Cold ischemia augments allogeneic-mediated injury in rat kidney allografts

Background. Some clinical studies demonstrate that kidney grafts with prolo nged cold ischemia experience early acute rejection more often than those w ith minimal ischemia. The mechanism, however, is putative. Therefore, the a im of this study was to unravel the impact of ischemia on the immune respon se in rat kidney allografts compared with that in isografts. Methods. To induce ischemic injury, donor kidneys were preserved for 24 hou rs in 4 degreesC University of Wisconsin solution before transplantation. N o immunosuppression was administered. The histomorphology according to the BANFF criteria for acute rejection and infiltrating cells were assessed at days 1, 2, 3, 4, 6, and 8 post-transplantation. Results. In allografts, exposure of the kidney to ischemia led to a signifi cantly earlier onset of interstitial cell infiltration and tubulitis compar ed with nonischemic allografts. The BANFF score of interstitial cell infilt ration was 1 +/- 0 vs. 0.25 +/- 0.29 at day 3 and 2 +/- 0 vs. 1.25 +/- 0.25 at day 4. In contrast, in isografts, the effect of ischemia on the histolo gy was not significant. From day 6, the histologic differences between isch emic and nonischemic grafts disappeared. Ischemia led to a more intense exp ression of P-selectin (day 1), intercellular adhesion molecule-1 (ICAM-1; d ay 2), and major histocompatibility complex (MHC) class II on endothelium a nd proximal tubular cells (day 2) in both allografts and isografts. Concurr ently with the up-regulated ICAM-1 and MHC expression, significantly more C D4(+) cells and macrophages infiltrated the ischemic allografts at days 2 a nd 3 and the ischemic isografts at day 4. Importantly, the influx of these cells after ischemia was significantly greater in allografts than in isogra fts. Conclusions. Cold ischemia augments allogeneic-mediated cell infiltration i n rat kidney allografts. The earlier onset of acute rejection in 24-hour co ld preserved allografts may be prevented by better preservation or treatmen t using tailored immunosuppression.