The prevalence of chronic kidney disease (CKD) is increasing worldwide, with primarily diabetic kidney disease (DKD), being a major public health concern. Although the detailed mechanisms of CKD progression are not fully understood, the transition to kidney failure has been suggested to occur via a final common pathway, which is thought to be associated with oxidative stress and inflammation as important factors.
The Kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor 2 (Keap1-Nrf2) pathway is a key regulator of anti-oxidative and anti-inflammatory response. A number of reports have described the association between this pathway and kidney diseases in animal studies.
Bardoxolone methyl, a semi-synthetic triterpenoids, is known to be a potent Nrf2 activator. Importantly, previous clinical trials demonstrated that bardoxolone methyl increases not only estimated glomerular filtration rate (eGFR) but measured GFR, which is a true indicator of kidney function, using the inulin clearance method in patients with DKD. A Japanese Phase 3 study is currently ongoing to assess the efficacy and safety of bardoxolone methyl in more than 1,000 patients with stages G3 and G4 DKD.
This presentation summarizes available knowledge on the therapeutic potential of bardoxolone methyl for treatment of DKD.