Abstract Body: Introduction: Chronic Kidney Disease (CKD) affects around 1 in 7 Americans but is more prevalent among former military service members, reaching nearly 1 in 3 in some cohorts. Metals, such as cadmium (Cd) and lead (Pb), and per-/polyfluoroalkyl substances (PFAS), such as perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), are known nephrotoxicants to which civilians are regularly exposed. However, military populations may experience higher exposures due to service-related activities. Despite elevated exposures and CKD burden, the relationship remains poorly characterized among US veterans.
Hypothesis: We hypothesized that (1) a higher concentration of a metal-PFAS mixture would be associated with lower eGFR for both military and civilian populations, and (2) the mixture composition most associated with eGFR would differ across subgroups defined by veteran status and sex.
Methods: In a cross-sectional analysis of the 2003-2018 NHANES, we assessed the association of a metal-PFAS mixture with eGFR among civilians and veterans and conducted sex-stratified analyses. Our sample included 5,503 men (4,244 civilians, 1,259 veterans), and 5,765 women (5,690 civilians, 75 veterans). We used weighted quantile sum regression (WQSR) to estimate the joint effect of blood Cd and Pb, and serum PFOA and PFOS on eGFR (mL/min/1.73m²). Covariates included age and BMI.
Results: Among veterans, a one unit higher mixture index was associated with a 1.4 mL/min/1.73m² (95%CI: 0.9, 1.9) lower eGFR, wherein Pb accounted for 74% of the mixture effect. Among civilians a one unit higher mixture index was associated with a 2.2 mL/min/1.73m² (95%CI: 1.9, 2.5) lower eGFR, wherein PFOS accounted for 47% of the mixture effect. We observed similar results among men in sex- and veteran status-stratified models. Pb accounted for 79% of the mixture effect among veteran men, while PFOS accounted for 64% among civilian men. Among women civilians a one unit higher mixture index was associated with a 2.3 mL/min/1.73m² (95%CI: 1.9, 2.6) lower eGFR, wherein PFOS and Cd accounted for 63% of the mixture effect. The mixture index was not significantly associated with eGFR in veteran women, potentially due to small sample size.
Conclusion: Metal-PFAS mixtures were associated with lower eGFR, with differing mixture profiles across sex and veteran status subgroups. Additional studies of the effects of environmental mixtures among military populations are needed, especially among women.