Skip to main content
SpringerLink
Log in

Long-term administration of tolvaptan ameliorates annual decline in estimated glomerular filtration rate in outpatients with chronic heart failure

  • Original Article
  • Published:
Heart and Vessels Aims and scope Submit manuscript

A Correction to this article was published on 09 March 2021

This article has been updated

Abstract

Protective effects of tolvaptan against worsening renal function in acute heart failure have been shown. However, long-term effects of its agent on renal function remain to be elucidated. The present study investigated retrospectively whether long-term treatment with tolvaptan exerts renoprotective effects in patients with chronic heart failure, by comparing serial changes in estimated glomerular filtration rate (eGFR) for years before and after tolvaptan administration. From 63 outpatients with chronic heart failure taking diuretics including tolvaptan, 34 patients whose eGFR levels were continuously measured for more than 6 months both before and after administration of tolvaptan (average dose, 7.8 mg/day at the end of the follow-up period) were selected as eligible for the present analyses. All eGFR values were separately plotted before and after the initiation of treatment with tolvaptan (except hospitalization periods) along the time course axis and the slope of the linear regression curve was calculated as an annual change in eGFR. The mean follow-up periods before and after tolvaptan administration were 1197 and 784 days (3.3 and 2.1 years), respectively. Changing rates of eGFR per year were significantly ameliorated after treatment with tolvaptan (mean ± SD, − 8.02 ± 9.35 to − 1.62 ± 5.09 mL/min/1.73m2 /year, P = 0.001). In echocardiographic parameters, inferior vena cava (IVC) diameter significantly decreased after tolvaptan administration, and the decrease in IVC diameter was correlated with the improvement of eGFR decline slope after administration of tolvaptan (P = 0.0075). This longitudinal observational study indicated that long-term treatment with tolvaptan ameliorated annual decline in eGFR in outpatients with chronic heart failure. Our findings suggest that tolvaptan has a protective effect against chronically worsening renal function in heart failure patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Change history

References

  1. Damman K, Valente MA, Voors AA, O’Connor CM, van Veldhuisen DJ, Hillege HL (2014) Renal impairment, worsening renal function, and outcome in patients with heart failure: an updated meta-analysis. Eur Heart J 35:455–469

    Article  Google Scholar 

  2. Chen HH, Redfield MM, Nordstrom LJ, Cataliotti A, Burnett JC Jr (2003) Angiotensin II AT1 receptor antagonism prevents detrimental renal actions of acute diuretic therapy in human heart failure. Am J Physiol Renal Physiol 284:F1115–F1119

    Article  CAS  Google Scholar 

  3. Maeder MT, Rickli H, Pfisterer ME, Muzzarelli S, Ammann P, Fehr T, Hack D, Weilenmann D, Dieterle T, Kiencke S, Estlinbaum W, Brunner-La Rocca HP, Investigators TIME-CHF (2012) Incidence, clinical predictors, and prognostic impact of worsening renal function in elderly patients with chronic heart failure on intensive medical therapy. Am Heart J 163:407–414

    Article  Google Scholar 

  4. Ikeda Y, Inomata T, Kida K, Shibagaki Y, Sato N, Izumi T, Ako J, Investigators KA (2019) Different diuretic properties between tolvaptan and furosemide in congestive heart failure patients with diuretic resistance and renal impairment: a subanalysis of the K-STAR. Heart Vessels 34:442–451

    Article  Google Scholar 

  5. Onogawa T, Sakamoto Y, Nakamura S, Nakayama S, Fujiki H, Yamamura Y (2011) Effects of tolvaptan on systemic and renal hemodynamic function in dogs with congestive heart failure. Cardiovasc Drugs Ther 25(Suppl 1):S67–S76

    Article  Google Scholar 

  6. Matsue Y, Suzuki M, Seya M, Iwatsuka R, Mizukami A, Nagahori W, Ohno M, Matsumura A, Hashimoto Y (2013) Tolvaptan reduces the risk of worsening renal function in patients with acute decompensated heart failure in high-risk population. J Cardiol 61:169–174

    Article  Google Scholar 

  7. Kimura K, Momose T, Hasegawa T, Morita T, Misawa T, Motoki H, Izawa A, Ikeda U (2016) Early administration of tolvaptan preserves renal function in elderly patients with acute decompensated heart failure. J Cardiol 67:399–405

    Article  Google Scholar 

  8. Jujo K, Saito K, Ishida I, Furuki Y, Kim A, Suzuki Y, Sekiguchi H, Yamaguchi J, Ogawa H, Hagiwara N (2016) Randomized pilot trial comparing tolvaptan with furosemide on renal and neurohumoral effects in acute heart failure. ESC Heart Fail 3:177–188

