Effects of cinacalcet treatment on serum soluble Klotho levels in haemodialysis patients with secondary hyperparathyroidism

被引:26
作者
Komaba, Hirotaka [1 ,2 ,3 ]
Koizumi, Masahiro [1 ,2 ,3 ]
Tanaka, Hisae [1 ]
Takahashi, Hiroo [1 ]
Sawada, Kaichiro [1 ]
Kakuta, Takatoshi [1 ]
Fukagawa, Masafumi [1 ,2 ,3 ]
机构
[1] Tokai Univ, Sch Med, Div Nephrol Endocrinol & Metab, Isehara, Kanagawa 25911, Japan
[2] Kobe Univ, Sch Med, Div Nephrol, Kobe, Hyogo 650, Japan
[3] Kobe Univ, Sch Med, Kidney Ctr, Kobe, Hyogo 650, Japan
关键词
cinacalcet hydrochloride; FGF23; haemodialysis; secondary hyperparathyroidism; soluble Klotho; DOSE VITAMIN-D; TRPV5; CHANNEL; FGF RECEPTOR; CALCIUM;
D O I
10.1093/ndt/gfr645
中图分类号
R3 [基础医学]; R4 [临床医学];
学科分类号
1001 ; 1002 ; 100602 ;
摘要
Background. Klotho is a transmembrane protein that acts as a cofactor for fibroblast growth factor 23 (FGF23). Klotho also exists as a soluble circulating protein, but its role in secondary hyperparathyroidism (SHPT) is largely unknown. Methods. We measured serum soluble Klotho levels in 51 haemodialysis patients, who participated and completed a 52-week, multicentre, open-label single-arm trial that examined the effectiveness of cinacalcet for treating SHPT. Results. After 12 weeks of cinacalcet treatment, serum soluble Klotho decreased significantly (P 0.03) but only marginally from 398 pg/mL [interquartile range (IQR), 268-588 pg/mL] to 378 pg/mL (IQR, 266-568 pg/mL) and returned to baseline levels. There were no significant associations between the changes in soluble Klotho levels and changes in any other parameters of mineral metabolism, including serum calcium, phosphorus, intact parathyroid hormone and FGF23. Conclusion. Despite significant alterations in mineral and bone metabolism during treatment with cinacalcet, this resulted in only small and transient reductions in serum levels of soluble Klotho.
引用
收藏
页码:1967 / 1969
页数:3
相关论文
共 18 条
[1]   Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis [J].
Block, GA ;
Martin, KJ ;
de Francisco, ALM ;
Turner, SA ;
Avram, MM ;
Suranyi, MG ;
Hercz, G ;
Cunningham, J ;
Abu-Alfa, AK ;
Messa, P ;
Coyne, DW ;
Locatelli, F ;
Cohen, RM ;
Evenepoel, P ;
Moe, SM ;
Fournier, A ;
Braun, J ;
McCary, LC ;
Zani, VJ ;
Olson, KA ;
Drüeke, TB ;
Goodman, WG .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 350 (15) :1516-1525
[2]   Removal of sialic acid involving Klotho causes cell-surface retention of TRPV5 channel via binding to galectin-1 [J].
Cha, Seung-Kuy ;
Ortega, Bernardo ;
Kurosu, Hiroshi ;
Rosenblatt, Kevin P. ;
Kuro-O, Makoto ;
Huang, Chou-Long .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (28) :9805-9810
[3]   The β-glucuronidase klotho hydrolyzes and activates the TRPV5 channel [J].
Chang, Q ;
Hoefs, S ;
van der Kemp, AW ;
Topala, CN ;
Bindels, RJ ;
Hoenderop, JG .
SCIENCE, 2005, 310 (5747) :490-493
[4]   Cinacalcet (KRN1493) effectively decreases the serum intact PTH level with favorable control of the serum phosphorus and calcium levels in Japanese dialysis patients [J].
Fukagawa, Masafumi ;
Yumita, Shigeru ;
Akizawa, Tadao ;
Uchida, Eiji ;
Tsukamoto, Yusuke ;
Iwasaki, Manabu ;
Koshikawa, Shozo .
NEPHROLOGY DIALYSIS TRANSPLANTATION, 2008, 23 (01) :328-335
[5]   Klotho Deficiency Causes Vascular Calcification in Chronic Kidney Disease [J].
Hu, Ming Chang ;
Shi, Mingjun ;
Zhang, Jianning ;
Quinones, Henry ;
Griffith, Carolyn ;
Kuro-o, Makoto ;
Moe, Orson W. .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2011, 22 (01) :124-136
[6]   Klotho: a novel phosphaturic substance acting as an autocrine enzyme in the renal proximal tubule [J].
Hu, Ming Chang ;
Shi, Mingjun ;
Zhang, Jianning ;
Pastor, Johanne ;
Nakatani, Teruyo ;
Lanske, Beate ;
Razzaque, M. Shawkat ;
Rosenblatt, Kevin P. ;
Baum, Michel G. ;
Kuro-o, Makoto ;
Moe, Orson W. .
FASEB JOURNAL, 2010, 24 (09) :3438-3450
[7]   Severely reduced production of Klotho in human chronic renal failure kidney [J].
Koh, N ;
Fujimori, T ;
Nishiguchi, S ;
Tamori, A ;
Shiomi, S ;
Nakatani, T ;
Sugimura, K ;
Kishimoto, T ;
Kinoshita, S ;
Kuroki, T ;
Nabeshima, Y .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2001, 280 (04) :1015-1020
[8]   Cinacalcet treatment and serum FGF23 levels in haemodialysis patients with secondary hyperparathyroidism [J].
Koizumi, Masahiro ;
Komaba, Hirotaka ;
Nakanishi, Shohei ;
Fujimori, Akira ;
Fukagawa, Masafumi .
NEPHROLOGY DIALYSIS TRANSPLANTATION, 2012, 27 (02) :784-790
[9]   Cinacalcet Effectively Reduces Parathyroid Hormone Secretion and Gland Volume Regardless of Pretreatment Gland Size in Patients with Secondary Hyperparathyroidism [J].
Komaba, Hirotaka ;
Nakanishi, Shohei ;
Fujimori, Akira ;
Tanaka, Motoko ;
Shin, Jeongsoo ;
Shibuya, Koji ;
Nishioka, Masato ;
Hasegawa, Hirohito ;
Kurosawa, Takeshi ;
Fukagawa, Masafumi .
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2010, 5 (12) :2305-2314
[10]   Depressed expression of Klotho and FGF receptor 1 in hyperplastic parathyroid glands from uremic patients [J].
Komaba, Hirotaka ;
Goto, Shunsuke ;
Fujii, Hideki ;
Hamada, Yasuhiro ;
Kobayashi, Akira ;
Shibuya, Koji ;
Tominaga, Yoshihiro ;
Otsuki, Naoki ;
Nibu, Ken-ichi ;
Nakagawa, Kimie ;
Tsugawa, Naoko ;
Okano, Toshio ;
Kitazawa, Riko ;
Fukagawa, Masafumi .
KIDNEY INTERNATIONAL, 2010, 77 (03) :232-238