Although there has been a considerable reduction in lead exposure over the last few decades, low level exposure is still common, globally. Concerns about chronic low-level lead toxicity are associated with gradual accumulation of the heavy metal in the body. In this blog, we will focus on the effect of lead exposure on kidney health.
Sources of lead exposure
Lead contamination can be due to exposure to various household products, water, soil, and air. Most significant sources of lead include:
- Homes built before 1978 (when lead-based paints were banned) probably contain lead-based paint.
- Water pipes may contain lead (recently we learned about the impact on which can lead to contamination of community water crisis as it has happened in Flint, MI).
- Some toys
- Jewelry
- Cosmetics
- People involved in jobs and hobbies working with stain glass, ceramic glazing, welding and batteries
- Aviation fuel (living near airports may increase risk of exposure in air and soil)
It is estimated that a large population of adults and children in the United States have blood lead levels that are higher than what is considered safe.
How does the body handle lead?
When it enters the GI tract, lead utilizes the iron gates (Divalent metal transporter (DMT1)) in the gut to enter systemic circulation. In the case of mineral deficiency, especially iron deficiency, lead can more easily compete for absorption via DMT1. This is significant, considering the low mineral status of the Standard American Diet (SAD). Furthermore, lead can compete with iron for incorporation into heme by inhibition of an enzyme called 6-aminolevulinic acid dehydratase (ALAD), increasing risk of iron-deficiency anemia.
Lead cannot be converted by the body, and is either stored in tissue (primarily in bone, replacing calcium) or eliminated (primarily through the kidneys and gut). It can accumulate and remain stored in the bones for decades, and is released into the blood under certain circumstances such as pregnancy, breast-feeding, menopause, weight loss and advancing age.
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How the kidneys handle lead
Lead competes with iron and calcium due to similarities in atomic size. After lead is filtered by the glomeruli, it enters the proximal tubular cells via calcium channels. In fact, lead is 10 times more efficient at utilizing calcium channels than calcium itself. Some of it returns to recirculate in the blood while some is transported back to the tubular lumen through other transporters. This constant exposure causes damage to the tubules and increases oxidative stress by using up glutathione, an antioxidant.
The effect of lead on the kidneys
The kidneys are the major site of elimination for lead and appear to be one of the primary sites of accumulation. Even exposure to small levels of lead early in life can lead to glomerular hypertrophy and may disrupt glomerular development leading to renal insufficiency later in life.
However, the majority of lead toxicity in the kidneys is due to its effects on the tubules. Chronic exposure has been shown to lead to progressive tubulointerstitial nephritis including inflammation, fibrosis, and atrophy. The mechanism involves oxidative stress, mitochondrial injury, and acting as a functional substitute to calcium and increasing unchecked activity of protein kinase C. Lead can also replace calcium in the cellular tight junctions compromising its integrity. Finally, lead decreases the ability of the tubules to eliminate uric acid.
Collectively, these lead to the classic triad of lead exposure which includes progressive kidney disease, elevated blood pressure, and gout.
Nutrients and lead exposure
It makes sense now to understand that a deficiency in iron and calcium can lead to an increase in lead toxicity. It has been documented that the absorption of lead in the gut is actually inversely proportional to dietary levels of calcium. Studies in children demonstrated a relationship between dietary calcium and blood levels of lead by linking a low dietary intake of calcium to higher lead levels. Indeed, increasing dietary calcium intake has been shown to decrease blood levels of lead.
Genetics and lead exposure
Genetic mutations in iron and calcium metabolism can greatly impact lead toxicity. In fact, genetic mutations in the gene coding for ALAD have been shown to affect blood and bone lead levels. In addition, polymorphisms in the gene for vitamin D receptor (VDR) was found to influence the accumulation of lead in bone. VDR is involved in calcium absorption from the gut and its placement in bone. Finally, variations in the hemochromatosis gene that codes for the HFE protein associated with iron absorption can also increase risk of lead absorption. These genetic variations can increase an individual’s susceptibility to lead toxicity even from relatively low-level exposure. In other words, what may be a “safe”exposure level to one person may be a toxic level to another depending on genetic variables especially when combined with other lifestyle or occupational factors.
The microbiome and lead exposure
Metabolomics is the study of the substrates and byproducts of metabolism of various microbes found in the body and their impact on the system. Studies in this emerging field have demonstrated that exposure to lead causes alterations in gut microbiome diversity and metabolic functions. These changes are responsible for the development of obesity when exposure to lead occurs in early childhood. Some of these changes are mediated through epigenetics.