    Article  Google Scholar 

  9. Tamaki S, Sato Y, Yamada T, Morita T, Furukawa Y, Iwasaki Y, Kawasaki M, Kikuchi A, Kondo T, Ozaki T, Seo M, Ikeda I, Fukuhara E, Abe M, Nakamura J, Fukunami M (2017) Tolvaptan reduces the risk of worsening renal function in patients with acute decompensated heart failure and preserved left ventricular ejection fraction: prospective randomized controlled study. Circ J 81:740–747

    Article  CAS  Google Scholar 

  10. Yamamoto T, Miura S, Shirai K, Urata H (2019) Renoprotective benefit of tolvaptan in acute decompensated heart failure patients with loop diuretic-resistant status. J Clin Med Res 11:49–55

    Article  CAS  Google Scholar 

  11. Kin H, Matsumura K, Yamamoto Y, Fujii K, Otagaki M, Takahashi H, Park H, Yoshioka K, Yokoi M, Sugiura T, Shiojima I (2020) Renoprotective effect of tolvaptan in patients with new-onset acute heart failure. ESC Heart Fail 7:1764–1770

    Article  Google Scholar 

  12. Mitsui M, Kataoka A, Nara Y, Nagura F, Kawashima H, Hioki H, Nakashima M, Watanabe Y, Yokoyama N, Kozuma K (2019) Clinical safety and efficacy of tolvaptan for acute phase therapy in patients with low-flow and normal-flow severe aortic stenosis. Heart Vessels 34:1684–1691

    Article  Google Scholar 

  13. Otsuka K, Nakanishi K, Shimada K, Nakamura H, Inanami H, Nishioka H, Fujimoto K, Kasayuki N, Yoshiyama M (2018) Associations of sensitive cardiac troponin-I with left ventricular morphology, function and prognosis in end-stage renal disease patients with preserved ejection fraction. Heart Vessels 33:1334–1342

    Article  Google Scholar 

  14. Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, Yamagata K, Tomino Y, Yokoyama H, Hishida A (2009) Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis 53:982–992

    Article  CAS  Google Scholar 

  15. Skupien J, Warram JH, Smiles AM, Stanton RC, Krolewski AS (2016) Patterns of estimated glomerular filtration rate decline leading to end-stage renal disease in type 1 diabetes. Diabetes Care 39:2262–2269

    Article  CAS  Google Scholar 

  16. Vistisen D, Andersen GS, Hulman A, Persson F, Rossing P, Jørgensen ME (2019) Progressive decline in estimated glomerular filtration rate in patients with diabetes after moderate loss in kidney function: even without albuminuria. Diabetes Care 42:1886–1894

    Article  Google Scholar 

  17. Imai E, Horio M, Yamagata K, Iseki K, Hara S, Ura N, Kiyohara Y, Makino H, Hishida A, Matsuo S (2008) Slower decline of glomerular filtration rate in the Japanese general population: a longitudinal 10-year follow-up study. Hypertens Res 31:433–441

    Article  Google Scholar 

  18. Inomata T, Ikeda Y, Kida K, Shibagaki Y, Sato N, Kumagai Y, Shinagawa H, Ako J, Izumi T, Investigators KA (2018) Effects of additive tolvaptan vs. increased furosemide on heart failure with diuretic resistance and renal impairment: results from the K-STAR Study. Circ J 82:159–167

    Article  CAS  Google Scholar 

  19. Kinugawa K, Sato N, Inomata T (2018) Effects of tolvaptan on volume overload in patients with heart failure. Int Heart J 59:1368–1377

    Article  CAS  Google Scholar 

  20. Uemura Y, Shibata R, Takemoto K, Uchikawa T, Koyasu M, Ishikawa S, Mitsuda T, Miura A, Imai R, Iwamiya S, Ozaki Y, Kato T, Miura T, Watarai M, Murohara T (2016) Clinical benefit of tolvaptan in patients with acute decompensated heart failure and chronic kidney disease. Heart Vessels 31:1643–1649

    Article  Google Scholar 

  21. Nakano Y, Mizuno T, Niwa T, Mukai K, Wakabayashi H, Watanabe A, Ando H, Takashima H, Murotani K, Waseda K, Amano T (2018) Impact of continuous administration of tolvaptan on preventing medium-term worsening renal function and long-term adverse events in heart failure patients with chronic kidney disease. Int Heart J 59:105–111

