Causes of Low Urate Levels
Low serum urate levels (hypouricemia) are primarily caused by decreased production of uric acid or increased renal excretion of uric acid.
Primary Causes of Low Urate Levels
Decreased Production of Uric Acid
- Genetic disorders:
- Deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) 1
- Xanthine oxidase deficiency (hereditary xanthinuria)
- Purine nucleoside phosphorylase deficiency
Increased Renal Excretion of Uric Acid
Medications that increase uric acid excretion:
Pathological conditions:
- Fanconi syndrome
- Wilson's disease
- Multiple myeloma with Fanconi syndrome
- Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Secondary Causes of Low Urate Levels
Medication-Induced
Xanthine oxidase inhibitors:
Other medications:
- Canagliflozin (SGLT2 inhibitor) 5
- High-dose corticosteroids
Dietary and Lifestyle Factors
Low purine diet 7
- Avoiding red meat, organ meats, seafood, and yeast supplements
- Limited alcohol consumption, especially beer
- Avoiding sugar-sweetened beverages with high fructose corn syrup
Weight loss 7
- A weight reduction of 5kg can result in a mean serum uric acid reduction of 1.1 mg/dl
- BMI reduction of >5% is associated with 40% lower odds of recurrent gout flares
Pathological Conditions
Liver disease:
- Severe hepatic dysfunction affecting purine metabolism
Malnutrition states:
- Severe protein-calorie malnutrition
- Starvation or extreme reducing diets 1
Other conditions:
- Neoplastic diseases with rapid tissue breakdown during chemotherapy 1
- Renal tubular defects affecting uric acid reabsorption
Clinical Significance of Low Urate Levels
Low urate levels themselves are generally not associated with significant morbidity or mortality. However, they may indicate underlying disorders that require attention. Extremely low levels (<2 mg/dL) can occur with high doses of allopurinol 1 and may potentially lead to:
- Increased reutilization of hypoxanthine and xanthine for nucleotide synthesis 1
- Rarely, xanthine crystalluria (reported in only three patients, two with Lesch-Nyhan syndrome and one with lymphosarcoma) 1
Monitoring Considerations
- For patients on urate-lowering therapy, the target serum urate level should be below 0.36 mmol/L (6 mg/dL) 2
- For patients with severe gout or tophi, a more aggressive target of <0.30 mmol/L (5 mg/dL) may be necessary 2, 7
- Regular monitoring of serum urate levels is essential to assess treatment efficacy 2, 7
Clinical Pitfalls
- Misinterpreting low urate levels as therapeutic success when they might indicate an underlying pathology
- Failing to recognize that even patients with apparent high urinary uric acid output may still have relative underexcretion of uric acid compared to controls 8
- Overlooking the possibility of medication-induced hypouricemia, especially in patients on multiple medications
Understanding the cause of low urate levels is important for proper management of patients with gout and for identifying potential underlying disorders in those with unexpectedly low urate levels.