What are the causes of hyperuricemia (elevated uric acid)?

From the Guidelines

Elevated uric acid levels are primarily caused by a combination of dietary factors, medical conditions, medications, and genetic factors, with the most significant contributors being obesity, alcohol intake, and poor kidney function, as supported by the American College of Physicians guideline 1. The causes of elevated uric acid can be broken down into several key categories:

• Dietary factors: excessive consumption of purine-rich foods like red meat, organ meats, seafood, and alcoholic beverages, particularly beer, as well as high-fructose foods and drinks 1.
• Medical conditions: obesity, metabolic syndrome, diabetes, kidney disease, and certain blood disorders, which can lead to decreased excretion of uric acid through the kidneys 1.
• Medications: diuretics (especially thiazides), low-dose aspirin, niacin, and some immunosuppressants like cyclosporine, which can raise uric acid levels 1.
• Genetic factors: inherited metabolic disorders like Lesch-Nyhan syndrome, which can cause severe hyperuricemia 1.
• Other factors: rapid cell turnover conditions such as cancer treatments, psoriasis, and hemolytic anemia, which can release purines that convert to uric acid, as well as fasting or crash dieting, which can temporarily increase levels as body tissues break down 1. To manage elevated uric acid, lifestyle modifications are essential, including maintaining a healthy weight, limiting alcohol intake, staying hydrated, and reducing consumption of purine-rich foods, as recommended by the multinational evidence-based recommendations for the diagnosis and management of gout 1. Medications like allopurinol, febuxostat, or probenecid may be prescribed for persistent hyperuricemia, especially if it causes gout attacks or kidney stones, with the goal of achieving a serum urate level below 0.36 mmol/L (6 mg/dL) and eventually eliminating gout attacks and resolving tophi 1.

From the FDA Drug Label

Hyperuricemia may be primary, as in gout, or secondary to diseases such as acute and chronic leukemia, polycythemia vera, multiple myeloma, and psoriasis It may occur with the use of diuretic agents, during renal dialysis, in the presence of renal damage, during starvation or reducing diets, and in the treatment of neoplastic disease where rapid resolution of tissue masses may occur.

• Causes of elevated uric acid include:
  • Primary causes, such as gout
  • Secondary causes, such as:
    • Acute and chronic leukemia
    • Polycythemia vera
    • Multiple myeloma
    • Psoriasis
  • Other causes, such as:
    • Use of diuretic agents
    • Renal dialysis
    • Renal damage
    • Starvation or reducing diets
    • Treatment of neoplastic disease with rapid resolution of tissue masses 2

From the Research

Causes of Elevated Uric Acid

Elevated uric acid levels can be caused by various factors, including:

• Diet rich in meat and seafood 3
• Alcohol intake 3, 4
• Diuretic use 3
• Chronic kidney disease 3, 5
• Diet heavy in fructose-rich food and beverages 3, 4
• Obesity 3
• Hypertension 3, 6
• Hyperlipidemia 6
• Diabetes mellitus 6
• Cardiovascular disease 6, 7

Demographic Factors

Certain demographic factors can also contribute to elevated uric acid levels, including:

• Male sex 3, 4
• Membership in certain ethnic groups, such as Taiwanese, Pacific Islander, and New Zealand Maori 3
• Living in high-income countries 3

Biochemical Parameters

Elevated uric acid levels can also be associated with various biochemical parameters, including:

• High levels of triglyceride 4
• High levels of C-reactive protein (CRP) 4
• High levels of vitamin B12 4
• Homeostatic model assessment of insulin resistance 4