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.

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.

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.

Glyphosate is positively associated with the formation of kidney stones and contributes to the development of kidney stone disease through multiple mechanisms. These mechanisms provide new perspectives for the formulation of strategies aimed at the prevention and treatment of kidney stones.