Antioxidants in Kidney Diseases: The Impact of Bardoxolone Methyl

Figure 2

Overview of RAAS blockers and bardoxolone in pathogenic pathways in kidney diseases. RAAS blockers target several pathogenic pathways in kidney injury, including those generating ROS. However, there are several escape mechanisms (aldosterone breakthrough, increased prorenin effects) as well as less sensitive lesions (significant loss of kidney function, ischemic disease, persistent immune activity). BARD promotes activation of the Nrf2 transcription factor, that is released of the inhibitory Keap1 protein and migrates to the nucleus where it regulates transcription of genes containing ARE sequences in their promoters. These phase 2 response genes are collectively involved in the reduction of ROS and inhibition of NF-kappaB. Thus, BARD could promote renal protection through antioxidants and anti-inflammatory effects be promoting the activity of the Nrf2 transcription factor and inhibiting the activity of the NF-kappaB transcription factor. ACE/ACEIs: angiotensin converting enzyme/angiotensin converting enzyme inhibitors, ARBs: angiotensin receptor blockers, AREs: antioxidant response elements, BARD: bardoxolone methyl, CKD: chronic kidney disease, DRI: direct renin inhibitor, mineralocorticoid receptor antagonists, Keap1: Kelch-like ECH-associated protein 1, MRA: mineralocorticoid receptor antagonists, NF-kappaB: nuclear factor kappa B, Nrf2: nuclear factor (erythroid derive 2)-like 2, RAAS: renin-angiotensin-aldosterone system, ROS: reactive oxygen species, TGFβ-1: transforming growth factor beta 1.