What is the relationship between Allopurinol (a xanthine oxidase inhibitor) and Acute Kidney Injury (AKI)?

From the Guidelines

Allopurinol should be used with caution in patients at risk of acute kidney injury (AKI), as it can cause an increase in serum levels of purine precursors, leading to xanthine crystal deposition in the renal tubules and potentially resulting in acute obstructive uropathy 1. When initiating allopurinol in patients with kidney disease, it is essential to start at a low dose (50-100mg daily) and gradually increase while monitoring kidney function, as the medication is excreted by the kidneys and requires dose reduction in patients with renal insufficiency 1. Some key points to consider when using allopurinol in patients with kidney disease include:

• Dose adjustment is necessary for patients with existing kidney impairment, typically 100mg daily for GFR 10-20 ml/min and 100mg every 2-3 days for GFR <10 ml/min 1.
• Allopurinol can cause AKI through hypersensitivity reactions, which typically occurs within the first 8 weeks of treatment and presents with rash, eosinophilia, and multi-organ involvement including the kidneys 1.
• Risk factors for allopurinol-associated AKI include higher starting doses, kidney impairment, concurrent diuretic use, and HLA-B*5801 genotype (particularly in Korean, Han Chinese, and Thai populations) 1.
• If AKI develops while on allopurinol, the medication should be immediately discontinued, and supportive care provided 1.
• Alternative medications like febuxostat may be considered for patients who require urate-lowering therapy but have experienced allopurinol-associated AKI, though febuxostat also requires dose adjustment in kidney disease and carries its own risks 1.

From the FDA Drug Label

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 Some patients with pre-existing renal disease or poor urate clearance have shown a rise in BUN during administration of allopurinol tablets Renal failure in association with administration of allopurinol tablets has been observed among patients with hyperuricemia secondary to neoplastic diseases. Patients with decreased renal function require lower doses of allopurinol tablets than those with normal renal function. In patients with severely impaired renal function or decreased urate clearance, the half-life of oxipurinol in the plasma is greatly prolonged.

Allopurinol and AKI: Allopurinol may increase the risk of acute kidney injury (AKI) in patients with pre-existing renal disease or poor urate clearance.

• Key points:
  • Patients with decreased renal function require lower doses of allopurinol.
  • Renal function should be monitored in patients taking allopurinol, especially those with pre-existing renal disease.
  • The dosage of allopurinol should be reassessed in patients with decreased renal function.
  • Allopurinol may increase the risk of AKI in patients with hyperuricemia secondary to neoplastic diseases. 2, 2

From the Research

Allopurinol and Acute Kidney Injury (AKI)

• Allopurinol is a commonly used medication for treating gout and hyperuricemia, but its use in patients with renal impairment requires careful consideration due to the risk of allopurinol hypersensitivity syndrome (AHS) 3.
• The risk of AHS is increased in patients with renal impairment, and the use of allopurinol in these patients requires careful monitoring of serum uric acid concentrations and adjustment of the dose according to creatinine clearance 3.

Effects of Allopurinol on AKI

• A meta-analysis of randomized controlled trials found that allopurinol significantly reduced the incidence of contrast-induced acute kidney injury (CI-AKI) in patients undergoing percutaneous coronary intervention, particularly in high-risk patients 4.
• Another study found that rasburicase was associated with significantly lower mean uric acid nadir at 7 days compared to allopurinol, but there was no significant difference in renal function recovery or creatinine nadir between the two groups 5.

Comparative Effectiveness of Allopurinol and Other Urate-Lowering Therapies

• A systematic review found that febuxostat may be more renoprotective than allopurinol in patients with hyperuricemia and chronic kidney disease (CKD), with a significantly higher estimated glomerular filtration rate and reduced risk for renal disease progression 6.
• Another study found that febuxostat was associated with greater reduction in serum uric acid level than allopurinol in patients with CKD, but there was no significant difference in renal function changes between the two groups 7.

Key Findings

• Allopurinol can increase the risk of AHS in patients with renal impairment, and careful monitoring and dose adjustment are necessary 3.
• Allopurinol may reduce the incidence of CI-AKI in high-risk patients, but its effectiveness in preventing AKI in other settings is unclear 4.
• The comparative effectiveness of allopurinol and other urate-lowering therapies, such as febuxostat, in preventing AKI and improving renal outcomes is still being studied, with some evidence suggesting that febuxostat may be more renoprotective in patients with CKD 6, 7.