Urea and Hyponatremia

Urea is a hyponatremia treatment long forgotten in the United States. Chronic SIADH isusually managed either by vaptans or a combination of fluid restriction, salt and furosemide. However, vaptans are very expensive and few patients can afford it. In a recent Belgian article,the use of urea as a comparable, cheaperalternative is being advocated.

What do we know about urea? Itis a very cheap powder (< $0.50/30 gram) that works by increasing free water excretion through osmotic diuresis. Shown below is the solute excretion as a determinant of free water excretion.

Free water clearance = solute excretion/Uosm x (1 - Uosm/Posm)

Physiologically it makes sense, but does it really work? In this article, 13 patients with SIADH were tried on vaptans (satavaptan or tolvaptan) for 12 months. Then vaptans were discontinued for 8 days and urea was started after ensuring that their Na level came down. The result? It worked as well as vaptans! Side effects included hypernatremia and gastric irritation but no osmotic myelinolysis has been reported with urea. It does not cause volume overload (unlike salt), hypokalemia (unlike diuretics), or uremia. You will not become uremic even if your BUN is 100 after you take urea (but you will be urinating a lot!).

So why are we not using it? Are you a fan of bitter drinks? We know Belgians are (great beer there!). In Belgium, only about 15% of patients discontinue to take urea due to its taste. In Canada, Dr. Bichet tried it himself (mixed with orange juice) and wrote “it does not smell of anything but the bitterness is strong”. On this side of the border, Dr. Berl wrote that it is “rarely compatible with North American palate”.

That being said, it may be a time to use urea again as a comparable, cheaper alternative for hyponatremia treatment. Across the Pacific (in Japan) there is a proverb “good medicine tastes bitter”. 


Posted by Tomoki Tsukahara