Abstract
Our understanding of hyponatremia, defined as a serum sodium < 135 mmol/L, and hyponatremia-related diseases is in a state of flux. A better understanding is now being established by abandoning the ineffective volume approach that has been in existence for over 50 years. We utilized comprehensive pathophysiologic phenomena that brought greater clarity to understanding and identifying the different causes of hyponatremia. An important message was to emphasize the difficulty in differentiating the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) from appropriate antidiuretic hormone secretion in patients with cerebral or renal salt wasting (RSW), a condition that was previously considered to be rare among internists. Both syndromes present with identical clinical parameters that need to be appreciated and emphasized. The new approach demonstrated a high prevalence of RSW in hyponatremic patients from the general medical wards of the hospital to raise the awareness that hyponatremia is not all due to SIADH. We demonstrated natriuretic activity in the plasma of 21 neurosurgical and 17 Alzheimer’s disease patients by performing rat renal clearance studies while infusing plasma from these patients. The natriuretic factor was later identified as haptoglobin related protein without signal peptide in both groups of patients. Interestingly, blood levels of HPRWSP appears to increase progressively as the dementia worsens below a mini mental state examination score of 12 in Alzheimer’s. Additional data suggest that RSW might be present at an early stage of Alzheimer’s and these patients may become more dehydrated as the dementia worsens. Future studies intend to prove the existence and extent of volume depletion in Alzheimer’s and to develop HPRWSP as a biomarker of RSW.