Perfusate Metabolites and Association with Pump Perfusion and Allograft Failure
1Johns Hopkins University School of Medicine, Baltimore, MD, 2Department of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD, 3University of Utah School of Medicine, Salt Lake City, UT, 4University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 5University of Columbia Vagelos College of Physicians & Surgeons, New York, NY, 6University of Michigan, Ann Arbor, MI
Meeting: 2022 American Transplant Congress
Abstract number: 364
Keywords: Graft failure, Kidney transplantation, Machine preservation, Perfusion
Topic: Basic Science » Basic Science » 15 - Machine Perfusion and Organ Rehabililtation - Basic
Session Information
Session Name: Machine Perfusion and Organ Rehabililtation - Basic
Session Type: Rapid Fire Oral Abstract
Date: Monday, June 6, 2022
Session Time: 5:30pm-7:00pm
Presentation Time: 6:10pm-6:20pm
Location: Hynes Ballroom A
*Purpose: While hypothermic machine perfusion (HMP) is associated with improved kidney graft viability, the exact biological mechanisms underlying this association are unknown. The goal of this study was to use metabolomic profiling to characterize perfusate metabolites and examine their association with death censored graft failure (dcGF).
*Methods: In this multicenter study, we measured metabolites in perfusate samples collected at the start and end (base and post) of HMP of deceased-donor kidneys transplanted between 2010-2013. Multivariable Cox regression and logistic regression were used to assess the relationship between perfusate metabolites and dcGF (primary outcome) and delayed graft function (DGF; secondary outcome), respectively.
*Results: In a cohort of 190 transplanted kidneys that underwent HMP, 553 known metabolites were identified in perfusate samples. After HMP time adjustment and false discovery correction, six metabolites in post-perfusate were significantly associated with dcGF. These metabolites include alpha-ketoglutarate (AKG), CMPF, 1-carboxyethylphenylalanine, and three glycerol-phosphatidylcholines. All six metabolites were associated with increased risk of dcGF (hazard ratios per median absolute deviation ranging from 1.04 to 1.45). Four of the six dcGF-associated metabolites were also associated with DGF. We observed significant associations for 74 metabolites between base-to-post changes and HMP duration. Via pathway analysis, we observed that production of reactive oxygen species and intracellular concentration of fatty acids were upregulated in perfusate of kidneys that subsequently had dcGF.
*Conclusions: We identified several metabolites that increased during HMP and six perfusate metabolites that were associated with increased risk of dcGF. Further understanding the role of these metabolites may help create better perfusion solutions and pumping protocols.
| Metabolite | Pathway | dcGF HR per MAD (95% CI) | DGF OR per MAD (95% CI) |
| alpha-ketoglutarate | TCA Cycle | 1.45 (1.17-1.79) | 1.30 (1.02-1.66) |
| CMPF | Fatty Acid-Dicarboxylate | 1.15 (1.06-1.24) | 1.15 (1.00-1.32) |
| 1-carboxyethylphenylalanine | Phenylalanine Metabolism | 1.04 (1.02-1.05) | 1.18 (0.96-1.45) |
| 1-palmitoyl-2-docosahexaenoyl-GPC | Phosphatidylcholine | 1.29 (1.13-1.47) | 1.30 (1.02-1.64) |
| 1-palmitoyl-2-dihomo-linolenoyl-GPC | Phosphatidylcholine | 1.17 (1.07-1.27) | 1.20 (0.98-1.49) |
| 1-stearoyl-2-docosahexaenoyl-GPC | Phosphatidylcholine | 1.28 (1.11-1.47) | 1.29 (1.01-1.66) |
To cite this abstract in AMA style:
Liu RX, Koyawala N, Philbrook HT, Hall I, Reese P, Mohan S, Doshi M, Parikh C. Perfusate Metabolites and Association with Pump Perfusion and Allograft Failure [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/perfusate-metabolites-and-association-with-pump-perfusion-and-allograft-failure/. Accessed November 21, 2024.« Back to 2022 American Transplant Congress