Kidney stones are an incredibly painful experience in those who form them. People often compare the passing of kidney stones to peeing glass, which certainly isn’t appealing. But what can we do to reduce our risk of stone formation?
Kidney stones are hard deposits that form in the kidneys. After formation, people pass the stones in their urine, an excruciating experience. Symptoms include:
- Sharp pain in the lower back
- Pain radiating to the abdomen and groin
- Discolored(red, pink, brown) or cloudy urine
- Frequent urination
- Incomplete urination
- Nausea and vomiting
Stone formation is higher in males than females and in older people versus younger people. Men over the age of 60 have the highest prevalence of stone formation at 17.8%, followed by 12.6% in men ages 40-59. Prevalence is lower in women, but it’s also growing more rapidly in women than men. In fact, it’s declining a bit in men.
Lifestyle factors such as obesity, Type 2 diabetes, NAFLD, diet, certain medications and supplements play a role in the formation of stones. Stones typically cause no permanent damage when passed normally. Thus, an effort to increase their passage through increased water intake, alpha blockers, and the use of pain medications provides relief.
However, if the stone becomes lodged somewhere in the urinary tract, surgery becomes necessary to break up the stone.
Types of kidney stones
There are 4 primary types of stones that people form.
- Calcium stones-Most stones formed in the kidneys are calcium oxalate(~80%), though calcium phosphate is also common. Oxalate is a metabolic byproduct created in the liver and gut, but is also found in our diet.
- Uric acid stones-Uric acid is another byproduct of metabolism, formed during purine metabolism. Commonly formed during fluid loss, high protein diets, and in people with metabolic syndrome
- Struvite stones-Formed when there is an infection in the urinary tract
- Cystine stones-Caused by high amounts of cystine in the urine. These stones occur in people with a genetic mutation that affects cystine reabsorption from the kidneys.
Lifestyle is a powerful way to prevent stone formation in the kidneys. Though, it’s important to point out that it will primarily affect the formation of calcium and uric acid stones.
The oxalate we take, and the oxalate we make
There are many different lifestyle approaches to reducing the production of stones in the kidneys. One very common way is the reduction of oxalate in the diet. While this can be effective, it may not be the best option, as we previously discussed in this blog.
Ultimately, we’re not entirely sure that oxalate from diet is the primary contributor to total oxalate exposure. In an otherwise healthy diet, oxalate may contribute up to 40% of urinary oxalate, with the remaining 60% created in the body.
Many of the foods we consume, such as nuts and spinach, contain quite a bit of oxalate. But, we also make oxalate in our liver, and our microbiome also produces oxalate. If dietary oxalate were the primary culprit, vegetarians would have an increased risk of stone formation, but they don’t.
How we deal with oxalate
Muddying the waters further, we have a pretty sophisticated system for dealing with oxalate. Though we can’t metabolize it, we are pretty effective at removing it from the body.
The oxalate in our diet is very poorly absorbed, with lower absorption at high calcium and low fat intakes. Thus, decreasing fat intake or increasing calcium are effective strategies for reducing oxalate absorption from our gut. Taken a step further, high fat and low calcium diets increase dietary oxalate absorption. Increasing magnesium intake also reduces oxalate absorption.
Furthermore, a healthy gut tends to excrete oxalate in the small intestine. This means when cells in the small intestine absorb dietary oxalate, they spit it right back out in to the gut for removal in our feces, rather than into the blood. Unfortunately, leaky gut tends to increase oxalate absorption.
The oxalate we make is mostly made in the liver, and passed primarily in the urine. Our liver makes oxalate from glyoxylate and its precursors, which are elevated in Type 2 diabetics. Microbes in our colon also make oxalate, which gets absorbed from the colon.
Increased oxidative stress increases glyoxylate AND the formation of calcium oxalate. This can happen in the liver, kidneys, as well as other tissues.
Lifestyle factors that promote kidney stones
A recent paper examined the effect of lifestyle factors and the microbiome in kidney stone formers. People who were stone formers tended to:
- Consume less fruit
- Sit more throughout the day
- Have high blood pressure
- Have non-alcoholic fatty liver disease(NAFLD)
In relation to the microbiome, stone formers had:
- Higher diversity
- Fewer bacteria that maintain barrier integrity
- More inflammatory pathways, including lipopolysaccharide(LPS) biosynthesis
- Fewer short chain fatty acid producers
- No difference in Oxalobacter formigenes(An oxalate degrader)
- Higher fecal acetate levels, which led to microbial oxalate synthesis
Interestingly, administration of short chain fatty acids reduced oxalate stone formation by lowering inflammation. This goes along with our stance that problems with oxalate likely have more to do with oxidative stress and inflammation than dietary oxalate intake.
