Diabetes and Kidney Disease: Role of Oxidative Stress

Antioxid Redox Signal. 2016 Oct 20;25(12):657-684. doi: 10.1089/ars.2016.6664. Epub 2016 Apr 1.


Intrarenal oxidative stress plays a critical role in the initiation and progression of diabetic kidney disease (DKD). Enhanced oxidative stress results from overproduction of reactive oxygen species (ROS) in the context of concomitant, insufficient antioxidant pathways. Renal ROS production in diabetes is predominantly mediated by various NADPH oxidases (NOXs), but a defective antioxidant system as well as mitochondrial dysfunction may also contribute. Recent Advances: Effective agents targeting the source of ROS generation hold the promise to rescue the kidney from oxidative damage and prevent subsequent progression of DKD. Critical Issues and Future Directions: In the present review, we summarize and critically analyze molecular and cellular mechanisms that have been demonstrated to be involved in NOX-induced renal injury in diabetes, with particular focus on the role of increased glomerular injury, the development of albuminuria, and tubulointerstitial fibrosis, as well as mitochondrial dysfunction. Furthermore, novel agents targeting NOX isoforms are discussed. Antioxid. Redox Signal. 25, 657-684.

Keywords: NADPH-oxidases; albuminuria; diabetic nephropathy; reactive oxygen species.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / genetics*
  • Acute Kidney Injury / pathology
  • Antioxidants / metabolism
  • Diabetic Nephropathies / genetics*
  • Diabetic Nephropathies / pathology
  • Humans
  • Kidney / metabolism
  • Kidney / pathology
  • NADPH Oxidases / genetics
  • Oxidative Stress / genetics*
  • Reactive Oxygen Species / metabolism


  • Antioxidants
  • Reactive Oxygen Species
  • NADPH Oxidases