**2. Definition of RSW**

In our view, RSW is most accurately defined as, "extracellular volume (ECV) depletion due to a renal sodium transport abnormality with or without high urinary sodium concentration (UNa), presence of hyponatremia or cerebral disease and normal renal, adrenal and thyroid function". (Maesaka et al, 2009) We will provide data to support our contention that UNa can be low in RSW, and how RSW can occur in normonatremic patients and in patients

Complexity of Differentiating Cerebral-Renal Salt Wasting

water excretion and increase serum sodium, figure 1.

from SIADH, Emerging Importance of Determining Fractional Urate Excretion 43

on ADH production, so a volume depleted patient continues to increase ADH production, increase free water reabsorption and decrease serum sodium and osmolality. (Robertson & Ganguly, 1986) Administration of saline in our patient with RSW eliminated the volume stimulus for ADH production to allow the coexisting hypoosmolality of plasma to inhibit ADH production to indeterminate levels, thus decreasing urine osmolality, increase free

Fig. 1. Urine osmolality and serum sodium concentration during saline infusion at 125 ml/hr. over 48 hour period. Note dilution of urine 13 hours after initiation of saline, at which time a previously increased plasma ADH was not detectable, appropriate AD

SIADH and RSW. (Maesaka et al, 2009, 1999; Oh & Carroll, 1999; Singh et al, 2002).

argues against any role of ANP in salt wasting. (Maesaka et al, 2007, Vogel, 1963)

This appropriate increase in plasma ADH in a patient with unequivocal RSW illustrates this important physiologic difference between RSW and SIADH. (Maesaka et al, 2007, 2009) As noted earlier, the task of clinically determining whether the increase in plasma ADH levels are appropriate or inappropriate rests solely on differences in ECV, since both present with hyponatremia, high urine osmolality and UNa. Our reliance on the assessment of ECV becomes critical in differentiating SIADH from RSW. Our inability to assess this critical parameter remains central to the unresolved controversy regarding the prevalence of

Atrial or brain natriuretic peptide (A/BNP) has been frequently mentioned as a possible cause of the salt wasting in RSW. (Ellison & Berl, 2007; Palmer, 2003*)* A/BNP has been reported to be increased in patients with subarachnoid hemorrhage (SAH), a condition that has been shown to have a high prevalence for RSW, but it has also been reported to be increased in a non salt wasting syndrome such as SIADH and salt-retaining conditions such as congestive heart failure. (Burnett et al, 1986; Fichman et al, 1974; Wijdicks et al, 1991) The low normal ANP level in RSW is consistent with the volume-depleted state and strongly

secretion. See text. (reproduced with permission from publisher)

**2.2 Natriuretic factor(s) in RSW** 

without cerebral disease. Although an increased FEurate has been demonstrated in a number of patients with RSW, we will withhold including FEurate to our definition of RSW until there are more confirmatory data.
