Controlled Oxygenated Rewarming Compensates for Cold Storage-induced Dysfunction in Kidney Grafts.

Background Normothermic machine perfusion (NMP) provides a promising strategy for preservation and conditioning of marginal organ grafts. However, at present high logistic effort limits normothermic renal perfusion to a short, postponed machine perfusion at site of the recipient transplant center. Thus, organ preservation during transportation still takes place under hypothermic conditions, leading to significantly reduced efficacy of NMP. Recently it was shown that gentle and controlled warming up of cold stored kidneys compensates for hypothermic induced damage in comparison to end ischemic NMP. This study aims to compare controlled oxygenated rewarming (COR) with continuous up- front normothermic perfusion in a porcine model of transplantation. Methods Following exposure to 30 minutes of warm ischemia kidneys (n=6/group) were removed and either cold stored for 8 hours (CS), cold stored for 6 hours with subsequent controlled rewarming up to 35 °C for 2 hours (COR) or directly subjected to 8 hours of continuous normothermic machine perfusion (NMP). Kidney function was evaluated using a preclinical autotransplant model with follow up for 7 days. Results NMP and COR both improved renal function in comparison to CS and displayed similar serum creatinine and urea levels during follow up. COR resulted in less tenascin C expression in the tissue compared to CS, indicating reduced proinflammatory upregulation in the graft by gentle rewarming. Conclusion COR seems to be a potential alternative in clinical application of NMP, thereby providing logistic ease and usability.