Kidney stone formation (urolithiasis) is a complex disease influenced by multiple factors including diet, genetics, and environment. They are painful, inconvenient, and when left untreated, they may contribute to more serious conditions including obstruction and kidney damage.

By Lara Zakaria, PharmD, CNS, CDN, IFMCP

Read more about the etiology and prevalence of kidney stones here.

In this series we’re building a case for a more integrative approach to preventing kidney stone formation.

Conventionally, the treatment approach does address kidney stones via a multi-pronged approach that may include medication, dietary and lifestyle, surgical removal, and using ultrasonic waves to break up stone.

However, these guidelines tend to focus too far downstream, on stone composition instead of on the underlying pathology upstream. Instead, we advocate for a more comprehensive approach that focuses on risk factors to prevent formation. Those factors include:

·       Type of stone

·       Socioeconomic factors

·       Environment

·       Diet

·       Hydration and electrolyte balance

·       Microbiome and gut health

·       Genetics

We covered individual dietary components in detail in a previous blog. Today we’ll look at the gut-kidney stone connection and the impact of the microbiome.

Gut Integrity and Kidney Stones: Leaky Gut

A normal and healthy GI tract has a natural barrier. This barrier serves to protect the GI and has three major jobs: 1. ensure proper digestion and absorption of nutrients and 2. ensure elimination of toxins and 3. protect the integrity of the microbiome – the “good” bacteria that lives in our GI tract and works with our body to maintain health.

Leaky gut describes a state when the cells that make up the lining of the GI tract separate enough to allow the contents of the gut to leak out. This is also sometimes called intestinal permeability or IP for short. This is a problem because it reduces absorption of nutrients, causes toxins to build up, alters the balance of the gut microbiome, and results in systemic inflammation.

One of the major contributors to leaky gut is the standard American diet (SAD), which seems to increase risk of kidney stone formation. When we use the term SAD, we are generally referring to a diet that includes:

·       Consumption of sugary beverages and soda (and high carbohydrate consumption in general)

·       Increased intake of processed/refined foods like cereals, crackers, baked goods, etc…

·       Processed, fried, conventionally raised, high-nitrate animal protein

·       Low intake of fiber and fresh produce in general

·       A “beige” diet (low in phytonutrients and antioxidants) from consuming a variety of colorful fruits and vegetables 

·       Inadequate amounts of healthy, anti-inflammatory fats, and high amounts of refined unhealthy fats

We have already established that eating more fresh produce, is protective from kidney stone formation, and we’ve done a deeper dive on specific nutrition impact on kidney stone risk in another blog if you’d like to learn more.

There are several factors that may contribute to development of leaky gut:

·       “Proinflammatory” SAD: too much processed and high-sugar foods, not enough fiber and the wrong inflammatory fats

·       Food sensitivities: consuming food that are cause reactivity

·       Overconsumption of caffeine and alcohol – irritants to gut lining

·       Use of certain medications, including NSIADs, steroids, antibiotics

·       Stress and poor-quality sleep

We address risk factors for intestinal permeability in more detail in a previous blog here, as well as dive into a comprehensive gut restoration strategy here in this 5-part series. 

The Microbiome and Kidney Stones

Balance of the gut bacteria also play an important role in causing or preventing kidney stones. The most studied organism is Oxalobacter formigenes, which has been found to be protective when present in adequate quantities as part of the GI microflora. This bacterium degrades oxalate in the gut decreasing its absorption and excretion in the urine.

When Oxalobacter was discovered, scientists thought they had pinpointed the key to curing kidney stones. They concluded that simply supplementing this missing species should reduce risk of stone formation in susceptible individuals. It would turn out that the connection wasn’t that simple.  

More recent evidence points to a more complex picture in the connection between microbiome diversity and kidney stone pathology. The emerging research shows increased risk in kidney stone formation in certain susceptible individuals also presented with alterations in normal microbiome and metabolome (metabolic byproducts from microflora) – also termed dysbiosis.

In other words, it’s likely that genetic factors might be “turned on” by dysbiosis leading to increased risk of kidney stone formation in certain individuals. The good news is that means they should be “turned off” when the microbiome balance is restored.

Studies that looked at the use of targeted probiotics have failed to show enough significant improvement of risk of urolithiasis. Although there’s been some limited and temporary reduction in oxalate excretion and kidney stone formation with the use of a combination of Lactobacillus, Bifidobacterium, Enterococcus, it’s been shown to be temporary and limited in benefit. This is because dysbiosis cannot be addressed by simply applying a band aid of a probiotic.

We recommend instead a more comprehensive approach to gut restoration and microbiome balance. You can read more about the 5R protocol in our comprehensive 5-part series on gut restoration. 

The Bottom Line

Although initial findings about the impact of the microflora that looked at Oxalobacter in isolation have not demonstrated significance in reducing incidence of kidney stone formation, more recent evidence pointing to an interplay of factors on microbiome diversity is promising. Furthermore, factors that impact kidney stone formation include dietary factors, including food quality, nutrient composition, and dehydration. Along with environmental factors, lifestyle, genetics, and gut integrity and microbiome balance should be addressed through a comprehensive and personalized approach. Practitioners working with individuals to prevent kidney stone formation should formulate a patient care plan that modifies all relevant components in their integrative approach to maximize effectiveness in preventing urolithiasis.

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.