FGF23 and kidney failure: Based on these findings, it can be stated that CYP27B1 has a major role in the production of 1,25(OH)2D. In addition, it has been well established that 1α-hydroxylase in kidney is the major if not the sole contributor for the circulating levels of 1,25(OH)2D. As a consequence, patients with kidney failure are deficient in circulating 1,25(OH)2D. In kidney, 1α-hydroxylase is regulated primarily by three hormones: i.e., parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and 1,25(OH)2D. PTH stimulates, but FGF23 and 1,25(OH)2D inhibits the expression of 1α-hydroxylase [19,20,21].