What are the possible causes of hyponatremia in a patient with liver disease?

From the Guidelines

Hyponatremia in patients with liver disease is most commonly caused by dilutional hyponatremia from fluid retention and ascites, and management typically involves fluid restriction, careful diuretic adjustment, and in severe cases, administration of hypertonic saline or vasopressin receptor antagonists like tolvaptan. The possible causes of hyponatremia in a patient with liver disease include:

• Dilutional hyponatremia from fluid retention and ascites, where excess fluid dilutes the sodium concentration in the blood, as a result of portal hypertension leading to increased aldosterone and antidiuretic hormone (ADH) secretion, promoting water retention 1
• Hepatorenal syndrome, where kidney function deteriorates due to reduced blood flow, impairing sodium handling 1
• Decreased effective arterial blood volume, triggering further ADH release despite low serum sodium 1
• Diuretic therapy, particularly with spironolactone and furosemide used to manage ascites, can exacerbate sodium losses 1
• Poor nutritional intake and low-sodium diets as part of their treatment, further contributing to hyponatremia 1
• Beer potomania syndrome in alcoholic cirrhosis patients who consume large volumes of beer with minimal food intake 1
• The use of lactulose for hepatic encephalopathy can cause diarrhea and subsequent sodium losses 1 According to the most recent guidelines, mild hyponatremia (Na 126-135 mEq/L) in cirrhosis without symptoms does not require specific management apart from monitoring and water restriction, while water restriction to 1,000 mL/day and cessation of diuretics is recommended in the management of moderate hyponatremia (120-125 mEq/L), and a more severe restriction of water intake with albumin infusion is recommended for severe hyponatremia (<120 mEq/L) 1.

From the FDA Drug Label

In two double-blind, placebo-controlled, multi-center studies (SALT-1 and SALT-2), a total of 424 patients with euvolemic or hypervolemic hyponatremia (serum sodium <135 mEq/L) resulting from a variety of underlying causes (heart failure, liver cirrhosis, syndrome of inappropriate antidiuretic hormone [SIADH] and others) were treated for 30 days with tolvaptan or placebo, then followed for an additional 7 days after withdrawal.

The possible causes of hyponatremia in a patient with liver disease include:

• Liver cirrhosis: as mentioned in the study, liver cirrhosis is one of the underlying causes of hyponatremia in the patients treated with tolvaptan.
• Syndrome of inappropriate antidiuretic hormone (SIADH): although not exclusively related to liver disease, SIADH is another underlying cause of hyponatremia mentioned in the study.
• Hypervolemic hyponatremia: the study mentions that patients with hypervolemic hyponatremia were included, which can be related to liver disease, particularly in cases of cirrhosis with ascites.

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From the Research

Possible Causes of Hyponatremia in Liver Disease Patients

• Excessive renal retention of water relative to sodium due to reduced solute-free water clearance 3
• Increased release of arginine vasopressin, leading to water reabsorption despite low serum osmolality 3, 4
• Secondary vasopressin stimulation, involving a baroreceptor mechanism, which is regularly found in the hyponatremia of liver cirrhosis 5
• Elevated levels of arginine vasopressin (AVP) hormone, which can occur in various clinical conditions, including cirrhosis 6

Underlying Mechanisms

• Hyponatremia is characterized by excessive renal retention of water relative to sodium, resulting in a dilutional effect on serum sodium concentration 3
• Arginine vasopressin plays a key role in the development of hyponatremia, as it promotes water reabsorption in the renal collecting ducts 4, 5
• The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common cause of hyponatremia, characterized by excessive secretion of antidiuretic hormone (ADH) 7

Clinical Implications

• Hyponatremia is associated with increased mortality in cirrhotic patients, those with end-stage liver disease (ESLD) on transplant waiting lists, and posttransplantation patients 3
• Hyponatremia can lead to numerous complications in liver disease patients, including severe ascites, hepatic encephalopathy, infectious complications, renal impairment, and increased hospital stay 3
• Correction of hyponatremia is crucial to prevent these complications and improve patient outcomes 3, 6