HDL-C as a mediator of PPCP-related kidney function decline in community-dwelling elderly: a mixture analysis...

Pharmaceuticals and personal care products (PPCPs) are widespread environmental contaminants, but their associations with kidney function and lipid metabolism remain incompletely understood. This study included 2758 adults aged ≥ 60 years in Anhui Province, China, during 2022-2023 and used a cross sectional design. Urinary concentrations of 48 PPCPs and two metabolites were measured using high-performance liquid chromatography-tandem mass spectrometry. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Individual associations were assessed using logistic and linear regression, and mixture associations using weighted quantile sum (WQS) regression and Bayesian kernel machine regression. Restricted cubic splines examined nonlinear associations, and exploratory mediation analyses assessed the statistical contribution of high-density lipoprotein cholesterol (HDL-C). Among nine PPCPs with detection frequencies > 50%, doxycycline, enrofloxacin, acetaminophen, metformin, and cotinine were associated with lower eGFR after full adjustment and Benjamini-Hochberg correction. Coefficients ranged from - 3.00 to - 0.93 mL/min/1.73 m² per tenfold increase in urinary concentration. Tylosin and caffeine were positively associated with eGFR. The WQS index was inversely associated with eGFR, with metformin receiving the largest weight. HDL-C showed a positive nonlinear association with eGFR. Under the mediation model assumptions, HDL-C statistically accounted for 12.21-29.30% of the associations involving enrofloxacin, metformin, and acetaminophen, and 13.78% of the mixture association. The indirect association for cotinine was nonsignificant. These findings remain exploratory. Prospective studies are needed to clarify temporal relationships and address possible reverse causation.