Biology of Fibroblast Growth Factor 23: From Physiology to Pathology

Fibroblast growth factor (FGF)23 is a phosphaturic hormone produced by osteocytes and osteoblasts that binds to FGF receptors in the presence of the transmembrane protein aKlotho. FGF23 mainly targets the renal proximal tubule to inhibit calcitriol production and the expression of the sodium/phosphate cotransporters NaPi2a and NaPi2c, thus inhibiting renal phosphate reabsorption. FGF23 also acts on the parathyroid glands to inhibit parathyroid hormone synthesis and secretion. FGF23 regulation involves many systemic and local factors, among them calcitriol, phosphate, and parathyroid hormone. Increased FGF23 is primarily observed in rare acquired or genetic disorders, but chronic kidney disease is associated with a reactional increase in FGF23 to combat hyperphosphatemia. However, high FGF23 levels induce left ventricular hypertrophy (LVH) and are associated with an increased risk of mortality. In this review, we describe FGF23 physiology and the pathological consequences of high or low FGF23 levels.