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Vaptans for the treatment of hyponatremia

Nature Reviews Endocrinology volume 7, pages 151–161 (2011)Cite this article

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Abstract

The vaptans constitute a new class of pharmaceuticals developed for the treatment of the hypervolemic and euvolemic forms of hyponatremia. These agents are nonpeptide vasopressin antagonists that interfere with the antidiuretic effect of the hormone by competitively binding to V2 receptors in the kidney. This blockade results in water diuresis (aquaresis) that, if not offset by increased fluid intake, reduces body water content and raises plasma sodium levels. Probably as a result of this rise in plasma sodium, thirst and plasma vasopressin concentration increase, potentionally limiting the effects of the vasopressin antagonists. Nonetheless, vaptans are particularly useful to treat hypervolemic hyponatremia associated with severe congestive heart failure or chronic liver failure, as the only other treatments currently available, such as fluid restriction and diuretics, are slow-acting and minimally effective. Vaptans are also useful for treating euvolemic hyponatremia associated with the syndrome of inappropriate antidiuretic hormone (SIADH), at least when it is chronic and/or minimally symptomatic. However, because their effects vary unpredictably from patient to patient, vaptans are less useful than hypertonic saline infusion in cases of acute, severe and symptomatic hyponatremia. Vaptan therapy is absolutely contraindicated in hypovolemic hyponatremia (in which total body water is reduced) and is ineffective in the vasopressin-independent form of inappropriate antidiuresis caused by constitutive activating mutations of V2 receptors.

Key Points

  • Vaptans are nonpeptide agents that antagonize the antidiuretic effect of vasopressin by competing with it for binding to V2 receptors in the kidney

  • Vaptans increase solute-free water excretion, reduce body water content and raise the plasma sodium level by reducing urine concentration, unless the aquaresis is offset by increased fluid intake

  • The vaptan-induced rise in plasma sodium often stimulates thirst and/or vasopressin secretion, which, in turn, may feed back to increase fluid intake and/or overcome blockade of the V2 receptor

  • In conjunction with modest restriction of fluid intake, vaptans have proven safe and effective in treating chronic hypervolemic and euvolemic hyponatremia

  • The use of vaptans to treat acute, symptomatic forms of hyponatremia is still debatable, because their effects on plasma sodium vary unpredictably from patient to patient

  • Vaptan therapy is contraindicated in hypovolemic hyponatremia, a disorder associated with decreased total body water and sodium levels, and is ineffective in a form of inappropriate antidiuresis that is independent of vasopressin

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Figure 1: Principal elements of the osmoregulatory system.
Figure 2: Osmoregulation of water balance in healthy adults.

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Acknowledgements

C. P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the MedscapeCME-accredited continuing medical education activity associated with this article.

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  1. Division of Endocrinology, Northwestern University Medical School, 303 East Superior Tarry 15–755, Chicago, 60611, IL, USA

    Gary L. Robertson

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Robertson, G. Vaptans for the treatment of hyponatremia. Nat Rev Endocrinol 7, 151–161 (2011). https://doi.org/10.1038/nrendo.2010.229

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