This blog is the first in a series discussing our integrative approach to kidney stones prevention and management.

Kidney stone, also called nephrolithiasis or urolithiasis, is a complex disease influenced by multiple factors including genetic and environmental factors. Stones are often painful, and left unaddressed can lead to more serious conditions such as obstruction of the urinary tract and permanent damage to the kidneys.

Kidney stones

By Majd Isreb, MD, FACP, FASN, IFMCP

The frequency of kidney stones has been on the rise in the United States (US) according to nationally published data. The National Health and Nutrition Examination Survey (NHANES) has analyzed the health and nutrition status of the general populations for the past 30 years. According to analyses from these publications, the lifetime chance for developing kidney stone in an adult (age 20-74) increased from 3.2% in the 1970’s to 5.2% in the 1980’s. Most recent survey using data between 2007 and 2010 showed that the lifetime chance for kidney stones in an adult is now up to 8.8%. That’s almost a three-fold increase over three decades. 

In addition to the inconvenience and pain associated with kidney stones, they also pose a significant healthcare burden and cost. Patients with kidney stones are likely to present to the emergency department and are often hospitalized for an average of 2-3 days. If patients cannot pass them, they may require surgical intervention. In 2000, the total costs for caring for patients with kidney stones in the US. was estimated at $2.1 billion. Furthermore, it is estimated that the cost of care will rise by $1.24 billion per year by 2030.

Kidney Stones: Types and Formation

There are five major types of kidney stones: calcium oxalate, calcium phosphate, uric acid, struvite (magnesium ammonium phosphate), and cystine. Calcium oxalate is by far the most common, comprising approximately 75% of kidney stones.

Figure 1: Nat Rev Dis Primers. ; 2: 16008. doi:10.1038/nrdp.2016.8.


Calcium oxalate and calcium phosphate stones

Calcium stones are the most common type of kidney stones. They are composed of either calcium oxalate or calcium phosphate compounds. They are formed when calcium binds to oxalate (or phosphate) in the urine. On the other hand, dietary calcium can bind oxalate in the intestine and prevents its absorption through the gut, so there is less in the urine to form stones.

Oxalates are compounds found naturally in certain foods (nuts, spinach, potatoes, tea, and chocolate). In those prone to calcium oxalate formation, eating high amounts of foods rich in oxalates can increase the amount of oxalate in the urine and increase risk of stone formation.

Calcium phosphate stones are less common than calcium oxalate stones. Causes include hyperparathyroidism (when the body produces too much parathyroid hormone), renal tubular acidosis (a kidney condition that causes a buildup of acid in the body), and urinary tract infections. It is important to understand if one of these conditions is behind the formation of calcium phosphate stones.

Inadequate hydration is a major risk factor for these types of stones. Certain medications can also reduce risk of stone formation, including thiazide diuretics (for example, hydrochlorothiazide) reduce calcium levels in the urine available to form stones. Potassium citrate binds to calcium, preventing it from binding to oxalate and phosphate to form stones.

Uric acid stones

Uric acid stones generally form when urine is too acidic, causing otherwise normal levels of uric acid to dissolve into the urine where it may crystallize forming stones. Therefore, by alkalizing the pH of the urine, we can prevent crystal formation.

In these cases, potassium citrate is the most common medication used to manage uric acid stone formation. Another medication, sodium bicarbonate can also be used to alkalinize the urine. 

However, in some individuals, consumption of too much animal protein can actually increase the production of uric acid. In these cases, dietary restriction of animal protein might be necessary to manage excessive uric acid production. Use of allopurinol, a medication that prevents uric acid formation from precursors xanthine and hypoxanthine may also be indicated.

Struvite stones

Struvite stones are composed of magnesium ammonium phosphate, and unlike other stones, form in alkaline urine. Most commonly, these types of stones form due to a bacterial infection that raises the urine pH to alkaline levels. To dissolve these stones, acetohydroxamic acid (AHA) is used to reduce urine pH and ammonia.

Cystine stones (least common kidney stone type)

Cystine stone formation (also called cystinuria) is a relatively uncommon type of stone and the result of a genetic condition. As a result, urinary elevations of the amino acid cystine result in stone formation. Cystine stones can often be managed by improving hydration and maintaining alkaline urinary pH through diet and medication.

