Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Klotho and endocrine fibroblast growth factors: markers of chronic kidney disease progression and cardiovascular complications?

Klotho and endocrine fibroblast growth factors: markers of chronic kidney disease progression and... ABSTRACTThree members of the fibroblast growth factor (FGF) family, FGF19, FGF21 and FGF23, are different from the other members in two major aspects. First, they are actually not growth factors but endocrine factors that regulate various metabolic processes. Second, their physiological receptors are not FGF receptors (FGFRs) but binary complexes of FGFRs and Klotho proteins. FGF23 and FGF21 have emerged as biomarkers that start increasing in early-stage chronic kidney disease (CKD). FGF23 is a bone-derived phosphaturic hormone that binds to the αKlotho–FGFR complex expressed in renal tubules to increase phosphate excretion per nephron. The FGF23 increase is deemed necessary to compensate for the decrease in the nephron number during CKD progression and to maintain the phosphate balance. However, the increase in phosphate excretion per nephron induces renal tubular damage and accelerates nephron loss. CKD progression is also associated with an increase in calciprotein particles (CPPs) in the blood. CPPs are calcium–phosphate nanoparticles with the ability to induce endothelial damage and inflammatory responses. The fact that serum CPP levels are correlated with vascular calcification/stiffness and mortality in CKD patients suggests that CPPs may serve as a ‘pathogen’ of cardiovascular complications. Like FGF23, FGF21 starts increasing in early-stage CKD. FGF21 is a liver-derived hormone that binds to the βKlotho–FGFR complex expressed in the central nervous system to induce stress responses, including activation of the sympathetic nervous system and the hypothalamus–pituitary–adrenal axis. Thus FGF21 and FGF23 are not merely biomarkers for CKD progression but potential pathogenic agents that accelerate CKD progression and aggravate cardiovascular complications. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nephrology Dialysis Transplantation Oxford University Press

Klotho and endocrine fibroblast growth factors: markers of chronic kidney disease progression and cardiovascular complications?

Kuro-o, Makoto
Nephrology Dialysis Transplantation , Volume 34 (1): 7 – Jan 1, 2019
Download PDF
7 pages

Loading next page...
 
/lp/ou_press/klotho-and-endocrine-fibroblast-growth-factors-marker-of-chronic-xv1yalglcb
Publisher
Oxford University Press
Copyright
© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
ISSN
0931-0509
eISSN
1460-2385
DOI
10.1093/ndt/gfy126
Publisher site
See Article on Publisher Site

Abstract

ABSTRACTThree members of the fibroblast growth factor (FGF) family, FGF19, FGF21 and FGF23, are different from the other members in two major aspects. First, they are actually not growth factors but endocrine factors that regulate various metabolic processes. Second, their physiological receptors are not FGF receptors (FGFRs) but binary complexes of FGFRs and Klotho proteins. FGF23 and FGF21 have emerged as biomarkers that start increasing in early-stage chronic kidney disease (CKD). FGF23 is a bone-derived phosphaturic hormone that binds to the αKlotho–FGFR complex expressed in renal tubules to increase phosphate excretion per nephron. The FGF23 increase is deemed necessary to compensate for the decrease in the nephron number during CKD progression and to maintain the phosphate balance. However, the increase in phosphate excretion per nephron induces renal tubular damage and accelerates nephron loss. CKD progression is also associated with an increase in calciprotein particles (CPPs) in the blood. CPPs are calcium–phosphate nanoparticles with the ability to induce endothelial damage and inflammatory responses. The fact that serum CPP levels are correlated with vascular calcification/stiffness and mortality in CKD patients suggests that CPPs may serve as a ‘pathogen’ of cardiovascular complications. Like FGF23, FGF21 starts increasing in early-stage CKD. FGF21 is a liver-derived hormone that binds to the βKlotho–FGFR complex expressed in the central nervous system to induce stress responses, including activation of the sympathetic nervous system and the hypothalamus–pituitary–adrenal axis. Thus FGF21 and FGF23 are not merely biomarkers for CKD progression but potential pathogenic agents that accelerate CKD progression and aggravate cardiovascular complications.

