OVERVIEW

What is Hyperuricemia?

Hyperuricemia, as the name suggests, literally means elevated levels of uric acid in the blood.

Currently, hyperuricemia (HUA) is defined in China as: under normal purine dietary conditions (as opposed to a high-purine diet, which will be discussed later), fasting blood uric acid levels >420 μmol/L (7 mg/dL) on two separate occasions in adults, regardless of gender^[1].

Although hyperuricemia is a lifelong condition, if there is no kidney damage, joint deformity, or other complications, timely and standardized treatment can allow patients to maintain normal daily life and work. Treatment typically includes general measures (e.g., dietary control) and medication^[2]. If left untreated, a small number of patients may develop gout^[2], worsening their condition.

How Common is Hyperuricemia?

The number of people with hyperuricemia is increasing yearly, with a trend toward younger onset^[3].

Studies show that the overall prevalence of hyperuricemia in China is 13.30%^[1], meaning about 13 out of 100 people have hyperuricemia, with more cases in men than women^[2].

There are also regional differences, with higher prevalence in southern and coastal economically developed areas compared to other regions. This may be related to excessive consumption of high-purine seafood, animal organs, meat, and alcohol in these areas^[2,3].

What is the Relationship Between Hyperuricemia and Gout?

Gout is always based on high uric acid levels, but high uric acid does not necessarily lead to gout. Some people may have elevated uric acid levels their entire lives without ever experiencing a gout attack.

The relationship between hyperuricemia and gout is as follows:

When blood uric acid levels remain excessively high for a long time without treatment, the uric acid can exceed its solubility in the blood and crystallize. These crystals deposit in joints, kidneys, and other tissues, leading to gout and gouty nephropathy.

Data shows that about 5%–19% of hyperuricemia patients develop gout^[4], meaning roughly 5–19 out of 100 hyperuricemia patients may progress to gout.

Whether hyperuricemia develops into gout varies by individual, but higher uric acid levels increase the likelihood of crystal formation and gout.

Therefore, if you notice elevated uric acid levels, adopt a healthy lifestyle: reduce meat-based broths, avoid alcohol and sugary drinks, drink at least 2,000 mL of water daily, and engage in 30 minutes of aerobic exercise once or twice a week. If your doctor recommends medication to lower uric acid, follow their advice for proper treatment.

Which Department Should You Visit for Hyperuricemia?

Hyperuricemia should be detected early and treated promptly to prevent complications. If diagnosed, visit the endocrinology or rheumatology department.

SYMPTOMS

What are the common manifestations of hyperuricemia?

1. Asymptomatic: The most common and frequent manifestation of hyperuricemia is the absence of symptoms, referred to as asymptomatic hyperuricemia. This means that most patients with hyperuricemia may never experience any discomfort throughout their lives and often only discover they have hyperuricemia through blood tests revealing elevated uric acid levels.

2. Joint lesions: Manifested as acute gouty arthritis, tophi, and chronic arthritis.

   • Acute gouty arthritis: Sudden onset, often without warning, typically occurring at night and waking the patient due to pain. Within hours, redness, swelling, heat, pain, and limited mobility develop in the joints and surrounding soft tissues. The first metatarsophalangeal joint (the joint connecting the big toe to the foot) is most commonly affected initially. Other frequently involved sites include the instep, ankle, knee, fingers, wrist, and elbow joints^[5].
   • Tophi: These are painless, yellowish-white growths of varying sizes formed by urate deposits, commonly found on the ear helix, first metatarsophalangeal joint, interphalangeal joints, metacarpophalangeal joints, and elbows. Superficial tophi may erode the skin, releasing white powdery urate crystals^[2]. Skin ulcers often heal poorly, but due to urate's antibacterial properties, infections are rare^[5].
   • Joint lesions: Chronic persistence may lead to progressive joint stiffness, limited mobility, and deformities.