The Integrative Approach to Kidney Stones Treatment 

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

There are a few conventional dietary guidelines, but guidelines tend to focus too far downstream, on stone composition, not on the underlying pathology and across risk factors upstream to prevent formation. By understanding the pathology and risk factors involved, we can better understand why some people develop stones, while others do not and effectively reduce the incidence of urolithiasis.

Socioeconomic and Environmental factors that impact the development of kidney stones

Studies of the distribution of kidney stones in the US suggest that geography is an important consideration in risk. For example, individuals who live in southern states, are more likely to have kidney stones than those who live in the North. In fact, inhabitants of the Southeast are nearly twice as likely to have a history of kidney stones as compared to those living in the Northwest. This has earned North Carolina, South Carolina, Georgia, Alabama, Mississippi, and Tennessee the nickname “the stone belt.” 

Incidentally, these states also lead the nation in obesity and the incidence of diabetes. Inhabitants of these states are also more likely to consume a Standard American Diet (SAD) increasing the risk of pH imbalance that can lead to kidney disease and risk of stone formation. 

Another factor to consider is climate. Higher ambient temperature and sunlight index are associated with a higher risk for kidney stones. Also, the incidence of kidney stones is higher in the summer than in the winter. This may in part explain why inhabitants of the warmer states in “the stone belt” have such a high incidence of kidney stone formation. 

Why is this significant? Understanding this disproportionate distribution can help us understand the complexity of kidney stone pathology to better build a better approach. Our integrative approach to prevention and treatment should be sensitive to underlying socioeconomic and environmental contributions as well as factors that reduced access to adequate healthcare and good nutrition. 

Impact of Diet on Kidney Stones

When the subject of urolithiasis and diet comes up, recommendations about the intake of calcium, oxalates, and hydration cannot be avoided. However, the reality is that we should be looking at broader considerations when it comes to the integrative approach to kidney stone prevention.

Consumption of the standard American diet (SAD) seems to increase the risk of kidney stone formation. SAD includes the consumption of sugary beverages and soda, as well as elevated intake of processed foods and animal protein. Interestingly, eating more fresh produce is protective. This is associated with the nutritional benefit, including (but not limited to) foods rich in potassium magnesium, and fiber. Furthermore, taking vitamin D, and good hydration risk were reversed. 

This topic deserves a deeper dive, and we do so in another blog [found here]. 

Genetics and Kidney Stones

There seems to be a familial link when it comes to the development of kidney stones. Recently, genome-wide association studies uncovered several genetic sequence variants (SNPs) that lead to an increased risk of kidney stone development. Single nucleotide polymorphisms (SNPs) have been associated with kidney stones including those found in CLDN14, ALPL, SLC34A1, CASR, VDR, OPN, and TRPV5.

These genes play a role in the way the kidney handles certain vitamins and minerals including vitamin D, calcium, and phosphate. Imbalances of these nutrients are involved in the pathophysiology of stone formation, therefore stands to reason that genetic variations that result in mishandling will increase the risk. There is still a lot more to learn about the contribution of genetic factors to stone formation. However, what we do know is that we can modulate these risks through environmental and dietary modification. 

Microbiome and Kidney Stones

Balance of the gut bacteria also plays 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. 

In addition, dysbiosis in general is linked to kidney stone formation in those people prone to stone formation due to genetic or environmental factors. Therefore (and unsurprisingly), gut health is an important consideration when addressing kidney stones. Antibiotics which negatively alter the gut microbiome, are linked to higher rates of kidney stones. 

More on the contribution of the microbiome on kidney stone formation will be the topic of another blog on the gut-kidney access here

The Bottom Line

Although genetic factors may impact risk of kidney stone formation, environmental, dietary, as well as factors affecting the integrity of the gut microbiome play a large role in turning on those genes and impacting stone formation. Therefore, the integrative approach to addressing kidney stones must account for a combination of all these factors and practitioners should formulate and personalized approach that modifies relevant lifestyle factors.

This blog was written with contributions from Lara Zakaria, RPh MS CNS CDN IFMCP