Hyperuricemia

What is Hyperuricemia?

Hyperuricemia is a condition where there’s too much uric acid in your blood, usually, more than 6 mg/dL in women and 7 mg/dL in men. It’s estimated that around 38 million Americans have higher uric acid levels, and the number is growing globally as more people adopt Western-style diets and lifestyles. Most people won’t have clear symptoms, but it is still unclear what the long-term effects of this condition might have on heart health, kidney function, and overall health.

Uric acid levels can rise due to either an increase in the production of uric acid, a decrease in its excretion, or a combination of both. Your diet contributes to around one-third of the daily uric acid production in your body, while the rest comes from processes within your body. High uric acid levels can also occur due to increased breakdown of substances called purines – found in certain foods and within our bodies – especially in situations where body cells are rapidly turning over (like in conditions of hemolysis, rhabdomyolysis, or tumor lysis). Decreased excretion might be due to genetic disorders, kidney issues, or metabolic syndrome. Normally, around two-thirds of uric acid is removed by the kidneys and one-third by the gastrointestinal (GI) tract. But this can vary based on medication or issues within the kidney or GI systems.

In most cases (85% to 90% of times), people with hyperuricemia don’t show any symptoms. But when uric acid levels stay high in the blood or urine, it could lead to health problems like gout or kidney stones. High uric acid levels have also been associated with other health conditions like metabolic syndrome, diabetes, heart disease, high blood pressure, hardening of the arteries, obesity, and chronic kidney disease.

What Causes Hyperuricemia?

Producing too much uric acid in your body can be caused by several things:

A diet rich in certain foods and drinks can cause an overproduction of uric acid. This includes alcohol (in particular, beer) and certain meats like bacon, beef, lamb, turkey, veal, venison and specific organs. Certain kinds of fish and shellfish like anchovies, cod, tuna, sardines, mussels, shrimp, lobster, codfish, scallops, trout, and haddock can also cause this.

Fructose, a type of sugar, can lead to high levels of uric acid. This is because when our bodies break down fructose in the liver, uric acid is produced. High-fructose corn syrup and sugary sodas can be particularly harmful. This is especially true for children and teenagers, as these sugary substances can also lead to obesity.

Problems with how your body handles purines, which are substances that can lead to the production of uric acid, can also cause high levels of uric acid. This includes conditions like hypoxanthine-guanine phosphoribosyltransferase (HPRT or HGPRT) deficiency, and phosphoribosylpyrophosphate (PRPP) synthetase overactivity.

Higher than normal cell breakdown can also cause high levels of uric acid. This can occur in certain diseases, after extreme exercises, or during chemotherapy.

Failure of your body to get rid of uric acid properly can also lead to high uric acid levels. This can occur in certain conditions like kidney disease, acid buildup in the body, low blood volume, certain medication use, or conditions like sarcoidosis, hyperparathyroidism, hypothyroidism, Bartter syndrome, and Down syndrome.

Certain water pills, called diuretics, can cause your uric acid level to go up, sometimes causing gout. These medications include thiazide and loop diuretics. The risk of developing gout with diuretics increases by almost 80%.

For patients who develop gout while on diuretics, a medication that lowers blood pressure, such as losartan or an angiotensin-converting enzyme inhibitor, is advised. In most cases, a medication that stops the formation of uric acid, such as allopurinol, is used for treatment. However, if there are no symptoms, treatment may not be needed.

Risk Factors and Frequency for Hyperuricemia

Around 21% of all people and 25% of patients in hospitals have a condition called asymptomatic hyperuricemia, where the level of uric acid in their blood is high, but they don’t have any symptoms. This condition can exist for 10 to 15 years before it leads to gout, a type of arthritis. Despite this, having high levels of uric acid isn’t always harmful, as 90% to 95% of people don’t experience any symptoms.

This condition is becoming more common worldwide, especially in countries that are becoming wealthier or are developing, as they start to consume more Western foods and adopt Western lifestyles. People living in Pacific islands have particularly high rates of this condition.

Men generally have higher levels of uric acid than women. This is because the female hormone estrogen helps to protect against high uric acid levels. However, women can also develop high uric acid levels after they go through menopause.

