Abstract: TH-PO0985
Evaluation of Renoprotective Agents and a Metabolic Reprogramming Drug Using Patient-Derived CKD Tubuloids
Session Information
- Transplantation: Basic - Immune Biology, Tissue Injury, and Emerging Technologies
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2001 Transplantation: Basic
Authors
- Mori, Makiko, Department of Nephrology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Bunkyo, Tokyo, Japan
- Sekiguchi, Yuta, Department of Nephrology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Bunkyo, Tokyo, Japan
- Nakao, Yuki, Department of Nephrology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Bunkyo, Tokyo, Japan
- Shindoh, Ryota, Department of Nephrology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Bunkyo, Tokyo, Japan
- Kikuchi, Hiroaki, Department of Nephrology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Bunkyo, Tokyo, Japan
- Arai, Yohei, Department of Nephrology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Bunkyo, Tokyo, Japan
- Ando, Fumiaki, Department of Nephrology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Bunkyo, Tokyo, Japan
- Mandai, Shintaro, Department of Nephrology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Bunkyo, Tokyo, Japan
- Mori, Takayasu, Department of Nephrology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Bunkyo, Tokyo, Japan
- Susa, Koichiro, Department of Nephrology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Bunkyo, Tokyo, Japan
- Sohara, Eisei, Department of Nephrology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Bunkyo, Tokyo, Japan
- Mori, Yutaro, Department of Nephrology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Bunkyo, Tokyo, Japan
Background
Tubular injury and cellular senescence are known to play critical roles in the progression of chronic kidney disease (CKD). However, there are limited human models that accurately recapitulate CKD pathology and allow evaluation of therapeutic responses. We previously established three-dimensional renal tubular organoids (“tubuloids”) derived from patient renal tubular epithelial cells and demonstrated that they reproduce CKD-like phenotypes. In this study, we investigated the therapeutic responses of CKD tubuloids to established renoprotective agents and our newly discovered metabolic reprogramming drug X.
Methods
Primary cultured renal tubular epithelial cells were established from the non-cancerous regions of nephrectomy specimens obtained from normal kidneys, mild CKD kidneys, and dialysis-dependent end-stage kidney disease (ESKD) kidneys. Tubuloids were generated using three-dimensional culture techniques and then treated with SGLT2 inhibitors (empagliflozin and dapagliflozin), the mineralocorticoid receptor antagonist finerenone, the angiotensin II receptor blocker losartan, and X. Morphological changes and immunostaining for KIM-1 and Na/K-ATPase were evaluated.
Results
CKD- and ESKD-derived tubuloids exhibited abnormal morphology, increased KIM-1 and p16 expression, and decreased Na/K-ATPase expression compared with normal tubuloids. Treatment with established renoprotective agents tended to decrease KIM-1 expression and restore Na/K-ATPase expression. In addition, X-treated tubuloids showed morphological improvement and reduced p16 expression, suggesting a protective effect on tubular epithelial structure.
Conclusion
Patient-derived CKD tubuloids may serve as a human disease model capable of reproducing tubular injury and therapeutic responses. Furthermore, this model may be useful as a platform for evaluating not only established renoprotective agents but also novel metabolic therapeutic strategies.