Trimarchi H M, Truong L D, Brennan S, Gonzalez J M, Suki W N
Department of Medicine, The Methodist Hospital and Baylor College of Medicine, Houston, Texas 77030, USA.
Transplantation. 1999 Feb 27;67(4):539-44. doi: 10.1097/00007890-199902270-00009.
FK506 is a recently developed immunosuppressant that has been useful in improving the survival of transplanted organs. Among the numerous adverse side effects of FK506, thrombotic microangiopathy (TMA) stands out as an infrequent but severe complication.
We report two cases of FK506-associated TMA and review the 19 previous reported cases.
From these 21 cases, the reported incidence of FK506-associated TMA is between 1% and 4.7%. It is more frequent in females, and the mean age at presentation is 47 years. Eighty-one percent of the cases occurred in patients with kidney allografts, and the remaining patients had liver, heart, or bone marrow transplants. Clinically, TMA was diagnosed at an average interval of 9.3 months from the time of transplantation. Patients may be asymptomatic or may present with the full-blown picture of hemolytic uremic syndrome. All patients had an elevated serum creatinine level but did not always show signs of hemolysis. Trough levels of FK506 were not predictive for the development of TMA, but generally a reduction of drug dose correlated with kidney function improvement and disappearance of the hemolytic picture. The renal allograft biopsy provided a conclusive diagnosis in all 17 cases in which this procedure was performed. Treatment, which mainly consisted of reduction or discontinuation of FK506, anticoagulation, and/or plasmapheresis with fresh-frozen plasma exchange, resolved TMA in most patients (57%). However, in one of these patients (5%), the graft was subsequently lost due to causes unrelated to TMA, such as acute or chronic rejection. Despite treatment, one patient (5%) lost the graft due to acute rejection and persistent TMA, and three other patients (14%) who had bone marrow, heart, and liver transplants, died of multiple organ failure, probably unrelated to TMA. In the remaining four patients (19%), response to treatment was not reported.
TMA must be considered in organ transplant patients treated with FK506 whenever kidney function deteriorates, even in the absence of microangiopathic hemolytic anemia. Although TMA usually responds to treatment, it may, in rare cases, lead to loss of kidney function or even the patient's death.
FK506是一种最近研发的免疫抑制剂，对提高移植器官的存活率很有帮助。在FK506众多的不良反应中，血栓性微血管病（TMA）是一种虽不常见但严重的并发症。
我们报告两例与FK506相关的TMA病例，并回顾之前报道的19例病例。
在这21例病例中，报道的与FK506相关的TMA发病率在1%至4.7%之间。女性更为常见，发病时的平均年龄为47岁。81%的病例发生在同种异体肾移植患者中，其余患者进行了肝、心或骨髓移植。临床上，从移植时起平均9.3个月诊断出TMA。患者可能无症状，也可能表现为典型的溶血尿毒综合征。所有患者血清肌酐水平均升高，但并非都有溶血迹象。FK506的谷浓度不能预测TMA的发生，但一般药物剂量的减少与肾功能改善及溶血症状消失相关。在进行肾移植活检的所有17例病例中，均得到了确诊。治疗主要包括减少或停用FK506、抗凝和/或用新鲜冷冻血浆进行血浆置换，大多数患者（57%）的TMA得到缓解。然而，其中一名患者（5%）随后因与TMA无关的原因（如急性或慢性排斥反应）失去了移植肾。尽管进行了治疗，一名患者（5%）因急性排斥反应和持续性TMA失去了移植肾，另外三名进行骨髓、心脏和肝脏移植的患者（14%）死于多器官功能衰竭，可能与TMA无关。其余四名患者（19%）未报告治疗反应。
在用FK506治疗的器官移植患者中，无论何时肾功能恶化，即使没有微血管病性溶血性贫血，也必须考虑TMA。尽管TMA通常对治疗有反应，但在极少数情况下，可能导致肾功能丧失甚至患者死亡。
