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Am J Kidney Dis. 2018 Jun;71(6):772-782. doi: 10.1053/j.ajkd.2017.12.002. Epub 2018 Feb 23.

Rapidity of Correction of Hyponatremia Due to Syndrome of Inappropriate Secretion of Antidiuretic Hormone Following Tolvaptan.

Author information

1
Division of Nephrology, Department of Medicine, Medical University of South Carolina, Charleston, SC.
2
Department of Clinical Pharmacy, Medical University of South Carolina, Charleston, SC.
3
Department of Pharmacy Practice, Mylan School of Pharmacy, Duquesne University, Pittsburgh, PA.
4
Department of Pharmacy, Wake Forest Baptist Medical Center, Winston-Salem, NC.
5
Department of Pharmacy, University of Florida Health at Jacksonville, Jacksonville, FL.
6
Division of Nephrology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI.
7
Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC.
8
Department of Nephrology, Ochsner Clinic Foundation, New Orleans, LA. Electronic address: juancarlos.velez@ochsner.org.

Abstract

BACKGROUND:

Tolvaptan effectively corrects hyponatremia due to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), but undesired overcorrection can occur. We hypothesized that pretherapy parameters can predict the rapidity of response to tolvaptan in SIADH.

STUDY DESIGN:

Multicenter historical cohort study.

SETTING & PARTICIPANTS:

Adults with SIADH or congestive heart failure (CHF) treated with tolvaptan for a serum sodium concentration ≤ 130 mEq/L at 5 US hospitals.

PREDICTORS:

Demographic and laboratory parameters.

OUTCOMES:

Rate of change in serum sodium concentration.

MEASUREMENTS:

Spearman correlations, analysis of variance, and multivariable linear mixed-effects models.

RESULTS:

28 patients with SIADH and 39 patients with CHF treated with tolvaptan (mean baseline serum sodium, 120.6 and 122.4 mEq/L, respectively) were studied. Correction of serum sodium concentration > 12 mEq/L/d occurred in 25% of patients with SIADH compared to 3% of those with CHF (P<0.001). Among patients with SIADH, the increase in serum sodium over 24 hours was correlated with baseline serum sodium concentration (r=-0.78; P<0.001), serum urea nitrogen concentration (SUN; r=-0.76; P<0.001), and estimated glomerular filtration rate (r=0.58; P=0.01). Baseline serum sodium and SUN concentrations were identified as independent predictors of change in serum sodium concentration in multivariable analyses. When patients were grouped into 4 categories according to baseline serum sodium and SUN median values, those with both low baseline serum sodium (≤121 mEq/L) and low baseline SUN concentrations (≤10mg/dL) exhibited a significantly greater rate of increase in serum sodium concentration (mean 24-hour increase of 15.4 mEq/L) than the other 3 categories (P<0.05). Among patients with CHF, only baseline SUN concentration was identified as an independent predictor of change in serum sodium concentration over time.

LIMITATIONS:

Lack of uniformity in serial serum sodium concentration determinations and documentation of water intake.

CONCLUSIONS:

Baseline serum sodium and SUN values are predictive of the rapidity of hyponatremia correction following tolvaptan use in SIADH. We advise caution when dosing tolvaptan in patients with both low serum sodium and SUN concentrations.

KEYWORDS:

Overcorrection; blood urea nitrogen (BUN); congestive heart failure (CHF); hyponatremia; hypouremia; kidney function; osmolality; serum sodium; syndrome of inappropriate secretion of antidiuretic hormone (SIADH); tolvaptan

PMID:
29478867
PMCID:
PMC5970971
[Available on 2019-06-01]
DOI:
10.1053/j.ajkd.2017.12.002

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