Complexity of Differentiating Cerebral-Renal Salt Wasting from SIADH, Emerging Importance of Determining Fractional Urate Excretion

The current approach to the diagnosis and treatment of hyponatremia is in a state of flux, largely because of an unresolved controversy regarding the relative prevalence of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and cerebral salt wasting, or preferably renal salt wasting (RSW). The recent awareness that symptoms are now being attributed to even mild hyponatremia has led to recommendations to treat virtually all hyponatremics. (Arief et al, 1976; Berl et al, 2010; Decaux, 2006, 2009; Gankam Kegne et al, 2008; Hoorn et al, 2009; Renneboog et al, 2006; Sterns et al,2009; Schrier, 2010) This tendency to treat even mild hyponatremia introduces an urgency to resolve the diagnostic dilemma of differentiating two syndromes, SIADH and RSW, with divergent therapeutic goals, to water-restrict in SIADH or administer salt and water in RSW. We propose to define RSW by supporting data and review the pathophysiology of RSW, the derivation and evolution of the controversy over the relative prevalence of SIADH and RSW, and methods to differentiate SIADH from RSW. We will also review the emerging value of determining fractional excretion (FE) of urate in the evaluation of patients with hyponatremia by emphasizing our recent observations in reset osmostat, identify conditions that predispose to RSW, amplify the possibility that RSW might exist in patients with an increased FEurate without hyponatremia and propose an algorithm where FEurate is central to the evaluation of hyponatremia. We will also advocate and hopefully justify changing the designation, cerebral salt wasting, to renal salt wasting, and briefly discuss different strategies to treat hyponatremia.