Complement activation and fibrinolysis dysregulation drive contrast-induced acute kidney injury: a 4D proteomics rat study

< 0.05), we identified 180 candidate differentially expressed proteins, including 92 upregulated and 88 downregulated proteins. Pathway-level analyses showed coordinated upregulation of complement-related proteins, including C3/C5 convertase-related components and terminal pathway proteins, such as C9, together with a C4 isoform annotated as C4a in the reference database. Coagulation and fibrinolysis pathways were also markedly altered, including fibrinogen chains (FGA, FGB, FGG), PLAU, SERPINA1, and SERPINF2. In contrast, proteins associated with AMPK and MAPK signaling (including HNF4α, PRKAA2, PRKAB1, and MAP2K3) were reduced. These pathway-level changes were supported by RT-qPCR and immunohistochemical analyses. Collectively, our findings support a multidimensional injury network in rat CI-AKI involving complement activation, coagulation-fibrinolysis dysregulation, and impaired metabolic/stress-response signaling, and provide a proteomic resource for future mechanistic and translational studies.