Likewise, markers of tubular injury (tubular dilatation, tubulointerstitial fibrosis, increased KIM-1 expression) and tubular senescence (expression of p21, SA-β-gal, γ-H2A.X, Ki-67, Lamin B) as well as reduced DNMT1 expression and p21 promoter demethylation were comparable in SGLT2i-treated (DM + SGLT2i) mice and mice with persistent hyperglycemia (DM-22, Fig. 7d–g, Supplementary Fig. 17). This evidence concerns the gene HAVCR1 and Hyperglycemia.