What is the treatment for hyperuricemia?

Treatment of Hyperuricemia

Urate-lowering therapy (ULT) should not be initiated for asymptomatic hyperuricemia but should be started for patients with recurrent gout attacks, tophi, chronic kidney disease, or history of urolithiasis. 1

Indications for Pharmacologic ULT

The decision to initiate urate-lowering therapy should be based on:

• Presence of tophi (clinically or on imaging)
• Frequent gout attacks (≥2 attacks/year)
• Chronic kidney disease stage 2 or worse
• History of urolithiasis 2, 1

First-Line Pharmacologic Treatment

When ULT is indicated, the treatment algorithm is as follows:

1. Xanthine Oxidase Inhibitors (XOIs):

   • Allopurinol is the preferred first-line agent
   • Start at low dose (100mg daily) and gradually titrate upward
   • Adjust dose based on renal function (100mg daily if CrCl <10 mL/min) 1, 3
   • Febuxostat is an alternative XOI

2. Alternative First-Line Option:

   • Probenecid can be used when XOIs are contraindicated
   • Not recommended as first-line in patients with CrCl <50 mL/min 2, 1, 4

3. For Refractory Cases:

   • Pegloticase is reserved for severe disease that has failed other treatments 1

Treat-to-Target Approach

• Target serum urate level should be <6 mg/dL for most patients
• A more aggressive target of <5 mg/dL may be needed for patients with tophi 2, 1
• Monitor serum urate levels every 2-5 weeks during dose adjustment
• Once target is achieved, check every 6 months 1

Prophylaxis During ULT Initiation

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

Non-Pharmacologic Management

• Lifestyle modifications:
  • Limit purine-rich foods (red meat, seafood)
  • Avoid high fructose corn syrup sweetened beverages
  • Limit alcohol consumption, particularly beer
  • Consume low-fat dairy products and vegetables
  • Maintain adequate hydration (goal: at least 2 liters of urine output daily) 1, 3
  • Weight reduction for obese individuals 1, 5

Duration of Treatment

• ULT is typically lifelong
• Discontinuing treatment after symptoms resolve is not recommended
• Continue all measures needed to maintain serum urate <6 mg/dL indefinitely 2, 1

Common Pitfalls to Avoid

1. Treating asymptomatic hyperuricemia without clinical indications
2. Failing to titrate ULT to achieve target serum urate levels
3. Not providing prophylaxis when initiating ULT
4. Discontinuing ULT after symptoms resolve
5. Using high-dose colchicine for acute attacks 1

Special Considerations

• Renal Impairment: Adjust allopurinol dosing based on creatinine clearance:

  • CrCl 10-20 mL/min: 200 mg daily
  • CrCl <10 mL/min: ≤100 mg daily
  • CrCl <3 mL/min: may need extended interval between doses 3

• When to Consider Specialist Referral:

  • Unclear etiology of hyperuricemia
  • Refractory signs or symptoms of gout
  • Difficulty reaching target serum urate, particularly with renal impairment
  • Multiple/serious adverse events from ULT 2

Remember that while hyperuricemia has been associated with various conditions including cardiovascular disease, hypertension, and metabolic syndrome 6, current guidelines do not recommend pharmacologic treatment for asymptomatic hyperuricemia to prevent these conditions 1.