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Core Concepts in Acute Kidney Injury pp 45–67Cite as

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

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Abstract

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.

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Abbreviations

AKI:

   Acute kidney injury

ATI:

    Acute tubular injury

ATN:

    Acute tubular necrosis

Bax:

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

CKD:

   Chronic kidney disease

CXCl16:

 Chemokine ligand 16

EDHF:

   Endothelium-derived hyperpolarising factor

ER:

   Endoplasmic reticulum

ESKD:

   End-stage kidney disease

FENa:

  Fractional excretion of sodium

GFR:

  Glomerular filtration rate

GST:

   Glutathione S-transferase

HR:

   Hazard ratio

ICAM-1:

 Intercellular adhesion molecule-1

ICU:

      Intensive care unit

IGFBP7:

 Insulin-like growth factor-binding protein 7

IL:

    Interleukin

im:

    Intramuscular

ip:

    Intraperitoneal

iv:

       Intravenous

KIM-1:

  Kidney injury molecule-1

L-FABP:

 Liver-associated fatty acid-binding protein

LPS:

    Lipopolysaccharide

MCP-1:

  Monocyte chemotactic protein-1

MIF:

  Migration inhibitory factor

MPT:

  Mitochondria permeability transition

NGAL:

  Neutrophil gelatinase-associated lipocalin

NO:

   Nitric oxide

NOS:

   Nitric oxide synthase

PIDD:

      p53-induced protein with death domain

PUMA-α[alpha]:

  p53 upregulated modulator of apoptosis-α[alpha]

ROS:

         Reactive oxygen species

SCr:

         Serum creatinine

TBARS:

      Thiobarbituric acid-reacting substances

TGF:

       Transforming growth factor

TIMP-2:

     Tissue inhibitor of metalloproteinases-2

TNF-α[alpha]:

   Tumour necrosis factor-α[alpha]

VEGF:

      Vascular endothelial growth factor

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Authors and Affiliations

  1. Northern Clinical School, University of Melbourne, Epping, VIC, Australia

    Timothy J. Pianta

  2. School of Medicine, Centre for Kidney Disease Research, University of Queensland, Brisbane, QLD, Australia

    Glenda C. Gobe

  3. Centre for Kidney Disease Research, The University of Queensland, Brisbane, QLD, Australia

    Evan P. Owens

  4. Department of Nephrology, Prince of Wales Hospital and Clinical School, University of New South Wales, Sydney, NSW, Australia

    Zoltan H. Endre

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  1. Timothy J. Pianta
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  2. Glenda C. Gobe
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  3. Evan P. Owens
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  4. Zoltan H. Endre
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Correspondence to Zoltan H. Endre .

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Editors and Affiliations

  1. Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Sushrut S. Waikar

  2. University College Dublin, Dublin, Ireland

    Patrick T. Murray

  3. Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Ajay K. Singh

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Pianta, T.J., Gobe, G.C., Owens, E.P., Endre, Z.H. (2018). Overview of Pathophysiology of Acute Kidney Injury: Human Evidence, Mechanisms, Pathological Correlations and Biomarkers and Animal Models. In: Waikar, S., Murray, P., Singh, A. (eds) Core Concepts in Acute Kidney Injury. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-8628-6_4

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