[Pathophysiology of secondary hyperparathyroidism: the role of FGF23 and Klotho].
Secondary hyperparathyroidism is a complex metabolic alteration secondary to chronic kidney disease (CKD). Reduction of 1,25(OH)2D3 synthesis is the first derangement, followed by an increase in PTH, and, lastly, calcium and phosphate modifications. Vitamin D is a hormone whose actions take place through a specific receptor, the vitamin D receptor (VDR), which is ubiquitous. Accordingly, heterogeneous biological effects can be added to the classical effects on mineral bone metabolism. In the pathophysiology of secondary hyperparathyroidism, an important role is also played by alterations of calcium transport, which is under the control of two receptors: VDR and CaSR (calcium-sensing receptor). The expression of these receptors is reduced during CKD. Recent findings have allowed to identify a new hormonal system, the FGF23-Klotho axis, that integrates the old and simple, but now inadequate, PTH-Vit D axis. FGF23 is a circulating factor produced by osteocytes that inhibits renal phosphate reabsorption and 1-alpha-hydroxylase activity. As such, FGF23 is involved in phosphate homeostasis and its serum levels increase along with the progression of CKD. Interestingly, FGF23 has very low affinity for its receptor and requires the activity of Klotho, an anti-aging gene, to become active. These new actors allow us to identify a bone-kidney axis, whose real physiological importance is still under evaluation.
Mazzaferro
S
S
Dipartimento di Scienze Cliniche, Nefrologia, Policlinico Umberto I, Roma - Italy. sandro.mazzaferro@uniroma1.it
Pasquali
M
M
Tartaglione
L
L
Rotondi
S
S
Pirrò
G
G
D015415:Biomarkers / Q000097:blood; D002118:Calcium / Q000097:blood; D002908:Chronic Disease; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005966:Glucuronidase / Q000097:blood*; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000201:enzymology / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D007674:Kidney Diseases / Q000150:complications; D000090265:Klotho Proteins; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood; D018167:Receptors, Calcitriol / Q000097:blood; D044169:Receptors, Calcium-Sensing / Q000097:blood
D015415:Biomarkers; C000717427:FGF23 protein, human; D010281:Parathyroid Hormone; D010710:Phosphates; D018167:Receptors, Calcitriol; D044169:Receptors, Calcium-Sensing; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins; D002118:Calcium