Cadmium (Cd) is a toxic heavy metal that can reach high concentrations in industrial areas and/or in foods and soil. The main routes of exposure of the general population are ingestion and inhalation.

The aim of the study is to mimic exposure to concentrations of Cd as might be found in the environment. Mice were exposed to 0, 1, 5, 10, 20 and 100 mg CdCl₂/L in the drinking water for 1, 4, 8, 16 and 23 weeks. Urine samples were taken regularly and protein and glucose content as well as proximal tubular (PT) enzymes were measured. At the end of the exposure time Cd was determined in blood, kidneys and liver. Kidneys were prepared for histological analysis.

Urine protein content significantly increased from 16 weeks on in the highest dose group (p-value < 0.05) compared to the controls, suggesting a tubular or mixed-type proteinuria. Other signs of pt damage (glucosuria, pt enzymes) could not be detected, although more vacuoles and lysosomes were present in the proximal tubule cells with increasing time and dose. Kidney cortex cd content increased linearly with time and dose, leading to a maximal value of 56 ± 10.5 mg (n = 4 mice) cd/g tissue. Blood and liver levels reached a plateau level at 8 (56 ± 15.2 mg cd/l; n = 4), respectively 16 weeks (21 ± 6.0 mg cd/g tissue; n = 8) for the highest dose group, where after both started to decrease.

Animals were arranged according to the amount of Cd taken in (volume of water drunk times Cd concentration). A multivariate regression model was applied to the data. The total amount of cadmium consumed was fixed at the quartiles, and the Cd content in blood, liver or kidney of animals within these quartiles was plotted as a function of exposure time. We see a decreasing trend for blood, indicating that blood is an indicator of acute exposure only. A similar trend is seen in the liver. Kidney Cd content in animals of the same quartile is constant over time, clearly indicating that the cadmium content in the kidney is a good and reliable indicator of the total amount of cadmium taken up.

The results indicate that chronic exposure to low doses of Cd induces functional and histological signs of early kidney damage, even if the kidney Cd accumulation did not yet reach the generally accepted toxic lower limit of 200 mg/g tissue.