Preprint
Urine recirculation during normothermic kidney preservation improves energy balance involving the urea and TCA cycles
- Abstract:
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Background: Deceased donor kidneys experience cellular stress before undergoing transplantation. To alleviate this, preservation techniques were developed including normothermic machine perfusion (NMP).
Methods: Here, we performed kidney NMP on discarded human kidneys for up to 24 hours. Volume management was regulated either by urine recirculation (UR) or urine replacement (NUR) with Ringers lactate. Notably, UR led to longer perfusion times compared to NUR. To investigate kidney NMP metabolic traits with or without UR over time, we performed longitudinal metabolomics analyses of perfusates of eight NMP kidneys by 2D-gas chromatography mass spectrometry (GCxGC-MS).
Results: Over 600 metabolic features were profiled, from which 74 were identified and 54 consistently quantified across 26 perfusate samples. Most notably, elevated levels of disaccharides (different isomers), hydroxy-purines, urea, glutamate and amino acids associated with the perfusion factor UR. Moreover, donor estimated glomerular filtration rate (eGFR) correlated significantly with the accumulation of lactate and gluconate. Most strikingly, lactate levels seemed to be more balanced in UR NMP perfusate, which otherwise accumulated rapidly within the first six hours.
Conclusions: Kidney preservation by NMP was previously limited to hours. UR-NMP affected kidney energy homeostasis, carbohydrate & purine metabolism and the Urea and TCA cycles. These insights add value to explain how urine-driven adaptations contribute to prolonged kidney function under NMP.
- Publication status:
- Published
- Peer review status:
- Not peer reviewed
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(Preview, Pre-print, pdf, 1.5MB, Terms of use)
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- Preprint server copy:
- 10.64898/2026.01.12.698950
Authors
+ Medical Research Council
More from this funder
- Funder identifier:
- https://ror.org/03x94j517
- Funding agency for:
- Ploeg, RJ
- Grant:
- MR/R014132/1
+ China Academy of Chinese Medical Sciences
More from this funder
- Funder identifier:
- https://ror.org/042pgcv68
- Funding agency for:
- Kessler, BM
- Grant:
- 2024-I2M-2-001-1
- Preprint server:
- bioRxiv
- Publication date:
- 2026-01-13
- DOI:
- Language:
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English
- Keywords:
- Pubs id:
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2358999
- UUID:
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uuid_46ccc2cf-6e37-4272-862b-d487792d6e45
- Local pid:
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pubs:2358999
- Deposit date:
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2026-01-14
- ARK identifier:
Terms of use
- Copyright holder:
- Weissenbacher et al.
- Copyright date:
- 2026
- Rights statement:
- The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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