What is Uric Acid Nephrolithiasis?
Uric acid nephrolithiasis is a type of kidney stone disease that happens when there’s a buildup of uric acid crystals in the kidneys. These crystals can cluster together to form stones, causing pain and possibly recurring blockages in the urinary tract. Usually, this condition is linked with high uric acid levels in the blood, known as hyperuricemia. Interestingly, nearly two-thirds of all uric acid kidney stones can be dissolved by managing the pH and volume of urine and by reducing hyperuricosuria, which is an excessive amount of uric acid in the urine.
Kidney stones are a common health issue, especially in developed countries. Studies suggest that 2 to 5% of the global population will have kidney stones at least once in their lifetime. Various factors can increase the risk of developing kidney stones, like genetic conditions, metabolic processes, dietary habits, and environmental elements. Health conditions like metabolic syndrome, obesity, diabetes, gout, high blood pressure, and chronic kidney disease can also be related to uric acid nephrolithiasis.
Did you know? The main acid component of bladder stones, now known as “uric acid,” was first identified by a Swedish pharmacist named C. Scheele in 1776. Throughout history, kidney and bladder stones made of uric acid have caused immense pain and distress. Before modern treatments, the only option to treat these painful stones was risky surgery with high chances of fatality. Noteworthy historical figures like Sir Isaac Newton and Michelangelo suffered reoccurring uric acid kidney stones.
What Causes Uric Acid Nephrolithiasis?
Uric acid is a waste product that comes from the breakdown of purines in our body. Purines come from three main sources: our body’s own cells when they die and get replaced, from the liver where they’re produced, and from certain foods we eat. Purines get broken down into a substance called xanthine, and an enzyme called xanthine oxidase further converts xanthine into uric acid. Certain medications can inhibit this enzyme, reducing the production of uric acid. While most other animals further break down uric acid into a chemical called allantoin that’s easily removed from the body, humans don’t, which can cause problems.
Our bodies produce around 300 to 400 milligrams of uric acid daily, with our diet contributing around half or less of this amount. Also, our diet can significantly increase the amount of uric acid we expel in our urine, especially if we consume foods high in purines.
The main issue with uric acid is when it builds up in the body and forms crystals in the kidneys, also known as uric acid stones. Acidic urine, often associated with low urinary ammonia levels, makes it more likely that these stones form. Other risk factors include high levels of uric acid in urine and not drinking enough fluids.
Uric acid stones are often categorized or classified based on their cause, such as caused by unknown reasons (idiopathic), having known causes (acquired or secondary), and being present from birth (congenital). Most often, they’re associated with metabolic disorders like diabetes, obesity, and metabolic syndrome, but they can also potentially be due to factors like gout, persistent diarrhea, cancer treatments, and high-purine diets. Some medications can also affect uric acid levels.
Rarely, certain genetic conditions can cause uric acid stones. Overall, the risk of uric acid stones has been noticed to increase in people with metabolic syndromes, impaired glucose tolerance, or diabetes.
Acidic urine significantly contributes to the formation of uric acid stones. This acidity can result from both dietary factors and underlying health conditions, such as metabolic syndrome. Also, the amount of acid in the urine can vary throughout the day, with acid levels being typically highest in the morning.
Gout and overly high uric acid levels in the blood are associated with uric acid causing problems in the kidneys in 15% to 25% of patients. Normally, uric acid is eliminated 70% by the kidneys and 30% in the intestines. However, this can change if there is a problem with the kidneys. High levels of uric acid can even damage the kidneys by causing constriction of the blood vessels, triggering inflammation, injuring the small blood vessels in the kidneys, and affecting the kidneys’ ability to regulate blood flow.
Risk Factors and Frequency for Uric Acid Nephrolithiasis
Uric acid stones make up about 10% of all urinary stones in the U.S and between 5% to 40% globally. Both men (10.6%) and women (7.6%) in the United States can end up having these stones in their lifetime. Without treatment, these stones can lead to abdominal pain, urinary tract infections, and even kidney failure. To add, the cost of treating this condition has risen from $1.3 billion in 1994 to $2 billion in 2000, despite advancements in patient care.
These stones most often occur in men aged 60 to 65, making up 10% to 15% of all urinary tract stones. Common factors contributing to these uric acid stones include obesity, high blood sugar, the metabolic syndrome, and high blood pressure.
The chance of getting uric acid stones changes with age, gender, and environmental factors. People older than 65 get uric acid stones twice as often as younger patients. Traditionally, men are affected three times more than women, but more women are also getting this condition now. And if you’ve had uric acid stones before, there’s a higher risk of them recurring and need for surgeries compared to calcium stones.
