Acute kidney injury to chronic kidney disease transition: insufficient cellular stress response.

Published

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

Pubmed Central ID

  • 29702491

Electronic International Standard Serial Number (EISSN)

  • 1473-6543

International Standard Serial Number (ISSN)

  • 1062-4821

Digital Object Identifier (DOI)

  • 10.1097/mnh.0000000000000424

Language

  • eng