According to the CDC, 1 in every seven people in the US has CKD. The majority of risk factors for CKD are related to lifestyle factors. Exposure to environmental chemicals and toxins is associated with the development and progression of kidney disease. Here, we will focus on cadmium and kidney disease.
Cadmium is naturally occurring in the environment as a pollutant derived from agricultural and industrial sources. Long-term exposure to cadmium leads to many adverse outcomes such as cancer and organ toxicity.
Cadmium and kidney disease
By Majd Isreb, MD, FACP, FASN, IFMCP
Source of Exposure
Exposure to cadmium mainly occurs through ingesting contaminated food, water, or inhalation. The most significant sources of cadmium exposure include:
- Batteries
- Pigments and coatings
- Plastics
- Phosphate fertilizers
- Tobacco cigarettes
Although there are more toxic chemicals, we are exposed to more cadmium. Phosphate fertilizers, for example, can lead to soil and water contamination with subsequent accumulation in plants, mainly root vegetables (carrots, etc.) Cadmium accumulates in these plants with a half-life of 25-30 years. In addition, it is estimated that individuals who smoke one pack of 20 cigarettes each day will absorb approximately 1–2 µg of Cadmium daily.
How does the body handle cadmium?
Cadmium absorption varies depending on the route of exposure. For example, absorption after inhalation is higher than that from food ingestion. Cadmium concentrations in the blood can be up to four or five times higher in tobacco smokers.
Normal individuals only absorb 6% of ingested cadmium. However, the absorption increases in those with iron deficiency. This is because cadmium uses the same transporter as iron (divalent metal transporter 1, DMT1) which is upregulated with iron deficiency. This also explains why women have higher levels of cadmium than men.
Cadmium has no biological function in the body. Once absorbed, it binds to metallothionein in the liver. Metallothioneinsare cysteine-rich, small metal-binding proteins that are present in the cell. They help balance metals such as zinc and copper in the body. They also protect against the toxicity of cadmium and other heavy metals.
The biggest problem with cadmium is its long half-life of 20-40 years. This is likely due to its incorporation into the bone.
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How the kidneys handle cadmium
The human body has no effective way to eliminate cadmium. When cadmium-metallothionein compound reaches the kidneys, it is filtered freely by the glomeruli. The problem is that most of that compound gets reabsorbed by the proximal tubular cells of the nephron. Inside these cells, cadmium is dissociated from metallothionein and reenters the circulation. There are other ways for cadmium to enter the tubular cells. This includes active transport into the tubular cells via the organic cation transporter 2. This makes the proximal tubules the primary site of cadmium-induced kidney injury. The kidneys accumulate 50% of the total body burden of cadmium in chronic exposure.
Testing for exposure
Blood cadmium levels are usually checked in cases of acute ingestion and toxicity. However, we are primarily concerned with chronic low-level exposure to cadmium. For that purpose, measuring urinary cadmium reflect the total body burden and long-term exposure. The level is checked on a single spot urine sample and is reported as a ratio to urinary creatinine. The result is usually expressed as mcg/g. Ideally, there should be no normal urinary cadmium, but according to the CDC,a level of < 0.19 mcg/g s normal. The level increases with age. In patients with CKD, urinary levels may not be reliable and may not reflect long-term exposure.
The effects of cadmium on the kidneys
Indirect
Several studies have shown that chronic exposure to cadmium increases the risk of developing diabetes and the severity of established diabetes. Cadmium appears to increase insulin release, increase insulin resistance, and enhance gluconeogenesis. Cadmium also increases the risk of developing diabetic kidney injury.
Cadmium exposure was associated with higher blood pressure and increased prevalence of hypertension in an analysis of the NHANES study. This is thought to be due to increased renin activity and increased reactivity to vasomotor stimulation.
Finally, cadmium was found to increase the risk for obesity. The presence of cadmium in maternal blood during pregnancy was also associated with the offspring.
