title: 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.
abstract: Several studies have demonstrated that tolvaptan (TLV) can improve hyponatremia in advanced heart failure (HF) 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 fi rst 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 < 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 < 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 < 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 < 0.05). TLV increased S-Na only in hyponatremic responders by way of pure aquaresis, but increased U-NaEx(24) only in normonatremic 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.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo.
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Imamura
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kinugawa
authors.forename: Shun
authors.initials: S
authors.lastname: Minatsuki
authors.forename: Hironori
authors.initials: H
authors.lastname: Muraoka
authors.forename: Naoko
authors.initials: N
authors.lastname: Kato
authors.forename: Toshiro
authors.initials: T
authors.lastname: Inaba
authors.forename: Hisataka
authors.initials: H
authors.lastname: Maki
authors.forename: Masaru
authors.initials: M
authors.lastname: Hatano
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yao
authors.forename: Issei
authors.initials: I
authors.lastname: Komuro
mesh_terms: D000328:Adult; D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines / Q000008:administration & dosage*; D004232:Diuretics / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D006955:Hypernatremia / Q000097:blood* / Q000188:drug therapy / Q000209:etiology; D007010:Hyponatremia / Q000097:blood* / Q000188:drug therapy / Q000209:etiology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012964:Sodium / Q000097:blood / Q000652:urine*; D000077602:Tolvaptan; D016896:Treatment Outcome
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D004232:Diuretics; D000077602:Tolvaptan; D012964:Sodium