Association of Chronic Kidney Disease With Allopurinol Use in Gout Treatment

Abstract

IMPORTANCE Clinicians are often cautious about use of allopurinol in patients with gout when renal function declines. OBJECTIVE To assess the association of allopurinol use in gout with the risk of developing chronic kidney disease stage 3 or higher. DESIGN, SETTING, AND PARTICIPANTS A time-stratified propensity score–matched, population-based, prospective cohort study of individuals with newly diagnosed gout who initiated allopurinol (≥300 mg/d) compared with those who did not initiate allopurinol, using the Health Improvement Network (THIN), a United Kingdom general practitioner electronic health records database, was carried out. The data were analyzed using Cox proportional hazards regression. Among adults aged 18 to 89 years with newly diagnosed gout, we propensity score matched 4760 initiators of allopurinol (≥300 mg/d) to the same number of noninitiators of allopurinol, excluding those with chronic kidney disease stage 3 or higher or urate-lowering therapy use before their gout diagnosis. EXPOSURES Allopurinol initiation at a dose of 300 mg or more per day. MAIN OUTCOMES AND MEASURES Development of chronic kidney disease stage 3 or higher. RESULTS Of the 4760 allopurinol initiators (3975 men, 785 women) and same number of noninitiators (3971 men, 789 women), 579 and 623, respectively, developed chronic kidney disease stage 3 or higher, with a mean follow-up time of 5 and 4 years, mean age of 57 years, and mean body mass index (calculated as weight in kilograms divided by height in meters squared) of 30 for both groups. Use of allopurinol of at least 300 mg/d was associated with lower risk of developing chronic kidney disease stage 3 or higher compared with nonusers, with a hazard ratio (HR) of 0.87 (95% CI, 0.77–0.97). Allopurinol initiation at less than 300 mg/d was not associated with renal function decline (HR, 1.00; 95% CI, 0.91–1.09). CONCLUSIONS AND RELEVANCE In this large cohort, allopurinol initiation of at least 300 mg/d was associated with a lower risk of renal function deterioration. Because allopurinol does not appear to be associated with renal function decline, clinicians should consider evaluating other potential causes when patients with gout experience renal function decline.

Hyperuricemia, the heart, and the kidneys – to treat or not to treat?

“…A recent meta-analysis regarding use of allopurinol has shown a mean difference in lower eGFR decline of 3.2 mL/min/ 1.73 m 2 compared to placebo, which was observed in other meta-analyses on CKD patients as well [15]. A study published recently by Vargas-Santos et al showed that allopurinol initiation of at least 300 mg/ day in newly diagnosed gout was associated with a lower risk of renal function decline [82]. Similar data were also published regarding the use of febuxostat, with additional effects on lowering blood pressure, while some researchers witnessed no effect of febuxostat on eGFR in CKD stage 3 patients with asymptomatic hyperuricemia [63,[83][84][85][86][87][88].…”

On the Clinical Pharmacology of Reactive Oxygen Species

“…It has been suggested that close monitoring should be taken into account in patients with impaired renal function (Jordan and Gresser, 2018). A recent study argues, however, against such a risk (Vargas-Santos et al, 2018).…”

Hyperuricemia treatment in acute heart failure patients does not improve their long‐term prognosis: A propensity score matched analysis from the AHEAD registry

“…On the other hand, some studies have suggested that allopurinol treatment might have a beneficial effect on the all‐cause mortality in the general population and on the cardiovascular mortality in patients with gout . Only a higher dose of allopurinol (≥300 mg) might have a protective effect against the progression of renal dysfunction in patients with hyperuricemia …”