title: Thrombotic micro-angiopathy with sirolimus-based immunosuppression: potentiation of calcineurin-inhibitor-induced endothelial damage?
abstract: Thrombotic microangiopathy is a rare but important finding in the context of organ transplantation. Acute renal insufficiency in the setting of hemolysis and thrombocytopenia, a triad that constitutes 'hemolytic uremic syndrome', can be associated with, or triggered by, conditions such as verocytotoxin-producing Escherichia coli, viral infections, malignant hypertension, scleroderma, allograft rejection, lupus erythematosus, pregnancy, and medications including mitomycin C, calcineurin inhibitors, and oral contraceptives. After renal transplantation, it can occur, as either a de novo episode, or recurrent disease. Calcineurin inhibitors have long been associated with post-transplantation thrombotic microangiopathy. Sirolimus has been used as a primary immunosuppressant in patients transplanted with a history of earlier hemolytic-uremic syndrome, and also as rescue therapy in patients with calcineurin-inhibitor-associated thrombotic microangiopathy. We describe four cases where there was significant thrombotic microangiopathy in the context of contemporaneous or contiguous calcineurin inhibitor and sirolimus usage. As the intrarenal cyclosporin concentration is thought to be significantly elevated when cyclosporin and sirolimus are used together, this may explain these findings, and mandates caution in their co-administration.
authors.affiliation: Renal Unit, Guy's Hospital, London SE1 9RT, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Robson
authors.forename: Isabelle
authors.initials: I
authors.lastname: Côte
authors.forename: Ian
authors.initials: I
authors.lastname: Abbs
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Koffman
authors.forename: David
authors.initials: D
authors.lastname: Goldsmith
mesh_terms: D000328:Adult; D065095:Calcineurin Inhibitors; D002648:Child; D003925:Diabetic Angiopathies / Q000175:diagnosis; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*; D013927:Thrombosis / Q000175:diagnosis
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D020123:Sirolimus