 的可归因原因。组间的组织学差异很小。超微结构特征的检测通常与 ABMR 相关，可能有助于将 ABMR 确立为 TMA 的病因。
尽管 CNI 和 ABMR 似乎是移植后 TMA 的主要原因，但大多数病例的病因可能是多因素的，TMA 不能明确归因于单一潜在病因。TMA 的形态学特征没有区别，但电子显微镜可能有助于识别与 ABMR 相关的 TMA。
