What is the treatment for hyponatremia (low sodium levels) in patients with End-Stage Renal Disease (ESRD) undergoing dialysis?

From the Guidelines

Treating hyponatremia in ESRD patients on dialysis primarily involves adjusting the dialysate sodium concentration and carefully managing ultrafiltration, along with dietary sodium restriction and fluid limitation. The goal is to match or slightly exceed the patient's serum sodium level with the dialysate sodium concentration, typically using a dialysate sodium of 138-140 mEq/L for mild hyponatremia or higher (up to 145 mEq/L) for more severe cases, as suggested by general principles of managing electrolyte imbalances in dialysis patients 1. Key aspects of management include:

• Adjusting dialysate sodium concentration to the patient's serum sodium level
• Careful ultrafiltration to avoid rapid fluid shifts
• Restricting fluid intake to 1-1.5 liters per day between dialysis sessions
• Limiting dietary sodium to 2-3 grams daily
• Considering increased dialysis frequency for persistent hyponatremia
• Discontinuing medications that may contribute to hyponatremia, if possible
• Avoiding vasopressin receptor antagonists and hypertonic saline due to risks associated with their use in dialysis patients
• Gradually correcting sodium levels to prevent osmotic demyelination syndrome, with increases limited to 8-10 mEq/L in 24 hours, based on the principles outlined for managing severe hyponatremia 1. The use of diuretics, such as furosemide, bumetanide, or torsemide, may be considered to promote sodium and water loss, but their use should be approached with caution 1. Addressing the underlying cause of hyponatremia, whether it's excessive free water intake, malnutrition, or other comorbidities, is also crucial for effective management.

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.

Patients were randomized to receive either placebo (N = 220) or tolvaptan (N = 223) at an initial oral dose of 15 mg once daily. The dose of tolvaptan could be increased at 24-hour intervals to 30 mg once daily, then to 60 mg once daily, until either the maximum dose of 60 mg or normonatremia (serum sodium >135 mEq/L) was reached

The treatment for hyponatremia in patients, including those with End-Stage Renal Disease (ESRD) on dialysis, is not directly addressed in the provided drug label. However, based on the information provided for patients with hyponatremia due to other causes, tolvaptan can be used to treat hyponatremia.

• The initial dose is 15 mg once daily, which can be increased to 30 mg once daily, then to 60 mg once daily as needed and tolerated.
• Fluid restriction should be avoided if possible during the first 24 hours of therapy to avoid overly rapid correction of serum sodium.
• Patients should be monitored for changes in serum sodium concentrations and for the need for fluid restriction. However, it is essential to note that the provided label does not specifically address the treatment of hyponatremia in ESRD patients on dialysis. Therefore, the use of tolvaptan in this specific population should be approached with caution and under the guidance of a healthcare professional, considering the potential risks and benefits 2.

From the Research

Treatment Options for Hyponatremia in ESRD on Dialysis

• The treatment of hyponatremia in patients with end-stage renal disease (ESRD) on dialysis involves correcting the underlying cause of the disorder and managing the patient's fluid and electrolyte balance 3, 4.
• Vasopressin receptor antagonists (VRAs) have been shown to be effective in treating euvolemic and hypervolemic hyponatremia by increasing the excretion of free water and correcting serum sodium levels 5.
• VRAs, such as conivaptan, tolvaptan, and lixivaptan, can be used to treat hyponatremia in patients with ESRD on dialysis, but their use should be carefully monitored to avoid rapid correction of serum sodium levels and osmotic demyelination 6.
• In addition to VRAs, other treatment options for hyponatremia in ESRD on dialysis include fluid restriction, hypertonic saline, and loop diuretics, but these treatments may have limitations and potential side effects 4, 6.
• The management of hyponatremia in patients with ESRD on dialysis should be individualized and based on the patient's underlying condition, the severity of the hyponatremia, and the presence of any comorbidities 7.

Considerations for Treatment

• The decision to initiate treatment for hyponatremia in patients with ESRD on dialysis should be based on the patient's symptoms, serum sodium levels, and overall clinical condition 3, 4.
• Patients with severe hyponatremia (serum sodium <120 mEq/L) may require more aggressive treatment, including the use of hypertonic saline and VRAs 6.
• Monitoring of serum sodium levels, urine output, and clinical symptoms is essential to guide treatment and avoid complications such as osmotic demyelination 5, 6.
• The use of VRAs in patients with ESRD on dialysis may be associated with an increased risk of adverse events, such as thirst, dry mouth, and constipation, which should be carefully monitored and managed 5.