title: The effect of tolvaptan on autosomal dominant polycystic kidney disease patients: a subgroup analysis of the Japanese patient subset from TEMPO 3:4 trial.
abstract: BACKGROUND
  Japan is the first country in the world to approve tolvaptan for the treatment of autosomal dominant polycystic kidney disease (ADPKD), which was based on the results of Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes (TEMPO) 3:4 trial. To evaluate the safety and efficacy of tolvaptan, we performed a subgroup analysis in the participating Japanese ADPKD patient population.
  
  
  METHODS
  The primary outcome was the annual rate of percentage change in the total kidney volume (TKV). The secondary endpoint was the rate of kidney function change.
  
  
  RESULTS
  The tolvaptan and placebo groups included 118 and 59 patients, respectively. The annual rate of percentage changes in TKV were 1.3 % [95 % confidence interval (CI) 0.4-2.1] in the tolvaptan group, and 5.0 % (95 % CI 3.9-6.2) in the placebo group (P < 0.001). The annual estimated glomerular filtration rate change was -3.83 mL/min/1.73 m(2) in the tolvaptan group and -5.05 mL in the placebo group for a treatment effect of +1.22 mL/min/1.73 m(2) (95 % CI 0.41-2.02: P = 0.003). Hepatic function abnormal as a serious adverse event was observed in 3 patients (2.5 %) in the tolvaptan group.
  
  
  CONCLUSIONS
  Administration of tolvaptan in the Japanese sub-population reduced the annual rate of TKV growth and slowed the rate of kidney function decline over 36 months compared to patients on placebo, thus providing a novel and effective therapy for the treatment of ADPKD. (TEMPO 3:4 ClinicalTrials.gov number, NCT00428948).
authors: Department of Urology, Teikyo University School of Medicine, Tokyo, Japan.
authors: Satoru
authors: S
authors: Muto
authors: Department of Urology, Juntendo University Graduate School of Medicine, Hongo 3-1-3, Bunkyo-ku, Tokyo, 113-8431, Japan.
authors: Haruna
authors: H
authors: Kawano
authors: Department of ADPKD Research, Kyorin University School of Medicine, Tokyo, Japan.
authors: Eiji
authors: E
authors: Higashihara
authors: Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors: Ichiei
authors: I
authors: Narita
authors: Nephrology Center and Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan.
authors: Yoshifumi
authors: Y
authors: Ubara
authors: Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan.
authors: Takayuki
authors: T
authors: Matsuzaki
authors: Otsuka Pharmaceutical Development & Commercialization, Inc., Rockville, MD, USA.
authors: John
authors: J
authors: Ouyang
authors: Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
authors: Vicente E
authors: VE
authors: Torres
authors: Department of Urology, Juntendo University Graduate School of Medicine, Hongo 3-1-3, Bunkyo-ku, Tokyo, 113-8431, Japan. shorie@juntendo.ac.jp.
authors: Shigeo
authors: S
authors: Horie
mesh_terms: D000293:Adolescent; D000328:Adult; D065092:Antidiuretic Hormone Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D044466:Asian People; D001552:Benzazepines / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D023381:Endpoint Determination; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D007564:Japan; D007668:Kidney / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D016891:Polycystic Kidney, Autosomal Dominant / Q000188:drug therapy* / Q000473:pathology; D000077602:Tolvaptan; D055815:Young Adult
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D000077602:Tolvaptan
keywords: Autosomal dominant polycystic kidney disease; Japanese population; Kidney function decline; TEMPO 3:4 trial; Tolvaptan; Total kidney volume