Urine sodium excretion after tolvaptan administration is dependent upon baseline serum sodium levels: a possible explanation for the improvement of hyponatremia with scarce chance of hypernatremia by a vasopressin receptor antagonist
2014 (English)In: International Heart Journal, ISSN 1349-2365, Vol. 55, no 2, 131-137 p.Article in journal (Refereed) Published
Several studies have demonstrated that tolvaptan (TLV) can improve hyponatremia in advanced heart failure (BF) patients with rare chance of hypernatremia. However, changes in serum sodium concentrations (S-Na) in patients with or without hyponatremia during TLV treatment have not been analyzed. Ninety-seven in-hospital patients with decompensated HF who had received TLV at 3.75-15 mg/day for 1 week were enrolled. Among 68 "responders", who had achieved any increases in urine volume (UV) during the first day, urinary sodium excretion during 24 hours (U-NaEx(24)) increased significantly during one week of TLV treatment along with higher baseline S-Na (P less than 0.05 and r = 0.325). Considering a cut-off value (S-Na, 132 mEq/L; AUC, 0.711) for any increases in U-NaEx(24), we defined "hyponatremia" as S-Na less than 132 mEq/L. In hyponatremic responders (n = 25), S-Na increased significantly, although 1 week was not sufficient for normalization (125.8 +/- 5.0 versus 128.9 +/- 4.3 mEq/L, P less than 0.05), along with unchanged U-NaEx(24) (2767 +/- 2703 versus 2972 +/- 2950 mg/day, NS). In contrast, in normonatremic responders (n = 43), S-Na remained unchanged (136.6 +/- 3.1 versus 137.4 +/- 2.9 mEq/L, NS) along with increased U-NaEx(24) (2201 +/- 1644 versus 4198 +/- 3550 mg/day, P less than 0.05). TLV increased S-Na only in hyponatemic responders by way of pure aquaresis, but increased U-NaEx(24) only in nonnonatremic responders, which explains the scarcity of hypernatremia. Epithelial Na-channels in the distal nephrons, whose repression by TLV increases urinary sodium excretion, may be attenuated by reduced ATP-supply in worse hemodynamics under hyponatremia.
Place, publisher, year, edition, pages
International Heart Journal Association , 2014. Vol. 55, no 2, 131-137 p.
Heart failure; Vasopressin; Urine osmolality
IdentifiersURN: urn:nbn:se:liu:diva-111176DOI: 10.1536/ihj.13-221ISI: 000336465600008PubMedID: 24632953OAI: oai:DiVA.org:liu-111176DiVA: diva2:754554
Funding Agencies|Japan Society for the Promotion of Science ; Japanese Heart Foundation; Japanese Association for Cerebro-Cardiovascular Disease Control and AstraZeneca; Pfizer Health Research Foundation2014-10-102014-10-102014-10-21Bibliographically approved