**9. New approach to hyponatremia and how to differentiate SIADH from RSW**

The evaluation of the patient with hyponatremia traditionally starts with an assessment of ECV, whether or not they are euvolemic, hypovolemic or hypervolemic. While this approach is fundamentally correct, we are again unable to assess accurately whether the patient is euvolemic or hypovolemic, realizing that hypervolemic patients can be identified by the presence of edema. We attempted to use UNa to support the volume approach by dividing the hypovolemic group into two categories, those with hypovolemia and normal kidney function, UNa < 20 mmol/L and those with rSW, UNa > 20 mmol/L. Those with euvolemia or mainly SIADH, UNa is usually > 20 mmol/L and hypervolemia, UNa < 20 mmol/L. The major differential is a UNa of > 20 mmol/L, which reverts back to differentiating SIADH from RSW. Differentiating the hypovolemic patient with normal renal function from hypervolemic hyponatremics, UNa < 20 mmol/L, is simplified by the presence or absence of edema. (Maesaka, 1996) The interpretation of UNa is also complicated by many factors, such as diuretics, the acutely vomiting patient with bicarbonaturia, acute and chronic kidney diseases and low UNa in the patient with SIADH and RSW on a low sodium diet. Limitations of UNa in the evaluation of patients with hyponatremia have been noted by others. (Chung et al, 1987)

Determinations of plasma renin and aldosterone can under proper circumstances contribute to differentiating SIADH from RSW. However, many factors can affect one or both values, such as the use of diuretics, ACE inhibitors, ARB, NSAIDS, heparin or saline.(Mulatero et al,

production and excretion via gut and urine. Moreover, the arbitrary definition of hypouricemia ranging from 1.5-4 mg/dL reflect the uncertainty of the value of serum urate as compared to well-defined parameters that have been established for FEurate. (Beck, 1979; Maesaka et al, 1990 e; Ramsdell & Kelley, 1973) These studies also introduce the possibility that RO is pathophysiologically different from the more traditional SIADH by virtue of the

The 2 cases of RSW without clinical cerebral disease were the impetus to propose replacing the designation, cerebral salt wasting, to renal salt wasting. (Bitew et al, 2009; Maesaka et al, 2007, 2009) Based on these reports, cerebral salt wasting should be considered an outmoded and inappropriate designation; it should now be called RSW because RSW will be considered in any hyponatremic patient with or without cerebral disease. (Maesaka et al, 2009) Although we feel that RSW might be rare in patients without clinical cerebral disease, these cases of RSW without clinical cerebral disease support our contention that the true prevalence of RSW cannot be viewed as rare until future studies can accurately determine the prevalence of SIADH and RSW in patients with and without clinical evidence of cerebral disease. This would depend on our ability to differentiate SIADH from RSW. The volume studies indicate that RSW is much more common than SIADH in neurosurgical patients. We hope this expanded approach to hyponatremia and RSW will eliminate the inappropriate treatment of RSW by fluid restriction, which has been shown to increase morbidity and mortality when misdiagnosed as SIADH. (, Gutierrez & Lin, 2009; Maesaka et al, 1990, 2007;

**9. New approach to hyponatremia and how to differentiate SIADH from RSW**  The evaluation of the patient with hyponatremia traditionally starts with an assessment of ECV, whether or not they are euvolemic, hypovolemic or hypervolemic. While this approach is fundamentally correct, we are again unable to assess accurately whether the patient is euvolemic or hypovolemic, realizing that hypervolemic patients can be identified by the presence of edema. We attempted to use UNa to support the volume approach by dividing the hypovolemic group into two categories, those with hypovolemia and normal kidney function, UNa < 20 mmol/L and those with rSW, UNa > 20 mmol/L. Those with euvolemia or mainly SIADH, UNa is usually > 20 mmol/L and hypervolemia, UNa < 20 mmol/L. The major differential is a UNa of > 20 mmol/L, which reverts back to differentiating SIADH from RSW. Differentiating the hypovolemic patient with normal renal function from hypervolemic hyponatremics, UNa < 20 mmol/L, is simplified by the presence or absence of edema. (Maesaka, 1996) The interpretation of UNa is also complicated by many factors, such as diuretics, the acutely vomiting patient with bicarbonaturia, acute and chronic kidney diseases and low UNa in the patient with SIADH and RSW on a low sodium diet. Limitations of UNa in the evaluation of patients with

Determinations of plasma renin and aldosterone can under proper circumstances contribute to differentiating SIADH from RSW. However, many factors can affect one or both values, such as the use of diuretics, ACE inhibitors, ARB, NSAIDS, heparin or saline.(Mulatero et al,

normal FEurate and predictability of ADH responses to plasma osmolality.

**8. Change cerebral salt wasting to renal salt wasting** 

hyponatremia have been noted by others. (Chung et al, 1987)

Wijdicks et al, 1985)

2002)Even under ideal circumstances the delay in obtaining these results does not assist us on first encounter with the patient.

It is evident that the evaluation of the volume status or determining UNa has limited utility. This dilemma persists to this day on first encounter with the nonedematous hyponatremic patient. We developed an algorithm, which emphasizes FEurate in the evaluation of hyponatremia, table 1. We propose with supporting data to determine FEurate in any nonedematous patient with hyponatremia. If the FEurate is 5-10%, we should consider psychogenic polydipsia, RO and prerenal causes, such as congestive heart failure, cirrhosis, nephrosis and pre eclampsia, or hypovolemia with normal renal function. Psychogenic polydipsia can be eliminated from the history of increased water intake and very dilute urines. (Ali et al, 2009) Edematous states can be ruled out by the presence of edema. The major obstacle might be the hypovolemic patient with normal renal function and classic prerenal azotemia, but the low mean FEurate of 2.85%, possibly high serum urate and UNa < 20 mmol/l might assist in differentiating this group from RO. (Steele, 1969) In patients who do not fall into the groups mentioned, we would consider RO and search diligently for a dilute urine in a random urine collection. In the absence of a dilute random urine, we do not recommend performing a water-loading test to prove the diagnosis of RO. (Imbriano et al, 2011) We would instead treat them with water restriction and salt supplementation, however unsuccessful they are, and consider using ADH receptor inhibitors, vaptans.

If the FEurate exceeds preferably 12%, there are three possibilities to consider, SIADH, RSW, thiazide diuretics and drugs that induce an SIADH-like picture. Thiazide diuretics and neurotropics can be readily eliminated by a proper history so the major differential would be SIADH and RSW. We propose to correct serum sodium either by water-restriction with salt supplementation or 1.5% hypertonic saline and determine FEurate. (Drakakis et al, 2011) If FEurate corrects to < 10%, we would proceed with treatment for SIADH or if it exceeds 10%, preferably >12%, we would treat the patient for RSW with saline. The question represented as dotted lines in table 1 depends on whether the coexistence of increased FEurate with normonatremia would be diagnostic of RSW. While there are supporting data to suggest this to be a valid conclusion, especially in patients with neurosurgical diseases, future studies will hopefully provide further insights into this relationship. Because neurosurgical patients are routinely treated with hypertonic saline, an increased FEurate with normonatremia or hypernatremia would be suggestive of RSW, see above. We have found this algorithm to be superior to the previous approach as discussed above and expect to make further refinements to this algorithm in the future.
