title: Sirolimus-induced thrombotic microangiopathy in a renal transplant recipient.
abstract: A rare but well-documented serious adverse reaction to the administration of the calcineurin inhibitors tacrolimus and cyclosporine in renal transplant recipients is the development of medication-induced thrombotic microangiopathy. The recently introduced immunosuppressive medication sirolimus has a very similar molecular structure to tacrolimus and also binds to the same intracellular proteins. Despite these similarities with tacrolimus, sirolimus has a different side-effect profile and reportedly lacks documented specific renal toxicity. This is a case report of the isolated administration of sirolimus without a concomitant calcineurin inhibitor being associated with the development of renal transplant biopsy-proven thrombotic microangiopathy. The patient is a 47-year-old African-American woman whose primary cause of renal failure was not thrombotic micrangiopathy, and she received a 5-antigen mismatched cadaveric renal transplant. Because of preexisting nephrosclerosis in the renal transplant, this patient was never administered a calcineurin inhibitor but was always maintained on sirolimus. With recent animal data showing that sirolmus can be nephrotoxic in a renal ischemic-reperfusion model (similar to what happens with a renal transplant), the authors speculate on a mechanism for this adverse reaction.
authors.affiliation: Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, AK 72205, USA. baronegary@uams.edu
authors.forename: Gary W
authors.initials: GW
authors.lastname: Barone
authors.forename: Bill J
authors.initials: BJ
authors.lastname: Gurley
authors.forename: Sameh R
authors.initials: SR
authors.lastname: Abul-Ezz
authors.forename: Neriman
authors.initials: N
authors.lastname: Gökden
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007668:Kidney / Q000098:blood supply* / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000150:complications / Q000601:surgery; D016030:Kidney Transplantation; D007683:Kidney Tubular Necrosis, Acute / Q000150:complications; D008875:Middle Aged; D009400:Nephrosclerosis / Q000150:complications; D011183:Postoperative Complications / Q000139:chemically induced*; D020123:Sirolimus / Q000009:adverse effects*; D012907:Smoking; D013927:Thrombosis / Q000139:chemically induced*; D014019:Tissue Donors; D014180:Transplantation; D014652:Vascular Diseases / Q000139:chemically induced*
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus