Do thiazide diuretics cause hyperkalemia?

From the Guidelines

Thiazide diuretics do not cause hyperkalemia; they typically cause hypokalemia (low potassium). Thiazide diuretics like hydrochlorothiazide, chlorthalidone, and indapamide work by blocking sodium and chloride reabsorption in the distal convoluted tubule of the kidney, which increases sodium, chloride, and water excretion. This mechanism also enhances potassium excretion, leading to decreased potassium levels in the blood. Some key points to consider:

• The Systolic Hypertension in the Elderly Program, a multicenter, randomized, double-blind, placebo-controlled RCT, found that after 1 year of active treatment with chlorthalidone, the incidence of hypokalemia was 7.2% compared with 1% in the control group (p < 0.001) 1.
• The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) also found that individuals with hypertension and other risk factors who were given chlorthalidone had lower mean potassium levels and higher occurrence of hypokalemia compared with individuals on amlodipine and lisinopril after 4 years 1.
• A meta-analysis of 25 RCTs involving chlorthalidone and hydrochlorothiazide found dose-dependent reductions in serum potassium with increasing dosage, with chlorthalidone having a higher potency than hydrochlorothiazide 1. Patients on thiazide diuretics often need to monitor their potassium levels and may require potassium supplements or potassium-rich foods to prevent hypokalemia. In contrast to potassium-sparing diuretics (like spironolactone, eplerenone, and amiloride) and angiotensin-converting enzyme (ACE) inhibitors, which can cause hyperkalemia, thiazide diuretics are not typically associated with this condition. If a patient on thiazide diuretics develops hyperkalemia, clinicians should investigate other causes such as kidney dysfunction, medication interactions, or excessive potassium intake.

From the Research

Thiazide Diuretics and Hyperkalemia

• Thiazide diuretics are not typically associated with hyperkalemia, but rather with hypokalemia, as evidenced by studies such as 2, which found that thiazide diuretics cause hypokalemia and depletion of body potassium.
• In fact, thiazide-induced hypokalemia is a well-documented side effect, with a prevalence of 7%-56% in patients taking thiazide diuretics, according to 3.
• The risk of thiazide-induced hypokalemia is influenced by factors such as age, dosage, and concomitant use of other medications, as reported in 4.
• Potassium supplementation is often recommended to mitigate the risk of hypokalemia in patients taking thiazide diuretics, although its effectiveness in preventing thiazide diuretic-induced abnormalities in glucose and uric acid metabolisms is still a topic of debate, as seen in 5 and 6.

Mechanisms and Associations

• The mechanisms underlying thiazide diuretic-induced hypokalemia are complex and involve the depletion of body potassium, as described in 2.
• There is a significant correlation between thiazide-induced hypokalemia and increased blood glucose, as suggested by the weighted statistical model in 6.
• The association between thiazide diuretics and hyperkalemia is not well-established, and the available evidence suggests that thiazide diuretics are more likely to cause hypokalemia than hyperkalemia, as reported in 3 and 4.