Cerebral Hyponatremia | Fractional Urate Excretion in Nonedematous Hyponatremia

Cerebral Hyponatremia research study

What is the primary objective of this study?

Hyponatremia, defined as a serum sodium < 135 mmol/l, in patients without edema has undergone significant changes where it is now evident that even mild hyponatremia should be treated because of its association with symptoms, especially a fourfold increase in falls over the age of 65 years. There is an unresolved controversy over the relative prevalence of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and cerebral/renal salt wasting (C/RSW). Resolution of this diagnostic dilemma becomes urgent because of divergent therapeutic goals, to water-restrict in SIADH or to give salt and water supplementation in C/RSW. The dilemma is compounded by recent reports of C/RSW occurring in patients without cerebral disease, thus adding further confusion in defining the relative prevalence of both syndromes. Because of overlapping laboratory and clinical findings in both syndromes, only differences in the state of extracellular volume differentiates one syndrome from the other, being high normal to increased in SIADH and decreased in C/RSW. The investigators have used fractional excretion (FE) of urate to categorize patients with hyponatremia. The increased FEurate that is observed in hyponatremic patients with SIADH and C/RSW can be used to differentiate both syndromes by correcting the hyponatremia and determining whether FEurate normalizes as in SIADH or remains increased in C/RSW. The present studies have been designed to determine total body water by deuterium and extracellular water by sodium bromide in patients with nonedematous hyponatremia with normal and increased FEurate to differentiate more conclusively whether the patient has normal or decreased water volumes. The investigators will also correct serum sodium rapidly with judicious administration of hypertonic saline over approximately three days and determine whether FEurate normalizes as in SIADH or remains increased as in C/RSW. In another group of patients, The investigators have data to suggest that those with normal sodium and increased FEurate is consistent with C/RSW. The investigators intend to do the same water volume studies to determine whether an increased FEurate with normonatremia would have decreased total and extracellular water that these patients have C/RSW without the need to correct a prior hyponatremia.

Who is eligible to participate?

Inclusion Criteria: - Nonedematous hyponatremia with normal renal, adrenal and thyroid function. -Non-hyponatremia with increased fractional excretion of urate. Exclusion Criteria: - Subjects < 18 years of age - Pregnancy - Serum creatinine > 1.4 mg/dl

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

Cerebral Hyponatremia


Cerebral Salt-wasting Syndrome

Reset Hypothalamic Osmostat

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Drug:Tolvaptan in euvolemic hyponatremiaThis arm will test the effectiveness of tolvaptan in treating the hyponatremia of patients with euvolemic hyponatremia.

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

Tolvaptan in euvolemic hyponatremiaThis arm will test the effectiveness of tolvaptan in treating the hyponatremia of patients with euvolemic hyponatremia.

Study Status


Start Date: November 2011

Completed Date: December 2014

Phase: N/A

Type: Interventional


Primary Outcome: Etiologic categorization of nonedematous hyponatremia

Secondary Outcome:

Study sponsors, principal investigator, and references

Principal Investigator: John K Maesaka, MD

Lead Sponsor: Winthrop University Hospital


More information:

Discuss Hyponatraemia