From the Guidelines
Low sodium, or hyponatremia, is primarily caused by excessive water intake, certain medications, and medical conditions that affect fluid balance, such as heart failure, kidney disease, liver cirrhosis, and syndrome of inappropriate antidiuretic hormone secretion (SIADH) 1. The most common causes of hyponatremia can be categorized into three main types: hypovolemic, euvolemic, and hypervolemic hyponatremia.
- Hypovolemic hyponatremia is often caused by excessive diuretic use, dehydration, or other factors that lead to a decrease in blood volume.
- Euvolemic hyponatremia is commonly associated with the syndrome of inappropriate antidiuretic hormone secretion (SIADH), hypothyroidism, or adrenal insufficiency.
- Hypervolemic hyponatremia is typically seen in patients with heart failure, liver cirrhosis, or kidney disease, where there is an excess of fluid in the body. Medications that can cause low sodium include diuretics, antidepressants, and some anti-seizure medications 1. Treatment of hyponatremia depends on the underlying cause and severity, but may include fluid restriction, sodium supplementation, medication adjustments, or in severe cases, intravenous hypertonic saline 1. It is essential to identify and address the underlying cause of hyponatremia to prevent further complications and improve patient outcomes. Symptoms of hyponatremia can range from mild to severe and include headache, confusion, nausea, seizures, and coma, emphasizing the need for prompt medical attention when symptoms appear 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 causes of low sodium (hyponatremia) mentioned in the drug label include:
- Heart failure
- Liver cirrhosis
- Syndrome of inappropriate antidiuretic hormone (SIADH)
- Other underlying causes
Note that the label does not provide a comprehensive list of all possible causes of hyponatremia, but rather mentions specific causes that were represented in the patient population of the clinical trials. 2
From the Research
Causes of Low Sodium
- Low sodium, also known as hyponatremia, is a common and challenging disorder that can be caused by various factors, including elevated vasopressin levels 3
- Vasopressin plays an important role in the pathogenesis of hyponatremia through its action on the vasopressin type 2 receptor (V(2)R), leading to electrolyte-free water reabsorption 4
- Conditions such as congestive heart failure, liver cirrhosis, and the syndrome of inappropriate antidiuretic hormone secretion can lead to hyponatremia due to elevated vasopressin levels 3, 4
- Decreases in the concentration of sodium in plasma can also be caused by other factors, but the exact mechanisms are not always well understood 5
Mechanisms of Hyponatremia
- The result of elevated vasopressin is renal water retention and hyponatremia, a low serum sodium concentration 3
- Vasopressin receptor antagonists can help to correct hyponatremia by inducing urinary dilution with an aquaresis that leads to an increase in serum sodium concentration 6
- The use of vasopressin receptor antagonists has been shown to be effective in the treatment of hyponatremia, particularly in patients with euvolemic and hypervolemic hyponatremia 6, 4
Clinical Implications
- Hyponatremia is associated with excess morbidity and mortality, and its presence conveys an increased mortality risk even when the decrement is mild 5
- Chronic and apparently asymptomatic hyponatremia is associated with increased morbidity, including neurocognitive deficits and bone fractures 5
- The treatment of hyponatremia is crucial to prevent these complications, and vasopressin receptor antagonists provide a promising treatment option 5, 7