Perfusate Proteomes Provide Biological Insight Into Oxygenated Versus Standard Hypothermic Machine Perfusion in Kidney Transplantation.

Autor:	Mulvey JF; Nuffield Department of Surgical Sciences, and Oxford Biomedical Research Centre, University of Oxford, Oxford, UK., Shaheed SU; Nuffield Department of Surgical Sciences, and Oxford Biomedical Research Centre, University of Oxford, Oxford, UK., Charles PD; Nuffield Department of Medicine, Big Data Institute, University of Oxford, Oxford, UK., Snashall C; Nuffield Department of Surgical Sciences, and Oxford Biomedical Research Centre, University of Oxford, Oxford, UK., Lo Faro ML; Nuffield Department of Surgical Sciences, and Oxford Biomedical Research Centre, University of Oxford, Oxford, UK., Sutton CW; Institute of Cancer Therapeutics, University of Bradford, Bradford, UK., Jochmans I; Department of Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium.; Lab of Abdominal Transplantation, Transplantation Research Group, Leuven, Belgium; Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium., Pirenne J; Department of Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium.; Lab of Abdominal Transplantation, Transplantation Research Group, Leuven, Belgium; Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium., van Kooten C; Department of Internal Medicine Nephrology, Leiden University Medical Centre, Leiden, The Netherlands.; Transplant Center, Leiden University Medical Centre, Leiden, The Netherlands., Leuvenink HGD; Department of Surgery, University Medical Centre Groningen, Groningen, The Netherlands., Kaisar M; Nuffield Department of Surgical Sciences, and Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.; Research and Development, NHS Blood and Transplant Oxford & Bristol, UK., Ploeg RJ; Nuffield Department of Surgical Sciences, and Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.; Transplant Center, Leiden University Medical Centre, Leiden, The Netherlands.; Research and Development, NHS Blood and Transplant Oxford & Bristol, UK.
Jazyk:	angličtina
Zdroj:	Annals of surgery [Ann Surg] 2023 Nov 01; Vol. 278 (5), pp. 676-682. Date of Electronic Publication: 2023 Jul 28.
DOI:	10.1097/SLA.0000000000006046
Abstrakt:	Objective: To provide mechanistic insight into key biological alterations in donation after circulatory death kidneys during continuous pefusion we performed mass spectrometry profiling of perfusate samples collected during a phase 3 randomized double-blind paired clinical trial of hypothermic machine perfusion with and without oxygen (COMPARE). Background: Despite the clinical benefits of novel perfusion technologies aiming to better preserve donor organs, biological processes that may be altered during perfusion have remained largely unexplored. The collection of serial perfusate samples during the COMPARE clinical trial provided a unique resource to study perfusate proteomic profiles, with the hypothesis that in-depth profiling may reveal biologically meaningful information on how donor kidneys benefit from this intervention. Methods: Multiplexed liquid chromatography-tandem mass spectrometry was used to obtain a proteome profile of 210 perfusate samples. Partial least squares discriminant analysis and multivariate analysis involving clinical and perfusion parameters were used to identify associations between profiles and clinical outcomes. Results: Identification and quantitation of 1716 proteins indicated that proteins released during perfusion originate from the kidney tissue and blood, with blood-based proteins being the majority. Data show that the overall hypothermic machine perfusion duration is associated with increasing levels of a subgroup of proteins. Notably, high-density lipoprotein and complement cascade proteins are associated with 12-month outcomes, and blood-derived proteins are enriched in the perfusate of kidneys that developed acute rejection. Conclusions: Perfusate profiling by mass spectrometry was informative and revealed proteomic changes that are biologically meaningful and, in part, explain the clinical observations of the COMPARE trial. Competing Interests: I.J. reports speaker fees from XVIVO Perfusion paid to her institution. R.J.P. has been advising Bridge to Life Ltd in UK on organ preservation. The remaining authors report no conflicts of interest. (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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