What is the treatment for hyperuricemia?

Treatment for Uric Acid Uria (Hyperuricemia)

Start with allopurinol as first-line therapy at 100 mg daily (50 mg daily if stage 4 or worse CKD), titrating upward every 2-5 weeks to achieve a target serum urate below 6 mg/dL, while implementing dietary modifications including limiting purine-rich meats, seafood, and high-fructose beverages. 1, 2, 3

Initial Assessment

Before initiating treatment, perform the following evaluations:

• Measure urinary uric acid levels to distinguish between uric acid overproduction and underexcretion, particularly in patients with gout onset before age 25 or history of kidney stones 1, 2
• Screen for secondary causes including medications (thiazides, loop diuretics, niacin, calcineurin inhibitors), obesity, hypertension, diabetes, and kidney disease 2, 4
• Assess renal function as this determines drug selection and dosing 1, 3
• Check for history of urolithiasis, which contraindicates first-line uricosuric therapy 1

Non-Pharmacologic Management

Implement these dietary and lifestyle modifications, though recognize they typically provide only 10-18% reduction in serum urate and are usually insufficient as monotherapy for sustained hyperuricemia above 7 mg/dL 4:

• Limit purine-rich foods including red meat and seafood 2, 4, 5
• Avoid high-fructose corn syrup sweetened beverages and energy drinks 2, 4
• Reduce alcohol consumption, particularly beer and spirits, with complete abstinence during acute gout attacks 4
• Encourage low-fat or non-fat dairy products which have urate-lowering effects 4, 5
• Promote weight reduction if obese 4
• Maintain fluid intake sufficient to produce at least 2 liters of urine daily 3

Pharmacologic Treatment Algorithm

First-Line: Xanthine Oxidase Inhibitors (XOIs)

Allopurinol is the preferred initial agent 1, 2, 4:

• Starting dose: 100 mg daily for most patients; 50 mg daily for stage 4 or worse CKD 1, 3
• Titration: Increase every 2-5 weeks to reach target serum urate 1
• Maximum dose: Can exceed 300 mg daily even with renal impairment, with appropriate monitoring for toxicity (pruritus, rash, elevated liver enzymes) 1
• Special consideration: Consider HLA-B*5801 screening before initiation in high-risk populations (Koreans with stage 3 or worse CKD; Han Chinese and Thai patients regardless of renal function) 1
• Renal dosing: With creatinine clearance 10-20 mL/min, use 200 mg daily; with clearance <10 mL/min, do not exceed 100 mg daily 3

Febuxostat is an alternative XOI with similar efficacy 2, 4:

• Use when allopurinol is not tolerated or contraindicated 1
• Can be substituted after initial failure of upward dose titration of allopurinol 1
• Important: Do not use in combination with allopurinol 1

Second-Line: Uricosuric Therapy

Probenecid is the first choice among uricosurics 1, 6:

• Use as alternative first-line therapy when XOIs are contraindicated or not tolerated 2, 4
• Contraindications: Creatinine clearance <50 mL/min, history of urolithiasis, elevated urinary uric acid indicating overproduction 1
• Before initiation: Measure urinary uric acid 1
• During therapy: Continue monitoring urinary uric acid 1
• Risk mitigation: Consider urine alkalinization with potassium citrate and monitor urine pH, plus increase fluid intake to prevent urolithiasis 1

Alternative uricosurics with clinically significant effects include fenofibrate and losartan, useful as components of comprehensive therapy 1

Combination Therapy for Refractory Disease

When monotherapy fails 1:

• First step: Attempt upward dose titration of one XOI to maximum appropriate dose 1
• Second step: Add a uricosuric agent (probenecid, fenofibrate, or losartan) to an XOI, or vice versa 1
• Third step: Consider switching between allopurinol and febuxostat if drug intolerance occurs 1

Third-Line: Pegloticase

Reserved for patients with severe gout disease burden and refractoriness to, or intolerance of, conventional and appropriately dosed urate-lowering therapy 1, 2:

• Not recommended as first-line therapy 1
• Important: Discontinue oral urate-lowering agents during pegloticase therapy to avoid masking loss of efficacy and increased risk of infusion reactions 1

Target Serum Urate Levels

• Standard target: Below 6 mg/dL for all gout patients 2, 4, 7
• Intensive target: Below 5 mg/dL for patients with greater disease severity and urate burden (tophi, chronic tophaceous gout) 2, 4, 7
• Avoid: Targeting levels <3 mg/dL for long-term therapy 7

Monitoring Protocol

• During titration: Check serum urate every 2-5 weeks 2, 4, 7
• After reaching target: Continue measurements every 6 months to monitor adherence 2, 4, 7
• Maintain neutral or slightly alkaline urine pH, particularly with uricosuric therapy 3

Special Populations

Chronic Kidney Disease

• Preferred agents: Xanthine oxidase inhibitors over uricosurics 2, 7
• Dose adjustment: Required based on creatinine clearance 3, 8
• For acute flares: Use low-dose colchicine or glucocorticoids rather than NSAIDs 2, 4

Tumor Lysis Syndrome

• Rasburicase is recommended for rapid uric acid reduction, allowing prompt continuation of chemotherapy 2, 7

Common Pitfalls to Avoid

• Inadequate allopurinol dosing: Many patients require doses above 300 mg daily; failure to titrate appropriately leads to suboptimal outcomes 4
• Starting at high doses: Increases risk of adverse events; always start low and titrate upward 4
• Poor adherence: Regular monitoring of serum urate helps address this common problem 4, 7
• Neglecting flare prophylaxis: When initiating urate-lowering therapy, failure to provide prophylaxis against acute flares leads to poor medication adherence 4
• Overreliance on diet alone: Dietary measures typically provide insufficient urate-lowering for most patients with sustained hyperuricemia substantially above 7 mg/dL 4, 7