Effects of erythropoietin on ischaemia/reperfusion injury in a controlled nonheart beating donor kidney model

Abstract

Erythropoietin (EPO) has been shown to have an anti-apoptotic action and has the potential to protect against ischaemia/reperfusion injury. This study investigated the effect of high dose EPO (5000 U), administered as a bolus at the onset of reperfusion and at the onset of cold storage in a model of controlled nonheart beating donors kidneys. Porcine kidneys(n = 6) were subjected to 10min warm ischaemia and preserved as follows: Group 1:16 h Cold storage +2 h Normothermic perfusion (16 h CS + 2 h NP) Group 2:16 h CS + 2 h NP + EPO given at the onset of reperfusion Group 3:18 h CS (static hypothermic storage) Group 4:18 h CS + EPO given at the onset of cold storage Haemodynamic and functional parameters were assessed during 3-h reperfusion using autologous blood. Renal blood flow improved in Groups 1 and 2 vs. Groups 3 and 4 though no difference was noted between Groups 3 and 4 (563 +/- 119 vs. 491 +/- 95 vs. 325 +/- 70 vs. 418 +/- 112, respectively; P = 0.012). Total urine output showed no difference between Groups (271 +/- 172 vs. 359 +/- 184 vs. 302 +/- 21 vs. 421 +/- 88; P = 0.576). Percentage serum creatinine fall at 3 h was significantly better in Groups 1 and 2 vs. Group 3 (64 +/- 17 vs. 60 +/- 11 vs. 44 +/- 13 vs. 52 +/- 8; P = 0.04). Fractional-excretion of sodium was significantly lower for Groups 1 and 2 vs. Group 3 and 4 (17 +/- 14 vs. 18 +/- 9 vs. 49 +/- 21 vs. 45 +/- 16 respectively; P = 0.002). There was significant improvement in oxygen consumption in Groups 2 vs. Groups 3 and 4 (P = 0.037) (39 +/- 10 vs. 46 +/- 10 vs. 24 +/- 12 vs. 24 +/- 7 respectively). EPO added at the time of reperfusion improved oxygen consumption when added to NP in comparison to static hypothermic storage but did not exert any other major benefits.