title: Environmental Chemicals in Urine and Blood: Improving Methods for Creatinine and Lipid Adjustment.
abstract: BACKGROUND
  Investigators measuring exposure biomarkers in urine typically adjust for creatinine to account for dilution-dependent sample variation in urine concentrations. Similarly, it is standard to adjust for serum lipids when measuring lipophilic chemicals in serum. However, there is controversy regarding the best approach, and existing methods may not effectively correct for measurement error.
  
  
  OBJECTIVE
  We compared adjustment methods, including novel approaches, using simulated case-control data.
  
  
  METHODS
  Using a directed acyclic graph framework, we defined six causal scenarios for epidemiologic studies of environmental chemicals measured in urine or serum. The scenarios include variables known to influence creatinine (e.g., age and hydration) or serum lipid levels (e.g., body mass index and recent fat intake). Over a range of true effect sizes, we analyzed each scenario using seven adjustment approaches and estimated the corresponding bias and confidence interval coverage across 1,000 simulated studies.
  
  
  RESULTS
  For urinary biomarker measurements, our novel method, which incorporates both covariate-adjusted standardization and the inclusion of creatinine as a covariate in the regression model, had low bias and possessed 95% confidence interval coverage of nearly 95% for most simulated scenarios. For serum biomarker measurements, a similar approach involving standardization plus serum lipid level adjustment generally performed well.
  
  
  CONCLUSIONS
  To control measurement error bias caused by variations in serum lipids or by urinary diluteness, we recommend improved methods for standardizing exposure concentrations across individuals.
authors.affiliation: Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA.
authors.forename: Katie M
authors.initials: KM
authors.lastname: O'Brien
authors.forename: Kristen
authors.initials: K
authors.lastname: Upson
authors.forename: Nancy R
authors.initials: NR
authors.lastname: Cook
authors.forename: Clarice R
authors.initials: CR
authors.lastname: Weinberg
mesh_terms: D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D003404:Creatinine / Q000652:urine*; D004781:Environmental Exposure; D004784:Environmental Monitoring / Q000379:methods*; D004785:Environmental Pollutants / Q000652:urine*; D006801:Humans; D050356:Lipid Metabolism; D012044:Regression Analysis
chemical_list: D015415:Biomarkers; D004785:Environmental Pollutants; D003404:Creatinine