What Does "Potassium-Sparing" Diuretic Mean?
A potassium-sparing diuretic is a class of medication that promotes sodium and water excretion while preventing potassium loss in the urine, acting primarily in the distal tubule and collecting duct of the kidney. 1
Mechanism of Action
Potassium-sparing diuretics work through two distinct mechanisms 1, 2:
Aldosterone antagonists (spironolactone, eplerenone) block mineralocorticoid receptors in the distal tubule, preventing aldosterone from stimulating sodium reabsorption and potassium secretion 3, 2, 4
Epithelial sodium channel (ENaC) blockers (amiloride, triamterene) directly inhibit sodium channels in the luminal membrane of distal tubule cells, reducing the electrochemical gradient that drives potassium secretion 3, 2, 4
Both mechanisms result in increased sodium and water excretion while retaining potassium in the body 5, 6.
Site of Action
Unlike loop diuretics (furosemide, bumetanide, torsemide) that act at the loop of Henle, or thiazides that act in the early distal tubule, potassium-sparing agents work in the distal portion of the tubule and collecting duct 1. This is the final site where potassium secretion occurs in exchange for sodium reabsorption 2, 4.
Clinical Significance
The term "potassium-sparing" distinguishes these diuretics from loop and thiazide diuretics, which cause significant urinary potassium losses 6, 4. Loop diuretics increase sodium delivery to the distal tubule and stimulate secondary aldosterone secretion, both of which enhance potassium excretion 6, 2. Thiazides similarly increase distal sodium delivery and flow rate, stimulating net potassium secretion 2, 4.
Potassium-sparing diuretics are typically used in combination with loop or thiazide diuretics to prevent or correct hypokalemia 7, 5, 6. When combined, they reduce the risk of hypokalemia and hypomagnesemia that commonly occurs with more potent diuretics 5, 6.
Relative Diuretic Potency
Potassium-sparing diuretics have weak diuretic effects compared to loop or thiazide diuretics 1, 7. They increase sodium excretion to only a modest degree because the distal tubule reabsorbs a relatively small fraction of filtered sodium 2. The ACC/AHA guidelines note that amiloride "has little additive diuretic or antihypertensive effect when added to a thiazide diuretic" 7.
These agents should rarely be used alone for diuresis or blood pressure control 7. The FDA label for amiloride explicitly states it "should rarely be used alone" and notes that "used as single agents, potassium-sparing diuretics result in an increased risk of hyperkalemia (approximately 10% with amiloride)" 7.
Primary Clinical Indications
According to FDA labeling and guidelines, potassium-sparing diuretics are indicated to 7, 5:
- Restore normal serum potassium in patients who develop hypokalemia on loop or thiazide diuretics 7
- Prevent hypokalemia in high-risk patients (those on digoxin or with significant cardiac arrhythmias) 7
- Treat conditions with aldosterone excess (primary hyperaldosteronism, cirrhosis with ascites) 3, 5
Important Safety Consideration
The defining characteristic—potassium retention—also represents the primary risk: hyperkalemia 7, 6. When used alone, amiloride causes hyperkalemia in approximately 10% of patients 7. This risk increases substantially when combined with ACE inhibitors, ARBs, or in patients with renal impairment 3, 6.
Potassium-sparing diuretics should be avoided in patients with eGFR <45 mL/min, baseline potassium >5.0 mEq/L, or when combined with ACE inhibitors/ARBs without close monitoring 3.