Increased circulating FGF-23 (Figure 7E) has also been reported as a consequence of decreasing nephron numbers with age, progression of CKD [39,44], and loss of the integrity of the Klotho signaling pathway, which accompanies mild hypercalcemia, vascular calcification, and elevated 1,25(OH)2 vitamin D3 [45,46]. This evidence concerns the gene KL and hypercalcemia disease.