Background The risk of end-stage renal disease (ESRD) in both hypertension and gout has been examined in the clinical literature. However, the impact of allopurinol adherence on primary prevention of ESRD has not been assessed.
Objectives To evaluate the impact of better adherence to allopurinol therapy on ESRD onset.
Methods A cohort of 2752 patients with gout diagnosis was reconstructed using the Québec RAMQ and MED-ECHO administrative databases. Patients were eligible if they were new users of allopurinol, aged between 45 and 85 years, had a diagnosis of hypertension and were treated with an antihypertensive drug between 1997 and 2007. A nested case-control design was used to study the occurrence of ESRD. Every case of ESRD was matched for age, sex and duration of follow-up for up to 15 controls. Adherence level was assessed as a medication possession ratio. Conditional logistic regression models were used to estimate the rate ratio (RR) of ESRD adjusting for covariables.
Results Patients had a mean age of 68 years, 82% were men, close to 50% had ≥1 cardiovascular disorder, 33% had dyslipidemia, 21% had diabetes, 15% had chronic kidney disease, 21% were thiazides users, 33% were low-dose aspirin users, and 42% were NSAID users. Clinical characteristics among patients adherent to allopurinol were similar to those who were non-adherent. Major risk factor for ESRD onset was chronic kidney disease at stages 1 to 3 (RR: 8.00; CI: 3.16 -22.3) and the severity of hypertension (≥3 vs. <3 treatments with antihypertensives) was a trending risk factor as a crude estimate (RR: 1.94; CI: 0.68-5.51). Of 341 patients, cases (n=22) and controls (n=319), high adherence level (≥80%) to allopurinol therapy, compared with lower adherence level (<80%), was associated with a lower rate of ESRD onset (RR: 0.35; confidence interval [CI]: 0.13-0.91).
Conclusions This population-based study suggests that better adherence to allopurinol may be associated with risk reduction of new-onset ESRD in the hypertensive population. Further research is needed to confirm this risk, as this study was limited by the small number of cases and potential of residual confounding factors.
Muntner P, Davis BR, Cushman WC, et al. Treatment-resistant hypertension and the incidence of cardiovascular disease and end-stage renal disease: results from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Hypertension. 2014 Nov;64(5):1012-1021.
Johnson ES, Smith DH, Thorp ML, et al. Predicting the risk of end-stage renal disease in the population-based setting: a retrospective case-control study. BMC Nephrol. 2011;12:17.
Roy L, White-Guay B, Dorais M, Dragomir A, Lessard M, Perreault S. Adherence to Antihypertensive Agents improves risk reduction of end-stage renal disease. Kidney Int. 2013 Sep;84(3):570-7.
Yu KH, Kuo CF, Luo SF, et al. Risk of end-stage renal disease associated with gout: a nationwide population study. Arthritis Res Ther. 2012;14(2):R83.
Acknowledgements Funding for this study was provided by AstraZeneca. Editorial support was provided by PAREXEL and was funded by AstraZeneca.
Disclosure of Interest S. Perreault Grant/research support from: AstraZeneca, J. Nuevo Employee of: AstraZeneca, S. Baumgartner Employee of: Ardea Biosciences, Inc., a member of the AstraZeneca Group., R. Morlock Employee of: Ardea Biosciences, Inc., a member of the AstraZeneca Group.