Physiological effects of altering oxygenation during kidney normothermic machine perfusion.

Kidney normothermic machine perfusion (NMP) has historically used a 95% O2-5% CO2 gas mixture. Using a porcine model of organ retrieval, NMP, and reperfusion, we tested the hypothesis that reducing perfusate oxygenation ( PpO2 ) would be detrimental to renal function and cause injury. In the minimal ischemic injury experiment, kidneys sustained 10 min of warm ischemia and 2 h of static cold storage before 1 h of NMP with either 95%, 25%, or 12% O2 with 5% CO2 and N2 balance. In the clinical injury experiment, kidneys with 10-min warm ischemia and 17-h static cold storage underwent 1-h NMP with the above gas combinations or 18-h static cold storage as a control. They were then reperfused with whole blood and 95% O2 for 3 h. Overall, reducing PpO2 did not significantly influence renal function in either experiment. Furthermore, there were no differences in the injury markers urinary neutrophil gelatinase-associated lipocalin or tissue high-motility group box protein 1. In the minimal ischemic injury experiment, a PpO2 of 25% significantly reduced renal blood flow and increased vascular resistance. Oxygen delivery, consumption, and extraction (oxygen extraction ratio) were significantly greater at 95% PpO2 . In the clinical injury experiment, renal blood flow was significantly increased at 25% PpO2 and Na+ excretion decreased. At 95% PpO2 , the oxygen content and oxygen extraction ratio were significantly increased. During reperfusion, renal blood flow was significantly increased in the 25% group. The control group pH was significantly decreased compared with the 25% group. Our data suggest that reducing PpO2 during NMP does not have detrimental effects on renal function or markers of injury.

Lowering Perfusate Temperature From 37°C to 32°C Diminishes Function in a Porcine Model of Ex Vivo Kidney Perfusion.

BACKGROUND: Ex vivo perfusion (EVP) is a novel method of preservation. However, optimal perfusion conditions remain undetermined. Reducing the temperature of the perfusate to subnormothermia may be beneficial during EVP and improve early graft function. The aim of this study was to investigate whether subnormothermia would influence the conditioning effect of EVP when compared with normothermic perfusion, and standard cold static storage (CS). METHODS: Porcine kidneys underwent static CS for 23 hours followed by 1 hour of EVP using leukocyte-depleted blood at a mean temperature of 32°C or 37°C. After this, kidneys were reperfused with whole autologous blood at 37°C for 3 hours to assess renal function and injury. These were compared with a control group that underwent 24 hours CS. RESULTS: During EVP, kidneys perfused at 37°C had a higher level of renal blood flow and oxygen consumption compared with EVP at 32°C (P = 0.001, 0.002). During reperfusion, 32°C EVP kidneys had lower creatinine clearance and urine output than control (P = 0.023, 0.011) and a higher fractional excretion of sodium, serum potassium, and serum aspartate transaminase than 37°C EVP kidneys (P = 0.01, 0.023, 0.009). CONCLUSIONS: Tubular and renal functions were better preserved by a near-physiological temperature of 37°C during 1 hour of EVP, when compared to EVP at 32°C or cold storage.