Getting Insights from Oral Metabolomics into Vascular Calcification in Patients with End-Stage Kidney Disease

<title>Abstract</title> <p>This study investigated the association between oral metabolomics and vascular calcifi-cation (VC) in patients with end-stage kidney disease (ESKD). Thirty patients were stratified into a high VC group (Kauppila score ≥ 8) and a low VC group (Kauppila score &lt; 8), matched for age, sex, and diabetes status. Differential metabolites were identified using t-tests and VIP scores, with group discrimination assessed by PLS-DA and heatmaps. Biomarker discovery involved uni- and multivariate analyses, and pathway enrichment was performed to explore underlying mechanisms. Correlations between the potential biomarkers and clinic-serologic features were examined. A total of 37 metabolites, in-cluding citrate, citraconic acid, and taurine, exhibited distinct distribution patterns be-tween the two groups. Key pathways included taurine and hypotaurine metabolism, purine metabolism, galactose metabolism, sphingolipid metabolism, phenylacetate metabolism, and β-oxidation of very long-chain fatty acids. Fifteen candidate biomarkers demonstrated strong predictive performance for high VC (maximum AUC = 0.994). Several metabolites were significantly correlated with Kauppila score, partly independent of calcium–phosphate metabolism. These findings suggest that oral metabolites and re-lated pathways are closely linked to VC and oral inflammation in ESKD, highlighting their potential as biomarkers for improved understanding and management of VC in ESKD.</p>