Fibroblast growth factor 23 and bone metabolism in children with chronic kidney disease

被引:57
作者
van Husen, Michael [1 ]
Fischer, Ann-Katrin [1 ]
Lehnhardt, Anja [1 ]
Klaassen, Ilka [1 ]
Moeller, Kristina [1 ]
Mueller-Wiefel, Dirk-E. [1 ]
Kemper, Markus J. [1 ]
机构
[1] Univ Med Ctr, Dept Pediat Nephrol, Hamburg, Germany
关键词
bone; children; chronic kidney disease; pediatric nephrology; phosphate; SECONDARY HYPERPARATHYROIDISM; PHOSPHATE HOMEOSTASIS; MISSENSE MUTATION; FGF RECEPTOR; IN-VIVO; FIBROBLAST-GROWTH-FACTOR-23; EXPRESSION; PHOSPHORUS; LENGTH; MICE;
D O I
10.1038/ki.2010.107
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Fibroblast growth factor 23 (FGF23) is a circulating protein that regulates the renal reabsorption of phosphate and also inhibits 1-alpha-hydroxylase production. In adults FGF23 is increased in chronic kidney disease (CKD) and is an important prognostic factor for cardiovascular morbidity. In order to gain insight into the role of FGF23 and other biochemical variables of bone metabolism in children we studied 69 patients at different stages of CKD. FGF23 was found to be significantly elevated in stage 3 compared with stages 1 and 2 of CKD, preceding significant hyperphosphatemia in stage 4 disease. The highest levels of FGF23 were found in stage 5 compared with stages 1 and 2 CKD. The levels of FGF23 positively correlated with parathyroid hormone and phosphate concentrations and negatively with 1,25-dihydroxyvitamin D, the estimated glomerular filtration rate, and tubular phosphate reabsorption. Using multivariate analysis, hyperphosphatemia and low estimated glomerular filtration rate remained the most significant factors. Thus we found that FGF23 likely has an important role in pediatric calcium and phosphate homeostasis, and in vitamin D metabolism, even at an early stage of CKD. Further studies are needed to clarify the role of FGF23 on the pathogenesis of renal osteodystrophy and its impact on cardiovascular morbidity in pediatric patients with CKD. Kidney International (2010) 78, 200-206; doi:10.1038/ki.2010.107; published online 21 April 2010
引用
收藏
页码:200 / 206
页数:7
相关论文
共 37 条
[11]   Vitamin D deficiency [J].
Holick, Michael F. .
NEW ENGLAND JOURNAL OF MEDICINE, 2007, 357 (03) :266-281
[12]   A homozygous missense mutation in human KLOTHO causes severe tumoral calcinosis [J].
Ichikawa, Shoji ;
Lmel, Erik A. ;
Kreiter, Mary L. ;
Yu, Xijie ;
Mackenzie, Donald S. ;
Sorenson, Andrea H. ;
Goetz, Regina ;
Moharnmadi, Moosa ;
White, Kenneth E. ;
Econs, Michael J. .
JOURNAL OF CLINICAL INVESTIGATION, 2007, 117 (09) :2684-2691
[13]   Postprandial mineral metabolism and secondary hyperparathyroidism in early CKD [J].
Isakova, Tamara ;
Gutierrez, Orlando ;
Shah, Anand ;
Castaldo, Lorraine ;
Holmes, Julie ;
Lee, Hang ;
Wolf, Myles .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2008, 19 (03) :615-623
[14]   The Fgf families in humans, mice, and zebrafish: Their evolutional processes and roles in development, metabolism, and disease [J].
Itoh, Nobuyuki .
BIOLOGICAL & PHARMACEUTICAL BULLETIN, 2007, 30 (10) :1819-1825
[15]   Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia. [J].
Jonsson, KB ;
Zahradnik, R ;
Larsson, T ;
White, KE ;
Sugimoto, T ;
Imanishi, Y ;
Yamamoto, T ;
Hampson, G ;
Koshiyama, H ;
Ljunggren, Ö ;
Oba, K ;
Yang, IM ;
Miyauchi, A ;
Econs, MJ ;
Lavigne, J ;
Jüppner, H .
NEW ENGLAND JOURNAL OF MEDICINE, 2003, 348 (17) :1656-1663
[16]   Novel regulators of phosphate homeostasis and bone metabolism [J].
Juppner, Harald .
THERAPEUTIC APHERESIS AND DIALYSIS, 2007, 11 :S3-S22
[17]   Prevention and treatment of renal osteodystrophy in children on chronic renal failure:: European guidelines [J].
Klaus, G ;
Watson, A ;
Edefonti, A ;
Fischbach, M ;
Rönnholm, K ;
Schaefer, F ;
Simkova, E ;
Stefanidis, CJ ;
Strazdins, V ;
Vande Walle, J ;
Schröder, C ;
Zurowska, A ;
Ekim, M .
PEDIATRIC NEPHROLOGY, 2006, 21 (02) :151-159
[18]   K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Children with Chronic Kidney Disease - Foreword [J].
Langman, CB ;
Salusky, IB .
AMERICAN JOURNAL OF KIDNEY DISEASES, 2005, 46 (04) :S6-S121
[19]   Regulation of fibroblastic growth factor 23 expression but not degradation by PHEX [J].
Liu, SG ;
Guo, R ;
Simpson, LG ;
Xiao, ZS ;
Burnham, CE ;
Quarles, LD .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (39) :37419-37426
[20]   How fibroblast growth factor 23 works [J].
Liu, Shiguang ;
Quarles, L. Darryl .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2007, 18 (06) :1637-1647