title: Increased urine aquaporin-2 relative to plasma arginine vasopressin is a novel marker of response to tolvaptan in patients with decompensated heart failure.
abstract: BACKGROUND
  Preserved function of the renal collecting duct may be essential for response to the vasopressin V2receptor antagonist, tolvaptan (TLV), but the predictors of response to TLV are unknown. METHODS AND RESULTS: Sixty consecutive patients with stage D decompensated heart failure (HF) who had received TLV on a de novo basis were retrospectively enrolled (TLV(+) group). Among them, 41 patients were responders defined according to urine volume (UV) increase after TLV initiation. In the UV-defined responders, plasma arginine vasopressin (P-AVP) had a close correlation with urine aquaporin-2 (U-AQP2; 5.42±3.54 ng/ml; r=0.843, P<0.001). In contrast, 19 were UV-defined non-responders, and they had extremely low U-AQP2 (0.76±0.59 ng/ml, P<0.001 vs. responders) regardless of P-AVP level. On receiver operating characteristic analysis, U-AQP2/P-AVP ≥0.5×10(3)clearly separated the UV-defined responders from the non-responders. We then identified AQP-defined responders as having U-AQP2/P-AVP ≥0.5×10(3). Sixty propensity score-matched HF patients without TLV treatment were examined, and exactly the same number of patients as that of the AQP-defined responders (n=41) was selected. These patients had a poorer survival without TLV than the TLV-treated responders during a 2-year observation period (73.8% vs. 94.8%, P=0.034).
  
  
  CONCLUSIONS
  U-AQP2/P-AVP is a novel predictor of response to TLV in patients with decompensated HF. AQP-defined responders may have a better prognosis on TLV treatment.
authors: Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo.
authors: Teruhiko
authors: T
authors: Imamura
authors: Koichiro
authors: K
authors: Kinugawa
authors: Takeo
authors: T
authors: Fujino
authors: Toshiro
authors: T
authors: Inaba
authors: Hisataka
authors: H
authors: Maki
authors: Masaru
authors: M
authors: Hatano
authors: Atsushi
authors: A
authors: Yao
authors: Issei
authors: I
authors: Komuro
mesh_terms: D000328:Adult; D000368:Aged; D065092:Antidiuretic Hormone Receptor Antagonists / Q000008:administration & dosage*; D051399:Aquaporin 2 / Q000652:urine*; D001127:Arginine Vasopressin / Q000097:blood*; D001552:Benzazepines / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D018572:Disease-Free Survival; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy / Q000378:metabolism / Q000652:urine; D006801:Humans; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D000077602:Tolvaptan
chemical_list: C496023:AQP2 protein, human; D065092:Antidiuretic Hormone Receptor Antagonists; D051399:Aquaporin 2; D001552:Benzazepines; D015415:Biomarkers; D001127:Arginine Vasopressin; D000077602:Tolvaptan