title: Novel criteria of urine osmolality effectively predict response to tolvaptan in decompensated heart failure patients--association between non-responders and chronic kidney disease.
abstract: BACKGROUND
  A newly-developed vasopressin type 2 receptor antagonist, tolvaptan (TLV), has a unique feature of diuresis, but the response to this drug can be unpredictable.
  
  
  RESULTS
  Data were collected from hospitalized patients with decompensated congestive heart failure who were administered TLV at 3.75-15 mg/day (n=61). A responder/non-responder to TLV was determined as having any increase/decrease in urine volume (UV) during the next 24h after TLV treatment on the first day. Logistic regression analyses for increases in UV were performed, and independent predictors of the responder were the following: C1, baseline urine osmolality (U-OSM) >352 mOsm/L; and C2, %decrease in U-OSM >26% at 4-6h after TLV administration. Criteria consisting of C1 and C2 had a good predictability for responders by receiver-operating characteristic analysis (area under the curve=0.960). Kidneys of the non-responders no longer had diluting ability (%decrease of U-OSM at 4-6h=2.7 ± 14.6%*), but also barely kept concentrating ability (baseline U-OSM=296.4 ± 68.7*mOsm/L) with markedly reduced estimated glomerular filtration ratio (35.5 ± 29.4 m l · min(-1) · 1.73 m(-2)*) (*P<0.05 vs. patients who had at least 1 positive condition [n=42]).
  
  
  CONCLUSIONS
  More than 26% decrease in U-OSM from a baseline >352 mOsm/L for the first 4-6h predicts responders to TLV. Unresponsiveness to TLV is attributable to nephrogenic diabetes insipidus complicated by chronic renal disease.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Imamura
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kinugawa
authors.forename: Taro
authors.initials: T
authors.lastname: Shiga
authors.forename: Naoko
authors.initials: N
authors.lastname: Kato
authors.forename: Hironori
authors.initials: H
authors.lastname: Muraoka
authors.forename: Shun
authors.initials: S
authors.lastname: Minatsuki
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: Shunei
authors.initials: S
authors.lastname: Kyo
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines / Q000627:therapeutic use*; D001806:Blood Urea Nitrogen; D003401:Creatine / Q000097:blood / Q000652:urine; D018500:Diabetes Insipidus, Nephrogenic / Q000188:drug therapy / Q000652:urine*; D004232:Diuretics / Q000008:administration & dosage; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000652:urine*; D006801:Humans; D020896:Hypovolemia / Q000188:drug therapy / Q000652:urine; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D011188:Potassium / Q000097:blood / Q000652:urine; D011237:Predictive Value of Tests; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy / Q000652:urine; D012680:Sensitivity and Specificity; D012964:Sodium / Q000097:blood / Q000652:urine; D000077602:Tolvaptan; D014463:Ultrasonography; D014556:Urine; D055815:Young Adult
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D004232:Diuretics; D000077602:Tolvaptan; D012964:Sodium; D003401:Creatine; D011188:Potassium