In addition, 1,25(OH)2D is thought to cooperate with Klotho in retarding vascular calcification by the induction of OPN (Fig. S1C), a powerful antimineralization factor.(60) Ironically, the two renal hormones that are deficient in patients with chronic renal failure because of renal mass loss, namely 1,25(OH)2D and Klotho, are two vital effectors of renal and vascular health, suggesting a strategy for the prevention and treatment of vascular disease, as well as CKD. This evidence concerns the gene SPP1 and chronic kidney disease.