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What does the latest article in the Journal of the American Medical Association say about Urea for the treatment of SIADH?

The article “Use of Urea for the Syndrome of Inappropriate Secretion of Antidiuretic Hormone and Systematic Review” was published in JAMA open in October 2023.  This was a large review of 23 separate studies involving 537 patients with SIADH, one of the most common causes of Hyponatremia. 

Some of the key points discussed included: 

  1. Hyponatremia, low sodium, is associated with increased mortality (death), gait disturbances (trouble walking/balance), and neuro-cognitive impairments (concentration, brain fog). 
  2. SIADH is one of the most common reasons for low sodium.
  3. Urea therapy is recommended by joint guidelines in Europe by both Endocrinology and Critical Care societies as well as the European Renal Association
  4. The Average starting Sodium was 125 meq/L.
  5. The Average dose of Urea was 15-30 grams per day.

So what did the researchers discover?  

Most importantly, on average patients improved their sodium levels with Urea therapy by 9.6 points. Urea worked quickly with an average increase in blood sodium levels of 4.9 points in 24 hours. The majority of the studies reviewed were short in duration and follow up, however a small percentage followed patients longer, out as far as 1 year, 2 years and in one case report over 5 years. Urea was very well tolerated with only minimal side effects which were distaste, nausea or acid reflux. Urea therapy rarely led to over correction and zero cases of osmotic demyelination syndrome (ODS) were reported. ODS is a rare but serious condition that can manifest several days after Hyponatremia treatment and may include coma, seizures, or paralysis. ODS can occur with other Hyponatremia treatment options such as vaptans or hypertonic saline especially with overly rapid correction. Urea is thought to have a protective effect from this condition and is therefore felt to be one of the best and safest options available. 2

In closing the authors of this systematic review concluded: Urea is safe, effective and a inexpensive treatment option for patients with low sodium due to SIADH.

To see the full report and learn more click on the references below. 

1.  doi:10.1001/jamanetworkopen.2023.40313