Abstract
BackgroundThe use of allopurinol in people with chronic kidney disease (CKD) remains one of the most controversial areas in gout management. The aim of this study was to determine the effect of baseline kidney function on safety and efficacy of allopurinol dose escalation to achieve serum urate (SU) <6 mg/dl.MethodsWe undertook a post hoc analysis of a 24-month allopurinol dose escalation treat-to-target SU randomized controlled trial, in which 183 people with gout were randomized to continue current dose allopurinol for 12 months and then enter the dose escalation phase or to begin allopurinol dose escalation immediately. Allopurinol was increased monthly until SU was <6 mg/dl. The effect of baseline kidney function on urate lowering and adverse effects was investigated.ResultsIrrespective of randomization, there was no difference in the percentage of those with creatinine clearance (CrCL) <30 ml/min who achieved SU <6 mg/dl at the final visit compared to those with CrCL ≥30 to <60 ml/min and those with CrCL ≥60 ml/min, with percentages of 64.3% vs. 76.4% vs. 75.0%, respectively (p = 0.65). The mean allopurinol dose at month 24 was significantly lower in those with CrCL <30 ml/min as compared to those with CrCL ≥30 to <60 ml/min or CrCL ≥60 ml/min (mean (SD) 250 (43), 365 (22), and 460 (19) mg/day, respectively (p < 0.001)). Adverse events were similar among groups.ConclusionsAllopurinol is effective at lowering urate even though and accepting that there were small numbers of participants with CrCL <30 ml/min, these data indicate that allopurinol dose escalation to target SU is safe in people with severe CKD. The dose required to achieve target urate is higher in those with better kidney function.Trial registrationAustralian and New Zealand Clinical trials Registry, ACTRN12611000845932. Registered on 10 August 2011.
Highlights
The use of allopurinol in people with chronic kidney disease (CKD) remains one of the most controversial areas in gout management
While recommendations from the American College of Rheumatology (ACR) [1] and European League Against Rheumatism (EULAR) [2] both advocate allopurinol as a first-line urate lowering therapy (ULT), for dosing guidance the ACR advocates a gradual dose escalation even in those with CKD [1], while EULAR recommends dose restriction based on creatinine clearance (CrCL) [2]
The Hande dosing strategy does not differentiate between starting dose, which has been associated with allopurinol hypersensitivity syndrome (AHS) [5], and maintenance dose (i.e. dose required to achieve target serum urate (SU))
Summary
The use of allopurinol in people with chronic kidney disease (CKD) remains one of the most controversial areas in gout management. While recommendations from the American College of Rheumatology (ACR) [1] and European League Against Rheumatism (EULAR) [2] both advocate allopurinol as a first-line urate lowering therapy (ULT), for dosing guidance the ACR advocates a gradual dose escalation even in those with CKD [1], while EULAR recommends dose restriction based on creatinine clearance (CrCL) [2]. This discrepancy is due to concerns over increased risk of adverse effects, allopurinol hypersensitivity syndrome (AHS) and limited data on the use of allopurinol in CKD. Once AHS occurs, people with CKD have higher mortality [6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
