FK506-associated thrombotic microangiopathy - Report of two cases and review of the literature

Background. FK506 is a recently developed immunosuppressant that has been u seful 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. Methods. We report two cases of FK506-associated TMA and review the 19 prev ious reported cases. Results. From these 21 cases, the reported incidence of FK506-associated TM A 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 pa tients with kidney allografts, and the remaining patients had liver, heart, or bone marrow transplants. Clinically, TMA was diagnosed at an average in terval of 9.3 months from the time of transplantation. Patients may be asym ptomatic or may present with the full-blown picture of hemolytic uremic syn drome. All patients had an elevated serum creatinine level but did not alwa ys show signs of hemolysis. Trough levels of FK506 were not predictive for the development of TMA, but generally a reduction of drug dose correlated w ith 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 o f reduction or discontinuation of FK506, anticoagulation, and/or plasmapher esis with fresh-frozen plasma exchange, resolved TMA in most patients (57%) . However, in one of these patients (5%), the graft was subsequently lost d ue to causes unrelated to TMA, such as acute or chronic rejection. Despite treatment, one patient (5%) lost the graft due to acute rejection and persi stent TMA, and three other patients (14%) who had bone marrow, heart, and l iver transplants, died of multiple organ failure, probably unrelated to TMA . In the remaining four patients (19%), response to treatment was not repor ted. Conclusions. TMA must be considered in organ transplant patients treated wi th FK506 whenever kidney function deteriorates, even in the absence of micr oangiopathic 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.