Bardoxolone methyl (Bard)-mediated strong suppression of calcium oxalate crystal formation in renal crystal recurrence model

The oxidative stress response during renal crystal recurrence and the dynamics of calcium oxalate (CaOx) crystal formation and clearance in a glyoxylate (GOX)-induced mouse model were examined. CaOx crystals gradually accumulated during five consecutive days of GOX administration, decreased by half in the ten days after administration, and required five weeks for near-complete clearance. HO-1 expression was strongly induced by the initial GOX administration through Nrf2 activation but diminished on continuing the administration. When GOX was readministered after a 10-day interval, HO-1 induction was minimal; however, after a 5-week interval, HO-1 expression returned to its initial levels. Readministration of GOX after crystal clearance resulted in reduced crystal formation and individual differences in crystal volume compared with the initial episode. Preadministration of bardoxolone methyl (Bard), a potent Nrf2 activator, significantly suppressed recurrent CaOx crystal formation. These findings strongly suggest the existence of an interaction between oxidative stress responses and renal crystal recurrence, highlighting the potential of Nrf2 activation as a preventive strategy for recurrent stone formation.