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Identifying Common Molecular Mechanisms in Experimental and Human Acute Kidney Injury

  • Louisa M.S. Gerhardt
    Correspondence
    Address reprint requests to Louisa M. S. Gerhardt, MD, Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, 1425 San Pablo St, BCC, Los Angeles, CA 90033-9080.
    Affiliations
    Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, CA
    Search for articles by this author
  • Andrew P. McMahon
    Affiliations
    Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, CA
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      Summary

      Acute kidney injury (AKI) is a highly prevalent, heterogeneous syndrome, associated with increased short- and long-term mortality. A multitude of different factors cause AKI including ischemia, sepsis, nephrotoxic drugs, and urinary tract obstruction. Upon injury, the kidney initiates an intrinsic repair program that can result in adaptive repair with regeneration of damaged nephrons and functional recovery of epithelial activity, or maladaptive repair and persistence of damaged epithelial cells with a characteristic proinflammatory, profibrotic molecular signature. Maladaptive repair is linked to disease progression from AKI to chronic kidney disease. Despite extensive efforts, no therapeutic strategies provide consistent benefit to AKI patients. Since kidney biopsies are rarely performed in the acute injury phase in humans, most of our understanding of AKI pathophysiology is derived from preclinical AKI models. This raises the question of how well experimental models of AKI reflect the molecular and cellular mechanisms underlying human AKI? Here, we provide a brief overview of available AKI models, discuss their strengths and limitations, and consider important aspects of the AKI response in mice and humans, with a particular focus on the role of proximal tubule cells in adaptive and maladaptive repair.

      Keywords

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