title: Metabolic differences between cold stored and machine perfused porcine kidneys: A1H NMR based study.
abstract: Hypothermic machine perfusion (HMP) and static cold storage (SCS) are the two methods used to preserve deceased donor kidneys prior to transplant. This study seeks to characterise the metabolic profile of HMP and SCS porcine kidneys in a cardiac death donor model. Twenty kidneys were cold flushed and stored for two hours following retrieval. Paired kidneys then underwent 24 h of HMP or SCS or served as time zero controls. Metabolite quantification in both storage fluid and kidney tissue was performed using one dimensional1H NMR spectroscopy. For each metabolite, the net gain for each storage modality was determined by comparing the total amount in each closed system (i.e. total amount in storage fluid and kidney combined) compared with controls. 26 metabolites were included for analysis. Total system metabolite quantities following HMP or SCS were greater for 14 compared with controls (all p < 0.05). In addition to metabolic differences with control kidneys, the net metabolic gain during HMP was greater than SCS for 8 metabolites (all p < 0.05). These included metabolites related to central metabolism (lactate, glutamate, aspartate, fumarate and acetate). The metabolic environments of both perfusion fluid and the kidney tissue are strikingly different between SCS and HMP systems in this animal model. The total amount of central metabolites such as lactate and glutamate observed in the HMP kidney system suggests a greater degree of de novo metabolic activity than in the SCS system. Maintenance of central metabolic pathways may contribute to the clinical benefits of HMP.
authors.affiliation: Department of Renal Surgery, University Hospitals Birmingham, Birmingham, UK; Institute of Metabolism and Systems Research (IMSR), College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Jay
authors.initials: J
authors.lastname: Nath
authors.affiliation: Institute of Metabolism and Systems Research (IMSR), College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Tom B
authors.initials: TB
authors.lastname: Smith
authors.affiliation: Department of Renal Surgery, University Hospitals Birmingham, Birmingham, UK; Institute of Metabolism and Systems Research (IMSR), College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Kamlesh
authors.initials: K
authors.lastname: Patel
authors.affiliation: Institute of Metabolism and Systems Research (IMSR), College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Sam R
authors.initials: SR
authors.lastname: Ebbs
authors.affiliation: Institute of Metabolism and Systems Research (IMSR), College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Alex
authors.initials: A
authors.lastname: Hollis
authors.affiliation: Institute of Metabolism and Systems Research (IMSR), College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Tennant
authors.affiliation: Institute of Metabolism and Systems Research (IMSR), College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Christian
authors.initials: C
authors.lastname: Ludwig
authors.affiliation: Department of Renal Surgery, University Hospitals Birmingham, Birmingham, UK.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Ready
mesh_terms: D019342:Acetic Acid / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D015925:Cryopreservation / Q000379:methods* / Q000662:veterinary; D004734:Energy Metabolism / Q000502:physiology*; D005650:Fumarates / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D007036:Hypothermia, Induced / Q000379:methods; D007668:Kidney / Q000502:physiology*; D019344:Lactic Acid / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D023421:Models, Animal; D009926:Organ Preservation / Q000379:methods / Q000662:veterinary*; D010477:Perfusion / Q000379:methods*; D006435:Renal Dialysis / Q000379:methods; D013552:Swine
chemical_list: D005650:Fumarates; D001224:Aspartic Acid; D019344:Lactic Acid; D018698:Glutamic Acid; C032005:fumaric acid; D019342:Acetic Acid
keywords: Hypothermic machine perfusion; Kidney; Metabolism; NMR; Organ preservation; Transplantation