Can Hydrochlorothiazide Cause Gout?
Yes, hydrochlorothiazide can cause gout by elevating serum uric acid levels and reducing uric acid excretion, though actual gout attacks remain uncommon at standard doses (≤50 mg/day). 1
Mechanism and Risk
Hydrochlorothiazide decreases uric acid excretion through the kidneys, leading to hyperuricemia in many patients receiving thiazide diuretics. 2
The FDA drug label explicitly warns that hyperuricemia or acute gout may be precipitated in certain patients receiving thiazide diuretics. 2
Uric acid levels will increase in many patients receiving a diuretic, but the JNC 7 guidelines emphasize that the occurrence of gout is uncommon with dosages ≤50 mg/day of hydrochlorothiazide or ≤25 mg of chlorthalidone. 1
Evidence from Clinical Studies
A large population-based case-control study of 91,530 incident gout cases found that current use of thiazide diuretics was associated with a 1.70-fold increased risk of developing incident gout (adjusted OR 1.70,95% CI 1.62-1.79) compared to past use. 3
Thiazide and loop diuretics are among the most common medications that contribute to hyperuricemia and gout, as they reduce uric acid excretion by the kidneys, according to the American College of Rheumatology. 4
The rising prevalence of gout in recent decades has been partly attributed to widespread prescription of thiazide and loop diuretics for cardiovascular diseases. 1
Dose-Related Considerations
Higher doses add little additional antihypertensive efficacy but are associated more with hyperuricemia and other adverse effects. 1
In a study comparing hydrochlorothiazide and spironolactone, uric acid levels rose in all patients receiving hydrochlorothiazide, though clinical gout did not develop in any subject during the study period. 5
The pharmacodynamic effects show that serum uric acid clearance decreases with hydrochlorothiazide use, though co-administration with urate-lowering therapy like febuxostat can still effectively manage uric acid levels. 6
Clinical Management Recommendations
The 2020 ACR guidelines conditionally recommend switching hydrochlorothiazide to an alternate antihypertensive when feasible for patients with gout, regardless of disease activity. 1
Consider using losartan preferentially as an antihypertensive when feasible, as it has uricosuric effects that can help lower uric acid levels. 1, 4
Calcium channel blockers or losartan are preferred alternatives in patients with gout and hypertension, as they do not adversely affect uric acid levels. 4
If diuretics cannot be discontinued, current use of calcium channel blockers or losartan slightly attenuates the risk of gout in patients taking diuretics. 3
Important Caveats
While hydrochlorothiazide increases uric acid levels biochemically, the absolute risk of developing clinical gout attacks remains relatively low at standard therapeutic doses, particularly when doses are kept at or below 50 mg/day. 1
Combined use of loop diuretics and thiazide diuretics carries the highest risk (adjusted OR 4.65), so avoid this combination when possible in patients at risk for gout. 3
Potassium-sparing diuretics were not associated with increased gout risk (adjusted OR 1.06,95% CI 0.91-1.23), making them a potential alternative if diuretic therapy is essential. 3
The decision to continue or switch from hydrochlorothiazide should weigh the cardiovascular benefits of the medication against the gout risk, particularly in patients with established cardiovascular disease where discontinuation may not be appropriate. 1