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

PLoS One. 2024 Feb 14;19(2):e0298729. doi: 10.1371/journal.pone.0298729. eCollection 2024.

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.

MeSH terms

  • Fabaceae*
  • Genome-Wide Association Study
  • Glycine
  • Mannose
  • Mendelian Randomization Analysis
  • Renal Insufficiency, Chronic* / genetics

Substances

  • Glycine
  • Mannose

Grants and funding

This project was sponsored by the National Natural Science Foundation of China (NSFC 81870494). We would like to clarify that while the funding supported the research, the funder had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The research team independently conducted all aspects of the study, ensuring that the analysis and findings were solely the result of the researchers' efforts and methodologies.