Objective Numerous epidemiological and toxicological studies suggest that exposure to per- and polyfluoroalkyl substances (PFASs) may compromise renal function. However, existing research predominantly focuses on adolescent and adult cohorts, with limited investigation targeting elderly populations. This study, based on the Guankou Ageing Cohort Study (GACS) and employing a nested case-control design, aimed to systematically evaluated the association between serum PFAS exposure levels and chronic kidney disease (CKD) prevalence in elderly populations, providing scientific evidence for comprehensive health risk assessment of novel persistent organic pollutants. Methods We enrolled 111 participants aged 60-83 years (38 cases, 73 controls). Baseline health data and serum samples were collected, with CKD defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m². Concentrations of 34 PFAS compounds in serum were quantified using HPLC-MS/MS. Adjusted GLM analyses were used to assess the association between PFAS exposure and CKD prevalence. Results A total of 28 out of 34 target compounds were detected, and 15 of them had detection rates exceeding 60%, mainly including PFOS, PFOA, 6:2Cl-PFESA, and PFDA. The three compounds with the highest serum concentrations were PFOS (median: 36.1 ng/mL), 6:2Cl-PFESA (median: 15.5 ng/mL), and PFOA (median: 3.0 ng/mL). Adjusted GLM analyses revealed inverse associations between serum concentrations of PFDA, PFDoDA, PFOA, PFTrDA, PFUnA, and 8:2 FTSA with CKD risk (P<0.05), suggesting potential protective effects, while remaining compounds showed no significant associations. Conclusion These findings reveal widespread PFAS exposure in this population. Certain long-chain perfluorinated compounds showed negative correlations with CKD prevalence, potentially attributable to age-specific physiological and metabolic characteristics, complex dose-response relationships, or epidemiological biases including the "healthy survivor effect." This study provides epidemiological evidence for assessing health risks of persistent organic pollutants in aging populations, though the biological mechanisms underlying these associations require further investigation through more prospective studies and mechanistic research.

Per- and polyfluoroalkyl substances; Chronic kidney disease; Elderly populations; Nested case-control study