title: Exposure to perfluoroalkyl acids and markers of kidney function among children and adolescents living near a chemical plant.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Epidemiology, Brown University, Providence, Rhode Island, USA. deborah_watkins@brown.edu
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Watkins
authors.forename: Jyoti
authors.initials: J
authors.lastname: Josson
authors.forename: Beth
authors.initials: B
authors.lastname: Elston
authors.forename: Scott M
authors.initials: SM
authors.lastname: Bartell
authors.forename: Hyeong-Moo
authors.initials: HM
authors.lastname: Shin
authors.forename: Veronica M
authors.initials: VM
authors.lastname: Vieira
authors.forename: David A
authors.initials: DA
authors.lastname: Savitz
authors.forename: Tony
authors.initials: T
authors.lastname: Fletcher
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Wellenius
mesh_terms: D000293:Adolescent; D017738:Alkanesulfonic Acids / Q000097:blood; D015415:Biomarkers; D002210:Caprylates / Q000097:blood*; D002617:Chemical Industry; D002648:Child; D003404:Creatinine / Q000097:blood; D003430:Cross-Sectional Studies; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D005466:Fluorocarbons / Q000097:blood*; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male
chemical_list: D017738:Alkanesulfonic Acids; D015415:Biomarkers; D002210:Caprylates; D005466:Fluorocarbons; C023036:perfluorooctanoic acid; C076994:perfluorooctane sulfonic acid; D003404:Creatinine