Kidney Week

Abstract: TH-OR102

Restoring Glycine Amidinotransferase (GATM) via Extracellular Vesicles Mitigates Kidney Fibrosis and Prevents AKI-to-CKD Transition in Kidney Transplantation

Session Information

• The Next Frontier in Kidney Transplantation: Omics, Gene Editing, and Precision Medicine
  October 22, 2026 | Location: Mile High Ballroom 4A, Convention Center
  Abstract Time: 04:50 PM - 05:00 PM

Category: Transplantation

• 2001 Transplantation: Basic

Authors

• Zhao, Shengji, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea (the Republic of)

Shengji Zhao, MS, MSc

• Cho, Bo Gyeong, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea (the Republic of)

Bo Gyeong Cho

• Li, Dazhong, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea (the Republic of)

Dazhong Li, MBBS

• Choi, Da Som, Seoul National University Seoul Metropolitan Government Boramae Medical Center, Dongjak-gu, Seoul, Korea (the Republic of)

Da Som Choi, MD

• Lee, Jeonghwan, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea (the Republic of)

Jeonghwan Lee, MD, PhD

• Lee, Jung Pyo, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea (the Republic of)

Jung Pyo Lee, MD, PhD

Background

Kidney transplantation is an effective treatment for end-stage kidney disease; however, borderline rejection (BDR) and ischemia–reperfusion injury (IRI) can lead to allograft fibrosis and functional decline. This study integrates a clinical cohort with experimental models to identify key metabolic checkpoints and explore targeted therapeutic strategies.

Methods

We analyzed 156 longitudinal urine samples from a prospective cohort of 51 BDR patients using NMR-based untargeted metabolomics to identify metabolic signatures associated with graft decline. Integrated single-cell RNA sequencing (scRNA-seq) was performed on a murine unilateral IRI (uIRI) model to map cell-specific metabolic alterations. Furthermore, we engineered GATM-enriched extracellular vesicles (GATM-EVs) and evaluated their therapeutic efficacy in stress-induced HK-2 cells and a 2-week uIRI model, which specifically represents the critical AKI-to-CKD transition phase.

Results

Untargeted metabolomics identified urinary guanidinoacetate (GAA) downregulation as a core metabolic signature in patients at risk of subsequent graft dysfunction. scRNA-seq showed that GAA-synthesizing rate-limiting enzyme GATM is exclusively expressed in proximal tubule cells; its expression dropped drastically after uIRI, correlating with injury severity and maladaptive repair cell accumulation. In vitro, oxidative stress and hypoxia inhibited GATM expression dose-dependently, whereas GATM-EVs efficiently restored GATM and cellular metabolic function. In the uIRI model, GATM-EV treatment alleviated renal fibrosis, reduced pro-fibrotic markers including COL1A1, recovered renal GATM to near baseline, and blocked progression to chronic kidney disease.

Conclusion

Our findings demonstrate that GATM deficiency is a metabolic driver of the AKI-to-CKD transition in transplanted kidneys. Replenishing GATM via targeted EV delivery not only mitigates renal fibrosis but also restores metabolic homeostasis, offering a promising and novel therapeutic strategy to improve long-term kidney allograft survival.

Acknowledgment

This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIT) (RS-2025-00554766)

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number : RS-2025-25459975)

Funding

• Government Support – Non-U.S.