Influence of Different Partial Pressures of Oxygen During Continuous Hypothermic Machine Perfusion in a Pig Kidney Ischemia-reperfusion Autotransplant Model

Transplantation. 2020 Apr;104(4):731-743. doi: 10.1097/TP.0000000000003051.

Abstract

Background: The optimal perfusate partial pressure of oxygen (PO2) during hypothermic machine perfusion (HMP) is unknown. The aims of the study were to determine the functional, metabolic, structural, and flow dynamic effects of low and high perfusate PO2 during continuous HMP in a pig kidney ischemia-reperfusion autotransplant model.

Methods: The left kidneys of a ±40 kg pigs were exposed to 30 minutes of warm ischemia and randomized to receive 22-hour HMP with either low perfusate PO2 (30% oxygen, low oxygenated HMP [HMPO2]) (n = 8) or high perfusate PO2 (90% oxygen, HMPO2high) (n = 8), before autotransplantation. Kidneys stored in 22-hour standard HMP (n = 6) and 22-hour static cold storage (n = 6) conditions served as controls. The follow-up after autotransplantation was 13 days.

Results: High PO2 resulted in a 3- and 10-fold increase in perfusate PO2 compared with low HMPO2 and standard HMP, respectively. Both HMPO2 groups were associated with superior graft recovery compared with the control groups. Oxygenation was associated with a more rapid and sustained decrease in renal resistance. While there was no difference in functional outcomes between both HMPO2 groups, there were clear metabolic differences with an inverse correlation between oxygen provision and the concentration of major central metabolites in the perfusion fluid but no differences were observed by oxidative stress and metabolic evaluation on preimplantation biopsies.

Conclusions: While this animal study does not demonstrate any advantages for early graft function for high perfusate PO2, compared with low perfusate PO2, perfusate metabolic profile analysis suggests that aerobic mechanism is better supported under high perfusate PO2 conditions.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Biomarkers / blood
  • Cold Ischemia
  • Creatinine / blood
  • Energy Metabolism
  • Equipment Design
  • Female
  • Hypothermia, Induced / adverse effects
  • Hypothermia, Induced / instrumentation*
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney / surgery*
  • Kidney Transplantation / adverse effects
  • Kidney Transplantation / instrumentation*
  • Models, Animal
  • Oxygen / metabolism*
  • Partial Pressure
  • Perfusion / adverse effects
  • Perfusion / instrumentation*
  • Random Allocation
  • Sus scrofa
  • Time Factors
  • Transplantation, Autologous
  • Warm Ischemia

Substances

  • Biomarkers
  • Creatinine
  • Oxygen