Can allopurinol be used in a patient with Acute Kidney Injury (AKI)?

From the Guidelines

Allopurinol should be used with caution in patients with acute kidney injury (AKI), with a recommended starting dose of 50 mg daily in severe cases, due to the increased risk of severe cutaneous adverse reactions (SCARs) and the need for careful monitoring of renal function and uric acid levels. The use of allopurinol in patients with AKI requires careful consideration of the potential risks and benefits, as the drug and its active metabolite oxypurinol are primarily eliminated by the kidneys, leading to potential accumulation and toxicity in impaired renal function 1.

Key Considerations

• The dose of allopurinol should be adjusted according to the creatinine clearance to minimize the risk of SCARs, which can be fatal 1.
• Alternative medications like febuxostat may be considered as they require less dosage adjustment in renal impairment and have been found to be more effective in patients with chronic kidney disease (CKD) than allopurinol given at doses adjusted to creatinine clearance 1.
• Close monitoring for hypersensitivity reactions, which can be more common in renal dysfunction, is essential, and adequate hydration should be maintained to reduce the risk of crystalluria and further kidney damage.
• The American College of Rheumatology guidelines recommend starting allopurinol at a dose of no greater than 100 mg/day, with a starting dose of 50 mg/day in stage 4 or worse CKD, and gradually titrating the maintenance dose upwards every 2–5 weeks to achieve the chosen serum urate (SUA) target 1.

Clinical Decision-Making

• Allopurinol may still be indicated during AKI if the patient has symptomatic hyperuricemia or tumor lysis syndrome, where the benefits outweigh the risks.
• However, the use of allopurinol in patients with AKI should be individualized, taking into account the patient's specific clinical circumstances, including the severity of renal impairment, the presence of other comorbidities, and the potential risks and benefits of alternative treatments.

From the FDA Drug Label

Some patients with pre-existing renal disease or poor urate clearance have shown a rise in BUN during administration of allopurinol tablets Although the mechanism responsible for this has not been established, patients with impaired renal function should be carefully observed during the early stages of administration of allopurinol tablets and the dosage decreased or the drug withdrawn if increased abnormalities in renal function appear and persist Patients with decreased renal function require lower doses of allopurinol tablets than those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

Allopurinol can be used in patients with Acute Kidney Injury (AKI), but with caution. The dosage should be lowered, and the patient should be closely monitored for any signs of worsening renal function. The dose may need to be adjusted based on the patient's renal function, with a possible dose of 100 mg per day or 300 mg twice a week, or perhaps less. Periodic laboratory tests, including BUN and serum creatinine or creatinine clearance, should be performed to reassess the patient's dosage 2 2.

From the Research

Allopurinol in Acute Kidney Injury (AKI)

• There is limited direct evidence on the use of allopurinol in patients with AKI.
• A study comparing rasburicase and allopurinol in cancer patients with renal dysfunction and hyperuricemia found that rasburicase was associated with significantly lower mean uric acid nadir at 7 days, but the likelihood of renal function recovery did not significantly differ between the two groups 3.
• Another study suggested that correction of hyperuricemia as a surrogate endpoint may not be associated with significant renal function improvement, particularly if renal dysfunction is unrelated to tumor lysis syndrome 3.
• There is no direct evidence in the provided studies that specifically addresses the use of allopurinol in the context of AKI.
• The management of AKI typically involves careful attention to hemodynamic status, fluid management, and the use of diuretics, but the role of allopurinol in this context is not clearly established 4, 5.