What is the management approach for patients with gout and Chronic Kidney Disease (CKD)?

Management of Gout in Patients with Chronic Kidney Disease

Allopurinol is the strongly recommended first-line urate-lowering therapy for all patients with gout and CKD, including those with stage 3 or worse renal impairment, starting at ≤100 mg/day (or ≤50 mg/day in stage 3 CKD) with gradual dose titration to achieve a serum urate target of <6 mg/dL. 1, 2

Initial Pharmacologic Approach

Urate-Lowering Therapy (ULT) Initiation

• Xanthine oxidase inhibitors (allopurinol or febuxostat) are strongly preferred over uricosuric agents like probenecid in patients with CKD stage ≥3. 1
• Allopurinol is specifically recommended as first-line over febuxostat due to superior safety profile, lower cost, and proven non-inferiority in the STOP-Gout trial for stage 3 CKD patients. 1, 2
• Probenecid should not be used as first-line monotherapy when creatinine clearance is below 50 mL/min. 1

Allopurinol Dosing Strategy in CKD

Start with ≤100 mg/day, and consider even lower doses (≤50 mg/day) in stage 3 CKD patients to mitigate risk of allopurinol hypersensitivity syndrome. 1, 2

• Dose titration should occur gradually at weekly intervals by 100 mg increments until serum urate <6 mg/dL is achieved, without exceeding 800 mg/day maximum. 3
• For creatinine clearance 10-20 mL/min, use 200 mg daily maximum. 3
• For creatinine clearance <10 mL/min, do not exceed 100 mg daily and consider lengthening the interval between doses. 3
• Despite traditional dose-capping concerns, allopurinol can be safely titrated above 300 mg/day even in CKD patients when needed to reach target serum urate. 1

When to Consider Febuxostat

• Febuxostat may be used as an alternative if documented allopurinol hypersensitivity or severe cutaneous adverse reactions occur. 2
• However, febuxostat carries an FDA black box warning regarding cardiovascular risk, and the American College of Rheumatology conditionally recommends switching from febuxostat to alternative ULT for patients with cardiovascular disease history or new cardiovascular events. 2
• Febuxostat lacks published safety data in stage 4 or worse CKD. 1

Acute Gout Flare Management in CKD

For symptomatic treatment of acute gout flares in CKD, low-dose colchicine or intra-articular/oral glucocorticoids are strongly preferable to NSAIDs. 1, 2

Colchicine Dosing in CKD

• The FDA-approved dosing for acute flares is 1.2 mg followed by 0.6 mg one hour later, but this standard loading dose should be avoided in patients with moderate-to-severe renal impairment. 1, 4
• For prophylaxis during ULT initiation, use low-dose colchicine (0.3-0.6 mg daily) with careful dose adjustment based on renal function. 4
• Colchicine must never be combined with strong CYP3A4 or P-glycoprotein inhibitors (macrolide antibiotics, azole antifungals, diltiazem, verapamil, cyclosporine, ritonavir/nirmatrelvir) in patients with any degree of renal impairment due to extreme toxicity risk. 1, 4

Alternative Anti-inflammatory Options

• Intra-articular or oral glucocorticoids are first-line alternatives when colchicine is contraindicated or not tolerated. 4
• NSAIDs are not recommended in CKD because they can exacerbate or cause acute kidney injury. 5

Anti-inflammatory Prophylaxis During ULT Initiation

Strongly recommend initiating concomitant anti-inflammatory prophylaxis therapy (colchicine, NSAIDs, or prednisone/prednisolone) when starting any ULT to prevent gout flares. 1, 3

• Continue prophylaxis for 3-6 months rather than <3 months, with ongoing evaluation and continued prophylaxis as needed if the patient continues to experience flares. 1
• Maintenance doses of colchicine should generally be given prophylactically when allopurinol is begun. 3
• Low-dose prednisone or prednisolone (≤10 mg/day) can be used as alternative prophylaxis in patients with colchicine intolerance or contraindications. 4

Timing of ULT Initiation

ULT can be started during an acute gout flare, provided that effective anti-inflammatory management has been instituted. 1

• Consider initiating ULT after the first episode of gout in CKD patients, particularly when there is no avoidable precipitant or serum uric acid concentration is >9 mg/dL (535 μmol/L). 1

Monitoring Requirements

• Monitor serum urate every 2-5 weeks during ULT titration, then every 6 months once target is achieved to assess adherence. 1
• In CKD patients on colchicine, monitor creatine phosphokinase (CPK) levels, complete blood count for neutropenia, liver enzymes, renal function, and proteinuria every 6 months for stable patients. 4
• Maintain fluid intake sufficient to yield daily urinary output of at least 2 liters and neutral or slightly alkaline urine. 3

Nonpharmacologic Interventions

Recommend limiting consumption of purine-rich meat and seafood, high fructose corn syrup sweetened beverages, and alcohol (particularly beer). 1

• Encourage consumption of low-fat or non-fat dairy products. 1
• Recognize that diet and lifestyle measures alone provide therapeutically insufficient serum urate-lowering effects (only ~10-18% decrease) for most patients with sustained hyperuricemia. 1

Critical Pitfalls to Avoid

• Do not use probenecid in patients with creatinine clearance <50 mL/min. 1
• Do not start allopurinol at doses >100 mg/day in CKD patients due to hypersensitivity risk. 1, 2
• Do not combine colchicine with CYP3A4 inhibitors in any patient with renal impairment—this is absolutely contraindicated. 1, 4
• Do not avoid dose titration of allopurinol above 300 mg/day in CKD patients if needed to reach serum urate target. 1
• Do not use NSAIDs for acute flares in CKD patients. 1, 5
• Do not treat asymptomatic hyperuricemia with urate-lowering agents solely to delay CKD progression—this is not recommended. 1

Special Considerations for Advanced CKD

• In patients with stage 4-5 CKD or end-stage renal disease, gout with CKD is itself an appropriate indication for pharmacologic ULT in patients with prior gout attacks and current hyperuricemia. 1
• Pegloticase is appropriate for patients with severe gout disease burden and refractoriness to, or intolerance of, appropriately dosed oral ULT therapy options, but requires further investigation in advanced CKD populations. 1, 5