Abstract: FR-PO0680
Selective Peroxisome Proliferator-Activated Receptor-α (PPARα) Modulator Inhibits Cyst Enlargement in PKD
Session Information
- Cystic Kidney Diseases: Basic and Translational Research
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases
Authors
- Noda, Yuhei, Nagoya Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Nagoya, Aichi Prefecture, Japan
- Kato, Noritoshi, Nagoya Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Nagoya, Aichi Prefecture, Japan
- Yasuda, Yoshinari, Gifu Daigaku, Gifu, Gifu Prefecture, Japan
- Maruyama, Shoichi, Nagoya Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Nagoya, Aichi Prefecture, Japan
Background
Autosomal dominant polycystic kidney disease (ADPKD) is one of the most frequent single-gene disorders. Nevertheless, therapeutic agents for polycystic kidney disease remain limited, and the search for new therapeutic intervention points is essential. The peroxisome is one of the intracellular organelles responsible for cellular metabolic functions such as the oxidation of fatty acids and the removal of reactive oxygen species. The interactions with mitochondria have also been increasingly emphasized. It is known that peroxisome proliferator-activated receptor-α (PPARα) activity, a nuclear receptor of peroxisome, is decreased during renal cyst enlargement. Although fenofibrate, a PPARα modulator, has been reported to suppress renal cyst enlargement, it has not yet been applied clinically due to concerns about renal metabolism and nephrotoxicity. This study focused on pemafibrate, a selective PPARα modulator, because its main metabolic pathway is in the liver and is generally considered less likely to cause renal dysfunction. We used this selective PPARα modulator, pemafibrate, to evaluate its effects on renal and hepatic cysts in vitro and in vivo trials.
Methods
In vivo study, a mixed diet was prepared using pemafibrate and administered to a cystic kidney rat model (PCK rat). Renal and hepatic functions were evaluated by blood tests in the control and pemafibrate treated groups, and we evaluated renal cysts, hepatic cysts, and kidney fibrosis histologically. In vitro, we evaluated the effect of pemafibrate on renal cyst enlargement under 3D culture in MDCK2 cells, which generally used in cystic kidney suppression experiments.
Results
In a rat model of cystic kidney disease, long-term treatment with pemafibrate suppressed the growth of renal cysts and improved renal function. Cyst size reduction was also observed in in vitro 3D culture experiment.
Conclusion
The favorable effects of pemafibrate in animal models of cystic kidney disease and cellular experiments demonstrated its potential as a clinical treatment for ADPKD. We will evaluate the optimal dosage and toxicity of pemafibrate treatment.
Funding
- Commercial Support – Kowa Company, Ltd., Tokyo, Japan.