Metabolic changes and plasma glycine predict the risk of acute cellular rejection in heart transplantation.

OBJECTIVE

Brain death in organ donors may trigger tissue injury that can negatively influence transplant outcome. We analyzed plasma metabolomic profiles in heart transplant donors and tested whether any donor metabolite may predict the risk of acute cellular rejection after heart transplantation.

METHODS

Plasma samples from 83 heart transplant donors and 20 healthy volunteers were profiled using quantitative targeted metabolomics of 102 metabolites. Plasma samples from another set of 48 heart transplant donors were used for validation.

RESULTS

The plasma levels of 24 metabolites representing 24% of the targeted metabolites were significantly altered in brain-dead heart transplant donors, compared with healthy controls. Alterations in the purine metabolism pathway were most prominent: adenine, xanthosine, allantoin, xanthine, and inosine monophosphate were upregulated, whereas adenosine monophosphate and adenosine were downregulated, indicating an energy metabolism shift and oxidative stress. Donor plasma glycine levels predicted the risk of acute cellular rejection (concordance = 0.74, area under the curve = 0.75; P < .01) in both the training and the validation cohort within 1-year after transplantation. Donor plasma glycine levels moderately correlated with other plasma metabolites linked to collagen formation and extracellular matrix organization.

CONCLUSIONS

Targeted metabolomics revealed altered purine metabolism in brain-dead heart transplant donors, suggesting increased energy demand and oxidative stress. Donor plasma glycine was identified as a risk predictor for acute cellular rejection after heart transplantation and may serve as a donor-side biomarker to guide posttransplant risk stratification and monitoring.