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The Effects of Oxygenation on Ex Vivo Kidneys Undergoing Hypothermic Machine Perfusion.
Transplantation 2019; 103(2):314-322T

Abstract

BACKGROUND

Supplemental oxygenation of the standard hypothermic machine perfusion (HMP) circuit has the potential to invoke favorable changes in metabolism, optimizing cadaveric organs before transplantation.

METHODS

Eight pairs of porcine kidneys underwent 18 hours of either oxygenated (HMP/O2) or aerated (HMP/Air) HMP in a paired donation after circulatory death model of transplantation. Circulating perfusion fluid was supplemented with the metabolic tracer universally labeled glucose.Perfusate, end-point renal cortex, and medulla samples underwent metabolomic analysis using 1-dimension and 2-dimension nuclear magnetic resonance experiments in addition to gas chromatography-mass spectrometry. Analysis of C-labeled metabolic products was combined with adenosine nucleotide levels and differences in tissue architecture.

RESULTS

Metabolomic analysis revealed significantly higher concentrations of universally labeled lactate in the cortex of HMP/Air versus HMP/O2 kidneys (0.056 mM vs 0.026 mM, P < 0.05). Conversely, newly synthesized [4,5-C] glutamate concentrations were higher in the cortex of HMP/O2 kidneys inferring relative increases in tricarboxylic acid cycle activity versus HMP/Air kidneys (0.013 mmol/L vs 0.003 mmol/L, P < 0.05). This was associated with greater amounts of adenoside triphosphate in the cortex HMP/O2 versus HMP/Air kidneys (19.8 mmol/mg protein vs 2.8 mmol/mg protein, P < 0.05). Improved flow dynamics and favorable ultrastructural features were also observed in HMP/O2 kidneys. There were no differences in thiobarbituric acid reactive substances and reduced glutathione levels, tissue markers of oxidative stress, between groups.

CONCLUSIONS

The supplementation of perfusion fluid with high-concentration oxygen (95%) results in a greater degree of aerobic metabolism versus aeration (21%) in the nonphysiological environment of HMP, with reciprocal changes in adenoside triphosphate levels.

Authors+Show Affiliations

Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom. Department of Renal Surgery, University Hospitals Birmingham, Birmingham, United Kingdom.Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.Department of Histopathology, University Hospitals Birmingham, Birmingham, United Kingdom.Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.Department of Histopathology, University Hospitals Birmingham, Birmingham, United Kingdom.School of Biosciences, University of Birmingham, Birmingham, United Kingdom.School of Biosciences, University of Birmingham, Birmingham, United Kingdom.Department of Renal Surgery, University Hospitals Birmingham, Birmingham, United Kingdom.Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom. Department of Renal Surgery, University Hospitals Birmingham, Birmingham, United Kingdom.Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30461718

Citation

Patel, Kamlesh, et al. "The Effects of Oxygenation On Ex Vivo Kidneys Undergoing Hypothermic Machine Perfusion." Transplantation, vol. 103, no. 2, 2019, pp. 314-322.
Patel K, Smith TB, Neil DAH, et al. The Effects of Oxygenation on Ex Vivo Kidneys Undergoing Hypothermic Machine Perfusion. Transplantation. 2019;103(2):314-322.
Patel, K., Smith, T. B., Neil, D. A. H., Thakker, A., Tsuchiya, Y., Higgs, E. B., ... Ludwig, C. (2019). The Effects of Oxygenation on Ex Vivo Kidneys Undergoing Hypothermic Machine Perfusion. Transplantation, 103(2), pp. 314-322. doi:10.1097/TP.0000000000002542.
Patel K, et al. The Effects of Oxygenation On Ex Vivo Kidneys Undergoing Hypothermic Machine Perfusion. Transplantation. 2019;103(2):314-322. PubMed PMID: 30461718.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Effects of Oxygenation on Ex Vivo Kidneys Undergoing Hypothermic Machine Perfusion. AU - Patel,Kamlesh, AU - Smith,Thomas B, AU - Neil,Desley A H, AU - Thakker,Alpesh, AU - Tsuchiya,Yugo, AU - Higgs,Ellen B, AU - Hodges,Nikolas J, AU - Ready,Andrew R, AU - Nath,Jay, AU - Ludwig,Christian, PY - 2018/11/22/pubmed PY - 2019/8/6/medline PY - 2018/11/22/entrez SP - 314 EP - 322 JF - Transplantation JO - Transplantation VL - 103 IS - 2 N2 - BACKGROUND: Supplemental oxygenation of the standard hypothermic machine perfusion (HMP) circuit has the potential to invoke favorable changes in metabolism, optimizing cadaveric organs before transplantation. METHODS: Eight pairs of porcine kidneys underwent 18 hours of either oxygenated (HMP/O2) or aerated (HMP/Air) HMP in a paired donation after circulatory death model of transplantation. Circulating perfusion fluid was supplemented with the metabolic tracer universally labeled glucose.Perfusate, end-point renal cortex, and medulla samples underwent metabolomic analysis using 1-dimension and 2-dimension nuclear magnetic resonance experiments in addition to gas chromatography-mass spectrometry. Analysis of C-labeled metabolic products was combined with adenosine nucleotide levels and differences in tissue architecture. RESULTS: Metabolomic analysis revealed significantly higher concentrations of universally labeled lactate in the cortex of HMP/Air versus HMP/O2 kidneys (0.056 mM vs 0.026 mM, P < 0.05). Conversely, newly synthesized [4,5-C] glutamate concentrations were higher in the cortex of HMP/O2 kidneys inferring relative increases in tricarboxylic acid cycle activity versus HMP/Air kidneys (0.013 mmol/L vs 0.003 mmol/L, P < 0.05). This was associated with greater amounts of adenoside triphosphate in the cortex HMP/O2 versus HMP/Air kidneys (19.8 mmol/mg protein vs 2.8 mmol/mg protein, P < 0.05). Improved flow dynamics and favorable ultrastructural features were also observed in HMP/O2 kidneys. There were no differences in thiobarbituric acid reactive substances and reduced glutathione levels, tissue markers of oxidative stress, between groups. CONCLUSIONS: The supplementation of perfusion fluid with high-concentration oxygen (95%) results in a greater degree of aerobic metabolism versus aeration (21%) in the nonphysiological environment of HMP, with reciprocal changes in adenoside triphosphate levels. SN - 1534-6080 UR - https://www.unboundmedicine.com/medline/citation/30461718/The_Effects_of_Oxygenation_on_Ex_Vivo_Kidneys_Undergoing_Hypothermic_Machine_Perfusion_ L2 - http://Insights.ovid.com/pubmed?pmid=30461718 DB - PRIME DP - Unbound Medicine ER -