Thursday, July 12, 2012

Urea and Hyponatremia

Urea is a hyponatremia treatment long forgotten in the United States. Chronic SIADH is usually 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, cheaper alternative is being advocated.

What do we know about urea? It is 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


Dr. Helbert Rondon said...

Another advantage of urea is that it has been shown that urea protects against the development of osmotic demyelination syndrome (ODS) when overcorrection of serum sodium occur. Aparently, urea causes rapid reaccumulation of organic osmolytes in the brain cells. That is why ODS occurs very rarely in chronic hemodialysis patients.

Tomoki Tsukahara said...

Thank you for sharing your insights, Dr. Rondon. It makes sense. We have to be careful about overcorrection anyway, and I think the potential protective effect of urea against ODS is a big plus given the grave prognosis of ODS. I appreciate your points.

Anonymous said...

An alternative in patients who find urea powder unpalatable is having the pharmcy compress it into tablets that can be swallowed whole. This means swallowing a number of relatively big tablets, but they have no taste. Routine practice, here in Belgium.

Tomoki Tsukahara said...

Dear anonymous, thank you for your comment based on your experience, I found it helpful. I was wondering if there is such an alternative option over there. T

alain soupart said...

Dear Dr Tsukahara ,dear collegues ,
Thank for your interest for urea .
Indeed it is easy to use (we treat the majority of our patients with SIADH with urea,some of them for more than 5 years and they get use generally over time (weeks) to the taste but which is greatly attenuated by the mixture with syrup (grenadine or another one),orange juice..For those who really cannot take urea like this , another alternative is to prescribe urea as effervescent preparation :( urea 10g + sodium bicarbonate 2g+ citric acid 1.5gr + sucrose 200mg )for each bag and patient takes for instance 2 bags/day (dose must then be adapted). Alain Soupart

Dr. Chirag Faldu said...

I am treating a patient of mine with urea 30g (3 table spoon) daily and his Na has improved from ~ 130 to 135. I found a compounding pharmacy here in Florida that is selling the powder ~ 25-50 $ per month (which I think is very pricy) depending on the dose. I am interested to find out if anyone else knows of a pharmacy or online store that sells it cheaper.

Jasmine said...

My son has a recently discovered genetic condition which causes hyponatremia (syndrome of inappropriate of antidiaresis). I have the same condition but his is much worse with a sodium getting down to 114. After 15 days in the hospital, we administer 4.5 grams of urea 4x a day (he is 10 months old). It was a total nightmare to get into him. He is also on fluid restriction. One local compounding pharmacy only charges $15 per month, however, another pharmacy quoted close to $200!! It is a very difficult product to get. right now we are administering it by syringe mixed with water and stevia powder between sips of his bottle. It tastes HORRIBLE and it makes me crazy when doctors talk about how not awful it tastes. Maybe diluted in a big cup of OJ it's fine, but I can tell you, concentrated, it is extremely bitter. Imagine getting about 10cc per dose into an infant. Not fun! Also, not finding that it helps all that much. Sodium this week was 126. :(

Vanessa said...

Hi Jasmine, I hope all the best for your son. Could you please tell me the pharmacies where you got the urea? It is hard to find. My email is Thank you

jennyram said...

My mother started on urea treatment for her siadh. She had a sodium level of 132 that they couldn't get up and even though not that low, still her balance and thinking were somewhat off. Got a nephrologist to prescribe from a compound pharmacy 3 tablespoons a day of urea. 3 was too much for my Mom. It caused diarrhea. We cut down to about 2 tablespoons. We got her sodium tested this week and it was the highest it has ever been, 140. But this time her confusion didn't go away. It seems to be worse. She had a high bun of 73. Could there be any link to the confusion and this urea and her sodium level going up?

Anonymous said...

I have been taking medicinal urea powder for chronic SIADH for about 18 months and my serum Na is usually between 135 and 137 (increased from around 131-133). Not a big increase but my energy improved at first. But then it began to decrease after the first year of treatment, along with a weight decrease from 100 lbs to 94 (my height is 5'2"). So my nephrologist said to take it only every 3 or 4 days. The new schedule seems to work because my Na is still 135 (blood test every 2-3 months). But I still feel like my body is being flushed out, all my energy going out in the urine. What else can I do?
Karen Gadke, Capron, Illinois
June 16, 2016