3. Kidney damage: Manifested as chronic hyperuricemic nephropathy, kidney stones, and acute renal failure.

   • Chronic hyperuricemic nephropathy: Early symptoms may include hematuria, proteinuria, and increased nocturia, progressing to renal insufficiency (manifested as fatigue, loss of appetite, reduced urine output, lower limb edema, etc.).
   • Kidney stones: Symptoms may include renal colic, hematuria, and recurrent urinary tract infections.
   • Acute renal failure: Massive urate crystal deposits can obstruct the urinary tract, causing acute renal failure, characterized by sudden oliguria or anuria. The inability to excrete toxins and excess fluids may lead to systemic symptoms such as vomiting, diarrhea, confusion, and seizures.

What adverse effects can hyperuricemia cause?

• Hyperuricemia harms multiple tissues and organs in the body:
• Excess uric acid deposits in bones and joints can trigger gout.
• Deposits in the kidneys can cause nephropathy, kidney stones, and even renal failure.
• Hyperuricemia also significantly increases the risk of metabolic disorders (e.g., obesity, diabetes, hypertension, dyslipidemia) and cardiovascular diseases (e.g., arteriosclerosis, coronary heart disease, stroke).

CAUSES

What are the causes of hyperuricemia?

Uric acid is a substance produced as part of human metabolism. After being generated, it is transported through the bloodstream and excreted via urine by the kidneys.

Under normal circumstances, the production and excretion of uric acid are balanced. However, when purine metabolism is disrupted, leading to increased uric acid production and/or reduced excretion in the blood, hyperuricemia occurs.
Increased uric acid production: There are two types—exogenous and endogenous:

• Exogenous uric acid comes from the breakdown of purines in food. Consuming high-purine foods such as organ meats, seafood, mushrooms, and seaweed can elevate blood uric acid levels. Additionally, alcohol consumption, especially long-term beer drinking, is another cause of increased uric acid.
• Endogenous uric acid is produced naturally during human metabolism. Congenital enzyme deficiencies leading to excessive uric acid production are the primary cause of primary hyperuricemia. Approximately 80% of blood uric acid comes from endogenous sources, while 20% is derived from food^[5]. Furthermore, certain diseases, such as malignancies, can cause a sharp rise in endogenous uric acid levels due to the destruction of tumor cells during radiotherapy or chemotherapy, which is a major cause of secondary hyperuricemia.

Reduced uric acid excretion: About two-thirds of uric acid is excreted through the kidneys. If kidney function declines due to kidney disease or other health issues, uric acid excretion decreases, leading to elevated blood uric acid levels.

Who is more likely to develop hyperuricemia?

• Individuals with specific dietary habits: Those who consume large amounts of alcohol or high-purine foods over a long period are more prone to hyperuricemia due to excessive uric acid production.
• People with a family history: Those with a family history of hyperuricemia or gout are more likely to develop the condition^[5].
• Men: The prevalence of hyperuricemia varies by gender, with rates of 9.2%–26.2% in men and 0.7%–10.5% in women^[2].
• Overweight or obese individuals: Studies show that overweight and obese people are more likely to develop hyperuricemia, with risks 1.822 and 2.534 times higher, respectively, compared to those with normal weight^[6].

Is hyperuricemia hereditary?

Possibly.

The genetic pattern of hyperuricemia is complex. In short, the condition is closely related to genetics and influenced by multiple factors, including environmental ones. People with a family history of gout have a significantly higher prevalence of hyperuricemia, meaning their likelihood of developing it increases, but it does not guarantee that all family members will be affected^[7].

What is the relationship between hyperuricemia and the other "three highs"?

Hyperuricemia is closely linked to the development of the other "three highs"—high blood sugar, high blood pressure, and high cholesterol.

This condition is an independent risk factor for diabetes and hypertension, meaning higher uric acid levels correlate with a greater risk of developing these diseases, and a causal relationship may exist^[1].

Uric acid levels are positively correlated with total cholesterol, triglycerides, and LDL ("bad" cholesterol), often appearing together, while negatively correlated with HDL ("good" cholesterol). Therefore, managing both cholesterol and uric acid levels is essential.

DIAGNOSIS

How is hyperuricemia diagnosed?

In healthy individuals, blood uric acid levels tend to rise due to poor dietary habits and lifestyle changes. Consuming high-purine foods or alcohol may cause a temporary increase in blood uric acid.

