From the Guidelines
Febuxostat is generally safe to use in patients with impaired renal function, including those with moderate to severe chronic kidney disease, as it does not require dose adjustment for patients with mild to moderate renal impairment (creatinine clearance 30-89 mL/min) 1.
Key Considerations
- Febuxostat offers an advantage over allopurinol in renal disease because it undergoes primarily hepatic metabolism rather than renal excretion, making it useful for patients with gout and concurrent kidney disease 1.
- For patients with severe renal impairment (creatinine clearance less than 30 mL/min), a reduced starting dose of 40 mg daily is recommended, with careful monitoring 1.
- Patients should still be monitored for potential side effects, including liver function abnormalities and cardiovascular events, as febuxostat carries a boxed warning regarding increased risk of cardiovascular death compared to allopurinol 1.
Monitoring and Treatment
- Regular monitoring of serum uric acid levels is important to ensure therapeutic efficacy 1.
- A treat-to-target strategy should be used, aiming to maintain serum uric acid levels below 6 mg/dL, with a lower target of <5 mg/dL for patients with severe gout until total crystal dissolution has occurred 1.
- Febuxostat can be used in combination with other urate-lowering therapies, such as benzbromarone, in patients with moderate renal impairment, but not in those with eGFR <30 mL/min 1.
From the Research
Safety of Febuxostat in Renal Disease
- Febuxostat has been shown to be safe and efficacious in patients with moderate-to-severe kidney dysfunction, with a low incidence of drug-related adverse events 2.
- A study comparing febuxostat and allopurinol in patients with chronic kidney disease found that febuxostat was more effective in reducing serum uric acid levels and had a positive effect on renal function, with no obvious adverse reactions 3.
- A systematic review of long-term renal outcomes in patients with hyperuricemia and chronic kidney disease found that febuxostat may be more renoprotective than allopurinol, with a significantly higher estimated glomerular filtration rate and reduced risk of renal disease progression 4.
- A meta-analysis of observational studies found that febuxostat had acceptable urate-lowering efficacy and renal safety in patients with stage 4-5 chronic kidney disease not yet on dialysis, with no significant change in renal function 5.
- A case report found that the addition of probenecid to febuxostat therapy resulted in a significant reduction in uric acid levels in a patient with chronic kidney disease, highlighting the potential for combination therapy in patients with refractory hyperuricemia 6.
Key Findings
- Febuxostat is generally well-tolerated in patients with renal disease, with a low risk of adverse events.
- Febuxostat has been shown to be effective in reducing serum uric acid levels in patients with chronic kidney disease.
- Febuxostat may have a positive effect on renal function, with a reduced risk of renal disease progression.
- Combination therapy with probenecid may be effective in patients with refractory hyperuricemia and chronic kidney disease.
Renal Function and Febuxostat
- Febuxostat has been found to have a positive effect on renal function, with an increase in estimated glomerular filtration rate and a reduced risk of renal disease progression 2, 3, 4.
- A meta-analysis found that febuxostat did not significantly change renal function in patients with stage 4-5 chronic kidney disease not yet on dialysis 5.