Journal article
Urine recirculation prolongs normothermic kidney perfusion 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 better cope with ischemia reperfusion injury in discarded kidneys.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, 1.8MB, Terms of use)
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- Publisher copy:
- 10.1111/ajt.16334
Authors
- Publisher:
- Wiley
- Journal:
- American Journal of Transplantation More from this journal
- Volume:
- 21
- Issue:
- 5
- Pages:
- 1740-1753
- Publication date:
- 2020-10-05
- Acceptance date:
- 2020-10-05
- DOI:
- EISSN:
-
1600-6143
- ISSN:
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1600-6135
- Language:
-
English
- Keywords:
- Pubs id:
-
1136343
- Local pid:
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pubs:1136343
- Deposit date:
-
2020-10-07
Terms of use
- Copyright holder:
- Weissenbacher et al.
- Copyright date:
- 2020
- Rights statement:
- ©2020 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
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