A comparative assessment of dilution correction methods for spot urinary analyte concentrations in a UK population exposed to arsenic in drinking water

Abstract

Spot urinary concentrations of environmental exposure biomarkers require correction for dilution. There is no consensus on the most appropriate method, with creatinine used by default despite lacking theoretical robustness. We comparatively assessed the efficacy of creatinine; specific gravity (SG); osmolality and modifications of all three for dilution correcting urinary arsenic. For 202 participants with urinary arsenic, creatinine, osmolality and SG measurements paired to drinking water As, we compared the performance corrections against two independent criteria: primarily, (A) correlations of corrected urinary As and the dilution measurements used to correct them - weak correlations indicating good performance and (B) correlations of corrected urinary As and drinking water As - strong correlations indicating good performance. More than a third of variation in spot urinary As concentrations was attributable to dilution. Conventional SG and osmolality correction removed significant dilution variation from As concentrations, whereas conventional creatinine over-corrected, and modifications of all three removed measurable dilution variation. Modified creatinine and both methods of SG and osmolality generated stronger correlations of urinary and drinking water As concentrations than conventional creatinine, which gave weaker correlations than uncorrected values. A disparity in optima between performance criteria was observed, with much smaller improvements possible for Criterion B relative to A. Conventional corrections – particularly creatinine - limit the utility spot urine samples, whereas a modified technique outlined here may allow substantial improvement and can be readily retrospectively applied to existing datasets. More studies are needed to optimize urinary dilution correction methods. Covariates of urinary dilution measurements still warrant consideration.

Relationship between Urine Creatinine and Urine Osmolality in Spot Samples among Men and Women in the Danish Diet Cancer and Health Cohort

“…In our case-cohort studies, we did not observe strong differences in hazard ratio estimates after adjustment for creatine versus osmolality [19,20]. Two other studies showed osmolality adjustment to be superior to creatinine adjustment in associations with predictors of exposure or urinary flow rate [17,18], in line with the presupposition that osmolality may be less susceptible to underlying physiology or pathophysiology, such as differences in muscle catabolism, in comparison with creatinine. Nonetheless, both measures appear to be influenced by BMI, sex, and other covariates (results not shown), suggesting that covariate-adjusted standardization, which has been proposed for creatinine [21], may also be useful when correcting urinary biomarker concentrations for osmolality.…”

“…A few recent studies compared the impact of different methods of dilution adjustment on exposure estimates or disease outcomes [16][17][18][19][20]. One study showed no difference in associations between creatinine adjustment and osmolality adjustment using metabolomic data in a small study of 51 samples [16].…”

Environmental and human iodine and selenium status: lessons from Gilgit-Baltistan, North-East Pakistan

“…In the context of this study, corrections with creatinine may be questionable due to the prevalence of malnutrition, with low protein intake within the Pakistani population (Aziz & Hosain, 2014;GoP/UNICEF, 2018). By contrast, correction with specific gravity may be a more reliable approach as it is also considered a proxy for osmolality-the most reliable approach for urinary dilution correction (Middleton et al, 2018(Middleton et al, , 2019Watts et al, 2019). However, there are limited data available on, or discussion about, utilising alternative correction methods to creatinine.…”

Machine Learning for Investigation on Endocrine-Disrupting Chemicals with Gestational Age and Delivery Time in a Longitudinal Cohort

“…However, our study has its limitations. The concentration of compounds in the urine may be affected by urine volume; the specific gravity (SG) of urine samples has been employed to reduce the urinary dilution effect [ 39 ]. Meanwhile, some individual EDCs interacting with the endocrine system were not included in this study, such as polybrominated diphenyl ethers (PBDE) [ 40 ], polychlorinated biphenyls [ 41 ], and perfluorooctane sulfonate (PFOS) [ 42 ].…”