What is the management for hyperuricemia (elevated uric acid levels)?

Management of Hyperuricemia (Elevated Uric Acid Levels)

For patients with hyperuricemia, management should include both non-pharmacological lifestyle modifications and pharmacological therapy tailored to the individual's specific risk factors, with a target serum uric acid level below 6 mg/dL (360 μmol/L) for long-term maintenance.1

Initial Assessment

• Evaluate for specific risk factors including previous gout attacks, radiographic signs, and clinical phase (acute/recurrent gout, intercritical gout, or chronic tophaceous gout) 1
• Consider causes of hyperuricemia by checking for comorbidities such as obesity, hypertension, hyperlipidemia, diabetes, and kidney disease 1
• Screen for medications that may elevate uric acid levels, particularly thiazide and loop diuretics, niacin, and calcineurin inhibitors 1
• For patients with early onset hyperuricemia (before age 25) or history of urolithiasis, screen for uric acid overproduction through urine uric acid evaluation 1

Non-Pharmacological Management

• Provide patient education about the disease, treatment objectives, and lifestyle modifications 1
• Recommend weight loss if the patient is overweight or obese 1
• Advise reduction in alcohol consumption, especially beer and spirits 1
• Recommend avoiding sugar-sweetened drinks and foods rich in fructose 1
• Limit intake of purine-rich foods (red meat, seafood) 1
• Encourage consumption of low-fat dairy products 1
• Advise regular physical activity 1
• Ensure adequate fluid intake to maintain sufficient urinary output 2

Pharmacological Management

When to Initiate Urate-Lowering Therapy (ULT)

• ULT should not be started during an acute gout attack but should be continued if already initiated 3
• For patients with recurrent gout attacks, chronic tophaceous gout, or urate arthropathy, ULT is indicated 1

First-Line ULT

• Allopurinol is recommended as first-line therapy in patients with normal kidney function 1
  • Start at a low dose (100 mg/day) and increase by 100 mg increments every 2-4 weeks until target serum uric acid level is reached 1
  • Maintain serum uric acid level <6 mg/dL (360 μmol/L) lifelong 1
  • For patients with renal impairment, adjust maximum dosage according to creatinine clearance 1, 2
    • With creatinine clearance 10-20 mL/min: 200 mg/day
    • With creatinine clearance <10 mL/min: maximum 100 mg/day
    • With extreme renal impairment (<3 mL/min): dosing interval may need to be extended 2

Alternative ULT Options

• If target serum uric acid level cannot be reached with allopurinol or if allopurinol is not tolerated:

  • Switch to febuxostat 1
  • Consider a uricosuric agent (e.g., probenecid) 1, 3
  • Use combination therapy of allopurinol with a uricosuric agent 1

• For patients with renal impairment who cannot achieve target serum uric acid with adjusted allopurinol dosing:

  • Switch to febuxostat or use benzbromarone (except in patients with eGFR <30 mL/min) 1

• For severe tophaceous gout where target serum uric acid cannot be reached with other medications at maximum dosage, pegloticase is indicated 1

Probenecid (Uricosuric Agent)

• Starting dose: 250 mg twice daily for one week, then 500 mg twice daily 3
• May increase by 500 mg increments every 4 weeks if needed (usually not above 2000 mg per day) 3
• Not effective in patients with significant renal impairment, particularly when GFR ≤30 mL/minute 3
• Consider alkalization of urine with sodium bicarbonate (3-7.5 g daily) or potassium citrate (7.5 g daily) to prevent uric acid crystallization 3

Management of Medication-Induced Hyperuricemia

• When hyperuricemia occurs in patients receiving diuretics, consider substituting the diuretic if possible 1, 4
• For hypertension management in patients with hyperuricemia, consider losartan or calcium channel blockers 1
• For hyperlipidemia management, consider statins or fenofibrate 1

Monitoring and Follow-up

• Monitor serum uric acid levels regularly to ensure target level is maintained 1
• Once target serum uric acid level is achieved, continue ULT indefinitely to prevent recurrence 1
• When acute attacks have been absent for 6 months or more and serum urate levels remain normal, consider decreasing the daily dosage by 500 mg every 6 months, but maintain dosage sufficient to keep serum urate levels within normal range 3

Special Considerations

• Avoid targeting serum uric acid levels <3 mg/dL for long-term therapy 1
• In patients with chronic tophaceous gout, more aggressive urate lowering may be required until tophi resolve 1
• Consider referral to a specialist for unclear etiology of hyperuricemia, refractory symptoms, difficulty reaching target serum urate level, or multiple/serious adverse events from ULT 1