Nrf2 activation for kidney disease treatment—a mixed blessing?

Activation of cellular antioxidative signaling is expected to be a silver bullet against kidney diseases, and clinical trials of compounds activating the antioxidant transcription factor Nrf2 have revealed their renoprotective effects. However, cardiac events have been observed in some cases with elevated urinary albumin excretion in these trials. Therefore, elucidating the negative effects of Nrf2 activation is essential. Rush and colleagues demonstrated that Nrf2 activation aggravates podocyte injury, a factor related to proteinuria and cardiac failure.