Plasma Metabolomic Profile of Human Brain-Dead Organ Donors

Abstract

Profound metabolic and molecular changes triggered by solid organ donor brain death may significantly affect posttransplant graft function. However, the effects of brain death on transplanted organs are poorly understood and no clinical biomarker or targeted therapy is available to predict or prevent primary or late graft dysfunction, respectively. This study elaborates the plasma metabolomic profile of human brain-dead organ donors. We compared plasma samples from 119 human brain-dead multi-organ donors, taken immediately before organ procurement, to samples from 48 healthy volunteers. We employed targeted ultra-performance liquid chromatography-tandem mass spectrometry to profile over 100 metabolites. The metabolite profiles of the brain-dead donors and healthy individuals overlapped, but both groups also exhibited unique metabolites. Based on unsupervised and supervised multivariate analysis of metabolite profiles, 29 metabolites were found to be expressed at significantly different levels between brain-dead donors and controls. Pathway enrichment analysis suggested that these metabolites were involved in purine metabolism, methylhistidine metabolism, glycine metabolism, and phosphatidylethanolamine biosynthesis. Interestingly, brain death induced the rapid up-regulation of purine nucleosides as well as an increase in serine levels in plasma. The metabolomic profile of brain-dead organ donors described in this study sheds light on the molecular level effects of brain injury on a systemic level. Whether the metabolites presented here represent the systemic inflammatory reaction or predict later allograft function, remains to be fully elucidated. The complete analysis will be presented at the ISHLT 2020 congress.