On the other hand, there is some evidence that preexisting depletions in the diversity and quantity of the gut microbiome increases the risk for lead toxicity. This may be independent or further complicated by the impact of dysbiosis on digestion, especially on calcium and iron absorption.
Neutralizing lead exposure
There are medications that are used to chelate lead including calcium disodium edetate (EDTA) which can be used for assessing body stores of lead and for treatment. Interestingly, calcium channel blockers such as verapamil have been found to protect the kidneys against the effects of lead toxicity.
Curcumin has been found to protect kidney cells from the oxidative stress of lead toxicity.
In addition, baicalin, a traditional Chinese herb, has been found to protect the kidneys in a similar manner.
Therapeutic treatment of iron or calcium deficiency can also be effective in reducing lead absorption. Therefore, monitoring mineral levels and supplementation might be a useful approach in management of these cases.
Protecting the body from lead
There are ways to protect the body from the negative effects of heavy metals, including lead. Incorporating therapeutic foods on a regular basis such as cilantro, blueberries, garlic, ginger, onion, green tea, and tomato supplies the body with vitamins, minerals, and nutrients that decrease the risk of lead toxicity. Certain essential metals and vitamins (zinc, calcium, iron, selenium, magnesium, vitamin C, B1 and B6) may be supplemented to provide protection and boost antioxidant levels. Other practices that help the body with detox are exercise, sweating, dry brushing, drinking enough water, and lymphatic massage. Correcting nutrient deficiencies through food and supplements, as well as incorporating routine detox practices, is key to prevent lead absorption and safely remove it from the body, especially in those at high-risk of exposure.
The Bottom Line
Lead exposure remains a global public health issue. Even low levels of lead exposure have been associated with decreased kidney function. In addition to addressing possible sources of exposure, an integrative medicine approach to lead toxicity should use appropriate nutritional evaluations and interventions, as well as biotransformation and antioxidant support to help decrease the impact of toxicity and the risk of chronic kidney disease.
The post Lead Exposure and Kidney Health appeared first on Integrative Kidney.]]>
It has been suggested that it could be due to agricultural chemicals, heavy metal exposure, silica inhalation, infectious diseases, genetic predisposition. Many of these workers regularly work in hot conditions for long hours. More recently, they identified repeated heat stress as a cause and a risk factor for kidney disease.
There is no doubt that the prevalence of kidney disease is rising in the United States (US) and throughout the world. In fact, one in seven people in the US has kidney disease. It is one of the fastest growing causes of death throughout the globe. An estimated 5–10 million people die annually from kidney disease worldwide. Unfortunately, due to poor data, lack of awareness, early detection and access to care these numbers could underestimate the exact burden of kidney disease in the world.
Chronic Kidney Disease of Unknown Origin (CKDu)
The type of chronic kidney disease that affected the agricultural workers in Central America is now called chronic kidney disease of unknown origin (or CKDu). Since the nineties, CKDu has been identified in studies of similar etiologies in Siri Lanka, India, Africa, South America and the Middle East. The common thread is the hot and humid climate.
CKDu does not follow the conventional risk factors for kidney disease and, therefore, it’s challenging to detect early and prevent. It disproportionately impacts areas with underprivileged communities and poor infrastructure. However, it would be a mistake to assume that this problem is limited to developing countries. Acute kidney injury has been reported in agricultural workers exposed to hot conditions in California and Florida.
Primary Impact: Global Temperature & Kidney Injury
It has been documented that global temperature have increased by about 1 degree centigrade (1.8 degrees Fahrenheit) in the past 50-100 years. Scientists agree that these changes have contributed with record heat waves, melting ice caps and rising sea levels, and extreme weather patterns. This pattern is posing significant health risks, some directly and some indirectly.
According to a United Nations report, climate change is expected to exacerbate health problems that already pose a major burden to vulnerable populations including children and the elderly. Climate change has been associated with a rise in many infectious diseases, especially water-borne illnesses like cholera, typhoid, and dysentery. It is also expected to contribute to the chronic disease burden and bring on new health epidemics. Not surprisingly, CKDu is one of these health issues.
Secondary Impact: Kidney Disease, Pollution, Water & Food Security
So how does rising temperature affect kidney health? The evidence points to heat stress and dehydration can result in chronic kidney disease as playing an important role in the epidemic of CKD worldwide. In fact, the progression of kidney injury has been found to worsen with rising core body temperature.
The mechanism seems to be linked with a decrease in adenosine triphosphate (ATP) levels and reduced mitochondria. These energy powerhouses are particularly abundant in the kidneys, and with reduced ATP and mitochondria, oxidative stress and cellular damage increases. Combine that with a diet with low nutrient-density and inadequate antioxidant content to neutralize oxidative stress, and risk of CKD significantly elevates. In laboratory studies, the supplementation of antioxidants prevented rats who were exposed to heat stress from developing kidney injury.
