Open-Label, Randomized, Controlled, Crossover Trial on the Effect of Dapagliflozin in Patients With ADPKD Receiving Tolvaptan

Kiyotaka Uchiyama; Daisuke Kamano; Tomoki Nagasaka; Eriko Yoshida Hama; Ryoichi Shirai; Rena Sumura; Ei Kusahana; Akane Yanai; Takashin Nakayama; Takahide Kimura; Rina Takahashi; Takahiro Kasai; Takaya Tajima; Koji Hosoya; Tatsuhiko Azegami; Shintaro Yamaguchi; Jun Yoshino; Jun Ito; Matsuhiko Hayashi; Takeshi Kanda; Yoshitaka Ishibashi; Naoki Washida; Hiroshi Itoh; Kaori Hayashi

doi:10.1016/j.ekir.2025.01.023

Open-Label, Randomized, Controlled, Crossover Trial on the Effect of Dapagliflozin in Patients With ADPKD Receiving Tolvaptan

Kidney Int Rep. 2025 Jan 18;10(4):1063-1075. doi: 10.1016/j.ekir.2025.01.023. eCollection 2025 Apr.

Authors

Kiyotaka Uchiyama^{1

2}, Daisuke Kamano², Tomoki Nagasaka³, Eriko Yoshida Hama³, Ryoichi Shirai², Rena Sumura², Ei Kusahana³, Akane Yanai⁴, Takashin Nakayama³, Takahide Kimura⁵, Rina Takahashi³, Takahiro Kasai⁵, Takaya Tajima³, Koji Hosoya⁶, Tatsuhiko Azegami³, Shintaro Yamaguchi³, Jun Yoshino⁷, Jun Ito¹, Matsuhiko Hayashi⁸, Takeshi Kanda⁷, Yoshitaka Ishibashi², Naoki Washida¹, Hiroshi Itoh³, Kaori Hayashi³

Affiliations

¹ Department of Nephrology, International University of Health and Welfare Narita Hospital, Chiba, Japan.
² Department of Nephrology, Japanese Red Cross Medical Center, Tokyo, Japan.
³ Division of Endocrinology, Metabolism and Nephrology Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
⁴ Department of Nephrology, Tokyo Shinagawa Hospital, Tokyo, Japan.
⁵ Department of Nephrology, International University of Health and Welfare Atami Hospital, Shizuoka, Japan.
⁶ Department of Nephrology, International University of Health and Welfare Hospital, Tochigi, Japan.
⁷ Division of Nephrology, Shimane University Hospital, Shimane, Japan.
⁸ Department of Nephrology, Kawakita General Hospital, Tokyo, Japan.

Abstract

Introduction: Although dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, delays the progression of chronic kidney disease (CKD), its effect on patients with autosomal dominant polycystic kidney disease (ADPKD) has not been established. We conducted an open-label, randomized controlled crossover trial to evaluate the additive effects of dapagliflozin in patients with ADPKD receiving tolvaptan.

Methods: A total of 27 patients were randomly counterbalanced to receive dapagliflozin 10 mg or usual care without dapagliflozin for 6 months. The primary endpoint was the slope of the estimated glomerular filtration rate (eGFR) determined by linear regression from 1 to 6 months, and the secondary endpoints included changes in total kidney volume (TKV). eGFR was calculated based on creatinine levels (eGFR_cr), cystatin C levels (eGFR_cys), and the mean of eGFR_cr and eGFR_cys (eGFR_cr-cys).

Results: There were significant attenuations in the eGFR_cr-cys and eGFR_cys slopes during the dapagliflozin trial compared with the one without dapagliflozin (2.57 ± 7.88 vs. -5.65 ± 9.57 ml/min per 1.73 m² per year, P = 0.002; 3.91 ± 11.40 vs. -8.43 ± 13.44 ml/min per 1.73 m² per year, P = 0.003, respectively). Meanwhile, the eGFR_cr slope was potentially moderate during the trial with dapagliflozin (1.03 ± 10.78 vs. -3.66 ± 8.88 ml/min per 1.73 m² per year, P = 0.06). The 6-month change in TKV was significantly attenuated during the trial with dapagliflozin compared with the one without dapagliflozin (-0.44 ± 4.91% vs. 5.04 ± 8.09%, P = 0.01).

Conclusion: In patients with ADPKD treated with tolvaptan, dapagliflozin may have an additive effect in slowing ADPKD progression.

Keywords: autosomal dominant polycystic kidney disease; dapagliflozin; estimated glomerular filtration rate; sodium–glucose cotransporter 2 inhibitor; tolvaptan; total kidney volume.