Allopurinol does not increased mortality in gout and chronic kidney disease patients

1. In patients with gout and chronic kidney disease, the initiation of allopurinol was not associated with increased mortality.

2. In patients with gout and chronic kidney disease, dose escalation of allopurinol nor achieving target serum urate levels was associated with increased mortality.

Evidence Rating Level: 2 (Good)

Study Rundown: Serum urate (SU) lowering medications such as allopurinol are the mainstay of treating gout, a form of inflammatory arthritis. However, previous studies have reported that allopurinol use increases the risk of death in patients with renal disease. Therefore, there is a gap in knowledge as to understanding the impact of mortality that allopurinol has on patients with gout and concurrent chronic kidney disease (CKD). This study found that there was no significantly associated increase in mortality for patients with gout and concurrent CKD when initiating allopurinol or escalating the dosage. This study was limited by potential variations in causes of CKD such as IgA nephropathy which can lead to residual confounding, as well as the possibility that allopurinol users may have received better healthcare for their overall health needs which can influence lower mortality rates. Nevertheless, these study’s findings are significant, as they demonstrate that using population-based data, the use of allopurinol was not significantly associated with increased risk for death in patients with gout and concurrent moderate-to-severe CKD.

Click to read the study in AIM

Relevant Reading: In older adults, new use of allopurinol or febuxostat was linked to hypersensitivity reactions versus colchicine

In-Depth [population-based cohort study]: This population-based cohort study used data from the Health Improvement Network (THIN) database from the United Kingdom. Patients who were 40 to 89 years old, had gout and concurrent moderate-to-severe CKD, and had at least 1 year of continuous enrollment with a general practitioner were included in the study. Patients who had cancer, kidney transplant, or were prescribed other urate-lowering medications were excluded from the study. The primary outcome measure was all-cause mortality over 5 years after the initial recording date. Death date was recorded in the THIN database automatically as it was linked to the National Health Service. Outcomes in the primary analysis were assessed via Kolmogorov supremum test and Cox proportional hazards models. In patients who initiated allopurinol compared to those who did not, mortality was 4.9 and 5.8 per 100 person-years (hazard ratio, 0.85; 95% confidence interval [CI], 0.77 to 0.93). Additionally, in those achieving target SU level, compared to not achieving target SU level, the difference in 5-year mortality was -1.6% (95% CI, -3.6 to -0.5) and the hazard ratio was 0.87 (95% CI, 0.75 to 1.01). Furthermore, in those who escalated their dose of allopurinol, compared to those who did not escalate their dose, the difference in 5-year mortality was -1.4% (95% CI, -3.7 to 0.4), and the corresponding hazard ratio was 0.88 (95% CI, 0.73 to 1.07). Overall, this study demonstrates that neither allopurinol initiation, achieving target SU level, nor allopurinol dose escalation was associated with increased mortality in patients with gout and concurrent moderate-to-severe CKD.

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