Joint effects of per- and polyfluoroalkyl substance alternatives and heavy metals on renal health: A community-based population study in China

Previous studies have indicated that chlorinated polyfluorinated ether sulfonic acids (Cl-PFESAs), when used as an alternative to per- and polyfluoroalkyl substances (PFASs), result in kidney toxicity. However, their co-exposure with heavy metals, has not yet been described.To explore the joint effects of Cl-PFESAs and heavy metal exposure on renal health in Chinese adults, and identify specific pollutants driving the associations.Our sample consists of 1312 adults from a cross-sectional survey of general communities in Guangzhou, China. We measured Cl-PFESAs, legacy PFASs (perfluorooctanoic acid [PFOA] and perfluorooctane sulfonated [PFOS]), and heavy metals (arsenic, cadmium, and lead). The relationship between single pollutant and glomerular filtration rate (eGFR) and the odds ratio (OR) of chronic kidney disease (CKD) was studied using Generalized additive models (GAMs). Bayesian Kernel Machine Regression (BKMR) models were applied to assess joint effects of Cl-PFESAs and heavy metals. Additionally, we conducted a sex-specific analysis to determine the modification effect of this variable.In single pollutant models, CI-PFESAs, PFOA, PFOS and arsenic were negatively associated with eGFR. Additionally, PFOA and heavy metals were positively correlated with the OR of CKD. For example, the estimated change with 95% confidence intervals (CI) of eGFR at from the highest quantile of 6:2 Cl-PFESA versus the lowest quantile was -5.65 ng/mL (95% CI: -8.21, -3.10). Sex played a role in modifying the association between 8:2 Cl-PFESA, PFOS and eGFR. In BKMR models, pollutant mixtures had a negative joint association with eGFR and a positive joint effect on CKD, especially in women. Arsenic appeared to be the primary contributing pollutant.We provide epidemiological evidence that Cl-PFESAs independently and jointly with heavy metals impaired kidney health. More population-based human and animal studies are needed to confirm our results.