From the Guidelines
Allopurinol is the preferred first-line urate-lowering therapy (ULT) for patients with chronic kidney disease (CKD), including those with moderate-to-severe CKD (stage >3), and should be initiated at a low starting dose of ≤100 mg/day, with lower doses used in CKD. When managing patients with CKD and gout, it is essential to consider the potential benefits and risks of allopurinol therapy. According to the 2020 American College of Rheumatology guideline for the management of gout 1, allopurinol is recommended as the preferred first-line ULT, including for patients with moderate-to-severe CKD. The guideline suggests using a low starting dose of allopurinol (≤100 mg/day) and titrating the dose guided by serial serum urate measurements, with an target of <6 mg/dl.
Key considerations when using allopurinol in patients with CKD include:
- Starting with a low dose (50-100 mg daily) and gradually increasing by 50-100 mg every 2-4 weeks until reaching the target serum uric acid level
- Dose adjustments based on kidney function, with maximum doses of 300 mg daily for eGFR 60-90 mL/min, 200-250 mg daily for eGFR 30-60 mL/min, and 100-150 mg daily for eGFR <30 mL/min
- Monitoring kidney function and uric acid levels regularly during dose titration
- Considering HLA-B*5801 testing in selected patients, specifically in higher risk sub-populations for severe allopurinol hypersensitivity reaction 2
Overall, the current evidence suggests that allopurinol can be safely used in patients with CKD and may provide renoprotective benefits, making it a valuable treatment option for patients with gout and CKD.
From the FDA Drug Label
Patients with decreased renal function require lower doses of allopurinol tablets than those with normal renal function. Lower than recommended doses should be used to initiate therapy in any patients with decreased renal function and they should be observed closely during the early stages of administration of allopurinol tablets In patients with severely impaired renal function or decreased urate clearance, the half-life of oxipurinol in the plasma is greatly prolonged. Therefore, a dose of 100 mg per day or 300 mg twice a week, or perhaps less, may be sufficient to maintain adequate xanthine oxidase inhibition to reduce serum urate levels Allopurinol and its primary active metabolite, oxipurinol, are eliminated by the kidneys; therefore, changes in renal function have a profound effect on dosage In patients with decreased renal function or who have concurrent illnesses which can affect renal function such as hypertension and diabetes mellitus, periodic laboratory parameters of renal function, particularly BUN and serum creatinine or creatinine clearance, should be performed and the patient’s dosage of allopurinol tablets reassessed
Key Considerations for Allopurinol and CKD:
- Patients with decreased renal function require lower doses of allopurinol.
- Dose adjustment is necessary in patients with severely impaired renal function.
- Monitoring of renal function, particularly BUN and serum creatinine, is recommended in patients with CKD.
- Concurrent illnesses that can affect renal function, such as hypertension and diabetes mellitus, should be considered when adjusting the dose of allopurinol. 3
From the Research
Allopurinol and CKD: Safety and Efficacy
- Allopurinol is commonly used to treat hyperuricemia and gout in patients with chronic kidney disease (CKD) 4, 5.
- However, the safety and efficacy of allopurinol in CKD patients have shown inconsistent results, with some studies demonstrating an increased risk of adverse events and others showing no significant risk 5.
- A systematic review found that febuxostat may be more renoprotective than allopurinol in patients with hyperuricemia and CKD, but the results were based on small, long-term retrospective studies with serious risk of bias 4.
- Another study found that allopurinol can be effective in lowering uric acid levels in CKD patients, but the dose should be titrated to effect and reduced in patients with renal insufficiency to minimize the risk of adverse events 5.
Comparison with Other Urate-Lowering Therapies
- A network meta-analysis found that febuxostat, allopurinol, and benzbromarone did not exert superior renoprotective effects compared to placebo in CKD patients with hyperuricemia 6.
- However, febuxostat was found to be superior to allopurinol in lowering uric acid levels and controlling blood pressure 6.
- The choice of urate-lowering therapy should be individualized based on patient factors, such as renal function and comorbidities 6.
Drug Stewardship in CKD
- Patients with CKD often require polypharmacy, which can increase the risk of adverse events and drug interactions 7.
- Drug stewardship is essential to maximize medication safety and effectiveness in CKD patients, and involves medication reconciliation, selection, dose adjustment, and monitoring 7.
- Healthcare providers should be aware of the potential risks and benefits of medications in CKD patients and adjust doses accordingly to minimize adverse events 8.