Overview of Pathophysiology of Acute Kidney Injury: Human Evidence, Mechanisms, Pathological Correlations and Biomarkers and Animal Models

  • Timothy J. Pianta
  • Glenda C. Gobe
  • Evan P. Owens
  • Zoltan H. EndreEmail author


Mortality and morbidity associated with acute kidney injury (AKI) are high. Depending on the definition used, AKI has been estimated to occur in 3–30% of hospitalised patients and up to 60% of critically ill patients, with severe AKI that requires dialysis complicating the care of more than 5% of patients in intensive care. It is an increasingly important global clinical problem with adverse effects on patient prognosis and healthcare costs. The causes of AKI range from, but are not limited to, septic shock, major surgery, cardiogenic shock, hypovolaemia, nephrotoxic drugs, liver disease (hepato-renal syndrome) and obstruction. This review will examine the pathophysiology of AKI, including the human evidence, mechanisms, pathological correlations and animal models. Mechanisms that might contribute to failure to recovery are highlighted, along with clinico-pathological correlations that allow development or use of novel biomarkers that diagnose AKI early or herald non-recovery.


AKI and ATI Ischaemia-reperfusion injury Apoptosis Necroptosis Autophagy Maladaptive repair Inflammation and immunity Biomarkers of AKI 



   Acute kidney injury


    Acute tubular injury


    Acute tubular necrosis


    B-cell lymphoma 2/Bcl-2-associated X protein


   Chronic kidney disease


 Chemokine ligand 16


   Endothelium-derived hyperpolarising factor


   Endoplasmic reticulum


   End-stage kidney disease


  Fractional excretion of sodium


  Glomerular filtration rate


   Glutathione S-transferase


   Hazard ratio


 Intercellular adhesion molecule-1


      Intensive care unit


 Insulin-like growth factor-binding protein 7










  Kidney injury molecule-1


 Liver-associated fatty acid-binding protein




  Monocyte chemotactic protein-1


  Migration inhibitory factor


  Mitochondria permeability transition


  Neutrophil gelatinase-associated lipocalin


   Nitric oxide


   Nitric oxide synthase


      p53-induced protein with death domain


  p53 upregulated modulator of apoptosis-α[alpha]


         Reactive oxygen species


         Serum creatinine


      Thiobarbituric acid-reacting substances


       Transforming growth factor


     Tissue inhibitor of metalloproteinases-2


   Tumour necrosis factor-α[alpha]


      Vascular endothelial growth factor


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Timothy J. Pianta
    • 1
  • Glenda C. Gobe
    • 2
  • Evan P. Owens
    • 3
  • Zoltan H. Endre
    • 4
    Email author
  1. 1.Northern Clinical SchoolUniversity of MelbourneEppingAustralia
  2. 2.School of Medicine, Centre for Kidney Disease ResearchUniversity of QueenslandBrisbaneAustralia
  3. 3.Centre for Kidney Disease ResearchThe University of QueenslandBrisbaneAustralia
  4. 4.Department of NephrologyPrince of Wales Hospital and Clinical School, University of New South WalesSydneyAustralia

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