Kidney Week

Abstract: FR-PO0084

Selective Peroxisome Proliferator-Activated Receptor α Modulator Inhibits Cyst Growth in Two Animal Models of Polycystic Kidney Disease

Session Information

• ADPKD and Cystic Kidney Disease - 2
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1201 Genetic Diseases of the Kidneys: Cystic (Monogenic)

Authors

• Noda, Yuhei, Nagoya Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Nagoya, Aichi Prefecture, Japan

Yuhei Noda, MD, PhD

• Tanabe, Kota, Nagoya Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Nagoya, Aichi Prefecture, Japan

Kota Tanabe, MD

• Kato, Noritoshi, Nagoya Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Nagoya, Aichi Prefecture, Japan

Noritoshi Kato, MD, PhD

• Tanaka, Akihito, Nagoya Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Nagoya, Aichi Prefecture, Japan

Akihito Tanaka, MD, PhD

• Matsuyama, Tetsuya, Nagoya Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Nagoya, Aichi Prefecture, Japan

Tetsuya Matsuyama, MD

• Maeda, Kayaho, Nagoya Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Nagoya, Aichi Prefecture, Japan

Kayaho Maeda, MD

• Furuhashi, Kazuhiro, Nagoya Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Nagoya, Aichi Prefecture, Japan

Kazuhiro Furuhashi, MD, PhD

• Yasuda, Yoshinari, Gifu Daigaku, Gifu, Gifu Prefecture, Japan

Yoshinari Yasuda, MD, PhD

• Kosugi, Tomoki, Nagoya Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Nagoya, Aichi Prefecture, Japan

Tomoki Kosugi, MD, PhD

• Maruyama, Shoichi, Nagoya Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Nagoya, Aichi Prefecture, Japan

Shoichi Maruyama, MD, PhD

Background

Autosomal dominant polycystic kidney disease is one of the most common monogenic disorders, yet effective therapeutic options remain limited. Peroxisomes play important roles in fatty acid oxidation and reactive oxygen species metabolism, and their interactions with mitochondria have recently attracted attention. Peroxisome proliferator-activated receptor-α (PPARα) activity is reduced during renal cyst progression. Although fenofibrate, a PPARα modulator, has demonstrated renoprotective effects in experimental models, its clinical use has been limited by concerns about nephrotoxicity. Pemafibrate, a selective PPARα modulator mainly metabolized in the liver, is considered less likely to induce renal dysfunction. Previously, we demonstrated that pemafibrate suppressed renal and hepatic cyst progression in PCK rats. In this study, we further showed that pemafibrate attenuated renal cyst growth and improved survival in pcy mice.

Methods

In vivo, pemafibrate-containing chow was administered to animal models of cystic kidney disease, including PCK rats and pcy mice. Renal and hepatic function were assessed by blood biochemical analyses in both the control and pemafibrate-treated groups, and renal and hepatic cyst progression was evaluated histologically. In addition, RNA sequencing was performed on tissue samples from each group. Furthermore, metabolomic analyses were conducted using kidney and liver tissues from PCK rats. In vitro, we evaluated the effect of pemafibrate on renal cyst enlargement under 3D culture in MDCK2 cells.

Results

In PCK rats, long-term treatment with pemafibrate suppressed renal cyst growth and improved renal function. Similar suppression of renal cyst progression was observed in the pcy mouse, accompanied by improved survival. RNA sequencing revealed pathway activity patterns characteristic of each tissue. Cyst size reduction was also observed in in vitro 3D culture experiments.

Conclusion

The favorable effects of pemafibrate observed in two animal models of cystic kidney disease, including suppression of renal cyst progression and improved survival, together with findings from cellular experiments, support its potential as a therapeutic strategy for ADPKD. Further studies are needed to evaluate the optimal dosage and safety profile of pemafibrate treatment.

Funding

• Commercial Support – Kowa Company, Ltd., Tokyo, Japan.