Chapter 13 - Clinical Aspects of Fibroblast Growth Factor 23

Abstract

Fibroblast growth factor 23 (FGF23) is produced by bone and decreases serum phosphate and 1,25-dihydroxyvitamin D [1,25(OH) 2 D] levels by binding to the FGF receptor–Klotho complex in kidney. FGF23 is also reported to inhibit the secretion of parathyroid hormone. Excess actions of FGF23 cause several kinds of hypophosphatemic rickets/osteomalacia characterized by impaired proximal tubular phosphate reabsorption and inappropriately low 1,25(OH) 2 D level for hypophosphatemia. In contrast, deficient actions of FGF23 result in hyperphosphatemic tumoral calcinosis. In addition, FGF23 was shown to play important roles in the development of chronic kidney disease-mineral and bone disorder (CKD-MBD). Many epidemiological studies show an association between higher FGF23 levels and several adverse events such as cardiovascular events, left ventricular hypertrophy, progression of CKD, and death. FGF23 was also reported to induce ventricular hypertrophy in a Klotho-independent manner. It remains to be established whether modulation of FGF23 level and activity could be a new therapeutic maneuver for disordered phosphate metabolism and CKD-MBD.