• Annals of surgery · Oct 2023

    Ischemia-Induced Metabolic Patterns Associate With Kidney Function During Normothermic Kidney Perfusion, a Preclinical Study.

    • Julie De Beule, Sam De Craemer, Laurence Verstraeten, Bart Ghesquière, and Ina Jochmans.
    • Department of Microbiology, Immunology, and Transplantation, Laboratory of Abdominal Transplantation, Transplantation Research Group, KU Leuven, 3000 Leuven, Belgium.
    • Ann. Surg. 2023 Oct 23.

    ObjectiveTo investigate if ischemia alters donor kidney metabolism and whether these changes associate with organ function.Summary Background DataAn unmet need in kidney transplantation is the ability to predict post-transplant organ function before transplantation. Key to such viability testing is a profound understanding of the organ's complex biochemistry and how ischemia, inevitable during the transplantation process, influences this.MethodsFirst, metabolic changes in glucose, lactate and 20 amino acids induced by no, 1h of warm, or 22h of cold ischemia were investigated during 4h perfusion of pig kidneys with autologous whole blood (n=6/group), simulating the ischemia-reperfusion phase of transplantation. Next, we confirmed similar metabolic changes during normothermic preservation of pig (n=3/group; n=4 for cold ischemia) and discarded human kidneys (n=6) perfused with a red-blood cell based perfusate.ResultsAt 2h of perfusion with autologous whole blood, abundances of 17/20 amino acids were significantly different between groups, reflecting the type of ischemia. Amino acid changes at 15 min and 2h of perfusion correlated with future kidney function during perfusion. Similar metabolic patterns were observed during perfusion preservation of pig and discarded human donor kidneys, suggesting an opportunity to assess kidney viability before transplantation.ConclusionsPerfusate metabolite changes during normothermic kidney perfusion represent a unique non-invasive opportunity to assess graft viability. These findings now need validation in transplant studies.Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

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