The impact of oxygen supply and erythrocytes during normothermic kidney perfusion

Abstract

The influence of erythrocytes and oxygen concentration on kidneys during long-term normothermic kidney perfusion is under debate. This study compares acellular and erythrocyte-based NMP with focus on oxygen delivery to the tissue as well as the effects of high oxygenation on tissue integrity. Pig kidneys were connected to NMP for six hours. The first group (n = 6; AC500) was perfused without addition of oxygen carriers, arterial perfusate pO2 was maintained at 500 mmHg. In the second group (n = 6; RBC500) washed erythrocytes were added to the perfusate at pO2 of 500 mmHg. Third group (n = 6; RBC200) was perfused with erythrocyte containing perfusate at more physiological pO2 of 200 mmHg. Addition of RBC did not relevantly increase oxygen consumption of the kidneys during perfusion. Likewise, there were no differences in kidney functional and injury parameters between AC500 and RBC500 group. Expression of erythropoietin as indicator of tissue hypoxia was comparable in all three groups. Cell free NMP at supraphysiological oxygen partial pressure seems to be a safe alternative to erythrocyte based perfusion without adverse effect on kidney integrity and provides a less cumbersome application of NMP in clinical practice.

Acellular Perfusate is an Adequate Alternative to Packed Red Blood Cells During Normothermic Human Kidney Perfusion

“…Glomerular function, evaluated by renal clearance of creatinine, did not differ significantly between the groups. This is consistent with another study 27 in which perfusion of porcine kidneys with an acellular media (Aqix RS I) supplemented with 40 g/L of bovine serum albumin resulted in similar creatine clearance compared to perfusion with RBCs. However, this differs from another study 28 using porcine kidneys subjected to 30 min of warm ischemia, HMP for 3 h, and NMP for 4 h. In the latter, perfusion of DCD pig kidneys with diluted blood during NMP reduced renal injury, improved Na reabsorption and creatine clearance, and was associated with increased tissue ATP levels.…”

“…However, this differs from another study 28 using porcine kidneys subjected to 30 min of warm ischemia, HMP for 3 h, and NMP for 4 h. In the latter, perfusion of DCD pig kidneys with diluted blood during NMP reduced renal injury, improved Na reabsorption and creatine clearance, and was associated with increased tissue ATP levels. Of interest, Von Horn et al 27 also demonstrated that creatinine clearance and oxygen consumption were reduced when the perfusate oxygenation was diminished from >500 mm Hg (similar to our study and supraphysiologic) to 200 mm Hg, at a flow rate of ~0.5 L/min. This suggests that the requirement for an O 2 carrier (RBCs or synthetic) depends on the amount of dissolved O 2 provided.…”

“…In addition, we did not correlate perfusion parameters or ATP levels with kidney function in vivo or after transplantation. Although our group 3 , 16 and others 8 , 27 have used a combination of EC, kidney metabolism, perfusion parameters, urine output, macroscopic and microscopic assessment, and gene-associated damage to provide an overall measure of kidney quality during NMP, it remains to be established whether these interventions have an impact on both short-term (eg, DGF) 1 and long-term kidney graft function. 31 However, early human data suggest that NMP reduces DGF compared with SCS.…”

Loss of Endothelial Glycocalyx During Normothermic Machine Perfusion of Porcine Kidneys Irrespective of Pressure and Hematocrit

“…Data on hematocrit are minimal in NMP studies, but a recent study showed no effect of increased RBC concentrations in the perfusate on fractional sodium excretion or creatinine clearance. 46 In our study, no effects on tubular function were seen as well. It could be that the supplied oxygen range is more than sufficient for the marginal donor kidneys in our model.…”

The association between hemoglobin levels and renal function parameters during normothermic machine perfusion: A retrospective cohort study using porcine kidneys

“…43 Indeed, NMP without RBCs, but with a colloid-rich preservation solution and a supraphysiological partial oxygen pressure, results in similar renal function markers during NMP compared to perfusion with a hemoglobin-rich preservation solution (around 3 mmol/L). 44 In contrast, others have shown that renal oxygen consumption rates are significantly higher in kidneys perfused in the presence of RBCs (with hemoglobin levels of 4 mmol/L) compared with the absence of RBCs. 31 These contradictory results might be explained by differences in type of pigs, slaughterhouse, or laboratory, used as donors.…”