Abstract: FR-PO0174
Splenectomy Impairs Kidney Repair and Modulates B Cell Responses in Ischemic AKI
Session Information
- AKI: Mechanisms - 2
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Lee, Kyungho, Division of Nephrology, Department of Medicine, Samsung Medical Center, Cell and Gene Therapy Institute, Sungkyunkwan University School of Medicine, Seoul, Korea (the Republic of)
- Jeon, Hojin, Division of Nephrology, Department of Medicine, Samsung Medical Center, Cell and Gene Therapy Institute, Sungkyunkwan University School of Medicine, Seoul, Korea (the Republic of)
- Park, Jeehyang, Division of Nephrology, Department of Medicine, Samsung Medical Center, Cell and Gene Therapy Institute, Sungkyunkwan University School of Medicine, Seoul, Korea (the Republic of)
- Lee, Kyungsub, Samsung Advanced Institute for Health Sciences and Technology, Seoul, Korea (the Republic of)
- Jeon, Junseok, Division of Nephrology, Department of Medicine, Samsung Medical Center, Cell and Gene Therapy Institute, Sungkyunkwan University School of Medicine, Seoul, Korea (the Republic of)
- Lee, Jung eun, Division of Nephrology, Department of Medicine, Samsung Medical Center, Cell and Gene Therapy Institute, Sungkyunkwan University School of Medicine, Seoul, Korea (the Republic of)
- Huh, Wooseong, Division of Nephrology, Department of Medicine, Samsung Medical Center, Cell and Gene Therapy Institute, Sungkyunkwan University School of Medicine, Seoul, Korea (the Republic of)
- Jang, Hye Ryoun, Division of Nephrology, Department of Medicine, Samsung Medical Center, Cell and Gene Therapy Institute, Sungkyunkwan University School of Medicine, Seoul, Korea (the Republic of)
Background
Lymphocytes play a role in organ repair and fibrosis. As the spleen is a major reservoir of lymphocytes, splenectomy may influence kidney lymphocyte composition and disrupt immune regulation in AKI. But the role of splenectomy in AKI repair is less understood. We hypothesized that splenectomy affects post-AKI repair and fibrosis by altering spleen-derived kidney immune responses.
Methods
We induced severe ischemic AKI with 45-min unilateral ischemia-reperfusion injury (IRI) surgery in C57BL/6 mice. Mice were divided into two groups: IRI alone and IRI with concurrent splenectomy (IRI+SPX). Kidneys were collected during late recovery phase, at 1 month after AKI. Kidney sections were stained with H&E, Masson’s trichrome, and CD45 immunohistochemistry. Kidney lymphocytes were isolated and analyzed with flow cytometry. Cytokine/chemokine expression was quantified from kidney protein extracts.
Results
Post-AKI kidneys of IRI+SPX group showed greater tubular damage (cortex, IRI alone vs. IRI+SPX, 38.0±3.7% vs. 68.0±8.0%, P=0.032; outer medulla, 38.0±7.4 vs. 82.0±2.0 %, P=0.008) and fibrosis (cortex, 26.0±2.5 vs. 36.0±6.8, P=0.476; outer medulla, 12.0±2.0% vs. 20.0±0.0%, P=0.047) compared to IRI alone group. Leukocyte infiltration was also more pronounced in IRI+SPX group than in IRI alone group (CD45+ cells among total nucleated cells, 4.2±0.5% vs. 8.1±0.7%, P<0.001). While T cell profiles were comparable between groups, splenectomy induced significant changes in B cell composition in post-AKI kidneys. The proportions of activated B cells (9.7±1.2% vs. 19.3±2.6%, P=0.008), MHCII+ B cells (7.0±1.2% vs. 13.6 ± 1.5%, P=0.008), and memory B cells (8.6±0.4 vs. 15.9±0.8%, P=0.008) were significantly higher in post-AKI kidney of IRI+SPX group. Pro-inflammatory and fibrotic cytokine levels, including IL-17 (2.1±0.2 vs. 2.9±0.2pg/mg, P=0.024), CCL2 (170.8±15.1 vs. 226.7±17.2pg/mg, P=0.040), and TGF-β (1122±55.5 vs. 1436±60.2pg/mg, P=0.016), were upregulated in IRI+SPX group compared to IRI alone group.
Conclusion
Splenectomy aggravated tubular injury and fibrosis after AKI and significantly altered kidney immune responses, particularly by reshaping B cell composition. These findings suggest a potential reparative role of the kidney–spleen axis, which may serve as a therapeutic target to mitigate AKI-to-CKD transition.