Kidney Week

Abstract: FR-PO0351

C5aR Deficiency Attenuates Kidney Ischemia-Reperfusion Injury by Enhancing Lipid Metabolism

Session Information

• AKI: Mechanisms - Metabolism and Repair
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Ma, Jingyuan, The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, Hong Kong

Jingyuan Ma, PhD

• Yiu, Wai Han, The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, Hong Kong

Wai Han Yiu, PhD

• Wong, Siu Chung Jerry, The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, Hong Kong

Siu Chung Jerry Wong, MPhil

• Lam, Derek Kong, The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, Hong Kong

Derek Kong Lam, PhD

• Liu, Dan, The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, Hong Kong

Dan Liu, PhD

• Ruan, Yuyi, The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, Hong Kong

Yuyi Ruan, MBBS, MPhil

• Luo, Xu, The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, Hong Kong

Xu Luo, PhD

• Chen, Min, Peking University First Hospital, Beijing, China

Min Chen, MD, PhD

• Lai, Kar Neng, The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, Hong Kong

Kar Neng Lai, MD, PhD

• Tang, Sydney, The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, Hong Kong

Sydney Tang, MD, MBBS, PhD

Background

Increasing evidence suggests that the complement system plays a pivotal role in metabolism beyond its regulation of innate immunity, though the underlying mechanisms remain poorly understood. Given that lipid accumulation is a known pathogenetic factor in kidney disease, we investigated whether activation of the C5a/C5aR axis contributes to lipid metabolism dysregulation in kidney ischemia-reperfusion injury (IRI)-induced acute kidney injury (AKI).

Methods

Wild type (WT) C5aR^+/+ and knockout (KO) C5aR^-/- mice were subjected to bilateral ischemia-reperfusion injury (BIRI) for 24 hrs. Kidney injury was assessed by evaluating kidney function, histopathological changes and expression levels of pro-inflammatory, oxidative stress and kidney injury markers. Metabolic alterations were further analyzed by RNA sequencing (RNA-seq).

Results

Compared to WT controls, C5aR^-/- KO mice exhibited significant improvement in kidney function with lower serum creatinine levels after BIRI. Along with reduction of inflammation (TNFα and IL6) in KO mice, the expression of cleaved caspase-3 and number of apoptotic tubular cells were significantly decreased, resulting in less tubular injury (Kim1 and Ngal) and preserved morphology. RNA-seq analysis revealed enrichment of pathways related to energy homeostasis including autophagy, AMPK signaling pathway and glycerolipid metabolism, as evidenced by increased expression of the key enzyme in fatty acid oxidation (CPT1) in KO mice. Furthermore, Oil Red O staining showed reduced lipid droplet deposition and expression of the lipid droplet marker PLIN2 in KO mice, and decreased autophagic substrate p62, indicating that C5aR deficiency promotes the activation of lipophagy.

Conclusion

Deficiency of C5aR mitigates IRI-induced kidney damage by reducing lipid accumulation and restoring energy metabolism dysfunction.

Acknowledgment

This project is supported by National Natural Science Foundation of China/RGC Joint Research Scheme (N_HKU7120/24), Health and Medical Research Fund (Health Bureau, grant no. 13242126), Hong Kong Society of Nephrology Research Grant (2025).

Funding

• Government Support – Non-U.S.