Cerebral Salt-Wasting Syndrome 

First described by Peters et al in 1950, cerebral salt-wasting syndrome (CSWS) is defined by the development of extracellular volume depletion due to a renal sodium transport abnormality in patients with intracranial disease and normal adrenal and thyroid function.^[1] As such, it may be more appropriately termed renal salt wasting [RSW].

Differentiation of this disorder from the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), a common cause of hyponatremia, can be difficult because both can present with hyponatremia and concentrated urine with natriuresis. However, the distinction is important because treatment options differ. Cerebral salt-wasting syndrome is considered a definite clinical entity and may be more common than perceived. It should also be considered in patients without cerebral disease.^[2]

Possible mechanisms for cerebral salt-wasting syndrome are shown in the image below.

Cerebral salt-wasting syndrome, or renal salt wasting, may be more common than SIADH and may even occur in the absence of cerebral disease.^[3] The exact mechanism underlying this disorder remains unclear. In the setting of cerebral injury, one hypothesis is an exaggerated renal pressure–natriuresis response caused by increased activity of the sympathetic nervous system and dopamine release is responsible for urinary sodium loss. Another hypothesis involves release of natriuretic factors, possibly including brain natriuretic peptide (C-type natriuretic peptide) or urodilatin by the injured brain. Kojima et al have described an animal model of cerebral salt-wasting syndrome that may allow better clarification of cerebral salt-wasting syndrome pathophysiology.^[4]

Regardless of the specific cause, the initiating defect in renal sodium transport leads to extracellular volume (ECV) depletion, and a cascade of compensatory changes occur. Abnormalities in the proximal tubule result in excessive sodium losses, which lead to decreased effective circulating volume. This activates baroreceptors which increase antidiuretic hormone (ADH) secretion. This results in water conservation and a return to an equilibrated state. In contrast, SIADH primarily occurs due to a euvolemic inappropriate rise in ADH secretion.

The relationship among serum urate, fractional excretion of urate, and hyponatremia in cerebral salt-wasting syndrome is unclear. Fractional excretion of urate may remain elevated even after correction of hyponatremia in patients with cerebral salt-wasting syndrome. This is distinct from SIADH, in which the fractional excretion of urate returns to the reference range once the hyponatremia is corrected.^[2] The physiologic basis for this in cerebral salt-wasting syndrome may be related to the receptor-mediated processing of both sodium and urate in the proximal tubule, which may be defective in this syndrome. The physiologic basis for hypouricemia in SIADH remains unclear.

The abnormalities in proximal tubular transport may be secondary to a plasma natriuretic factor that reduces proximal and, possibly, distal sodium transport in cerebral salt-wasting syndrome. It may also inhibit the tubular transport of urate, phosphate, and urea in addition to sodium.^[5]

Frequency

United States

Exact incidence data for this disorder are not available. Approximately 60% of children with brain injuries or tumors develop hyponatremia during their hospital course. Some experts suggest that CSWS/RSW is responsible for hyponatremia at least as often as SIADH, particularly in neurosurgical patients. Other studies indicate that this syndrome explains the development of hyponatremia in no more than 6% of patients with acute brain injuries.^[6]

Mortality/Morbidity

Cerebral salt-wasting syndrome, or renal salt wasting, usually appears in the first week after brain injury and spontaneously resolves in 2-4 weeks. The exact incidence of renal salt wasting syndrome without cerebral disease is unknown. Death and complication rates for this syndrome are not available. Failure to distinguish cerebral salt-wasting syndrome from SIADH as the cause of hyponatremia could lead to improper therapy (ie, fluid restriction), thereby exacerbating intravascular volume depletion and potentially jeopardizing cerebral perfusion.

Age

Cerebral salt-wasting syndrome can occur at any age. Published reports include patients aged 6 months to 65 years.