Regulation of parathyroid function in chronic kidney disease (CKD).
In chronic kidney disease (CKD), several abnormalities in bone and mineral metabolism develop in the majority of patients. The parathyroid plays a very important role in regulating bone and mineral metabolism; thus, control of parathyroid function is one of the main targets of the management of CKD-mineral and bone disorder (CKD-MBD). In the development of secondary hyperparathyroidism, it has recently been suggested that fibroblast growth factor 23 (FGF23) plays a crucial role, both as a phosphaturic factor and as a suppressor of active vitamin D (1,25D) production in the kidney. FGF23 is originally secreted to prevent hyperphosphatemia in CKD, but this occurs at the expense of low 1,25D and hyperparathyroidism ("trade-off" hypothesis revisited). Furthermore, recent data suggest that FGF23 could be another useful marker for the prognosis of hyperparathyroidism, because a high serum level may reflect the cumulative dose of vitamin D analogues previously administered. We have also demonstrated that severe hyperparathyroidism was associated with the production and secretion of a new form of parathyroid hormone (PTH) molecule, which can be detected by third-generation assays for PTH, but not by the second-generation assays. For the regression of already established nodular hyperplasia, the more advanced type of parathyroid hyperplasia, it is certainly necessary, in the near future, to develop new agents that specifically induce apoptosis in parathyroid cells. Until such agents are developed, prevention and early recognition of nodular hyperplasia is mandatory for the effective and safe management of hyperparathyroidism in CKD.
Fukagawa
Masafumi
M
Division of Nephrology and Dialysis Center, Kobe University School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan. fukagawa@med.kobe-u.ac.jp
Nakanishi
Shohei
S
Fujii
Hideki
H
Hamada
Yasuhiro
Y
Abe
Takaya
T
D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D002118:Calcium / Q000097:blood; D002908:Chronic Disease; D000089703:Fibroblast Growth Factor-23; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006965:Hyperplasia / Q000473:pathology / Q000517:prevention & control; D007674:Kidney Diseases / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D010280:Parathyroid Glands / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D010281:Parathyroid Hormone / Q000378:metabolism; D010710:Phosphates / Q000097:blood
C000717427:FGF23 protein, human; D010281:Parathyroid Hormone; D010710:Phosphates; D000089703:Fibroblast Growth Factor-23; D002118:Calcium