| [ Summary ] |
Traditionally, decreased 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], hyperphosphatemia, and resulting hypocalcemia have been known to contribute to the pathogenesis of secondary hyperparathyroidism. However, the precise mechanism of PTH hypersecretion in early-stage CKD has been unclear. Recently, the discovery of FGF-23 has clarified the early pathogenesis of secondary hyperparathyroidism associated with CKD. In patients with CKD, FGF-23 levels increase progressively to compensate for phosphate retention, resulting in suppression of renal 1,25(OH)2D3 production and thereby triggering the early development of secondary hyperparathyroidism. FGF-23 also acts directly on the parathyroid to decrease parathyroid hormone synthesis. However, in patients with end-stage renal disease, markedly increased FGF-23 fails to exert this effect, owing to the downregulation of the parathyroid complex of Klotho and FGF receptor 1. It is hoped that further research in this area will facilitate advances in our understanding of secondary hyperparathyroidism. |