ABSTRACT:Thrombotic microangiopathy (TMA) is a well-recognised complication following transplantation, often due to an underlying genetic predisposition, medications or rejection. The use of eculizumab in these settings has been previously described, but its role still remains to be clarified. A 45-year-old man, with a history of type 1 diabetes mellitus and subsequent end-stage kidney failure, presented for a simultaneous pancreas-kidney transplant. Immunologically, he was well matched with the donor, and he received standard induction immunosuppression including tacrolimus. His early transplant course was complicated by Haemophilus parainfluenzae paronychia and a Pseudomonas aeruginosa catheter-associated urinary tract infection. Within 1 week, he developed thrombotic microangiopathy with significant renal dysfunction and eventual dialysis dependence, without evidence of transplant rejection on biopsy. He was also noted to have antiphospholipid antibodies in moderate titres. The TMA did not resolve despite cessation of tacrolimus, and he was subsequently commenced on eculizumab. The patient achieved a partial remission from TMA, with ongoing biochemical evidence of haemolysis, although now with stable graft function, despite significant damage. His transplanted pancreas remained seemingly unaffected by TMA, and continues to function well. This case describes an unusual presentation of TMA post-transplantation and is the only described case of eculizumab use following pancreas-kidney transplant. It remains unclear in this case what the likely precipitant for TMA was, although it seems to be, at least in part, controlled by ongoing use of eculizumab, presumably by terminal complement inhibition.Development of thrombotic microangiopathy (TMA) after kidney transplantation is a well-recognized complication, which can significantly affect the function of the graft. Dysregulation of the alternative complement pathway is thought to be intrinsically involved, culminating in production of the membrane attack complex (MAC, C5-9). Eculizumab, a high-affinity humanized anti-C5 monoclonal antibody, prevents generation of the MAC, thereby attenuating complement-mediated injury in diseases such a paroxysmal nocturnal haemoglobinuria and atypical haemolytic uraemic syndrome (aHUS). As yet, its utility in management of TMA post-solid organ transplantation due to various causes is unknown.Here, we present a case of a 45-year-old man who developed TMA of unclear aetiology after simultaneous pancreas and kidney transplantation, which has been managed with eculizumab.
CASE REPORTA 45-year-old man presented for a simultaneous pancreaskidney transplant. He had developed type 1 diabetes mellitus at 24 years of age, with end stage kidney disease presumed secondary to diabetic nephropathy. He undertook peritoneal dialysis for 2 years prior to transplantation. His other past history included diabetic retinopathy, hypertension and hypercholesterolaemia.Immunologically, the patient was well matched to the donor, being blood group matched a...