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
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...
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| Format: | Article |
| Language: | English |
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BMC
2017-12-01
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| Series: | Arthritis Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13075-017-1491-x |
| _version_ | 1811257002470408192 |
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| author | Lisa K. Stamp Peter T. Chapman Murray Barclay Anne Horne Christopher Frampton Paul Tan Jill Drake Nicola Dalbeth |
| author_facet | Lisa K. Stamp Peter T. Chapman Murray Barclay Anne Horne Christopher Frampton Paul Tan Jill Drake Nicola Dalbeth |
| author_sort | Lisa K. Stamp |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T17:49:42Z |
| format | Article |
| id | doaj.art-3c7805f325954c71900018f63a531238 |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-04-12T17:49:42Z |
| publishDate | 2017-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-3c7805f325954c71900018f63a5312382022-12-22T03:22:32ZengBMCArthritis Research & Therapy1478-63622017-12-011911910.1186/s13075-017-1491-xThe 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 trialLisa K. Stamp0Peter T. Chapman1Murray Barclay2Anne Horne3Christopher Frampton4Paul Tan5Jill Drake6Nicola Dalbeth7Department of Medicine, University of Otago, ChristchurchDepartment of Rheumatology, Immunology and Allergy, Christchurch HospitalDepartment of Medicine, University of Otago, ChristchurchDepartment of Medicine, University of AucklandDepartment of Medicine, University of Otago, ChristchurchDepartment of Medicine, University of AucklandDepartment of Medicine, University of Otago, ChristchurchDepartment of Medicine, University of AucklandAbstract 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.http://link.springer.com/article/10.1186/s13075-017-1491-xAllopurinolChronic kidney diseaseGoutSerum urate |
| spellingShingle | Lisa K. Stamp Peter T. Chapman Murray Barclay Anne Horne Christopher Frampton Paul Tan Jill Drake Nicola Dalbeth 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 Arthritis Research & Therapy Allopurinol Chronic kidney disease Gout Serum urate |
| 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Allopurinol Chronic kidney disease Gout Serum urate |
| url | http://link.springer.com/article/10.1186/s13075-017-1491-x |
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