medwireNews: Individuals with gout and concurrent chronic kidney disease (CKD) are no more likely to die following allopurinol initiation, dose escalation, or achievement of target serum urate (SU) levels than those not taking the drug, study findings indicate.
Guanghua Lei (Central South University, Changsha, China) and colleagues say their results “are clinically relevant in gout care because CKD is a common comorbidity of gout, and allopurinol is most commonly used with escalating doses to achieve and maintain a SU target below a subsaturation point of urate crystals, which will eventually decrease gout flare frequency and tissue urate crystal burden.”
However, they note that two recent randomized controlled trials (RCTs) for patients with CKD but no gout showed that escalating allopurinol dose was associated with a potentially increased risk for death and this has “raised concerns about whether a treat-to-target approach of lowering SU level would be safe for patients with gout and concurrent CKD.”
To investigate, Lei and team conducted a population-based cohort study using data from The Health Improvement Network UK primary care database.
The researchers identified 5277 individuals aged 40 years or older with gout and moderate-to-severe CKD (≥stage 3) who initiated allopurinol between 2000 and 2018, and propensity-score matched them to an equal number of nonusers.
In both groups, mean baseline SU was 0.52 mmol/L and mean estimated glomerular filtration rate (eGFR) was 47.5 mL/min per 1.73 m2. At 5 years, mean SU had fallen to 0.42 mmol/L in allopurinol initiators and 0.48 mmol/L in nonusers, while mean eGFR had fallen to a respective 47.2 and 46.1 mL/min per 1.73 m2.
Lei and co-authors report in the Annals of Internal Medicine that the 5-year mortality rate was 15.4% among the allopurinol users and 17.5% among the nonusers, corresponding to 4.9 and 5.8 deaths per 100 person–years and a significant hazard ratio (HR) of 0.85 in favor of allopurinol use.
The investigators then carried out two hypothetical cohort studies emulating RCTs to evaluate the effects of achieving target SU level (<0.36 mmol/L) with allopurinol and allopurinol dose escalation on 5-year mortality risk.
They found that, in allopurinol users, the 5-year weighted mortality rate was 13.2% among individuals who achieved a target SU level and 14.8% among those who did not, giving a nonsignificant HR of 0.87.
In addition, the HR for mortality was a nonsignificant 0.88 when allopurinol users with dose escalation were compared with those who had no dose escalation, while the weighted 5-year mortality rates were 13.9% and 15.2%, respectively.
Lei et al conclude that their “findings provide empirical evidence that adopting current gout treatment guidelines does not seem to have a detrimental effect on mortality in patients with both gout and CKD.”
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