Tacrolimus
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Thrombotic microangiopathy in an elderly patient: case report A male renal transplant recipient developed thrombotic microangiopathy while receiving immunosuppressive therapy with tacrolimus. The 68-year-old man presented in March 2004 with stage V chronic kidney disease. In May 2008, he received a renal transplant from a deceased donor. A reperfusion biopsy at the time of surgery revealed moderate acute tubular damage, and he displayed delayed graft function, requiring haemodialysis. Immunosuppression consisted of antithymocyte globulin, methylprednisolone, prednisone, mycophenolate sodium, and tacrolimus 2mg twice daily on days 5-8 postoperatively, 3mg twice daily on days 9-10, and 2mg twice daily on days 11-12 [route not stated]. The average tacrolimus concentration between days 6-12 was 11.9 ng/mL with a peak of 27.9 ng/mL on day 9. A biopsy, performed on day 11 for persistent delayed graft function, revealed prominent changes in the arterioles with swelling of endothelial cells and the subendothelial space, associated with luminal narrowing. Fibrinoid necrosis and entrapped RBCs in arteriole vessel walls with fibrin thrombi were also observed. Diffuse atrophy with hydrophobic swelling of epithelial cells was evident in the proximal tubules, and he was found to be anaemic. Tacrolimus, suspected to be the cause of thrombotic microangiopathy, was replaced with sirolimus. A biopsy performed on day 20 showed persistent thrombotic microangiopathy. The man’s creatinine level decreased and he was discharged on day 41. He was subsequently readmitted on two occasions with an elevated serum creatinine level. No evidence of active thrombotic microangiopathy was obtained, but fibrosis, most likely reflecting repair of his acute injury, and signs of chronic, active rejection were apparent. At last observation, his creatinine level was 2.4 mg/dL. Author comment: "It is our conclusion, however, that the major causative factor involved in this case is tacrolimus, with its toxicity possibly enhanced by ischemia-reperfusion injury (DGF)." Carson JM, et al. Tacrolimus-induced thrombotic microangiopathy: Natural history of a severe, acute vasculopathy. Clinical Nephrology 77: 79-84, No. 1, Jan 2012. 803067504 Available from: URL: http://dx.doi.org/10.5414/cn107036 - USA
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