To describe the available and emerging treatment options for acute and chronic hyponatremia, including the efficacy, safety, and recommendations regarding appropriate use, monitoring, and treatment individualization.
Summary
Arginine vasopressin (AVP) receptor antagonists provide an opportunity to address some of the unmet medical needs of patients with hyponatremia. Traditional therapies, including diuretics, fluid restriction, and saline infusions, have variable effects, potential toxicities, and issues with patient adherence. Furthermore, these therapies are not specific to the underlying pathophysiology causing the hyponatremia. The recently approved AVP receptor antagonists target the underlying abnormal release of AVP that is very likely at the core of the physiology.
Conclusion
Management of hyponatremia requires balancing the benefits of therapeutic intervention for the restoration of normal serum sodium against the potential risks. The data available indicate that this new class of medications, the AVP receptor antagonists, can favorably affect serum sodium and clinical outcomes in patients with hypervolemic and euvolemic hyponatremia.
KumarS., BerlT. In: SchrierR.W., eds. Atlas of Diseases of the Kidney. Vol 1.Philadelphia: Current Medicine, Inc; 1999; 1.1–1.22.
4.
FallP.J.Hyponatremia and hypernatremia: a systematic approach to causes and their corrections. Postgrad Med.2000; 107(5): 75–82.
5.
MohmandH.K., IssaD., AhmadZ.Hypertonic saline for hyponatremia: risk of inadvertent overcorrection. Clin J Am Soc Nephrol.2007; 2(6): 1110–1117.
6.
ZietseR., van der LubbeN., HoornE.J.Current and future treatment options in SIADH. NDT Plus.2009; 2(Suppl 3): iii12–iii19.
7.
SternsR.H., NigwekarS.U., HixJ.K.The treatment of hyponatremia. Semin Nephrol.2009; 29: 282–299.
8.
GoldsmithS.R.Current treatments and novel pharmacologic treatments for hyponatremia in congestive heart failure. Am J Cardiol.2005; 95(suppl): 14B–23B.
9.
AyusJ.C., ArieffA.I.Chronic hyponatremic encephalopathy in postmenopausal women: association of therapies with morbidity and mortality. JAMA.1999; 281: 2299–2304.
10.
ForrestJ.N.Jr, CoxM., HongC.Superiority of demeclocycline over lithium in the treatment of chronic syndrome of inappropriate secretion of antidiuretic hormone. N Engl J Med.1978; (26);298(4): 173–177.
11.
RobertsonG.L.Vaptans for the treatment of hyponatremia. Nat Rev Endocrinol.2011; 7: 151–161.
Samsca (tolvaptan) package insert.Rockville, MD: Otsuka America Pharmaceutical, Inc; 2009.
14.
LeeC.R., WatkinsM.K., OattersonJ.H.Vasopressin: a new target for the treatment of heart failure. Am J Heart.2003; 146: 9–18.
15.
DecauxG., SoupartA., VassartG.Nonpeptide argininevasopressin antagonists: the vaptans. Lancet.2008; 371(9624): 1624–1632.
16.
GhaliJ.K., HamadB., YasothanU.Tolvaptan. Nat Rev Drug Discov.2009; 8: 611–612.
17.
KondoK., OgawaH., YamashitaH.7-Chloro-5-hydroxy-1-[2-methyl-4-(2-methylbenzoyl-amino)benzoyl]-2,3,4,5-tetrahydro-1H-1-benzazepine (OPC-41061): a potent, orally active nonpeptide arginine vasopressin V2 receptor antagonist. Bioorg Med Chem.1999; 7(8): 1743–1754.
18.
ShoafS.E., BramerS.L., BricmontP.Pharmacokinetic and pharmacodynamic interaction between tolvaptan, a nonpeptide AV antagonist and furosemide or hydrochlorothiazide. J Cardiovasc Pharmacol.2007; 50: 213–222.
19.
ZeltserD., RosanskyS., van RensburgH., for the Conivaptan Study Group. Assessment of the efficacy and safety of intravenous conivaptan in euvolemic and hypervolemic hyponatremia. Am J Nephrol.2007; 27: 447–457.
20.
MurphyT., DharR., DiringerM.Conivaptan bolus dosing for the correction of hyponatremia in the neurointensive care unit. Neurocrit Care.2009; 11(1): 14–19.
21.
VelezJ.C., DopsonS.J., SandersD.S.Intravenous conivaptan for the treatment of hyponatraemia caused by the syndrome of inappropriate secretion of antidiuretic hormone in hospitalized patients: a single-centre experience. Nephrol Dial Transplant.2010; 25(5): 1524–1531.
22.
SchrierR.W., GrossP., GheorghiadeM.D.Tolvaptan, a selective oral vasopressin V2–receptor antagonist, for hyponatremia. N Engl J Med.2006; 355: 2099–2112.
23.
BerlT., Quittnat-PelletierF., VerbalisJ.G.Oral tolvaptan is safe and effective in chronic hyponatremia. J Am Soc Nephrol.2010; 21: 705–712.
24.
Treatment of hyponatremia: medical utility of vasopressin V2 receptor antagonism, briefing document. Advisory Committee of the Cardiovascular and Renal Drugs Division of the US Food and Drug Administration. June 25, 2008. www.fda.gov/ohrms/dockets/ac/08/briefing/2008-4373b1-05.pdf. Accessed April 5, 2011.
25.
GheorghiadeM.D., AbrahamW.T., AlbertN.M.Relationship between admission serum sodium concentration and clinical outcomes in patients hospitalized for heart failure: an analysis from the OPTIMIZE-HF registry. Eur Heart J.2007; 128: 980–988.
26.
GheorghiadeM., GattisW.A., O'ConnorC.M.Effects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening heart failure: a randomized controlled trial. JAMA.2004; 291(16): 1963–1971.
27.
RossiJ., BayramM., UdelsonJ.E.Improvement in hyponatremia during hospitalization for worsening heart failure is associated with improved outcomes: insights from the Acute and Chronic Therapeutic Impact of a Vasopressin Antagonist in Chronic Heart Failure (ACTIV in CHF) trial. Acute Card Care.2007; 9(2): 82–86.
28.
KonstamM.A., GheorghiadeM., BurnettJ.C.Jr. Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST outcome trial. JAMA.2007; 297(12): 1319–1331.
29.
Rozen-ZviB., YahavD., GheorghiadeM.Vasopressin receptor antagonists for the treatment of hyponatremia: systematic review and meta-analysis. Am J Kidney Dis.2010; 56(2): 325–337.
