In this study, we report that reduced BDH1 levels are associated with the pathogenesis of DKD in vivo and with glucotoxicity and lipotoxicity in vitro. We demonstrate that BDH1 functions as a previously unrecognized activator of NRF2 through the enhancement of βOHB-AcAc-succinate-fumarate metabolic flux. Here, BDH1 is linked to diabetic kidney disease.