Perfluoroalkyl substances follow inverted U-shaped distributions across various stages of glomerular function: Implications for future research.

Data (N = 6844) from National Health and Nutrition Examination Survey for US adults aged ≥ 20 years for the years 2007-2014 were analyzed to evaluate distributional characteristics of selected perfluoroalkyl substances (PFAS) - perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorodecanoic acid (PFDA), perfluorohexane sulfonate (PFHxS) and perfluorononanoic acid (PFNA) with declining glomerular function. The population was stratified according to the estimated glomerular filtration rates (eGFR) that accompany the stages of kidney disease, designated as glomerular function-1 (GF-1, eGFR>90 mL/min/1.73 m2); GF-2 (eGFR 60-89 mL/min/1.73 m2), GF-3A (eGFR 45-59 mL/min/1.73 m2), and GF-3B and 4 combined (eGFR 15-44 mL/min/1.73 m2). Unadjusted as well as adjusted geometric means for serum PFOA, PFDA, PFHxS, and PFNA increased as expected through stage GF-3A but decreased below the concentrations associated with GF-1 for those who were in GF-3B/4. For example, unadjusted geometric means for PFOA were 2.59, 3.02, 3.01, and 2.22 ng/mL for GF-1, GF-2, GF-3A, and GF-3B/4 respectively. Adjusted geometric means for PFOA were 2.34, 2.83, 2.83, and 1.81 ng/mL for GF-1, GF-2, GF-3A, and GF-3B/4 respectively. Thus, PFAS were found to follow inverted U-shaped distributions across different stages of glomerular function. For females, decreases in adjusted PFAS serum levels were initiated at GF-3A, while decreases for males began as early as GF-2. Usually, females are known to have lower levels of PFAS but when in GF-3A and GF-3B/4, females were found to have higher levels of PFAS than males. Thus, inverted U-shaped curves for males and females intersected between GF-2 and GF-3A for PFOA and PFHxS and at GF-3A for PFOS and PFNA. Associations between PFAS and biomarkers of kidney function may be modified in both magnitude and even in direction as kidney function deteriorates. These findings have implications for studies that evaluate associations between PFAS and disease states that affect kidney function, as well as outcome biomarkers known to be affected by kidney function.

Jain RB ，Ducatman A 《-》

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.

Jain RB ，Ducatman A 《-》

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

Jain RB ，Ducatman A 《-》

Perfluoroalkyl acids and their isomers, diabetes, anemia, and albuminuria: Variabilities with deteriorating kidney function.

Data for US adults aged ≥20 years from National Health and Nutrition Examination Survey for the years 2003-2014 were analyzed to evaluate how adjusted (N = 8481) and unadjusted (N = 9080) levels of selected perfluoroalkyl acids (PFAA) vary across the different stages of glomerular function (GF) among those who did not have diabetes, anemia, or albuminuria as compared to those who had diabetes only, anemia only, and albuminuria only. PFAAs selected for analyses were: perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorodecanoic acid (PFDA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA). Irrespective of GF stage, there was no noticeable evidence to suggest that adjusted levels of PFAA for those with diabetes only are any lower than those with no diabetes, no anemia, and no albuminuria. Those who had anemia only were found to have lower adjusted levels of at least PFOA, PFOS, PFDA, and PFHxS than those who had no diabetes, no anemia, and no albuminuria. These results were seen in the presence (eGFR < 60 mL/min/1.73 m2) as well as the absence of chronic kidney disease. For GF-1 (eGFR > 90 mL/min/1.73 m2), GF-2 (60 ≤ eGFR ≤ 90 mL/min/1.73 m2), and GF-3B/4 (15 < eGFR ≤ 45 mL/min/1.73 m2), those who had albuminuria only had lower adjusted levels of PFOA, PFOS, and PFHxS than those who had no diabetes, no anemia, and no albuminuria. In general, adjusted levels of those who had albuminuria only were lower than those who had anemia only at GF-3 and more often than not at GF-1 and GF-2. Rise in adjusted levels of PFAA from GF-1 to GF-3A (45 < eGFR < 60 mL/min/1.73 m2) was faster for those with anemia only than any other comparison group for the total population and females.

Jain RB 《-》

Isomers of per- and polyfluoroalkyl substances and uric acid in adults: Isomers of C8 Health Project in China.

Greater levels of serum per- and polyfluoroalkyl substances (PFAS) are known to be associated with higher uric acid which itself leads to a number of chronic diseases. However, whether this association varies across PFAS isomers which recently have been found to be associated with human health remains unknown. To address this research gap, we explored isomer-specific associations between serum PFAS and uric acid in Chinese adults. We conducted a cross-sectional study of associations between serum PFAS isomer and serum uric acid in 1612 participants from the Isomer of C8 Health Project. We used multivariable linear and logistic regression models to analyze serum isomers of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and other PFASs as continuous and categorical predictors of uric acid, adjusted for confounders. The association was also stratified by kidney function stage based on estimated glomerular filtration rate (GF-1, GF-2, GF-3a, and GF-3b/4). We found positive associations between serum PFAS isomer concentrations and uric acid. Uric acid levels were greater for each log-unit increase in branched PFOA (β = 0.30, 95% CI: 0.21, 0.40), linear PFOA (β = 0.18, 95% CI: 0.09, 0.26), branched PFOS (β = 0.09, 95% CI: 0.02, 0.17) and linear PFOS (β = 0.06, 95% CI: -0.01, 0.14) concentration. The associations between PFAS and uric acid showed an inverted 'U' shaped pattern across kidney function stages. For example, uric acid level was greater with each log-unit increase in total-PFOA among GF-1 (β = 0.21, 95% CI: 0.06, 0.37), this relationship was greater in GF-3a (β = 0.49, 95% CI: 0.09, 0.89) and decreased in GF-3b/4 (β = -0.22, 95% CI: -0.83, 0.39). We also found the odds of hyperuricemia increased linearly with increasing branched PFOA in quartiles (odds ratio = 2.67, 95% CI: 1.86, 3.85 at the highest quartile). We report novel results in which PFAS associations with uric acid varied according to isomer and adult kidney function. Besides, our findings are consistent with previous epidemiologic studies in finding a positive association between serum PFAS concentrations and serum uric acid, especially for PFOA. Our results indicate that more research is needed to more clearly assess the impact of PFAS isomers on human health, which will help to refine regulation policies for PFAS.

Zeng XW ，Lodge CJ ，Dharmage SC ，Bloom MS ，Yu Y ，Yang M ，Chu C ，Li QQ ，Hu LW ，Liu KK ，Yang BY ，Dong GH ... -  《-》