Fig. 3.

Proposed model and time profile of changes in serum Klotho, fibroblast growth factor 23 (FGF23), phosphate (Pi), and hormones relevant to mineral metabolism in relation to chronic kidney disease (CKD) progression. The decline in Klotho (black line) is an early event which is followed by other changes as CKD progresses. Low Klotho may induce FGF23 resistance causing a compensatory increase in blood FGF23 levels (red line) to maintain Pi homeostasis in CKD. The compensatory increase in FGF23 then suppresses 1,25-(OH)₂-vitamin D₃ (1,25-(OH)₂D₃) production (blue line). Low 1,25-(OH)₂D₃ and high blood Pi (purple line) due to progressive decline in renal function increase parathyroid hormone (PTH) (green line), which may contribute to high FGF23 in advanced CKD.