Kidney Week

Abstract: FR-PO0088

Longitudinal Changes in miRNAs Involved in Cyst Growth in Polycystic Kidney Disease and Therapeutic Potential of Anti-miRNA Treatment

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

• Tanabe, Kota, Nagoya Daigaku, Nagoya, Aichi Prefecture, Japan

Kota Tanabe, MD

• Kato, Noritoshi, Nagoya Daigaku, Nagoya, Aichi Prefecture, Japan

Noritoshi Kato, MD, PhD

• Noda, Yuhei, Nagoya Daigaku, Nagoya, Aichi Prefecture, Japan

Yuhei Noda, MD, PhD

• Matsuyama, Tetsuya, Nagoya Daigaku, Nagoya, Aichi Prefecture, Japan

Tetsuya Matsuyama, MD

• Tanaka, Akihito, Nagoya Daigaku, Nagoya, Aichi Prefecture, Japan

Akihito Tanaka, MD, PhD

• Maeda, Kayaho, Nagoya Daigaku, Nagoya, Aichi Prefecture, Japan

Kayaho Maeda, MD

• Furuhashi, Kazuhiro, Nagoya Daigaku, Nagoya, Aichi Prefecture, Japan

Kazuhiro Furuhashi, MD, PhD

• Kosugi, Tomoki, Nagoya Daigaku, Nagoya, Aichi Prefecture, Japan

Tomoki Kosugi, MD, PhD

• Kamiya, Yukiko, Kobe Yakka Daigaku, Kobe, Hyogo Prefecture, Japan

Yukiko Kamiya, PhD

• Shimizu, Shinobu, Nagoya Daigaku, Nagoya, Aichi Prefecture, Japan

Shinobu Shimizu, PhD

• Asanuma, Hiroyuki, Nagoya Daigaku, Nagoya, Aichi Prefecture, Japan

Hiroyuki Asanuma, DrPH

• Maruyama, Shoichi, Nagoya Daigaku, Nagoya, Aichi Prefecture, Japan

Shoichi Maruyama, MD, PhD

Background

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited kidney diseases, but limited therapeutic options are available. Recent studies have revealed that aberrantly overexpressed miRNA contribute to cyst enlargement and may serve as therapeutic targets. Anti-miR-17 oligonucleotide therapy has successfully completed Phase 1b clinical trial. Separately, we have also reported therapeutic efficacy of anti-miR-21 oligonucleotide therapy. However, there is currently limited evidence regarding the optimal timing for initiating anti-miRNA therapy.

Methods

Using a spontaneous model of polycystic kidney disease, we evaluated the longitudinal kidney expression changes of miR-17 and miR-21 to identify the optimal timing for therapeutic intervention. Other than miR-17 and miR-21, we performed a temporal analysis of several miRNAs which are known to involved in cyst growth using wild-type and pcy mice at 4, 10, and 15 weeks of age. We also explore these miRNAs longitudinal expression in PCK rat kidney and liver. Then, we conducted a 6-week treatment study in pcy mice from 4w to 10w using anti-miR-21 oligonucleotide synthesized from SNA (serinol nucleic acid).

Results

In pcy mice, renal expression of both miR-21 and miR-17 increased progressively from 4w to 10w, correlating with disease advancement compared to age-matched wild-type controls. On the other hand, both miRNA expression was reduced at 15w. Notably, even at 4 weeks of age, when renal cyst formation remained limited, miR-17 and miR-21 expression levels were already markedly elevated by 4.4-fold and 11-fold, respectively compared with wild-type mice. In vivo experiment, anti-miR-21 therapy from early stage (4w) effectively suppressed cyst growth.

Conclusion

Many cyst growth–associated miRNAs exhibited altered intrarenal expression even before overt cyst enlargement developed. Therefore, imaging modalities alone, including kidney volume assessment, may be insufficient for determining the optimal timing of anti-miRNA therapeutic intervention, underscoring the need for reliable biomarkers.