What Mineralocorticoid Receptor Antagonist (MRA) is recommended for patients with cirrhosis and hyponatremia?

MRA Recommendation for Cirrhosis with Hyponatremia

In patients with cirrhosis and hyponatremia, spironolactone should be reduced or discontinued rather than continued at full dose, as severe hyponatremia is a recognized complication requiring diuretic dose reduction or cessation. 1

Critical Management Algorithm

When to Reduce or Stop MRAs

Spironolactone (and other aldosterone antagonists) must be reduced or stopped in the following scenarios: 1

• Severe hyponatremia (serum sodium <125 mmol/L) - diuretics should be carefully reduced or discontinued 1
• Acute kidney injury 1
• Overt hepatic encephalopathy 1
• Severe muscle spasm 1

Specific Sodium Thresholds

The 2021 Gut guidelines provide clear thresholds: 1

• Serum sodium <125 mmol/L (severe hyponatremia): Fluid restriction to 1-1.5 L/day should be reserved for those who are clinically hypervolemic with this degree of hyponatremia 1
• Hypovolaemic hyponatremia during diuretic therapy: Discontinue diuretics and expand plasma volume with normal saline 1

If MRA Must Be Continued

If ascites control is absolutely necessary despite hyponatremia, spironolactone remains the preferred MRA because: 1

• It is the primary diuretic drug recommended for cirrhotic ascites (A1 recommendation) 1
• Starting dosage: 50-100 mg/day, with maximum of 400 mg/day 1
• The FDA label specifically warns that spironolactone can cause sudden alterations of fluid and electrolyte balance which may precipitate impaired neurological function, worsening hepatic encephalopathy and coma in patients with hepatic disease with cirrhosis and ascites 2

Important Caveats

Hyponatremia as a Diuretic-Induced Complication

Hyponatremia meeting specific criteria defines "diuretic-intractable ascites": 1

• Decrease of serum sodium by >10 mEq/L to serum sodium of <125 mEq/L is classified as a diuretic-induced complication that precludes effective diuretic dosage 1
• This represents refractory ascites requiring alternative management strategies such as large-volume paracentesis 1

Alternative to Spironolactone

Amiloride (10-40 mg/day, 1/10 dose of spironolactone) can be substituted for spironolactone in patients with specific side effects like tender gynecomastia, but this does not address the hyponatremia issue 1

Monitoring Requirements

When any MRA is used in cirrhosis, mandatory monitoring includes: 1

• Changes in body weight 1
• Vital signs 1
• Serum creatinine 1
• Serum sodium and potassium 1
• The FDA label emphasizes that clearance of spironolactone and its metabolites is reduced in patients with cirrhosis, requiring initiation at the lowest dose with slow titration 2

Clinical Reality

The practical answer is that no MRA is "recommended" when severe hyponatremia is present - the guidelines uniformly state that diuretics should be reduced or stopped in this scenario. 1 The focus should shift to managing the hyponatremia itself through fluid restriction (if hypervolemic with sodium <125 mmol/L), discontinuing diuretics, and considering alternative ascites management such as large-volume paracentesis with albumin replacement. 1