How to manage hyperuricemia?

Management of Hyperuricemia

The most effective approach to manage hyperuricemia is a combination of pharmacologic therapy with allopurinol or febuxostat as first-line agents, along with specific dietary and lifestyle modifications, with the goal of achieving serum urate levels below 6 mg/dL. 1

Pharmacologic Management

First-Line Therapy

• Xanthine Oxidase Inhibitors (XOIs) are recommended as first-line pharmacologic treatment:
  • Allopurinol: Start at 100 mg daily (50 mg daily in patients with stage 4 or worse CKD) and gradually titrate upward 1
  • Febuxostat: Alternative first-line XOI with similar efficacy 1
  • Both medications work by inhibiting the formation of uric acid rather than increasing its excretion

Dosing and Titration

• Start with low doses and increase gradually to minimize risk of gout flares
• For allopurinol: Increase by 100 mg weekly until target serum urate is achieved 2
• Maximum recommended allopurinol dosage is 800 mg daily 2
• Adjust dosage based on renal function:
  • Creatinine clearance 10-20 mL/min: 200 mg daily
  • Creatinine clearance <10 mL/min: ≤100 mg daily 2

Alternative Agents

• Probenecid: Recommended as an alternative first-line option when XOIs are contraindicated or not tolerated 1
  • Not recommended as monotherapy in patients with creatinine clearance <50 mL/min
  • Has multiple drug interactions and ~10% risk of urolithiasis

Combination Therapy

• For refractory cases, combination therapy with XOI plus uricosuric agent may be considered
• Options include probenecid or medications with lesser uricosuric effects (fenofibrate, losartan) 1

Target Serum Urate Levels

• Primary goal: Achieve serum urate <6 mg/dL in all gout patients 1
• For patients with severe disease or tophi, target may need to be <5 mg/dL 1
• Regular monitoring of serum urate every 2-5 weeks during dose titration, then every 6 months once target is achieved 1

Dietary and Lifestyle Modifications

Recommended Dietary Changes

• Limit consumption of:

  • Purine-rich meats and seafood (Evidence B) 1
  • High fructose corn syrup sweetened beverages (Evidence C) 1
  • Alcohol, particularly beer (Evidence B) 1

• Encourage consumption of:

  • Low-fat or non-fat dairy products (Evidence B) 1
  • Vegetables, nuts, legumes, and whole grains 3
  • Coffee and vitamin C supplementation (may help lower urate levels) 3

Weight Management

• Weight reduction with daily exercise helps reduce uric acid levels 3
• Even modest weight loss can improve insulin sensitivity and reduce uric acid levels

Important Considerations

Monitoring and Follow-up

• Monitor serum urate regularly during treatment
• Continue anti-inflammatory prophylaxis during initiation of urate-lowering therapy
• ULT can be started during an acute gout attack if effective anti-inflammatory management is in place 1

Pitfalls to Avoid

1. Diet alone is insufficient: While dietary modifications are important, they typically only reduce serum urate by 10-18%, which is inadequate for most patients with significant hyperuricemia 1

2. Underdosing allopurinol: Doses of 300 mg or less daily often fail to achieve target serum urate in most gout patients 1

3. Neglecting comorbidities: Hyperuricemia is often associated with metabolic syndrome, cardiovascular disease, and kidney disease that require concurrent management 3, 4

4. Discontinuing therapy prematurely: ULT should be continued long-term, as discontinuation leads to recurrence of hyperuricemia 4

5. Ignoring medication adherence: Poor adherence to ULT is common and should be addressed through patient education and regular monitoring 1

Special Populations

Chronic Kidney Disease

• Gout with CKD stage 2-5 is an appropriate indication for pharmacologic ULT 1
• Allopurinol dosing must be adjusted based on creatinine clearance 2
• Consider HLA-B*5801 screening in high-risk populations (e.g., Koreans with stage 3 or worse CKD, Han Chinese, Thai) before starting allopurinol 1

By following this comprehensive approach to hyperuricemia management, patients can achieve target serum urate levels, reduce the frequency of gout attacks, and potentially slow the progression of associated comorbidities.