The likelihood of developing uric acid stones is very high in certain ethnic groups. About half of the Hmong people (from Laos and Thailand) suffer from this condition, while only 10% of non-Hmong people from the same countries do. In the Middle East, uric acid can make up a third of all urinary stones. Asian countries tend to have very low rates of uric acid stones, with an incidence of less than 1%. A notable exception is Okinawa, where uric acid stones account for 15% of all urinary stones. These variations are because of genetic, dietary, and climate factors.
Environmental conditions also significantly impact the frequency of uric acid disorders. For example, nephrolithiasis (the condition of having urinary stones) is much more prevalent in hot, dry regions. In fact, one study showed that factory workers in hot conditions were ten times more likely to have nephrolithiasis than their counterparts working at room temperature.
Signs and Symptoms of Uric Acid Nephrolithiasis
Uric acid nephrolithiasis, a condition where uric acid forms into kidney stones, often accompanies other health problems such as obesity, diabetes, a condition called metabolic syndrome (which includes high blood pressure and high cholesterol), and some gastrointestinal problems like irritable bowel syndrome or Crohn’s disease. Common symptoms of uric acid nephrolithiasis are intense fluctuating pain in the abdomen, back, or groin, blood in the urine, dark or brown urine, and pain or discomfort while urinating.
During a physical exam, a doctor might uncover more clues that uric acid kidney stones may be the problem. Tenderness in the back area around the kidneys or symptoms of gout – like painful, reddened, and swollen joints – could be present. In particular, the base of the big toe (referred to as the podagra) may exhibit these symptoms. Also, signs of acute kidney injury, such as flank tenderness could be seen. The doctor will typically look for all these signs to confirm the diagnosis.
Testing for Uric Acid Nephrolithiasis
If you’re suspected of having kidney stones, the first step your doctor might take is to order a simple urine test. The urine test will show if there is blood in your urine and if it’s too acidic. They may also find a crystal, shaped like a diamond or a star, that can be yellow or reddish-brown – this crystal is uric acid.
Your doctor might also want to see how much uric acid accumulates in your urine over a full day (24 hours). They would be interested in knowing the pH level of your urine, which is a measure of how acidic or alkaline it is. If your urine’s pH is less than 5.5, it generally suggests kidney stones made from uric acid. Along with uric acid, the doctor would also check the citrate – a substance in your urine that helps prevent stones from forming, creatinine – a waste product that provides information about how well your kidneys are working, and the amount of urine your body produces in a day. They would also need to check the levels of uric acid and other crucial chemicals in your blood.
Sometimes, your doctor might want to get a simple X-ray of your abdomen (known as a KUB X-ray) to see if there are any stones in your kidneys or bladder. This X-ray can show stones that contain calcium, but it may not show stones made of uric acid, as they don’t absorb the X-rays as well.
Your doctor might also order an ultrasound, which uses sound waves to create a picture of your kidneys. It’s an easy and safe procedure, and it’s particularly good at showing if a stone is causing a blockage. However, an ultrasound might not be able to show small stones or tell what type of stone it is (uric acid or calcium). Also, while the ultrasound is good at showing blockages, it might not be able to differentiate it from a normal variation in your kidney’s anatomy or from a slow-draining section of your kidney.
Often, the doctor will use a combination of X-rays and ultrasound. This can be very effective, especially when a more advanced scan, like a CT scan, isn’t available.
The doctor might also perform a type of CT scan known as noncontrast enhanced computed tomography. This scan doesn’t use any dye and is very good at showing the size, type, and location of any kidney stones. It’s considered the standard test for diagnosing kidney stones. If your urine’s pH level is 5.5 or less and your kidney stones are less dense (usually this is measured in something called Hounsfield units) on the CT scan, it typically suggests that your stones are made from uric acid.
Treatment Options for Uric Acid Nephrolithiasis
The treatment for uric acid kidney stones can involve changes in lifestyle, medical treatments that help to lower uric acid production and enhance its removal from our bodies, and urinary alkalinization — the process of making the urine more alkaline (less acidic). Increasing the alkalinity of urine is widely considered as the most effective approach, with the aim being to adjust the pH levels of urine to between 6 and 6.5. For these type of kidney stones, medical practitioners can use kidney ultrasonography — a technique to visualize organs — to track progress as these kidney stones are not visible using traditional kidney, ureter, and bladder X-ray imaging (KUB)
When managing dietary changes, the most significant thing to remember is to drink at least 2 litres of water daily to increase the volume of urine, which will aid in kidney stone prevention. It is also advised to consume fewer foods rich in purines and animal proteins to reduce uric acid production. Some people recommend drinking orange juice and lemonade, but be careful as fructose present in them can also increase uric acid stone formation. Other crucial actions include maintaining a healthy weight, managing high blood pressure and keeping diabetes under control, all of which can help control uric acid kidney stones.
