TRIMETAZIDINE PREVENTS RENAL INJURY IN THE ISOLATED-PERFUSED PIG-KIDNEY EXPOSED TO PROLONGED COLD ISCHEMIA

Background. Ischemia caused by cold storage (CS) and reperfusion of th e kidney is often responsible for delayed graft function after transpl antation, Significant attention has been focused on She cascade of eve nts involved in ischemia-reperfusion injury, with the objective of ide ntifying drugs to ameliorate the functional damage that occurs, Method s. The purpose of this study was to evaluate the renal function of iso lated perfused pig kidneys after 48 hr of CS with Euro-Collins (EC) so lution plus trimetazidine (EC+TMZ), standard FC solution, or Universit y of Wisconsin (UW) solution, Normothermic isolated perfused pig kidne ys were randomized into five experimental groups: (A) control group (c old flush with cold heparinized saline and immediately reperfused; n = 6); (B) cold flush with cold heparinized saline with TMZ (10(-6) M), n = 6; (C) 48 hr of CS with EC and reperfusion (n = 8); (D) 48 hr of C S with EC + TMZ alone and reperfusion (n = 8); (E) 48 hr of GS with UW and reperfusion (n = 8), Proton nuclear magnetic resonance spectrosco py and biochemical studies were performed for the functional evaluatio n during reperfusion, Lipid peroxidation was also determined, Histolog ical examination (optical and electron microscopy) was performed after CS and reperfusion,Results. Using TMZ, the renal perfusate flow fate as well as the glomerular filtration rate and proximal tubular functio n were significantly improved, This improvement of renal function duri ng reperfusion was correlated with a less significant cellular and int erstitial edema, In addition, tubular injury markers were significantl y lower in the group preserved with EC + TMZ, and TMZ reduced lipid pe roxidation dramatically during reperfusion, Conclusions. The addition of TMZ to the EC solution increased the preservation quality and renal tubular function, and gave protection from reperfusion injury better than EC alone or UW. These results strongly suggest that TMZ has a cyt oprotective effect and may therefore be useful for kidney preservation .