Urinary Creatinine Concentrations in the U.S. Population: Implications for Urinary Biologic Monitoring Measurements

Abstract

Biologic monitoring (i.e., biomonitoring) is used to assess human exposures to environmental and workplace chemicals. Urinary biomonitoring data typically are adjusted to a constant creatinine concentration to correct for variable dilutions among spot samples. Traditionally, this approach has been used in population groups without much diversity. The inclusion of multiple demographic groups in studies using biomonitoring for exposure assessment has increased the variability in the urinary creatinine levels in these study populations. Our objectives were to document the normal range of urinary creatinine concentrations among various demographic groups, evaluate the impact that variations in creatinine concentrations can have on classifying exposure status of individuals in epidemiologic studies, and recommend an approach using multiple regression to adjust for variations in creatinine in multivariate analyses. We performed a weighted multivariate analysis of urinary creatinine concentrations in 22,245 participants of the Third National Health and Nutrition Examination Survey (1988–1994) and established reference ranges (10th–90th percentiles) for each demographic and age category. Significant predictors of urinary creatinine concentration included age group, sex, race/ethnicity, body mass index, and fat-free mass. Time of day that urine samples were collected made a small but statistically significant difference in creatinine concentrations. For an individual, the creatinine-adjusted concentration of an analyte should be compared with a “reference” range derived from persons in a similar demographic group (e.g., children with children, adults with adults). For multiple regression analysis of population groups, we recommend that the analyte concentration (unadjusted for creatinine) should be included in the analysis with urinary creatinine added as a separate independent variable. This approach allows the urinary analyte concentration to be appropriately adjusted for urinary creatinine and the statistical significance of other variables in the model to be independent of effects of creatinine concentration.

Estimated daily intake of phthalates in occupationally exposed groups

“…Creatinine concentrations in spot urine samples from NHANES III were significantly higher among non-Hispanic blacks as compared with other racial/ethnic groups (Barr et al, 2005); however, race/ethnicity was confounded within sector in our study (Hines et al, 2009). Demographic characteristics such as education, family income, and place of residence have also been associated with concentrations of certain urinary phthalate metabolites in a subset of NHANES III participants (Koo et al, 2002).…”

Associations between IVF outcomes and essential trace elements measured in follicular fluid and urine: a pilot study

“…We evaluated bivariate associations among FF trace elements, demographic factors, and clinical factors using Spearman correlation coefficients, Wilcoxon rank-sum tests, and Kruskal-Wallis tests as appropriate; we previously reported bivariate associations for urine trace elements [23]. To correct for difference in urine dilution among the women, all urine trace element were adjusted for creatinine [24] and are expressed as μg/g creatinine.…”

Pilot study testing a European human biomonitoring framework for biomarkers of chemical exposure in children and their mothers: experiences in the UK

“…Higher cadmium levels were observed in the children who had higher levels of urinary creatinine, although the creatinine levels were within the range recommended by WHO (1996). It may not be appropriate to draw conclusions from this because of the small study number, but it has previously been identified that creatinine adjustment is not always the most (Miklavčič et al 2011) GM geometric mean, P75 75th percentile, P90 90th percentile, P95 95th percentile, min minimum, max maximum appropriate method for cadmium analysis (Barr et al 2005;Pirard et al 2014). The levels of urinary cadmium in the mothers were low and comparable (within 1 μg/L) with the population-based reference values from a UK study (Bevan et al 2013), the Flemish human biomonitoring program (Milieu Gezondheid 2010) and the US NHANES study (Centers for Disease Control and Prevention 2014, and the German Environmental Survey value for non-smoking adults shown in Table 4.…”