From the Guidelines
Allopurinol can be safely used in patients with chronic kidney disease (CKD) and may even provide renoprotective benefits, with a recommended starting dose of 50 mg/day in stage 4 or worse CKD. When initiating allopurinol in patients with CKD, it is essential to start with a low dose and gradually titrate upwards every 2–5 weeks to achieve the target serum uric acid level of <6 mg/dL or a maximum tolerated dose 1. The dose can be raised above 300 mg daily, even with renal impairment, as long as this is accompanied by adequate patient education and monitoring for drug toxicity, such as pruritis, rash, and elevated hepatic transaminases 1.
Key Considerations
- Prior to initiation, consider HLA-B*5801 in selected patients, specifically in higher risk sub-populations for severe allopurinol hypersensitivity reaction, such as Koreans with stage 3 or worse CKD, and Han Chinese and Thai irrespective of renal function 1.
- Monitor kidney function and uric acid levels regularly during dose titration and maintenance therapy.
- Watch for signs of hypersensitivity reactions, particularly in the first few months of treatment.
Recent Guidelines
The 2020 American College of Rheumatology guideline for the management of gout strongly recommends allopurinol as the preferred first-line urate-lowering therapy (ULT) for all patients, including those with moderate-to-severe CKD (stage >3) 1. The guideline also recommends starting at a low dose with subsequent dose titration to target, rather than starting at a higher dose.
Dosing and Titration
- Start with a low dose of 50-100mg daily in patients with CKD.
- Gradually increase by 50-100mg every 2-4 weeks until reaching the target serum uric acid level of <6 mg/dL or a maximum tolerated dose.
- Dose adjustment is necessary based on kidney function, with a maximum dose of 300mg daily for eGFR 60-90 mL/min, 200mg daily for eGFR 30-60 mL/min, and 100mg daily for eGFR <30 mL/min.
Benefits and Risks
Allopurinol works by inhibiting xanthine oxidase, reducing uric acid production, which may decrease oxidative stress and inflammation in the kidneys. Some studies suggest allopurinol may slow CKD progression by reducing uric acid-mediated kidney damage, improving endothelial function, and decreasing oxidative stress. Despite traditional concerns, current evidence indicates that properly dosed allopurinol is generally safe in CKD patients and may offer kidney protection beyond just treating hyperuricemia 1.
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 Points:
- 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 is crucial in patients with decreased renal function or concurrent illnesses that can affect renal function.
- The dosage of allopurinol should be reassessed based on periodic laboratory parameters of renal function. 2
From the Research
Allopurinol and CKD
- Allopurinol is a commonly used urate-lowering therapy in patients with chronic kidney disease (CKD) and hyperuricemia 3, 4.
- The effectiveness of allopurinol in improving renal outcomes in CKD patients is still a topic of debate, with some studies suggesting that febuxostat may be more renoprotective than allopurinol 3.
- A systematic review and network meta-analysis of randomized controlled trials found that febuxostat, allopurinol, and benzbromarone did not exert superior effects over placebo on renoprotective effect, but febuxostat was superior to allopurinol in lowering urate levels 4.
- When prescribing allopurinol to patients with CKD, it is essential to consider dosage adjustments to avoid toxicity, as many medications and their metabolites are eliminated through the kidney 5, 6, 7.
- Appropriate medication dosing is critical for patient safety, and healthcare providers should work together to ensure safe drug prescribing and minimize further damage to the kidneys 5, 6, 7.