Serum per- and polyfluoroalkyl substances levels among young adults at risk for chronic kidney disease of unknown etiology in Nicaragua

Chronic kidney disease of unknown etiology (CKDu) affects young adults in rural Mesoamerica, but environmental drivers remain unclear. Per- and polyfluoroalkyl substances (PFAS) are persistent nephrotoxic contaminants, yet evidence from CKDu-endemic regions is limited. This study assessed serum PFAS concentrations and their association with kidney function in young adults in northwestern Nicaragua. A nested cross-sectional study was conducted within a community-based cohort study in northwestern Nicaragua. Serum samples from 85 young participants (18–30 years) were selected in year four and stratified by glomerular filtration rate (eGFR). Targeted and non-targeted PFAS were measured using liquid chromatography–quadrupole time-of-flight mass spectrometry. Sex-stratified linear regression models assessed associations with eGFR, adjusting for age, body mass index, and smoking. Six PFAS were detected in > 50% of participants. PFOS and PFOA were most prevalent, with higher concentrations in men. Elevated concentrations were observed among workers in banana plantations, commerce, and construction. PFOS was positively associated with eGFR (β = 1.12 mL/min/1.73m 2 per µg/L; 95%CI: 0.14, 2.10), with no other significant associations. This study provides the first PFAS biomonitoring data from a CKDu-endemic region in Mesoamerica. While most PFAS showed no association with kidney function, the sex-specific PFOS–eGFR association in men warrants further longitudinal investigation. Chronic kidney disease of unknown etiology (CKDu), Per- and polyfluoroalkyl substances (PFAS), Kidney function, Longitudinal study, Nicaragua