Amino terminal cleavage of PTH(1-84) to PTH(7-84) is regulated by serum calcium concentration via calcium-sensing receptor in hemodialysis patients.
BACKGROUND
Secondary hyperparathyroidism is one of the critical complications of end-stage renal disease patients. Conventionally intact parathyroid hormone (iPTH) was used to assess secondary hyperparathyroidism, but this assay measures both PTH(1-84) (full-length parathyroid hormone) and PTH(7-84) (amino (N)-terminal-cleaved parathyroid hormone). PTH(7-84) is biologically inactive or antagonistic for PTH. In this study, we examined the relationship between serum calcium concentration and PTH(7-84)/PTH(1-84) ratio and the effect of calcimimetics on the ratio in hemodialysis (HD) patients.


METHODS
Ionized-calcium (iCa), iPTH, and whole PTH (wPTH) were measured at the start of HD sessions on HD patients. Patients were divided into four groups by presence (+) or absence (-) of vitamin D (VD) and calcimimetics (CM).


RESULTS
PTH(7-84)/PTH(1-84) ratios of the four groups [VD(-)CM(-), VD(+)CM(-), VD(-)CM(+) and VD(+)CM(+)] were 0.735, 0.799, 0.844, and 1.156, respectively. In VD(-)CM(-) and VD(+)CM(-) groups, iCa and PTH(7-84)/PTH(1-84) ratio showed equilateral correlation (r = 0.634, p < 0.001 and r = 0.360, p < 0.01, respectively). In calcimimetics-treated group, iCa and PTH(7-84)/PTH(1-84) ratio did not show correlation.


CONCLUSIONS
Whereas in the absence of calcimimetics cleavage of N-terminal PTH was regulated by serum calcium concentration, this regulation was abolished in the presence of calcimimetics. This suggests that cleavage of N-terminal PTH is regulated by calcium concentration via a calcium-sensing receptor and that calcimimetics may have a novel effect to reduce PTH level.
Koshikawa
Masao
M
Department of Nephrology, Osaka Saiseikai Nakatsu Hospital, Shibata, Kita-ku, Osaka, 530-0012, Japan. mkoshi@kuhp.kyoto-u.ac.jp
Nishiguchi
Kensuke
K
Yorifuji
Soshi
S
Shimazu
Keiji
K
Takaori
Koji
K
Mori
Keita
K
Eguchi
Eriko
E
Okada
Kikuo
K
Tanaka
Atsuo
A
Kuwahara
Takashi
T
D002118:Calcium / Q000097:blood*; D000069449:Cinacalcet; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000627:therapeutic use; D010281:Parathyroid Hormone / Q000097:blood* / Q000378:metabolism; D010446:Peptide Fragments / Q000097:blood*; D044169:Receptors, Calcium-Sensing / Q000502:physiology*; D006435:Renal Dialysis / Q000009:adverse effects; D014807:Vitamin D / Q000627:therapeutic use
D009281:Naphthalenes; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D044169:Receptors, Calcium-Sensing; C414937:parathyroid hormone (7-84); D014807:Vitamin D; D002118:Calcium; D000069449:Cinacalcet