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Initial decline in eGFR to predict tolvaptan response in autosomal-dominant polycystic kidney disease

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Abstract

Background

Tolvaptan, a vasopressin V2 receptor antagonist, is used to treat autosomal-dominant polycystic kidney disease (ADPKD). Although tolvaptan curbs disease progression, a few reports have examined factors related to treatment response. The estimated glomerular filtration rate (eGFR) decreases soon after tolvaptan is initiated. We investigated whether initial eGFR decline affects renal prognosis of patients.

Methods

This was a single-center, retrospective observational cohort study. Eighty-three patients with ADPKD who initiated tolvaptan were selected. We analyzed the relationship of the initial eGFR change with clinical parameters and analyzed the annual eGFR change in terms of renal prognostic value using univariable and multivariable linear regression analyses.

Results

The initial eGFR change was − 4.6 ± 8.0%/month. The initial eGFR change correlated significantly with the annual eGFR change in multivariable analysis, suggesting that the larger decline in the initial eGFR change, the better the renal prognosis. Furthermore, the change in fractional excretion (FE) of free water (FEH2O) correlated positively with initial eGFR change. FEH2O and urea nitrogen FE (FEUN) increased significantly; however, sodium FE (FENa) level remained unchanged. In approximately half of the patients, FENa unexpectedly decreased.

Conclusions

The initial eGFR decline might be caused by suppressing glomerular hyperfiltration, due to the pharmacological effect of tolvaptan, and/or by reducing renal plasma flow, due to potential volume depletion. The initial eGFR change reflects the tolvaptan effect, can be easily evaluated in clinical practice, and may be useful as one of the clinical indicator for predicting renal prognosis in patients under tolvaptan.

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Acknowledgements

We express our sincere appreciation to all the patients, collaborating physicians, and other medical staff for their important contributions to the study. This study was supported in part by a Grant-in-Aid for Intractable Renal Diseases Research, Research on rare and intractable diseases, Health and Labor Sciences Research Grants from the Ministry of Health, Labor and Welfare of Japan.

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Authors and Affiliations

  1. Department of Nephrology, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan

    Taro Akihisa, Hiroshi Kataoka, Shiho Makabe, Shun Manabe, Rie Yoshida, Yusuke Ushio, Masayo Sato, Toshio Mochizuki & Kosaku Nitta

  2. Department of Blood Purification, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan

    Ken Tsuchiya

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  1. Taro Akihisa
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Correspondence to Toshio Mochizuki.

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Conflict of interest

Toshio Mochizuki received honoraria for lectures from Otsuka Pharmaceutical Co. Toshio Mochizuki and Hiroshi Kataoka belong to an endowed department sponsored by Otsuka Pharmaceutical Co, Chugai Pharmaceutical Co, Kyowa Kirin Co, and JMS Co.

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All procedures involving human participants were performed in accordance with the ethical standards of the institutional research committee of Tokyo Women’s Medical University (IRB approval number 5118) and with the tenets of the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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

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Akihisa, T., Kataoka, H., Makabe, S. et al. Initial decline in eGFR to predict tolvaptan response in autosomal-dominant polycystic kidney disease. Clin Exp Nephrol 26, 540–551 (2022). https://doi.org/10.1007/s10157-022-02192-2

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  • DOI: https://doi.org/10.1007/s10157-022-02192-2

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