Metallothionein and Other Factors Influencing Cadmium-Induced Kidney Dysfunction: Review and Commentary

Cadmium is widely recognized as an important environmental toxicant that may give rise to kidney dysfunction, bone disease, and cancer in humans and animals. Kidney dysfunction occurs at very low exposures and is often considered as the most sensitive or critical effect. Cadmium exposures of concern occur in many countries. In low- and middle-income countries with small-scale mining, excessive exposure to cadmium and other metals occurs in occupational and environmental settings. This is of particular importance in view of the growing demand for metals in global climate change mitigation. Since the 1970s, the present authors have contributed evidence concerning the role of metallothionein and other factors in influencing the toxicokinetics and toxicity of cadmium, particularly as it relates to the development of adverse effects on kidneys in humans and animals. The findings gave a background to the development of biomarkers employed in epidemiological studies, demonstrating the important role of metallothionein in protection against cadmium-induced kidney dysfunction in humans. Studies in cadmium-exposed population groups demonstrated how biomarkers of kidney dysfunction changed during 8 years after drastic lowering of environmental cadmium exposure. Other epidemiological studies showed the impact of a good zinc status in lowering the prevalence of cadmium-related kidney dysfunction. Increased susceptibility to Cd-induced kidney dysfunction was shown in a population with high exposure to inorganic arsenic when compared with a group with low such exposure. Several national and international organizations have used part of the reviewed information, but the metallothionein-related biomarkers and the interaction effects have not been fully considered. We hope that these data sets will also be included and improve risk assessments and preventive measures.