title: Demonstration of natriuretic activity in urine of neurosurgical patients with renal salt wasting.
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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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 3 μg protein/ml, by 10-25%, versus to vehicle alone, and by 15-40% at concentrations of 5-20 μg/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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine, Old Westbury, NY, 11568, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Youmans
authors.affiliation: Graduate Program in Genetics, State University of New York, Stony Brook, NY, 21814, USA ; Cold Spring Harbor Laboratory, Cold Spring Harbour, NY, 11724, USA.
authors.forename: Miriam R
authors.initials: MR
authors.lastname: Fein
authors.affiliation: Department of Neurology, Winthrop-University Hospital, Mineola, NY, 11501, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Wirkowski
authors.affiliation: Department of Medicine, Division of Nephrology and Hypertension, Winthrop-University Hospital, Mineola, NY, 11501, USA ; SUNY Downstate Medical Center, Stony Brook, NY, 21814, USA.
authors.forename: John K
authors.initials: JK
authors.lastname: Maesaka