Signs and Symptoms of Hyperuricemia

Having high levels of uric acid alone, known as hyperuricemia, is not a sure sign that treatment is necessary, even though it can lead to other complications like diabetes, heart disease, and high blood pressure. In fact, most people with high uric acid don’t have symptoms and don’t need long-term treatment. People with hyperuricemia may have a history of eating a lot of foods rich in purines, a type of protein, or consuming a lot of alcohol. It’s crucial to look at any correlation between a person’s medical history or current medications and a decrease in the body’s ability to excrete uric acid or an increase in the creation of uric acid.

Gout and uric acid kidney stones are the two most common issues associated with hyperuricemia. Symptoms of a gout attack include swollen, painful, red joints, commonly the big toe. For kidney stones, people may suffer from intense pain in the side, abdomen, or back that can radiate to the groin; blood in the urine or brownish-colored urine; pain when urinating, and sickness and vomiting. Some may also suffer from urinary tract symptoms like fever, cloudy urine, and an increase in the frequency of urination.

There are no specific physical examination findings that would suggest hyperuricemia unless the patient shows signs of a sudden gout attack or uric acid kidney stones. Signs of gout would include a red, warm, and swollen joint, often the big toe, or any joint. Usually, gout only affects one joint at a time. This usually presents as having an unusually high level of pain that doesn’t match the physical examination findings. There are no specific physical exam findings for kidney stones, but patients might feel pain when the area over the kidney is pressed.

Testing for Hyperuricemia

In simpler terms, when it comes to detecting high levels of uric acid in the blood, which could indicate a condition such as gout, various lab tests are conducted. A serum uric acid test is a good example. Normal values for this test are usually less than 6.8 mg/dL, but these could vary based on gender. If your test’s results show 8mg/dL or more, then you have a condition called ‘hyperuricemia’, which translates to having high levels of uric acid in your blood.

If you have kidney stones composed of uric acid, a urine test can find traces of blood that may not be visible to the naked eye, detect uric acid crystals, and measure the acid level in your urine. A pH value less than 5.5 in your urine is usually a sign of kidney stones.

Another test involving urine checks the quantity of uric acid your body disposes of over 24 hours. Ideally, on a diet low in purines (substances that break down into uric acid), the amount of uric acid in your urine should be less than 600 mg per day. If it surpasses 800 mg per day, it implies you have ‘hyperuricosuria’, too much uric acid in your urine. But that doesn’t exactly point out whether you’re producing more uric acid than usual or your body isn’t getting rid of enough.

There are other tests like the complete blood count, CMP, lipid profile, HgA1c, calcium, and phosphate levels test. These help to examine other potential underlying diseases like cancer, sickle cell disease, diabetes, and metabolic syndrome.

In instances where you’re experiencing unexplained swelling, a joint x-ray could help evaluate it. However, an x-ray isn’t necessarily required to diagnose gout.

If you have kidney stones suspected to be made of uric acid, then a renal ultrasound or a non-contrast CT scan might be recommended. A contrast CT scan is not advised because it can make the stones hard to see.

In some cases, your doctor could suggest a joint aspiration procedure. They will draw out some fluid from the swollen joint to look for uric acid crystals under a microscope. These crystals tend to be needle-shaped and appear differently under polarized light.

Treatment Options for Hyperuricemia

If you have high levels of uric acid in your blood (known as hyperuricemia), it is not always necessary to start treatment unless you are undergoing treatment for cancer that might lead to tumor lysis syndrome, a dangerous rapid break down of cancer cells. In most cases, the potential side effects of medication outweigh the benefits if you do not show any symptoms.

Experts in treating joint disease (rheumatologists) recommend treatment if you have two or more gout attacks per year. However, starting treatment can be considered depending on how severe your gout symptoms are, or if you prefer to be started on medication. Other reasons to consider treatment include if your gout is causing bone damage, injuring your joints, or affecting multiple joints. Treatment is also considered if you have kidney stones or tophi (hard, uric acid deposits under the skin) due to high uric acid levels.

