How to manage high uric acid levels?

Management of High Uric Acid Levels

For patients with asymptomatic hyperuricemia (uric acid >6.8 mg/dL without gout symptoms), do not initiate urate-lowering therapy—treatment is not recommended and potentially harmful. 1, 2

When NOT to Treat

• Asymptomatic hyperuricemia alone is not an indication for pharmacologic therapy, regardless of how elevated the uric acid level is 1, 2
• Treatment should be avoided in patients without prior gout flares, tophi, or radiographic damage from gout 1
• The number needed to treat is 24 patients for 3 years to prevent a single gout flare, making routine treatment unjustified 1

When to Initiate Urate-Lowering Therapy (ULT)

Strong Indications (Must Treat):

• Presence of tophi on physical exam or imaging 1
• Radiographic damage attributable to gout 1
• Frequent gout attacks (≥2 per year) 1
• Chronic kidney disease stage 2 or worse 1
• History of urolithiasis (kidney stones) 1

Conditional Indications (Consider Treatment):

• First gout flare with CKD stage ≥3, uric acid >9 mg/dL, or urolithiasis 1
• Infrequent flares (<2/year) but more than one prior episode 1

Initial Assessment Before Treatment

Screen for Secondary Causes:

• Check for medications elevating uric acid: thiazide/loop diuretics, niacin, calcineurin inhibitors, low-dose aspirin 1, 3
• Evaluate comorbidities: obesity, hypertension, hyperlipidemia, diabetes, chronic kidney disease 1, 3
• For early-onset gout (age <25) or urolithiasis history: obtain 24-hour urine uric acid to screen for overproduction 1, 3

Eliminate Non-Essential Urate-Elevating Drugs:

• Discontinue thiazide or loop diuretics if alternative antihypertensives are suitable 1, 3
• Consider losartan or calcium channel blockers for hypertension management 3
• Consider fenofibrate or statins for hyperlipidemia 3

Non-Pharmacologic Management (All Patients)

Dietary Modifications:

• Weight loss if BMI >25 1, 3, 4
• Limit alcohol consumption, especially beer and spirits 1, 3, 4
• Avoid sugar-sweetened beverages and high-fructose foods 1, 3, 4
• Reduce purine-rich foods: red meat, organ meats, certain seafood 1, 3, 4
• Encourage low-fat dairy products 1, 3, 4
• Consider coffee and vitamin C supplementation (may lower uric acid) 4

Pharmacologic Treatment Algorithm

First-Line Therapy: Allopurinol

• Start allopurinol 100 mg daily (even with renal impairment, contrary to older teaching) 1, 3, 5
• Titrate by 100 mg increments every 2-4 weeks until target uric acid achieved 1, 3, 5
• Maximum dose: 800 mg daily (FDA-approved) 1
• Adjust for creatinine clearance but do not avoid in renal disease 1, 3

HLA-B*5801 Screening (Specific Populations):

• Screen before starting allopurinol in patients of Korean, Han Chinese, or Thai descent 1
• If positive, use alternative agent (febuxostat or uricosuric) 1
• Screening not recommended for Caucasians (low prevalence ~2%) 1

Target Uric Acid Level:

• Maintain serum uric acid <6 mg/dL lifelong for all patients 1, 3, 5
• Target <5 mg/dL for severe disease (tophi, chronic arthropathy) until complete crystal dissolution 5
• Never target <3 mg/dL long-term 3

Second-Line Options (If Target Not Reached):

Option 1: Switch to Febuxostat

• Use if allopurinol fails to reach target or is not tolerated 1, 3, 5
• Dose: 40-80 mg daily (FDA-approved); up to 120 mg daily (international guidelines) 1

Option 2: Add or Switch to Uricosuric Agent

• Probenecid is first choice among available uricosurics in the US 1, 3
• Starting dose: 250 mg twice daily for 1 week, then 500 mg twice daily 6
• Titrate by 500 mg increments every 4 weeks (maximum 2000 mg daily) 6
• Contraindications: history of urolithiasis, uric acid overproduction (>800 mg/day in men, >750 mg/day in women), creatinine clearance <50 mL/min 1, 6
• Require urine alkalinization (sodium bicarbonate 3-7.5 g daily or potassium citrate 7.5 g daily) and increased fluid intake 1, 6

Option 3: Combination Therapy

• Combine allopurinol (or febuxostat) with probenecid if monotherapy inadequate 1, 5

Third-Line: Pegloticase

• Reserved for refractory chronic tophaceous gout unresponsive to conventional therapy 7
• Dose: 8 mg IV every 2 weeks 7
• Requires premedication with antihistamines and corticosteroids 7
• Monitor uric acid before each infusion; discontinue if levels rise >6 mg/dL on two consecutive measurements 7

Gout Flare Prophylaxis During ULT Initiation

• Mandatory for first 6 months of urate-lowering therapy 1, 5, 7
• First choice: Colchicine 0.5-1 mg daily 5, 7
• Alternative: Low-dose NSAID if colchicine contraindicated 5
• Do not discontinue ULT if flare occurs during treatment 1, 7

Monitoring Strategy

• Check uric acid every 2-4 weeks during dose titration 3, 5
• Once target achieved, monitor regularly (every 3-6 months) to ensure maintenance 3, 5
• Continue ULT indefinitely—this is lifelong therapy even after symptoms resolve 1, 3, 5

When to Refer to Specialist

• Unclear etiology of hyperuricemia 1, 3
• Refractory symptoms despite appropriate therapy 1, 3
• Difficulty reaching target uric acid, particularly with renal impairment after XOI trial 1, 3
• Multiple or serious adverse events from ULT 1, 3

Common Pitfalls to Avoid

• Do not treat asymptomatic hyperuricemia—this is explicitly not recommended and wastes resources 1, 2
• Do not underdose allopurinol—titrate to target uric acid, not to arbitrary dose limits 1, 5
• Do not avoid allopurinol in renal disease—dose adjust but do not withhold 1, 3
• Do not stop ULT during acute flares—continue therapy and treat flare separately 1, 7
• Do not use uricosurics in patients with urolithiasis or uric acid overproduction 1, 6
• Do not forget flare prophylaxis—failure to provide prophylaxis leads to treatment discontinuation 5, 7