Dataset Information

Urine recirculation prolongs normothermic kidney perfusion for via more optimal metabolic homeostasis – a proteomics study

ABSTRACT: 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.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Kidney Epithelium, Kidney

DISEASE(S): End Stage Renal Disease

SUBMITTER: Benedikt Kessler

LAB HEAD: Benedikt Kessler

PROVIDER: PXD021507 | Pride | 2020-10-20

REPOSITORIES: Pride

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			Action	DRS
	FL609_MSQ1100_HongLei_gel_1.raw	Raw
	FL609_MSQ1100_HongLei_gel_10.raw	Raw
	FL609_MSQ1100_HongLei_gel_11.raw	Raw
	FL609_MSQ1100_HongLei_gel_12.raw	Raw
	FL609_MSQ1100_HongLei_gel_13.raw	Raw

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Urine recirculation prolongs normothermic kidney perfusion via more optimal metabolic homeostasis-a proteomics study.

Weissenbacher Annemarie A Huang Honglei H Surik Tomas T Lo Faro Maria L ML Ploeg Rutger J RJ Coussios Constantin C CC Friend Peter J PJ Kessler Benedikt M BM

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 20201104 5

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) ...[more]

PMID: 33021021

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