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Longitudinal tracking of acute kidney injury reveals injury propagation along the nephron

Author

Listed:
  • Luca Bordoni

    (Aarhus University
    University of Oslo)

  • Anders M. Kristensen

    (Aarhus University)

  • Donato Sardella

    (Aarhus University)

  • Hanne Kidmose

    (Aarhus University)

  • Layla Pohl

    (Aarhus University)

  • Søren Rasmus Palmelund Krag

    (Aarhus University Hospital)

  • Ina Maria Schiessl

    (Aarhus University)

Abstract

Acute kidney injury (AKI) is an important risk factor for chronic kidney disease (CKD), but the underlying mechanisms of failed tubule repair and AKI-CKD transition are incompletely understood. In this study, we aimed for dynamic tracking of tubule injury and remodeling to understand if focal injury upon AKI may spread over time. Here, we present a model of AKI, in which we rendered only half of the kidney ischemic. Using serial intravital 2-photon microscopy and genetic identification of cycling cells, we tracked dynamic tissue remodeling in post- and non-ischemic kidney regions simultaneously and over 3 weeks. Spatial and temporal analysis of cycling cells relative to initial necrotic cell death demonstrated pronounced injury propagation and expansion into non-necrotic tissue regions, which predicted tubule atrophy with epithelial VCAM1 expression. In summary, our longitudinal analyses of tubule injury, remodeling, and fate provide important insights into AKI pathology.

Suggested Citation

  • Luca Bordoni & Anders M. Kristensen & Donato Sardella & Hanne Kidmose & Layla Pohl & Søren Rasmus Palmelund Krag & Ina Maria Schiessl, 2023. "Longitudinal tracking of acute kidney injury reveals injury propagation along the nephron," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40037-y
    DOI: 10.1038/s41467-023-40037-y
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    References listed on IDEAS

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    1. Leyuan Xu & Jiankan Guo & Dennis G. Moledina & Lloyd G. Cantley, 2022. "Immune-mediated tubule atrophy promotes acute kidney injury to chronic kidney disease transition," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
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