Thrombotic Microangiopathy In A Sirolimus-Treated Renal Transplant Patient Receiving Gemcitabine For Lung Cancer

Background: Many etiologies lead to thrombotic microangiopathy (TMA), amongst which are antineoplastic chemotherapies. Gerricitabine, a nucleoside analogue, has been approved for the treatment of bladder and advanced non-small cell lung carcinomas (NSCLC). The reported incidence of gemcitabine-associated TMA in the literature is low, ranging from 0.015-0.31%. Methods: Herein, we describe the first reported case of gemcitabine-induced TMA in a renal transplant patient. This occurred in a 54-year-old male transplant recipient undergoing sirolimus-based immunosuppression. In February 2005, he was diagnosed to have NSCLC, for which he received dual chemotherapy, including carboplatin and gemcitabine. After the third cycle he developed TMA. Results: On admission, he presented with weakness, edema, normal blood pressure, leucopenia (2,440/mm(3)), thrombopenia (11,000/mm(3)), hemolytic anemia with hemoglobin at 8 g/dl, schistocytes between 18-33 parts per thousand, increase in lactate dehydrogenase at 600 IU/1 (N < 3 80), and decreased haptoglobin at 0.29 g/l. Renal function was stable: serum creatinine was 1.3 mg/dI, albuminemia 30 g/l, proteinuria was present at 3 g/l in association with microscopic hematuria, and sirolimus trough level was 6.4 ng/ml. Treatment included infusions of fresh frozen plasma, withdrawal of sirolimus, which was replaced by mycophenolate mofetil, and suspension of chemotherapy. He fully recovered from TMA within 4 weeks. The concomitant use of sirolimus, which inhibits vascular endothelial growth factor, plus gemcitabine may have resulted in TMA.