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Biomarkers in Kidney Disease pp 1–13Cite as

Cell Cycle Arrest Biomarkers in Kidney Disease

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Abstract

Acute kidney injury remains one of the most common and deadly complications of critical illness. Early recognition of this syndrome potentially allows more efficient prophylactic and potentially therapeutic options. The functional biomarkers of kidney injury are very insensitive to the changes of kidney function early in the course of AKI and also nonspecific to the etiology of kidney damage. The critical need for novel biomarkers of AKI resulted in a significant number of efforts which concluded discovery and validation of several new AKI biomarkers. The most recent and indeed the most specific biomarkers of kidney stress are recently discovered and validated and currently approved by the Food and Drug Administration (FDA) for identification of AKI high-risk individuals among ICU patients. These biomarkers, i.e., insulin growth factor-binding protein-7 (IGFBP7) and tissue inhibitor metalloproteinases-2 (TIMP-2), are able to identify high-risk patients in ICU, 12 h before the functional biomarkers are able to detect AKI. These proteins are involved in the pathophysiology and natural history of AKI by halting the progression of the cell cycle following injury during the G1- to S-phase transition. In this review, we will describe the role of the cell cycle during AKI and the relationship between the cell cycle arrest and maladaptive recovery of the kidney following an injury. Then we focus on cell cycle arrest biomarkers and their relationship with AKI, their physiological roles, and finally potential clinical applications.

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Abbreviations

βFGF:

β fibroblast growth factor

AKI:

Acute kidney injury

CDK:

Cyclin-dependent protein kinase

DAMP:

Damage-associated molecular pattern

DDR:

DNA Damage Response

DNA:

Deoxyribonucleic acid

EGF:

Epithelial growth factor

FDA:

Food and Drug Administration

G1 :

Gap 1

G2 :

Gap 2

ICU:

Intensive care unit

IGFBP7:

Insulin-like Growth Factor Binding Protein-7

IL-18:

Interleukin-18

ITG α3 β1:

Integrin α3/β1

KDIGO:

Kidney Disease Improving Global Outcomes

KIM-1:

Kidney injury molecule -1

L-FABP:

Liver fatty acid binding protein

M:

Mitosis

MMP:

Metalloproteinases

NGAL:

Neutrophil gelatinase-associated lipocalin

NGF:

Nerve growth factor

PAMP:

Pathogen-associated molecular pattern

PCNA:

Proliferating cell nuclear antigen

ROS:

Reactive oxygen species

S:

Synthesis

SA-β-gal:

Senescence-associated galactosidase

TIMP-2:

Tissue Inhibitor Metalloproteinases-2

TGF-β:

Transforming growth factor- β

VEGF:

Vascular endothelial growth factor

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Authors and Affiliations

  1. Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN, USA

    Kianoush Kashani

  2. Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, Rochester, MN, USA

    Kianoush Kashani

  3. Hospital Pharmacy Services, Mayo Clinic, Rochester, MN, USA

    Erin N. Frazee

  4. The Center for Critical Care Nephrology, CRISMA, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, 604 Scaife Hall, Pittsburgh, PA, 15206, USA

    John A. Kellum

Authors
  1. Kianoush Kashani
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  2. Erin N. Frazee
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  3. John A. Kellum
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Correspondence to John A. Kellum .

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Editors and Affiliations

  1. Department of Biomedical Sciences, University of Westminster, London, United Kingdom

    Vinood B. Patel

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Kashani, K., Frazee, E.N., Kellum, J.A. (2015). Cell Cycle Arrest Biomarkers in Kidney Disease. In: Patel, V. (eds) Biomarkers in Kidney Disease. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7743-9_45-1

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  • DOI: https://doi.org/10.1007/978-94-007-7743-9_45-1

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  • Online ISBN: 978-94-007-7743-9

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