Fractional Urate Excretion in Nonedematous Hyponatremia
| Status: | Withdrawn |
|---|---|
| Conditions: | Metabolic |
| Therapuetic Areas: | Pharmacology / Toxicology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 2/8/2019 |
| Start Date: | November 2011 |
| End Date: | December 2014 |
Study of Nonedematous Hyponatremia and the Utility of Fractional Urate Excretion in Hyponatremia and Suspected Renal Salt Wasting Without Hyponatremia-
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.
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.
The investigators have demonstrated that a normal FEurate in a nonedematous hyponatremic
patient is highly consistent with the diagnosis of reset osmostat (RO). Since as much as 36%
of patients with SIADH have RO, the investigators will evaluate these patients by either
noting dilute urines in spontaneously excreted urines or after a modified water-loading test.
The investigators have found that a normal FEurate in a nonedematous hyponatremic patient is
highly consistent with RO.
The investigators intend to treat euvolemic patients with hyponatremia with tolvaptan, the V2
ADH receptor blocker, to determine the effectiveness of this form of therapy in a group of
patients in whom correction of hyponatremia has been difficult to achieve by usual methods.
Nonedematous hyponatremic patients with serum sodium < 135 mmol/l will be recruited from
Winthrop-University Hospital and from our outpatient practice.
It is anticipated that the present studies will provide valuable information on the relative
prevalence of SIADH and C/RSW in patients with nonedematous hyponatremia. One possible
drawback to these studies is our inability to determine total and extracellular water volumes
in patient who are admitted to the neuro/neurosurgical ICU where the acute illnesses require
parenteral therapy that will create a nonsteady state situation where total and extracellular
water volumes cannot be accurately determined. This is an important possible omission because
volume studies in this population of studies have indicated more that two thirds of patients
having decreased volumes that were consistent with C/RSW, yet the medical literature states
that C/RSW is rare. Studies in hyponatremics elsewhere in the hospital should shed important
light on the methods to differentiate SIADH from C/RSW, data which can assist us in
differentiating both syndromes in the neuro/neurosurgical ICU, where the investigators intend
to perform FEurates.
It is anticipated that volume studies in patients with Alzheimer's disease with normal serum
sodium and increased FEurate will demonstrated decreased volumes and confirm our earlier
observations that many of these patients are renal salt wasters. It would be interesting to
test whether volume repletion with saline will improve them mentally and physically.
patient is highly consistent with the diagnosis of reset osmostat (RO). Since as much as 36%
of patients with SIADH have RO, the investigators will evaluate these patients by either
noting dilute urines in spontaneously excreted urines or after a modified water-loading test.
The investigators have found that a normal FEurate in a nonedematous hyponatremic patient is
highly consistent with RO.
The investigators intend to treat euvolemic patients with hyponatremia with tolvaptan, the V2
ADH receptor blocker, to determine the effectiveness of this form of therapy in a group of
patients in whom correction of hyponatremia has been difficult to achieve by usual methods.
Nonedematous hyponatremic patients with serum sodium < 135 mmol/l will be recruited from
Winthrop-University Hospital and from our outpatient practice.
It is anticipated that the present studies will provide valuable information on the relative
prevalence of SIADH and C/RSW in patients with nonedematous hyponatremia. One possible
drawback to these studies is our inability to determine total and extracellular water volumes
in patient who are admitted to the neuro/neurosurgical ICU where the acute illnesses require
parenteral therapy that will create a nonsteady state situation where total and extracellular
water volumes cannot be accurately determined. This is an important possible omission because
volume studies in this population of studies have indicated more that two thirds of patients
having decreased volumes that were consistent with C/RSW, yet the medical literature states
that C/RSW is rare. Studies in hyponatremics elsewhere in the hospital should shed important
light on the methods to differentiate SIADH from C/RSW, data which can assist us in
differentiating both syndromes in the neuro/neurosurgical ICU, where the investigators intend
to perform FEurates.
It is anticipated that volume studies in patients with Alzheimer's disease with normal serum
sodium and increased FEurate will demonstrated decreased volumes and confirm our earlier
observations that many of these patients are renal salt wasters. It would be interesting to
test whether volume repletion with saline will improve them mentally and physically.
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
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