Verbalis JG, et al.. Diagnosis, evaluation, and treatment of hyponatremia: Expert panel recommendations. Am J Med 2013; 126 (10 Suppl 1):S1−S42. doi: 10.1016/j.amjmed.2013.07.006
Rondon-Berrios H. Urea for chronic hyponatremia. Blood Purif 2020; 49:212−218. doi: 10.1159/000503773
Sterns RH, et al.. Urea for hyponatremia? Kidney Int 2015; 87:268−270. doi: 10.1038/ki.2014.320
Crawford H, McIntosh JF. The use of urea as a diuretic in heart failure. Arch Intern Med (Chic) 1925; 36:530−541. doi:10.1001/archinte.1925.00120160088004
Decaux G, et al.. Hyponatremia in the syndrome of inappropriate secretion of antidiuretic hormone. Rapid correction with urea, sodium chloride, and water restriction therapy. JAMA 1982; 247:471−474. doi: 10.1001/jama.1982.03320290017021
Spasovski G, et al.. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Intensive Care Med 2014; 40:320−331. doi: 10.1007/s00134-014-3210-2
Rondon-Berrios H, et al.. Urea for the treatment of hyponatremia. Clin J Am Soc Nephrol 2018; 13:1627−1632. doi: 10.2215/CJN.04020318
Decaux G, et al.. Treatment of euvolemic hyponatremia in the intensive care unit by urea. Crit Care 2010; 14:R184. doi: 10.1186/cc9292
Nervo A, et al.. Urea in cancer patients with chronic SIAD-induced hyponatremia: Old drug, new evidence. Clin Endocrinol (Oxf) 2019; 90:842−848. doi: 10.1111/cen.13966
Soupart A, et al.. Efficacy and tolerance of urea compared with vaptans for long-term treatment of patients with SIADH. Clin J Am Soc Nephrol 2012; 7:742−747. doi: 10.2215/CJN.06990711
Lockett J, et al.. Urea treatment in fluid restriction refractory hyponatremia. Clin Endocrinol (Oxf) 2019; 90:630−636. doi: 10.1111/cen.13930
Soupart A, et al.. Azotemia (48 h) decreases the risk of brain damage in rats after correction of chronic hyponatremia. Brain Res 2000; 852:167−172. doi: 10.1016/s0006-8993(99)02259-3
Pierrakos C, et al.. Urea for treatment of acute SIADH in patients with subarachnoid hemorrhage: A single-center experience. Ann Intensive Care 2012; 2:13. doi: 10.1186/2110-5820-2-13
Gankam Kengne F, et al.. Urea minimizes brain complications following rapid correction of hyponatremia compared with vasopressin antagonist or hypertonic saline. Kidney Int 2015; 87:323−331. doi: 10.1038/ki.2014.273
Rondon-Berrios H. Urea for chronic hyponatremia. ClinicalTrials.gov: NCT04588207. https://clinicaltrials.gov/ct2/show/NCT04588207?cond=urea+hyponatremia&draw=2&rank=1
The conventional first-line therapy for any patient presenting with hypotonic hyponatremia due to SIAD (syndrome of inappropriate antidiuresis) is that of fluid restriction. However, we recognize that fluid restriction alone does not always work. The Expert Panel Recommendations on Diagnosis, Evaluation, and Treatment of Hyponatremia, published in 2013, identified certain criteria that are predictive of which patients are less likely to respond to fluid restriction alone (
It has been suggested that those patients