The effects of donor brain death on renal function and arachidonic acid metabolism in a large animal model of hypothermic preservation injury.

Abstract

Donor brain death (BD) has been implicated as a risk factor for the poor performance of kidneys after transplantation in small but not large animal models. This study determined the effects of donor BD on renal function and lipid mediator metabolism in a large animal model of renal hypothermic preservation injury. Adult beagle donors were subjected to explosive BD for 16 hr. After BD, the kidneys were removed, cold stored for 24 hr in cold University of Wisconsin solution, and allotransplanted into recipient dogs for either 4 hr (group 1) or 7 days (group 2). Controls for both groups consisted of kidneys obtained from living donors. Renal allograft function and tissue arachidonic acid (AA) metabolism were determined after reperfusion. Short-term renal function after transplantation was generally unaffected by BD. Renal blood flow decreased after reperfusion but was not altered during the 16-hr BD period. Neutrophil infiltration significantly increased in kidneys from brain-dead donors before storage and after 4 hr of reperfusion. Renal cortex and medulla AA metabolism were not significantly affected by BD after short-term reperfusion except when thiol-ether leukotrienes (LTC(4)/D(4)/E(4)) were increased with BD. Serum creatinine was elevated during 7 days, but, surprisingly, BD significantly attenuated this injury. BD in large mammals does not significantly affect renal allograft function or AA metabolism after transplantation. The role of BD in human renal preservation injury and inflammation should be reevaluated.