Untargeted NMR-based metabolomics identifies a metabolic signature depending on the type of kidney transplant donor

Background: Kidney transplant outcomes differ between kidneys from brain-dead donors (DBD) and circulatory-dead donors (DCD). While DCD grafts are more often associated with delayed graft function (DGF), DBD grafts that develop DGF tend to show poorer long-term survival. These differences suggest distinct underlying injury mechanisms depending on donor type. In this context, identifying metabolic biomarkers may offer valuable insights into graft quality and help refine pre-transplant evaluation to improve both short- and long-term outcomes.

Objective: This study applies untargeted NMR-based metabolomics to investigate metabolic alterations between DBD and DCD kidney tissues.

Methods: Kidney samples from rats (7 controls, 7 DCD, 9 DBD) were collected. Tissue powders were analysed by 1H-NMR spectroscopy, followed by multivariate OPLS-DA and univariate statistical analyses (ANOVA, t-tests).

Results:

OPLS-DA revealed distinct metabolic profiles between DBD and DCD and controls.
ANOVA identified 34 significantly different metabolites across groups.
T-tests (DBD versus DCD) identified 19 metabolites, including increased levels of pyridoxine, 2-hydroxybutyrate and 2-oxocaproate in DCD kidneys, while glutamate, lysine, and pyroglutamate were decreased.
Metabolomic signatures were partly consistent between kidney tissue and previously analysed perfusate samples.
Conclusion: This study demonstrates that NMR-based metabolomics can differentiate DBD from DCD kidneys and identify specific metabolic patterns. Further validation in larger human or animal cohorts could establish metabolomics as a tool for pre-transplant graft assessment, improving decision-making.