title: Urinary excretion of the water channel aquaporin 2 correlated with the pharmacological effect of tolvaptan in cirrhotic patients with ascites.
abstract: BACKGROUND
  The water channel aquaporin 2 (AQP2) at the apical membrane of renal collecting duct cells mediates water reabsorption. The expression of AQP2 at the apical membrane is tightly regulated by vasopressin and was quantitated by measurement of the urinary form by a recently developed ELISA. Tolvaptan, an antagonist of vasopressin type 2 receptor, inhibits water reabsorption in cirrhosis. The aim of this study was to determine the correlation between the pharmacological effect of tolvaptan and the dynamics of urinary AQP2 levels.
  
  
  METHODS
  Tolvaptan was administered to 41 cirrhotic patients with ascites unresponsive to standard diuretic therapy. Urinary excretion of AQP2 and urinary osmolarity were measured at the baseline and at 4, 8, and 24 h after administration of tolvaptan.
  
  
  RESULTS
  At the baseline, urinary AQP2/creatinine ratios were significantly higher in cirrhotic patients with ascites than in healthy controls (P < 0.0001). After administration of tolvaptan, urinary AQP2/creatinine ratios decreased by 45.0 % at 4 h and 77.0 % at 8 h. Similarly, urinary osmolarity decreased by 42.0 % at 4 h and 41.5 % at 8 h. Urinary AQP2 levels and urinary osmolarity significantly correlated at the baseline and at all time points after tolvaptan administration. The degree of the decrease in urinary AQP2 levels and degree of the decrease in urinary osmolarity correlated significantly at 4 h (r = 0.452, P = 0.009) and 8 h (r = 0.384, P = 0.030) after tolvaptan administration.
  
  
  CONCLUSIONS
  These results indicate that the vasopressin-AQP2 system plays a major role in fluid retention in cirrhosis and that the pharmacological effect of tolvaptan to inhibit water reabsorption can be monitored by measurement of the dynamics of urinary AQP2 levels.
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Kyonancho 1-26-1, Musashino-shi, Tokyo, 180-8610, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakanishi
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Kyonancho 1-26-1, Musashino-shi, Tokyo, 180-8610, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kurosaki
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Kyonancho 1-26-1, Musashino-shi, Tokyo, 180-8610, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Hosokawa
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Kyonancho 1-26-1, Musashino-shi, Tokyo, 180-8610, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Kyonancho 1-26-1, Musashino-shi, Tokyo, 180-8610, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Itakura
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Kyonancho 1-26-1, Musashino-shi, Tokyo, 180-8610, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Kyonancho 1-26-1, Musashino-shi, Tokyo, 180-8610, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yasui
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Kyonancho 1-26-1, Musashino-shi, Tokyo, 180-8610, Japan.
authors.forename: Nobuharu
authors.initials: N
authors.lastname: Tamaki
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Kyonancho 1-26-1, Musashino-shi, Tokyo, 180-8610, Japan.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Nakakuki
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Kyonancho 1-26-1, Musashino-shi, Tokyo, 180-8610, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Takada
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Kyonancho 1-26-1, Musashino-shi, Tokyo, 180-8610, Japan.
authors.forename: Mayu
authors.initials: M
authors.lastname: Higuchi
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Kyonancho 1-26-1, Musashino-shi, Tokyo, 180-8610, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Komiyama
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Kyonancho 1-26-1, Musashino-shi, Tokyo, 180-8610, Japan.
authors.forename: Tsubasa
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Kyonancho 1-26-1, Musashino-shi, Tokyo, 180-8610, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Takaura
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Kyonancho 1-26-1, Musashino-shi, Tokyo, 180-8610, Japan.
authors.forename: Tsuguru
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Kyonancho 1-26-1, Musashino-shi, Tokyo, 180-8610, Japan.
authors.forename: Konomi
authors.initials: K
authors.lastname: Kuwabara
authors.affiliation: Department of Nephrology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Sei
authors.initials: S
authors.lastname: Sasaki
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Kyonancho 1-26-1, Musashino-shi, Tokyo, 180-8610, Japan. izumi012@musashino.jrc.or.jp.
authors.forename: Namiki
authors.initials: N
authors.lastname: Izumi
mesh_terms: D000368:Aged; D065092:Antidiuretic Hormone Receptor Antagonists / Q000494:pharmacology*; D051399:Aquaporin 2 / Q000652:urine*; D001201:Ascites / Q000150:complications / Q000188:drug therapy / Q000652:urine*; D001552:Benzazepines / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000188:drug therapy / Q000652:urine*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D000077602:Tolvaptan
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D051399:Aquaporin 2; D001552:Benzazepines; D000077602:Tolvaptan
keywords: Ascites; Hyponatremia; Tolvaptan; Urinary aquaporin 2