Furthermore, heat has been associated with increased risk of kidney stones and kidney stones are known risk factors for kidney disease. Since the kidneys are major site for the metabolism and elimination of toxins, exposure to toxins such as glyphosate contributes to kidney injury due to oxidative damage. Glyphosate in particular also impacts dysbiosis and gut health, which may be a confounding factor in the equation when we consider the gut-kidney connection.
As droughts become a more frequent occurrence as a consequence of climate change, dehydration from heat exposure and inadequate water consumption can lead to concentration of these toxins and, therefore, amplification of their negative effects.
Another factor to consider is the increase of pollution like heavy metal, plastics, and chemicals like pesticides and herbicides. Contamination of air and soil with pollutants increases inhalation and ingestion through food, including rise of mercury contamination in fish and arsenic in rice for example. These toxins have been associated with the rise in incidence of KDas well as other chronic diseases like diabetes and hypertension.
Last but not least, as climate change impacts food security and farming practices, access to fresh food and produce might be compromised. This may shift consumption to processed foods with less nutrient value, including less vitamins, minerals, phytonutrients, and antioxidants needed to promote healthy kidneys. Increased consumption of processed foods also leads to reduced fiber consumption, which impacts gut health and the microbiome which might be the most significant factor as we’ve discussed in our blog on the gut-kidney connection.
Other Considerations
It may sound like a cliché, but hydration is key. For those in labor industries or who work in agriculture or at increased risk of extended heat and chemical exposure, extra effort should be made to adequately hydrate. Broader public health measure and policy should be put in place to improve worker safety.
The risk increases for those taking medications that:
· Increases risk for dehydration, including diuretics (furosemide, hydrochlorothiazide, etc) or SGLT-2 inhibitors (canagliflozin, dapagliflozin, etc), or
· Decreases circulation to the kidneys, including ACE inhibitors (lisinopril, captopril, etc), angiotensin receptor antagonists (ARBS like losartan, Olmesartan, etc). However, as we mentioned earlier, heat lead to energy depletion in the kidneys and supplementing with antioxidants may further decrease the risk of kidney injury due to extreme heat.
Bottom Line
Rising global temperatures are posing increasing risk for kidney disease and contributing to a worldwide rise in chronic kidney disease. Extended exposure to heat and dehydration can lead to kidney injury and kidney stones. Improved hydration, improved nutrient-density diet, and use of antioxidants maybe be preventive. Other confounding factors cannot be ignored, including increased environmental pollution, factors that impact on gut health, and medications. Although individuals can take steps to reduce our carbon footprint, but broad public health measures must advocate for policy changes that reduce contributions to climate change and the resulting global health impacts.
The post Impact of Climate Change on Kidney Health appeared first on Integrative Kidney.]]>By Majd Isreb, MD, FACP, FASN, IFMCP
Exposure to Arsenic has been associated with increased risk for cancer and it is also linked to kidney disease. In this blog we discuss the sources of arsenic exposure, how our body handle arsenic, its effects on the kidneys, and the genetic and epigenetics of arsenic.
Sources of exposure
Drinking water appears to be the greatest source of arsenic exposure worldwide. In addition, exposure from ingested foods comes from food crops grown in arsenic-contaminated soil or irrigated with arsenic-contaminated water. Even if the water you drink is filtered and does not have arsenic, it is possible that the food that you eat is contaminated with arsenic, particularly rice. Arsenic is also found in high concentrations in cigarettes.
Even if the water you drink is filtered and does not have arsenic, it is possible that the food that you eat is contaminated with arsenic, particularly rice
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Found naturally in the environment, arsenic is mobile and cannot be destroyed. When arsenic compounds interact with oxygen or other molecules or bacteria it changes into different forms that can dissolve in water. Cosmetics and personal care products are another often overlooked major source of exposure.
How our body detoxifies arsenic
After ingestion or exposure, arsenic is metabolized and detoxified by a process called methylation. An enzyme called arsenic methyltransferase (AS3MT) adds a methyl groups to arsenic compounds to help neutralize it and eliminate it. This enzyme has been detected in human liver, kidney, bladder, heart, lung, testes and adrenal glands. Glutathione, known as the master antioxidant also plays a key role in arsenic detoxification.
