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.
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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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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