Abstract
We have utilized the persistent elevation of fractional excretion (FE) of urate, > 10%, to differentiate cerebral/renal salt wasting (RSW) from the syndrome of inappropriate antidiuretic hormone secretion (SIADH), in which a normalization of FEurate occurs after correction of hyponatremia. Previous studies suggest as well that an elevated FEurate with normonatremia, without pre-existing hyponatremia, is also consistent with RSW, including studies demonstrating induction of RSW in rats infused with plasma from normonatremic neurosurgical and Alzheimer's disease patients. The present studies were designed to test whether precipitates from the urine of normonatremic neurosurgical patients, with either normal or elevated FEurate, and patients with SIADH, display natriuretic activity. Ammonium sulfate precipitates from the urine of 6 RSW and 5 non-RSW Control patients were dialyzed (10 kDa cutoff) to remove the ammonium sulfate, lyophilized, and the reconstituted precipitate was tested for its effect on transcellular transport of (22)Na across LLC-PK1 cells grown to confluency in transwells. Precipitates from 5 of the 6 patients with elevated FEurate and normonatremia significantly inhibited the in vitro transcellular transport of (22)Na above a concentration of 3μg protein/ml, by 10-25%, versus to vehicle alone, and by 15-40% at concentrations of 5-20μg/ml as compared to precipitates from 4 of the 5 non-RSW patients with either normal FEurate and normonatremia (2 patients) or with SIADH (2 patients). These studies provide further evidence that an elevated FEurate with normonatremia is highly consistent with RSW. Evidence in the urine of natriuretic activity suggests significant renal excretion of the natriuretic factor. The potentially large source of the natriuretic factor that this could afford, coupled with small analytical sample sizes required by the in-vitro bioassay used here, should facilitate future experimental analysis and allow the natriuretic factor to be investigated as a potential biomarker for RSW.
Highlights
The unresolved controversy over the prevalence of the cerebral salt-wasting, or the preferred term, renal saltwasting (RSW) syndrome, can be ascribed, in large part, to difficulties in differentiating RSW, where extracellular volume is depleted, from the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), where volume is normal or expanded
Group III, RSW, had increased FEurate with normonatremia, a combination that is consistent with RSW but not SIADH
This study demonstrates the presence of a factor, in the urine of 5 of 6 neurosurgical patients with increased FEurate and normonatremia, that inhibits transcellular transport of 22Na in LLC-PK1 cells grown to confluency in transwells (Group III)
Summary
The unresolved controversy over the prevalence of the cerebral salt-wasting, or the preferred term, renal saltwasting (RSW) syndrome, can be ascribed, in large part, to difficulties in differentiating RSW, where extracellular volume is depleted, from the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), where volume is normal or expanded. RSW has been found to be much more common than SIADH in neurosurgical patients and our reports of RSW occurring in patients without clinical cerebral disease introduce new challenges to determine the true prevalence of RSW5,6. This diagnostic dilemma poses a therapeutic dilemma that has significant clinical outcomes, such as the risk inherent in fluid restricting a volume-depleted patient with RSW. Our recent proposal to replace the inappropriate and outdated term, cerebral salt wasting, with RSW, has great clinical relevance because RSW would not in the past be considered unless the patient had evidence of cerebral disease[1]
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