Influence of biological and analytical variation on urine measurements for monitoring exposure to cadmium.

Abstract

Objective-To define the mean intraindividual biological variation in urinary concentrations of cadmium and retinol binding protein (RBP) in untimed, random urine samples and the influence of creatinine or specific gravity correction on reducing this variation. The relation between biological variation and analytical variation in defining uncertainty in a single measurement and significant differences between successive measurements was explored. Methods-Repeat measurement study in subjects with either high historical exposure to cadmium but without current exposure, or unexposed volunteers. Standard statistical tools used in clinical laboratory medicine were applied to define intraindividual biological and analytical variation. Results and conclusion-Both creatinine and specific gravity correction of urinary cadmium measurements in random urine samples seem to reduce the intraindividual variability compared with uncorrected values. With a standard definition, acceptable long term analytical precision for measurements of cadmium and RBP combined with creatinine analyses should be <9% and <15% respectively. The mean intraindividual biological variation of cadmium and RBP, expressed as creatinine corrected, was 18% and 40% respectively in the subjects exposed to cadmium. With the analytical precision used, significant diVerences (p<0.05) between consecutive measurements for creatinine corrected urinary cadmium and RBP would need to show changes of >54% and >110% respectively. The relation between significant diVerences in consecutive results and diVerences in the analytical precision of the method used to measure the samples is described. (Occup Environ Med 1998;55:132-137)

Effects of aging on cadmium and tubular dysfunction markers in urine from adult women in non-polluted areas

“…Although it has been a common practice in Cd epidemiology (World Health Organization 1996; American Conference of Governmental Industrial Hygienists 2003) to correct urinary analyte concentration by CR concentration; Berlin et al (1985), for example, did not find any advantage of CR correction over the use of observed values, although Mason et al (1998) observed that CR correction might reduce intra-individual variation when multiple samples were collected from the same individuals.…”

Biological variations in cadmium, α1-microglobulin, β2-microglobulin and N-acetyl-β-d-glucosaminidase in adult women in a non-polluted area

“…Nevertheless, biological variation of urinary Cd as a Cd exposure marker, separately from possible analytical problems (such as instrument-dependent bias; Zhang et al 1997), has been calling attention of several researchers (Arisawa et al 1997;Mason et al 1998;Ikeda et al 2005). This study group also has reported wide variation in Cd-U (Yamagami et al 2006), assumedly due to seasonal changes in types of foods consumed (Kruzynski 2004;Bragigand et al 2004).…”

Urinary cadmium, osteopenia, and osteoporosis in the US population

“…During the physical examination, a 10-ml specimen of urine was collected as a "spot" or untimed sample in a container previously screened for cadmium. Studies of timed urine specimens indicate that urinary cadmium levels do not show significant diurnal variation [10] and that urinary cadmium in spot specimens correlates well with urinary cadmium levels in 12-and 24-h specimens [11]. Urinary cadmium was measured by Zeeman effect graphite furnace atomic absorption spectrometry [12] to adjust for variation in urine concentration.…”