This was an important consideration, particularly because Nrf2 activators, such as SFN and the pentacyclic cyanoenones bardoxolone methyl and RTA-408 (used in this study), are currently in clinical trials for multiple indications, including chronic kidney disease, liver disease, pulmonary arterial hypertension, mitochondrial myopathy, and autism spectrum disorder (Cuadrado et al., 2019). Here, NFE2L2 is linked to chronic kidney disease.