Which class of diuretics, thiazides or loop diuretics, is more likely to increase uric acid levels?

From the Guidelines

Thiazide diuretics are more likely to increase uric acid levels compared to loop diuretics. According to the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1, thiazide or thiazide-type diuretics, such as chlorthalidone, hydrochlorothiazide, and indapamide, can cause an increase in uric acid levels. This is because thiazides reduce uric acid excretion by competing with uric acid for transport in the proximal tubule of the kidney, leading to increased reabsorption and higher serum uric acid levels.

Some key points to consider when using thiazide diuretics include:

• Monitoring for hyponatremia and hypokalemia, as well as uric acid and calcium levels 1
• Using with caution in patients with a history of acute gout unless the patient is on uric acid–lowering therapy 1
• Considering alternative diuretics, such as loop diuretics, in patients with a history of gout or hyperuricemia

In contrast, loop diuretics like furosemide, bumetanide, and torsemide can also affect uric acid levels, but to a lesser extent than thiazides. For patients with a history of gout or hyperuricemia, this difference may be clinically relevant when selecting an appropriate diuretic. If hyperuricemia or gout develops during thiazide treatment, switching to a loop diuretic might be considered as an alternative approach.

From the FDA Drug Label

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

Thiazide diuretics are more likely to increase uric acid levels.

• Hyperuricemia is a potential side effect of thiazide diuretics, which can lead to acute gout in certain patients.
• This information is specific to thiazide diuretics, and there is no direct comparison to loop diuretics in the provided drug label. 2

From the Research

Comparison of Diuretics

• Thiazide diuretics are more likely to increase uric acid levels compared to loop diuretics 3, 4, 5, 6, 7
• The increase in uric acid levels is due to volume contraction and competition with uric acid for renal tubular secretion 4
• Thiazide-induced hyperuricemia is a common occurrence, especially in patients taking thiazide diuretics for an extended period 5
• Loop diuretics, on the other hand, do not have a significant effect on uric acid levels 3, 4

Thiazide Diuretics and Uric Acid Levels

• Studies have shown that thiazide diuretics can increase uric acid levels, with an average increase of 0.6 mg/dL in one study 5
• The increase in uric acid levels is more significant in patients taking higher doses of thiazide diuretics (> or = 25 mg/day) 7
• Thiazide diuretics can also increase the risk of initiating anti-gout therapy, especially in elderly patients 7

Loop Diuretics and Uric Acid Levels

• Loop diuretics do not have a significant effect on uric acid levels, and are not typically associated with hyperuricemia 3, 4
• Loop diuretics are often used in patients with clinically significant fluid overload, such as those with heart failure or advanced renal failure 4