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Acute kidney injury to chronic kidney disease transition: insufficient cellular stress response
Sarah A Strausser1, Daisuke Nakano2, Tomokazu Souma1
1Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
Purpose Of Review:
Recent epidemiological and preclinical mechanistic studies provide strong evidence that acute kidney injury (AKI) and chronic kidney disease (CKD) form an interconnected syndrome. Injured kidneys undergo a coordinated reparative process with an engagement of multiple cell types after injury; however, maladaptation to the injury subjects kidneys to a vicious cycle of fibrogenesis and nephron loss. In this review, we will outline and discuss the pathogenesis of AKI-to-CKD transition with an emphasis on dysregulated 'cellular stress adaptation' as a potential therapeutic target.
Recent Findings:
Recent studies identify the crucial role of injured tubular epithelial cells in the transition from AKI to CKD. Damaged tubular cells undergo reactivation of developmental and epithelial-mesenchymal transition signaling, metabolic alteration, and cell-cycle arrest, thereby driving inflammation and fibrogenesis. Recent work highlights that cellular stress-adaptive pathways against hypoxic and oxidative stress provide insufficient protection after severe AKI episode.
Summary:
Insufficient cellular stress adaptation may underpin the persistent activation of inflammatory and fibrogenic signaling in damaged kidneys. We propose that harnessing cellular stress-adaptive responses will be a promising therapeutic strategy to halt or even reverse the deleterious process of AKI-to-CKD transition.
Insights
Acute kidney injury (AKI) can progress to chronic kidney disease (CKD) due to maladaptive cellular repair. Enhancing cellular stress adaptation may offer a therapeutic strategy to prevent this kidney disease progression.
Area of Science:
- Nephrology
- Cellular Biology
- Pathophysiology
Background:
- Acute kidney injury (AKI) and chronic kidney disease (CKD) are increasingly recognized as an interconnected syndrome.
- Kidney injury triggers a complex reparative process involving multiple cell types.
- Maladaptive repair can lead to a cycle of kidney fibrosis and nephron loss, transitioning AKI to CKD.
Purpose of the Study:
- To review the pathogenesis of the AKI-to-CKD transition.
- To highlight the role of dysregulated cellular stress adaptation as a therapeutic target.
- To discuss strategies for harnessing cellular stress responses to halt or reverse kidney disease progression.
Main Methods:
- Review of recent epidemiological and preclinical mechanistic studies.
- Analysis of cellular signaling pathways involved in kidney injury and repair.
- Emphasis on tubular epithelial cell responses to stress.
Main Results:
- Injured tubular epithelial cells play a critical role in AKI-to-CKD transition.
- These cells exhibit reactivation of developmental signaling, metabolic alterations, and cell-cycle arrest.
- Cellular stress-adaptive pathways are often insufficient to protect against severe AKI, leading to persistent inflammation and fibrosis.
Conclusions:
- Insufficient cellular stress adaptation contributes to sustained inflammation and fibrogenesis in damaged kidneys.
- Targeting cellular stress-adaptive responses presents a promising therapeutic avenue.
- Harnessing these responses could halt or reverse the AKI-to-CKD transition, improving kidney outcomes.
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