• John F Mulvey, ShaheedSadr UlSUNuffield Department of Surgical Sciences, and Oxford Biomedical Research Centre, University of Oxford, Oxford, UK., Philip D Charles, Corinna Snashall, Maria Letizia Lo Faro, Christopher W Sutton, Ina Jochmans, Jacques Pirenne, Cees van Kooten, LeuveninkHenri G DHGDDepartment of Surgery, University Medical Centre Groningen, Groningen, The Netherlands., Maria Kaisar, and Rutger J Ploeg.
• Nuffield Department of Surgical Sciences, and Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
• Ann. Surg. 2023 Nov 1; 278 (5): 676682676-682.

ObjectiveTo 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).BackgroundDespite 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.MethodsMultiplexed 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.ResultsIdentification 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.ConclusionsPerfusate 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.Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

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