Clinical question: Is urea a safe and effective treatment option for syndrome of inappropriate antidiuretic hormone secretion (SIADH)-associated hyponatremia?
Background: The management of hyponatremia, particularly that which is due to SIADH, can be challenging. Fluid restriction adherence can often be difficult, and salt administration can often lead to adverse effects such as fluid retention and elevated blood pressure. Urea is emerging as a potential second-line treatment, though comprehensive data and randomized clinical trials are lacking.
Study design: Systematic review and meta-analysis
Setting: Articles obtained across four databases, the majority of which were retrospective studies.
Synopsis: There were 16 studies included in this review that reported at least one outcome related to serum sodium concentration, symptom resolution, or adverse effects related to urea administration among patients with SIADH-associated hyponatremia. The studies varied in size, ranging from three to 50 patients. Some studies included hospitalized patients followed for a short term, while others followed patients up to a year. Pooled data showed that urea significantly increased sodium and urea levels, though with high heterogeneity in the absolute change. In studies with comparator treatments, urea was comparable to fluid restriction and vasopressin receptor antagonists. Compared to an untreated control group, urea was associated with a significant increase in serum sodium level. Urea was well tolerated, with poor palatability being the most common adverse effect. A rare incidence of hypernatremia was reported in three studies. The study has limitations, the most notable being publication bias and the inclusion of primarily observational or retrospective studies. However, randomized controlled trials are limited. Therefore, this study is a helpful review that supports the use of urea as a safe and effective therapy for SIADH-related hyponatremia.
Bottom line: Urea is a safe, effective, and well-tolerated treatment for SIADH-associated hyponatremia.
Citation: Chander S, et al. Urea to treat hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion: a systematic review and meta-analysis. Am J Kidney Dis. 2024;85(3):303-319. doi:10.1053/j.ajkd.2024.07.011.
Dr. Aldrich
Dr. Aldrich is a hospitalist and assistant professor of internal medicine at the University of North Carolina in Chapel Hill, N.C.