How to manage gout in patients with chronic kidney disease (CKD) and impaired renal function?

Managing 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 moderate-to-severe disease (stage ≥3), and should be initiated in CKD patients after even their first gout flare when serum urate is >9 mg/dL or when there is no avoidable precipitant. 1

When to Initiate Urate-Lowering Therapy in CKD Patients

CKD stage >3 is a specific indication for earlier ULT initiation:

• Strongly recommend initiating ULT in patients with frequent gout flares (≥2/year), subcutaneous tophi, or radiographic damage attributable to gout 1
• Conditionally recommend initiating ULT after the first gout flare in patients with CKD stage >3, serum urate >9 mg/dL, or urolithiasis 1
• The rationale is that CKD patients have higher likelihood of gout progression, tophus development, and limited treatment options for acute flares 1
• ULT may provide added benefit in preventing progression of renal disease 1

Do NOT initiate ULT for asymptomatic hyperuricemia, even in CKD patients - the number needed to treat is 24 patients for 3 years to prevent a single incident gout flare, and benefits do not outweigh risks 1

Choice of Urate-Lowering Therapy

Allopurinol is the preferred first-line agent for all patients, including those with moderate-to-severe CKD (stage ≥3):

• Start at low dose (50-100 mg daily) and titrate upward by 100 mg every 2-4 weeks as needed, up to maximum FDA-approved dose of 800 mg/day 1
• Dose adjustment is required based on renal function, but higher doses than traditionally recommended can be used safely with careful monitoring 1, 2
• Allopurinol and benzbromarone have been shown to improve renal function in gout patients with CKD 2

Xanthine oxidase inhibitors are preferred over uricosuric agents in CKD patients 1

Febuxostat is an alternative if allopurinol is not tolerated:

• Febuxostat 80 mg achieves target serum urate <6 mg/dL in 44-71% of patients with renal insufficiency 2
• Has not been studied in patients with creatinine clearance <30 mL/min 3

Managing Acute Gout Flares in CKD

Oral corticosteroids (prednisone/prednisolone 30-35 mg daily for 3-5 days) are the safest and most effective first-line option for acute flares in CKD patients, particularly when colchicine and NSAIDs must be avoided: 1, 4, 5, 6

Treatment Options by CKD Severity:

Mild-to-moderate CKD (eGFR 30-80 mL/min):

• Colchicine (1 mg loading dose followed by 0.5 mg one hour later, within 12 hours of symptom onset) can be used without dose adjustment, but monitor closely for adverse effects 1, 7
• NSAIDs should be avoided due to risk of acute kidney injury 1, 3
• Oral corticosteroids remain a safe alternative 4, 5

Severe CKD (eGFR <30 mL/min) or dialysis:

• Colchicine and NSAIDs should be avoided 1, 4
• Oral corticosteroids are the drug of choice (prednisone 30-35 mg daily for 3-5 days, or 0.5 mg/kg/day for 5-10 days then stop or taper) 4, 5, 6
• No dose adjustment required for corticosteroids in renal impairment 4, 6
• For dialysis patients requiring colchicine, reduce to single 0.6 mg dose, not repeated more than once every two weeks 7

Alternative acute treatment options:

• Intra-articular corticosteroid injection for 1-2 affected joints (highly effective, avoids systemic exposure) 4, 5
• Parenteral glucocorticoids (IM or IV) when oral medications cannot be taken 4, 5
• IL-1 inhibitors (canakinumab 150 mg subcutaneously) for patients with contraindications to colchicine, NSAIDs, AND corticosteroids, with at least 12 weeks between doses 4, 5

Critical Drug Interactions and Contraindications

Colchicine is absolutely contraindicated when combined with strong CYP3A4 or P-glycoprotein inhibitors in patients with any degree of renal impairment - this combination can cause fatal toxicity 1, 4, 7

Specific contraindicated combinations in CKD:

• Colchicine + cyclosporine 1, 7
• Colchicine + clarithromycin 1, 7
• Colchicine + ritonavir/nirmatrelvir (Paxlovid) 1
• Colchicine + other macrolide antibiotics, diltiazem, verapamil, azole antifungals 1

Prophylaxis During ULT Initiation

Mandatory anti-inflammatory prophylaxis for 3-6 months when initiating or restarting ULT: 1, 5

• First-line: Colchicine 0.5-1 mg daily (if renal function permits) 1
• Second-line: Low-dose prednisone (<10 mg/day) if colchicine and NSAIDs are contraindicated 4, 5
• In severe CKD, start colchicine at 0.3 mg/day or use low-dose prednisone 7

Monitoring and Target Goals

Target serum urate <6 mg/dL (360 μmol/L) to promote crystal dissolution and prevent crystal formation 1

Monitor serum urate within 6 months of initiating ULT and adjust doses accordingly - however, adherence to this guideline is poor, with only 48% of patients monitored appropriately 8

Calculate eGFR at diagnosis and monitor regularly in parallel with serum urate measurement 1

Common Pitfalls to Avoid

• Failing to treat acute flares early - effectiveness is significantly reduced with delayed treatment; educate patients on "pill in pocket" approach 1, 5
• Using NSAIDs in CKD patients - can cause acute kidney injury and cardiovascular complications 1, 4, 3
• Not recognizing colchicine drug interactions - particularly with CYP3A4 inhibitors in CKD patients, which can be fatal 1, 4
• Underdosing allopurinol in CKD - higher doses than traditionally recommended can be used safely with monitoring 2
• Not initiating ULT prophylaxis - failure to provide anti-inflammatory prophylaxis when starting ULT leads to treatment-induced flares 5
• Stopping corticosteroids too abruptly in severe flares - consider restarting or combination therapy if flare recurs 4

Monitoring Considerations for Corticosteroid Use

• Monitor for dysphoria, mood disorders, elevated blood glucose, and fluid retention 4, 5
• Increase frequency of blood glucose monitoring in patients with diabetes 1, 5
• Corticosteroids are contraindicated in patients with systemic fungal infections 4, 5

When to Involve Specialists

Comanagement with rheumatology is advocated for acute and recurrent symptomatic gout in CKD patients 1