Perfluoroalkyl acids serum concentrations and their relationship to biomarkers of renal failure: Serum and urine albumin, creatinine, and albumin creatinine ratios across the spectrum of glomerular function among US adults

Associations between selected perfluoroalkyl acids (PFAAs) and biomarkers of renal function were evaluated for US adult aged >= 20 years (N = 8220) in the National Health and Nutrition Examination Survey for 2005-2014. Glomerular filtration (GF) stage-stratified regression models were classified by estimated glomerular filtration rate (eGFR) with GF-1 (eGFR > 90 mL/min/1.73 m(2)), GF-2 (eGFR 60-89 mL/min/1.73 ma), GF-3A (45-59 mL/min/1.73 m(2)), and GF-3B/4 (15-44 mL/min/1.73 m(2)). For GF-1, PFOA, PFOS, and PFHxS were positively and significantly associated with serum creatinine. Serum albumin levels were positively associated with the PFAA considered at all stages and most associations were significant. Further, PFAS serum concentration associations to serum albumin were about 2-3 times stronger at GF-3B/4 than at GF-1. In contrast, urine albumin was negatively and significantly associated with PFOA and PFHxS serum concentrations at all stages of renal function, while, PFOS and PFNA were negatively and significantly associated to urine albumin at GF-3A and GF-3B/4. Urine albumin/creatinine ratios were negatively and significantly associated with PFOA, PFOS, and, and PFHxS serum concentrations at all stages of renal function, as well as with PFNA and PFDA at GF-3A and GF-3B/4. Recent work revealed that serum PFAAs have an inverted U-shaped association to the calculated stages of renal failure based on eGFR; this work adds that albuminuria makes additional negative contributions to already existing negative associations of PFAA to eGFR in advancing stages of renal failure. We hypothesize that both progressive renal failure per se and especially renal failure with albuminuria cause the kidneys to reabsorb less and to excrete more of the PFAAs studied. We suspect this finding may generalize to some other perfluoroalkyl substances (PFAS). The findings also imply study design considerations for evaluating associations to diseases and biomarkers associated with renal failure, such as diabetes.