What are the treatment options for gout in patients with advanced Chronic Kidney Disease (CKD)?

From the Guidelines

For patients with gout in advanced chronic kidney disease (CKD), allopurinol is recommended as the first-line urate-lowering therapy, starting at a low dose (less than 100 mg/day) with subsequent dose titration to target, due to its moderate certainty of evidence and recommendation from the 2020 American College of Rheumatology guideline 1. When managing gout in advanced CKD, it is crucial to consider the altered drug clearance and increased risk of adverse effects.

Key Considerations

• Xanthine oxidase inhibitors, such as allopurinol or febuxostat, are preferred over uricosuric agents like probenecid in patients with CKD and symptomatic hyperuricemia 1.
• For acute gout flares, low-dose colchicine or intra-articular/oral glucocorticoids are preferable to nonsteroidal anti-inflammatory drugs (NSAIDs) due to the potential of NSAIDs to worsen kidney function 1.
• Dietary modifications, including limiting high-purine foods, alcohol (especially beer), and sugary beverages, are important adjuncts in managing gout in advanced CKD.
• Adequate hydration within fluid restrictions is essential, and uric acid levels should be monitored regularly, targeting levels below 6 mg/dL.

Treatment Approach

• Allopurinol can be used but requires significant dose reduction, starting at 50-100 mg daily, with gradual titration based on uric acid levels and kidney function 1.
• Febuxostat (20-40 mg daily) may be safer in advanced CKD as it undergoes less renal elimination.
• Consultation with both nephrology and rheumatology is recommended to balance gout management with kidney protection, as medications that might be standard in patients with normal kidney function can accumulate to toxic levels in advanced CKD, potentially causing further kidney damage or other serious complications.

From the FDA Drug Label

For prophylaxis of gout flares in patients with mild (estimated creatinine clearance [Cl cr] 50 to 80 mL/min) to moderate (Cl cr 30 to 50 mL/min) renal function impairment, adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects of colchicine. However, in patients with severe impairment, the starting dose should be 0.3 mg/day and any increase in dose should be done with close monitoring. For the prophylaxis of gout flares in patients undergoing dialysis, the starting doses should be 0.3 mg given twice a week with close monitoring. For treatment of gout flares in patients with mild (Cl cr 50 to 80 mL/min) to moderate (Cl cr 30 to 50 mL/min) renal function impairment, adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects of colchicine However, in patients with severe impairment, while the dose does not need to be adjusted for the treatment of gout flares, a treatment course should be repeated no more than once every two weeks. For patients undergoing dialysis, the total recommended dose for the treatment of gout flares should be reduced to a single dose of 0.6 mg (one tablet). For these patients, the treatment course should not be repeated more than once every two weeks.

The recommended dose modification for gout treatment in patients with advanced CKD is as follows:

• For patients with severe renal impairment, the starting dose for prophylaxis of gout flares should be 0.3 mg/day and for treatment of gout flares, the dose does not need to be adjusted, but the treatment course should be repeated no more than once every two weeks.
• For patients undergoing dialysis, the starting dose for prophylaxis of gout flares should be 0.3 mg given twice a week and for treatment of gout flares, the total recommended dose should be reduced to a single dose of 0.6 mg (one tablet), and the treatment course should not be repeated more than once every two weeks 2.

From the Research

Gout Treatment in Advanced CKD

• Gout and chronic kidney disease (CKD) frequently coexist, but quality evidence to guide gout management in people with CKD is lacking 3.
• The use of urate-lowering therapy (ULT) in the context of advanced CKD varies greatly, and professional bodies have issued conflicting recommendations regarding the treatment of gout in people with concomitant CKD 3.
• Allopurinol and febuxostat are the most commonly used urate-lowering therapies with established safety and efficacy in CKD patients 4.
• Febuxostat may be more renoprotective than allopurinol in patients with both hyperuricemia and CKD based on evidence from small long-term retrospective studies with serious risk of bias 4.

Treatment Options

• Acute gout flares are treated with various agents, including nonsteroidal anti-inflammatory drugs, colchicine, glucocorticoids, and IL-1 inhibitors 5.
• ULT is recommended to treat recurrent flares, tophaceous deposits, and patients with moderate-to-severe CKD with a serum urate goal of <6 mg/dl recommended to prevent flares 5.
• Allopurinol and febuxostat achieved serum urate goals in patients with gout; allopurinol was noninferior to febuxostat in controlling flares 6.
• Similar outcomes were noted in participants with stage 3 chronic kidney disease 6.

Challenges in Treatment

• Treating patients with CKD and gout is challenging because of the lack of quality data to guide management in this specific population 5.
• Concerns regarding the efficacy and safety of available gout therapies in this population often result in significant interphysician variability in treatment regimens and dosages 5.
• Medication interactions and comorbidities, such as diabetes and hypertension, can complicate treatment 5.
• The management of gout in renal disease requires a comprehensive approach, involving nephrologists and other healthcare professionals 7.