1887 Comparison of the efficacy of preservation at 22°C versus 4°C in warm ischemic kidneys from MHC-inbred CLAWN miniature swine

Abstract Background and Aims Static cold preservation, the standard in transplantation, is primarily aimed at reducing metabolic and oxygen demand. Kidney transplantation from donors after cardiac death (DCD) addresses the shortage of donor organs, but these kidneys are susceptible to cold preservation. A previous study using small animal models demonstrated the potential benefits of preserving DCD kidneys at a warmer temperature of 22°C using extracellular-type solutions (Iwai S., PLoS One 2012). Based on this foundational research, our study aimed to evaluate the efficacy of preserving warm ischemic kidneys at temperatures of either 4°C or 22°C using preclinical large animal miniature swine models. Method After 2 hours of warm ischemia, the pig kidneys were preserved for 60 minutes at either 4°C or 22°C with extracellular-type solutions (ETK®). In Experiment 1, these preserved kidneys underwent ex-vivo perfusion for 120 minutes at 37°C with a mean arterial pressure of 85 mmHg. This perfusion used a Ringer's solution supplemented with red blood cells, aiming to determine the early functionality of kidneys subjected to 2-hour warm ischemia in transplantation and to assess whether preservation at 4°C or 22°C could maintain renal function during the acute postoperative period (n = 3 in each group). During this period, both physiological parameters (renal blood flow, intrarenal resistance, and urine output) and metabolic parameters (oxygen consumption) were evaluated. In Experiment 2, kidneys that underwent similar warm ischemia and preservation procedures were transplanted into MHC-matched recipients. These recipients received continuous tacrolimus treatment for 12 days to minimize rejection due to minor antigen differences. After transplantation, renal function was monitored and assessed by serum creatinine levels and renal biopsies for 14 days (n = 3 in each group). Results Experiment 1 demonstrated that kidneys subjected to 2 hours of warm ischemia and then preserved at 22°C had better physiological and metabolic indices during a subsequent 2-hour ex-vivo perfusion compared to those preserved at 4°C. The results were as follows: 22°C vs. 4°C—mean renal blood flow (27 ± 5 vs. 10 ± 0 ml/min), intrarenal resistance (3.5 ± 0.5 vs. 8.7 ± 0.1 mmHg/ml/min), total urine volume (14 ± 5 vs. 5 ± 4 ml), and oxygen consumption (224 ± 39 vs. 93 ± 16 ml/min/g). Importantly, there was no complete cessation of blood flow in either group, indicating the potential for long-