    Article  CAS  Google Scholar 

  22. Ono Y, Takamatsu H, Inoue M, Mabuchi Y, Ueda T, Suzuki T, Kurabayashi M (2018) Clinical effect of long-term administration of tolvaptan in patients with heart failure and chronic kidney disease. Drug Discov Ther 12:154–160

    Article  CAS  Google Scholar 

  23. Imamura T, Kinugawa S, Muramatsu T, Shiga T, Ogimoto A, Anzai T, Hagiwara N, Tsutsui H, Komuro I, Kinugawa K (2019) Long-term tolvaptan treatment in refractory heart failure. Circ Rep 1:431–437

    Article  Google Scholar 

  24. Udelson JE, McGrew FA, Flores E, Ibrahim H, Katz S, Koshkarian G, O’Brien T, Kronenberg MW, Zimmer C, Orlandi C, Konstam MA (2007) Multicenter, randomized, double-blind, placebo-controlled study on the effect of oral tolvaptan on left ventricular dilation and function in patients with heart failure and systolic dysfunction. J Am Coll Cardiol 49:2151–2159

    Article  CAS  Google Scholar 

  25. Konstam MA, Gheorghiade M, Burnett JC Jr, Grinfeld L, Maggioni AP, Swedberg K, Udelson JE, Zannad F, Cook T, Ouyang J, Zimmer C, Orlandi C (2007) Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial. JAMA 297:1319–1331

    Article  CAS  Google Scholar 

  26. Mullens W, Abrahams Z, Francis GS, Sokos G, Taylor DO, Starling RC, Young JB, Tang WHW (2009) Importance of venous congestion for worsening of renal function in advanced decompensated heart failure. J Am Coll Cardiol 53:589–596

    Article  Google Scholar 

  27. Afsar B, Ortiz A, Covic A, Solak Y, Goldsmith D, Kanbay M (2016) Focus on renal congestion in heart failure. Clin Kidney J 9:39–47

    Article  CAS  Google Scholar 

  28. Morooka H, Iwanaga Y, Tamaki Y, Takase T, Akahoshi Y, Nakano Y, Fujiki H, Miyazaki S (2012) Chronic administration of oral vasopressin type 2 receptor antagonist tolvaptan exerts both myocardial and renal protective effects in rats with hypertensive heart failure. Circ Heart Fail 5:484–492

    Article  CAS  Google Scholar 

  29. Ishikawa M, Kobayashi N, Sugiyama F, Onoda S, Ishimitsu T (2013) Renoprotective effect of vasopressin V2 receptor antagonist tolvaptan in Dahl rats with end-stage heart failure. Int Heart J 54:98–106

    Article  CAS  Google Scholar 

  30. Chiba H, Seo Y, Sai S, Namekawa M, Ishizu T, Aonuma K (2019) Renoprotective effects of tolvaptan in hypertensive heart failure rats depend on renal decongestion. Hypertens Res 42:319–328

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Nozomi Matoba (Information Technology Section, Ishikiriseiki Hospital) and Yoko Saito (Education and Research Center, Ishikiriseiki Hospital) for their assistance with collecting patient clinical data.

Funding

None.

Author information

Authors and Affiliations

  1. Department of Cardiovascular Medicine, Ishikiriseiki Hospital, 18-28, Yayoi-cho, Higashi-Osaka, 579-8026, Japan

    Kazuhiro Nakao, Takeshi Horio, Ryutaro Yoshimura, Ryosuke Fujiwara, Yujiro Matsuoka, Go Yokouchi, Haruo Nakamura, Yuya Sakamoto, Kohei Fujimoto & Noriaki Kasayuki

  2. Department of Cardiovascular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan

    Kazuhiro Nakao, Yasuhiro Izumiya & Minoru Yoshiyama

Authors
  1. Kazuhiro Nakao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takeshi Horio
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ryutaro Yoshimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ryosuke Fujiwara
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yujiro Matsuoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Go Yokouchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Haruo Nakamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yuya Sakamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kohei Fujimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yasuhiro Izumiya
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Minoru Yoshiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Noriaki Kasayuki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Takeshi Horio.

Ethics declarations

Conflict of interest

The authors have no conflict of interest to declare.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The original online version of this article was revised due to affiliation 1 was published incorrectly and corrected in this version.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nakao, K., Horio, T., Yoshimura, R. et al. Long-term administration of tolvaptan ameliorates annual decline in estimated glomerular filtration rate in outpatients with chronic heart failure. Heart Vessels 36, 1175–1182 (2021). https://doi.org/10.1007/s00380-021-01801-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00380-021-01801-6

Keywords

Search

Navigation