Related Experiment Video
Updated: Apr 11, 2026
Bilateral Renal Ischemia-Reperfusion Model for Acute Kidney Injury in Mice
Published on: February 2, 2024
Cell-cycle arrest and acute kidney injury: the light and the dark sides
John A Kellum1, Lakhmir S Chawla2
1Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
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.
Insights
Early detection of acute kidney injury (AKI) is possible using urinary biomarkers tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7). These markers indicate cell-cycle arrest, revealing both protective and detrimental aspects of AKI.
Area of Science:
- Nephrology
- Biomarker Discovery
- Cellular Biology
Background:
- Acute kidney injury (AKI) is a frequent complication of systemic diseases and major surgeries.
- Early detection and understanding of AKI pathogenesis remain significant challenges in clinical management and research.
- Cell-cycle arrest is implicated in AKI development, with potential links to chronic kidney disease progression.
Purpose of the Study:
- To validate urinary biomarkers for early AKI detection.
- To explore the dual role of cell-cycle arrest in AKI pathogenesis.
Main Methods:
- Multi-center studies were conducted.
- Validation of urinary biomarkers tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) for AKI prediction.
- Analysis of cell-cycle arrest as a mechanism in AKI.
Main Results:
- Urinary TIMP-2 and IGFBP7 levels were validated as predictors of AKI development, preceding clinical signs like azotemia and oliguria.
- Cell-cycle arrest was identified as a key component in AKI pathogenesis.
- Evidence suggests cell-cycle arrest has both detrimental ('dark side') and protective ('light side') roles in cellular response to injury.
Conclusions:
- Urinary TIMP-2 and IGFBP7 serve as early diagnostic biomarkers for AKI.
- Cell-cycle arrest is a critical mechanism in AKI, influencing disease progression and potentially offering therapeutic targets.
- Further research is needed to harness the protective aspects of cell-cycle arrest for AKI prevention.
Related Concept Videos
01:22Acute Kidney Injury I: Introduction
01:29Acute Kidney Injury II: Pathophysiology
01:30Acute Kidney Injury IV: Diagnostic Studies and Prevention
01:29Acute Kidney Injury III: Clinical Manifestations
01:20Acute Kidney Injury V: Interprofessional Care
01:27Dialysis
Acute kidney injury develops suddenly and can be caused by pre-renal causes (e.g., hypovolemia, shock), intrinsic renal causes (e.g., acute tubular necrosis), or post-renal causes (e.g., urinary obstruction). In contrast, chronic renal failure progresses gradually over time and is often...