title: Urine osmolality in the US population: implications for environmental biomonitoring.
abstract: BACKGROUND
  For many environmental chemicals, concentrations in spot urine samples are considered valid surrogates of exposure and internal dose. To correct for urine dilution, spot urine concentrations are commonly adjusted for urinary creatinine. There are, however, several concerns about the use of urine creatinine. While urine osmolality is an attractive alternative; its characteristics and determinants in the general population remain unknown. Our objective was to describe the determinants of urine osmolality and to contrast the difference between osmolality and creatinine in urine.
  
  
  METHODS
  From the National Health and Nutrition Examination Survey (NHANES) (2009-2010), 10,769 participants aged 16 years or older with measured urine osmolality and creatinine were used in the analysis. Very dilute and very concentrated urine was defined as urine creatinine lower than 0.3g/l and higher than 3g/l, respectively. Linear and logistic regression analyses were performed to investigate the associations of interest.
  
  
  RESULTS
  Urine osmolality and creatinine were highly correlated (Pearson correlation coefficient=0.75) and their respective median values were 648 mOsm/kg and 1.07 g/l. The prevalence of very dilute and very concentrated urine samples was 8.1% and 3.1%, respectively. Factors associated in the same direction with both urine osmolality and urine creatinine included age, sex, race, body mass index (BMI), hypertension, water intake, and blood osmolality. The magnitude of associations expressed as percent change was significantly stronger with creatinine than osmolality. Compared to urine creatinine, urine osmolality did not vary by diabetes status but was affected by daily total protein intake. Participants with chronic kidney disease (CKD) had significantly higher urine creatinine concentrations but lower urine osmolality. Both very dilute and concentrated urine were associated with a diverse array of sociodemographic, medical conditions, and dietary factors. For instance, females were approximately 3.3 times more likely to have urine over-dilution than male [the adjusted odds ratios (95% CI)=3.27 (2.10-5.10)].
  
  
  CONCLUSIONS
  Although the determinants of urine osmolality were generally similar to those of urine creatinine, the relative influence of socio-demographic and medical conditions was less on urine osmolality than on urine creatinine. Protocols for spot urine sample collection could recommend avoiding excessive and insufficient water intake before urine sampling to improve urine adequacy. The feasibility of adopting urine osmolality adjustment and water intake recommendations before providing spot urine samples for environmental biomonitoring merits further investigation.
authors.affiliation: Kidney Institute and Division of Nephrology, Department of Internal Medicine, China Medical University Hospital and College of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Hung-Chieh
authors.initials: HC
authors.lastname: Yeh
authors.affiliation: Department of Environmental and Occupational Health, University of North Texas Health Science Center, Fort Worth, TX, USA.
authors.forename: Yu-Sheng
authors.initials: YS
authors.lastname: Lin
authors.affiliation: Kidney Institute and Division of Nephrology, Department of Internal Medicine, China Medical University Hospital and College of Medicine, China Medical University, Taichung, Taiwan; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Chin-Chi
authors.initials: CC
authors.lastname: Kuo
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Division of Nephrology, Department of Pediatrics, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Darcy
authors.initials: D
authors.lastname: Weidemann
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Virginia
authors.initials: V
authors.lastname: Weaver
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Division of Nephrology, Department of Pediatrics, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Fadrowski
authors.affiliation: Division of Nephrology, Department of Pediatrics, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Alicia
authors.initials: A
authors.lastname: Neu
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Navas-Acien
mesh_terms: D004781:Environmental Exposure; D004784:Environmental Monitoring; D005260:Female; D006801:Humans; D008297:Male; D009749:Nutrition Surveys; D009994:Osmolar Concentration; D014481:United States; D014556:Urine
keywords: Biomonitoring; Urine adequacy; Urine creatinine; Urine dilution; Urine osmolality