Let’s talk about heavy metal toxicity (Cadmium) and your kidney function today

**Taken from the U.S. National Library of Medicine

The heavy metal cadmium (Cd) is known to be a widespread environmental contaminant and a potential toxin that may adversely affect human health. Exposure is largely via the respiratory or gastrointestinal tracts; important non-industrial sources of exposure are cigarette smoke and food (from contaminated soil and water). The kidney is the main organ affected by chronic Cd exposure and toxicity. Cd accumulates in the kidney as a result of its preferential uptake by receptor-mediated endocytosis of freely filtered and metallothionein bound Cd (Cd-MT) in the renal proximal tubule. Internalised Cd-MT is degraded in endosomes and lysosomes, releasing free Cd(2+) into the cytosol, where it can generate reactive oxygen species (ROS) and activate cell death pathways.

An early and sensitive manifestation of chronic Cd renal toxicity, which can be useful in individual and population screening, is impaired reabsorption of low molecular weight proteins (LMWP) (also a receptor-mediated process in the proximal tubule) such as retinol binding protein (RBP). This so-called ‘tubular proteinuria’ is a good index of proximal tubular damage, but it is not usually detected by routine clinical dipstick testing for proteinuria. Continued and heavy Cd exposure can progress to the clinical renal Fanconi syndrome, and ultimately to renal failure.

Environmental Cd exposure may be a significant contributory factor to the development of chronic kidney disease, especially in the presence of other co-morbidities such as diabetes or hypertension; therefore, the sources and environmental impact of Cd, and efforts to limit Cd exposure, justify more attention.

How Cadmium (Cd) exposure can lead to decreased kidney function

Cadmium (Cd) is a toxic metal with a propensity to accumulate in the proximal tubules cells (PTC) of the kidney where it can lead to tubular dysfunction and eventually renal failure. Although Cd(2+)-induced nephrotoxicity has been well described there is still uncertainty about how this metal gains entry into these cells to induce toxicity.

As a non-essential metal, specific transport proteins for Cd are unlikely to exist. Rather transport proteins/channels used by essential metals (iron, zinc, calcium) are thought to be responsible. When these dietary essential metals are in short supply and deficiencies develop, Cd absorption and toxicity are enhanced. This is primarily due to increased expression of essential metal transport proteins such as divalent metal transporter 1 (DMT1) which can transport Cd in the intestine and enhance toxicity in the kidney. The zinc/bicarbonate sympoters ZIP8 and 14 are expressed at the apical membrane of enterocytes and PTC, and can transport Cd into cells. TRPV5 and 6 are major transporters for calcium in intestine and kidney and may be involved in Cd transport in these locations.

Cd in the circulation is bound to proteins such as metallothioneins (MT) which are readily filtered. Two multiligand receptors, megalin and cubulin, reabsorb filtered proteins including albumin and MT by the process of receptor-mediated endocytosis. This review summarises the transport pathways for Cd in the intestine and kidney proximal tubule focusing in particular at how Cd uses essential metal transport processes to gain entry to the circulation and the kidney.

We hope that this important information has helped you to be more informed on heavy metal toxicity. We appreciate your feedback and like to hear your comments.

 

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