Many insults including high phosphate, vitamin D deficiency, angiotensin II, oxidative stress and indoxyl sulfate 30, 31 transcriptionally suppress Klotho expression by repressing Klotho promoter via complex signal networks, such as Wnt/β-catenin 15, 32, 33, TGF-β 34-36 and NF-κB 37, 38. Here, KL is linked to vitamin D deficiency.