AKI on CKD: heightened injury, suppressed repair, and the underlying mechanisms

Kidney Int. 2017 Nov;92(5):1071-1083. doi: 10.1016/j.kint.2017.06.030. Epub 2017 Sep 8.

Abstract

Acute kidney injury (AKI) and chronic kidney disease (CKD) are interconnected. Although AKI-to-CKD transition has been intensively studied, the information of AKI on CKD is very limited. Nonetheless, AKI, when occurring in patients with CKD, is known to be more severe and difficult to recover. CKD is associated with significant changes in cell signaling in kidney tissues, including the activation of transforming growth factor-β, p53, hypoxia-inducible factor, and major developmental pathways. At the cellular level, CKD is characterized by mitochondrial dysfunction, oxidative stress, and aberrant autophagy. At the tissue level, CKD is characterized by chronic inflammation and vascular dysfunction. These pathologic changes may contribute to the heightened sensitivity of, and nonrecovery from, AKI in patients with CKD.

Keywords: acute kidney injury; cell signaling; chronic kidney disease; fibrosis; inflammation; mitochondria.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acute Kidney Injury / etiology
  • Acute Kidney Injury / pathology*
  • Autophagy*
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • DNA Methylation
  • Epigenesis, Genetic
  • Humans
  • Inflammation / pathology*
  • Kidney / blood supply
  • Kidney / pathology
  • Mitochondria / metabolism
  • Mitochondria / pathology*
  • Oxidative Stress
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / genetics
  • Renal Insufficiency, Chronic / pathology*
  • Risk Factors
  • Signal Transduction
  • Transforming Growth Factor beta / metabolism
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • TP53 protein, human
  • Transforming Growth Factor beta
  • Tumor Suppressor Protein p53