The various arsenic forms bind to glutathione. The compound arsenic-glutathione can easily exit the cells and circulate in the blood. The glutathione-bound arsenic compound can be excreted by the kidneys or in the bile. The kidneys are the major site of elimination of arsenic and they are, therefore, highly exposed to it. Arsenic can also accumulate in the kidneys. Many transporters have been implicated in arsenic excretion in the tubules portion of the filtering units of the kidneys (the nephron). Inhibition or genetic changes in these transporters can lead to enhanced arsenic toxicity.
The kidneys are the major site of elimination of arsenic and they are, therefore, highly exposed to it. Arsenic can also accumulate in the kidneys.
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Interestingly, the water channel, aquaporin 3, has been found to increase the uptake of arsenic in the kidneys. These channels play a crucial role in water handling by the kidneys. They help our body preserve water. Increasing water intake decrease the incorporation of these channels to the cells of the tubules in the kidneys. Therefore, increasing filtered water intake can help decreasing the kidney exposure to arsenic.
Finally, a transporter called multidrug resistance transport protein 2 (MRP2) transport arsenic-glutathione complexes and excrete them out of kidney cells into the urine. Studies show that the increase in the production of glutathione and MRP-2 increase the body’s ability to detoxify arsenic. Selenium is important for this process and selenium deficiency can enhance arsenic toxicity.
Selenium and zinc deficiencies can enhance arsenic toxicity.
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Arsenic effects on the kidneys
Acute exposure of the kidneys to toxic levels of arsenic leads to inflammation in the tubules of the kidneys. This can lead to protein loss in the urine. It can also lead to elevated calcium levels in the blood. Arsenic exposure activates cell growth can lead to cancer. Arsenic can also lead to oxidative stress and cellular injury. Arjunolic acid (an anti-oxidant which is present in fruit specially guava) was found to decrease the toxicity of the arsenic on the kidneys. Zinc is also protective. Chronic exposure can lead to high blood pressure, protein loss in the urine, and chronic kidney disease.
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Genetics and Genomics Impact on Arsenic Toxicity
You can now see that various processes are involved in the handling of arsenic by the body from detoxification to transport to elimination. Genetic variants of any of these steps can either be protective or can increase arsenic toxicity. For example, a single nucleotide polymorphism (SNP), or genetic mutation, that increases glutathione production can be protective since glutathione helps to eliminate arsenic safely. However, a SNP in the gene that codes for MRP2 may potentially decrease arsenic excretion leading to increased toxicity.
Arsenic accumulation and toxicity can lead to oxidative DNA damage. It also inhibits DNA repair. This explains the increased risk for cancer after exposure to arsenic. Chronic exposure to even small concentrations of arsenic can have synergistic effect on other factors that can cause cancer such as UV light and smoking.
Arsenic exposure can cause indirect DNA damage through processes of DNA methylation and histone acetylation. These altered epigenetic expressions have been linked to kidney inflammation and damage. More recently, it was noted that long term exposure to low level of arsenic (below what is considered safe by the EPA guidelines) were associated with epigenetic changes that caused kidney scarring.
it was noted that long term exposure to low level of arsenic (below what is considered safe by the EPA guidelines) were associated with epigenetic changes that caused kidney scarring.
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The Bottom Line
Most arsenic exposure is due to drinking and showering with unfiltered water. Arsenic exposure leads to extensive cellular damage which increases the risk for cancer and kidney disease. Nutritional deficiencies can enhance its toxicity, but you can take steps to reduce your risks.
- Choose a home filtration device that effectively removes heavy metals, including arsenic. Not all consumer filters will remove arsenic, consider upgrading to Clearly filtered, Multipure and Aquasauna water filter systems.
- Always choose organic produce whenever possible, However, when it comes to rice and teas – organic isn’t enough. Look for products that screen for arsenic levels.
- Antioxidants are protective against arsenic 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.
- Load up on fiber and mineral-rich root veggies, which help trap and eliminate toxins through your digestive system.
- There are several lifestyle modifications that can support improved detoxification, including Epsom-salt baths, sauna, lymphatic massage, sweat-inducing workouts, and dry brushing.
- If like many Americans you’re not having consistent daily bowel movements, you’re not adequately detoxifying and should consider working with a healthcare provider to address your digestion and motility.
Foot Note:
There are different forms of arsenic compounds. There are organic and inorganic forms with different oxidation states. The inorganic forms are easier to absorb by the gut and, therefore, are more hazardous. The most commonly ingested inorganic compounds are the trivalent and the pentavalent forms (depending on the level of oxidation). The trivalent forms appear to be the most toxic.
