Targeting the Transcription Factor Nrf2 to Ameliorate Oxidative Stress and Inflammation in Chronic Kidney Disease
By Stacey Ruiz, P. Pergola, R. Zager, N. Vaziri. Kidney International, 2013
692 citations recorded by the source corpus.
Oxidative stress and inflammation are mediators in the development and progression of chronic kidney disease (CKD) and its complications, and they are inseparably linked as each begets and amplifies the other. CKD-associated oxidative stress is due to increased production of reactive oxygen species (ROS) and diminished antioxidant capacity. The latter is largely caused by impaired activation of Nrf2, the transcription factor that regulates genes encoding antioxidant and detoxifying molecules. Protective effects of Nrf2 are evidenced by amelioration of oxidative stress, inflammation, and kidney disease in response to natural Nrf2 activators in animal models, while Nrf2 deletion amplifies these pathogenic pathways and leads to autoimmune nephritis. Given the role of impaired Nrf2 activity in CKD-induced oxidative stress and inflammation, interventions aimed at restoring Nrf2 may be effective in retarding CKD progression. Clinical trials of the potent Nrf2 activator bardoxolone methyl showed significant improvement in renal function in CKD patients with type 2 diabetes. Results of the ongoing BEACON trial investigating the effect of this drug on time to end-stage renal disease or cardiovascular death will help further characterize the efficacy of Nrf2 pharmacological modulation in CKD. This article provides an overview of the role of impaired Nrf2 activity in the pathogenesis of CKD-associated oxidative stress and inflammation and the potential utility of targeting Nrf2 in the treatment of CKD.
Subfields: Molecular Biology, Pediatrics, Perinatology and Child Health
View Paper: https://www.semanticscholar.org/paper/c6ccacf543701b54cd514b8955edee78bd8d8cbc
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Citations in the corpus
- Diabetic Nephropathy: Challenges in Pathogenesis, Diagnosis, and Treatment (2021, background): “The occurrence of inflammation in DN can also occur through NF-κB activation induced by an increase in AGE, which will then be followed by an increase in ROS production [81].”