The role of oxidative stress and hypoxia in renal disease

Abstract

Oxygen is required to sustain aerobic organisms. Reactive oxygen species (ROS) are constantly released during mitochondrial oxygen consumption for energy production. Any imbalance between ROS production and its scavenger system induces oxidative stress. Oxidative stress, a critical contributor to tissue damage, is well-known to be associated with various diseases. The kidney is susceptible to hypoxia, and renal hypoxia is a common final pathway to end stage kidney disease, regardless of the underlying cause. Renal hypoxia aggravates oxidative stress, and elevated oxidative stress, in turn, exacerbates renal hypoxia. Oxidative stress is also enhanced in chronic kidney disease, especially diabetic kidney disease, through various mechanisms. Thus, the vicious cycle between oxidative stress and renal hypoxia critically contributes to the progression of renal injury. This review examines recent evidence connecting chronic hypoxia and oxidative stress in renal disease and subsequently describes several promising therapeutic approaches against oxidative stress.

Keywords: Hypoxia; Hypoxia-inducible factor; Nuclear factor erythroid 2-related factor 2; Oxidative stress; Renal insufficiency; chronic.

Figure 1

The link between hypoxia and oxidative stress in chronic kidney disease (CKD) and tools for intervention. Hypoxia and oxidative stress are intricately linked in CKD via diverse signaling pathways. Hypoxia-inducible factor (HIF) and nuclear factor erythroid 2-related factor 2 (Nrf2) activation reduce oxidative stress. Mitogen-activated protein kinase/c-Jun amino terminal kinase (p38 MAPK/JNK) signaling activated by increased oxidative stress upregulates inflammation. Vascular adhesion protein-1 (VAP-1) increases oxidative stress by generating inflammation; ASK-1, apoptosis signal-regulating kinase 1.