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Effects of Oxygen During Long-term Hypothermic Machine Perfusion in a Porcine Model of Kidney Donation After Circulatory Death

Venema, Leonie H. MSc1; Brat, Aukje MSc1; Moers, Cyril MD, PhD1; ‘t Hart, Nils A. MD, PhD2; Ploeg, Rutger J. MD3; Hannaert, Patrick PhD4; Minor, Thomas MD5; Leuvenink, and Henri G.D. PhD1 on behalf of the COPE consortium

doi: 10.1097/TP.0000000000002728
Original Basic Science–General
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Background. Hypothermic machine perfusion (HMP) has become standard care in many center’s to preserve kidneys donated after circulatory death (DCD). Despite a significant reduction in metabolism at low temperatures, the remaining cellular activity requires oxygen. Because of the role and safety of oxygen during HMP has not been fully clarified, its supply during HMP is not standard yet. This study investigates the effect of administering oxygen during HMP on renal function in a porcine DCD model.

Methods. After 30 minutes of warm ischemia, porcine slaughterhouse kidneys were preserved for 24 hours by means of cold storage (CS), or HMP with Belzer Machine Perfusion Solution supplemented with no oxygen, 21% or 100% oxygen. Next, kidneys were reperfused for 4 hours in a normothermic machine perfusion setup.

Results. HMP resulted in significantly better kidney function during normothermic machine perfusion. Thiobarbituric acid-reactive substances, markers of oxidative stress, were significantly lower in HMP preserved kidneys. HMP preserved kidneys showed significantly lower aspartate aminotransferase and lactate dehydrogenase levels compared with kidneys preserved by CS. No differences were found between the HMP groups subjected to different oxygen concentrations. Adenosine triphosphate levels significantly improved during HMP when active oxygenation was applied.

Conclusions. This study showed that preservation of DCD kidneys with HMP is superior to CS. Although the addition of oxygen to HMP did not result in significantly improved renal function, beneficial effects were found in terms of reduced oxidative stress and energy status. Oxygen addition proofed to be safe and did not show detrimental effects.

1 Department of Surgery, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.

2 Department of Pathology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.

3 Department of Surgery, Nuffield Department of Surgical Science, University of Oxford, Oxford, United Kingdom.

4 IRTOMIT, INSERM U1082, Faculté de Médecine et de Pharmacie, Université de Poitiers, Poitiers, France.

5 Department for Surgical Research/General Surgery, University Hospital Essen, Essen, Germany.

Received 1 August 2018. Revision received 8 January 2019.

Accepted 27 February 2019.

L.H.V. participated in research design, performance of the experiments, participated in data analysis, and wrote the paper. A.B. participated in research design, performance of the experiments, and wrote the paper. C.M. participated in research design. N.A.T. participated in research design and contributed to histology analysis. R.J.P. participated in research design. P.H. participated in research design and participated in data analysis. T.M. participated in research design. H.G.D.L. participated in research design and supervising role.

Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.transplantjournal.com).

The authors declare no conflicts of interest.

The experiments presented in this paper are funded by the Consortium for Organ Preservation in Europe (COPE).

Correspondence: Leonie H. Venema, MSc, CMC V Y2144, BA44, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. (l.h.venema@umcg.nl).

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