In the renal system, Klotho deficiency is greatly linked with ionic imbalance, calcification in vessels, inflammation and fibrosis in the renal parenchyma, and skeletal disorders, which represents CKD. Stage 2 CKD shows a premature reduction in Klotho protein levels in the blood, and stage 1 CKD shows even an earlier premature reduction in urinary Klotho levels. This evidence concerns the gene KL and chronic kidney disease.