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

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 novel 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 previously uninjured tissue regions, which predicted tubule atrophy with epithelial VCAM-1 expression. In summary, our longitudinal analysis of tubule injury, remodeling, and fate, provided important novel insights into AKI pathology.