Blog by Dr. Barry

Urea has been used for many years and in many countries for the treatment of SIADH/Hyponatremia. Urea is considered a GRAS (generally recognized as safe) product by the FDA1. In fact, an interesting study took place in Belgium in 2012. They looked at 12 patients with chronic SIADH, with an average sodium of 125 meq/L (low). The first year, they were given the new, very expensive, pharmaceutical drug class Vaptans daily. The average Sodium came up to a normal level of 135 meq/L. 1 patient out of the 12 dropped out due to severe thirst. Next, the patients had an 8 day “holiday” without treatment, and as expected the Sodium went back down (pictured above). Over the next 12 months, the SIADH patients were given oral Urea therapy. The patients now on Urea have a similar normal sodium level of 135 meq/L. However, this time there were no dropouts nor any significant adverse events. The authors, therefore concluded that oral Urea was safe, well tolerated and as effective as the Vaptans at a much lower cost.2 This study impacted the current European best practice guidelines which advocate for Urea over Vaptans for SIADH/Hyponatremia.3
Another study, this time out of Italy, looked back from years 2013-2018 on 36 patients with cancer associated SIADH/Hyponatremia. They were treated with Urea, and had an average sodium 1 point lower at 124 meq/L (low). They noted after only 24 hours of treatment, the sodium improved on average by 5 meq/L. Secondarily, the Italian physician scientists discovered over 90% of patients on 60 days of treatment with Urea, achieved a normal sodium level. The authors, therefore concluded oral Urea was safe, effective beginning first day of treatment, and very well tolerated.4

Urea has been used for many years in multiple countries for SIADH/Hyponatremia. Urea has always shown to be safe and effective even when taken for a year or more. Our version of this miraculous medical food is UreaAide which can be found by clicking here KidneyAide.

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Links to the FDA, CJASN and Endocrinology studies + European guidelines for Hyponatremia.
1.https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=184.1923

2.https://cjasn.asnjournals.org/content/7/5/742

3. http://www.european-renal-best-practice.org/sites/default/files/u33/short%20version%20hyponatraemia%20English%20FINAL.pdf

4.https://onlinelibrary.wiley.com/doi/full/10.1111/cen.13966

Hyponatremia, or low sodium, is quite common affecting estimates of 1.7-2.1% of the US population1. There are many causes of Hyponatremia (low serum sodium). For completeness, there are less common causes of Hyponatremia, such as the type associated with hyperglycemia (very high blood sugar) or seen with extremely high lipids or protein levels termed ‘’pseudohyponatremia’. These types are looked at and treated differently then the more common hypotonic Hyponatremia that most patients have.
It’s very important that we recognize something first, nearly all Hyponatremia is caused by the dilution effect of excess water in the blood. This excess water dilutes the sodium level to below 135 meq/L. It’s in this context that we discuss the major causes of Hyponatremia.

Lets start with medications. There are many medications that lead to Hyponatremia, thiazides diuretics being the most common culprits.
Other drugs commonly implicated are antidepressants and anticonvulsants. Street drugs such as ecstasy, bath salts, and amphetamines are also possible causes.

One question that is often brought up is, ‘doctor can I drink too much water?’
Answer, a resounding yes with some caveats.
​Its relative to the solute or food you consume. Your kidney can usually do a great job of ridding your body of excess water. Even the great kidneys, however, have their limits. The lowest dilution the kidneys can ever get down to is 50. 50 what you ask? 50 milliosmoles/Liter (mOsm/L). This implies that your kidney needs at least 50 mOsm/L of ‘stuff’ to get rid of that Liter of water you drank. The ‘stuff’ is food like protein (Urea), salt and potassium. The average person eats about 900 mOsm per day. So consider that scenario of 50 osm/L. The implication here is 900 mOsm/50 mOsm/L is 18 liters a day of water one could excrete. That’s over 4 gallons! So if your eating normally you’d have to drink an awful lot to dilute your sodium. This is actually termed psychogenic polydypsia when it happens. On the other hand, if your not eating all that well, say only 250 mOsm/day, then it’s 250/50= 5 liters. Often however, as we age the kidney may only get down to 100 osm dilution. Now 250/100 is only 2.5 liters of water before you start diluting. This type of Hyponatremia is called ‘’tea and toast’ or ‘beer potomania’ (when it’s beer as the main liquid). So yes you can drink too much water even if your kidney is doing it’s very best. Now what if your kidney is getting the wrong signal?

Syndrome of inappropriate ADH secretion or SIADH is just that, inappropriate signal. ADH is anti-diuretic hormone, meaning when it’s around you anti diurese (make less urine). When ADH is on board the kidney holds water very tight and your urine turns darker and more concentrated. Over several days of drinking water and other liquids, your serum sodium will become diluted.
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So what causes the ADH to be excreted?
Common triggers for ADH are nausea and pain; that’s why we often see SIADH after surgeries. Other triggers are Lung disease including cancer (especially small cell) and brain diseases such as stroke, bleed, or infection. These SIADH scenarios respond best to UreaAide because the Urea induces a nice osmotic diuresis. The osmotic diuresis will counteract the dilution effect and raise the serum sodium level.

Another cause of low sodium levels are true volume depletion from vomiting and diarrhea. Here your body will also excrete ADH but this time the signal is appropriate. This is termed effective arterial volume depletion. This type of hypovolemic Hyponatremia usually corrects with iv fluids.

Other reasons your sodium could be low include: heart failure, cirrhosis of the liver, hypothyroidism, and adrenal Insufficiency. These tend to be obvious in terms of heart or liver disease, however thyroid or adrenal must be considered and tested for.

As you see their are a lot of scenarios in which the sodium may drop and your doctor will work with you to figure out why. The key is making the correct diagnosis and then recommending the best treatment.



1. Am J Med. 2013 Dec; 126(12): 1127–37.e1.
doi: 10.1016/j.amjmed.2013.07.021
PMID:24262726