Multi-omics pathway integration identifies central hub genes involved in the acute kidney injury to chronic kidney disease transition

Understanding the transition from acute kidney injury (AKI) to chronic kidney disease (CKD) requires resolving complex immune-metabolic networks. To define this pathological shift, we integrated transcriptomic and label-free proteomic profiles from a folic acid (FA)-induced mouse model under normal, day 14, and day 28 conditions. Using pathway-level concordance filtering, topological network prioritization, and direct cross-omics comparison, we narrowed systemic alterations to 10 core hub candidates. Functional analysis of these hubs revealed a profound metabolic collapse, characterized by defective fatty acid oxidation and a Warburg-like glycolytic shift along with a self-amplifying immune response driven by neutrophil extracellular traps (NETs) and complement activation. To substantiate these findings, we performed independent ex vivo validation. qPCR analysis of seven representative hub genes confirmed their robust phase-specific regulation. Spatial expression validation based on immunohistochemistry demonstrated a transition-specific condensation of immune activity together with the progressive expansion of profibrotic mediator such as Mmp3 in the damaged interstitium, translating multi-omics signals into histological evidence of maladaptive remodeling. In conclusion, our integrated computational and experimental framework captured the dynamic molecular landscape of the AKI-to-CKD transition and yielded a validated panel of hub genes as putative targets for limiting CKD progression.