What are the indications for treatment of hyperuricemia?

Indications for Treatment of Hyperuricemia

Pharmacologic urate-lowering therapy (ULT) is indicated for patients with established gouty arthritis who have tophi (detected by clinical exam or imaging), frequent attacks of acute gouty arthritis (≥2 attacks/year), chronic kidney disease stage 2 or worse, or past urolithiasis. 1

Diagnostic Considerations

• Definitive diagnosis of gout requires identification of monosodium urate crystals in joint fluid or tophi aspirate 1
• Clinical evaluation should include assessment of:
  • Frequency and severity of acute gout attacks 1
  • Presence of tophi on physical examination 1
  • Evaluation of potential secondary causes of hyperuricemia (see below) 1

Indications for Pharmacologic ULT

Pharmacologic treatment is indicated in the following scenarios:

• Any patient with established diagnosis of gouty arthritis AND:
  • Presence of tophi detected by clinical exam or imaging study 1
  • Frequent attacks of acute gouty arthritis (≥2 attacks/year) 1
  • Chronic kidney disease stage 2 or worse 1
  • History of urolithiasis 1

Non-Indications for Treatment

• Asymptomatic hyperuricemia is NOT an indication for pharmacologic ULT 1, 2
  • There is insufficient evidence that treating asymptomatic hyperuricemia prevents gouty arthritis, renal disease, or cardiovascular events 2

Secondary Causes of Hyperuricemia to Consider

• Medications: thiazide and loop diuretics, low-dose aspirin, niacin, calcineurin inhibitors 1
• Medical conditions: obesity, metabolic syndrome, hypertension, chronic kidney disease 3, 4
• Dietary factors: excessive alcohol intake (particularly beer), high purine foods, high fructose corn syrup 1

Treatment Approach When ULT is Indicated

1. Set a serum urate target:

   • Minimum target is <6 mg/dL for all patients 1
   • Target <5 mg/dL may be needed for patients with severe gout or tophi 1

2. First-line pharmacologic therapy:

   • Xanthine oxidase inhibitors (XOI) - either allopurinol or febuxostat 1
     • Allopurinol starting dose should be no greater than 100 mg/day (50 mg/day in stage 4 or worse CKD) 1, 5
     • Gradually titrate dose upward every 2-5 weeks to reach serum urate target 1

3. Alternative or add-on therapy if target not achieved:

   • Probenecid (uricosuric agent) - can be used as alternative first-line therapy if XOI is contraindicated 1, 6
     • Not recommended as first-line monotherapy if creatinine clearance <50 ml/min 1
   • Combination therapy with XOI plus uricosuric agent (probenecid, fenofibrate, or losartan) if target not achieved with monotherapy 1

Monitoring and Long-Term Management

• Monitor serum urate every 2-5 weeks during ULT titration 1
• Once target is achieved, continue monitoring every 6 months 1
• Continue ULT indefinitely to maintain serum urate below target level 1
• After resolution of tophi and cessation of gout attacks, continue ULT to maintain serum urate <6 mg/dL 1

Common Pitfalls to Avoid

• Undertreating gout: Failing to titrate ULT to achieve target serum urate levels 1
• Discontinuing ULT prematurely: ULT should be continued indefinitely in patients with established gout 1
• Ignoring renal function: Allopurinol dosing should be adjusted based on creatinine clearance 5
• Overlooking prophylaxis: When initiating ULT, prophylaxis against acute flares should be considered 1
• Treating asymptomatic hyperuricemia: This is not recommended and lacks evidence for preventing gout or other conditions 1, 2

By following these evidence-based recommendations, clinicians can effectively manage hyperuricemia in patients with gout, reducing the frequency of attacks and preventing long-term complications.