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Clinical Trial
. 2023 Nov 1;278(5):676-682.
doi: 10.1097/SLA.0000000000006046. Epub 2023 Jul 28.

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

John F Mulvey  1 , Sadr Ul Shaheed  1 , Philip D Charles  2 , Corinna Snashall  1 , Maria Letizia Lo Faro  1 , Christopher W Sutton  3 , Ina Jochmans  4   5 , Jacques Pirenne  4   5 , Cees van Kooten  6   7 , Henri G D Leuvenink  8 , Maria Kaisar  1   9 , Rutger J Ploeg  1   7   9
Affiliations
Clinical Trial

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

John F Mulvey et al. Ann Surg. .

Abstract

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.

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Conflict of interest statement

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.

References

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    1. Moers C, Smits JM, Maathuis M-HJ, et al. Machine perfusion or cold storage in deceased-donor kidney transplantation. N Engl J Med. 2009;360:7–19.
    1. Jochmans I, Moers C, Smits JM, et al. Machine perfusion versus cold storage for the preservation of kidneys donated after cardiac death: a multicenter, randomized, controlled trial. Ann Surg. 2010;252:756–764.
    1. Jochmans I, Brat A, Davies L, et al. Oxygenated versus standard cold perfusion preservation in kidney transplantation (COMPARE): a randomised, double-blind, paired, phase 3 trial. Lancet. 2020;396:1653–1662.
    1. Buchs J-B, Lazeyras F, Ruttimann R, et al. Oxygenated hypothermic pulsatile perfusion versus cold static storage for kidneys from non heart-beating donors tested by in-line ATP resynthesis to establish a strategy of preservation. Perfusion. 2011;26:159–165.

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