Identification of a novel natriuretic protein in patients with cerebral-renal salt wasting - implications for enhanced diagnosis

Cisplatin is known to induce Fanconi syndrome and renal salt wasting (RSW). RSW typically only requires transient normal saline (NS) support. We report a severe RSW case that required 12 liters of 3% saline. A 57-year-old woman with limited stage small cell cancer was admitted for cisplatin (80 mg/m2) and etoposide (100 mg/m2) therapy. Patient’s serum sodium (SNa) decreased from 138 to 133 and 125 mEq/L within 24 and 48 hours of cisplatin therapy, respectively. A diagnosis of syndrome of inappropriate antidiuretic hormone secretion (SIADH) was initially made. Despite free water restriction, patient’s SNa continued to decrease in association with acute onset of headaches, nausea, and dizziness. Three percent saline (3%S) infusion with rates up to 1400 mL/day was required to correct and maintain SNa at 135 mEq/L. Studies to evaluate Fanconi syndrome revealed hypophosphatemia and glucosuria in the absence of serum hyperglycemia. The natriuresis slowed down by 2.5 weeks, but 3%S support was continued for a total volume of 12 liters over 3.5 weeks. Attempts of questionable benefits to slow down glomerular filtration included the administration of ibuprofen and benazepril. To our knowledge, this is the most severe case of RSW ever reported with cisplatin.

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Differentiating SIADH from Cerebral/Renal Salt Wasting: Failure of the Volume Approach and Need for a New Approach to Hyponatremia

Journal of Clinical Medicine ◽

10.3390/jcm3041373 ◽

2014 ◽

Vol 3 (4) ◽

pp. 1373-1385 ◽

Cited By ~ 22

Author(s):

John Maesaka ◽

Louis Imbriano ◽

Joseph Mattana ◽

Dympna Gallagher ◽

Naveen Bade ◽

...

Keyword(s):

New Approach ◽

Salt Wasting ◽

Renal Salt Wasting

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Prenatal programming of renal salt wasting resets postnatal salt appetite, which drives food intake in the rat

Clinical Science ◽

10.1042/cs1220485 ◽

2012 ◽

Vol 122 (10) ◽

pp. 485-485 ◽

Cited By ~ 1

Author(s):

S. H. Alwasel ◽

D. J. P. Barker ◽

N. Ashton

Keyword(s):

Food Intake ◽

Salt Appetite ◽

Prenatal Programming ◽

Salt Wasting ◽

Renal Salt Wasting

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Plasma natriuretic factor(s) in patients with intracranial disease, renal salt wasting and hyperuricosuria

Life Sciences ◽

10.1016/0024-3205(93)90008-q ◽

1993 ◽

Vol 52 (23) ◽

pp. 1875-1882 ◽

Cited By ~ 18

Author(s):

John K. Maesaka ◽

Jeyanti Venkatesan ◽

Joanne M. Piccione ◽

Robert Decker ◽

Albert W. Dreisbach ◽

...

Keyword(s):

Salt Wasting ◽

Renal Salt Wasting ◽

Intracranial Disease ◽

Natriuretic Factor

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Demonstration of natriuretic activity in urine of neurosurgical patients with renal salt wasting

F1000Research ◽

10.12688/f1000research.2-126.v2 ◽

2013 ◽

Vol 2 ◽

pp. 126 ◽

Cited By ~ 5

Author(s):

Steven J Youmans ◽

Miriam R Fein ◽

Elizabeth Wirkowski ◽

John K Maesaka

Keyword(s):

Ammonium Sulfate ◽

Hormone Secretion ◽

Transcellular Transport ◽

Inappropriate Antidiuretic Hormone Secretion ◽

Salt Wasting ◽

Renal Salt Wasting ◽

Natriuretic Factor ◽

Potential Biomarker ◽

Neurosurgical Patients

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 22Na 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 22Na 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).Conclusion: 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.

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