ORIGINAL ABSTRACT

Glyphosate (GLY), a widely used herbicide, poses potential health risks even at low exposure levels and is prevalent in the general population through dietary and environmental residues. GLY accumulation may contribute to renal injury, but population-based evidence remains limited. We retrospectively studied 110 non-occupationally exposed patients undergoing renal biopsy,classified into two groups based on tubular injury score: mild (score 1, n = 69) and moderate-to-severe injury (score 2-4, n = 41). Median urinary GLY concentration was 2.50 ng/ml (IQR 1.40-3.12), higher in the moderate-to-severe group. Urinary GLY levels were positively correlated with tubular injury score. After full adjustment in multivariable logistic regression, individuals in the third quartile of urinary GLY (2.50-3.12 ng/ml) had a 26.30-fold higher risk of moderate-to-severe tubular injury compared with the lowest quartile (p = 0.008). Restricted cubic spline (RCS) analysis confirmed a significant nonlinear association between urinary GLY and moderate-to-severe injury. Urinary GLY demonstrated good predictive performance for moderate-to-severe tubular injury (AUC = 0.707). Literature review and network toxicology analysis suggested that GLY may induce cytotoxicity and genetic damage, contributing to renal injury in humans. These findings support the potential nephrotoxic effects of low-dose glyphosate exposure in a clinical cohort and add to the limited epidemiological evidence linking environmental exposure to renal pathological injury.