title: Sirolimus use in recipients of expanded criteria donor kidneys.
abstract: With changing donor characteristics and the growing shortage in organ supply, renal transplant practitioners have sought to optimize the use of expanded criteria donor (ECD) kidneys, which have poorer outcomes than standard criteria donor (SCD) kidneys. The outcomes may represent an acceptable trade-off if ECD transplants offer enhanced overall patient survival by reducing waiting times. ECD kidneys may be more susceptible to toxicity associated with calcineurin inhibitors (CNIs); therefore, a potential strategy to improve outcomes in this growing demographic is the use of CNI-free immunosuppressive protocols. To date, published clinical studies have demonstrated encouraging outcomes using sirolimus-based CNI-free regimens in SCD kidney transplant recipients. We conducted a pilot study to examine outcomes in ECD kidney transplant recipients receiving a CNI-free quadruple drug regimen, consisting of antithymocyte globulin (ATG), sirolimus, mycophenolate mofetil (MMF) and a corticosteroid, compared with outcomes in a retrospective CNI-control group of ECD recipients who had received standard CNI-based immunosuppressive treatment. Patient survival and allograft survival at 1 year were not significantly different between the CNI-free group (n = 13) and the CNI-control group (n = 13) [100% vs 92% and 92% vs 85%, respectively]; nor was the incidence of rejection (26% and 31%) or delayed graft function (38% of patients in both groups). Serum creatinine was significantly lower and the estimated glomerular filtration rate was significantly higher for the CNI-free group at 3-6 months but not at 1 year. Protocol biopsies in the CNI-free patients at 1 year revealed no significant progression of chronic vascular lesions. Banff chronic/sclerosing allograft nephropathy scores were 42% grade I, 25% grades II and III, and 33% grade 0. Thus, a sirolimus-based CNI-free regimen may improve outcomes in ECD kidney transplant recipients and merits further study.
authors.affiliation: University of Western Ontario Faculty of Medicine, London, Ontario, Canada. andrew.house@lhsc.on.ca
authors.forename: Andrew A
authors.initials: AA
authors.lastname: House
authors.forename: Christopher Y
authors.initials: CY
authors.lastname: Nguan
authors.forename: Patrick P
authors.initials: PP
authors.lastname: Luke
mesh_terms: D002986:Clinical Trials as Topic; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation; D020123:Sirolimus / Q000627:therapeutic use*; D015996:Survival Rate; D014019:Tissue Donors / Q000600:supply & distribution; D016896:Treatment Outcome; D014850:Waiting Lists
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus