What are the management options for hyperuricemia?

Management of High Uric Acid (Hyperuricemia)

The management of hyperuricemia should include both lifestyle modifications and pharmacologic therapy, with xanthine oxidase inhibitors like allopurinol or febuxostat as first-line medications for patients with gout, targeting serum urate levels below 6 mg/dL. 1

Diagnostic Approach and Treatment Indications

When to Treat Hyperuricemia

• Asymptomatic hyperuricemia should not be treated with pharmacologic urate-lowering therapy 1
• Indications for urate-lowering therapy include:
  • Recurrent gout attacks
  • Presence of tophi
  • Chronic kidney disease with history of gout
  • History of urolithiasis with gout
  • Early-onset gout 1

Non-Pharmacologic Management

Dietary Recommendations

• Limit consumption of:

  • Purine-rich meats and seafood
  • High fructose corn syrup sweetened beverages
  • Sugar-sweetened drinks 2, 1

• Avoid:

  • Alcohol overconsumption, particularly beer and spirits
  • Complete alcohol abstinence during active gout attacks 2

• Encourage consumption of:

  • Low-fat or non-fat dairy products
  • Vegetables
  • Coffee (may help lower urate levels) 2, 1

Weight Management and Exercise

• Weight reduction for obese individuals with hyperuricemia 1, 3
• Regular physical activity to decrease mortality associated with chronic hyperuricemia 2
• Maintain adequate hydration (goal: at least 2 liters of urine output daily) 1, 4

Pharmacologic Management

First-Line Therapy

• Xanthine oxidase inhibitors (XOIs):
  • Allopurinol: Start at 100 mg/day and increase by 100 mg increments every 2-4 weeks until target serum urate is reached 2, 4
  • Febuxostat: Alternative first-line agent, particularly in patients with renal impairment 2, 1
  • Both effectively reduce serum urate levels 2

Dose Adjustments for Special Populations

• Renal impairment:
  • Allopurinol: With creatinine clearance 10-20 mL/min, use 200 mg/day; with clearance <10 mL/min, use ≤100 mg/day 4
  • Febuxostat: Preferred in patients with moderate renal impairment 2, 1
  • For patients with eGFR <30 mL/min, avoid probenecid 2

Alternative and Combination Therapies

• Uricosuric agents (e.g., probenecid):

  • Consider when XOIs are contraindicated or not tolerated 2, 1
  • May be combined with XOIs when target serum urate is not achieved with monotherapy 2

• Other uricosuric options:

  • Losartan or fenofibrate can be used as adjunctive therapy for their uricosuric effects 2

• Pegloticase:

  • Reserved for patients with severe tophaceous gout refractory to or intolerant of appropriately dosed oral urate-lowering therapy 2, 1
  • Not recommended as first-line therapy 2

Treatment Targets and Monitoring

• Serum urate target:

  • <6 mg/dL for most patients
  • <5 mg/dL for patients with tophi or severe gout 2, 1

• Monitoring:

  • Check serum urate every 2-5 weeks during dose adjustment
  • Once target is achieved, check every 6 months
  • Track frequency of gout attacks and tophi size 1

Prophylaxis During Initiation of Urate-Lowering Therapy

• Prophylaxis against acute flares is essential when starting urate-lowering therapy
• Options include:
  • Low-dose colchicine (up to 1.2 mg/day)
  • NSAIDs
  • Low-dose glucocorticoids 1

Common Pitfalls to Avoid

1. Failing to titrate urate-lowering therapy to achieve target serum urate levels
2. Not providing prophylaxis when initiating urate-lowering therapy
3. Discontinuing urate-lowering therapy after symptoms resolve (therapy is typically lifelong)
4. Treating asymptomatic hyperuricemia without appropriate indications
5. Using high-dose colchicine for acute attacks 1

Special Considerations

• Patients with the HLA-B*5801 haplotype (prevalent in Asian populations) have increased risk for serious adverse effects with allopurinol 2
• Consider specialist referral for patients with:
  • Unclear etiology of hyperuricemia
  • Refractory symptoms
  • Difficulty reaching target serum urate
  • Multiple/serious adverse events from urate-lowering therapy 1

Remember that urate-lowering therapy is typically lifelong, and discontinuing treatment after symptoms resolve is not recommended, as this will lead to recurrence of hyperuricemia and gout attacks.