Thrombotic thrombocytopenic purpura associated with everolimus use in a renal transplant patient

Abstract

Thrombotic microangiopathy (TMA) in renal transplantation (RTX) generally develops during treatment with calcineurin inhibitors. We present a RTX case that developed TMA under everolimus treatment. A 40-year-old woman received a kidney allograft from her 77-year-old mother. She initially received tacrolimus, mycophenolate mofetil and steroids. She was discharged with a creatinine level of 2.2 mg/dl after treatment for a cellular rejection attack within the first two weeks after transplantation. Later on, tacrolimus was replaced with everolimus. One year later, she presented with fever and increased creatinine level (4 mg/dl), anemia and thrombocytopenia. Her peripheral blood smear revealed signs of microangiopathic hemolysis. Bone marrow examination revealed an increased number of megakaryocytes. We diagnosed the case as TMA and initiated plasma exchange, I.V. pulse steroid treatment and stopped everolimus. This approach improved laboratory and clinic abnormalities. The development of TMA after treatment with everolimus and the exclusion of other possible causes suggested TMA associated with proliferating signal inhibitors (PSIs) in our case.

American Society of Nephrology Quiz and Questionnaire 2013

“…Our patient's medications included sirolimus. Like cyclosporine and tacrolimus, the mammalian target of rapamycin inhibitors sirolimus and everolimus have been implicated in causing thrombotic microangiopathy (TMA) (31)(32)(33). Our patient's sirolimus level was elevated at 17.1 ng/ml.…”

Everolimus-Associated Thrombotic Microangiopathy and Acute Kidney Injury in a Patient with Breast Cancer

“…Olgumuzda öncelikle sorumlu ajanın kesilmesi ve dehidratasyonun düzeltilmesinin etkili olduğunu düşünmekteyiz. Hızlı yanıtta steroid ve plazmaferez tedavilerinin katkısının ne ölçüde olduğu bilinmemektedir (6).…”

“…Böbrek podositlerinde de sirolimusa bağlı olarak VEGF üretimi engellenmesi, proteinüri ve endotliyozise neden olmaktadır ki bu bulgular preeklempsi ve TMA'da görülen glomerüler lezyonlardır (5). Literatürde solid organ nakli hastalarında mTOR ve/veya kalsinörin inhibitörlerinin birlikte kullanımına bağlı olarak gelişen TMA olguları bildirilmiştir (6)(7)(8).…”

Steroid or tacrolimus withdrawal in renal transplant recipients using sirolimus

“…Interestingly, there were no differences between groups. Although we withdrew TAC after the adverse event thrombotic microangiopathy in TAC/SRL group, proliferating signal inhibitors must be recognized as a possible cause of thrombotic microangiopathy in renal transplant recipients [21].…”