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Effects of oxygen during long-term hypothermic machine perfusion in a porcine model of kidney donation after circulatory death.

Abstract

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, remaining cellular activity requires oxygen. Since 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 (UW- MPS) supplemented with no oxygen, 21% or 100% oxygen. Next, kidneys were reperfused for 4 hours in a normothermic machine perfusion (NMP) setup.

RESULTS

HMP resulted in significantly better kidney function during NMP. Thiobarbituric acid-reactive substances (TBARS), markers of oxidative stress, were significantly lower in HMP preserved kidneys. HMP preserved kidneys showed significantly lower ASAT and LDH levels compared to kidneys preserved by CS. No differences were found between the HMP groups subjected to different oxygen concentrations. ATP levels significantly improved during HMP when active oxygenation was applied.

CONCLUSION

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.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

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  • Authors+Show Affiliations

    ,

    Dept of Surgery, University Medical Centre Groningen, University of Groningen, The Netherlands.

    ,

    Dept of Surgery, University Medical Centre Groningen, University of Groningen, The Netherlands.

    ,

    Dept of Surgery, University Medical Centre Groningen, University of Groningen, The Netherlands.

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    Dept of Pathology, University Medical Centre Groningen, University of Groningen, The Netherlands.

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

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

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

    ,

    Dept of Surgery, University Medical Centre Groningen, University of Groningen, The Netherlands.

    Source

    Transplantation : 2019 Apr 02 pg

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    30951018

    Citation

    Venema, Leonie H., et al. "Effects of Oxygen During Long-term Hypothermic Machine Perfusion in a Porcine Model of Kidney Donation After Circulatory Death." Transplantation, 2019.
    Venema LH, Brat A, Moers C, et al. Effects of oxygen during long-term hypothermic machine perfusion in a porcine model of kidney donation after circulatory death. Transplantation. 2019.
    Venema, L. H., Brat, A., Moers, C., 't Hart, N. A., Ploeg, R. J., Hannaert, P., ... Leuvenink, H. G. D. (2019). Effects of oxygen during long-term hypothermic machine perfusion in a porcine model of kidney donation after circulatory death. Transplantation, doi:10.1097/TP.0000000000002728.
    Venema LH, et al. Effects of Oxygen During Long-term Hypothermic Machine Perfusion in a Porcine Model of Kidney Donation After Circulatory Death. Transplantation. 2019 Apr 2; PubMed PMID: 30951018.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Effects of oxygen during long-term hypothermic machine perfusion in a porcine model of kidney donation after circulatory death. AU - Venema,Leonie H, AU - Brat,Aukje, AU - Moers,Cyril, AU - 't Hart,Nils A, AU - Ploeg,Rutger J, AU - Hannaert,Patrick, AU - Minor,Thomas, AU - Leuvenink,Henri G D, AU - ,, Y1 - 2019/04/02/ PY - 2019/4/6/entrez JF - Transplantation JO - Transplantation N2 - 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, remaining cellular activity requires oxygen. Since 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 (UW- MPS) supplemented with no oxygen, 21% or 100% oxygen. Next, kidneys were reperfused for 4 hours in a normothermic machine perfusion (NMP) setup. RESULTS: HMP resulted in significantly better kidney function during NMP. Thiobarbituric acid-reactive substances (TBARS), markers of oxidative stress, were significantly lower in HMP preserved kidneys. HMP preserved kidneys showed significantly lower ASAT and LDH levels compared to kidneys preserved by CS. No differences were found between the HMP groups subjected to different oxygen concentrations. ATP levels significantly improved during HMP when active oxygenation was applied. CONCLUSION: 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.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. SN - 1534-6080 UR - https://www.unboundmedicine.com/medline/citation/30951018/Effects_of_oxygen_during_long_term_hypothermic_machine_perfusion_in_a_porcine_model_of_kidney_donation_after_circulatory_death_ L2 - http://dx.doi.org/10.1097/TP.0000000000002728 DB - PRIME DP - Unbound Medicine ER -