Kidney Week

Abstract: TH-PO0155

In Vivo Tracking Reveals Age-Dependent Cell Cycle Response to Kidney Injury

Session Information

• AKI: Mechanisms - 1
  November 06, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Morita, Keisuke, Kyoto Daigaku Daigakuin Igaku Kenkyuka Igakubu, Kyoto, Kyoto Prefecture, Japan

Keisuke Morita, MD

• Iwashige, Yohei, Kyoto Daigaku Daigakuin Igaku Kenkyuka Igakubu, Kyoto, Kyoto Prefecture, Japan

Yohei Iwashige, MD

• Konishi, Ryo, Kyoto Daigaku Daigakuin Igaku Kenkyuka Igakubu, Kyoto, Kyoto Prefecture, Japan

Ryo Konishi

• Ikeda, Hiroyuki, Kyoto Daigaku Daigakuin Igaku Kenkyuka Igakubu, Kyoto, Kyoto Prefecture, Japan

Hiroyuki Ikeda

• Morinishi, Takuya, Kyoto Daigaku Daigakuin Igaku Kenkyuka Igakubu, Kyoto, Kyoto Prefecture, Japan

Takuya Morinishi, MD

• Muro, Koji, Kyoto Daigaku Daigakuin Igaku Kenkyuka Igakubu, Kyoto, Kyoto Prefecture, Japan

Koji Muro, MD

• Yamada, Ryo, Kyoto Daigaku Daigakuin Igaku Kenkyuka Igakubu, Kyoto, Kyoto Prefecture, Japan

Ryo Yamada, MD

• Yamamoto, Shigenori, Kyoto Daigaku Daigakuin Igaku Kenkyuka Igakubu, Kyoto, Kyoto Prefecture, Japan

Shigenori Yamamoto, MD

• Katagiri, Hideki, Tohoku Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Sendai, Miyagi Prefecture, Japan

Hideki Katagiri, MD, PhD

• Yanagita, Motoko, Kyoto Daigaku Daigakuin Igaku Kenkyuka Igakubu, Kyoto, Kyoto Prefecture, Japan

Motoko Yanagita, MD, PhD

Background

A significant number of kidney proximal tubular cells enter the cell cycle following ischemia-reperfusion injury (IRI). However, the correlation between the degree of cell cycle entry and kidney injury at the chronic phase remains inadequately understood.

Methods

We used proximal tubule-specific hKi67p-Gaussia luciferase (Gluc) transgenic mice (Nature Communications. 2023), in which Gluc is driven under human Ki67 promotor, and serum Gluc reflects proximal tubular cell (PTCs)-specific mKi67 transcription via secretion into circulation. We performed unilateral IRI in young and aged transgenic male mice, followed by multiple blood collections for luminescence assays.

Results

Peak increases in Gluc activity were observed on days 2 and 3, with a decrease on day 5. In the 30-min ischemia model, Gluc levels on day14 had returned to approximately the same level as on day 0; while, in the 45-min ischemia model, Gluc levels on day14 did not return to day 0 values. In young mice, the 45-min ischemia model displayed a significantly higher and delayed Gluc peak values compared with the 30-min ischemia model. The area under the curve (AUC) of Gluc up to day 3 post-injury (the Gluc AUC), the indicator of PTCs proliferation during the acute phase, positively correlated with kidney fibrosis in the chronic phase. Interestingly, this correlation was observed more strongly in the 30-min ischemia model than in the 45-min ischemia model, indicating a limited proliferative capacity in response to injury. The AUC of Gluc was smaller in aged mice than that in young mice, while kidney fibrosis was much more severe in aged mice. In addition, the Gluc AUC in aged mice did not correlate with kidney fibrosis, regardless of the severity of kidney injury. Conversely, Gluc levels in the chronic phase showed a significant positive correlation with kidney fibrosis in aged mice.

Conclusion

We identified variations in the cell cycle progression of PTCs and kidney prognosis in young and aged mice following kidney injury. Our analysis will offer insights into the dynamics of the cell cycle response to kidney injury over time and enhance our understanding of its prognostic significance.

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025rvhd9yhd