Cross-species transcriptomic insights into the maladaptive transition from acute kidney injury to chronic kidney disease
Description
Chronic kidney disease (CKD) affects an estimated 37 million adults in the United States, with approximately 15% of the population showing evidence of disease. Acute kidney injury (AKI) is a major contributor to CKD development and progression to end-stage kidney disease. AKI can induce CKD through a complex interplay of maladaptive responses that remain incompletely understood. In this study, we aimed to advance understanding of the molecular pathways driving the transition from AKI to CKD. We conducted a comparative analysis of 16 published transcriptomic datasets on AKI and CKD across human, rat, and mouse models. Differentially expressed genes (DEGs) were identified using a cutoff of at least 1.5-fold change for downstream analysis. KEGG pathway enrichment analysis was then performed using p and q value thresholds of 0.05 to identify both conserved and unique pathways and their associated genes across species. Our analysis revealed five overarching pathway categories: cellular processes, metabolism, organismal systems, genetic information processing, and environmental information processing. Within these categories, we identified 226 conserved pathways associated with metabolic alterations, immune dysregulation, and aberrant cellular stress responses, including those implicated in IL-17 and PI3K-Akt signaling. Furthermore, we discovered 141 unique pathways including ErbB signaling pathway, necroptosis, and NOD-like receptor signaling that were enriched in CKD models but not AKI. This comparative analysis identifies conserved pathways that may contribute to the maladaptive transition from AKI to CKD, along with variable molecular pathways that may provide opportunities for targeted interventions to slow disease progression and reduce the burden of CKD.
Citation Information
Nemcek, Mark; Suda, Parik G.; Mulder, Lane C.; Babich, Victor; and Di Sole, Francesca, "Cross-species transcriptomic insights into the maladaptive transition from acute kidney injury to chronic kidney disease" (2026). Office of Research DMU Research Symposium. 71.
https://digitalcommons.dmu.edu/researchsymposium/2025rs/2025abstracts/71
Cross-species transcriptomic insights into the maladaptive transition from acute kidney injury to chronic kidney disease
Chronic kidney disease (CKD) affects an estimated 37 million adults in the United States, with approximately 15% of the population showing evidence of disease. Acute kidney injury (AKI) is a major contributor to CKD development and progression to end-stage kidney disease. AKI can induce CKD through a complex interplay of maladaptive responses that remain incompletely understood. In this study, we aimed to advance understanding of the molecular pathways driving the transition from AKI to CKD. We conducted a comparative analysis of 16 published transcriptomic datasets on AKI and CKD across human, rat, and mouse models. Differentially expressed genes (DEGs) were identified using a cutoff of at least 1.5-fold change for downstream analysis. KEGG pathway enrichment analysis was then performed using p and q value thresholds of 0.05 to identify both conserved and unique pathways and their associated genes across species. Our analysis revealed five overarching pathway categories: cellular processes, metabolism, organismal systems, genetic information processing, and environmental information processing. Within these categories, we identified 226 conserved pathways associated with metabolic alterations, immune dysregulation, and aberrant cellular stress responses, including those implicated in IL-17 and PI3K-Akt signaling. Furthermore, we discovered 141 unique pathways including ErbB signaling pathway, necroptosis, and NOD-like receptor signaling that were enriched in CKD models but not AKI. This comparative analysis identifies conserved pathways that may contribute to the maladaptive transition from AKI to CKD, along with variable molecular pathways that may provide opportunities for targeted interventions to slow disease progression and reduce the burden of CKD.
