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Variability of urinary cadmium excretion in spot urine samples, first morning voids, and 24 h urine in a healthy non-smoking population: Implications for study design

Abstract

When selecting the least biased exposure surrogate, for example, the concentration of a biomarker in a urine sample, information on variability must be taken into consideration. We used mixed-effects models to estimate the variability and determinants of urinary cadmium (U-Cd) excretion using spot urine samples collected at six fixed times during 2 days about 1 week apart, from 24 healthy non-smokers. The urine samples were analysed for U-Cd, the concentrations were adjusted for dilution, and the excretion rates were calculated. Between-individual variability dominated the total variability for most measures of U-Cd excretion, especially for 24 h urine and first morning samples. The U-Cd excretion showed a circadian rhythm during the day, and time point of sampling was a significant factor in the mixed-effects models, thus a standardised sampling time, such as first morning urine samples, needs to be applied. Gender, urinary flow rate, age, and urinary protein excretions were also significant determinants for U-Cd excretion. The choice of biomarker for U-Cd excretion was found to be more important in individually-based studies of exposure–response relationships than in studies of comparing Cd levels of groups. When planning a study, this variability of U-Cd in spot samples must be acknowledged.

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Acknowledgements

We thank Lena Samuelsson and Caroline Johansson for help with the data collection. For funding, our thanks go to the Graduate School in Environment and Health, a cooperation between the University of Gothenburg, the Chalmers University of Technology, and the Västra Götaland Region, coordinated by the Centre for Environment and Sustainability (GMV).

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Correspondence to Magnus Akerstrom.

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Supplementary Information accompanies the paper on the Journal of Exposure Science and Environmental Epidemiology website

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Akerstrom, M., Barregard, L., Lundh, T. et al. Variability of urinary cadmium excretion in spot urine samples, first morning voids, and 24 h urine in a healthy non-smoking population: Implications for study design. J Expo Sci Environ Epidemiol 24, 171–179 (2014). https://doi.org/10.1038/jes.2013.58

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