A New Algorithm to Differentiate Salt-wasting Syndrome from SIADH

In cerebral salt-wasting (CSW), natriuretic factor is produced in response to a central insult.  Natriuretic factor decreases sodium transport in proximal renal tubule which leads to urinary loss of sodium (and water) and depletion of extracellular volume.  Hypovolemia then triggers secretion of ADH, renin and aldosterone, which provides a negative feedback to decrease secretion of natriuretic factor.

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Differentiating CSW from syndrome of inappropriate antidiuretic hormone (SIADH) is problematic, laboratory work-up (urine and plasma sodium levels and urine and plasma osmolarity) is similar in both conditions.  CSW patients are usually volume depleted while SIADH patients are euvolemic.  The traditional approach of examining patient clinically to to determine volume status is inaccurate.

An interesting paper published in 2014 suggested a new algorithm to differentiate SIADH from CSW based on the effect of sodium correction on the fractional excretion of urate (FEUa).  FEurate is calculate using the folllowing formula:

c

 

Expanded:

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Another formula:

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Normal FEUa = 4-11%, SIADH & CSW FEUa = >11%.  FEUa determines the percent excertion of the filtered load of urate at the glomerulus.

In SIADH, FEUa normalizes after correction of hyponatremia (see graph below):

a

whereas in CSW, FEUa remains elevated >11% after correction of hyponatremia.  The reason is probably because natriuretic factor also decreases urate transport in the proximal tubule.

b.JPG

 

Based on this finding, the paper suggests a new algorithm for determining the etiology of hyponatremia that omits reliance of UNa (and also plasma renin, aldosterone, atrial or brain antriuretic peptide, BUN/creatinine ratio).

d.JPG

Based on this algorithm, a patient with hyponatremia should undergo correction of sodium by any means (water restriction or isotonic / hypertonic saline). Observing whether FEUa normalizes or remains increased would differentiate SIADH from CSW syndrome.

 

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Reference:

Maesaka, J., Imbriano, L., Mattana, J., Gallagher, D., Bade, N. and Sharif, S. (2014). Differentiating SIADH from Cerebral/Renal Salt Wasting: Failure of the Volume Approach and Need for a New Approach to Hyponatremia. Journal of Clinical Medicine, 3(4), pp.1373-1385.

 

 

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