Long-Term Per- and Polyfluoroalkyl Substances Exposure and Kidney Function in Taiwanese Adolescents and Young Adults: A 10-Year Prospective Cohort Study

<b>Background and hypothesis</b>: Per- and polyfluoroalkyl substances (PFAS) are highly persistent synthetic chemicals that can accumulate in renal tissue and potentially disrupt kidney function. Most prospective studies on PFAS-renal associations have focused on middle-aged or older adults, leaving uncertainty about whether similar patterns exist in younger populations. <b>Methods</b>: We investigated decade-long trajectories of plasma concentrations of 11 PFAS and their longitudinal associations with estimated glomerular filtration rate (eGFR) among 529 Taiwanese adolescents and young adults (aged 12-30 years) enrolled in the prospective YOung TAiwanese Cohort (YOTA), with measurements obtained in 2006-2008 and 2017-2019. <b>Results</b>: Nearly all plasma PFAS declined significantly over the 10-year period. Despite these reductions, higher baseline levels and greater annualized increases (Δln-PFAS/Δt) in linear perfluorooctanoic acid (PFOA), linear and branched perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) were consistently associated with larger eGFR gains over time (β = 0.33-0.40, q < 0.05). In complementary models using follow-up eGFR as the outcome, both baseline and cumulative PFAS changes (Δln-PFAS) remained positively associated with higher eGFR (β = 1.71-3.84, q < 0.05). Polynomial analyses further indicated mild non-linear exposure-response patterns for several PFAS, suggesting that renal effects may deviate from linearity across exposure ranges. The composite PFAS exposure index (mean of standardized ln-PFAS concentrations) was robustly associated with higher eGFR across sensitivity analyses excluding participants with chronic conditions. These associations were more pronounced among individuals with greater metabolic or physiological vulnerability. <b>Conclusions</b>: Higher PFAS exposure was associated with elevated eGFR in young adults, which may be consistent with early glomerular hyperfiltration or other renal hemodynamic alterations. These findings raise the hypothesis of early renal stress in early life and underscore the need for ongoing biomonitoring and longitudinal follow-up with additional kidney injury markers to clarify long-term renal consequences.