Thrombotic microangiopathy in renal transplantation.
Thrombotic microangiopathy in renal transplantation.
复制标题
肾移植中的血栓性微血管病。
作者：
C. Chiurchiu;P. Ruggenenti;G. Remuzzi
血栓性微血管病（TMA）一词包括血小板减少症、微血管性溶血性贫血、神经功能缺陷、肾功能障碍和器官损害的各种症状。儿童期TMA伴主要肾衰竭的病例通常被称为溶血性尿毒症综合征（HUS），而伴有主要神经系统病变的成人病例被称为血栓性血小板减少性紫癜（TTP）。大多数情况下由大肠杆菌o157:H7产生的外毒素与腹泻相关性溶血性尿毒综合征（D +溶血性尿毒综合征）有关。抗癌药物（丝裂霉素）、免疫抑制药物（环孢素、他克莫司和OKT3）以及一些抗血小板药物（噻氯匹定、氯匹罗凝胶）与溶血性尿毒综合征和TTP有关。缺陷因子H或vWF蛋白酶活性已发现与熟悉和复发形式。内皮损伤和功能障碍很可能是致病过程的初始事件，最终导致血小板聚集、微血管血栓形成和组织缺血。TMA可能发生在接受非肾脏移植的患者的原生肾脏中，也可能发生在因非溶血性尿毒综合征而发展为ESRD的患者的移植肾脏中。钙调磷酸酶抑制剂和血管排斥反应最常发生在这些病例中。由于溶血性尿毒综合征/TTP而发展为ESRD的患者的移植肾也可能复发。对于D +溶血性毒血症，移植后复发的风险可以忽略不计，但在与低C3和因子H生物利用度或活性降低相关的家族性/复发形式中，这一风险接近100%。停药或处理沉淀因素是最有效的方法。血浆治疗通常是为了限制微血管病变过程，但其改善移植物存活的功效尚未得到证实。复发形式的结果几乎总是很差。
The term thrombotic microangiopathy (TMA) encompasses syndromes of thrombocytopenia, microangiopathic haemolytic anaemia, neurologic deficits, renal dysfunction and variable signs of organ impairment. Childhood cases of TMA with predominant renal failure are usually referred as Haemolytic Uremic Syndrome (HUS), and adult cases with major neurological involvement as Thrombotic Thrombocytopenic Purpura (TTP). Exotoxins, produced in most cases by E. Coli O 157:H7, have been related to diarrhea associated HUS(D + HUS). Anticancer (mitomycin), immunosuppressive drugs (cyclosporin, tacrolimus and OKT3) and as well as some antiplatelet agents (ticlopidine, clopidrogel) have been associated with both HUS and TTP. Defective factor H or vWF protease activity have been found with familiar and recurrent forms. Endothelial damage and dysfunction is most likely the initial event of the pathogenic process that eventually leads to platelet aggregation, microvascular thrombosis and tissue ischemia. TMA may occur de novo in the native kidneys of patients who received a non-kidney transplant or in the transplanted kidney of patients who progressed to ESRD because of a disease other than HUS. Calcineurin inhibitors and vascular rejection are most often involved in these cases. The disease may also recur on the transplanted kidney in patients who progressed to ESRD because of HUS/TTP. The risk of postransplant recurrence is negligible for D + HUS but is close to 100% in familial/recurrent forms associated with low C3 and decreased factor H bioavailability or activity. Withdrawal or treatment of precipitating factors are the most effective approach. Plasma therapy is usually attempted with the rationale to limit the microangiopathic process, but its efficacy for improving graft survival is unproven. The outcome of recurrent forms is almost invariably poor.