A soluble form of Klotho can be also detected in blood, urine, and cerebrospinal fluid [48], and several studies relate the loss of soluble Klotho in plasma, and also in the kidney, with the progression of CKD [49], the pathogenesis of diabetic nephropathy [50], and cardiovascular disease (CVD) [51], and with metabolic and mineral-bone disorders [52,53]. This evidence concerns the gene KL and abnormal mineralization disorder.