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Abstract: TH-PO116

Prioritizing Pathways Shared Between Humans and Mice in AKI-to-CKD Transition

Session Information

  • AKI: Mechanisms - I
    November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms


  • Abdank, Kathrien, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
  • Cetin, Sena Zeynep, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
  • Abedini, Amin, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Susztak, Katalin, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Eckardt, Kai-Uwe, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
  • Balzer, Michael S., Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany

Gaps in our understanding of the transition from acute kidney injury (AKI) to chronic kidney disease (CKD) remain a major unmet medical need due to lack of effective therapeutics for CKD in >850 million people worldwide. Pathways with important roles in AKI-to-CKD transition have not been prioritized on a cross-species level, potentially impairing the development of new target approaches and drugs for human kidney disease.


Here, we analyzed recent single-cell datasets from humans with AKI and CKD as well as several mouse models along the AKI-to-CKD spectrum. Using 3 human and 3 mouse datasets generated by different research groups, we performed differential gene expression analysis between disease and physiological conditions. Differentially expressed genes (DEGs) were mapped to orthologous human genes, if necessary, and fed into pathway enrichment analysis, allowing for a standardized, unified comparison of datasets and disease conditions on the pathway level. Finally, we validated our results on 2 separate human and mouse proximal tubule trajectory datasets.


Despite an unexpectedly low overlap among top DEGs of clinically similar models/conditions along the AKI-to-CKD axis (suggesting high disease state specificity), biological processes and pathways along this continuum were well-conserved: processes already enriched during mild AKI, such as hypoxia, TNFα/NFκB signaling, immune processes, epithelial-to-mesenchymal transition, and IL18 signaling, were sustained and increasingly enriched as AKI severity increased and AKI transitioned to CKD. Conversely, cell matrix and adhesion pathways were enriched specifically in milder AKI, whereas solute carrier-mediated ion transport predominated in successfully repaired and healthy control states. Our studies inform on commonalities of human and murine renal pathophysiology after AKI. Nonetheless, our analysis called out inconsistencies and considerable inter-dataset variability, which is important when considering future research prioritizing potential drug targets for people with AKI.


Our studies inform on the consensus of human and murine renal pathophysiology after AKI, call out inconsistencies between single-cell datasets, and are meant to serve as a primer to prioritize efforts for future research in the AKI-to-CKD community.


  • Government Support – Non-U.S.