Approach Considerations
Failure to distinguish cerebral salt-wasting syndrome (renal salt wasting) from SIADH as the cause of hyponatremia may lead to improper therapy (ie, fluid restriction), thereby exacerbating intravascular volume depletion and potentially jeopardizing cerebral perfusion.
The following lab studies may be indicated in patients with cerebral salt-wasting syndrome:
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Serum sodium concentration - Patients with untreated cerebral salt-wasting syndrome are often hyponatremic
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Serum osmolality - If measured serum osmolality exceeds twice the serum sodium concentration and azotemia is not present, suspect hyperglycemia or mannitol as the cause of hyponatremia
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Urinary output - Urine flow rate is often high in cerebral salt-wasting syndrome; urine flow rate is low in SIADH
Urinary sodium concentrations
Urinary sodium concentrations are typically elevated in SIADH and in cerebral salt-wasting syndrome (>40 mEq/L). However, urinary sodium excretion (urinary sodium concentration [mEq/L] x urinary volume [L/24 h]) is substantially higher than sodium intake in cerebral salt-wasting syndrome but generally equals sodium intake in SIADH. Therefore, net sodium balance (intake minus output) is negative in cerebral salt-wasting syndrome.
Urinary sodium excretion and urinary volume
A retrospective study by Arieff et al indicated that in patients with cerebral lesions who exhibit hyponatremia, urinary sodium excretion and urinary volume can be used to differentiate cerebral salt-wasting syndrome from SIADH. In patients with cerebral salt-wasting syndrome, these values were 394 ± 369 mmol/24 h and 2603 ± 996 mL/24 h, respectively. In comparison, the values were significantly lower—51 ± 25 mmol/24 h and 745 ± 298 mL/24 h, respectively—in patients with SIADH. [17]
Cerebral salt-wasting syndrome and central diabetes insipidus
A retrospective study by Wu et al found that distinctive features of combined central diabetes insipidus and cerebral salt-wasting syndrome following traumatic brain injury include massive polyuria (the most typical presentation) that responds to vasopressin plus cortisone acetate but not to vasopressin alone, low central venous pressure, a high level of brain natriuretic peptide precursor in the absence of cardiac dysfunction, high 24-hour urine sodium excretion and hypovolemia, and a much greater osmolarity for urine than for serum. [18]
Fractional Excretion of Uric Acid and Phosphate
Uric acid
Fractional excretion of uric acid (FEUA) is defined as the percentage of urate filtered by glomeruli that is excreted in urine. It is calculated by dividing the product of (urinary uric acid [mg/mL] x serum creatinine [mg/mL]) by the product of (serum uric acid [mg/mL] x urinary creatinine [mg/mL]) and multiplying the result by 100%. Normal values are less than 10%.
Patients with either cerebral salt-wasting syndrome or SIADH can have hypouricemia and elevated FEUA. However, after correction of hyponatremia, hypouricemia and elevated FEUA may normalize in SIADH but persist in cerebral salt-wasting syndrome (renal salt wasting). [5, 6]
A report by Bardanzellu et al indicated that, while the continued elevation of FEUA following correction of hyponatremia has been used diagnostically for cerebral salt-wasting syndrome in adults, it would also be valid to employ in the diagnosis of children over age 1 year. [19]
Phosphate
Fractional excretion of phosphate (FEP) should be determined when evaluating patients with hyponatremia and hypouricemia. Elevated FEP suggests cerebral salt-wasting syndrome as opposed to SIADH. [6]
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Possible mechanisms for cerebral salt-wasting syndrome. The injured brain may release natriuretic proteins that act directly on the kidney. In addition, cerebral injury may increase sympathetic nervous system activity, elevating renal perfusion pressure and releasing dopamine.
