Metabolomic perfusate analysis during kidney machine perfusion : the pig provides an appropriate model for human studies

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Authors

  • Jay Nath
  • Alison Guy
  • Thomas B. Smith
  • Mark Cobbold
  • James Hodson
  • Andrew R. Ready

Abstract

Introduction Hypothermic machine perfusion offers great promise in kidney transplantation and experimental studies are needed to establish the optimal conditions for this to occur. Pig kidneys are considered to be a good model for this purpose and share many properties with human organs. However it is not established whether the metabolism of pig kidneys in such hypothermic hypoxic conditions is comparable to human organs. Methods Standard criteria human (n = 12) and porcine (n = 10) kidneys underwent HMP using the LifePort Kidney Transporter 1.0 (Organ Recovery Systems) using KPS-1 solution. Perfusate was sampled at 45 minutes and 4 hours of perfusion and metabolomic analysis performed using 1-D 1H-NMR spectroscopy. Results There was no inter-species difference in the number of metabolites identified. Of the 30 metabolites analysed, 16 (53.3%) were present in comparable concentrations in the pig and human kidney perfusates. The rate of change of concentration for 3-Hydroxybutyrate was greater for human kidneys (p<0.001). For the other 29 metabolites (96.7%), there was no difference in the rate of change of concentration between pig and human samples. Conclusions Whilst there are some differences between pig and human kidneys during HMP they appear to be metabolically similar and the pig seems to be a valid model for human studies.

Details

Original languageEnglish
Article numbere114818
JournalPLoS ONE
Volume9
Issue number12
Publication statusPublished - 12 Dec 2014

Keywords

  • Absorption spectroscopy, Cadaveric renal transplantation, Kidneys, Metabolic analysis, Metabolites, Metabolomics, Pig models, Renal transplantation