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
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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
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Associations between selected perfluoroalkyl acids in serum and hemoglobin in whole blood, a biomarker of anemia: Impact of deteriorating kidney function.
Data (N = 11251) from National Health and Nutrition Examination Survey (NHANES) for 2003-2016 for US adults aged ≥20 years were stratified by gender and anemia and analyzed to evaluate the associations between the concentrations of whole blood hemoglobin (WBHGB) and selected perfluoroalkyl acids (PFAAs) in serum by stages of glomerular filtration (GF). Investigated PFAAs were perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorodecanoic acid (PFDA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA). Females with whole blood hemoglobin concentrations <12 g/dL and males with whole blood hemoglobin concentrations <13 g/dL were classified as being anemic. Regression models with log10 transformed concentrations of whole blood hemoglobin as dependent variable and age, poverty income ratio, body mass index, serum cotinine, daily alcohol intake, survey year, and log10 concentrations of one of the PFAA as independent variables were fitted. For anemic females, association between WBHGB and PFAA concentrations were uniformly positive across worsening stages of renal failure and percent increases for 10% increases in PFAAs varied between 0.03% and 0.39%. For anemic males, association between WBHGB and PFAA concentrations were positive except at GF-3A (45 ≤ eGFR<60 mL/min/1.73 m2) and percent increases for 10% increases in PFAAs varied between 0.02% and 0.53%. Thus, more often than not, presence of positive associations between WBHGB and PFAA among anemics imply elevated levels of PFAA are associated with higher levels of WBHGB. Similar results were observed for non-anemic males and females, however strengths of associations between whole blood hemoglobin and PFAAs were several fold higher among anemic compared to non-anemic participants. Hemoglobin is consistently associated with serum PFAAs.
Jain RB
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Impact of the co-occurrence of obesity with diabetes, anemia, hypertension, and albuminuria on concentrations of selected perfluoroalkyl acids.
Data (N = 10644) for US adults aged ≥20 years for 2003-2016 from National Health and Nutrition Examination Survey were analyzed to evaluate the impact of co-occurrence of obesity with diabetes, anemia, albuminuria, and hypertension on concentrations of five perfluoroalkyl acids (PFAA), namely, perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorodecanoic acid (PFDA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA). For the total population, males, and females, co-occurrence of obesity with hypertension, albuminuria, anemia, and diabetes was found to be associated with lower adjusted geometric means (AGM) than nonobese for every PFAA. For example for females, for PFOS, AGMs for obese with no diseases, hypertension, albuminuria, anemia, and diabetes were 8.2, 10.8, 5.8, 4.6, and 7.7 ng/mL respectively. In comparison, for PFOS, for nonobese females, AGMs for those with no diseases, hypertension, albuminuria, anemia, and diabetes were found to be 8.9, 13.4, 7.7, 6.0, and 10.2 ng/mL respectively. This implies obesity is associated with higher excretion rates. Females, in general, had lower AGMs than males for both obese and nonobese for every PFAA for every disease group. For example, percent ratios of obese females to males AGMs for PFOA were 66.7%, 87.1%, 88.2%, 70.6%, and 90% for those with no diseases, hypertension, albuminuria, anemia, and diabetes respectively. The ratios of obese to nonobese AGMs for females were lower than males for every PFAA for those with no diseases and hypertension only. For example, for PFOA for those with no diseases, obese to nonobese AGM ratios were 87% for females and 100% for males. Thus, additional excretion of certain PFAAs due to obesity is higher in females than males for those with no diseases and hypertension only.
Jain RB
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