Donor preconditioning with a calcineurin inhibitor improves outcome in rat syngeneic kidney transplantation.
Ischemia-reperfusion injury (IRI) in the early posttransplant period affects immediate graft function and late allograft dysfunction. This study determines the influence of pharmacologic preconditioning with a calcineurin inhibitor on IRI in a syngeneic F344 rat kidney transplant model. Donor rats were pretreated with one dose of cyclosporine (10 mg/kg) or tacrolimus (1 mg/kg) administered at 24 hr or 7 days before being subjected to 2 hr of cold ischemia and then transplanted. Pharmacologic preconditioning significantly improved renal function, as assessed by serum creatinine and inulin clearance, and histologic score versus vehicle-treated rats. There were no differences between cyclosporine and tacrolimus in the measured outcomes. This renoprotective effect, although not complete, was seen with only one dose of calcineurin inhibitor, and the effect was sustained for at least 7 days before IRI. This approach may represent a viable pharmacologic intervention to decrease IRI at the time of organ transplantation.
Shihab
Fuad S
FS
Department of Internal Medicine, Division of Nephrology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA. Fuad.Shihab@hsc.utah.edu
Bennett
William M
WM
Andoh
Takeshi F
TF
D000818:Animals; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007249:Inflammation; D016030:Kidney Transplantation / Q000276:immunology* / Q000502:physiology; D007684:Kidney Tubules / Q000473:pathology; D023421:Models, Animal; D009336:Necrosis; D051381:Rats; D011916:Rats, Inbred F344; D016559:Tacrolimus / Q000627:therapeutic use; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous / Q000276:immunology / Q000473:pathology; D014185:Transplantation, Isogeneic / Q000276:immunology; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine; D016559:Tacrolimus