Title : Haptoglobin-related protein without signal peptide as biomarker of renal salt wasting (HPRWSP) in hyponatremia, hyponatremia-related diseases and as new syndrome in alzheimer’s disease
Abstract:
Application of pathophysiologic tenets has created significant changes in our approach to hyponatremia and hyponatremia-related conditions. This approach incorporated the determination of fractional excretion (FE) of urate before and after the correction of hyponatremia and the response to isotonic saline infusion to differentiate the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) from renal salt wasting (RSW). FEurate better identified the different causes of hyponatremia. Differentiating SIADH from RSW has been difficult because both have identical clinical parameters, but successfully overcome by carrying out this new approach. A study of 62 hyponatremic patients from the general medical wards of the hospital identified 17 (27%) to have SIADH, 19 (31%) with reset osmostat, and 24 (38%) with RSW with 21 of these RSW patients presenting without clinical evidence of cerebral disease to warrant changing the nomenclature from cerebral to renal salt wasting. The natriuretic activity found in the plasma of 21 and 18 patients with neurosurgical and Alzheimer’s disease (AD), respectively, was later identified as HPRWSP. The high prevalence of RSW creates a therapeutic dilemma of deciding whether to water-restrict water-logged patients with SIADH as compared to administering saline to volume-depleted patients with RSW. Future studies should achieve the following: 1. Abandon the ineffective volume approach; 2. Develop HPRWSP as a biomarker to identify hyponatremic and a projected large number of normonatremic patients at risk of developing RSW, including new syndrome of RSW in AD; 3. Facilitate differentiating SIADH from RSW on the first encounter and improve clinical outcomes, 4. Need to develop an inhibitor to HPRWSP to treat RSW and 5 be a potent diuretic to remove edema in heart failure when combined with distal diuretics such as furosemide.