Perfluoroalkyl Chemicals and Chronic Kidney Disease in US Adults

American Journal of Epidemiology ª The Author 2011. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: . Vol. 174, No. 8 DOI: 10.1093/aje/kwr171 Advance Access publication: August 26, 2011 Original Contribution Perfluoroalkyl Chemicals and Chronic Kidney Disease in US Adults Anoop Shankar*, Jie Xiao, and Alan Ducatman * Correspondence to Dr. Anoop Shankar, Department of Community Medicine, School of Medicine, West Virginia University, 1 Medical Center Drive, PO Box 9190, Morgantown, WV 26506 (e-mail: ). Initially submitted June 7, 2010; accepted for publication April 25, 2011. fluorocarbons; kidney diseases; nutrition surveys Abbreviations: BMI, body mass index; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; NHANES, National Health and Nutrition Examination Survey; PFCs, perfluoroalkyl chemicals; PFOA, perfluorooctanoic acid; PFOS, perfluorooctane sulfonate; SE, standard error. Chronic kidney disease (CKD), defined as a glomerular filtration rate of less than 60 mL/minute/1.73 m2 (1, 2), is present in approximately 13.1% of the adult US population (3). CKD is a stage early in the renal disease continuum in which prevention and/or delay of irreversible kidney damage that leads to end-stage renal disease may be possible. CKD is also known to be an independent risk factor for cardiovascular disease and early death (4). In a recent study in which 2 consecutive national surveys were compared, Coresh et al. (3) reported an increase in the prevalence of CKD from 1988–1994 to 1999–2004, suggesting it to be a growing public health problem. From a public health point of view, identifying new risk factors for CKD, particularly widely available environmental exposures that have not been previously studied, is therefore important. There is growing concern regarding human exposure to perfluoroalkyl chemicals (PFCs), including perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), because these chemicals are persistent in the environment, bioaccumulated, and biomagnified along food chains and have been shown to cause developmental and other adverse health effects in laboratory animals (5, 6). PFCs have been widely used in the manufacture of industrial and consumer products such as surfactants, lubricants, polishes, paper and textile coatings, food packaging, and fire-retarding foams. PFCs have been detected in the blood of more than 98% of the US population (7). Although both PFOS and PFOA share a ubiquitous presence among both humans and wildlife, PFOS has a wider distribution that is attributed in part to its resistance to degradation in ecologic systems and its 893 Am J Epidemiol. 2011;174(8):893–900 Chronic kidney disease (CKD) is a major public health problem. Identifying novel risk factors for CKD, including widely prevalent environmental exposures, is therefore important. Perfluoroalkyl chemicals (PFCs), including perfluorooctanoic acid and perfluorooctane sulfonate, are manmade chemicals that have been detected in the blood of more than 98% of the US population. Results from experimental animal studies have suggested that an association between PFCs and CKD is plausible. However, in humans, the relation between serum PFCs and CKD has not been examined. The authors examined the relation of serum PFCs and CKD in 4,587 adult participants (51.1% women) from the combined 1999–2000 and 2003–2008 cycles of the National Health and Nutritional Examination Survey for whom PFC measurements were available. The main outcome was CKD, defined as a glomerular filtration rate of less than 60 mL/minute/1.73 m2. The authors found that serum levels of PFCs, including perfluorooctanoic acid and perfluorooctane sulfonate, were positively associated with CKD. This association was independent of confounders such as age, sex, race/ethnicity, body mass index, diabetes, hypertension, and serum cholesterol level. Compared with subjects in quartile 1 (referent), the multivariable odds ratio for CKD among subjects in quartile 4 was 1.73 (95% confidence interval: 1.04, 2.88; P for trend ¼ 0.015) for perfluorooctanoic acid and 1.82 (95% confidence interval: 1.01, 3.27; P for trend ¼ 0.019) for perfluorooctane sulfonate. The present results suggest that elevated PFC levels are associated with CKD. 894 Shankar et al. MATERIALS AND METHODS The current study was based on merged data from the 1999–2000, 2003–2004, 2005–2006, and 2007–2008 cycles of the National Health and Nutrition Examination Survey (NHANES). Detailed descriptions of the NHANES study design and methods have been published previously (32). In brief, the NHANES survey includes a stratified, multistage probability sample representative of the civilian noninstitutionalized US population. Selection is based on counties, blocks, households, and individuals within households and includes oversampling of low-income persons, persons 60 years of age or older, African Americans, and Mexican Americans to provide stable estimates for these groups. The survey also includes biomonitoring for PFCs by the National Center for Environmental Health in a random subsample of one-third of the participants. Subjects are required to sign a consent form before participation, and approval was obtained from the Human Subjects Committee of the US Department of Health and Human Services. The present study sample consisted of 5,717 NHANES participants 20 years of age or older for whom PFC measurements were available. We further excluded subjects with self-reported cardiovascular disease (n ¼ 572) or missing data (n ¼ 558) on serum creatinine or covariates included in the multivariable model, including educational level, body mass index (BMI), and cholesterol levels. This resulted in 4,587 participants (51.1% women). Main outcome of interest: CKD In NHANES 1999–2000, serum creatinine measurements were performed at the Coulston Foundation Laboratory (Boston, Massachusetts) using a Roche Hitachi 917 analyzer (Roche Diagnostics, Indianapolis, Indiana; kinetic alkaline picrate) (33). We used the following Deming regression equation provided by Selvin et al. (34) in a calibration substudy to standardize NHANES 1999–2000 serum creatinine levels: standard creatinine ¼ 0.147 þ 1.013 3 (NHANES 1999–2000 uncalibrated serum creatinine). In NHANES 2003–2006, serum creatinine measurements were performed at Collaborative Laboratory Services (Ottumwa, Iowa) using the Beckman Coulter Synchron LX20 (Beckman Coulter, Fullerton, California; kinetic alkaline picrate) (35, 36). We did not correct the NHANES 2003–2004 serum creatinine values as recommended by the calibration study (34). However, we applied the following equation to standardize NHANES 2005–2006 serum creatinine levels as recommended by the National Center for Health Statistics on the basis of their calibration study (36): standard creatinine ¼
0.016 þ 0.978 3 (NHANES 2005–2006 uncalibrat (...truncated)