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Abstract
Introduction: The coordinated activation of Nrf-2-dependent signaling pathway is currently being investigated in a range of chronic diseases. Bardoxolone methyl is a potent, orally bioavailable Nrf-2 agonist. In a recent 52-week study, treatment with bardoxolone methyl improved renal function in patients with chronic kidney disease (CKD) and type 2 diabetes. This improvement was sustained for the duration of the treatment. Such agonists potentially offer new options for the complex management of renal impairment.
Areas covered: A literature search was performed to analyze the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of bardoxolone methyl in both healthy volunteers and patients. Updated information about bardoxolone methyl, either after single administration or after chronic administration is also included. A special focus has been put on the putative mechanisms of action and potential toxicity profiles as well as an ongoing trials in patients with CKD and type 2 diabetes.
Expert opinion: The development of an agent that leads to sustained improvement in renal function comes as a welcome relief to the millions of individuals with diabetes and CKD. However, much remains to be established regarding its actions in a complex and pleiotropic signalling cascade. Other triterpenoids with different PK/PD profiles are currently under development.