Therefore, under normal purine dietary conditions, hyperuricemia can be diagnosed if fasting blood tests on two separate days show uric acid levels exceeding 420 μmol/L in adults, regardless of gender.

Are additional tests needed after detecting hyperuricemia? Why?

Besides measuring blood uric acid levels, other auxiliary tests are required for further confirmation, disease assessment, treatment planning, and post-treatment evaluation.

1. Blood tests:

   • Complete blood count (CBC): During acute gouty arthritis, white blood cell counts may increase, aiding diagnosis. Some cases of secondary hyperuricemia caused by hematologic diseases (e.g., chronic leukemia, multiple myeloma) may show relevant clues in CBC.
   • Erythrocyte sedimentation rate (ESR): ESR may significantly increase during gouty arthritis flare-ups.
   • Kidney function tests: Assess whether kidney impairment is a cause (reduced uric acid excretion) or a consequence (uric acid nephropathy or gouty tophi damaging the kidneys) of hyperuricemia.

2. Urine tests:

   • 24-hour urinary uric acid excretion: Determines if hyperuricemia is related to poor uric acid excretion. Increased excretion in renal failure may aid in diagnosing gouty nephropathy and differentiating it from chronic glomerulonephritis-induced renal failure.
   • Urinalysis: Red blood cells and urate crystals may appear if uric acid stones form. Urine pH helps decide whether alkalization is needed to facilitate uric acid excretion.

3. Imaging tests: X-rays, CT scans, or MRI can evaluate stones and joints. Dual-energy CT is particularly valuable for gout diagnosis, detecting tophi and quantifying disease severity. High-frequency ultrasound (musculoskeletal ultrasound) can reveal urate crystal deposits and bone erosion in joints and surrounding tissues.

What should hyperuricemia patients consider when testing uric acid levels?

Blood uric acid tests should be repeated.

Healthy individuals may show rising uric acid levels due to dietary or lifestyle changes. High-purine foods or alcohol can cause temporary spikes. A single elevated reading is insufficient for diagnosis; fasting blood tests must be repeated on two separate days under normal purine intake.

24-hour urinary uric acid test: During acute flare-ups, urate and inflammatory diuresis increase urinary uric acid excretion, reducing diagnostic value. Testing is recommended after the acute phase resolves, following five days of normal purine intake.

Does hyperuricemia with joint pain always mean gout?

Not necessarily. Other joint conditions must be ruled out.

• Rheumatoid arthritis: Typically affects women aged 30–50, targeting small joints, wrists, knees, ankles, sacroiliac joints, or the spine. Symptoms include migratory, symmetrical polyarthritis, spindle-shaped swelling, morning stiffness, positive rheumatoid factor, and distinct X-ray findings compared to gout.
• Septic arthritis: Joint fluid cultures reveal bacteria.
• Traumatic arthritis: History of joint injury.

TREATMENT

Does hyperuricemia require treatment?

Yes.

Hyperuricemia is closely associated with metabolic diseases such as hyperglycemia, hyperlipidemia, and hypertension, as well as cardiovascular and cerebrovascular diseases such as arteriosclerosis, coronary heart disease, and stroke. Therefore, regardless of whether hyperuricemia is symptomatic, active treatment should be administered.

How is hyperuricemia treated?

Treatment for hyperuricemia includes^[1,2]:

1. General treatment: Lifestyle changes, including controlling total caloric intake, limiting high-purine foods, reducing alcohol and tobacco use, maintaining regular exercise, and managing weight.
   Active treatment of metabolic and cardiovascular risk factors related to elevated uric acid levels: Treating conditions such as diabetes, hypertension, hyperlipidemia, coronary heart disease, stroke, and chronic kidney disease.
   Medication:
2. Uric acid-lowering drugs: Depending on the condition, medications that reduce uric acid production or increase excretion may be prescribed, such as allopurinol, febuxostat, and benzbromarone.
3. Urine-alkalizing drugs: Appropriate alkalization of urine is necessary when urine pH is below 6.0. Common medications include sodium bicarbonate or potassium sodium hydrogen citrate to adjust urine pH to 6.2–6.9, facilitating urate excretion.

What are the common side effects of uric acid-lowering drugs?

