Causes of Hyperuricemia Besides Alcohol
Beyond alcohol, the primary causes of elevated uric acid include chronic kidney disease, medications (especially diuretics, low-dose aspirin, cyclosporine, and tacrolimus), obesity, and dietary factors including high-fructose corn syrup, purine-rich meats, and shellfish. 1
Medication-Related Causes
Medications are a critical and often overlooked cause of hyperuricemia:
- Diuretics are among the most common culprits, reducing renal uric acid excretion 1
- Low-dose aspirin impairs uric acid excretion even at cardioprotective doses 1
- Calcineurin inhibitors (cyclosporine and tacrolimus) significantly elevate uric acid levels 1
These medications should be reviewed in every patient with hyperuricemia, as they represent modifiable risk factors. 1
Renal Dysfunction
Chronic kidney disease is a major cause of hyperuricemia through underexcretion:
- The kidney normally excretes approximately 70% of daily uric acid production 2
- Renal impairment reduces uric acid clearance, leading to accumulation 1, 3
- CKD must be systematically assessed in all patients with hyperuricemia 1
Dietary Factors
High-purine foods and fructose-containing products elevate uric acid:
- Purine-rich meats (organ meats, red meat, game) increase uric acid through enhanced purine metabolism 1, 4, 5
- Shellfish and seafood increase gout risk with a relative risk of 1.51 4, 5
- Sugar-sweetened beverages and high-fructose corn syrup raise uric acid through increased production and/or decreased excretion 1, 4
- Fructose ingestion (1 gm/kg body weight) increases serum uric acid by 1-2 mg/dL within 2 hours 6
- Non-diet sodas contribute to hyperuricemia 1
Metabolic and Endocrine Factors
Obesity and metabolic conditions significantly contribute to hyperuricemia:
- Overweight and obesity are independent risk factors for elevated uric acid 1, 7
- Weight loss of 5 kg results in mean serum uric acid lowering of 1.1 mg/dL 6
- Metabolic syndrome components (dysglycemia, dyslipidemia, central obesity, hypertension) are commonly associated with hyperuricemia 8, 2
- Insulin resistance may increase URAT1 and GLUT9 expression, contributing to hyperuricemia 2
Comorbid Conditions Requiring Systematic Assessment
The following comorbidities should be screened in all patients with hyperuricemia: 1
- Hypertension
- Ischaemic heart disease and heart failure
- Diabetes mellitus
- Dyslipidaemia
- Hypothyroidism 7
Pathophysiologic Mechanisms
Hyperuricemia results from three main mechanisms: 3
- Overproduction type: Accelerated purine nucleotide degradation, ATP breakdown, and enhanced purine de novo biosynthesis 3
- Underexcretion type: Drugs affecting renal urate handling and renal insufficiency 3
- Mixed type: Conditions like alcohol or fructose overintake affecting both production and excretion 3
Common Pitfalls to Avoid
- Overlooking medication review: Always evaluate diuretics, low-dose aspirin, and immunosuppressants as reversible causes 1
- Ignoring renal function: CKD is both a cause and consequence of hyperuricemia and requires assessment 1, 2
- Underestimating dietary fructose: High-fructose corn syrup in beverages is a significant modifiable risk factor often missed 1, 4
- Failing to address obesity: Weight reduction can lower uric acid by >1 mg/dL and should be prioritized in overweight patients 6, 5
- Missing comorbidities: Hyperuricemia clusters with cardiovascular and metabolic diseases that require concurrent management 1, 8