Use of Urea for the Syndrome of Inappropriate Secretion of Antidiuretic Hormone

Abstract

ImportanceHyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) are associated with significant mortality and morbidity. The effectiveness and safety of oral urea for SIADH are still debated.ObjectiveTo evaluate the efficacy and safety of urea for the treatment of SIADH.Evidence ReviewA systematic search of Medline and Embase was conducted for controlled and uncontrolled studies of urea for SIADH in adult patients. The primary outcome was serum sodium concentration after treatment. Secondary outcomes included the proportion of patients with osmotic demyelination syndrome (ODS), intracranial pressure, and resource use such as length of stay.FindingsTwenty-three studies involving 537 patients with SIADH were included, of which 462 were treated with urea. The pooled mean baseline serum sodium was 125.0 mmol/L (95% CI, 122.6-127.5 mmol/L). The median treatment duration with oral urea was 5 days. Urea increased serum sodium concentration by a mean of 9.6 mmol/L (95% CI, 7.5-11.7 mmol/L). The mean increase in serum sodium after 24 hours was 4.9 mmol/L (95% CI, 0.5-9.3 mmol/L). Adverse events were few, mainly consisting of distaste or dysgeusia, and no case of ODS was reported. Resource use was too infrequently reported to be synthesized.Conclusions and RelevanceIn this systematic review of the use of urea in SIADH and despite the lack of randomized clinical trials, lower-quality evidence was identified that suggests that urea may be an effective, safe, and inexpensive treatment modality that warrants further exploration.

Hyponatremia After Colonoscopy Bowel Preparation: Challenges in Managing Syndrome of Inappropriate Antidiuretic Hormone Without Established Guidelines

“…Since starting the patient on salt tablets four times a day did not produce satisfactory results, we started additionally started her on urea, an osmotic diuretic, to increase free water excretion. Current data on the use of urea for SIADH is limited, and a recent systematic review found no definite evidence for the use of urea as a treatment for SIADH [10]. However, our patient showed significant improvement with urea, providing anecdotal support for the consideration of oral urea in refractory SIADH.…”

Urea transporter UT‐A1 as a novel drug target for hyponatremia

“…58 Desmopressin (dDAVP), an AVP analog, is stabler and has higher V2R selectivity than AVP. Exogenous dDAVP increases intracellular cAMP that promotes insertion of AQP2 and UT-A1 in the luminal membrane of principal cells by activating their phosphorylation, 59,60 which allows urea to diffuse into the inner medullary interstitium. 61,62 The decreased urea excretion and increased water reabsorption lead to hyponatremia.…”

“…65 Also, oral urea is an effective treatment for SIADH but it could increase the burden on the liver and kidneys of patients, and is not suitable to use in patients with hepatic or renal failure. 60,65 Furthermore, loop diuretics promote urinary sodium in the absence of excessive blood volume, which may lead to further exacerbation of hyponatremia. More importantly, loop diuretics may cause acute kidney injury and electrolyte disorders such as hypokalemia.…”