From the Guidelines
Allopurinol can be used to treat high uric acid levels in patients with chronic kidney disease (CKD), but dosing must be adjusted based on kidney function, with a recommended starting dose of ≤100 mg/day, and lower in patients with CKD, as stated in the 2020 American College of Rheumatology guideline for the management of gout 1.
Key Considerations
- For patients with CKD, the starting dose is typically lower than standard—often 50-100 mg daily—with gradual increases as needed while monitoring uric acid levels.
- The maximum dose depends on kidney function, with severe CKD patients generally not exceeding 100-200 mg daily.
- Regular monitoring of kidney function, uric acid levels, and potential side effects is essential.
- Allopurinol works by inhibiting xanthine oxidase, the enzyme responsible for uric acid production, making it effective for preventing gout attacks and kidney stones in CKD patients.
- However, patients should be monitored for hypersensitivity reactions, which can be more common in those with kidney impairment.
- Starting at a low dose and increasing slowly helps reduce this risk.
- Adequate hydration should be maintained unless fluid restrictions are in place for advanced CKD.
Dosing and Monitoring
- 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, as suggested by the 2012 American College of Rheumatology guidelines for management of gout 1.
- A lower starting dose of any ULT reduces the risk of flare associated with initiation, and even lower initial allopurinol doses (e.g., ≤50 mg/day) should be considered in patients with CKD, as stated in the 2020 American College of Rheumatology guideline for the management of gout 1.
Safety and Efficacy
- Allopurinol has been shown to be effective in reducing SUA levels, with a significant dose–response relation between allopurinol and SUA, as demonstrated in a re-analysis based on individual patient data from two studies 1.
- The safety of allopurinol in patients with CKD has been evaluated, with one retrospective cohort study showing that the risk of adverse drug reactions was similar between patients whose allopurinol maintenance dose matched the recommended dose according to their creatinine clearance rate and patients whose maintenance dose exceeded the recommended dose 1.
From the FDA Drug Label
Allopurinol tablets reduce serum and urinary uric acid concentrations. Allopurinol tablets can substantially reduce serum and urinary uric acid levels in previously refractory patients even in the presence of renal damage serious enough to render uricosuric drugs virtually ineffective
Allopurinol can be used to reduce uric acid levels. However, its use in patients with Chronic Kidney Disease (CKD) should be carefully assessed, as the drug's effectiveness and potential risks need to be weighed. The fact that allopurinol can reduce uric acid levels even in the presence of renal damage suggests it may be beneficial for patients with CKD, but caution is advised due to the potential for increased toxicity in patients with impaired renal function 2 2.
From the Research
Uric Acid Levels in CKD
- Uric acid levels are increased in patients with chronic kidney disease (CKD) due to decreased glomerular filtration rate 3.
- Hyperuricemia is associated with various conditions, including hypertension, type 2 diabetes, obesity, and cardiovascular disease, in addition to CKD 3.
Allopurinol for Uric Acid Levels in CKD
- Allopurinol, a xanthine oxidase inhibitor, can be used to lower uric acid levels in patients with CKD 3, 4, 5, 6, 7.
- However, studies suggest that febuxostat may be more effective than allopurinol in reducing serum uric acid levels and slowing the progression of renal disease in CKD patients 4, 5, 6, 7.
Comparison of Allopurinol and Febuxostat
- A retrospective study found that febuxostat was more effective than allopurinol in reducing serum uric acid levels and had a positive effect on renal function in patients with CKD 4.
- Another study found that switching from allopurinol to febuxostat was associated with improved renal function and reduced serum uric acid levels in patients with CKD 6.
- A systematic review found that febuxostat may be more renoprotective than allopurinol in patients with hyperuricemia and CKD, but noted that the evidence was based on small, long-term retrospective studies with serious risk of bias 7.