The effect of kidney function on the urate lowering effect and safety of increasing allopurinol above doses based on creatinine clearance: a post hoc analysis of a randomized controlled trial.

Show simple item record Stamp, Lisa K en Chapman, Peter T en Barclay, Murray en Horne, Anne en Frampton, Christopher en Tan, Paul en Drake, Jill en Dalbeth, Nicola en 2018-11-28T21:59:08Z en 2017-12-21 en
dc.identifier.issn 1478-6354 en
dc.identifier.uri en
dc.description.abstract BACKGROUND:The 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. METHODS:We 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. RESULTS:Irrespective 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. CONCLUSIONS:Allopurinol 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 REGISTRATION:Australian and New Zealand Clinical trials Registry, ACTRN12611000845932 . Registered on 10 August 2011. en
dc.format.medium Electronic en
dc.language eng en
dc.relation.ispartofseries Arthritis research & therapy en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri en
dc.rights.uri en
dc.subject Humans en
dc.subject Gout en
dc.subject Creatinine en
dc.subject Allopurinol en
dc.subject Uric Acid en
dc.subject Gout Suppressants en
dc.subject Dose-Response Relationship, Drug en
dc.subject Adult en
dc.subject Aged en
dc.subject Middle Aged en
dc.subject Female en
dc.subject Male en
dc.subject Renal Insufficiency, Chronic en
dc.title The effect of kidney function on the urate lowering effect and safety of increasing allopurinol above doses based on creatinine clearance: a post hoc analysis of a randomized controlled trial. en
dc.type Journal Article en
dc.identifier.doi 10.1186/s13075-017-1491-x en
pubs.issue 1 en
pubs.begin-page 283 en
pubs.volume 19 en
dc.rights.holder Copyright: The author en
dc.identifier.pmid 29268756 en
pubs.publication-status Published en
dc.rights.accessrights en
pubs.subtype Research Support, Non-U.S. Gov't en
pubs.subtype research-article en
pubs.subtype Randomized Controlled Trial en
pubs.subtype Journal Article en
pubs.elements-id 720008 en Medical and Health Sciences en School of Medicine en Medicine Department en
dc.identifier.eissn 1478-6362 en
pubs.record-created-at-source-date 2017-12-23 en
pubs.dimensions-id 29268756 en

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