title: Mechanisms of maladaptive repair after AKI leading to accelerated kidney ageing and CKD.
abstract: Acute kidney injury is an increasingly common complication of hospital admission and is associated with high levels of morbidity and mortality. A hypotensive, septic, or toxic insult can initiate a cascade of events, resulting in impaired microcirculation, activation of inflammatory pathways and tubular cell injury or death. These processes ultimately result in acutely impaired kidney function and initiation of a repair response. This Review explores the various mechanisms responsible for the initiation and propagation of acute kidney injury, the prototypic mechanisms by which a substantially damaged kidney can regenerate its normal architecture, and how the adaptive processes of repair can become maladaptive. These mechanisms, which include G2/M cell-cycle arrest, cell senescence, profibrogenic cytokine production, and activation of pericytes and interstitial myofibroblasts, contribute to the development of progressive fibrotic kidney disease. The end result is a state that mimics accelerated kidney ageing. These mechanisms present important opportunities for the design of targeted therapeutic strategies to promote adaptive renal recovery and minimize progressive fibrosis and chronic kidney disease after acute insults.
authors: Renal Division and Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
authors: David A
authors: DA
authors: Ferenbach
authors: Renal Division and Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
authors: Joseph V
authors: JV
authors: Bonventre
mesh_terms: D058186:Acute Kidney Injury / Q000503:physiopathology*; D000818:Animals; D059447:Cell Cycle Checkpoints / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology*; D005355:Fibrosis; D006801:Humans; D007111:Immunity, Cellular; D007668:Kidney / Q000473:pathology / Q000503:physiopathology*; D007684:Kidney Tubules / Q000503:physiopathology; D051436:Renal Insufficiency, Chronic / Q000503:physiopathology*
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