title: Analysis of perfusates during hypothermic machine perfusion by NMR spectroscopy: a potential tool for predicting kidney graft outcome.
abstract: BACKGROUND
  Machine perfusion use has been reported to promote graft outcome in case of donation after cardiac death. Our objective was to evaluate the potential for nuclear magnetic resonance (NMR) to predict graft outcome by analyzing perfusates during machine perfusion time.
  
  
  METHODS
  We used a renal autotransplantation model mimicking deceased after cardiac death donors with pigs. Organs were subjected to 60 min of warm ischemia before the hypothermic machine preservation during 22 hr. We studied the correlation between creatinemia after transplantation and the NMR data from perfusates.
  
  
  RESULTS
  A metabonomic analysis allowed us to highlight the evolution of several metabolites during perfusion: the concentration of lactate, choline, or amino acids such as valine, glycine, or glutamate increased with time, whereas there was a diminution of total glutathione during this period. The changes in these biomarkers were less severe in the group with the better outcome. Statistical analysis revealed a strong association between the level of those metabolites during machine perfusion and function recovery (Spearman rank ≥0.89; P<0.05).
  
  
  CONCLUSIONS
  Multivariate analysis of lesion biomarkers during kidney perfusion using NMR data could be an interesting tool to assess graft quality, particularly because analyses times (2 hr total) are compatible with clinical application.
authors.affiliation: 1 Université de Poitiers, Poitiers, F-86000, France. 2 INSERM, U1082, Poitiers, F-86000, France. 3 CHU La Pitié Salpétriére, Service Urologie et transplantations rénales, Paris, F-75013, France. 4 COPE: Consortium for Organ Preservation in Europe, Oxford, United Kingdom. 5 CHU Poitiers, Hôpital de la Milétrie, Service de Biochimie, Poitiers, F-86000, France. 6 INRA, UE1372, GenESI, Plateforme Ibisa, Surgères, F-17700, France. 7 CHU Poitiers, Hôpital de la Milétrie, Service d'Urologie, Poitiers, F-86000, France. 8 Address correspondence to: Thierry Hauet, M.D., Ph.D., INSERM U1082, Université de Poitiers, CHU Poitiers, Rue de la Milétrie, B.P. 577, 86021 Poitiers Cedex, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Bon
authors.forename: Claire
authors.initials: C
authors.lastname: Billault
authors.forename: Billault
authors.initials: B
authors.lastname: Claire
authors.forename: Raphaël
authors.initials: R
authors.lastname: Thuillier
authors.forename: William
authors.initials: W
authors.lastname: Hebrard
authors.forename: Nadège
authors.initials: N
authors.lastname: Boildieu
authors.forename: Olivier
authors.initials: O
authors.lastname: Celhay
authors.forename: Jacques
authors.initials: J
authors.lastname: Irani
authors.forename: François
authors.initials: F
authors.lastname: Seguin
authors.forename: Thierry
authors.initials: T
authors.lastname: Hauet
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006085:Graft Survival; D007036:Hypothermia, Induced; D007668:Kidney / Q000378:metabolism* / Q000601:surgery; D016030:Kidney Transplantation / Q000379:methods*; D019344:Lactic Acid / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D055432:Metabolomics / Q000379:methods; D023421:Models, Animal; D010477:Perfusion / Q000379:methods*; D011237:Predictive Value of Tests; D034421:Sus scrofa; D014182:Transplantation, Autologous / Q000379:methods; D052096:Warm Ischemia / Q000379:methods
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D019344:Lactic Acid; D005978:Glutathione; D002794:Choline