From the Guidelines
Thiazide diuretics can trigger or worsen gout by increasing uric acid levels in the blood, and it is recommended to substitute the diuretic if possible, considering alternative antihypertensive medications like losartan or calcium channel blockers 1. The effect of thiazide diuretics on gout is well-established, with these medications reducing the kidney's ability to excrete uric acid while increasing its reabsorption in the proximal tubule, leading to hyperuricemia (elevated uric acid levels), the primary risk factor for gout attacks. Some key points to consider when managing gout in patients taking thiazide diuretics include:
- Monitoring patients with a history of gout or elevated uric acid levels closely when taking thiazides
- Considering alternative antihypertensive medications if gout attacks occur or worsen
- Using prophylactic medications like allopurinol or febuxostat to lower uric acid levels and prevent attacks in patients who must remain on thiazide therapy despite gout
- Being aware of the dose-dependent risk of thiazide-induced gout and using the lowest effective dose to minimize this side effect
- Considering the use of losartan, which has a uricosuric action and may lower both blood pressure and serum uric acid levels 1. It is essential to weigh the benefits and risks of thiazide diuretics in patients with gout and consider alternative treatment options to minimize the risk of gout attacks and improve patient outcomes.
From the FDA Drug Label
Hyperuricemia Hyperuricemia or acute gout may be precipitated in certain patients receiving thiazide diuretics.
Thiazide diuretics may precipitate hyperuricemia or acute gout in certain patients.
- The use of thiazide diuretics can increase the risk of developing gout.
- Patients taking thiazide diuretics should be monitored for signs of gout. 2
From the Research
Effect of Thiazide Diuretics on Gout
- Thiazide diuretics have been associated with an increased risk of gout, as shown in a population-based case-control study 3.
- The study found that current use of thiazide diuretics was associated with an adjusted odds ratio (OR) of 1.70 (95% CI 1.62-1.79) for incident gout, compared to past use of diuretics 3.
- Another study found that thiazide diuretic therapy was associated with a significantly increased risk for initiation of anti-gout therapy, with an adjusted relative risk of 1.99 (95% CI 1.21-3.26) 4.
- The risk of gout associated with thiazide diuretics may be mediated by an increase in serum urate levels, as shown in a prospective population-based cohort study 5.
- A cross-sectional study found that hyperuricemia was more common in thiazide diuretic users than non-users, with a higher mean serum uric acid (SUA) level in the thiazide group (5.9 ± 2.1 vs. 5.3 ± 2.7 mg/dL; p=0.02) 6.
Key Findings
- Thiazide diuretics are associated with an increased risk of gout, with an adjusted OR of 1.70 (95% CI 1.62-1.79) for incident gout 3.
- The risk of gout associated with thiazide diuretics may be mediated by an increase in serum urate levels 5.
- Hyperuricemia is more common in thiazide diuretic users than non-users, with a higher mean SUA level in the thiazide group 6.
- The use of thiazide diuretics for more than four years is associated with a significant increase in the number of hyperuricemic participants 6.
Study Results
- A study of 91,530 incident cases of gout and matched controls found that current use of thiazide diuretics was associated with an adjusted OR of 1.70 (95% CI 1.62-1.79) for incident gout 3.
- A retrospective cohort study of 9,249 enrollees in the New Jersey Medicaid program found that thiazide diuretic therapy was associated with a significantly increased risk for initiation of anti-gout therapy, with an adjusted relative risk of 1.99 (95% CI 1.21-3.26) 4.
- A prospective population-based cohort study of 5,789 participants with hypertension found that use of thiazide diuretics was associated with an increased risk of incident gout, with a hazard ratio (HR) of 1.44 (95% CI 1.00,2.10) 5.
- A cross-sectional study of 200 adult hypertensive patients found that hyperuricemia was more common in thiazide diuretic users than non-users, with a higher mean SUA level in the thiazide group (5.9 ± 2.1 vs. 5.3 ± 2.7 mg/dL; p=0.02) 6.