Journal

Nephrology Dialysis Transplantation – Oxford University Press

Published: Jan 1, 2019

Keywords: calciprotein particles; FGF-21; FGF-23; Klotho; PTH; vitamin D

References

  • Pituitary extracts and steroid hormones in the control of 3T3 cell growth
    Armelin, HA.
  • Localisation of a fibroblast growth factor and its effect alone and with hydrocortisone on 3T3 cell growth
    Gospodarowicz, D.
  • Fibroblast growth factors: from molecular evolution to roles in development, metabolism and disease
    Itoh, N; Ornitz, DM.
  • Molecular insights into the klotho-dependent, endocrine mode of action of fibroblast growth factor 19 subfamily members
    Goetz, R; Beenken, A; Ibrahimi, OA
  • Crystal structure of a ternary FGF-FGFR-heparin complex reveals a dual role for heparin in FGFR binding and dimerization
    Schlessinger, J; Plotnikov, AN; Ibrahimi, OA
  • Mutation of the mouse klotho gene leads to a syndrome resembling ageing
    Kuro-O, M; Matsumura, Y; Aizawa, H
  • Endocrine FGFs and Klothos: emerging concepts
    Kuro-O, M.
  • α-Klotho is a non-enzymatic molecular scaffold for FGF23 hormone signalling
    Chen, G; Liu, Y; Goetz, R
  • Regulation of fibroblast growth factor-23 signaling by klotho
    Kurosu, H; Ogawa, Y; Miyoshi, M
  • βKlotho is required for metabolic activity of fibroblast growth factor 21
    Ogawa, Y; Kurosu, H; Yamamoto, M
  • Tissue-specific expression of betaKlotho and fibroblast growth factor (FGF) receptor isoforms determines metabolic activity of FGF19 and FGF21
    Kurosu, H; Choi, M; Ogawa, Y
  • Structures of beta-klotho reveal a ‘zip code’-like mechanism for endocrine FGF signalling
    Lee, S; Choi, J; Mohanty, J
  • Fibroblast growth factor 23 and klotho: physiology and pathophysiology of an endocrine network of mineral metabolism
    Hu, MC; Shiizaki, K; Kuro-O, M
  • The parathyroid is a target organ for FGF23 in rats
    Ben-Dov, IZ; Galitzer, H; Lavi-Moshayoff, V
  • Research resource: comprehensive expression atlas of the fibroblast growth factor system in adult mouse
    Fon Tacer, K; Bookout, AL; Ding, X
  • Initial FGF23-mediated signaling occurs in the distal convoluted tubule
    Farrow, EG; Davis, SI; Summers, LJ
  • FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis
    Shimada, T; Hasegawa, H; Yamazaki, Y
  • Fibroblast growth factor 23 is a counter-regulatory phosphaturic hormone for vitamin D
    Liu, S; Tang, W; Zhou, J
  • Klotho in health and disease
    Kuro-O, M.
  • Calcium deficiency reduces circulating levels of FGF23
    Rodriguez-Ortiz, ME; Lopez, I; Munoz-Castaneda, JR
  • Interactions between calcium and phosphorus in the regulation of the production of fibroblast growth factor 23 in vivo
    Quinn, SJ; Thomsen, AR; Pang, JL
  • PTH increases FGF23 gene expression and mediates the high-FGF23 levels of experimental kidney failure: a bone parathyroid feedback loop
    Lavi-Moshayoff, V; Wasserman, G; Meir, T
  • 1,25-Dihydroxyvitamin D3/VDR-mediated induction of FGF23 as well as transcriptional control of other bone anabolic and catabolic genes that orchestrate the regulation of phosphate and calcium mineral metabolism
    Barthel, TK; Mathern, DR; Whitfield, GK
  • The substantial loss of nephrons in healthy human kidneys with aging
    Denic, A; Lieske, JC; Chakkera, HA
  • Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease
    Isakova, T; Wahl, P; Vargas, GS
  • Direct evidence for a causative role of FGF23 in the abnormal renal phosphate handling and vitamin D metabolism in rats with early-stage chronic kidney disease
    Hasegawa, H; Nagano, N; Urakawa, I
  • Renal toxicity of phosphate in rats
    Haut, LL; Alfrey, AC; Guggenheim, S
  • Phosphate excess and progressive renal failure: the precipitation-calcification hypothesis
    Lau, K.
  • Calcium phosphate-induced renal epithelial injury and stone formation: involvement of reactive oxygen species
    Aihara, K; Byer, KJ; Khan, SR.
  • Klotho, phosphate and FGF-23 in ageing and disturbed mineral metabolism
    Kuro-O, M.
  • Prevention and control of phosphate retention/hyperphosphatemia in CKD-MBD: what is normal, when to start, and how to treat?
    Martin, KJ; Gonzalez, EA.
  • Cardiovascular calcification in nondialyzed patients with chronic kidney disease
    Qunibi, WY.
  • Fetuin-mineral complex reflects extraosseous calcification stress in CKD
    Hamano, T; Matsui, I; Mikami, S
  • Phosphorylated fetuin-A-containing calciprotein particles are associated with aortic stiffness and a procalcific milieu in patients with pre-dialysis CKD
    Smith, ER; Ford, ML; Tomlinson, LA
  • Hierarchical role of fetuin-A and acidic serum proteins in the formation and stabilization of calcium phosphate particles
    Heiss, A; Eckert, T; Aretz, A
  • Structural basis of calcification inhibition by α2-HS glycoprotein/fetuin-A. Formation of colloidal calciprotein particles
    Heiss, A; DuChesne, A; Denecke, B
  • Fetuin-A regulation of calcified matrix metabolism
