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

Luca Bordoni, Anders M. Kristensen, Donato Sardella, Hanne Kidmose, Layla Pohl, Søren Rasmus Palmelund Krag and Ina Maria Schiessl ()
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Luca Bordoni: Aarhus University
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

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-40037-y

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