Serum perfluoroalkyl and polyfluoroalkyl substances and the risk of kidney function decline: Unraveling the mediating role of iron status

The effects of perfluoroalkyl and polyfluoroalkyl substances (PFAS) on kidney function across physiological conditions remain inconclusive, and previous research has not assessed the potential mediating effect of iron status. We aimed to examine the relationships between PFAS exposure and kidney function in various demographic groups, as well as to evaluate the potential mediating role of iron status. This study included 7369 Chinese adults aged 18 years or older from the China Health and Nutrition Survey (CHNS). Estimated glomerular filtration rate (eGFR) levels were used to reflect the efficiency of kidney function. Generalized linear models and weighted quantile sum regression models indicated negative associations between PFAS and eGFR levels, with PFNA and PFHxS emerging as the dominant contributors. Subgroup analysis revealed that the adverse effects of PFAS on eGFR levels were more pronounced in the males, young and middle age, non-hypertension, and non-diabetes subgroups. Further mediation analyses demonstrated that iron status (ferritin, transferrin, and hemoglobin) partially mediated these associations, with mediation proportions ranging from 8.89 % to 60.84 %. Our study established PFNA and PFHxS as critical nephrotoxic PFAS in China while pioneering the identification of iron status as a novel mechanistic mediator between PFAS exposure and kidney dysfunction, advancing mechanistic understanding of environmental nephrotoxicity.