Impact of serum albumin levels on the body fluid response to tolvaptan in chronic kidney disease patients

  • Takahiro MasudaEmail author
  • Ken Ohara
  • Izumi Nagayama
  • Ryo Matsuoka
  • Takuya Murakami
  • Saki Nakagawa
  • Kentanro Oka
  • Maki Asakura
  • Yusuke Igarashi
  • Yukimura Fukaya
  • Yasuharu Miyazawa
  • Akito Maeshima
  • Tetsu Akimoto
  • Osamu Saito
  • Daisuke Nagata
Nephrology - Original Paper



Tolvaptan exerts an aquaretic effect by blocking vasopressin V2 receptor. Although tolvaptan ameliorates body fluid retention even in patients with chronic kidney disease (CKD), predictors of body fluid reduction induced by tolvaptan remain unclear. We, therefore, examined the clinical parameters associated with the effect of tolvaptan on fluid volume in CKD patients.


Twelve CKD patients (stage 3–5) with fluid retention were treated with tolvaptan in addition to conventional diuretic treatment. Patients were divided into low and high responders by the median change in total body water (TBW) for 1 week measured by a bioimpedance analysis (BIA) device, and clinical parameters were compared between the groups.


The body weight significantly decreased by 2.0 ± 2.3 kg (p = 0.005), but the estimated glomerular filtration rate (eGFR) was not significantly changed (16.9 ± 11.9 vs. 17.4 ± 12.4 mL/min/1.73 m2, p = 0.139) after 1 week. The BIA showed that the intracellular water (ICW) decreased by 6.0% ± 4.7% (p < 0.001), the extracellular water (ECW) decreased by 6.7% ± 5.4% (p = 0.001), and the TBW decreased by 6.3% ± 4.9% (median value − 6.02%, p < 0.001). The serum albumin level in the high responders was significantly lower than in the low responders (2.3 ± 0.5 vs. 3.3 ± 0.8 g/dL, p = 0.013). Significant partial correlations adjusted for the eGFR were observed between the baseline serum albumin level and changes in the ICW (r = 0.440, p = 0.048), ECW (r = 0.593, p = 0.009) and TBW (r = 0.520, p = 0.020).


Serum albumin levels predict the body fluid response to tolvaptan in CKD patients. Tolvaptan may be a promising therapeutic option for ameliorating body fluid retention, especially in patients with hypoalbuminemia.


Tolvaptan Hypoalbuminemia Bioimpedance analysis Volume overload Fluid retention Responder 



We thank Kazuya Kikuchi (Nasu Minami Hospital) for his technical support and Takashi Fujita (Jichi Medical University) for his critical advice.

Author contributions

TMa conceived and designed the study. TMa, KOh, IN, TMu, SN, KOk, MA, YI and YF performed the data collection. TMa and KOh conducted the data analysis. TMa drafted the manuscript. TMa, IN, and RM interpreted results of the analysis. YM, AM, TA, OS and DN approved the final version of manuscript.


This study was supported in part by Jichi Medical University Young Investigator Award and a Grant-in-Aid for Research on Advanced Chronic Kidney Disease, Practical Research Project for Renal Diseases from the Japan Agency for Medical Research and Development (AMED).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Ethics approval

The study was approved by the Ethics Committees of Jichi Medical University (Shimotsuke, Japan) and Nasu Minami Hospital (Nasukarasuyama, Japan).

Informed consent

Informed consent was obtained from all individual participants included in the study.

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Takahiro Masuda
    • 1
    Email author
  • Ken Ohara
    • 1
  • Izumi Nagayama
    • 1
  • Ryo Matsuoka
    • 2
  • Takuya Murakami
    • 1
  • Saki Nakagawa
    • 1
  • Kentanro Oka
    • 1
  • Maki Asakura
    • 1
  • Yusuke Igarashi
    • 1
  • Yukimura Fukaya
    • 3
  • Yasuharu Miyazawa
    • 3
  • Akito Maeshima
    • 1
  • Tetsu Akimoto
    • 1
  • Osamu Saito
    • 1
  • Daisuke Nagata
    • 1
  1. 1.Division of Nephrology, Department of Internal MedicineJichi Medical UniversityShimotsukeJapan
  2. 2.Department of Clinical EngineeringJichi Medical UniversityShimotsukeJapan
  3. 3.Department of Internal MedicineNasu Minami HospitalNasukarasuyamaJapan

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