Studies analyze causes of hyperuricemia, kidney effects of gout treatment with allopurinol

Genetics contribute more than diet to hyperuricemia in healthy people, and 300 mg of allopurinol per day was associated with lower risk of chronic kidney disease in people with gout, recent research found.

Two recent studies looked at causes and treatments for gout.

The first study was a meta-analysis of cross-sectional data on 16,760 U.S. adults of European ancestry (8,414 men and 8,346 women). Eligible participants did not have kidney disease or gout and were not taking urate-lowering or diuretic drugs. All had serum urate measurements, dietary survey data, genome-wide genotypes, and information on potential confounders. Results were published online on Oct. 10 by The BMJ.

In the male, female, and full cohorts, seven foods were associated with increased urate levels (beer, liquor, wine, potato, poultry, soft drinks, and meat), while eight foods were associated with reduced serum urate levels (eggs, peanuts, cold cereal, skim milk, cheese, brown bread, margarine, and noncitrus fruits). Three diet scores (Healthy Eating, DASH diet, and Mediterranean diet) were associated with lower urate levels, but each dietary pattern explained just 0.28% or less of the variation in urate levels. In contrast, common genetic variants of serum urate heritability explained 23.9% of variance in urate levels in the full cohort (23.8% in the male cohort and 40.3% in the female cohort).

The authors noted that the main limitation of the study was the use of differing food frequency questionnaires across studies. They added that the findings may not be generalizable to people with gout or to populations other than individuals of European ancestry living in the U.S.

However, it is unlikely that the cause of hyperuricemia in the study is substantially different than in practice, an accompanying editorial noted. “People with gout often experience stigma from the societal misconception that gout is a condition caused by dietary habits and an unhealthy lifestyle. … [This study] provides important evidence that much of patients' predisposition to hyperuricaemia and gout is non-modifiable,” the authors wrote.

The second study found that gout patients who took allopurinol at a dose of at least 300 mg/d had lower risk of developing stage 3 chronic kidney disease or higher. Participants were adults ages 18 to 89 years with newly diagnosed gout in the U.K. Using a primary care database, researchers matched initiators of allopurinol to noninitiators by propensity score, excluding individuals with stage 3 chronic kidney disease or higher or urate-lowering therapy use before gout diagnosis. Results were published online on Oct. 8 by JAMA Internal Medicine.

Of 4,760 allopurinol initiators (3,975 men and 785 women) and 4,760 noninitiators (3,971 men and 789 women), 579 and 623 participants, respectively, developed stage 3 chronic kidney disease or higher over a mean follow-up of five and four years, respectively. Patients had a mean age of 57 years and a mean body mass index of 30 kg/m2.

Allopurinol use was associated with a 13% reduction in the risk of developing stage 3 chronic kidney disease or higher (hazard ratio [HR], 0.87; 95% CI, 0.77 to 0.97). Allopurinol use at doses less than 300 mg/d was not associated with renal function decline (HR, 1.00; 95% CI, 0.91 to 1.09). The study authors noted limitations, such as the study's observational design and the inability to confirm medication use, which was based on prescription data.

Emphasizing that association does not mean causation, an accompanying editorial noted that of nearly 43,000 eligible study participants, only 10% were started on 300 mg or more of allopurinol daily. “This leaves readers to wonder what motivated practitioners to start such doses, or, conversely, what it was about the remaining 90% of patients that led them to receive lower doses of allopurinol or none at all,” the editorialists wrote.

The bigger issue, they said, is how the study should influence practice, if at all, since clinicians already recognize that they can prescribe higher doses of allopurinol to many patients with gout without concerns about progression of chronic kidney disease. On balance, the study helps “soften our stance” on the use of allopurinol in patients with relative contraindications, they wrote.