Cited by 158Per- and polyfluoroalkyl substances researchFluoride Effects and RemovalChemical Analysis and Environmental Impact

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Exposure to Perfluoroalkyl Acids and Markers of Kidney Function among Children and Adolescents Living near a Chemical Plant

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Watkins, Deborah J., Josson, Jyoti, Elston, Beth, Bartell, Scott M., Shin, Hyeong-Moo, Vieira, Veronica M., Savitz, David A., Fletcher, Tony, Wellenius, Gregory A.·2013·Environmental Health Perspectives

DOI 10.1289/ehp.1205838PMC PMC3673193

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Abstract

BACKGROUND: Serum levels of perfluorooctanoic acid (PFOA) have been associated with decreased renal function in cross-sectional analyses, but the direction of the association is unclear. OBJECTIVES: We examined the association of measured and model-predicted serum PFOA concentrations with estimated glomerular filtration rate (eGFR), a marker of kidney function, in a highly exposed population (median serum PFOA, 28.3 ng/mL). METHODS: We measured serum creatinine, PFOA, perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS) and calculated eGFR in 9,660 children 1 to < 18 years of age at study enrollment. We predicted concurrent and historical serum PFOA concentrations using a validated environmental, exposure, and pharmacokinetic model based on individual residential histories, and used linear regression to estimate the association between eGFR and measured and predicted serum PFOA concentrations. We hypothesized that predicted serum PFOA levels would be less susceptible to reverse causation than measured levels. RESULTS: An interquartile range increase in measured serum PFOA concentrations [IQR ln(PFOA) = 1.63] was associated with a decrease in eGFR of 0.75 mL/min/1.73 m(2) (95% CI: -1.41, -0.10; p = 0.02). Measured serum levels of PFOS, PFNA, and PFHxS were also cross-sectionally associated with decreased eGFR. In contrast, predicted serum PFOA concentrations at the time of enrollment were not associated with eGFR (-0.10; 95% CI: -0.80, 0.60; p = 0.78). Additionally, predicted serum PFOA levels at birth and during the first ten years of life were not related to eGFR. CONCLUSIONS: Our findings suggest that the cross-sectional association between eGFR and serum PFOA observed in this and prior studies may be a consequence of, rather than a cause of, decreased kidney function.

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Figure 1 Mean change in eGFR by quartiles (Q) of measured PFAA concentrations in serum (mL/min/1.73 m2) adjusted for age, sex, race, smoking status, and household income. Error bars represent 95% CIs; p-values for trend = 0.30 for PFOA, 0.0001 for PFOS, 0.005 for PFNA, and 0.004 for PFHxS.CC0 · PubMed Central

Figure 2 Causal diagram illustrating potential for direct and reverse causation. (A) The causal effect of the biologically effective dose of PFOA (PFOA exposure) on kidney function was approximated by relating serum levels of PFOA (an imperfect marker of the biologic effective dose) to eGFR (an imperfect marker of kidney function), controlling for common causes of PFOA exposure and kidney function, which may confound the association. Reverse causation occurs when kidney function alters our marker of exposure, represented by the arrow from kidney function to serum PFOA. (B) Biological exposure is determined by environmental levels of PFOA, which can also be used to predict serum levels of PFOA. Because kidney function does not affect predicted PFOA, analyses using predicted PFOA cannot represent reverse causation.CC0 · PubMed Central

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Authors: Watkins, D. J., Josson, J., Elston, B., Bartell, S. M., Shin, H.-M., Vieira, V. M., Savitz, D. A., Fletcher, T., & Wellenius, G. A.
Affiliations: Brown University (US)
London School of Hygiene & Tropical Medicine (GB)
Program in Public Health, and
University of California, Irvine (US)
Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts, USA
Corresponding author: Watkins, Deborah J.
ORCID: Watkins, Deborah J.
Bartell, Scott M.
Shin, Hyeong-Moo
Savitz, David A.
Fletcher, Tony
Wellenius, Gregory A.
Venue: Environmental Health Perspectives
Publisher: American Chemical Society (ACS)
Published: 2013-03-11
Volume: 121
Issue: 5
Pages: 625-630
ISSN: 0091-6765 (ISSN-L)
1552-9924
DOI: 10.1289/ehp.1205838
PMC: PMC3673193
OpenAlex: W2062732713
Cited by: 158
References: 41
Citations by year: 2026: 11 · 2025: 15 · 2024: 14 · 2023: 11 · 2022: 20 · 2021: 17 · 2020: 17 · 2019: 8 · 2018: 13 · 2017: 8 · 2016: 9 · 2015: 9 · 2014: 6
FWCI: 6.38
Type: journal article
Language: en
Open access: gold
doi.org
Licence: public-domain
creativecommons.org/licenses/by/4.0/ (vor, 1754 d)
Locations: Environmental Health Perspectives (publishedVersion, public-domain)
Europe PMC (PubMed Central) (publishedVersion, public-domain)
PubMed Central (publishedVersion, public-domain)
PubMed (publishedVersion)
LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders: National Cancer Institute (R01CA121147, R01CA126939)
National Institute of Environmental Health Sciences (R00ES015774)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (R24HD041020)
Topics: Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
Physical Sciences › Environmental Science › Water Science and Technology › Fluoride Effects and Removal
Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Chemical Analysis and Environmental Impact
Keywords: perfluoroalkyl acids, perfluorooctanoic acid, PFOS, perfluorononanoic acid, PFHxS, estimated glomerular filtration rate, renal function, children and adolescents, residential exposure, reverse causality, PFAS exposure
MeSH terms: Adolescent, Caprylates, Chemical Industry, Child, Creatinine, Cross-Sectional Studies, Environmental Exposure, Female, Fluorocarbons, Glomerular Filtration Rate, Humans, Male, Biomarkers, Alkanesulfonic Acids

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Exposure to Perfluoroalkyl Acids and Markers of Kidney Function among Children and Adolescents Living near a Chemical Plant

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