Nrf2 activator for the treatment of kidney diseases

Kidney diseases are highly prevalent worldwide, and significantly reduce the quality of life of patients, creating an urgent need for effective therapeutic modalities. Despite this significant unmet medical need, none of the drugs launched to date have demonstrated promising potential to cure kidney diseases. This is likely due to the structural complexity of the kidney as well as difficulties in setting appropriate endpoints for clinical trials and identifying appropriate therapeutic targets. Recently, an alternative endpoint for clinical trials (i.e., a 30% or 40% reduction in estimated glomerular filtration rate [eGFR] from baseline following 2-3 years of observation) has been considered in the United States, European Union, and Japan, and is expected to contribute to the progress of drug development for kidney diseases. Further, oxidative stress and inflammation are currently thought to be key factors in the progression of kidney diseases, prompting more research on drugs targeting the mechanisms related to these factors for treatment. The Kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor 2 (Keap1-Nrf2) system has drawn much attention in recent years for its anti-oxidative and anti-inflammatory properties, and its pharmacological potential for treatment of kidney diseases is being widely investigated in both clinical and non-clinical studies. This review summarizes the current issues in the treatment of kidney diseases, including clinical endpoints, Nrf2 activators as treatment options, and perspectives on pharmaceutical applications of Nrf2 activators.