What is the approach to managing hyperuricemia?

Management of Hyperuricemia

The optimal approach to managing hyperuricemia requires both non-pharmacological and pharmacological interventions tailored to specific risk factors, clinical phase, and general risk factors, with the goal of maintaining serum urate below 6 mg/dL to prevent morbidity and mortality associated with gout and its complications. 1, 2

Initial Assessment

• Perform a thorough clinical evaluation of disease activity through history and physical examination for symptoms of arthritis, presence of tophi, and signs of acute or chronic synovitis 3
• Screen for causes of hyperuricemia, including comorbidities (obesity, hypertension, hyperlipidemia, diabetes, kidney disease) and medications that can elevate uric acid (thiazides, loop diuretics, niacin, calcineurin inhibitors) 2
• Consider urine uric acid evaluation for patients with gout onset before age 25 or history of urolithiasis to screen for uric acid overproduction 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 urate-lowering therapy (ULT) 2

Non-Pharmacological Management

• Provide patient education about the disease, treatment objectives, and lifestyle modifications 2, 4
• Recommend weight loss if the patient is overweight or obese 2, 5
• Advise reduction in alcohol consumption, especially beer and spirits 1, 5
• Recommend avoiding sugar-sweetened drinks and foods rich in fructose 2, 6
• Limit intake of purine-rich foods (red meat, seafood) 1, 6
• Encourage consumption of low-fat dairy products 1, 6
• Advise regular physical activity 2, 5

Pharmacological Management

Indications for ULT

• Gout with chronic kidney disease stage 2-5 or end-stage renal disease is an appropriate indication for pharmacologic ULT in patients with prior gout attacks and current hyperuricemia 1
• Consider ULT for patients with recurrent gout attacks, tophi, or chronic tophaceous gout 1

First-line ULT

• Xanthine oxidase inhibitors (XOI) - either allopurinol or febuxostat - are recommended as first-line pharmacologic ULT 1, 2
• Start allopurinol 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 2, 7
• For patients with renal impairment, adjust allopurinol dosing:
  • With creatinine clearance of 10-20 mL/min: 200 mg daily
  • With creatinine clearance <10 mL/min: not exceeding 100 mg daily
  • With extreme renal impairment (clearance <3 mL/min): consider lengthening interval between doses 7

Alternative ULT

• Probenecid is recommended as an alternative first-line therapy when XOIs are contraindicated or not tolerated 1
• Do not use probenecid as first-line ULT monotherapy in patients with creatinine clearance below 50 mL/min 1
• Consider febuxostat if target serum urate level cannot be reached with allopurinol or if allopurinol is not tolerated 2

Monitoring and Target Levels

• Monitor serum urate every 2-5 weeks during ULT titration and continue measurements every 6 months once target is achieved to monitor adherence 1
• The target serum urate level should be below 6 mg/dL for all gout patients 1, 2
• For patients with greater disease severity and urate burden (e.g., tophi), target serum urate below 5 mg/dL 1, 3
• ULT can be started during an acute gout attack, provided that effective anti-inflammatory management has been instituted 1

Special Considerations

Chronic Kidney Disease

• In patients with chronic kidney disease, xanthine oxidase inhibitors are preferred over uricosuric agents, but dose adjustment is necessary 2, 8
• Allopurinol dose should be reduced in renal impairment according to creatinine clearance 7

Tumor Lysis Syndrome

• For hyperuricemia associated with tumor lysis syndrome, rasburicase is recommended for rapid reduction of uric acid levels 1, 3
• Rasburicase allows rapid degradation of uric acid to allantoin, enabling prompt continuation of chemotherapy 3

Common Pitfalls and Caveats

• Diet and lifestyle measures alone typically provide insufficient serum urate-lowering effects (only ~10-18% decrease) and are usually inadequate for patients with sustained hyperuricemia substantially above 7 mg/dL 1
• Poor adherence to ULT is a common problem in gout patients, necessitating regular monitoring of serum urate levels 1
• Allopurinol can cause hypersensitivity reactions; consider HLA-B*5801 screening in high-risk populations (Koreans with stage 3 or worse CKD, and all those of Han Chinese and Thai descent) 1
• Avoid targeting serum uric acid levels <3 mg/dL for long-term therapy 2
• When transferring a patient from a uricosuric agent to allopurinol, gradually reduce the dose of the uricosuric agent over several weeks while gradually increasing allopurinol 7