What is the best management approach for a patient with hyperuricemia?

Management of Hyperuricemia with Uric Acid Level of 6.9 mg/dL

For a patient with a uric acid level of 6.9 mg/dL, no pharmacologic treatment is indicated unless there are specific symptoms of gout, tophi, frequent gout attacks, chronic kidney disease stage 2 or worse, or history of urolithiasis. 1

Assessment of Hyperuricemia

• Evaluate for symptoms and signs of gout including arthritis, tophi, and acute or chronic synovitis 1
• Consider secondary causes of hyperuricemia including medications (thiazides, loop diuretics, niacin, calcineurin inhibitors) 1
• Check for comorbidities commonly associated with hyperuricemia such as hypertension, chronic kidney disease, obesity, metabolic syndrome, diabetes, and hyperlipidemia 1, 2
• Consider screening for uric acid overproduction (via urine uric acid evaluation) if the patient had gout onset before age 25 or has a history of urolithiasis 1

Management Approach

Non-pharmacologic Interventions

• Implement dietary modifications: 1
  • Limit consumption of purine-rich meats and seafood
  • Reduce intake of high fructose corn syrup sweetened beverages
  • Encourage consumption of low-fat or non-fat dairy products
  • Reduce alcohol consumption, particularly beer
• Recommend lifestyle modifications including exercise and weight reduction for overweight patients 3
• Consider elimination of non-essential medications that elevate serum urate 1

Indications for Pharmacologic Urate-Lowering Therapy (ULT)

Pharmacologic ULT is indicated if the patient has any of the following: 1

• Tophi detected on physical exam or imaging
• Frequent attacks of acute gouty arthritis (≥2 attacks/year)
• Chronic kidney disease stage 2 or worse
• History of urolithiasis

Pharmacologic Treatment (if indicated)

If ULT is indicated based on the above criteria:

1. First-line therapy: Allopurinol 1

   • Start at low dose (100 mg/day or 50 mg/day if CKD stage 4 or worse)
   • Gradually titrate upward every 2-5 weeks to reach target serum urate
   • Target serum urate level <6 mg/dL (minimum) or <5 mg/dL for patients with severe disease or tophi
   • Dose can be raised above 300 mg daily with appropriate monitoring

2. Alternative first-line therapy: Febuxostat 1

   • Consider if allopurinol is not tolerated or contraindicated

3. Uricosuric therapy: Probenecid 1

   • Consider as alternative first-line therapy if XOI drugs are contraindicated
   • Not recommended if creatinine clearance <50 mL/min
   • Contraindicated in patients with history of urolithiasis

Treatment Targets and Monitoring

• The minimum serum urate target is <6 mg/dL 1, 4
• Serum urate lowering below 5 mg/dL may be needed for patients with tophi or severe disease 1
• Monitor serum urate regularly to ensure target levels are maintained 1
• Ensure adequate fluid intake (at least 2 liters daily) and maintain neutral or slightly alkaline urine 5

When to Consider Specialist Referral

Consider referral to a specialist if: 1

• Unclear etiology of hyperuricemia
• Refractory signs or symptoms of gout
• Difficulty reaching target serum urate level
• Multiple or serious adverse events from ULT

Important Caveats

• Asymptomatic hyperuricemia alone (without gout, tophi, or other indications) is not an indication for ULT 5
• Low-dose aspirin (≤325 mg daily) may elevate serum urate but should not be discontinued if used for cardiovascular disease prophylaxis 1
• Diet and lifestyle measures alone typically provide insufficient serum urate-lowering effects (only 10-18% decrease) for patients with established gout 1
• HLA-B*5801 screening should be considered before allopurinol initiation in high-risk populations (Koreans with CKD stage 3 or worse, Han Chinese, and Thai patients) 1