High prevalence of renal salt wasting induced by haptoglobin-related protein without signal peptide is linked to new syndrome of salt wasting in Alzheimer disease

The subject of hyponatremia is undergoing significant changes after developing a more pathophysiologic approach that is superior to the ineffective volume approach and can more effectively identify the different causes of hyponatremia. This new approach identified cerebral salt wasting (CSW) in 24 (38%) of 62 hyponatremic patients from the medical wards of the hospital with 21 showing no evidence of cerebral disease to support our proposal to change CSW to renal salt wasting (RSW). RSW had to be differentiated from the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) because of diametrically opposite therapeutic goals of water-restricting water-logged patients with SIADH or administering salt water to volume-depleted patients with RSW. Both syndromes present with identical clinical parameters that require a difficult protocol to make such a differentiation possible. We describe rat clearance studies demonstrating natriuretic activity in the plasma of patients with neurosurgical and Alzheimer diseases (AD) and eventually identify the protein as haptoglobin-related protein without signal peptide, which can serve as a biomarker to simplify diagnosis of RSW and delivery of the proper management to improve clinical outcomes. We also discuss the introduction of a new syndrome of RSW in AD and its implications. The high prevalence of RSW and identification of the natriuretic factor have created debates over the existence of RSW with none questioning or addressing the pathophysiologic data that identified patients with RSW. We also discuss the potentially large group of patients with RSW who are normonatremic

Haptoglobin-Related Protein without Signal Peptide as Biomarker of Renal Salt Wasting in Hyponatremia, Hyponatremia-Related Diseases and as New Syndrome in Alzheimer’s Disease

The application of pathophysiologic tenets has created significant changes in our approach to hyponatremia and hyponatremia-related conditions. This new 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 simplified the identification of the different causes of hyponatremia, especially the diagnosis of a reset osmostat and Addison’s disease. Differentiating SIADH from RSW has been extremely difficult because both syndromes present with identical clinical parameters, which could be overcome by successfully carrying out the difficult protocol of 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, respectively, was later identified as haptoglobin-related protein without signal peptide (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 will hopefully 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 Alzheimer’s disease; 3. Facilitate differentiating SIADH from RSW on the first encounter and improve clinical outcomes

Transepithelial sodium transport in neurosurgical patients with renal salt wasting

<p>This dataset contains the results of experiments measuring the transport of sodium across the monolayers. 22Na was used to make these measurements. The experiments tested the effects of resuspended urinary precipitates from renal salt wasting (RSW) patients and non-RSW Control patients. The amount of protein in the precipitates was used to quantitate the precipitates.</p> <p>The 'Summary' sheet tabulates the results of the individual experiments described below. The heading numbers such as 5ug or 10ug refer to the concentrations of resuspended precipitates (in micrograms protein/ml) to which the cultures were exposed. In all experiments, cultures were exposed to precipitates on both the mucosal and serosal sides. Numbers tabulated are the effects of various concentrations of precipitate on transepithelial Na movement, expressed as percentages relative to that seen side-by-side in vehicle-only wells.</p> <p>The control and RSW sheets contain the raw data and calculations, for 47 individual experiments in which the effects of precipitates from the urine of RSW-afflicted patients or non-RSW Control patients on sodium transport across cultured LLC monolayers were measured. Effects of the precipitates on sodium movements were calculated as described in the Methods section of the paper, in brief, the effect of treatment (change in the slope of the linear regression line of sodium movement after treatment versus before) in experimental culture wells versus the effect of vehicle treatment (change in the regression line after versus before treatment) seen in side-by-side Vehicle wells. The results for individual patients are grouped in sub-folders with the patients identified by index numbers.</p> <p>Other numbers quoted are percent change in transepithelial sodium transport (caused by addition of urinary precipitate, indexed by its protein content) relative to vehicle addition, as described in Methods in body of the paper. (Briefly, relative to Na movement in side-by-side culture wells in which only vehicle was added to the transport medium).</p

Passive leakage across monolayers using calcein as a fluorescent marker

<p>This dataset tabulates data on passive leakage across the monolayers using a fluorescent marker, calcein, a derivative of fluorescein. The purpose was to gauge the degree of confluence and whether tight junctions had formed between the epithelial cells.</p> <p>The sheet 'Leak rates' tabulates a summary of the data of the 17 calcein experiments in the raw data sheet. The sheet 'Raw data' contains the data and calculations of the 17 experiments.</p