Direct
As we saw above, the kidneys are one of the major organs affected by cadmium. The proximal renal tubules are the primary site of that injury. This leads to a decrease in the absorption of some proteins, glucose, amino acids, phosphate, and calcium. This syndrome is called Fanconi syndrome. Beta 2-microglobulin (B2M) is a protein typically reabsorbed in the tubules. The presence of B2M in the urine can be a marker for early cadmium kidney injury. Ultimately, the glomeruli are injured, and kidney function declines.
Even low-level exposure to cadmium increases the risk for chronic kidney disease.
The toxic effects of cadmium on the kidneys can be summarized as follows:
- Decreased kidney function
- Tubular injury (Fanconi’s Syndrome: loss of glucose, amino acids, phosphate, and calcium in the urine)
- Presence of protein in the urine
- Increase risk for kidney stones (due to increased calcium in the urine)
- Decreased activation of vitamin D, which usually occurs in the tubules
- Oxidative stress
- Faster progression of CKD from other causes
Nutrients and cadmium exposure
As mentioned above, iron deficiency increases the risk of cadmium exposure and toxicity. Adequate iron supplementationhas been found to decrease cadmium retention.
In addition, zinc has been found to protect the kidneys from cadmium injury. Zinc competes with cadmium for entry into cells. It has also been found to decrease cadmium-induced apoptosis in kidney cells.
Magnesium was also found to decrease cadmium toxicity. This is thought to be due to competition with cadmium decreasing its uptake by the cells. It stimulates glutathione synthesis and reduces oxidative stress.
Finally, animal studies showed a protective role of selenium against cadmium toxicity in the liver and kidney. The positive effect of selenium is mainly due to the increased activity of antioxidant selenoproteins such as glutathione peroxidase.
Genetics and cadmium exposure
There is not much literature about the role of genetic variation and the risk of cadmium exposure. However, it is conceivable that genetic variants in the metallothionein 2 A gene can be associated with a higher risk of cadmium toxicity. Other candidate genes affecting the risk for cadmium toxicity include the DMT1 gene, glutathione-related genes, and methylenetetrahydrofolate reductase.
The microbiome and cadmium exposure
Cadmium impacts the gut in two ways. On one side, exposure to cadmium causes significant changes to the gut microbiome (increased Bacteroidetes-to-Firmicutes ratio). It also leads to an increase in lipopolysaccharide (LPS) production. On the other side, it produces an inflammatory response, cell damage, and disruption of tight junctions. Cadmium, therefore, leads to increased intestinal permeability (leaky gut). This will lead to systemic inflammation and increase the risk for autoimmune diseases.
Protecting the body from cadmium
Optimizing nutritional status is essential for decreasing cadmium absorption and its effects. Several steps can be taken to reduce exposure to cadmium with its negative impact on kidney health. These include:
- Stop smoking!
- Choose a home filtration device that effectively removes heavy metals, including cadmium. Not all consumer filters will remove cadmium, consider upgrading to Clearly filtered, Multipure, and Aquasauna water filter systems.
- Always choose organic produce whenever possible. Conventionally grown produce fertilized with phosphate fertilizers may contain high levels of cadmium.
- Antioxidants are protective against Cadmium damage, so a diet high in antioxidants like citrus fruit, green tea, blueberries, and dark chocolate will be naturally protective. Enhance detoxification by eating dark leafy greens, cruciferous veggies (like broccoli, kale, and cabbage), and sulforaphane-rich foods like garlic and onion contain high concentrations of nutrients that increase our detoxification capacity.
- Eat a well-balanced plant-dominant diet that contains calcium, iron, magnesium, zinc, and selenium.
- Several lifestyle modifications can support improved detoxification, including Epsom-salt baths, sauna, lymphatic massage, sweat-inducing workouts, and dry brushing.
The bottom line
Most cadmium exposure is due to smoking cigarettes and food ingestion. Cadmium exposure is a huge problem due to its long half-life and kidney concentration. It causes significant kidney damage, especially in the tubules. Nutritional deficiencies can enhance its toxicity, but you can take steps to reduce your risks.
