Moreover, in the CKD setting, over production of reactive oxygen species [39], elevation of uremic toxins [40], high serum phosphate/excess FGF23 [41], and low serum 1,25-dihydroxy vitamin D3 (1,25 Vit D3) are expected to further suppress Klotho production [37,42,43]. Here, FGF23 is linked to chronic kidney disease.