In this study, we investigated whether 1) DPD induces ER stress and hypoxia in adenine-induced CKD mice, 2) DPD upregulates osteogenic markers and promotes calcification in adenine-induced CKD mice, 3) DPD induces PERK phosphorylation, ATF4, glucose-regulated protein 78 (GRP78), and CHOP expression in HAoSMCs, 4) DPD promotes calcification and osteogenic differentiation of HAoSMCs in an ER-stress and ATF4-dependent manner, and 5) there is a hierarchy between DPD-induced HIF-1α and ATF4 responses. This evidence concerns the gene ATF4 and chronic kidney disease.