What are the management options for hyperuricemia?

Management of Hyperuricemia

Hyperuricemia should be treated with a combination of lifestyle modifications and pharmacologic therapy, with xanthine oxidase inhibitors (allopurinol or febuxostat) as first-line medication, targeting serum uric acid levels below 6 mg/dL for most patients. 1

Clinical Evaluation

When evaluating patients with hyperuricemia, consider:

• Disease activity and burden through history and physical examination for:

  • Frequency and severity of acute gout attacks
  • Presence of tophi
  • Signs of acute or chronic synovitis 1

• Potential causes of hyperuricemia:

  • Medications (thiazide/loop diuretics, niacin, calcineurin inhibitors)
  • Comorbidities (hypertension, obesity, metabolic syndrome, diabetes)
  • Early-onset hyperuricemia (before age 25)
  • History of urolithiasis 1

Non-Pharmacologic Management

Dietary Recommendations

• Limit:

  • Purine-rich meats and seafood
  • High fructose corn syrup sweetened beverages
  • Alcohol (particularly beer, but also wine and spirits) 1

• Avoid:

  • Alcohol overuse
  • Complete abstinence from alcohol during active gout attacks 1

• Encourage:

  • Low-fat or non-fat dairy products
  • Regular physical activity
  • Weight loss if overweight/obese
  • Coffee consumption
  • Vitamin C supplementation 1, 2, 3

Note: Diet alone typically provides only 10-18% reduction in serum urate levels, which is insufficient for most patients with significant hyperuricemia 1

Lifestyle Modifications

• Weight reduction through daily exercise and caloric restriction
• Adequate hydration
• Avoid strenuous exercise that may trigger acute attacks
• Follow Mediterranean diet principles when possible 2, 3

Pharmacologic Management

First-Line Therapy

1. Xanthine Oxidase Inhibitors:

   • Allopurinol:

     • Start at 100 mg/day
     • Increase by 100 mg every 2-4 weeks
     • Titrate to achieve target serum urate level
     • Adjust dose in renal impairment 1, 4

   • Febuxostat:

     • Alternative first-line agent
     • Consider when allopurinol is contraindicated or not tolerated 1

Target Serum Urate Levels

• Standard target: < 6 mg/dL for most patients
• Lower target: < 5 mg/dL for patients with:
  • Tophi on physical examination
  • Chronic tophaceous gouty arthropathy (CTGA) 1

Treatment Escalation Algorithm

If target serum urate is not achieved with first-line therapy:

1. Maximize XO inhibitor dose (allopurinol or febuxostat)
2. If target still not achieved: Add uricosuric agent to XO inhibitor
   • Options include probenecid, or off-label use of losartan or fenofibrate 1
3. For severe refractory cases: Consider pegloticase
   • Reserved for patients with severe tophaceous gout
   • When target serum urate cannot be achieved with other medications 1

Special Considerations

Chronic Kidney Disease

• Hyperuricemia with CKD stage 2-5 is an indication for pharmacologic therapy
• Adjust allopurinol dosing based on creatinine clearance
• Consider febuxostat if target serum urate not achieved with adjusted allopurinol dose 1

Medication Adjustments

• Consider substituting diuretics if possible
• For hypertension, consider losartan as it has uricosuric effects
• For hyperlipidemia, consider fenofibrate which also has uricosuric effects 1

Monitoring

• Measure serum urate levels regularly until target is achieved
• Once target is reached, maintain therapy indefinitely to prevent recurrence
• Continue to monitor for medication side effects and adherence 1

Common Pitfalls

1. Inadequate dosing: Many patients remain on initial doses of allopurinol without appropriate titration to reach target urate levels
2. Discontinuing therapy prematurely: Urate-lowering therapy should be maintained long-term
3. Relying solely on diet: Dietary measures alone are usually insufficient for significant hyperuricemia
4. Ignoring comorbidities: Address associated conditions like hypertension, obesity, and metabolic syndrome
5. Failing to adjust medications: Patients with renal impairment require dose adjustments 1

By following this comprehensive approach to hyperuricemia management, clinicians can effectively reduce serum urate levels, prevent gout attacks, and potentially mitigate associated cardiovascular and renal risks.