Does hydrochlorothiazide (HCTZ) contribute to the development of gout?

From the Guidelines

Hydrochlorothiazide (HCTZ) can contribute to the development of gout, and switching to an alternate antihypertensive is conditionally recommended when feasible. This is based on the 2020 American College of Rheumatology guideline for the management of gout, which provides recommendations for managing concurrent medications in patients with gout 1. The guideline conditionally recommends switching HCTZ to an alternate antihypertensive when feasible, due to its potential to increase the risk of gout.

The mechanism by which HCTZ contributes to gout is through its diuretic action, which reduces uric acid excretion in the kidneys, leading to elevated serum uric acid levels (hyperuricemia). Key points to consider include:

• HCTZ enhances uric acid reabsorption in the proximal tubule of the kidney
• It reduces urine volume, further concentrating uric acid in the blood
• Patients taking HCTZ, especially at higher doses or for extended periods, should be monitored for symptoms of gout
• Those with a personal or family history of gout or existing hyperuricemia are at particularly increased risk

If a patient on HCTZ develops gout, healthcare providers may consider alternative antihypertensive medications, such as losartan, which is preferentially recommended as an antihypertensive when feasible 1. Additionally, uric acid-lowering therapy, such as allopurinol, may be considered if HCTZ must be continued for blood pressure management. It is essential to weigh the benefits and risks of HCTZ in patients with gout or at risk of developing gout, and to consider alternative treatment options to minimize the risk of gout.

From the FDA Drug Label

Hyperuricemia or acute gout may be precipitated in certain patients receiving thiazide diuretics.

Hydrochlorothiazide may contribute to the development of gout due to its effect on uric acid excretion. The drug label states that it decreases the excretion of uric acid, which can lead to hyperuricemia and potentially precipitate acute gout in certain patients 2. This is further supported by another drug label, which explicitly states that thiazide diuretics, including hydrochlorothiazide, may precipitate hyperuricemia or acute gout in certain patients 2.

• Key points:
  • Hydrochlorothiazide decreases uric acid excretion
  • May lead to hyperuricemia
  • Can precipitate acute gout in certain patients
  • Thiazide diuretics, including hydrochlorothiazide, may contribute to gout development 2, 2

From the Research

Hydrochlorothiazide and Gout

• Hydrochlorothiazide (HCTZ) is a type of diuretic that has 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, such as HCTZ, was associated with an increased risk of incident gout, with an adjusted odds ratio (OR) of 1.70 (95% CI 1.62-1.79) 3.
• Another study found that use of loop diuretics and thiazide diuretics, including HCTZ, was associated with an increased risk of gout, although the risk was higher with loop diuretics 3.
• A double-blind study of HCTZ and spironolactone found that HCTZ increased uric acid levels, but did not cause clinical gout in any of the patients 4.
• The study suggested that supplementation or replacement with spironolactone may be useful in controlling blood pressure while reducing side effects, including hyperuricemia and gout 4.

Mechanisms and Risk Factors

• Hyperuricemia, or high levels of uric acid in the blood, is a key factor in the development of gout 5, 6, 7.
• Other risk factors for gout include alcohol consumption, use of diuretics, and obesity 7.
• The interaction between uric acid level and other risk factors, such as alcohol consumption and diuretic use, can increase the risk of developing gout 7.
• HCTZ may contribute to the development of gout by increasing uric acid levels and interacting with other risk factors, such as alcohol consumption and obesity 3, 4, 7.