BackgroundEx-vivo normothermic perfusion strategies are a promising new instrument in organ transplantation. The perfusion conditions are designed to be protective however the artificial environment can induce a local inflammatory response. The aim of this study was to determine the effect of incorporating a Cytosorb adsorber into an isolated kidney perfusion system.MethodsPorcine kidneys were subjected to 22 h of cold ischaemia then reperfused for 6 h on an ex vivo reperfusion circuit. Pairs of kidneys were randomised to either control (n = 5) or reperfusion with a Cytosorb adsorber (n = 5) integrated into the circuit. Tissue, blood and urine samples were taken for the measurement of inflammation and renal function.ResultsBaseline levels of cytokines (IL-6, TNFα, IL-8, IL-10, IL-1β, IL-1α) were similar between groups. Levels of IL-6 and IL-8 in the perfusate significantly increased during reperfusion in the control group but not in the Cytosorb group (P = 0.023, 0.049). Levels of the other cytokines were numerically lower in the Cytosorb group; however, this did not reach statistical significance. The mean renal blood flow (RBF) was significantly higher in the Cytosorb group (162 ± 53 vs. 120 ± 35 mL/min/100 g; P = 0.022). Perfusate levels of prostaglandin E2 were significantly lower in the Cytosorb group (642 ± 762 vs. 3258 ± 980 pg/mL; P = 0.0001). Levels of prostacyclin were significantly lower in the Cytosorb group at 1, 3 and 6 h of reperfusion (P = 0.008, 0.003, 0.0002). Levels of thromboxane were also significantly lower in the Cytosorb group throughout reperfusion (P = 0.005). Haemoadsorption had no effect on creatinine clearance (P = 0.109).ConclusionHaemoadsorption can reduce the inflammatory response and improve renal blood flow during perfusion. Nonetheless, in this model haemoadsorption had no influence on renal function and this may relate to the broad-spectrum action of the Cytosorb adsorber that also removes potentially important anti-inflammatory mediators.

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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.