Blood Cadmium--A Useful Indicator of Dose in Long Term Follow-Up of Previously Cadmium Exposed Workers. L. Järup, C. G. Elinder, and B. Persson; Dept. of Environmental Health, Box 1186, S-172 24, Sundbyberg, Sweden
Cadmium is a well-known environmental and occupational hazard. The critical organs are the kidneys and the first sign of toxicity is a tubular damage with an increased urinary excretion of small proteins. Excessive or prolonged exposure causes more severe renal effects with a pronounced proteinuria and a decrease in the glomerular filtration rate. Dose-response relationships for cadmium and tubular proteinuria are well established. Different dose estimates have been used: cumulative inhaled or ingested amount of cadmium, current or cumulative blood cadmium level and urinary excretion of cadmium. In general, blood cadmium is regarded to mirror mainly present or recent exposure whereas urinary cadmium is said to reflect the kidney or body burden. Therefore, urinary cadmium has been frequently used as a dose estimate. Different indicators of early tubular dysfunction have been suggested: ß2-microglobulin, retinol binding protein and in more recent years also Protein HC (from human complex-forming glycoprotein (= symbol 97 \f "Symbol" \s 101-microglobulin)) and apolipoprotein D. These various compounds are all small serum proteins which are filtered through the glomeruli and reabsorbed by the tubular cells. Monitoring the concentration of these proteins in urine allows an early detection of small reabsorptive defects in the tubuli. Several other markers of nephrotoxicity have also been used, e.g. N-Acetyl-§-D-glucosaminidase (NAG), an enzyme localized in lysosomes of the tubular cells. An increased activity of NAG in urine has been related to persons with cadmium induced tubular dysfunction. We followed-up the tubular function (1993) in 46 workers initially examined in 1984 and heavily exposed to cadmium 1955 to 1978. The aims of the study was to investigate different markers of tubular dysfunction and to evaluate blood cadmium as an estimate of dose after cessation of cadmium exposure. Cadmium in blood (B-Cd) and urine (U-Cd) and the urinary excretion of §2-microglobulin (U-§2), protein HC (symbol 97 \f "Symbol" \s 101-microglobulin) and N-Acetyl-§-D-glucosaminidase (NAG) were determined. Although cadmium exposure ceased in 1978, 40 per cent of the workers showed signs of tubular dysfunction both in 1984 and in 1993. Current B-Cd was the best dose indicator. Dose-response relationships were found for B-Cd and various tubular markers (U-ß2-microglobulin, protein HC and NAG) . Protein HC appeared to be the most sensitive and early indicator of cadmium induced tubular dysfunction. The urinary excretion of cadmium had in average decreased by 48 per cent in individuals with a normal tubular function, by 56 per cent in those with a slight tubular dysfunction and by 62 per cent in workers with a severe tubular damage. We conclude that cadmium induced tubular dysfunction is irreversible and best assessed by analysis of protein HC (symbol 97 \f "Symbol" \s 101-microglobulin) in urine. B-Cd is the best dose estimate several years after cessation of exposure whereas U-Cd is less suitable for dose assessment in follow-up studies of individuals with persistent tubular damage.