EARLY MARKERS OF NEPHROTOXICITY - VARIATI ON FACTORS AND REPRODUCIBILITY

Epidemiological validity of early markers of nephrotoxicity currently used in occupational epidemiology has been poorly investigated The aim of this study was to identify variation factors of these markers, to quantify their intra- and inter-individual variability and to evaluate the consequences of these results on study size and power. A cross-se ctional survey was carried our in 1991 in a rotogravure plant includin g 168 male subjects (92 exposed to toluene and 76 controls). Blood and urine samples were taken twice : at study onset and one to five month s later for 40% of the subjects. Creatinine and beta-2-microglobulin ( beta 2M) were measured in both blood and urine ; microalbumin (mu ALB) , N-acetyl-beta-D-glucosaminidase (NAG), and alanine-aminopeptidase (A AP), in urine. Sources of physiological variation were reduced by stan dardization of collection and assay methods. Subjects completed a ques tionnaire to record information about their personal caracteristics, a lcohol, tobacco and drug consumption and their health. Statistical ana lysis of all subjects was adjusted for exposure status. Several factor s were significantly related to the markers : age with beta 2M, NAG an d AAP; smoking, alcohol drinking, and blood pressure with both mu ALB and NAG ; urinary pH with beta 2M. These factors explained from 13 to 21% of the total variance of these markers. Short-term reproducibility , i.e. the correlation between the two measurements, was high for mu A LB (r = 0.75), moderate for NAG (r = 0.51), and low for beta 2M (r = 0 .33) and AAP (r = 0.17). These results showed that confusion bias in t he evaluation of exposure-marker association can be reduced by adjusti ng for several factors and that accuracy and study power can be improv ed by repeating measurements, especially for beta 2M and AAP.