Normal fractional urate excretion identifies hyponatremic patients with reset osmostat

Reset osmostat (RO) occurs in 36% of patients with syndrome of inappropriate antidiuretic hormone secretion (SIADH) and is not often considered when evaluating hyponatremic patients. Patients with RO are not usually treated, but recent awareness that symptoms are associated with mild hyponatremia creates a therapeutic dilemma. We encountered patients with hyponatremia, hypouricemia and high urine sodium concentration (UNa), who had normal fractional excretion (FE) of urate and excreted dilute urines that were consistent with RO. We decided to test whether a normal FEurate in nonedematous hyponatremia irrespective of UNa or serum urate would identify patients with RO.

We determined FEurate in nonedematous hyponatremic patients. A diagnosis of RO was made if urine osmolality (Uosm) was <200 mOsm/kg in a random urine. We performed a modified water-loading test in patients with a normal FEurate whose random Uosm was >200 mOsm/kg.

All nonedematous hyponatremic patients with FEurate of 4%-11% had RO, as determined by Uosm <200 mOsm/kg on a random urine collection in 8 patients, or after a modified water-loading test in 6 patients. Plasma antidiuretic hormone (ADH) in 4 patients was undetectable at <1 pg/mL during water-loading. Nine patients had baseline concentrated urine, 12 had UNa >20 mmol/L, 9 were hypouricemic, yet all had a normal FEurate. Comorbidities were similar to those reported in RO.

RO, a benign form of SIADH, occurs commonly. A normal FEurate in a nonedematous hyponatremic patient is highly suggestive of RO. Determining FEurate is superior to serum urate. The therapeutic dilemma for RO must be resolved.