Trimetazidine reduces renal dysfunction by limiting the cold ischemia/reperfusion injury in autotransplanted pig kidneys

Ischemia/reperfusion injury leads to delayed graft function, which is a maj or problem in kidney transplantation. This study investigated the effects o f adding trimetazidine (TMZ) to the perfusate of cold-stored kidneys on the function of reperfused autotransplanted pig kidney. The left kidney was re moved and cold-flushed with Euro-Collins (EC), or University of Wisconsin ( UW) solutions with or without 10(-6)M TMZ and stored for 48 h at 4 degrees C. The kidneys were then autotransplanted and the contralateral kidneys wer e removed. Several parameters were analyzed over the 14 d after transplanta tion, The survival rate was 57% in pigs transplanted with kidneys cold-flus hed with UW and 43% for those flushed with EC solution; it was 100% for pig s having kidneys cold-flushed with TMZ-supplemented UW and EC solutions. Th e functions of the transplanted kidneys were also better preserved after co ld flush with TMZ-supplemented solutions than with TMZ-free solutions. Crea tinine clearance was higher and the urinary excretion of trimethylamine-N-o xide and dimethylamine, used as markers of renal medulla injury, were lower in animals transplanted with kidneys cold-flushed with TMZ-supplemented so lutions than with TMZ-free solutions. The cytoprotective action of TMZ also reduced interstitial and peritubular inflammation and the numbers of infil trating mononuclear CD45(+) and CD3(+) T cells. These results indicate that the tissue damage due to ischemia/reperfusisn injury may be prevented, at least in part, by adding TMZ to preservation solutions.