title: Cell-cycle arrest and acute kidney injury: the light and the dark sides.
abstract: Acute kidney injury (AKI) is a common consequence of systemic illness or injury and it complicates several forms of major surgery. Two major difficulties have hampered progress in AKI research and clinical management. AKI is difficult to detect early and its pathogenesis is still poorly understood. We recently reported results from multi-center studies where two urinary markers of cell-cycle arrest, tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) were validated for development of AKI well ahead of clinical manifestations--azotemia and oliguria. Cell-cycle arrest is known to be involved in the pathogenesis of AKI and this 'dark side' may also involve progression to chronic kidney disease. However, cell-cycle arrest has a 'light side' as well, since this mechanism can protect cells from the disastrous consequences of entering cell division with damaged DNA or insufficient bioenergetic resources during injury or stress. Whether we can use the light side to help prevent AKI remains to be seen, but there is already evidence that cell-cycle arrest biomarkers are indicators of both sides of this complex physiology.
authors.affiliation: Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Kellum
authors.affiliation: Department of Medicine, Division of Intensive Care Medicine and Division of Nephrology, Veterans Affairs Medical Center, Washington, DC, USA.
authors.forename: Lakhmir S
authors.initials: LS
authors.lastname: Chawla
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000473:pathology* / Q000652:urine; D000818:Animals; D015415:Biomarkers / Q000652:urine; D059447:Cell Cycle Checkpoints; D018450:Disease Progression; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000652:urine; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000652:urine
chemical_list: D015415:Biomarkers; D018969:Insulin-Like Growth Factor Binding Proteins; C560823:TIMP2 protein, human; C102529:insulin-like growth factor binding protein-related protein 1; D019716:Tissue Inhibitor of Metalloproteinase-2
keywords: acute kidney injury; cell-cycle arrest; insulin-like growth factor-binding protein 7; tissue inhibitor of metalloproteinases-2