Emerging role of a phosphatonin in mineral homeostasis and its derangements.
BACKGROUND
The study of a distinct group of renal phosphate wasting disorders with bone disease which comprise X-linked hypophosphatemic rickets (XLH), autosomal dominant hypophosphatemic rickets (ADHR) and tumour-induced osteomalacia (TIO) gave rise to the identification of different hormone-like peptides, also known as phosphatonins. These factors are responsible for the major disease features that characterize XLH, ADHR and TIO. Recent reports on one of these phosphatonins, fibroblast growth factor-23 (FGF-23), point to a general role of this factor in mineral ion metabolism.


OBJECTIVE
The main focus regards recent evidence implicating FGF-23 in normal and disordered mineral homeostasis with special emphasis on chronic kidney disease. The interactions of FGF-23 with phosphate, parathyroid hormone and vitamin D are discussed in detail.


CONCLUSIONS
The FGF-23 has been shown to increase urinary phosphate excretion, inhibit bone mineralization and suppress 1,25-dihydroxy vitamin D(3)[1,25(OH)(2)D(3)], the main characteristics that XLH, ADHR and TIO have in common. Apart from its role in these phosphate wasting disorders serum FGF-23 is elevated in hypoparathyroidism and humoral hypercalcaemia of malignancy and responds to altered dietary phosphate and calcium supply in healthy subjects. The FGF-23 is also variably elevated in chronic kidney disease and associated secondary hyperparathyroidism where it correlates positively with serum phosphate and parathyroid hormone and negatively with 1,25(OH)(2)D(3). Such relationships, along with data from experimental studies, raise the question of whether FGF-23 contributes to the pathophysiology of chronic kidney disease.
Bielesz
B
B
Institute of Physiology, Zurich, Switzerland. bernd.bielesz@gmx.net
D001842:Bone and Bones / Q000378:metabolism*; D002117:Calcitriol / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D053098:Familial Hypophosphatemic Rickets / Q000378:metabolism; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D040181:Genetic Diseases, X-Linked; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000503:physiopathology; D009154:Mutation; D010018:Osteomalacia / Q000209:etiology / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D014808:Vitamin D Deficiency / Q000378:metabolism*
C000717427:FGF23 protein, human; D010281:Parathyroid Hormone; D010710:Phosphates; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002117:Calcitriol; D002118:Calcium