1. Urea’s molecular formula is CO-(NH2)2. Pubchem.
2. Urea is also known as Carbamide, 57-13-6, Carbonyldiamide, IsoUrea. Pubchem
3. Urea is found naturally in our skin and is one of our body’s natural moisturizers. Many skin care products contain Urea at various percentages, Eucerin 10% Urea is an example of one.
4. Urea has a molecular weight of 60.056 g/mol very similar to Sodium Chloride 58.44 g/mol (that’s why 1 packet of 15 g UreaAide is equal to ~7 salt tablets).
5. Urea is formed naturally in the liver. The liver, via the urea cycle, takes 2 toxic Ammonia molecules from protein breakdown plus Carbon Dioxide to form 1 Urea molecule. Urea May then be excreted safely through the urine.
6. An IV formulation of Urea Ureaphil (40 grams/vial) was available, and first used in the 1960’s for increased intracerebral pressure. Ureaphil was later discontinued in 2006, as other products like mannitol came on to market.
7. Urea 13-C is a radiolabelled urea molecule used in the diagnosis of stomach ulcers by the bacterium Helicobacter Pylori. H. Pylori contains the enzyme Urease which will break down Urea to Ammonia and radioactive C02 where the CO2 can be detected in the breath. C-13 Urea breath test
8. Urea is considered extremely safe and there are no reports, to our knowledge, of Osmotic Demyelination with the us of Urea for Hyponatremia.
9. Urea has been used for SIADH since at least 1980 where G Decaux et al. showed it’s effectiveness and published the data in the American Journal of Medicine.
10. Over 90% of oral Urea is absorbed in the upper GI tract. Urea has a half life of only about 2 hours, and an oral dose of Urea is completely excreted by the kidneys by 12 hours. Blood Purif 2020;49:212–218
Pseudohyponatremia, as the name implies, is not what we consider true hyponatremia. In fact, it is a laboratory error (pseudo-greek derivation meaning false; feigned). When serum sodium is measured with the standard indirect ion-selective electrode (ISE) method it is measured in an aqueous solution, diluted, and there is always an assumption that plasma is precisely 93% water. When the samples are analyzed and something in the sample is "displacing" the plasma water, then the actual amount of sodium detected will be lower. What can displace the plasma water? Lipids, as in a very high triglyceride levels for starters. These elevated triglyceride levels, typically >1500 mg/dl, are often seen in conjunction with pancreatitis. Elevated proteins may also lead to Pseudohyponatremia; typically seen with diseases like Multiple Myeloma with total proteins in excess of 10 g/dL. Lastly, in severe biliary obstruction we may see very high levels of cholesterol and lipoproteins (lipoprotein x) usually with cholesterol levels over 1000 mg/dL.
This error can be avoided if a whole blood sample is drawn and analyzed with direct ion-selective electrode like the arterial blood gas method. Because this is not true hyponatremia, the treatment is directed at the underlying process and not on the low sodium.