Acute kidney injury to chronic kidney disease transition: insufficient cellular stress response.
Journal Article (Journal Article;Review)
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.
Full Text
Duke Authors
Cited Authors
- Strausser, SA; Nakano, D; Souma, T
Published Date
- July 2018
Published In
Volume / Issue
- 27 / 4
Start / End Page
- 314 - 322
PubMed ID
- 29702491
Electronic International Standard Serial Number (EISSN)
- 1473-6543
Digital Object Identifier (DOI)
- 10.1097/MNH.0000000000000424
Language
- eng
Conference Location
- England