What is the effect of aldosterone on pH and potassium levels?

Aldosterone Effects on pH and Potassium

Aldosterone increases renal acid excretion (raising pH) and increases potassium excretion (lowering serum potassium), acting primarily through mineralocorticoid receptors in the distal nephron to regulate both acid-base balance and potassium homeostasis. 1, 2, 3

Mechanism of Action on Potassium

Aldosterone causes potassium loss through competitive binding at aldosterone-dependent sodium-potassium exchange sites in the distal convoluted renal tubule. 1

• Aldosterone binds to mineralocorticoid receptors in epithelial tissues (particularly the kidney) and increases sodium reabsorption while simultaneously increasing potassium excretion 2
• This sodium-potassium exchange mechanism causes increased amounts of sodium and water to be retained while potassium is excreted 1
• In primary aldosteronism, the increased aldosterone production induces sodium retention, suppressed plasma renin activity, and increased potassium excretion, which may cause hypokalemia if prolonged and severe 4
• However, hypokalemia is absent in the majority of primary aldosteronism cases and has low negative predictive value for diagnosis 4

Mechanism of Action on pH (Acid-Base Balance)

Aldosterone stimulates renal acid excretion, acting on all subtypes of intercalated cells in the distal nephron to enhance proton secretion and maintain alkaline pH. 3

• During acidosis, circulating aldosterone levels increase and the hormone acts to stimulate renal acid excretion 3
• In acid-secretory type A intercalated cells, aldosterone stimulates proton secretion into urine 3
• In non-type A intercalated cells, aldosterone increases the activity of the luminal anion exchanger pendrin, stimulating bicarbonate secretion and chloride reabsorption 3
• Aldosterone indirectly stimulates renal acid excretion by enhancing sodium reabsorption through the epithelial sodium channel (ENaC), which increases the lumen-negative transepithelial voltage that facilitates proton secretion by neighboring intercalated cells 3

Clinical Implications When Blocking Aldosterone

When aldosterone is blocked with antagonists (spironolactone or eplerenone), the opposite effects occur: potassium is retained (causing hyperkalemia risk) and acid excretion is impaired (causing metabolic acidosis risk). 4, 3

Hyperkalemia Risk with Aldosterone Antagonists

• The major risk of aldosterone antagonists is hyperkalemia due to inhibition of potassium excretion 4
• Hyperkalemia rates reach 24% in clinical practice compared to only 2% in clinical trials 4
• Aldosterone antagonists should not be administered to patients with baseline serum potassium exceeding 5.0 mEq/L 4
• Potassium levels exceeding 5.5 mEq/L should trigger discontinuation or dose reduction of the aldosterone antagonist 4

Acid-Base Disturbances with Aldosterone Blockade

• Pharmacological blockade of aldosterone action impairs the renal response to acid loading and causes hyperkalemic renal tubular acidosis 3
• Inherited or acquired syndromes of impaired aldosterone release or action impair the renal response to acid loading 3
• Monitoring of acid-base status may be warranted in patients on aldosterone antagonists, particularly those with pre-existing acid-base disorders or renal impairment 5

Critical Monitoring Requirements

Potassium and renal function must be checked within 3 days after initiating aldosterone antagonists, then again at 7 days, followed by at least monthly monitoring for the first 3 months. 4, 6

• Subsequent monitoring should occur every 3 months thereafter 4
• Any addition or increase in dosage of ACE inhibitors or ARBs should trigger a new cycle of monitoring 4
• The triple combination of ACE inhibitor + ARB + aldosterone antagonist should be avoided due to dramatically increased hyperkalemia risk 4, 6