title: Sirolimus in liver transplant recipients with renal dysfunction offers no advantage over low-dose calcineurin inhibitor regimens.
abstract: The purpose of this study is to review the clinical experience with sirolimus immunosuppression in liver transplant patients with calcineurin inhibitor-induced chronic renal insufficiency. The study design is a case-control retrospective series. Fifty-seven liver transplant patients with renal insufficiency that were started on sirolimus at greater than 90 days postoperatively and treated for more than 90 days were identified. A control group of 57 patients maintained on low-dose calcineurin inhibitors, matched for gender, year of transplant, and baseline creatinine clearance, was also identified. There were no significant differences in the absolute creatinine clearance values between the sirolimus and control groups from 6 months before sirolimus conversion to 12 months after sirolimus conversion. Patients exposed to calcineurin inhibitors for more than 5 years or those with an initial creatinine clearance of less than 30 mL/minute who were converted to sirolimus did worse than control patients maintained on low-dose calcineurin inhibitors. Progression to renal replacement therapy, episodes of acute and chronic rejection, and death were similar between the sirolimus and control groups. The overall prevalence of side effects was significantly higher in the sirolimus group compared with the control group, although these were generally tolerable in most patients. In conclusion, this study suggests that conversion to sirolimus in liver transplant patients with chronic renal insufficiency is associated with stabilization of renal function but confers no additional benefit to low-dose calcineurin inhibitor regimens and may in fact be disadvantageous in patients with a creatinine clearance of less than 30 mL/minute.
authors.affiliation: Liver Transplant Unit, Multiorgan Transplant Program, University of Toronto and Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Derek
authors.initials: D
authors.lastname: DuBay
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Smith
authors.forename: Kenneth G
authors.initials: KG
authors.lastname: Qiu
authors.forename: Gary A
authors.initials: GA
authors.lastname: Levy
authors.forename: Leslie
authors.initials: L
authors.lastname: Lilly
authors.forename: George
authors.initials: G
authors.lastname: Therapondos
mesh_terms: D000328:Adult; D000368:Aged; D000963:Antimetabolites / Q000627:therapeutic use; D065095:Calcineurin Inhibitors; D016022:Case-Control Studies; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000209:etiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D008107:Liver Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D016031:Liver Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000139:chemically induced* / Q000378:metabolism / Q000401:mortality / Q000628:therapy; D017582:Renal Replacement Therapy; D012189:Retrospective Studies; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects*; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000963:Antimetabolites; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine; D020123:Sirolimus; D016559:Tacrolimus