Exposure to Perfluoroalkyl Acids and Markers of Kidney Function Among Children and Adolescents Living Near a Chemical Plant
Open accessAbstract
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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Multiple human studies have reported significant associations between PFAS exposure and lower eGFR and increased odds of CKD.
“Multiple studies have reported significant associations between PFAS exposure with lower eGFR and increased odds of CKD”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Watkins et al., 2013
The Results report an association between measured serum PFAAs and lower eGFR in this study, and the Discussion reports that an adult NHANES study found both lower eGFR and increased odds of CKD. The claim is supported as a summary of reported associations, but this paper did not itself report increased odds of CKD; that finding comes from the NHANES study it discusses. Page numbers are not available in the supplied passages. (LLM, conf=0.83)
Experimental — accuracy not yet measuredPFOA has been shown to interact with PPARα, γ, and β/δ and induce adipogenesis in 3T3-L1 cells.
“PFOA has been shown to interact with PPARα, γ, and β/δ and induce adipogenesis in 3T3-L1 cells”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Watkins et al., 2013
The Discussion passages address PFOA exposure and kidney function, not PPAR interactions or adipogenesis. Searches for PPARα, PPARγ, PPARβ/δ, 3T3-L1 cells, and adipocyte differentiation found no passage addressing the claim. Page numbers were not available in our copy. (LLM, conf=0.74)
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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
- 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
- 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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