Urea Use for SIADH: A Case Report and Review of the Literature

Abstract Introduction: Hyponatremia is the most frequent electrolyte abnormality among hospitalized patients associated with increased morbidity and mortality. There is a demanding need for affordable and well-tolerated therapies, and urea is a compelling alternative for the syndrome of inappropriate diuretic hormone (SIADH). Urea increases renal water excretion due to osmotic diuresis and reduce urinary sodium leading to an increase in serum sodium. This case illustrates the effect and safe use of urea in a hospitalized patient with SIADH. Clinical Case: An 80-year-old male with history of recurrent anterior chest wall chondrosarcoma despite 3 chest wall resections presented to the hospital for a 4th anterior chest wall resection with reconstruction. Physical examination was notable for euvolemia with no neurologic deficits. Pre-operative labs were significant for a plasma sodium (PNa) 118 mmol/L, potassium 4 mmol/L, BUN 9 mg/dL, Cr 0.72 mg/dL, TSH 2.9 mIU/L, cortisol 21.3 mcg/dL, serum osmolality 267 mOsm/kg, urine osmolality 423 mOsm/kg, and urine sodium 115 mmol/L. Underlying SIADH was initially treated with water restriction of 800 mL/24 h. Previously, he was given a trial of salt tabs, which he did not tolerate due to nausea and emesis. Due to profound hyponatremia, he was started on 2% hypertonic saline. Once PNa levels reached 130 mmol/L, 2% saline was discontinued. Repeated PNa showed a decrease to 128mmol/L. Tolvaptan was not initiated due to lack of insurance coverage and hepatotoxicity, and demeclocycline was not considered due to his known allergy. He was ultimately started on urea powder at 15 g/day and tittered to 30 g/day. In one week PNa improved to 135 mmol/L and remained stable until discharge. Clinical Lessons: The cornerstone of therapy for SIADH relies on reducing free water intake but this is not always feasible or sufficient. Winzer et al. [1] showed that fluid restriction is effective in only 59% of the patient with SIADH. As a result, pharmacology therapy is often needed. European guidelines, as compared to American guidelines, recommend the use of urea instead of vaptans therapy as second-line treatment. The above is based on different studies [2] that have shown that urea has similar efficacy, is more cost-effective, and safer since it does not cause liver toxicity like vaptans. Given this response, it appears that urea should be considered as a second-line therapy to fluid restriction given its tolerability and cost-effectiveness when compared to its alternatives. References: 1. Winzeler B, Lengsfeld S, Nigro N, Suter-Widmer I, et al. Predictors of nonresponse to fluid restriction in hyponatremia due to the syndrome of inappropriate antidiuresis. J Intern Med 280: 609–617, 20162. Soupart A, Coffernils M, Couturier B, Gankam-Kengne F, et al. Efficacy and tolerance of urea compared with vaptans for long-term treatment of patients with SIADH. Clin J Am Soc Nephrol 7: 742–747