Association between perfluoroalkyl acids and kidney function in a cross-sectional study of adolescents

Kataria et al. Environmental Health (2015) 14:89 DOI 10.1186/s12940-015-0077-9 RESEARCH Open Access Association between perfluoroalkyl acids and kidney function in a cross-sectional study of adolescents Anglina Kataria1, Howard Trachtman1, Laura Malaga-Dieguez1 and Leonardo Trasande1,2,3,4,5,6* Abstract Background: Perfluoroalkyl acids are synthetic compounds widely used in industrial and commercial applications. Laboratory studies suggest that these persistent and bioaccumulative chemicals produce oxidant stress and damage glomerular endothelial cells, raising concern regarding the impact of these compounds on renal function. Methods: We performed cross-sectional analyses of data 1960 participants aged 12–19 years of the 2003–2010 National Health and Nutrition Examination Surveys. PFAA exposure was assessed using levels of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid, and perfluorohexane sulfonic acid. Primary study outcomes were estimated glomerular filtration rate (eGFR) and serum uric acid. Results: While adjusting for demographics, cotinine, prehypertension, insulin resistance, body mass index, and hypercholesterolemia, adolescents in the highest PFOA and PFOS quartile had a lower eGFR, 6.84 mL/min/1.73 m2 (95 % CI: 2.19 to 11.48) and 9.69 mL/min/1.73 m2 (95 % CI: -4.59 to 14.78), respectively, compared to the lowest quartile. Highest PFOA and PFOS quartiles were also associated with 0.21 mg/dL (95 % CI: 0.056 to 0.37) and 0.19 mg/dL (95 % CI: 0.032 to 0.34) increases in uric acid, respectively. Conclusions: PFAAs are associated with a reduction in kidney function and increased uric acid levels in otherwise healthy adolescents. Reverse causation and residual confounding could explain the results. Our study results confirm and amplify previous findings, though longitudinal studies examining prenatal and childhood biomarkers in relationship with robust measures of childhood renal function are needed. Keywords: Perfluoroalkyl acids, eGFR, Uric acid, Adolescents Background Perfluoroalkyl acids (PFAAs) are synthetic organic compounds with a totally fluorinated carbon chain of varying length and a negatively charged functional group, such as carboxylic or sulfonic acid [1]. This imparts high stability and thermal resistance to these compounds. PFAAs have found wide utility when polymerized in stain-resistant sprays for carpets and upholstery, fireretarding foams, and nonstick cooking surfaces and food packaging, such as microwave popcorn bags and pizza packaging [2]. National biomonitoring surveys reveal * Correspondence: 1 Department of Pediatrics, New York University School of Medicine, 227 East 30th St, Room 735, New York, NY 10016, USA 2 Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA Full list of author information is available at the end of the article that >98 % of the US population have detectable levels of PFAAs in the blood including: perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonate (PFHxS) and perfluorononanoic acid (PFNA) [3]. In cell culture studies, exposure of microvascular endothelial cells to PFOS induces endothelial permeability through increased production of reactive oxidative species at concentrations relevant to human exposures [4]. This is important given that endothelial cells are vital to structure and function of the glomeruli in the kidney. Furthermore, endothelial permeability plays a critical role in ischemic renal injury [5]. The effect of PFOA, PFOS, PFNA and PFHxS on the kidneys is further magnified by the fact that these compounds are well absorbed orally but have poor renal elimination rates © 2015 Kataria et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Kataria et al. Environmental Health (2015) 14:89 and half-lives in humans of 2.3-8.5 years [6]. Children and adolescents are uniquely vulnerable to PFOA and PFOS as they have greater food consumption per pound body weight [7]. PFAAs are present in human breast milk, and serum levels in children are generally higher than in adults [6, 8]. Childhood exposure may present the additional risk of disrupting cardiovascular and renal physiologic functions, and so vulnerability may be greater than in adults. Cross-sectional studies have associated PFAA biomarkers with reduced renal function. In one recent large, community-based study of residents living near a fluoropolymer production facility which resulted in contamination of their drinking water with elevated PFOA, serum PFOA, PFOS, PFNA and PFHxS concentrations were inversely correlated with estimated glomerular filtration rate (eGFR) in otherwise healthy children and adolescents [9]. A study by Shankar et al revealed similar findings in adults [10]. The study also found that PFOA and PFOS were associated with increased odds of chronic kidney disease (CKD), defined as eGFR <60 ml/ min/1.73 m2 [10]. Several cross-sectional epidemiological studies in adults and children have also shown a positive association between PFOA and uric acid (UA) [10–13], though one failed to detect such an association [14]. This is relevant since hyperuricemia has long been thought to be an important marker of renal disease. Moreover, growing evidence suggests that hyperuricemia may be part of the causal pathway in the development of hypertension. Numerous clinical studies have shown that elevated UA levels are associated with increased risk of hypertension, independent of other risk factors [15–18]. UA levels >5.5 mg/dL were observed in 90 % of adolescents with essential hypertension, whereas UA levels were significantly lower in controls and teens with either white-coat or secondary hypertension [16]. Finally, hyperuricemia is an independent risk factor for disease progression in pediatric patients with CKD [19]. However, studies to date have not explored the association between low grade exposure to perfluoroalkyl chemicals in the range commonly experienced by children/ adolescents and kidney function. Therefore, we examined the association of PFAAs with kidney function i.e., eGFR and uric acid in a nationally representative sample of US adolescents. We sought to test the hypothesis that higher levels of exposure to PFAAs would be associated with a decrement in kidney function and an increment in serum uric acid concentration. Methods The current study is based on eight years o (...truncated)