Observed genes

Polygenic score

Influential genes: ALPL,SLC22A2,RGS14

Variants in the ALPL gene can potentially affect the body's metabolism of phosphate-containing compounds and contribute to the development of kidney stones.

The gene SLC22A2 encodes a protein involved in the transport of organic ions in the kidneys. Variations in this gene could potentially impact kidney function, which might also influence the risk of kidney stones.

A study conducted on the Chinese Han population found that genetic polymorphisms in the RGS14 gene were significantly associated with renal stone disease (RSD).

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Overview

Kidney stones are hard deposits made from minerals and salts in the urine that can cause an obstruction of the kidney as well as any other part of the urinary system. Usually, there are many waste products dissolved in the urine, but if the amount increases above the physiological value, due to many reasons (such as diet, not drinking enough water, excessive body weight, certain medical conditions, or medications), crystals begin to form. The formation is facilitated by states of dehydration. Most of those crystals get excreted via the urinary system and don't cause any problems, but they can form bigger structures over time. The passage of those stones begins to be problematic and patients can experience severe pain, often described as the worst pain one can feel. The chance of a 1 cm stone passing is around 10% and stones over 1 cm usually don't pass at all. If the passage isn't possible anymore, the stones can obstruct any part of the urinary system and restrict urine elimination, which can lead to the development of infections and other complications. When the excretion of the stones isn't possible naturally, even with medical help, intervention is inevitable. 

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Prevalence & Risk factors

Kidney stones are a very common health condition affecting almost 15% of the world's population and the numbers continue to increase. It's estimated that half of the patients dealing with kidney stones will experience them again in the next 5 years.^[1]

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There are many risk factors for the development of the disease: 

• Dehydration (caused by insufficient water income or excessive sweating) is the number one cause of kidney stones.
• Obesity
• Quick weight loss
• Diet high in salt, proteins, and sugar
• Age - kidney stones can develop at any age, but the most affected group are people between the ages of 40 to 65.^[2]
• Sex - the prevalence of kidney stones is twice as high in males in comparison with females. 
• Certain medical conditions - diabetes mellitus, gout, or inflammatory bowel disease
• Urinary tract infections
• Medications and supplements - vitamin D supplements, loop diuretics, some antacids

Genetics

Research into the causes of kidney stones has looked at both individual genetic factors and a combination of genetic influences. These factors involve different conditions and pathways that together contribute to the development of kidney stones. Some of these contributors include conditions like hypocitraturia and hypomagnesemia, as well as primary hyperoxaluria.^[3,4]

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While the study of single genetic variants has faced some challenges, scientists have found connections between over 30 genes and kidney stones. However, it's important to understand that these genetic changes are only confirmed in about 15% of cases. This suggests that most cases are influenced by a combination of multiple genes, rather than just one.^[5]

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Genetic testing gives us the opportunity to discover whether you have a predisposition to developing this disease. At Macromo, we use polygenic risk scores and causative evidence-based genetic variants foe evaluation. The polygenic risk score (PRS) represents the total number of genetic variants that increase an individual's risk of developing a particular disease. All variants across their genome are summed and ranked according to their effect on disease development.

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Signs & Symptoms

As kidney stones increase in size, patients begin to notice symptoms with different severity.  

• Severe sharp and cramping pain in the area of the lower back and side - when the stones cause irritation or obstruction, patients experience rapidly increasing severe pain. The pain starts suddenly, comes in waves, and often moves from the back to the groin. It's often described as one of the worst pains ever experienced. 
• Nausea, vomiting
• Blood in the urine
• Fever
• Atypical look and smell of the urine 

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Diagnosis

Diagnosis of kidney stones starts with a medical history and physical examination. It's necessary to settle the size and location of the stones, therefore imaging methods are indicated. The main method used for diagnosis is a CT scan. After gathering information about the stone, it's important to assess patients' general health. Blood tests are indicated to evaluate the state of the kidneys and to find the possible underlying cause (such as elevated lipid levels or medical conditions). 

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Therapy

The goal of kidney stones therapy is to allow the passing of the stones without surgery. Patients are instructed to drink high amounts of water and adhere to recommended treatment in managing pain and nausea. It is possible to prescribe ureter relaxing medicines, most commonly tamsulosin (sold as Flomax). If the stones are too big and cause a blockage or infection, intervention is unfortunately inevitable. There are many approaches, including invasive and non-invasive methods:

• Non-invasive

• Shock-wave lithotripsy - high-energy waves are used to break kidney stones into smaller pieces that can pass naturally. 

• Minimally invasive

• Ureteroscopy - kidney stones are retrieved or broken into smaller pieces by a small instrument inserted into the ureter through the urethra and urinary bladder. 
• Percutaneous nephrolithotomy/nephrolithotripsy - surgeons approach the kidney directly through a small incision in the patient's back.

• Invasive

• Open stone surgery - performed in less than 1% of the cases

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It's important to assess any known health condition and adhere to its treatment to prevent recurrence of the kidney stones. 

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Prevention

There are plenty of factors increasing the risk of developing kidney stones, but luckily enough, a lot of them are modifiable. What are the steps that can help you significantly decrease the risk? 

• Drink enough water -  drinking enough liquids, especially pure water, is the number one preventive step. Healthy individuals should drink around 2 liters of water per day, with the value changing regarding weather, activity, sweat amount, etc. Patients with kidney failure should consult their doctor about the right amount of water. 
• Diet changes

• Avoid high sodium foods (cheese, processed foods, bread, canned soups and vegetables, biscuits) and limit salt - high levels of sodium prevent calcium from being reabsorbed from urine to blood and allow calcium stones formation. 
• Avoid foods high in animal proteins (beef, poultry, fish, pork) - those foods are acidic and might increase urine acid.
• Reduce foods high in oxalate (the main substrate leading to kidney stones formation) - spinach, rhubarb, strawberries, nuts, dried peas, beans
• Avoid high sugar diet
• Eat fruits and vegetables - they're containing nutrients that can help prevent the formation of stones (potassium, fiber, magnesium, antioxidants)

• Manage your weight - obesity may change the acid levels in the urine and lead to stone formation. 

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Prognosis

In general, the prognosis of kidney stones is very positive, although there is a high possibility of recurrence. Therefore it's important to assess any possible source of origin and adhere to lifestyle changes and recommended medications. In 80 to 90%, kidney stones pass on their own and no treatment is needed.^[6] The surgical approach to the removal of larger kidney stones is in general very successful and the recovery time is very short. If larger stones aren't removed, the urine buildup could lead to infections and subsequent kidney failure. Kidney stones also increase the risk of developing chronic kidney disease. 

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Recommendations

• Adhere to the treatment if you experience problems with kidney stones. Their probability of coming back is 50%. 
• Ask your doctor before Ibuprofen usage when having a kidney stones attack, it may increase the risk of kidney failure.
• Try to limit salt usage to the minimum, as high sodium levels increase the probability of kidney stones formation. 
• Avoid foods high in animal proteins.
• Eat fruits and vegetables.
• Be physically active.

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