Klotho is defined as a transmembrane protein that is detected mainly in the brain and kidneys. Klotho is also expressed in kidney distal convoluted tubules and parathyroid cells, and it mediates the role of FGF-23 (a protein that is encoded by the FGF23 gene) in bone–kidney–parathyroid control of calcium and phosphate. It is possible to say that Klotho is considered an early biomarker for CKD (chronic kidney disease). CKD is a pan state of Klotho deficiency and premature aging disease. As CKD progresses, Klotho continues to decline, which causes resistance of FGF-23 and provokes the increase of FGF-23 and parathyroid hormone (PTH), as well as hypovitaminosis D. In order to reduce mineral and vascular derangement in patients with CKD, it is important to maintain normal phosphate levels with phosphate binders.
The progression of CKD is characterized by the following cycle: first, Klotho expression decreases by causing FGF-23 to increase, which lowers the circulation of 1,25(OH)2D3 (powerful regulator of mineral metabolism). Klotho expression keeps depressing, which leads to an increase in PTH (parathyroid hormone) expression. Increased PTH induces the further increase of FGF-23, which causes large decreases in 1,25(OH)2D3 and a continuous increase of PTH. This all leads to hyperphosphatemia, one of the symptoms of the late stage of CKD.
One of the most effective ways to fight this and stop the progression of CKD is Parathyroidectomy. Parathyroidectomy is a surgery used to remove the parathyroid glands or parathyroid tumors. Removal of the parathyroid glands helps reduce the FGF-23 production and increase Klotho expression. One of the studies showed that serum FGF-23 levels decreased in the transgenic mice after this surgery.
In conclusion, it is possible to say that phosphate retention induces complex aging-like phenotypes. Therefore, in order to reduce mineral vascular derangement in patients with CKD, it is important to maintain normal phosphate levels with phosphate binders.