This study also found elevated fecal acetate in stone formers, which associated with greater production of oxalate from the microbiome via Ruminococcaceae bacterium. Though acetate is a short chain fatty acid, SCFAs exert their benefits when absorbed into enterocytes or the blood, not when they remain in feces. SCFAs infused in to the blood of rats decreased stone formation in the kidneys.
Inflammation as a driver of kidney stone formation
Inflammation blocks our ability to absorb SCFAs from the gut and into the blood. The higher prevalence of genes in the microbiome that promote inflammation may impair acetate absorption, leaving more in the colon. Higher fecal acetate may promote the abundance of microbes that produce oxalate.
While the small intestine does a great job of excreting oxalate back into the gut, absorption of oxalate occurs in the colon. Thus, more oxalate produced in the colon leads to a greater oxalate burden in the blood and kidneys. Furthermore, inflammation causes increased intestinal permeability, further increasing oxalate absorption.
SCFAs decrease intestinal permeability in the gut, dependent on absorption by enterocytes. Since inflammation blocks this, SCFAs created in the gut cannot exert this effect, and remain in the feces. Additionally, they cannot get absorbed into the circulation and exert their anti-inflammatory and stone inhibiting effects in the kidney.
LPS is a component of the cell wall of gram-negative bacteria found in the gut. It’s highly inflammatory, and the higher production in stone formers increases inflammation and blocks SCFA absorption from the gut.
In addition, NAFLD presents with higher LPS biosynthesis in the gut and inflammation. This may be the link between NAFLD and the formation of kidney stones. Finally, NAFLD also presents with downregulation of alanine-glyoxylate aminotransferase (AGXT) in the liver. AGXT is the enzyme that detoxifies glyoxylate, preventing conversion to oxalate.
Thus, those with fatty liver disease generate more oxalate in their liver than healthy people, and produce more in their gut.
Improving fatty liver
Decreasing dietary oxalate does not address production of oxalate in the liver or microbiome. Therefore, steps to reduce fatty liver are likely more important than reducing dietary oxalate. This includes:
- Losing weight (~5-10% of your bodyweight)
- Avoiding a Western dietary pattern
- Reducing daily calorie intake
- Eating a Mediterranean diet
- Temporary use of a Very Low-Calorie Ketogenic Diet
- Fixing leaky gut
- Working on circadian rhythms (Covered here)
- Limit alcohol intake
- Regularly exercising
- Correcting Type 2 diabetes
If you have fatty liver disease, a low oxalate diet may be useful to address symptoms early on by reducing total oxalate exposure. However, in those with metabolic diseases such as Type 2 diabetes or NAFLD, long-term use of a low oxalate diet may be more of a diversion.
As a result, fewer symptoms may provide a false sense of security and lead to ambivalence towards addressing NAFLD and Type 2 diabetes. Therefore, improving metabolic health should be the focus of any program to reduce the formation of kidney stones in stone formers with metabolic dysfunction.
Kidney stones can be an incredibly painful and recurring problem for many. Calcium oxalate is the most common form of kidney stone, so reducing the formation of calcium oxalate stones is crucial to preventing stone formation.
Reducing dietary oxalate may help manage the formation of stones in people who experience them. However, we really don’t know how much dietary oxalate contributes to total oxalate exposure in the body.
In a healthy individual, dietary oxalate may contribute more oxalate than endogenous production. But healthy people don’t tend to form stones, likely a product of a healthy liver, normal immune function and low residual inflammation.
In those with NAFLD and Type 2 diabetes, endogenous production likely far outweighs that from diet, and presents with a chronic inflammatory state. In people with metabolic dysfunction, a low oxalate diet is likely insufficient.
Correcting metabolic dysfunction and improving gut health decreases the amount of oxalate created by the liver and microbiome and decreases oxalate absorption. It also decreases inflammation, another driver of stone formation. There are many ways to achieve these goals.
At the end of the day, consuming a diet that leads to weight loss and maintenance of a healthy weight along with preforming regular exercise are the best plans of attack. Though not as easy as removing nuts and spinach from your diet, it’s likely more effective at addressing the root of the problem.