Increased urine aquaporin-2 relative to plasma arginine vasopressin is a novel marker of response to tolvaptan in patients with decompensated heart failure

Teruhiko Imamura, Takeo Fujino, Toshiro Inaba, Hisataka Maki, Masaru Hatano, Atsushi Yao, Issei Komuro, Koichiro Kinugawa

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Background: Preserved function of the renal collecting duct may be essential for response to the vasopressin V2 receptor 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 ≥0.5×103 clearly separated the UV-defined responders from the non-responders. We then identified AQP-defined responders as having U-AQP2/P-AVP ≥0.5×103. 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.

Original languageEnglish
Pages (from-to)2240-2249
Number of pages10
JournalCirculation Journal
Volume78
Issue number9
DOIs
Publication statusPublished - Sep 1 2014

Fingerprint

Aquaporin 2
Arginine Vasopressin
Heart Failure
Urine
tolvaptan
Vasopressin Receptors
Propensity Score
ROC Curve
Observation

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Increased urine aquaporin-2 relative to plasma arginine vasopressin is a novel marker of response to tolvaptan in patients with decompensated heart failure. / Imamura, Teruhiko; Fujino, Takeo; Inaba, Toshiro; Maki, Hisataka; Hatano, Masaru; Yao, Atsushi; Komuro, Issei; Kinugawa, Koichiro.

In: Circulation Journal, Vol. 78, No. 9, 01.09.2014, p. 2240-2249.

Research output: Contribution to journalArticle

Imamura, Teruhiko ; Fujino, Takeo ; Inaba, Toshiro ; Maki, Hisataka ; Hatano, Masaru ; Yao, Atsushi ; Komuro, Issei ; Kinugawa, Koichiro. / Increased urine aquaporin-2 relative to plasma arginine vasopressin is a novel marker of response to tolvaptan in patients with decompensated heart failure. In: Circulation Journal. 2014 ; Vol. 78, No. 9. pp. 2240-2249.
@article{78faf323b0a54805a193272836f42c40,
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 V2 receptor 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 ≥0.5×103 clearly separated the UV-defined responders from the non-responders. We then identified AQP-defined responders as having U-AQP2/P-AVP ≥0.5×103. 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.",
author = "Teruhiko Imamura and Takeo Fujino and Toshiro Inaba and Hisataka Maki and Masaru Hatano and Atsushi Yao and Issei Komuro and Koichiro Kinugawa",
year = "2014",
month = "9",
day = "1",
doi = "10.1253/circj.CJ-14-0244",
language = "English",
volume = "78",
pages = "2240--2249",
journal = "Circulation Journal",
issn = "1346-9843",
publisher = "Japanese Circulation Society",
number = "9",

}

TY - JOUR

T1 - Increased urine aquaporin-2 relative to plasma arginine vasopressin is a novel marker of response to tolvaptan in patients with decompensated heart failure

AU - Imamura, Teruhiko

AU - Fujino, Takeo

AU - Inaba, Toshiro

AU - Maki, Hisataka

AU - Hatano, Masaru

AU - Yao, Atsushi

AU - Komuro, Issei

AU - Kinugawa, Koichiro

PY - 2014/9/1

Y1 - 2014/9/1

N2 - Background: Preserved function of the renal collecting duct may be essential for response to the vasopressin V2 receptor 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 ≥0.5×103 clearly separated the UV-defined responders from the non-responders. We then identified AQP-defined responders as having U-AQP2/P-AVP ≥0.5×103. 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.

AB - Background: Preserved function of the renal collecting duct may be essential for response to the vasopressin V2 receptor 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 ≥0.5×103 clearly separated the UV-defined responders from the non-responders. We then identified AQP-defined responders as having U-AQP2/P-AVP ≥0.5×103. 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.

UR - http://www.scopus.com/inward/record.url?scp=84906818882&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84906818882&partnerID=8YFLogxK

U2 - 10.1253/circj.CJ-14-0244

DO - 10.1253/circj.CJ-14-0244

M3 - Article

C2 - 24954239

AN - SCOPUS:84906818882

VL - 78

SP - 2240

EP - 2249

JO - Circulation Journal

JF - Circulation Journal

SN - 1346-9843

IS - 9

ER -