From the Guidelines
For patients with chronic kidney disease (CKD) who need uric acid lowering therapy, allopurinol is generally the first-line agent, as strongly recommended by the 2020 American College of Rheumatology guideline for the management of gout 1.
Key Considerations
- Start with a low dose of 50-100 mg daily and gradually increase as needed while monitoring kidney function.
- The dose should be adjusted based on kidney function, with lower doses for more severe CKD.
- Target serum uric acid levels below 6 mg/dL.
- Febuxostat (starting at 40 mg daily) is an alternative for patients who cannot tolerate allopurinol or have contraindications to it.
Prophylaxis and Monitoring
- When initiating therapy, consider prophylaxis with colchicine (0.6 mg once or twice daily) for the first 3-6 months to prevent gout flares.
- Regular monitoring of kidney function, liver enzymes, and complete blood count is important during treatment.
Rationale
Allopurinol is preferred in CKD because it's effective, relatively inexpensive, and has extensive clinical experience supporting its use. The medication works by inhibiting xanthine oxidase, the enzyme responsible for uric acid production, thereby reducing serum uric acid levels and preventing crystal deposition in joints and kidneys.
Important Notes
- The choice of either allopurinol or febuxostat over probenecid is strongly recommended for patients with moderate-to-severe CKD (stage ≥3) 1.
- The choice of pegloticase as a first-line therapy is strongly recommended against due to cost differences and potential adverse effects 1.
From the FDA Drug Label
Since allopurinol tablets and its metabolites are primarily eliminated only by the kidney, accumulation of the drug can occur in renal failure, and the dose of allopurinol tablets should consequently be reduced With a creatinine clearance of 10 to 20 mL/min, a daily dosage of 200 mg of allopurinol tablets is suitable. When the creatinine clearance is less than 10 mL/min, the daily dosage should not exceed 100 mg.
Allopurinol is the uric acid lowering agent to initiate in a patient with Chronic Kidney Disease (CKD), with a reduced dose based on the patient's creatinine clearance:
- 10 to 20 mL/min: 200 mg daily
- less than 10 mL/min: not to exceed 100 mg daily 2
From the Research
Uric Acid Lowering Agents in CKD
- Febuxostat has been shown to be safe and efficacious in reducing serum uric acid levels in patients with CKD stages 3b-5, with a reduction of >40% in CKD stage 3b and >50% in CKD stages 4 and 5 3.
- The use of febuxostat has been associated with an increase in estimated glomerular filtration rate (eGFR) and a tendency toward decreased proteinuria in patients with CKD 3.
- Allopurinol and febuxostat are the most commonly used urate-lowering therapies in patients with CKD, with febuxostat being a recommended treatment option for patients with CKD and hyperuricemia 4, 5.
Comparison of Febuxostat and Allopurinol
- Febuxostat has been shown to be more effective than allopurinol in reducing serum uric acid levels in patients with CKD and hyperuricemia, with a greater reduction in serum uric acid levels and a positive long-term eGFR slope 5, 6.
- Febuxostat may be more renoprotective than allopurinol in patients with both hyperuricemia and CKD, with a reduced risk for renal disease progression and reduced serum uric acid levels 6, 7.
- A systematic review and meta-analysis found that febuxostat might be more renoprotective than allopurinol, with a significant difference in the changes in albuminuria levels and serum uric acid from baseline between the two groups 7.
Initiation of Uric Acid Lowering Therapy in CKD
- The choice of uric acid lowering agent in patients with CKD should be based on the individual patient's characteristics, including their renal function and comorbidities 4.
- Febuxostat may be a suitable option for patients with CKD and hyperuricemia, particularly those with more advanced CKD or those who are intolerant to allopurinol 3, 5.