Abstract: FR-PO1082
The Pathogenic Role of C5a/C5aR Axis in AKI-to-CKD Transition
Session Information
- CKD Mechanisms: Progression, Fibrosis, and Beyond
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Ma, Jingyuan, The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, Hong Kong
- Yiu, Wai Han, The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, Hong Kong
- Lok, Sarah W.Y., The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, Hong Kong
- Zou, Yixin, The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, Hong Kong
- Feng, Yuchen, The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, Hong Kong
- Lai, Kar Neng, The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, Hong Kong
- Tang, Sydney C.W., The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, Hong Kong
Background
Activation of complement C5a/C5aR axis contributes to the pathogenesis of acute kidney injury (AKI). However, whether it plays a role in the transition to chronic kidney disease (CKD) after AKI remains unclear. In this study, we investigated the chronic effects of bilateral ischemia-reperfusion injury on C5aR deficient mice and dissected C5aR-dependent mechanisms during AKI-to-CKD transition.
Methods
Wild type C5aR+/+ and knockout C5aR-/- mice were subjected to bilateral ischemia and sacrificed at day 3 and 7 after reperfusion. Kidney damage was assessed by evaluating kidney function, histopathological changes and expression levels of pro-inflammatory, fibrotic, oxidative and injury markers.
Results
Compared to the C5aR+/+ controls, C5aR-/- mice showed significant decrease in serum creatinine and reduced expressions of Kim1 and Ngal in both the 3-day and 7-day BIRI models. The improvement in kidney injury in BIRI C5aR-/- mice was further confirmed by PAS staining. The expression levels of MCP-1, TNF-α, IL-6 and IL-1b were significantly decreased in C5aR-/- mice after BIRI. In particular, there was decreased infiltration of M1 macrophages with an increase in M2 macrophage number in C5aR-/- mice on day 7 after reperfusion. Sirius red and Masson Trichrome staining demonstrated a progressive development of interstitial fibrosis in C5aR+/+ mice after BIRI, which were suppressed in C5aR-/- mice with less deposition of collagen 1 and collagen 3 in the post-ischemic kidneys. Moreover, the oxidative stress markers NOX2 and 8-OHdG were significantly reduced in C5aR-/- mice after BIRI.
Conclusion
C5aR deficiency protected mice from kidney inflammation and fibrosis by reducing oxidative stress during AKI-to-CKD transition.
Funding: Research Grants Council of Hong Kong (General Research Fund, grant no. 17108222), Hong Kong Society of Nephrology Research Grant (2021)