Hyponatremia Etiology and Tolvaptan: Are we Optimally Targeting the Mechanism?

Arif Asif *, 1, Ketan Ghate1, Neena Jube1, Syed S. Haqqie1, Roy O. Mathew1, 2, Vishesh Kumar1, John Tietjen3, John Rosenberger4, Sunil Pokharel3, Syed F. Saeed3, Shervin Yousefian3, Donna Merrill1, Rizwan Shahid5, Muhammad U.T. Akmal5, Ali Nayer,5, Darius Mason11, Tushar Vachharajani 6, Loay Salman 5
1 Division of Nephrology and Hypertension, Albany Medical College, Albany, NY, USA
2 Stratton VA Medical Center, Albany, NY, USA
3 Division of Hospital Medicine, Albany Medical College, Albany, NY, USA
4 Division of General Medicine, Albany Medical College, Albany, NY, USA
5 Division of Nephrology and Hypertension, University of Miami Miller School of Medicine, Miami, FL, USA
6 Division of Nephrology and Hypertension, W.G. (Bill) Hefner Veterans Affairs Medical Center, Salisbury, NC, USA

Article Metrics

CrossRef Citations:
Total Statistics:

Full-Text HTML Views: 3360
Abstract HTML Views: 2611
PDF Downloads: 886
ePub Downloads: 771
Total Views/Downloads: 7628
Unique Statistics:

Full-Text HTML Views: 1466
Abstract HTML Views: 1329
PDF Downloads: 575
ePub Downloads: 527
Total Views/Downloads: 3897

Creative Commons License
Bentham Open.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.

* Address correspondence to this author at the Thomas Ordway Distinguished Professor of Medicine, Chief: Division of Nephrology and Hypertension, Albany Medical College, 25 Hacket Blvd, Albany, NY 12208, USA; Tel: 518-262-0769; E-mail:


Hyponatremia is associated with increased morbidity and mortality. Water restriction is usually the prescribed treatment for most forms of asymptomatic hyponatremia. An oral vasopressin V2-receptor antagonist, tolvaptan has been successfully used in the treatment of asymptomatic hyponatremia. In this retrospective study, tolvaptan (n=40) and a control group (n=40) were compared for asymptomatic hyponatremia etiology and response to treatment. The syndrome of inappropriate anti-diuretic hormone (SIADH) and congestive heart failure (CHF) were the most common causes of asymptomatic hyponatremia that were treated with tolvaptan. Of note, the cause of hyponatremia was not clarified in 50% of the control and 10% of the tolvaptan group. In the tolvaptan group, serum sodium concentration increased from 125±4.2 to 136±2.1 mEq/L (mean±SD, P<0.001) over 5±2 days while the control group did not show any change from its baseline value of 129.9±3 vs 128±4 mEq/L. SIADH and CHF were the most common disorders associated with asymptomatic hyponatremia and treated with tolvaptan. Importantly, 50% of the asymptomatic hyponatremia patients in the control group were labeled as unclear etiology and did not receive tolvaptan. Increased awareness of the etiology and mechanisms of asymptomatic hyponatremia development can identify individuals who benefit from tolvaptan therapy.

Keywords:: Hyponatremia, serum osmolality, serum sodium, tolvaptan, urine osmolality..