Heart and Vessels

, Volume 34, Issue 3, pp 442–451 | Cite as

Different diuretic properties between tolvaptan and furosemide in congestive heart failure patients with diuretic resistance and renal impairment: a subanalysis of the K-STAR

  • Yuki Ikeda
  • Takayuki InomataEmail author
  • Keisuke Kida
  • Yugo Shibagaki
  • Naoki Sato
  • Tohru Izumi
  • Junya Ako
  • Kanagawa Aquaresis Investigators
Original Article


We attempted to identify the difference in diuretic properties between tolvaptan (TLV) and furosemide (FUR) in congestive heart failure (CHF) patients with loop diuretic resistance and renal impairment. We investigated 81 CHF patients with loop diuretic treatment and renal impairment included in t he Kanagawa Aquaresis Investigators Trial of Tolvaptan on Heart Failure Patients with Renal Impairment (K-STAR). Predictive baseline factors and their changes during treatment periods were analyzed for correlation with percentage change in urine volume (%ΔUV) after additive introduction of TLV or increasing doses of FUR. Higher urine osmolality at baseline (β = 0.355; p = 0.033) in the TLV group and a lower ratio of blood urea nitrogen to serum creatinine (BUN/Cr, β = − 0.405; p = 0.020) in the FUR group were predictive of higher %ΔUV. Higher Δfree-water clearance (β = 0.667; p < 0.0001) in the TLV group, and higher %ΔBUN/Cr (β = 0.344; p = 0.030), higher %Δurine sodium concentration (β = 0.337; p = 0.037), and lower %Δstroke volume (β = − 0.390; p = 0.017) in the FUR group were correlated with %ΔUV. In conclusion, baseline urine osmolality and change in free-water clearance with additive introduction of TLV and a changing ratio of BUN/Cr with increasing doses of FUR were identified as key clinical parameters related to diuretic response.

Trial registration UMIN000009201.


Heart failure Congestion Diuretic resistance Tolvaptan 



We thank the collaborators and members of the Kanagawa Aquaresis Investigators and investigators at clinical sites for enrolling study patients.[11] The K-STAR was supported by the Kidney Foundation, Japan. Clinical trial registration ID was assigned by the University hospital Medical Information Network (UMIN) as UMIN000009201.

Compliance with ethical standards

Conflict of interest

Dr. Takayuki Inomata received lecture honoraria from Otsuka Pharmaceutical Co. and Daiichi-Sankyo Pharmaceutical. Dr. Yugo Shibagaki received lecture honoraria from Otsuka Pharmaceutical and Novartis Pharma; and research funding from Otsuka Pharmaceutical, Teijin Pharma and Kyowa-Hakko Kirin. Dr. Naoki Sato received consultancy fees from Novartis and Terumo; lecture honoraria from Otsuka, Daiichi-Sankyo, Ono, Eisai, Bayer, Boehringer-Ingelheim, Roche Diagnostics-Japan, Astellas, and Teijin; and research supports to institution from Roche-Japan and Astellas. The other authors have nothing to disclose.


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Copyright information

© Springer Japan KK, part of Springer Nature 2018

Authors and Affiliations

  • Yuki Ikeda
    • 1
  • Takayuki Inomata
    • 2
    Email author
  • Keisuke Kida
    • 3
  • Yugo Shibagaki
    • 4
  • Naoki Sato
    • 5
  • Tohru Izumi
    • 6
  • Junya Ako
    • 1
  • Kanagawa Aquaresis Investigators
  1. 1.Department of Cardiovascular MedicineKitasato University School of MedicineSagamiharaJapan
  2. 2.Department of Cardiovascular MedicineKitasato University Kitasato Institute HospitalTokyoJapan
  3. 3.Division of Cardiology, Department of Internal MedicineSt. Marianna University School of MedicineKawasakiJapan
  4. 4.Division of Nephrology and Hypertension, Department of Internal MedicineSt. Marianna University School of MedicineKawasakiJapan
  5. 5.Internal Medicine and CardiologyNippon Medical School Musashi-Kosugi HospitalKawasakiJapan
  6. 6.Niigata Minami HospitalNiigataJapan

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