One common drug for treating gout is colchicine. This medication works by inhibiting elements in our cells necessary for inflammation, making it helpful for reducing inflammation during acute gout attacks. Doctors also recommend colchicine when starting drugs that lower uric acid levels to decrease the risk of gout attacks. If these medications are started slowly and gradually, they also significantly lower the risk of gout attacks.

There are three types of drugs that can lower uric acid levels: uricosuric agents, xanthine oxidase inhibitors, and recombinant uricases. Five drugs in these categories are approved for use in the US. Uricosuric agents help the kidney get rid of more uric acid. Certain other medications, such as losartan (for high blood pressure) and atorvastatin, and fenofibrate (for high blood cholesterol) also have this effect and can be used along with other treatments.

There exist other types of uric acid-lowering drugs that, although effective, are not available in some parts of the world due to potential harm they might cause to the liver.

Another type of drug blocks the reaction in the liver that makes uric acid from Xanthine. Allopurinol is a common one of these drugs that is generally used in patients with gout, kidney stones due to high uric acid levels, or as prevention in certain cancer treatments where high uric acid level is a concern.

There currently exists drugs that work by converting uric acid to allantoin, a more water-soluble non-toxic compound that is then easily excreted from our body. Rasburicase, a drug that works in this way, is generally used to reduce extremely high uric acid levels in cancer patients undergoing chemotherapy.

So, in conclusion, if you have gout, high uric acid levels, or certain kidney conditions, various medications are available that can help lower your uric acid levels. Depending on your specific condition, your doctor will choose the most suitable treatment for you based on the condition’s severity, drug side-effects, your other diseases, cost, and your personal preference. Your doctor will also periodically test your uric acid level to monitor the effectiveness of your treatment.

What else can Hyperuricemia be?

Just having high levels of uric acid in your body doesn’t cause symptoms on its own. However, various other medical conditions can lead to symptoms similar to gout or kidney stones, which are often connected to high uric acid levels. These conditions might include:

• Rheumatoid arthritis
• Pseudogout (a type of arthritis caused by calcium pyrophosphate deposits)
• Arthritis
• Underactive thyroid (hypothyroidism)
• Alcoholic ketoacidosis (a life-threatening complication of heavy drinking)
• Kidney stones that aren’t caused by uric acid
• Hemolytic anemia (a condition where the body destroys red blood cells faster than it can produce new ones)
• Hyperparathyroidism (overactivity of the parathyroid glands)
• Certain types of cancer (malignancies)

What to expect with Hyperuricemia

Most people with high levels of uric acid in their blood, also known as hyperuricemia, do not experience any symptoms. If symptoms do occur, there are several types of medication that can effectively treat them.

Research indicates that having hyperuricemia could lead to developing high blood pressure, metabolic disease, diabetes, and diseases of the heart and kidneys. However, there is no definitive proof yet of a direct cause-and-effect relationship.

At the moment, it is not standard practice to use therapy to lower uric acid levels for patients who do not show any symptoms of hyperuricemia.

Possible Complications When Diagnosed with Hyperuricemia

Hyperuricemia mainly causes complications associated with kidney stones and gout. Here are some potential side effects that could occur:

• Bone loss
• Long-term kidney disease
• Gout
• High blood pressure
• Damage to the joints and changes in their shape
• Deposits of chalk-like substance known as tophi
• Loss of ability to move
• Kidney stones (made of uric acid and calcium oxalate)
• Limited range of motion
• Skin rashes
• Allergic reaction to a medicine used to treat gout, known as allopurinol sensitivity syndrome

Preventing Hyperuricemia

If you have high levels of uric acid in your blood, which can lead to conditions such as gout, kidney stones made of uric acid, or kidney stones made of calcium linked to excessive uric acid, you should be taking preventive treatment. The usual first step is taking a medication called allopurinol. If there’s a chance you might experience a sudden increase in symptoms (a “flare”), especially if you have kidney failure, your doctor will start you on a lower dosage of medicine to reduce uric acid, and then gradually increase it.

Your diet plays a key role too. You should learn about and adhere to a diet that is low in substances called purines, salt, and fructose. It might be helpful to see a dietitian on a regular basis who can guide you through this dietary adjustment. This type of diet will not only help manage your condition but can also improve your overall health.