Urea for the Treatment of Hyponatremia

Background and objectives: Current therapies for hyponatremia have variable effectiveness and tolerability, and in certain instances, they are very expensive. We examined the effectiveness, safety, and tolerability of urea for the treatment of inpatient hyponatremia.

Design, setting, participants, & measurements: We identified all patients hospitalized at the University of Pittsburgh Medical Center between July 2016 and August 2017 with hyponatremia (plasma sodium <135 mEq/L) who received urea, including a subgroup of patients who received urea as the sole drug therapy for hyponatremia (urea-only treated). We matched urea only-treated patients to a group of patients with hyponatremia who did not receive urea (urea untreated) and compared changes in plasma sodium at 24 hours and the end of therapy as well as the proportion of patients who achieved plasma sodium ≥135 mEq/L. We abstracted data on adverse events and reported side effects of urea.

Results: Fifty-eight patients received urea (7.5-90 g/d) over a median of 4.5 (interquartile range, 3-8) days and showed an increase in plasma sodium from 124 mEq/L (interquartile range, 122-126) to 131 mEq/L (interquartile range, 127-134; P<0.001). Among 12 urea only-treated patients, plasma sodium increased from 125 mEq/L (interquartile range, 122-127) to 131 mEq/L (interquartile range, 129-136; P=0.001) by the end of urea therapy. There was a larger increase in plasma sodium at 24 hours in urea only-treated patients compared with urea-untreated patients (2.5 mEq/L; interquartile range, 0-4.5 versus -0.5 mEq/L; interquartile range, -2.5 to 1.5; P=0.04), with no difference in change in plasma sodium by the end of therapy (6 mEq/L; interquartile range, 3.5-10 versus 5.5 mEq/L; interquartile range, 3-7.5; P=0.51). A greater proportion of urea only-treated patients achieved normonatremia, but this difference was not statistically significant (33% versus 8%; P=0.08). No patients experienced overly rapid correction of plasma sodium, and no serious adverse events were reported.

Conclusions: Urea seems effective and safe for the treatment of inpatient hyponatremia, and it is well tolerated.