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

TY - JOUR

T1 - Longitudinal tracking of acute kidney injury reveals injury propagation along the nephron

AU - Bordoni, Luca

AU - Kristensen, Anders M

AU - Sardella, Donato

AU - Kidmose, Hanne

AU - Pohl, Layla

AU - Krag, Søren Rasmus Palmelund

AU - Schiessl, Ina Maria

N1 - © 2023. The Author(s).

PY - 2023/7

Y1 - 2023/7

N2 - 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.

AB - 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.

KW - Humans

KW - Nephrons

KW - Acute Kidney Injury

KW - Kidney

KW - Renal Insufficiency, Chronic

KW - Atrophy

KW - Necrosis

U2 - 10.1038/s41467-023-40037-y

DO - 10.1038/s41467-023-40037-y

M3 - Journal article

C2 - 37479698

SN - 2041-1723

VL - 14

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 4407

ER -