Nephrology and Clinical Chemistry: The Essential Link

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Clinical chemistry is a science that requires specific knowledge and teaching. The e-book covers several topics in clinical nephrology. Patients suffering from severe chronic kidney disease may be ...
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Fibroblast Growth Factor 23: The Missing Link in Phosphate Homeostasis

Pp. 134-140 (7)

Dominique Prie

Abstract

The kidney plays a central role in phosphate homeostasis. It adapts urinary phosphate excretion to phosphate intake and to body needs maintaining serum phosphate concentration within the normal range. The mechanisms coupling renal phosphate excretion to intestinal phosphate absorption and bone mineralization have been unraveled over the last ten years. Fibroblast growth factor 23 (FGF23) has been identified as a major hormone involved in phosphate homeostasis. FGF23 is a circulating peptide synthesized by bone cells in response to an increase in serum phosphate concentration and to calcitriol. FGF23 inhibits renal sodium-phosphate co-transporter activity and calcitriol production by the kidney. It also controls PTH secretion. In animal models as well as in human pathology, defects of FGF23 secretion or stability induce an increase in serum phosphate concentration, calcitriol levels and are associated with tissue calcifications and early mortality. On the opposite, overproduction of FGF23 is responsible for hypophosphatemia due to renal phosphate loss and inappropriately low serum calcitriol concentration and bone demineralization. FGF23 receptor is a heterodimer composed of a FGF receptor and the transmembrane protein Klotho. The increase in plasma FGF23 concentration and the decrease in Klotho expression observed in chronic kidney diseases (CKD) seem to play a causal role in the genesis of CKD complications and mortality. The circulating level of FGF23 appears to be an important prognostic marker in CKD.

Keywords:

FGF-23, phosphate, klotho

Affiliation:

Universite Paris Descartes, Faculte de Medecine, INSERM U845, Service des Explorations Fonctionnelles, Hopital Necker-Enfants Malades, Paris, France