PXD021507

PXD021507 is an original dataset announced via ProteomeXchange.

Title	Urine recirculation prolongs normothermic kidney perfusion for via more optimal metabolic homeostasis – a proteomics study
Description	We describe a proteomics analysis to determine the molecular differences between normothermically perfused (normothermic machine perfusion, NMP) human kidneys with urine recirculation (URC) and urine replacement (UR). Proteins were extracted from 16 kidney biopsies with URC (n=8 donors after brain death (DBD), n=8 donors after circulatory death (DCD)) and three with UR (n=2 DBD, n=1 DCD), followed by quantitative analysis by mass spectrometry. Damage-associated molecular patterns (DAMPs) were decreased in kidney tissue after six hours NMP with URC, suggesting reduced inflammation. Vasoconstriction was also attenuated in kidneys with URC as angiotensinogen levels were reduced. Strikingly, kidneys became metabolically active during NMP, which could be enhanced and prolonged by URC. For instance, mitochondrial succinate dehydrogenase enzyme levels as well as carbonic anhydrase were enhanced with URC, contributing to pH stabilisation. Levels of cytosolic and the mitochondrial phosphoenolpyruvate carboxykinase were elevated after 24 hours of NMP, more prevalent in DCD than DBD tissue. Key enzymes involved in glucose metabolism were also increased after twelve and 24 hours of NMP with URC, including mitochondrial malate dehydrogenase and glutamic-oxaloacetic transaminase, predominantly in DCD tissue. We conclude that NMP with URC permits prolonged preservation and revitalises metabolism to possibly minimize better cope with ischemia reperfusion injury in discarded kidneys.
HostingRepository	PRIDE
AnnounceDate	2020-10-20
AnnouncementXML	Submission_2020-10-19_22:33:46.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Benedikt Kessler
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-16 01:22:50	ID requested
⏵ 1	2020-10-19 22:33:47	announced

Weissenbacher A, Huang H, Surik T, Lo Faro ML, Ploeg RJ, Coussios CC, Friend PJ, Kessler BM, Urine recirculation prolongs normothermic kidney perfusion via more optimal metabolic homeostasis-a proteomics study. Am J Transplant, 21(5):1740-1753(2021) [pubmed]

submitter keyword: kidney transplantation, nephrology, organ perfusion, ischemia reperfusion injury, IRI, proteomics, mass spectrometry

Benedikt Kessler
contact affiliation	Target Discovery Institute Nuffield Department of Medicine University of Oxford Roosevelt Drive Oxford OX3 FZ UK Tel: +44 (0) 1865 612 921 https://www.tdi.ox.ac.uk/research/research/tdi-mass-spectrometry-laboratory
contact email	benedikt.kessler@ndm.ox.ac.uk
lab head
Benedikt Kessler
contact affiliation	University of Oxford
contact email	benedikt.kessler@ndm.ox.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD021507
     1. Label: PRIDE project
     2. Name: Urine recirculation prolongs normothermic kidney perfusion for via more optimal metabolic homeostasis – a proteomics study