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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. Endre
Chapter

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.

Keywords

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

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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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
  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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