Cadmium Toxicity

Heavy metals & the kidney are an interesting topic all-around. Aberrant metabolism of heavy metals such as iron, copper, lead all contribute to significant renal pathology. And you can add the heavy metal cadmium to that list as well.

Cadmium toxicity is most notably manifest as renal tubular impairment, specifically in the proximal convoluted tubule, though it may also result in hepatotoxicity and osteoporosis.

Normal cadmium handling begins in the liver, where it binds to the small molecular weight protein metallotheionein. The metallotheionein-cadmium complexes are freely filtered at the glomerulus, then gets taken up at the proximal tubule by pinocytosis. The metallotheionein-cadmium complexes are degraded in lysosomes and excess cadmium is excreted into the tubular lumen via a specific transporter. Large amounts of cadmium can overwhelm this system and lead to proximal tubular damage. Not surprisingly, this results in a Fanconi's Syndrome which can include a proximal (type II) RTA, glucosuria, phosphaturia, and amino aciduria. One of the ways in which subtle proximal tubular damage via cadmium can be monitored is to look for urine b-2 microglobulin levels, which are handled in the PCT via a similar mechanism as metallotheionein.