    Jahnen-Dechent, W; Heiss, A; Schafer, C
  • The serum protein α2-Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification
    Schafer, C; Heiss, A; Schwarz, A
  • Increased inorganic phosphate induces human endothelial cell apoptosis in vitro
    Di Marco, GS; Hausberg, M; Hillebrand, U
  • Hyperphosphatemia-induced nanocrystals upregulate the expression of bone morphogenetic protein-2 and osteopontin genes in mouse smooth muscle cells in vitro
    Sage, AP; Lu, J; Tintut, Y
  • Phosphonoformic acid prevents vascular smooth muscle cell calcification by inhibiting calcium-phosphate deposition
    Villa-Bellosta, R; Sorribas, V.
  • Calcium phosphate crystals induce cell death in human vascular smooth muscle cells: a potential mechanism in atherosclerotic plaque destabilization
    Ewence, AE; Bootman, M; Roderick, HL
  • Fetuin-A-containing calciprotein particles reduce mineral stress in the macrophage
    Smith, ER; Hanssen, E; McMahon, LP
  • Calciprotein particle (CPP): a true culprit of phosphorus woes?
    Kuro-O, M.
  • Identification and quantification of plasma calciprotein particles with distinct physical properties in patients with chronic kidney disease
    Miura, Y; Iwazu, Y; Shiizaki, K
  • Relation between serum phosphate level and cardiovascular event rate in people with coronary disease
    Tonelli, M; Sacks, F; Pfeffer, M
  • Relationship of estimated GFR and coronary artery calcification in the CRIC (Chronic Renal Insufficiency Cohort) Study
    Budoff, MJ; Rader, DJ; Reilly, MP
  • Fibroblast growth factor 23 is not associated with and does not induce arterial calcification
    Scialla, JJ; Lau, WL; Reilly, MP
  • Fibroblast growth factor-23 and cardiovascular events in CKD
    Scialla, JJ; Xie, H; Rahman, M
  • Association of fibroblast growth factor 23 with atrial fibrillation in chronic kidney disease, from the chronic renal insufficiency cohort study
    Mehta, R; Cai, X; Lee, J
  • FGF23 regulates renal sodium handling and blood pressure
    Andrukhova, O; Slavic, S; Smorodchenko, A
  • FGF23 induces left ventricular hypertrophy
    Faul, C; Amaral, AP; Oskouei, B
  • Gene expression analysis of kidneys from transgenic mice expressing fibroblast growth factor-23
    Marsell, R; Krajisnik, T; Goransson, H
  • Antiaging gene klotho regulates adrenal CYP11B2 expression and aldosterone synthesis
    Zhou, X; Chen, K; Wang, Y
  • Up-regulation of FGF23 release by aldosterone
    Zhang, B; Umbach, AT; Chen, H
  • The renin-angiotensin-aldosterone system: cardiorenal effects and implications for renal and cardiovascular disease states
    Brewster, UC; Setaro, JF; Perazella, MA.
  • FGF-21 as a novel metabolic regulator
    Kharitonenkov, A; Shiyanova, TL; Koester, A
  • Endocrine regulation of the fasting response by PPARα-mediated induction of fibroblast growth factor 21
    Inagaki, T; Dutchak, P; Zhao, G
  • FGF21 regulates metabolism and circadian behavior by acting on the nervous system
    Bookout, AL; de Groot, MH; Owen, BM
  • Longevity and lifespan control in mammals: lessons from the mouse
    Chen, YF; Wu, CY; Kao, CH
  • The starvation hormone, fibroblast growth factor-21, extends lifespan in mice
    Zhang, Y; Xie, Y; Berglund, ED
  • Fibroblast growth factor 21 in chronic kidney disease
    Anuwatmatee, S; Tang, S; Wu, BJ
  • Association between circulating fibroblast growth factor 21 and mortality in end-stage renal disease
    Kohara, M; Masuda, T; Shiizaki, K
  • Inhibition of growth hormone signaling by the fasting-induced hormone FGF21
    Inagaki, T; Lin, VY; Goetz, R
  • Fibroblast growth factor 21 promotes bone loss by potentiating the effects of peroxisome proliferator-activated receptor gamma
    Wei, W; Dutchak, PA; Wang, X
  • Ambulatory blood pressure in chronic kidney disease
    Cohen, DL; Huan, Y; Townsend, RR.
  • Inhibitory neurotransmission in the nucleus tractus solitarii: implications for baroreflex resetting during exercise
    Potts, JT.
  • Baroreflex dysfunction in chronic kidney disease
    Kaur, M; Chandran, DS; Jaryal, AK
  • Association between depression and mortality in patients receiving long-term dialysis: a systematic review and meta-analysis
    Farrokhi, F; Abedi, N; Beyene, J
  • Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis
    Inagaki, T; Choi, M; Moschetta, A
  • FGF19 as a postprandial, insulin-independent activator of hepatic protein and glycogen synthesis
    Kir, S; Beddow, SA; Samuel, VT
  • Microbiota metabolites: pivotal players of cardiovascular damage in chronic kidney disease
    Cosola, C; Rocchetti, MT; Cupisti, A
  • Impaired postprandial fibroblast growth factor (FGF)-19 response in patients with stage 5 chronic kidney diseases is ameliorated following antioxidative therapy
    Li, M; Qureshi, AR; Ellis, E
  • Association of elevated serum PO4, Ca × PO4 product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis patients
    Ganesh, SK; Stack, AG; Levin, NW