Fractional urate excretion in hyponatremia differentiates cerebral renal salt wasting from inappropriate secretion of antidiuretic hormone

Abstract

Hyponatremia, defined as a serum sodium < 135 mmol/, is the most common electrolyte abnormality in hospitalized patients. There has been an unresolved controversy over the prevalence of cerebral renal salt-wasting (CRSW). Internists consider the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) dominates the field of hyponatremia and CRSW to be rare and neurologists, neurosurgeons and critical physicians consider CRSW to be common. Differentiating SIADH from CRSW is difficult because of identical essential blood and urinary parameters and cannot be resolved by the ineffectual volume approach. We developed a pathophysiologic approach by determining fractional excretion of urate and response to isotonic saine infusions that not only simplified differentiating SIADH from CRSW but simplified identification of other causes of hyponatremia such as a reset osmostat, psychogenic polydipsia, Addison's disease, prerenal azotemia with normal kidney function, heart failure, nephrosis, and cirrhosis. We also identified CRSW in 38% of hyponatremic patients in the general medical wards of the hospital, induced salt wasting in rats by infusing plasma of neurosurgical and Alzheimer patients, identified haptoglobin related protein without signal peptide (HPRWSP) from a normonatremic patient with subarachnoid hemorrhage and another with Alzheimer disease (AD) as the protein that causes CRSW and introduced a new syndrome of CRSW in AD. We intend to develop HPRSWP as a biomarker of CRSW to simplify diagnosis of CRSW in hyponatremic and a growing list of normonatremic patients on first encounter to improve therapeutic outcomes.