Dynamics of associations between perfluoroalkyl substances and uric acid across the various stages of glomerular function.

National Health and Nutrition Examination Survey 2007-2014 data (N = 6844) for adults aged ≥ 20 years were analyzed to estimate associations of perfluoroalkyl substances (PFAS), namely, PFOA, PFOS, PFDA, PFHxS, and PFNA with uric acid across stages of declining glomerular function. The population was stratified by the estimated glomerular filtration rates (eGFR) stages accompanying kidney disease: GF-1 with eGFR > 90 mL/min/1.73 m; GF-2 with eGFR 60-89 mL/min/1.73 m; GF-3A with eGFR 45-59 mL/min/1.73 m; and GF-3B/4 with eGFR 15-44 mL/min/1.73 m. Adjusted and unadjusted geometric means of uric acid increased from GF-1 to GF-3B/4 for males and females. Adjusted geometric means for uric acid were higher for males by 1.38, 1.03, and 0.62 mg/dL for GF-1, GF2, and GF-3 respectively but for GF-3B/4, females had higher adjusted geometric means than males by 0.16 mg/dL, revealing narrowing of sex differences in uric acid as glomerular function declines. The direction of association between PFAS and uric acid was positive for GF-1 and GF-2 for males and for every PFAS except PFDA for females. For males for GF-3B/4, association between every PFAS except PFHxS and uric acid was found to be negative (p < 0.01). For females, only PFHxS actually reverses its relationship with increasing stages of renal disease. Uric acid associations with PFAS reverse in males with advanced renal failure. An implication is that previously reported association of PFAS exposure with uric acid is not due to renal failure. Understanding of other biomarkers associated with both PFAS exposure and renal failure may benefit from similar evaluation.