Mannose and glycine: Metabolites with potentially causal implications in chronic kidney disease pathogenesis

Abstract

Background Chronic Kidney Disease (CKD) represents a global health challenge, with its etiology and underlying mechanisms yet to be fully elucidated. Integrating genomics with metabolomics can offer insights into the putatively causal relationships between serum metabolites and CKD. Methods Utilizing bidirectional Mendelian Randomization (MR), we assessed the putatively causal associations between 486 serum metabolites and CKD. Genetic data for these metabolites were sourced from comprehensive genome-wide association studies, and CKD data were obtained from the CKDGen Consortium. Results Our analysis identified four metabolites with a robust association with CKD risk, of which mannose and glycine showed the most reliable causal relationships. Pathway analysis spotlighted five significant metabolic pathways, notably including "Methionine Metabolism" and "Arginine and Proline Metabolism", as key contributors to CKD pathogenesis. Conclusion This study underscores the potential of certain serum metabolites as biomarkers for CKD and illuminates pivotal metabolic pathways in CKD’s pathogenesis. Our findings lay the groundwork for potential therapeutic interventions and warrant further research for validation.