Abstract
Assays of urine biomarkers often use urine creatinine to account for urinary dilution, even though creatinine levels are influenced by underlying physiology and muscle catabolism. Urine osmolality—a measure of dissolved particles including ions, glucose, and urea—is thought to provide a more robust marker of urinary dilution but is seldom measured. The relationship between urine osmolality and creatinine is not well understood. We calculated correlation coefficients between urine creatinine and osmolality among 1375 members of a subcohort of the Danish Diet, Cancer, and Health Cohort, and within different subgroups. We used linear regression to relate creatinine with osmolality, and a lasso selection procedure to identify other variables that explain remaining variability in osmolality. Spearman correlation between urine creatinine and osmolality was strong overall (ρ = 0.90; 95% CI: 0.89–0.91) and in most subgroups. Linear regression showed that urine creatinine explained 60% of the variability in urine osmolality, with another 9% explained by urine thallium (Tl), cesium (Cs), and strontium (Sr). Urinary creatinine and osmolality are strongly correlated, although urine Tl, Cs, and Sr might help supplement urine creatinine for purposes of urine dilution adjustment when osmolality is not available.
Highlights
Urine is often used for non-invasive assessment of exposure to many chemicals, including metals, drugs, nutrients, pollutants, and pesticides, both for research purposes and clinical evaluation
Urine creatinine and osmolality levels were similar between the subcohort and the case-cohort study population (Table S1)
Adjusting for variation in urine dilution is critical in understanding urine analyte concentrations in spot urine samples
Summary
Urine is often used for non-invasive assessment of exposure to many chemicals, including metals, drugs, nutrients, pollutants, and pesticides, both for research purposes and clinical evaluation. Analyte concentrations in spot urine samples are generally reported using an adjustment to account for variation in dilution across samples. Urine creatinine is the most commonly used method for standardizing assay results for urinary dilution. Urine creatinine is produced by elimination of serum creatine and creatinine phosphate as a result of muscle metabolic processes [1]. Because creatinine is associated with muscle mass, which can differ across different segments of the population, concerns have been expressed about its validity as an indicator of urine dilution [1,2,3]. Urine osmolality provides a measure of dissolved particles, including chloride, glucose, potassium, sodium, and urea in urine [4], and may be a better measure of urine dilution than urine creatinine because osmolality reflects multiple solutes in the urine
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