How is hyperuricemia managed?

Management of Hyperuricemia with Uric Acid Level of 11.2 mg/dL

For a patient with a uric acid level of 11.2 mg/dL, initiate urate-lowering therapy with allopurinol starting at 100 mg daily, titrating upward by 100 mg every 2-4 weeks until serum uric acid is reduced below 6 mg/dL, while implementing dietary modifications and evaluating for underlying causes of hyperuricemia. 1

Initial Assessment and Evaluation

Before starting treatment, determine whether this patient has symptomatic gout (prior attacks, tophi, or urolithiasis) or asymptomatic hyperuricemia:

• If the patient has documented gout attacks, tophi, or chronic gouty arthritis, treatment is clearly indicated to prevent further urate deposition, reduce acute attacks, and improve quality of life 1, 2
• If this is asymptomatic hyperuricemia discovered incidentally without any history of gout, tophi, or kidney stones, treatment is NOT recommended as no data support metabolic health benefits from treating asymptomatic hyperuricemia 2

Evaluate for secondary causes of hyperuricemia by checking for medications that elevate uric acid (thiazide and loop diuretics, niacin, calcineurin inhibitors) and consider discontinuing non-essential medications 1. Do not discontinue low-dose aspirin (≤325 mg daily) for cardiovascular prophylaxis, as its modest effect on serum urate is negligible 1.

Screen for uric acid overproduction with 24-hour urine uric acid collection if the patient has gout onset before age 25 or a history of kidney stones 1.

Pharmacologic Treatment Algorithm

First-Line Therapy: Allopurinol

Start allopurinol at 100 mg daily and increase by 100 mg increments every 2-4 weeks until serum uric acid reaches the target of <6 mg/dL 1, 3. The maximal recommended dosage is 800 mg daily 3.

• Normal serum urate levels are typically achieved in 1-3 weeks at the appropriate dose 3
• The upper limit of normal is 7 mg/dL for men and postmenopausal women, and 6 mg/dL for premenopausal women 3
• Take allopurinol following meals for better tolerability 3

Critical pitfall to avoid: Do not start with standard doses of 300 mg in patients with any degree of renal impairment, as this increases toxicity risk 4. Even with normal renal function, starting low and titrating reduces the risk of precipitating acute gout flares 3.

Flare Prophylaxis During Initiation

Continue colchicine and/or anti-inflammatory agents during allopurinol dose titration until serum uric acid has normalized and the patient has been free from acute gouty attacks for several months 3. This prevents the mobilization of urate from tissue deposits as serum uric acid begins to fall 3.

Alternative and Second-Line Options

If the serum uric acid target cannot be reached with appropriate allopurinol dosing:

• Switch to febuxostat or add a uricosuric agent (probenecid, or off-label fenofibrate or losartan) 1
• Febuxostat is preferred over uricosurics as it does not require dose adjustment in mild to moderate renal impairment 1, 4
• Combination therapy with allopurinol plus a uricosuric agent can be effective if monotherapy fails 1, 4

For patients with crystal-proven severe debilitating chronic tophaceous gout who cannot reach target uric acid with maximal doses of other agents (including combinations), pegloticase is indicated 1.

Lifestyle and Dietary Modifications

Implement these measures for all patients with hyperuricemia, regardless of whether pharmacologic therapy is initiated 1:

• Weight loss if overweight or obese 1
• Limit alcohol consumption, especially beer and spirits 1
• Avoid sugar-sweetened drinks and foods high in fructose (including orange and apple juice) 1
• Reduce intake of purine-rich meats and seafood 1
• Encourage low-fat dairy products (particularly skimmed milk and low-calorie yogurt) 1
• Maintain adequate hydration with fluid intake sufficient to yield at least 2 liters of daily urinary output 3
• Regular physical activity 1

These dietary changes lower uric acid as a secondary benefit but are primarily indicated for overall metabolic health and prevention of life-threatening comorbidities including coronary artery disease, obesity, metabolic syndrome, diabetes, and hypertension 1.

Monitoring and Long-Term Management

• Monitor serum uric acid every 2-4 weeks during dose titration to ensure levels are decreasing toward the target of <6 mg/dL 1, 4
• Maintain serum uric acid <6 mg/dL lifelong once the target is achieved 1
• A serum uric acid level <3 mg/dL is not recommended for long-term maintenance 1
• Continue treatment indefinitely to prevent total crystal dissolution and resolution of gout 1

Special Considerations for Renal Impairment

If this patient has any degree of renal impairment (not specified in the question but critical to assess):

• With creatinine clearance 10-20 mL/min, use 200 mg daily maximum 3
• With creatinine clearance <10 mL/min, do not exceed 100 mg daily 3
• With extreme renal impairment (creatinine clearance <3 mL/min), lengthen the interval between doses 3
• Allopurinol and its metabolites are primarily eliminated by the kidney, so accumulation occurs in renal failure 3

When to Refer to a Specialist

Consider referral to a rheumatologist for 1:

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