(490) Calcineurin Inhibitor-Induced Atypical Hemolytic Uremic Syndrome after Heart Transplantation

PurposeCalcineurin inhibitors (CNI) are the mainstay of immunosuppression after heart transplantation. Atypical hemolytic uremic syndrome (aHUS), defined as the constellation of microangiopathic hemolytic anemia, thrombocytopenia and renal dysfunction, is a rare complication of CNI use following solid organ transplantation. This is the first case series to describe the clinical features, treatment and outcomes of patients with CNI-induced aHUS after heart transplantation.MethodsHeart transplant recipients between 2014 and 2022 were retrospectively reviewed at our center; aHUS was defined by hemolytic anemia with elevated LDH, decreased haptoglobin, schistocytes on peripheral smear, thrombocytopenia and renal dysfunction.ResultsOf the 179 transplanted patients, 5 were identified to have clinically diagnosed CNI-induced aHUS (60% male, mean age 51.5 ± 11.8 years). Initial post-transplant immunosuppression was standardized as tacrolimus, mycophenolate mofetil and prednisone. Mean time from transplant to diagnosis of aHUS was 58.7 ± 34.2 days. Only one patient had abnormal ADAMST13 function. Upon diagnosis, tacrolimus was transitioned to cyclosporine in 2 patients, tacrolimus trough goals were decreased in 2 patients, and tacrolimus was transitioned to sirolimus in 1 patient. Monoclonal antibody therapy was the main therapeutic regimen (80%), with duration ranging 2 months to 6 years. Two patients received at least 2 sessions of plasmapheresis. Four of 5 experienced rehospitalization due to infection, and 2 of 5 ultimately died due to infection. Four required hemodialysis, of which one had renal recovery.ConclusionIn this case series of CNI-induced aHUS, despite resolution of initial hemolytic anemia in all and monoclonal antibody therapy in most, a high frequency of dialysis and readmission for infection was observed. Optimal management remains unclear, and further studies are needed to guide immunosuppressive strategies in this complication. Calcineurin inhibitors (CNI) are the mainstay of immunosuppression after heart transplantation. Atypical hemolytic uremic syndrome (aHUS), defined as the constellation of microangiopathic hemolytic anemia, thrombocytopenia and renal dysfunction, is a rare complication of CNI use following solid organ transplantation. This is the first case series to describe the clinical features, treatment and outcomes of patients with CNI-induced aHUS after heart transplantation. Heart transplant recipients between 2014 and 2022 were retrospectively reviewed at our center; aHUS was defined by hemolytic anemia with elevated LDH, decreased haptoglobin, schistocytes on peripheral smear, thrombocytopenia and renal dysfunction. Of the 179 transplanted patients, 5 were identified to have clinically diagnosed CNI-induced aHUS (60% male, mean age 51.5 ± 11.8 years). Initial post-transplant immunosuppression was standardized as tacrolimus, mycophenolate mofetil and prednisone. Mean time from transplant to diagnosis of aHUS was 58.7 ± 34.2 days. Only one patient had abnormal ADAMST13 function. Upon diagnosis, tacrolimus was transitioned to cyclosporine in 2 patients, tacrolimus trough goals were decreased in 2 patients, and tacrolimus was transitioned to sirolimus in 1 patient. Monoclonal antibody therapy was the main therapeutic regimen (80%), with duration ranging 2 months to 6 years. Two patients received at least 2 sessions of plasmapheresis. Four of 5 experienced rehospitalization due to infection, and 2 of 5 ultimately died due to infection. Four required hemodialysis, of which one had renal recovery. In this case series of CNI-induced aHUS, despite resolution of initial hemolytic anemia in all and monoclonal antibody therapy in most, a high frequency of dialysis and readmission for infection was observed. Optimal management remains unclear, and further studies are needed to guide immunosuppressive strategies in this complication.