What effect does spironolactone have on sodium levels?

Spironolactone Increases Urinary Sodium Excretion While Potentially Lowering Serum Sodium Levels

Spironolactone increases urinary sodium excretion by blocking aldosterone receptors in the distal renal tubule, causing sodium and water to be eliminated in the urine, but paradoxically can lower serum sodium levels through dilutional effects and impaired free water clearance. 1, 2

Mechanism: How Spironolactone Affects Sodium

Spironolactone acts as a competitive aldosterone antagonist at the distal convoluted renal tubule, causing increased amounts of sodium and water to be excreted while potassium is retained. 2 This mechanism directly increases urinary sodium elimination, which is the therapeutic goal in conditions like cirrhosis with ascites and heart failure. 3, 4

The drug increases urinary sodium excretion significantly:

• In heart failure patients, spironolactone 100 mg/day increased spot urine sodium levels to 84.13 ± 28.71 mmol/L compared to 70.74 ± 34.43 mmol/L in standard therapy alone at day 3 of treatment. 4
• The proportion of patients with inadequate urinary sodium (<60 mmol/L) was reduced from 45.7% to 18.8% with spironolactone therapy. 4
• In cirrhosis patients, spironolactone produces a significant increase in urinary sodium excretion, with responders showing increases from baseline values below 35 mEq/day to between 50-245 mEq/day after treatment. 5, 6

The Paradox: Increased Urinary Sodium But Decreased Serum Sodium

Despite increasing urinary sodium excretion, spironolactone can cause hyponatremia (low serum sodium) through two distinct mechanisms: 1

Type 1: Hypovolemic Hyponatremia

• Results from overzealous diuretic therapy with prolonged negative sodium balance and marked extracellular fluid loss. 1
• Requires cessation of diuretics and plasma volume expansion with normal saline. 1

Type 2: Hypervolemic Hyponatremia (More Common)

• Occurs in approximately 60% of cirrhosis patients due to impaired free water clearance. 1
• Caused by non-osmotic vasopressin hypersecretion and enhanced proximal sodium reabsorption. 1
• Spironolactone should be temporarily discontinued when serum sodium falls below 125 mmol/L. 1
• Fluid restriction is generally unnecessary unless serum sodium drops below 120-125 mmol/L. 1

Critical Monitoring Requirements

During the first month of diuretic therapy, frequent monitoring is essential: 1

• Serum sodium levels
• Serum creatinine
• Serum potassium (hyperkalemia is a major risk)
• Daily weight

Severity Classification of Hyponatremia

• Mild: 130-135 mmol/L 1
• Moderate: 125-129 mmol/L 1
• Severe: <125 mmol/L (requires spironolactone discontinuation) 1

Clinical Context: When to Use Spironolactone Despite Sodium Effects

Spironolactone is the mainstay of diuretic treatment in cirrhosis with ascites because secondary hyperaldosteronism in liver cirrhosis induces reabsorption of sodium and water in the distal renal tubule. 3 The drug is initiated at 50-100 mg/day with a maximum dose of 400 mg/day, requiring 3-4 days to achieve stable concentration. 3

Aldosterone antagonist monotherapy or combination with loop diuretics is recommended: 3

• Monotherapy with loop diuretics alone is not recommended. 3
• Initial combination therapy using a 100:40 ratio of spironolactone to furosemide maintains adequate serum potassium levels and provides faster ascites control. 3

Common Pitfalls to Avoid

Do not continue spironolactone when serum sodium drops below 120-125 mmol/L despite water restriction. 3, 1 This represents severe hyponatremia requiring drug discontinuation, not just dose adjustment.

Do not use intravenous diuretics routinely as oral administration is standard; IV use can cause kidney damage due to sudden body fluid loss. 3

Monitor for hyperkalemia aggressively as this is the most common reason for dose adjustment or discontinuation, occurring in 19-33% of patients. 1 The drug causes potassium retention while promoting sodium excretion. 2