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Are allopurinol dose and duration of use nephroprotective in the elderly? A Medicare claims study of allopurinol use and incident renal failure
  1. Jasvinder A Singh1,2,3,
  2. Shaohua Yu2
  1. 1Medicine Service, Birmingham VA Medical Center, Birmingham, Alabama, USA
  2. 2Division of Epidemiology, Department of Medicine School of Medicine, School of Public Health, University of Alabama at Birmingham (UAB), Birmingham, Alabama, USA
  3. 3Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
  1. Correspondence to Dr Jasvinder A Singh, University of Alabama, Faculty Office Tower 805B, 510 20th Street S, Birmingham, AL 35294, USA:{at}


Objective To assess the effect of allopurinol dose/duration on the risk of renal failure in the elderly with allopurinol use.

Methods We used the 5% random Medicare claims data from 2006 to 2012. Multivariable-adjusted Cox regression analyses assessed the association of allopurinol dose/duration with subsequent risk of developing incident renal failure or end-stage renal disease (ESRD) (no prior diagnosis in last 183 days) in allopurinol users, controlling for age, sex, race and Charlson–Romano comorbidity index. HRs with 95% CIs were calculated. Sensitivity analyses considered a longer baseline period (365 days), controlled for gout or used more specific codes.

Results Among the 30 022 allopurinol treatment episodes, 8314 incident renal failure episodes occurred. Compared with 1–199 mg/day, allopurinol dose of 200–299 mg/day (HR 0.81; 95% CI 0.75 to 0.87) and ≥300 mg/day, 0.71 (0.67 to 0.76), had significantly lower hazard of renal failure in multivariable-adjustment model, confirmed in multiple sensitivity analyses. Longer allopurinol use duration was significantly associated with lower hazards in sensitivity analyses (365-day look-back; reference, <0.5 year): 0.5–1 year, 1.00 (0.88, 1.15); >1–2 years, 0.85 (0.73 to 0.99); and >2 years, 0.81 (0.67 to 0.98). Allopurinol ≥300 mg/day was also associated with significantly lower risk of acute renal failure and ESRD with HR of 0.89 (0.83 to 0.94) and 0.57 (0.46 to 0.71), respectively.

Conclusions Higher allopurinol dose is independently protective against incident renal failure in the elderly allopurinol users. A longer duration of allopurinol use may be associated with lower risk of incident renal failure. Potential mechanisms of these effects need to be examined.

  • Gout
  • Outcomes research
  • Epidemiology

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  • Handling editor Tore K Kvien

  • Contributors JAS: study design, protocol, analysis plan, writing the first draft of the manuscript, critical revision of the paper and the decision to submit. SY: review of analysis plan, data management, data analysis, critical revision of the paper and the decision to submit.

  • Funding This material is the result of work supported by research funds from UAB Division of Rheumatology and the resources and use of facilities at the Birmingham VA Medical Center.

  • Competing interests JAS has received research grants from Takeda and Savient and consultant fees from Savient, Takeda, Regeneron, Iroko, Merz, Bioiberica, Crealta, and Allergan pharmaceuticals. JAS serves as the principal investigator for an investigator-initiated study funded by Horizon pharmaceuticals through a grant to DINORA, a 501c3 entity. JAS is a member of the executive of OMERACT, an organisation that receives arms-length funding from 36 companies; a member of the American College of Rheumatology's Annual Meeting Planning Committee; and a member of the Veterans Affairs Rheumatology Field Advisory Committee.

  • Ethics approval The University of Alabama at Birmingham's Institutional Review Board approved this study, and all investigations were conducted in conformity with ethical principles of research.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement We will share this database with other colleagues after appropriate permissions from privacy and ethics committees of our institution have been obtained. There are no unpublished data from this study.