Diuretics Acting on the Distal Nephron

Thiazide and Thiazide-Like Diuretics

The American College of Cardiology recommends thiazide and thiazide-like diuretics, such as chlorothiazide, chlorthalidone, hydrochlorothiazide, indapamide, and metolazone, for patients with certain medical conditions, with initial doses and maximum daily doses varying by medication 1
Thiazides block sodium and chloride reabsorption in the distal tubule, increasing fractional sodium excretion to 5-10% of filtered load, with a strength of evidence supported by multiple studies 3, 4
The American College of Cardiology notes that these agents tend to decrease free water clearance and lose effectiveness when creatinine clearance falls below 40 mL/min, except for metolazone which maintains efficacy even with impaired renal function 3, 4
Metolazone is useful for combination therapy with loop diuretics in refractory edema, as it maintains efficacy even with impaired renal function, according to the American College of Cardiology 1, 2

The American College of Cardiology recommends potassium-sparing diuretics, such as spironolactone, for patients with certain medical conditions, with a strength of evidence supported by multiple studies 1, 3, 4, 2
Potassium-sparing diuretics are primarily used in combination with thiazide or loop diuretics to minimize potassium losses, according to the American College of Cardiology 1

The American College of Cardiology notes that renal function matters, as thiazides (except metolazone) lose efficacy with creatinine clearance <40 mL/min, whereas loop diuretics maintain efficacy unless renal function is severely impaired 3, 4
The American College of Cardiology recommends caution when using combination therapy, as adding thiazides (especially metolazone) to loop diuretics should be reserved for patients unresponsive to moderate- or high-dose loop diuretics to minimize electrolyte abnormalities 1, 2
The American College of Cardiology warns of the risk of hyperkalemia when using potassium-sparing diuretics, and notes that routine potassium supplementation may be unnecessary and potentially dangerous 3