#0555

 Urinary Glyphosate Levels and Kidney Stone Incidence: A Combined Clinical and Network Toxicology Approach

Y. Xiao¹, S. GaoYang¹, Y. Yang², T. Lin¹

¹West China Hospital, UROLOGY, Chengdu, China
²West China Hospital, Department of Respiratory and Critical Care Medicine, Chengdu, China

Introduction:

This study investigates the association between glyphosate exposure and kidney stone prevalence, and further explores the mechanisms by which glyphosate may contribute to the development of kidney stone disease.

Material and methods:

We conducted a cross-sectional study using data from 49,693 participants in the National Health and Nutrition Examination Survey (2013–2018). Multivariable logistic regression models were employed to assess the relationship between glyphosate exposure and kidney stone disease. An integrated bioinformatics approach, combining network toxicology and molecular docking, was used to identify potential toxicological targets and elucidate the molecular mechanisms through which glyphosate may promote kidney stone formation.

Results:

Urinary glyphosate concentration is positively associated with kidney stone prevalence. In the fully adjusted model, glyphosate exposure in the fourth quartile was associated with a 53% higher risk of kidney stones compared to the first quartile (OR = 1.53, 95% CI: 1.03, 2.28). Systematic analysis of multiple databases identified 41 targets related to glyphosate exposure and kidney stone disease. Using STRING and Cytoscape tools, top 5 hub targets were selected, including MMP9, PTGS2, ESR1, EGFR, and MAPK3. Enrichment analysis indicated that glyphosate primarily influences multiple pathways, including immune responses, endocrine resistance, proteoglycans in cancer, calcium signaling, and relaxin signaling.