What is the treatment for elevated serum uric acid levels?

Treatment of Elevated Serum Uric Acid

For patients with gout, initiate urate-lowering therapy with allopurinol starting at 100 mg daily (50 mg if CKD stage ≥4), titrate every 2-4 weeks to achieve serum uric acid below 6 mg/dL, and maintain this target indefinitely. 1, 2

When to Treat Elevated Serum Uric Acid

Strongly recommended indications (treat these patients):

• One or more subcutaneous tophi detected on physical exam or imaging 1
• Radiographic damage from gout on any imaging modality 1
• Frequent gout flares (≥2 attacks per year) 1

Conditionally recommended indications (shared decision-making):

• Infrequent flares (<2 per year but >1 previous flare) 1
• First gout flare with high-risk features: CKD stage ≥3, serum uric acid >9 mg/dL, or history of urolithiasis 1
• CKD stage 2 or worse with prior gout attacks 1
• Past urolithiasis 1

Do NOT treat:

• Asymptomatic hyperuricemia (elevated uric acid without gout symptoms or tophi) - conditionally recommended against treatment 1, 3
• First gout flare without high-risk features - conditionally recommended against immediate treatment 1

Initial Evaluation Before Starting Treatment

Screen for secondary causes and modifiable factors:

• Calculate estimated glomerular filtration rate to assess CKD 2
• Screen for coronary heart disease, heart failure, stroke, peripheral arterial disease, diabetes, obesity, hyperlipidemia, and hypertension 1, 2
• For gout onset before age 25 or urolithiasis history, obtain 24-hour urine uric acid to detect overproduction 1, 2
• Eliminate non-essential medications that elevate uric acid: thiazide and loop diuretics, niacin, calcineurin inhibitors 1, 2
• Do NOT discontinue low-dose aspirin (≤325 mg daily) for cardiovascular prophylaxis despite modest uric acid elevation 1

Pharmacologic Treatment Algorithm

First-Line Therapy: Allopurinol

Starting dose:

• 100 mg daily for normal renal function 1, 2, 3
• 50 mg daily for CKD stage 4 or worse 1, 2

Titration strategy:

• Increase by 100 mg every 2-4 weeks until target achieved 1, 2
• Can dose above 300 mg daily with appropriate monitoring, including in CKD patients 1
• Check serum uric acid every 2-4 weeks during titration 1, 2

Special consideration for severe hypersensitivity risk:

• Consider HLA-B*5801 screening before starting in Koreans with CKD stage ≥3, all Han Chinese, and all Thai patients 1

Alternative First-Line Options

Febuxostat:

• Appropriate as first-line alternative to allopurinol 1
• No preferential recommendation between allopurinol and febuxostat 1

Probenecid:

• Use as alternative first-line only if at least one xanthine oxidase inhibitor is contraindicated or not tolerated 1
• Do NOT use as monotherapy if creatinine clearance <50 mL/min 1

Treatment Targets

Standard target:

• Serum uric acid <6 mg/dL for all patients 1, 2

Intensive target for severe disease:

• Serum uric acid <5 mg/dL for patients with tophi, chronic tophaceous gouty arthropathy, or frequent attacks until complete crystal dissolution 1, 2

Flare Prophylaxis During Treatment Initiation

All patients starting urate-lowering therapy require prophylaxis for the first 6 months: 2

First choice:

• Colchicine 0.5-1 mg daily 1, 2
• Loading dose of 1 mg followed by 0.5 mg one hour later for acute flares 1
• Avoid in severe renal impairment 1
• Do NOT give with strong P-glycoprotein or CYP3A4 inhibitors (cyclosporin, clarithromycin) 1

Alternative options:

• Low-dose NSAIDs (with proton pump inhibitor if appropriate) if colchicine contraindicated 1, 2
• Oral corticosteroids (30-35 mg prednisolone equivalent for 3-5 days) 1

Key principle:

• Urate-lowering therapy can be started during an acute flare if effective anti-inflammatory management is instituted 1

Lifestyle Modifications (Adjunctive to Pharmacotherapy)

Dietary recommendations:

• Limit purine-rich meats and seafood 1, 2
• Avoid high-fructose corn syrup sweetened beverages 1, 2
• Encourage low-fat or non-fat dairy products 1, 2
• Reduce alcohol consumption, especially beer; avoid during active arthritis 1, 2

Important caveat: Diet and lifestyle measures alone provide only 10-18% reduction in serum uric acid and are therapeutically insufficient for most patients with sustained hyperuricemia substantially above 7 mg/dL 1

Long-Term Monitoring

Once target achieved:

• Monitor serum uric acid every 6 months to ensure target maintained and assess adherence 1, 2
• Continue urate-lowering therapy indefinitely - this is lifelong treatment 2
• Continue prophylaxis until tophi and all acute/chronic gout symptoms resolve 1

When to Refer to Specialist

Consider referral for: 1

• Unclear etiology of hyperuricemia
• Refractory signs or symptoms despite treatment
• Difficulty reaching target serum urate, particularly with renal impairment after trial of xanthine oxidase inhibitor
• Multiple or serious adverse events from urate-lowering therapy

Common Pitfalls to Avoid

• Do NOT use the Hande algorithm for allopurinol dosing based solely on creatinine clearance - this non-evidence-based approach prevents adequate dose titration 1
• Do NOT stop urate-lowering therapy during acute flares - continue treatment and manage inflammation separately 1
• Do NOT undertitrate allopurinol - doses ≤300 mg daily fail to achieve target in the majority of patients 1
• Do NOT treat asymptomatic hyperuricemia - this is not an indication for therapy despite elevated levels 1, 3