Physiological effects of altering oxygenation during kidney normothermic machine perfusion

Am J Physiol Renal Physiol. 2019 May 1;316(5):F823-F829. doi: 10.1152/ajprenal.00178.2018. Epub 2019 Feb 20.

Abstract

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.

Keywords: acute kidney injury; ischemia-reperfusion injury; renal oxygenation; transplantation.

MeSH terms

  • Acute Kidney Injury / etiology
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / pathology
  • Animals
  • Cold Ischemia
  • Kidney / metabolism*
  • Kidney / pathology
  • Kinetics
  • Nephrectomy
  • Oxidative Stress
  • Oxygen / metabolism*
  • Oxygen Consumption*
  • Perfusion / adverse effects
  • Perfusion / instrumentation
  • Perfusion / methods*
  • Renal Circulation*
  • Reperfusion Injury / etiology
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Sus scrofa
  • Temperature*
  • Warm Ischemia

Substances

  • Oxygen