In the present study, we hypothesized that Nrf2 deficiency in T2D db/db mice (db/dbNrf2 KO) would attenuate DKD progression, attenuating hypertension, hyperglycemia, lipid accumulation, and renal morphological changes/dysfunction through the decreased expression of AGT, SGLT2, CD36, and FABP4 in renal proximal tubular cells (RPTCs). Here, SLC5A2 is linked to type 2 diabetes mellitus.