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. 2016 Jun 10;15(1):68.
doi: 10.1186/s12940-016-0152-x.

Assessing urinary flow rate, creatinine, osmolality and other hydration adjustment methods for urinary biomonitoring using NHANES arsenic, iodine, lead and cadmium data

Daniel R S Middleton  1   2 , Michael J Watts  2 , R Murray Lark  2 , Chris J Milne  2 , David A Polya  3
Affiliations

Assessing urinary flow rate, creatinine, osmolality and other hydration adjustment methods for urinary biomonitoring using NHANES arsenic, iodine, lead and cadmium data

Daniel R S Middleton et al. Environ Health. .

Abstract

Background: There are numerous methods for adjusting measured concentrations of urinary biomarkers for hydration variation. Few studies use objective criteria to quantify the relative performance of these methods. Our aim was to compare the performance of existing methods for adjusting urinary biomarkers for hydration variation.

Methods: Creatinine, osmolality, excretion rate (ER), bodyweight adjusted ER (ERBW) and empirical analyte-specific urinary flow rate (UFR) adjustment methods on spot urinary concentrations of lead (Pb), cadmium (Cd), non-arsenobetaine arsenic (As(IMM)) and iodine (I) from the US National Health and Nutrition Examination Survey (NHANES) (2009-2010 and 2011-2012) were evaluated. The data were divided into a training dataset (n = 1,723) from which empirical adjustment coefficients were derived and a testing dataset (n = 428) on which quantification of the performance of the adjustment methods was done by calculating, primarily, the correlation of the adjusted parameter with UFR, with lower correlations indicating better performance and, secondarily, the correlation of the adjusted parameters with blood analyte concentrations (Pb and Cd), with higher correlations indicating better performance.

Results: Overall performance across analytes was better for Osmolality and UFR based methods. Excretion rate and ERBW consistently performed worse, often no better than unadjusted concentrations.

Conclusions: Osmolality adjustment of urinary biomonitoring data provides for more robust adjustment than either creatinine based or ER or ERBW methods, the latter two of which tend to overcompensate for UFR. Modified UFR methods perform significantly better than all but osmolality in removing hydration variation, but depend on the accuracy of UFR calculations. Hydration adjustment performance is analyte-specific and further research is needed to establish a robust and consistent framework.

Keywords: Biomonitoring; Creatinine; Hydration adjustment; NHANES; Osmolality; Urinary flow rate.

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Figures

Fig. 1
Fig. 1
Unadjusted urinary Pb (a), Cd (b), AsIMM (c), I (d) and creatinine (e) plotted against UFR (NHANES 2009–2012 (CDC, 2015) training data). Multiple spot Cd measurements (Meharg et al., 2014) from a single volunteer are shown for comparison (f). Linear regression lines (blue) are displayed with regression slopes and r2 values. *** denotes significance to p < 0.001. Point density contours were plotted using two-dimensional kernel density estimation. In (c), the transition from green to red depicts increasing concentration of urinary dimethylarsonic acid (DMA)
Fig. 2
Fig. 2
Sensitivity of Pearson correlations to Araki’s b value for NHANES 2009–2012 (CDC, 2015) training data for Pb (a), Cd (b), AsIMM (c) and I (d) for criterion A (urinary analyte versus UFR, blue lines) and criterion B (urinary analyte versus blood analyte, red lines) with 95 % confidence intervals (grey lines). Optimum criterion A (blue diamonds) and criterion B (red diamonds) Araki’s b values are displayed and, in the case of Pb and Cd, the difference between these values is highlighted by double-headed arrows. Single-headed arrows illustrate the improvement in criterion A (decreasing correlation) and criterion B (increasing correlation) correlations relative to the equivalent Araki’s b value implicit of ER
Fig. 3
Fig. 3
Scatterplots of unadjusted (a, b); creatinine adjusted (c, d); osmolality adjusted (e, f); ER adjusted (g, h); ERBW adjusted (i, j); UFR adjusted with Araki’s b optimised to criterion A (k, l) and criterion B (m, n) urinary Pb concentrations vs UFR (criterion A) (a, c, e, g, i, k, m) or blood Pb concentrations (criterion B) (b, d, f, h, j, l, n). Data: NHANES 2009–2012 (CDC, 2015) testing dataset. *** denotes significance to p < 0.001
Fig. 4
Fig. 4
Optimum Criterion A (a) and Criterion B (b) Araki’s b values derived for different age groups for the range of analytes investigated
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