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

Abstract

BackgroundThere 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.MethodsCreatinine, 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 (AsIMM) 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.ResultsOverall performance across analytes was better for Osmolality and UFR based methods. Excretion rate and ERBW consistently performed worse, often no better than unadjusted concentrations.ConclusionsOsmolality 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12940-016-0152-x) contains supplementary material, which is available to authorized users.

Effect of hyperhydration on the pharmacokinetics and detection of orally administered budesonide in doping control analysis

“…Briefly, the "conventional" SG adjustment method, used by WADA as the official adjustment method, is based on the Levine-Fahy equation 16 where the non-adjusted (measured) concentration is adjusted to a population reference SG value of 1.020. Alternative adjustment methods, selected from the literature, 17,18 were applied and compared to the official WADA method. More specifically, the following adjustment methods were examined: a. the UFR-adjustment method developed by Araki et al 19 based on a log-linear relationship between the UFR and the non-adjusted concentrations where the slope (referred to as Araki's b slope) is analyte dependent and was established per analyte and study phase; b. the SG (z) -adjustment method, a modified SG adjustment method proposed by Vij and Howell, 20 introducing the value z which is the slope of the log-linear relationship between the non-adjusted concentration and the SG, expressed as SG-1, that is also analyte dependent; c. an adjustment method using CRE concentration 21 applied, where the correction of the measured concentrations is performed using a reference CRE value and the CRE value per sample.…”

“…Briefly, the “conventional” SG adjustment method, used by WADA as the official adjustment method, is based on the Levine‐Fahy equation where the non‐adjusted (measured) concentration is adjusted to a population reference SG value of 1.020. Alternative adjustment methods, selected from the literature, were applied and compared to the official WADA method. More specifically, the following adjustment methods were examined: a. the UFR‐adjustment method developed by Araki et al based on a log‐linear relationship between the UFR and the non‐adjusted concentrations where the slope (referred to as Araki's b slope) is analyte dependent and was established per analyte and study phase; b .…”

“…To examine the reliability and robustness of the routine anti‐doping analysis on the detection sensitivity of BDS and its metabolites under normal and hyperhydration conditions, a clinical trial was conducted, as part of a WADA research grant (10D21CG). In the context of investigating if hyperhydration could influence the excretion and subsequent detection of BDS and its metabolites during doping control analysis by leading to concentrations below the WADA reporting level (30 ng/mL), adjustment of the urinary concentrations was performed applying different adjustment methods . Different hyperhydration agents were examined, that is water and a commercial sports drink.…”

“…In the context of investigating if hyperhydration could influence the excretion and subsequent detection of BDS and its metabolites during doping control analysis by leading to concentrations below the WADA reporting level (30 ng/mL), adjustment of the urinary concentrations was performed applying different adjustment methods. [16][17][18][19][20][21][22] Different hyperhydration agents were examined, that is water and a commercial sports drink.…”

Lipid and Creatinine Adjustment to Evaluate Health Effects of Environmental Exposures

“…Several studies using simulated or NHANES data have compared traditional approaches to those using urine flow rate to calculate biomarker excretion rates (4, 16, 17). In these studies, urine flow rate is estimated by dividing void volume by time since last void and biomarker excretion rate is then computed by multiplying urine flow rate by urinary analyte concentration.…”