Biomarker Differences between Cadaveric Grafts Used in Human Orthotopic Liver Transplantation as Identified by Coulometric Electrochemical Array Detection (CEAD) Metabolomics

Research output: Contribution to journalArticle

Authors

  • Thamara Perera
  • Roger Higdon
  • Michael A. Silva
  • Nick Murphy
  • Eugene Kolker
  • Darius F. Mirza

External organisations

  • The Liver Unit, Queen Elizabeth Hospital Birmingham, Edgbaston, Birmingham, United Kingdom
  • Bioinformatics and High-throughput Analysis Lab, Center for Developmental Therapeutics, Seattle Children's Research Institute, Seattle, Washington.
  • The Liver Unit, Queen Elizabeth Hospital Birmingham, Edgbaston, Birmingham, United Kingdom
  • Department of Critical Care and Anaesthesia, Queen Elizabeth Hospital Birmingham, Edgbaston, Birmingham, United Kingdom.
  • The Liver Unit, University Hospital Birmingham NHS Foundation Trust, Birmingham, United Kingdom.

Abstract

Metabolomics in systems biology research unravels intracellular metabolic changes by high throughput methods, but such studies focusing on liver transplantation (LT) are limited. Microdialysate samples of liver grafts from donors after circulatory death (DCD; n=13) and brain death (DBD; n=27) during cold storage and post-reperfusion phase were analyzed through coulometric electrochemical array detection (CEAD) for identification of key metabolomics changes. Metabolite peak differences between the graft types at cold phase, post-reperfusion trends, and in failed allografts, were identified against reference chromatograms. In the cold phase, xanthine, uric acid, and kynurenine were overexpressed in DCD by 3-fold, and 3-nitrotyrosine (3-NT) and 4-hydroxy-3-methoxymandelic acid (HMMA) in DBD by 2-fold (p<0.05). In both grafts, homovanillic acid and methionine increased by 20%–30% with each 100 min increase in cold ischemia time (p<0.05). Uric acid expression was significantly different in DCD post-reperfusion. Failed allografts had overexpression of reduced glutathione and kynurenine (cold phase) and xanthine (post-reperfusion) (p<0.05). This differential expression of metabolites between graft types is a novel finding, meanwhile identification of overexpression of kynurenine in DCD grafts and in failed allografts is unique. Further studies should examine kynurenine as a potential biomarker predicting graft function, its causation, and actions on subsequent clinical outcomes.

Details

Original languageEnglish
Pages (from-to)767-777
Number of pages11
JournalOMICS: A Journal of Integrative Biology
Volume18
Issue number12
Early online date29 Oct 2014
Publication statusPublished - 2 Dec 2014

Keywords

  • Biomarkers, Homovanillic Acid, Humans, Kynurenine, Liver Transplantation, Metabolomics, Methionine, Tyrosine, Uric Acid, Xanthine