Urine recirculation prolongs normothermic kidney perfusion via more optimal metabolic homeostasis—a proteomics study
| Autor: | Benedikt M. Kessler, Rutger J. Ploeg, M. Letizia Lo Faro, Peter J. Friend, Honglei Huang, Tomas Surik, Constantin C. Coussios, Annemarie Weissenbacher |
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| Rok vydání: | 2021 |
| Předmět: |
Proteomics
kidney biology medicine.medical_specialty Ischemia 030230 surgery Carbohydrate metabolism Kidney Malate dehydrogenase 03 medical and health sciences 0302 clinical medicine Basic Science Internal medicine medicine Homeostasis Humans Immunology and Allergy Pharmacology (medical) kidney transplantation / nephrology Transplantation Machine perfusion biology kidney (allograft) function / dysfunction organ perfusion and preservation business.industry Succinate dehydrogenase Organ Preservation medicine.disease Perfusion ischemia reperfusion injury (IRI) medicine.anatomical_structure Endocrinology biology.protein Original Article translational research / science ORIGINAL ARTICLES Phosphoenolpyruvate carboxykinase business Reperfusion injury |
| Zdroj: | American Journal of Transplantation |
| ISSN: | 1600-6135 |
| DOI: | 10.1111/ajt.16334 |
| Popis: | 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 6 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 stabilization. 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 12 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 revitalizes metabolism to possibly better cope with ischemia reperfusion injury in discarded kidneys. The authors perform a proteomics analysis to identify molecular differences between normothermically machine perfused and discarded human kidneys with urine recirculation and urine replacement using lactated Ringers. |
| Databáze: | OpenAIRE |
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