Targeting Nrf2 in Protection Against Renal Disease

Abstract

Background: Renal disease is a serious health problem, with increasing incidence and prevalence. Oxidative stress and inflammation play a key role in the pathogenesis and progression of renal disease. Therefore, therapeutic approaches to decrease oxidative stress should be of interest.

Objective: This review aims to provide a comprehensive and updated overview of the protective mechanisms mediated by Nrf2 (nuclear factor erythroid 2-related factor 2), a description of novel compounds that target Nrf2, its effectiveness to prevent renal disease and the on-going clinical trials for this pathological condition.

Methods: We undertook a structured search of bibliographic databases for peer-reviewed research in literature about Nrf2 activators and renal disease.

Results: The transcription factor Nrf2 is an emerging regulator of cellular resistance to oxidants and inflammation. Nrf2 controls the basal and induced expression of a couple of cytoprotective and antiinflammatory genes that regulate the physiological and pathophysiological outcomes of oxidant exposure. We have analyzed numerous findings showing that Nrf2 induction protects against oxidative stress and modulates inflammation in acute kidney injury and chronic kidney disease progression. However, few clinical trials have been performed in humans. Recent studies suggested that renoprotective effects of Nrf2 activation are observed at low doses, whereas harmful effects appear at higher concentrations.

Conclusion: The findings of this review confirm that novel studies are necessary to address whether Nrf2-targeting may be a safe therapeutic approach to decrease renal disease progression in humans.

Keywords: Nrf2; acute and chronic kidney injury; inflammation; oxidation; renal damage; therapy.