Getting Insights from Oral Metabolomics into Vascular Calcification among Patients with ESKD

Background: Oral inflammatory diseases, chronic kidney disease (CKD), and vascular calcification (VC) are closely related. Here, we investigated the changes in oral metabolites caused by vascular calcification among patients with end-stage kidney disease. Methods: Patients were divided into VC group (Kauppila score ≥ 8) and HC group (Kauppila < 8). The patients in the two groups were matched according to their age, gender, and diabetes status. Gingival crevicular fluid was extracted and non-target metabolomics was performed. Two normalization methods were used, one was the total amount normalization, and the other was the creatinine value normalization. Metabolites were compared between the two groups. Differential metabolites were included in the enrichment analysis to find the key metabolites and pathways. Pearson correlation analysis was performed between differential metabolites of key pathways involved in the enrichment analysis and clinical indicators. Results: The gingival crevicular fluid samples of 30 patients (VC group 15 cases vs. HC group 15 cases) were examined. In enrichment analysis, 35 and 105 differential metabolites were observed. Four key metabolic pathways, including taurine and the secondary metabolism of taurine, arginine and proline metabolism, arginine biosynthesis, and glutathione metabolism, were discovered. It is shown that the key metabolites including taurine, 3-sulfinoalanine, 1-dihydropyrrolo-2-carboxylic acid, creatine, putamyldiamine, glycine, ornithine, and acetylornithine were found to be correlated with CKD-MBD parameters, inflammatory factors, and periodontal disease parameters. Conclusion: Oral metabolites were diverse in ESRD patients with and without severe VC and linked closely to the CKD-MBD parameters, indicating the pivotal role of oral disease in the development of CKD-MBD.Correlation analysis between metabolites involved in key pathways and clinical indicators