In regard to medical treatments, urinary alkalinization can help dissolve and ward off uric acid stones with the aim being to achieve a urinary pH above 6.5 consistently. Tracking treatment response can be done using ultrasound and CT scans. The usually chosen medicine is potassium citrate, although sodium citrate and sodium bicarbonate can be utilized as well. Nevertheless, sodium-based alkaline agents can increase urinary calcium removal and may lead to the formation of calcium-based kidney stones.
Medications that inhibit xanthine oxidase are used for patients with high uric acid in blood (hyperuricemia) or urine (hyperuricosuria). These drugs need to be adjusted for optimal serum uric acid levels to be 6 mg/dL or less and urinary levels to be 600 mg/d or less.
In cases where uric acid cannot be lowered through diet or medications, recombinant uricase — a type of enzyme therapy — may be used. Current therapies include pegloticase and rasburicase, which have proven very effective but are commonly used as a second-line approach after diet and medications because they are expensive, necessitate IV infusions, can cause reactions, and can have potential cardiovascular side effects.
Additionally, medication to help pass stones (medical expulsive therapy) is typically used for smaller kidney stones. Specific medications, such as alpha-blockers like tamsulosin, may help pass kidney stones naturally. This technique is most useful for smaller stones located in the lower part of the ureter — the tube that connects your kidney to your bladder. New experimental treatment involves the use of theobromine, a natural compound found in cocoa beans and dark chocolate, which has been used in the treatment of high blood pressure. Theobromine is a potent inhibitor of uric acid crystallization.
Even though medical management is the default, surgery may be used when medical treatment is not effective, especially when there’s a severe urinary tract infection present. In such cases, immediate action may be required which may involve inserting a double J stent (a small tube that ensures the passage of urine from the kidney to the bladder) or putting in a percutaneous nephrostomy (insertion of a small, flexible rubber tube into your kidney). Different types of surgery may be suggested based on the nature of the kidney stones.
What else can Uric Acid Nephrolithiasis be?
Uric acid kidney stones have symptoms that are the same as kidney stones made from calcium. There are other conditions that a doctor may consider when diagnosing kidney stones because they cause similar symptoms. These conditions include:
- Appendicitis
- Gallbladder inflammation (acute cholecystitis)
- Urinary tract infection that has reached the kidney (pyelonephritis)
- Gallstone pain (biliary colic)
- Constipation
- Pregnancy outside the womb (ectopic pregnancy)
- Swelling of the kidneys due to a backlog of urine (hydronephrosis)
- Blockage of the gut (intestinal obstruction)
- Inflammation in the female reproductive system (pelvic inflammatory disease)
What to expect with Uric Acid Nephrolithiasis
Medical treatment for breaking down existing uric acid stones (hard deposits that form in the kidneys) tends to work really well. The outlook is usually positive if the right treatment is consistently followed for uric acid nephrolithiasis, a kidney condition where these stones are formed from uric acid.
You can prevent these stones from coming back by eating a healthy diet, staying well hydrated, managing high levels of uric acid in your blood and urine, and correctly using medications that make your urine less acidic (alkalinizing agents).
Possible Complications When Diagnosed with Uric Acid Nephrolithiasis
Uric acid stones often come with complications like blocking the urinary tract, potentially leading to kidney failure and widespread infection (sepsis). Treating these stones with a technique called extracorporeal shock wave lithotripsy has its own potential complications, such as the need for repeat treatments, urinary tract infections, internal bleeding (hematoma), and sepsis. Similar issues can arise with a procedure called ureteroscopy: pain from the stent, injury to the ureter, need for retreatment, urinary tract infections, urinoma (a pool of urine that forms outside the bladder or ureter), and sepsis. Lastly, complications of percutaneous nephrolithotomy (another urinary stone treatment) include sepsis, bloody urine, internal bleeding near the kidneys, significant blood loss, and the possible need for arterial embolization to control excessive bleeding.
Potentially related complications:
- Urinary tract obstruction
- Renal or kidney failure
- Sepsis or widespread infection
- Need for retreatment
- Urinary tract infections
- Hematoma or internal bleeding
- Stent pain
- Ureteral injury
- Urinoma formation
- Blood loss
- Need for arterial embolization to control excessive bleeding
Preventing Uric Acid Nephrolithiasis
People with uric acid kidney stones often show symptoms that are very similar to those seen in individuals with calcium-based kidney stones. However, the way these uric acid stones come into existence is different. Spotting uric acid stones with imaging methods such as X-ray or ultrasound can be more tricky, and the treatment plans also tend to be significantly different from those for other types of kidney stones.
It’s very important for patients to understand how to prevent these uric acid stones. Specifically, it’s crucial to drink enough fluids and control your diet. Regularly taking prescribed medications also has a big role in successfully managing this condition.
