Exenatide Reduces Graft Injury in a Rat Transplantation Model Using Kidneys Donated after Cardiac Death.

Abstract

Besides being used in the therapy of type 2 diabetes, exenatide reduces cerebral ischemia-reperfusion (I/R) injury. We evaluated the potential effects of exenatide on inhibition of apoptosis in kidney grafts donated after cardiac death and on reduction of I/R injury after kidney transplantation (KTx) in a rat model. We used a rat syngeneic KTx model with kidney grafts obtained after cardiac death, and apoptosis was detected in the graft before KTx. Graft function, rat survival, morphologic examination, and activation of inflammatory molecules were analyzed after KTx. By the end of the cold storage, exenatide pretreatment donors had significantly reduced caspase pathway activation, terminal deoxynucleotidyl transferase dUTP nick-end labeling--positive cells, release of mitochondrial porin proteins into the cytosol, and expression of cleaved caspase-3 and poly (ADP-ribose) polymerase in kidney grafts. Exenatide pretreatment improved renal function survival rate with lower scores of acute tubular necrosis, infiltrating macrophages, and interstitial fibrosis as well as reduced messenger RNA expression of inflammatory mediators (tumor necrosis factor α, interleukin-6, interleukin-1β, and intercellular adhesion molecule-1) after KTx. Our study showed that exenatide reduced I/R injury in kidneys donated after cardiac death in a rat transplantation model and improved recipient survival and graft function.