Potassium-Sparing Diuretics

Potassium-Sparing Diuretics

1. Definition, scope & place in the diuretic family

• Potassium-sparing diuretics are agents that act on the late distal tubule (late DCT) and collecting duct (CD) to produce a mild natriuresis while conserving K⁺ (and H⁺) — the opposite of the kaliuresis caused by all more proximally acting diuretics (G&G 14e Ch.29; KDT 8e Ch.42, pp.634–6).
• Two mechanistically distinct sub-classes are pooled under this label because they share the net urinary-electrolyte signature (↑Na⁺, ↓K⁺, ↑Cl^-, slight ↑HCO₃^-, urine mildly alkalinised) (KDT 8e Ch.42, p.636; G&G 14e Ch.29 Table 29-6/29-7):
  • (a) Antagonists of the mineralocorticoid receptor (MR) — "aldosterone antagonists": spironolactone, eplerenone, finerenone (and, outside the U.S./India, canrenone and potassium canrenoate).
  • (b) Inhibitors of the renal epithelial Na⁺ channel (ENaC) — "Na⁺ channel blockers": amiloride, triamterene.
• They are low-efficacy (weak) diuretics: maximal fractional Na⁺ excretion ≈ 2–3 % of the filtered load, because >90 % of filtered Na⁺ is already reabsorbed upstream of their site of action (KDT 8e Ch.42, p.624 & Table 42.2, p.637; G&G 14e Ch.29).
• Consequently they are rarely used as sole agents; their principal roles are (i) to offset the K⁺ (and Mg²⁺) loss of loop/thiazide diuretics, (ii) to add a small natriuretic/antihypertensive increment, and (iii) MR antagonists specifically — to deliver disease-modifying benefit in heart failure, primary aldosteronism, cirrhotic ascites and diabetic CKD (G&G 14e Ch.29; KDT 8e Ch.42, pp.634–6).
• Historical note: spironolactone (aldosterone antagonist) and the ENaC blockers triamterene/amiloride were developed in parallel with the thiazides and loop diuretics in the late 1950s–1960s, expressly to counter diuretic-induced hypokalaemia (KDT 8e Ch.42, p.625).

Comparative urinary-electrolyte signature and efficacy (KDT 8e Ch.42 Table 42.2, p.637)

• Spironolactone — Na⁺ ↑, K⁺ ↓, Cl^- ↑, HCO₃^- –/↑; max ~3 % filtered Na⁺ excreted; efficacy Low.
• Amiloride — Na⁺ ↑, K⁺ ↓, Cl^- ↑, HCO₃^- –/↑; max ~3 % filtered Na⁺ excreted; efficacy Low.
• (Contrast: furosemide 25 % / High; thiazide 8 % / Intermediate; acetazolamide 5 % / Mild.)