Associations of PFAS and Metal Mixtures with Kidney Function: Potential Mediation by Systemic and Dietary Inflammation

People encounter many environmental chemicals simultaneously, yet the combined effects of these exposures on kidney function and underlying biological pathways remain poorly understood. This study examined the joint association of a mixture of per- and polyfluoroalkyl substances (PFAS) and metals with estimated glomerular filtration rate (eGFR) and evaluated whether systemic or dietary inflammation mediated this association. The analytic sample comprised 1303 adults (≥18 years) drawn from the 2017–2018 cycle of the National Health and Nutrition Examination Survey. The exposure mixture consisted of six PFAS: perfluorodecanoic acid (PFDeA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFUA), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonic acid (PFOS), along with three metals: cadmium, lead and mercury. Systemic inflammation was assessed using C-reactive protein (CRP), and the Dietary Inflammatory Index (DII) captured the inflammatory potential of diet. The analyses used multivariable linear regression, Bayesian kernel machine regression (BKMR), and BKMR-causal mediation analysis. In the regression models, PFDeA, PFHxS, PFUA, PFOA, and PFOS were each linked to higher eGFR, whereas cadmium and lead were each linked to lower eGFR. BKMR showed that the association between the mixture and eGFR differed across age levels. At the 10th percentile of age, the total effect was −5.04 mL/min/1.73 m2 (95% credible interval: −9.39, −0.83), whereas at the 90th percentile, it was 6.37 mL/min/1.73 m2 (95% credible interval: 2.20, 10.48). PFOS had highest posterior inclusion probability in the outcome and total-effect models. Posterior medians of the natural direct effect matched the total-effect estimates in sign and approximate size, but uncertainty was substantial. Posterior distributions for the natural indirect effects were centered near zero with appreciable mass on both sides, so indirect effects through CRP and DII were not resolved. The findings suggest that the association may vary with age, warranting further investigation.