What are the effects of aldosterone on the kidney?

From the Guidelines

Aldosterone has a significant impact on the kidney, primarily acting on the distal tubules and collecting ducts to increase sodium reabsorption and potassium excretion, leading to increased blood volume and blood pressure due to sodium and water retention, along with decreased serum potassium levels. The effects of aldosterone on the kidney are crucial in understanding its role in various physiological and pathological conditions.

Key Effects of Aldosterone on the Kidney

• Increases sodium reabsorption from the tubular fluid back into the bloodstream by activating sodium channels (ENaC) on the luminal membrane and sodium-potassium pumps (Na⁺/K⁺-ATPase) on the basolateral membrane 1.
• Drives potassium secretion into the urine, creating an electrochemical gradient as sodium moves into the cell.
• Stimulates hydrogen ion secretion, contributing to acid-base balance.
• Leads to increased blood volume and blood pressure due to sodium and water retention, along with decreased serum potassium levels.

Clinical Implications

The understanding of aldosterone's effects on the kidney is vital for managing conditions like heart failure, hypertension, and edema. Medications that block aldosterone effects, such as spironolactone or eplerenone, are used to treat these conditions by promoting sodium and water excretion while conserving potassium 1. However, the use of these medications requires careful monitoring of potassium levels and renal function to avoid hyperkalemia and worsening renal function.

Monitoring and Management

• Potassium levels and renal function should be monitored closely when initiating or adjusting aldosterone antagonist therapy.
• The development of potassium levels >5.5 mEq/L should trigger discontinuation or dose reduction of the aldosterone receptor antagonist unless other causes are identified 1.
• Patients should be instructed to stop the aldosterone receptor antagonist during episodes of diarrhea, dehydration, or while loop diuretic therapy is interrupted.

From the FDA Drug Label

Spironolactone and its active metabolites are specific pharmacologic antagonists of aldosterone, acting primarily through competitive binding of receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule. The effects of aldosterone on the kidney include:

• Sodium retention: Aldosterone promotes the reabsorption of sodium in the distal convoluted renal tubule.
• Potassium excretion: Aldosterone increases the excretion of potassium in the distal convoluted renal tubule.
• Water retention: Aldosterone indirectly leads to water retention by promoting the reabsorption of sodium, which in turn increases water reabsorption. Since spironolactone acts as an aldosterone antagonist, it counteracts these effects, leading to increased excretion of sodium and water, and retention of potassium 2, 2.

From the Research

Effects of Aldosterone on the Kidney

• Aldosterone has profound effects on acid-base balance in the kidney, stimulating renal acid excretion during acidosis 3
• The mineralocorticoid receptor (MR) mediating the genomic effects of aldosterone is expressed in all cells of the distal nephron, including intercalated cells 3
• Aldosterone stimulates proton secretion into urine in acid-secretory type A intercalated cells and increases bicarbonate secretion and chloride reabsorption in non-type A intercalated cells 3
• Aldosterone also indirectly stimulates renal acid excretion by enhancing sodium reabsorption through the epithelial sodium channel ENaC 3

Aldosterone-Induced Effects on the Kidney

• Beyond its classical effect on sodium reabsorption, aldosterone has a range of effects on the kidney, including regulation of fluid and electrolyte homeostasis and blood pressure 4, 5
• Aldosterone via its receptor can have deleterious effects, including renal inflammation, fibrosis, podocyte injury, and mesangial cell proliferation, particularly in patients with primary hyperaldosteronism (PHA) 5
• Aldosterone can also contribute to the progression of kidney disease in patients with chronic kidney disease (CKD) 3

Mechanisms of Aldosterone Action

• Aldosterone exerts its action principally through the mineralocorticoid receptor (MR), which acts as a ligand-dependent transcription factor in target tissues 6
• Aldosterone also stimulates the activation of protein kinases and secondary messenger signaling cascades that act independently on specific molecular targets in the cell membrane 6
• The mechanisms of aldosterone action in the kidney involve both genomic and non-genomic pathways, leading to changes in renal physiology and pathophysiology 6, 7