The post Arsenic and Kidney Health appeared first on Integrative Kidney.]]>By Majd Isreb, MD, FACP, FASN, IFMCP
Sources of Exposure
The impact of environmental exposure to these chemicals is increasingly recognized. In the past, the focus was on heavy metals such as lead and cadmium. The major risk to kidney health was job-related exposure. More recently, emerging research is proving that the general public is also at risk for exposure to a wide range of chemicals as a consequence of normal daily activities.
The activities that increase exposure to chemicals that negatively impact kidney health include:
- Dietary intake of food or drink, such as contamination of drinking water with these chemicals
- Domestic and commercial food preparation due to food additives
- Textile and household maintenance procedures as in preparing furniture with flame retardants
- Routine medical and dental care can be associated with exposure to toxic chemicals, for example, implants or dental fillings
The increase in environmental pollution, a result of accelerated urbanization worldwide, has become a global public health challenge.
Persistent Organic Pollutants (POP) and Kidney Health
Recently, POPs have been detected on military bases, as well as in public water supplies from industrial contamination and in agricultural and crop products. Exposure to POP has been linked to cancer including cancer of the kidney. There is also mounting evidence that POPs contribute to kidney disease. The kidneys are very sensitive organs. Studies demonstrated that the kidneys are the major site of elimination of these substances which makes them vulnerable to their negative effects.
In fact, studies point to PFAS as contributing directly to the worsening of kidney function. They can also indirectly lead to changes in human metabolism, which can lead to kidney disease.
Toxicology studies show that the tubules of the kidneys are the most affected (see our blog about the nephron). When part of the kidneys is affected, their function is reduced. This leads to a further buildup of these chemicals increasing their toxicity on the body and the kidneys. This creates a vicious cycle that amplifies the effect of toxic exposure. What is most concerning is that children and adolescents are and will be more exposed to these substances throughout their life span.
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The Role of Genetics
Our bodies detoxify foreign chemicals in the liver via specific processes and they are eliminated in the kidney by other routes. The failure of these processes of detoxification and elimination may lead to greater toxicity of POPs. Genetics, epigenetics, or minor changes in the detoxification processes can have a significant impact on kidney health. Therefore, a normal exposure level for one person may be toxic for another, especially in the long term. Therefore, checking for genetic abnormalities is a crucial element in identifying the risk of exposure.
Therefore, a normal exposure level for one person may be toxic for another, especially in the long term
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Heavy Metals
For years, kidney doctors (nephrologists) have known that heavy metals can impact kidney health. The most well-known of these include Arsenic, Lead, and Cadmium.
Arsenic is used in the pressure treatment of wood. It can lead to structural changes in the kidneys which can lead to kidney disease. Contamination of drinking water, soil, and rice with arsenic has been linked to hypertension and kidney injury leading to kidney disease.
Cadmium is used in batteries, pigments, coatings, and plastics. It has also been used in phosphate fertilizers and can lead to soil and water contamination with subsequent accumulation in plants, particularly root vegetables (carrots, etc.) It can also be found in tobacco cigarettes and inhaled in second-hand smoke. In fact, it is estimated that individuals who smoke one pack of cigarettes each day will absorb 1-2 mcg of cadmium daily. Cadmium exposure leads to the development of diabetes, decreased renal function, increased urine output, and loss of some minerals from the kidneys. It appears that vitamin D and Zinc can protect the kidneys from cadmium.
Lead is used in welding, batteries, and in the production of pottery, glazing of ceramic pots, and water pipes (which can lead to contamination of community water as happened in Flint, MI). Many children are exposed to lead by ingestion of contaminated soil or food and herbs grown in those soils. Sadly, as recently as 2017, a large population of adults and children in the United States have blood lead levels that are higher than what is considered safe. In addition to cognitive delays in children, relatively modest levels of Lead in the body can cause progressive kidney damage, elevated blood pressure, and gout.
Testing for Exposure
Unfortunately, after chronic exposure to these pollutants, our body adapts and stores them in tissues such as fat or bone. So, a simple blood test may not detect these substances. The best analysis to detect them is a provoked urine collection. This requires a physician familiar with carefully provoked urine testing to order a medication that encourages the release of these toxins from storage so that they can be collected in your urine. If you suspect you are exposed ask your Integrative or Functional Medicine nephrologist to test you.
References
- John W. Stanifer, et al. Perfluorinated Chemicals as Emerging Environmental Threats to Kidney Health. Clin. J. Am. Soc. Nephrol. 2018. 13:1479-1492
- Sarah E. Orr, Christy C. Bridges. Chronic Kidney Disease and Exposure to Nephrotoxic Metals. Int. J. Mol. Sci. 2017. 18, 1039