A causal connection: cadmium damages kidneys and bones. (Science Selections).

Long-term exposure to cadmium has long been suspected of causing kidney and bone damage in humans. Until now, the most common method of assessing the body burden of cadmium has been to measure the presence of cadmium in urine. However, elevated concentrations of cadmium in urine can also be caused by renal dysfunction, and this potentially confounding factor has left open to question any results that imply a direct causal link between cadmium exposure and adverse kidney and bone effects. In this month's issue, researchers from the Karolinska Institute in Sweden led by Tobias Alfven use measurements of cadmium in blood to strengthen the evidence that such a causal link does in fact exist [EHP 110:699-702].

The investigators studied 1,021 residents of two communities in southeastern Sweden with documented cadmium and lead pollution. The pollution was a result of two local factories' production of nickel--cadmium and lead batteries over the course of many decades. The subjects were required to have lived in the area for at least five years between 1910, when battery production began, and 1992. One hundred seventeen of the subjects currently or had previously worked in one of the battery plants and were considered occupationally exposed to the pollutants.

The authors measured blood lead and cadmium concentrations among the subjects, and also looked at the incidence of two conditions. The first, low bone mineral density, is a marker for osteoporosis. The second, tubular proteinuria (an increase in the presence of low-molecular-weight proteins in the urine), is an indication of kidney dysfunction.

The authors found no associations between lead and low bone mineral density or tubular proteinuria. In the case of cadmium, however, the researchers found a clear relationship between blood concentrations and both conditions. That relationship was particularly strong for tubular proteinuria.

Even when the occupationally exposed participants were excluded, the subgroup with the highest blood cadmium concentrations had a fourfold increased risk of having tubular proteinuria, compared with the subgroup with the lowest blood cadmium concentrations. It's also interesting to note that even 15 years after the cessation of exposure, cadmium-exposed workers showed a stronger association between blood cadmium and tubular proteinuria than between urinary cadmium and tubular proteinuria, implying that there may be a dose--response relationship involved.

Like lead, cadmium apparently accumulates in the body, and even after exposure ceases, the concentration in the blood will not decrease to the preexposure level. The authors found that the effect of cadmium on bone mineral density was much more pronounced in older people. In the older group (more than 60 years old), the risk of low bone mineral density for the subgroup with the highest blood cadmium concentrations was almost three times that of the group with the lowest blood cadmium concentrations. Whether this is attributable to bone becoming more sensitive to cadmium as it ages or to the fact that it could take decades for cadmium to affect bone, or to both of these explanations, it's still an alarming relationship.