Downregulation of the klotho gene in chronic renal failure is thought to be associated with the development of vascular calcification (VC) (103) Specifically, defects in klotho lead to phosphate retention, and elevated blood phosphate concentrations trigger calcium phosphate precipitation, a product that is adsorbed by the serum protein fetuin-A and induces ectopic calcification (104, 105). The gene discussed is KL; the disease is chronic kidney disease.