Involvement of alpha-klotho and fibroblast growth factor receptor in the development of secondary hyperparathyroidism.

Objective: Fibroblast growth factor 23 (FGF23) has been shown to suppress parathyroid hormone (PTH) secretion. alpha-Klotho has been demonstrated to function as a fibroblast growth factor receptor (FGFR) cofactor for FGF23. Thus, both alpha-Klotho and FGFR may play roles in PTH synthesis and/or secretion. Functions of alpha-Klotho and FGFR in secondary hyperparathyroidism (SHPT) remain to be studied. The present studies explore the role of alpha-Klotho and FGFR in SHPT.

Methods: Hyperplastic parathyroid glands (n = 44) were obtained from patients with SHPT.

Results: Immunohistochemical study showed that both alpha-Klotho and FGFR1c expression in hyperplastic glands was significantly decreased compared with that in normal glands (Klotho p < 0.01, and FGFR1c p < 0.05). A significant positive correlation was observed between alpha-Klotho and FGFR1c (r(2) = 0.375, p < 0.01) indicating a cooperative system. Both alpha-Klotho (r(2) = 0.235, p < 0.05) and FGFR1c (r(2) = 0.181, p < 0.05) correlated positively with the calcium-sensing receptor (CaR), which plays an important role in the development of SHPT. In addition, expression of alpha-Klotho correlated negatively with parathyroid cell proliferation, as confirmed by Ki67 staining (r(2) = 0.148, p < 0.05).

Conclusions: Decreased expression of alpha-Klotho and FGFR1c in parallel with CaR expression and parathyroid cell growth may be involved in the pathogenesis of SHPT.