How does hydrochlorothiazide (HCTZ) affect patients with gout?

Hydrochlorothiazide and Gout

If you have a patient with gout who is taking hydrochlorothiazide, you should switch to an alternative antihypertensive agent when feasible, as hydrochlorothiazide elevates serum uric acid levels and increases gout risk. 1

Mechanism of Harm

Hydrochlorothiazide directly impairs uric acid metabolism through two mechanisms:

• Decreases renal uric acid excretion, leading to elevated serum urate levels that promote crystal formation 2
• Reduces glomerular filtration rate, which further impairs uric acid clearance 3
• The FDA label explicitly states that hydrochlorothiazide "decreases the excretion of uric acid" 2

Clinical Impact

The actual risk of gout attacks varies by dose:

• Clinical gout remains uncommon at standard doses ≤50 mg/day, though biochemical hyperuricemia occurs frequently 4
• Higher doses provide minimal additional blood pressure benefit but substantially increase hyperuricemia risk 4
• In clinical studies, patients on hydrochlorothiazide had significantly higher serum uric acid levels compared to those not taking diuretics 3
• Uric acid levels rise in essentially all patients on hydrochlorothiazide, though not all develop symptomatic gout 5

Management Algorithm

For patients with established gout on hydrochlorothiazide:

1. Switch to losartan as the preferred alternative antihypertensive, which has uricosuric effects that actively lower uric acid 1

2. Consider calcium channel blockers as another alternative that does not adversely affect uric acid levels 1, 3

3. Avoid other diuretics (loop diuretics also elevate uric acid) and beta-blockers (which also raise serum urate) 4, 3

Important caveats:

• Do not discontinue hydrochlorothiazide if it is essential for cardiovascular disease management without careful risk-benefit assessment 4
• The decision to switch should weigh cardiovascular benefits against gout burden 4
• Medication changes should only occur when the uric acid/gout benefits exceed the risks of changing blood pressure control 1

If Hydrochlorothiazide Cannot Be Discontinued

When switching is not feasible due to cardiovascular indications:

• Initiate or optimize urate-lowering therapy (allopurinol or febuxostat) to counteract the hyperuricemic effect 1
• Target serum uric acid <6 mg/dL (or <5 mg/dL for severe gout with tophi) 1
• Febuxostat efficacy is not diminished by concurrent hydrochlorothiazide use, so dose adjustment of urate-lowering therapy is not necessary 6

Evidence Quality

The 2020 American College of Rheumatology guidelines provide a conditional recommendation to switch hydrochlorothiazide in gout patients, reflecting moderate certainty evidence 1. The 2017 EULAR guidelines similarly recommend substituting diuretics when gout occurs in patients receiving them 1. This represents consensus across major rheumatology societies that the hyperuricemic effect is clinically meaningful enough to warrant medication changes when feasible.