Longitudinal and cross-sectional analysis of perfluoroalkyl substances and kidney function.

Background: Perfluoroalkyl substances (PFAS) constitute a diverse group of chemical compounds used in various consumer products. While the associations between PFAS and certain adverse human health effects are well-documented, their impact on kidney function remains less known.

Objective: The main aim of this study is to investigate the relationship between PFAS levels and kidney function (estimated glomerular filtration rate [eGFR]) utilizing a longitudinal design.

Methods: The population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study included 997 individuals at baseline (all aged 70 years, 50% females). Follow-up investigations were performed at 75 and 80 years of age. Seven major PFAS were determined in plasma using ultra-high performance liquid chromatography-mass spectrometry. Longitudinal and cross-sectional associations between PFAS and eGFR were analyzed using linear regression and mixed effects models following adjustment for sex, HDL and LDL-cholesterol, triglycerides, glucose, BMI, statin use and smoking.

Results: Longitudinal models demonstrated statistically significant positive associations between perfluoroundecanoic acid (PFUnDA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA)and eGFR (all P < 0.001). The associations between linear perfluorooctane sulfonic acid (PFOS) and perfluorohexanesulfonic acid (PFHxS) followed a similar trend. In contrast, an inverse relationship between perfluoroheptanoic acid (PFHpA) and perfluorooctanesulfonamide (PFOSA) with eGFR was observed. The findings were largely corroborated by cross-sectional analyses.

Impact statement: This longitudinal study found that changes in certain PFAS concentrations were positively associated with the change in kidney function, though the direction of association varied across PFAS. These findings were further supported by cross-sectional analysis. The complexity of associations remains incompletely understood as some PFAS showed positive associations while others were inverse. Further longitudinal studies with repeated measures are needed to better elucidate the relationship between PFAS exposure and kidney function.