Common drugs that inhibit uric acid production include allopurinol and febuxostat^[2].

• Side effects of allopurinol: Include gastrointestinal discomfort (abdominal pain, diarrhea, etc.), rash, fever, liver damage, and bone marrow suppression. About 5% of patients cannot tolerate it. Rare but severe "allopurinol hypersensitivity syndrome" may occur, typically within the first few months of use, manifesting as exfoliative dermatitis, severe erythema multiforme, or toxic epidermal necrolysis, with a mortality rate of 20%–25%^[9].
• Common side effects of febuxostat: Gastrointestinal reactions (e.g., nausea), joint pain, rash, and liver damage.
• Drugs that promote uric acid excretion include benzbromarone, probenecid, and sulfinpyrazone. Benzbromarone is the most commonly used, with side effects such as gastrointestinal reactions (e.g., stomach discomfort, diarrhea), rash, and mild granulocytopenia in some patients^[2].

How long should uric acid-lowering drugs be taken?

Uric acid-lowering drugs should be taken continuously. Approximately 80% of uric acid is endogenous (produced by the body's metabolism), while 20% comes from food. Dietary control can reduce blood uric acid levels by 60–90 μmol/L. Thus, most patients with hyperuricemia or gout cannot achieve target levels through diet alone, necessitating ongoing uric acid-lowering therapy, which is more effective than intermittent use in preventing gout attacks.

Additionally, once target uric acid levels are achieved, the dosage should be optimized to the minimum maintenance level and continued, with regular monitoring. If the condition is stable, monitoring every three months is recommended to assess uric acid control and potential side effects.

Can long-term use of uric acid-lowering drugs cause dependence?

No, it does not cause dependence.

Hyperuricemia results from the body's disrupted purine metabolism, leading to increased uric acid production and/or reduced excretion, disrupting the balance. Medications help restore this balance.

Stopping medication arbitrarily may cause recurrence or relapse, but this does not indicate drug dependence. There is no evidence that long-term use of uric acid-lowering drugs leads to dependency.

Why does gout occur during uric acid-lowering treatment?

At the start of treatment, a rapid drop in blood uric acid levels can cause urate crystals deposited in joint synovium or soft tissues to dissolve and dislodge, triggering inflammation. Uric acid may re-enter the bloodstream and migrate to other joints, inducing gout attacks. This phenomenon is called "secondary gout" or "transitory gout."

Although it may cause short-term pain, this process aids in clearing urate crystals from joints and surrounding tissues, promoting long-term recovery.

For acute arthritis, if uric acid-lowering drugs were not previously taken, they should be started after the acute phase (about 2–4 weeks later). If a gout attack occurs while already on medication, the drugs should not be stopped.

Should uric acid-lowering drugs be stopped during a gout attack?

No. Patients experiencing an acute gout attack while on uric acid-lowering therapy should continue their medication^[1]. Additional treatment with colchicine, NSAIDs (e.g., diclofenac, ibuprofen), or corticosteroids (e.g., prednisone) may be used to control inflammation.

Can hyperuricemia be completely cured?

Depending on the cause, some forms of hyperuricemia (e.g., congenital purine metabolism disorders or malignancy-related hyperuricemia) cannot currently be cured and require long-term or lifelong treatment with regular monitoring.

Does hyperuricemia require follow-up? How?

Yes, regular follow-up is necessary to evaluate treatment efficacy, adjust medications, and monitor side effects.
Initially, blood uric acid levels should be checked every 2–4 weeks until target levels are achieved (below 360 μmol/L, or below 300 μmol/L for patients with tophi or frequent gout attacks^[7]).

After stabilization, monitor every three months (uric acid, kidney/liver function, blood tests). Once controlled, follow-ups can be reduced to every six months for a year, then annually.

Can hyperuricemia recur?

Yes, if healthy lifestyle habits are not maintained, medications are discontinued without medical advice, or follow-ups are neglected. Adhering to prescribed treatment and regular monitoring is crucial.

Is lower uric acid always better?

No.

While uric acid was once considered a metabolic waste product that causes gout and kidney stones when crystallized, recent research suggests it acts as an antioxidant, protecting the brain and nervous system^[10].

