Normal variability of biomarkers - examined in a "variability biobank"

Abstract

BACKGROUND AND AIM: For most biomarkers there is limited information about normal within-individual (day-to-day or within-day) and between-individual variability. For urine there may be diurnal variability making it important to fix the time of day for sampling. Our aim was to examine normal variability. METHODS: We established a “variability biobank” of blood (plasma, erythrocytes, and whole blood) and urine (six fixed times: first morning, 9:30, 12:00, 14:30, 17:30, 22:00, and 24h excretion) samples from 60 healthy non-smoking participants aged 21-64 years (29 men, 31 women). Blood and urine samples were collected about one week apart. Aliquots are stored frozen (-80°C). Height, weight, estimated glomerular filtration rate are available, as well as flow rate, creatinine, and specific gravity for each urine sample. ICC=between-individual variability/total variability. RESULTS:Up to now we can report 1) ICCs for24h excretion of 22 elements were high (0.75–0.90) for Cd, Co, Hg, Pb, Sn, Se, V, and Zn, moderate (0.35–0.75) for As, Br, Cu, Fe, Li, Mn, Mo, Ni, P, S, U, and W, and low for Cr and Sb (0.35). 2) ICCs for urinary creatinine showed ICC=0.64 for 24h excretion, 0.48 for overnight samples, and 0.23 for all spot samples. 3) For Pb excretion ICCs were 0.81 for 24h urine, 0.71 for overnight, and 0.57 (men) and 0.41 (women) for all spot samples. CONCLUSIONS:Although 24h excretion is the gold standard for urinary biomonitoring, day-to-day- and within-day-variability is high for some elements. The ICC for urinary creatinine depends on the time of day and the excretion is affected by urinary flow rate. Lead in urine has a diurnal variability. The biobank (≥ 20 000 aliquots) is open for researchers to examine normal variability of their favorite biomarker(s). It is especially suitable for analysis of diurnal variation in urine (12 samples per subject) but could also be used for blood biomarker concentrations. KEYWORDS: biomarkers of exposure, methodological study design chemical exposure, heavy metals, exposure assessment