Amino terminal cleavage of PTH(1–84) to PTH(7–84) is regulated by serum calcium concentration via calcium-sensing receptor in hemodialysis patients

• Published in: Clinical and experimental nephrology Vol. 14; no. 3; pp. 233 - 238
• Main Authors: Koshikawa, Masao, Nishiguchi, Kensuke, Yorifuji, Soshi, Shimazu, Keiji, Takaori, Koji, Mori, Keita, Eguchi, Eriko, Okada, Kikuo, Tanaka, Atsuo, Kuwahara, Takashi
• Format: Journal Article
• Language: English
• Published: Japan Springer Japan 01.06.2010; Springer Nature B.V
• Subjects: Calcium - blood; Cinacalcet Hydrochloride; Female; Humans; Male; Medicine; Medicine & Public Health; Middle Aged; Naphthalenes - therapeutic use; Nephrology; Original Article; Parathyroid Hormone - blood; Parathyroid Hormone - metabolism; Peptide Fragments - blood; Receptors, Calcium-Sensing - physiology; Renal Dialysis - adverse effects; Urology; Vitamin D - therapeutic use; Carboxyl-terminal (C-) fragment; Parathyroid hormone (PTH); Calcium-sensing receptor; Vitamin D; Secondary hyperparathyroidism; Calcimimetics
• ISSN: 1342-1751; 1437-7799
• DOI: 10.1007/s10157-010-0264-5

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). Result 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. Conclusion 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.