NEW YORK (Reuters Health) – Diuretic use is associated with an increased incidence of gout, an association mediated by increases in serum urate levels, according to findings published in the September 27th online Arthritis & Rheumatism.

Both hypertension and diuretic use have been associated with an increased risk of gout, and previous studies have not been able to differentiate which causes gout.

Dr. Mara A. McAdams DeMarco from Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland and colleagues quantified the hazard of incident gout by diuretic use and class of diuretic agent over 9 years of follow-up among 5789 hypertensive middle-aged adults participating in the Atherosclerosis Risk in the Communities (ARIC) study. They also tested whether serum urate acts as an intermediate on the pathway between diuretic use and incident gout.

The risk of incident gout was 72% higher among participants with diuretic use (5.5%) than among participants without diuretic use (2.9%), a risk that declined to 1.48-fold higher after adjustment for other potential confounders.

In the diuretic subgroups, thiazide diuretic use was associated with a 44% increase in incident gout risk, and loop diuretics were associated with a 2.31-fold increased risk of incident gout.

All these associations disappeared, however, after further adjustment for serum urate level, suggesting, the investigators say, “that serum urate may be a key intermediate on the pathway between diuretic use and incident gout.”

In contrast, nondiuretic antihypertensive use was associated with a 36% reduction in the risk of incident gout, even after adjusting for serum urate level.

Initiation of diuretics was associated with increases in serum urate, whereas initiation of nondiuretic antihypertensive medication was associated with decreases in serum urate levels.

Most patients (74/86, 86%) who were taking a diuretic prior to the onset of gout were still on a diuretic at the visit after their gout onset, and only 3 (3%) patients with gout switched from a diuretic at the visit prior to gout onset to another antihypertensive medication at the visit after gout onset.

These findings “support the hypothesis that diuretic use increases serum urate levels and is related to an increase in incidence of gout,” the researchers conclude.

“Future studies should not only confirm the risk of gout associated with diuretic-induced hyperuricemia but also further elucidate the complicated relationship of hypertension, diuretics, uric acid, and gout,” they add. “Although diuretic use has proven to be a safe and effective first-line treatment for hypertension, our results contribute to the evidence that diuretic use is associated with an increased risk of gout independent of hypertension and other chronic conditions.”

Reference:

Diuretic use, increased serum urate and the risk of incident gout in a population-based study of hypertensive adults: The atherosclerosis risk in the communities cohort

Arthritis Rheum 27 September 2011.