Ex vivo evaluation of organ function after cold ischemia

An ex vivo perfusion of kidneys was performed at 34 degrees C after cold ischemia of 24, 48, 72, and 96 hours to evaluate organ function prospectively. The prospective evaluation of organ function followed static hypothermic storage of the kidneys in a solution representative of clinical organ preservation. The warm perfusion was performed with an acellular solution that supports oxidative metabolism of sufficient magnitude to restore urine flow ex vivo. The parameters of organ function evaluated included oxygen consumption, vascular resistance, urine flow, and glomerular filtration rates, which were correlated with the histologic findings. The results of this study suggest that kidneys exposed to 24 and 48 hours of cold ischemia demonstrated oxygen consumption rates and vascular dynamics similar to control kidneys without exposure to cold ischemia, indicating cell viability. When the cold ischemic period was increased beyond 48 hours of preservation, substantially reduced rates of oxygen consumption and increased vascular resistances were observed, representing a loss of viability confirmed histologically. However, organ function was found to be impaired after exposure to cold ischemia at every time point. These results suggest that cold ischemic exposure had a negative impact on immediate renal function once oxidative metabolism was restored, which was exacerbated as the cold ischemic period was extended. Furthermore, these findings suggest that although the renal cells were viable after cold ischemic exposure, the viability status did not result in immediate function. Therefore, assessment of an organ based solely on cell viability may falsely indicate a functional organ. It will be necessary to identify parameters of organ function that can distinguish reversibility from non-reversibility of cellular impairment to distinguish permanent functional disturbances. The ability to predict organ function prospectively will be an important aspect of any effective future expansion of the organ donor pool.