Thus, excessively low uric acid (below 180 μmol/L) is not recommended.

Which drugs can interfere with uric acid-lowering medications?

Thiazide diuretics (e.g., hydrochlorothiazide), loop diuretics (e.g., furosemide), pyrazinamide, aspirin, niacin, and alcohol can increase uric acid by competitively inhibiting renal excretion^[11]. Their use should be carefully evaluated.

For patients requiring diuretics and with hyperuricemia, thiazide diuretics should be avoided^[7]. Low-dose aspirin (below 325 mg daily), despite raising uric acid, should not be discontinued for cardiovascular prevention^[12]. Always follow medical advice.

DIET & LIFESTYLE

What should hyperuricemia patients pay attention to in their diet?

• Ensure adequate protein intake, especially low-fat dairy products, but reduce consumption of red meat (such as beef, lamb, pork, etc.) and seafood (such as anchovies, kelp, nori, etc.)^[7].
• Avoid beverages high in fructose, such as sugary juices, freshly squeezed juices, and drinks containing high-fructose corn syrup (e.g., corn juice). Excessive fructose intake can increase uric acid production^[13].
• Limit high-purine foods (not completely avoid), such as animal offal (heart, liver, kidney, brain), clams, crabs, oysters, sardines, etc.
• Moderate consumption of meat, fish, shrimp, legumes, or soy products, which contain moderate purine levels.
• Most melons, root/tuber or leafy vegetables (e.g., cucumber, pumpkin, potato, sweet potato, cabbage), fruits (e.g., watermelon, coconut, grapes, strawberries), milk, and egg whites are low or free of purines and are encouraged^[7].
• Quit smoking and alcohol. Alcohol increases uric acid production and reduces its excretion, so all alcoholic beverages should be strictly limited.
• Drink plenty of water to promote urination, which helps lower uric acid. Aim for 2000–3000 mL daily to ensure urine output exceeds 1500 mL (preferably over 2000 mL)^[7]. Increase intake if sweating heavily.

Which foods are high in purines?

High-purine foods include: animal offal (heart, liver, kidney, brain, intestines); certain seafood (e.g., ribbon fish, catfish, anchovies, shrimp); rich soups (e.g., meat broth, fish broth, seafood hotpot broth); shellfish (e.g., clams, scallops, crabs). These should be limited.

What lifestyle changes should hyperuricemia patients adopt?

Exercise regularly and maintain a healthy weight when gout is not active. Engage in moderate-intensity activities (e.g., jogging, tai chi, brisk walking) for at least 30 minutes daily, five days a week. Overweight individuals should aim for a normal BMI.

Does hyperuricemia affect fertility?

Currently, no research or data suggests a correlation between the two.

Can hyperuricemia patients exercise? What types are suitable?

During gout flare-ups, rest and protect affected joints to ease pain. Resume gentle exercise only after symptoms fully resolve and joints return to normal, waiting an additional three days.

For asymptomatic hyperuricemia or gout intervals, moderate exercise is encouraged. High-intensity workouts produce lactic acid, reducing uric acid excretion and raising levels, so they are not recommended.

Opt for low-to-moderate aerobic activities like walking, brisk walking, jogging, tai chi, dancing, shuttlecock kicking, or yoga. Progress gradually and avoid overexertion.

PREVENTION

How to prevent or avoid recurrence of hyperuricemia?

A healthy diet, drinking plenty of water, quitting smoking and limiting alcohol, exercising regularly, and losing weight are important for preventing hyperuricemia. Taking medication as prescribed and regular follow-up examinations help prevent recurrence.

How can hyperuricemia patients prevent gout?

At the beginning of uric acid-lowering medication, starting with a low dose and gradually increasing it helps avoid or reduce gout attacks^[1].

To prevent acute gouty arthritis, low-dose colchicine may also be added. If patients cannot tolerate colchicine, low-dose NSAIDs or glucocorticoids are equally effective^[1].

For patients with gout attacks, maintaining uric acid levels below 360 μmol/L (but not lower than 180 μmol/L) long-term—or below 300 μmol/L for some patients—helps prevent recurrent episodes.