Physiological effects of altering oxygenation during kidney normothermic machine perfusion

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 ([Formula: see text]) 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 [Formula: see text] 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 [Formula: see text] of 25% significantly reduced renal blood flow and increased vascular resistance. Oxygen delivery, consumption, and extraction (oxygen extraction ratio) were significantly greater at 95% [Formula: see text]. In the clinical injury experiment, renal blood flow was significantly increased at 25% [Formula: see text] and Na+ excretion decreased. At 95% [Formula: see text], 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 [Formula: see text] during NMP does not have detrimental effects on renal function or markers of injury.

Haematocrit differences modify the association of cardiopulmonary bypass reoxygenation with acute kidney injury after paediatric Tetralogy of Fallot repair

“…However, little is known about whether higher CPB oxygenation is an independent risk factor for AKI following Tetralogy of Fallot repair. A recent experimental report from Adams and colleagues 11 investigated the potential effect of reducing the PpO2 on renal function. In this minimal ischaemic injury experiment, reducing the PpO2 did not significantly influence renal function overall, in terms of no differences developing in the injury markers, urinary neutrophil gelatinase-associated lipocalin or tissue high-motility group box protein 1, which suggested that reducing the PpO2 does not have detrimental effects on renal function or markers of injury.…”

Kidney Perfusion as an Organ Quality Assessment Tool—Are We Counting Our Chickens Before They Have Hatched?

“…In vivo, high fractional sodium excretion (FeNa) (usually >1%) is suggestive of tubular necrosis [80]. Several normothermic perfusion models, making use of pig kidneys or kidneys found not suitable for transplantation, report FeNa with a high variability and a wide range (5%-200%) [81][82][83][84][85]. Extrapolating in vivo findings, it seems logical that the lower the FeNa during normothermic perfusion, the better tubular function is preserved.…”

“…Therefore, measuring oxygen consumption could be a potential viability marker. Indeed, oxygen consumption is measured in different models as a marker of kidney metabolic activity [81,84,85,88]. What limits direct comparison between studies is the use of a multitude of formulas to calculate oxygen consumption.…”

“…It is also important to correct for temperatures other than body temperature. Furthermore, there is evidence that oxygen consumption in the kidney during normothermic perfusion is dependent on the oxygen concentrations offered to the kidney [81]. Metabolomics analysis could offer additional information.…”

Genetic Engineering of the Kidney to Permanently Silence MHC Transcripts During ex vivo Organ Perfusion

“…Previous studies have indicated the benefits of oxygenating the perfusion solution already during hypothermic perfusion by reducing oxidative stress and supporting the energy status in presence of low metabolic rates (50,51). During sub-normothermic to normothermic perfusion the increased metabolism demands an appropriate oxygen supply, but recent studies indicate that normothermic perfusion with reduced perfusate oxygenation for a limited period of time may also be possible without severely compromising renal function or tissue integrity (52).…”