What is the role of urea in the management of hyponatremia?

Role of Urea in the Management of Hyponatremia

Urea is an effective treatment option for syndrome of inappropriate antidiuretic hormone (SIADH)-related hyponatremia, particularly in cases that are refractory to fluid restriction. 1, 2

Mechanism and Indications

Urea works by:

• Inducing renal water excretion
• Promoting sodium retention
• Creating an osmotic water drive

Urea is specifically indicated for:

• SIADH-related hyponatremia 1, 2
• Fluid restriction-refractory hyponatremia 3
• Both acute and chronic hyponatremia cases 4, 5

Efficacy

Research demonstrates urea's effectiveness:

• In a study of fluid restriction-refractory hyponatremia, 64.1% of patients achieved serum sodium ≥130 mmol/L within 72 hours of urea treatment 3
• Critically ill patients showed significant increases in serum sodium from the second day of treatment (131.4 ± 3.5 mEq/L) with normalization by the fourth day (136.2 ± 4.1 mEq/L) 4
• A median serum sodium increase of 2 mEq/L per day has been observed with urea administration 6

Dosing and Administration

• Starting dose: ≥30 g/day 3, 6
• Can be administered orally for both acute and chronic cases
• Long-term oral treatment has been shown to be successful and well-tolerated, even in pediatric patients 5

Safety Considerations

While generally safe, clinicians should be aware of:

• Risk of overcorrection (increase >8 mEq/L in 24 hours) observed in approximately 8% of patients 6
• The serum sodium level should not be corrected by more than 10 mmol/L/day to prevent osmotic demyelination syndrome 1
• Patient tolerance issues, with discontinuation due to intolerance reported in about 27% of patients 6
• Common side effects include distaste and gastric intolerance 2, 3

Monitoring

• Serum sodium levels should be checked every 2 hours initially, and every 4 hours during treatment 7
• Monitor BUN levels, which typically increase with urea treatment 6
• Watch for signs of overcorrection and adjust treatment accordingly

Practical Algorithm for Urea Use in Hyponatremia

1. Confirm SIADH diagnosis through clinical assessment and laboratory findings
2. Try fluid restriction first in mild to moderate cases
3. Consider urea when:
   • Fluid restriction fails
   • Moderate to profound hyponatremia is present
   • Patient has SIADH, particularly with neurological etiology
4. Start with 30 g/day of urea
5. Monitor serum sodium every 2-4 hours initially
6. Adjust dose based on response and tolerance
7. Continue until target sodium level is achieved or maintenance therapy is established

Comparison with Other Treatments

Urea offers advantages over other treatments:

• Unlike vaptans, urea has lower risk of overly rapid correction of hyponatremia 2
• More effective than fluid restriction alone in many cases 3
• Can be used for long-term management of chronic SIADH 5

Limitations include poor palatability and potential gastric intolerance, which may affect patient adherence 2.