Associations of neonicotinoid exposure with renal function: A cross-sectional study with long-term toxicological validation

Neonicotinoids (NEOs) continuously exert chronic effects on human health, yet their impacts on renal function remain understudied. This study investigates the association between NEOs and renal function utilizing an integrated epidemiological and toxicological approach. Urinary NEOs and their characteristic metabolites were quantified using ultra-performance liquid chromatography-tandem mass spectrometry in 847 individuals from a Yinchuan community-dwelling elderly cohort. Multiple epidemiological models were employed to systematically evaluate both single and mixed exposure associations with renal parameters. Concurrently, a long-term imidacloprid (IMI) exposure mouse model (based on human equivalent exposure, 103 μg/kg/day) was established to validate the epidemiological findings. The population study revealed significant positive associations between all measured NEOs and serum uric acid (UA) levels (P < 0.05). In mixture analyses, IMI-olefin was identified as the predominant contributor to elevated UA and the primary driver of decreased estimated glomerular filtration rate among all NEOs. In animal models, environmentally relevant IMI exposure functionally validated these findings by significantly elevating UA and blood urea nitrogen levels (P < 0.05). Collectively, low-dose NEOs exposure is positively associated with renal dysfunction in elderly adults, a risk corroborated by murine models at population-relevant exposure levels.