Core principle

1. Acute flare

• Oral prednisone 30-40 mg/day (about 0.5 mg/kg) for 5-7 days. A short taper over 7-10 days also works.
• If only one or two joints are involved, use an intra-articular injection. It has the least systemic effect.
• Watch for fluid retention, hypertension, and hyperglycemia, especially in diabetic patients.

• Standard low-dose flare regimen: 1.2 mg, then 0.6 mg an hour later.
• With eGFR below 30: give a single 0.6 mg dose and do not repeat the flare course more often than every 2 weeks.
• On dialysis: single 0.6 mg dose, no repeat for 2 weeks. It is not removed by dialysis.
• Avoid or reduce the dose with strong CYP3A4 or P-gp inhibitors (clarithromycin, cyclosporine, azole antifungals, diltiazem, verapamil). Toxicity includes myopathy, neuropathy, and marrow suppression.

• They cause AKI, worsen CKD, and cause hyperkalemia and fluid retention. They interact with ACE inhibitors, ARBs, and diuretics. Avoid them at eGFR below 30 and use extreme caution at eGFR 30-60.

• IL-1 inhibitors (anakinra, canakinumab). Anakinra needs dose spacing in severe renal impairment.

2. Long-term urate lowering

• Strong: tophi, radiographic damage, or two or more flares a year.
• Conditionally recommended: a first flare in a patient with CKD stage 3 or worse, serum urate above 9 mg/dL, or urolithiasis.
• So many CKD patients with even a single flare qualify.

• Start low: 50 mg/day, or up to 100 mg/day, and lower in advanced CKD. A low start reduces hypersensitivity risk and flares.
• Titrate every 2-5 weeks to target. Doses above 300 mg/day are acceptable in CKD if tolerated and monitored. The old "dose by creatinine clearance" cap is not recommended as a ceiling.
• On dialysis, give the dose after the session.
• Screen for HLA-B*58:01 before starting in people of Southeast Asian (Han Chinese, Thai) or Korean descent, and in African American patients. Risk of allopurinol hypersensitivity syndrome is higher with CKD, thiazide use, and a high starting dose.

• Febuxostat: start at 40 mg, up to 80 mg. It needs no adjustment in mild to moderate CKD and has limited data in severe CKD. It has an FDA boxed warning for cardiovascular death, based on the CARES trial. Reserve it for allopurinol intolerance or failure, and use it cautiously in patients with CVD.
• Probenecid: poorly effective and ineffective at low GFR. Avoid it when CrCl is below about 50 mL/min or in patients with kidney stones.
• Benzbromarone (where available): it works at lower GFR but carries a risk of liver toxicity.
• Pegloticase (refractory tophaceous gout): check G6PD first. Co-prescribing methotrexate improves response. Stop it if serum urate rises above 6 mg/dL on two consecutive measurements, because of infusion reaction and anaphylaxis risk.
• Combination therapy: a xanthine oxidase inhibitor plus a uricosuric, if monotherapy fails and renal function allows.

• Low-dose colchicine, 0.3-0.6 mg daily, reduced for CKD. Alternatively, low-dose prednisone (under 10 mg/day) if colchicine is not suitable. Avoid NSAIDs.

3. Medications and comorbidities

• Review diuretics. Thiazides and loop diuretics raise urate. Switch where possible; losartan is mildly uricosuric, and calcium channel blockers are neutral.
• Low-dose aspirin raises urate slightly but should be continued if it is indicated.
• SGLT2 inhibitors lower serum urate and may reduce gout flares. They are already indicated for many patients with CKD, diabetes, or heart failure.
• Manage hypertension, diabetes, dyslipidemia, and obesity, since all are common in these patients.
• Uric acid stones: encourage fluids and consider urinary alkalinization.

4. Lifestyle

• Limit alcohol (especially beer and spirits), organ meats, and shellfish. Avoid fructose-sweetened drinks.
• Lose weight if overweight, and stay hydrated.
• Keep dietary protein within CKD-appropriate limits. Diet alone rarely reaches target in CKD.

5. Monitoring

• During titration: serum urate every 2-5 weeks.
• At target: serum urate about every 6 months.
• Other labs: creatinine/eGFR, liver enzymes, and CBC periodically. For allopurinol, watch for rash, fever, eosinophilia, and rising creatinine.

6. Does lowering urate protect the kidney?

• Trials in people with CKD but without gout have not shown that allopurinol slows eGFR decline. These include CKD-FIX and the febuxostat FEATHER trial.
• So treat gout to prevent flares, tophi, and joint damage. Do not give ULT only to protect kidney function in asymptomatic hyperuricemia.

Quick summary