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Fibroblast growth factor 23--structure, function and role in kidney diseases.
Adv Clin Exp Med. 2012 May-Jun; 21(3):391-401.AC

Abstract

The fibroblast growth factor (FGF) family comprises a number of polypeptides which share a common homology core region. FGF-23, produced by osteoblasts and osteocytes, belongs to the FGF-19 subfamily and serves as the main phosphatonine. Two forms of circulating FGF-23 are detectable in serum: full-length FGF-23--intact FGF-23 (iFGF-23), which is biologically active, and the inactive C-terminal FGF-23 (cFGF-23). FGF-23 with a coreceptor (Klotho protein) inhibits renal phosphate reabsorption and synthesis of calcitriol by reducing 1alpha-hydroxylase (CYP27B1) activity, reducing vitamin D-dependent phosphate intestinal absorption. High phosphorus intake, 1,25-dihydroxyvitamin D3 and PTH are the main stimuli for FGF-23 secretion. Impaired FGF-23 metabolism is involved in phosphate disturbances manifesting as rickets or osteomalacia or increased tissue calcinosis. FGF-23 may be also produced by some tumors leading to hypophosphatemia. Both cFGF-23 and iFGF-23 concentrations start to increase with mild impairment of the glomerular filtration rate in stage 2 or 3 of chronic kidney disease (CKD) as a consequence of the increased FGF-23 production. It seems that enhanced FGF-23 secretion may constitute a protective mechanism against enhanced phosphate accumulation in the early stages of CKD. However, it may lead to calcitriol deficiency and escalation of secondary hyperparathyroidism. Increased FGF-23 level is supposed to be an independent factor increasing mortality of CKD patients. There is ambiguous data if FGF-23 only reflects disturbances in calcium-phosphate metabolism or if it exerts a detrimental effect itself by diminishing calcitriol synthesis, inducing cell proliferation or acting through low-affinity, Klotho-independent receptors in the heart and endothelium. So far, little evidence supports direct FGF-23 toxicity.

Authors+Show Affiliations

Department of Pathophysiology, Medical University of Silesia, Katowice, Poland. pkocelak@sum.edu.plNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

23214203

Citation

Kocełak, Piotr, et al. "Fibroblast Growth Factor 23--structure, Function and Role in Kidney Diseases." Advances in Clinical and Experimental Medicine : Official Organ Wroclaw Medical University, vol. 21, no. 3, 2012, pp. 391-401.
Kocełak P, Olszanecka-Glinianowicz M, Chudek J. Fibroblast growth factor 23--structure, function and role in kidney diseases. Adv Clin Exp Med. 2012;21(3):391-401.
Kocełak, P., Olszanecka-Glinianowicz, M., & Chudek, J. (2012). Fibroblast growth factor 23--structure, function and role in kidney diseases. Advances in Clinical and Experimental Medicine : Official Organ Wroclaw Medical University, 21(3), 391-401.
Kocełak P, Olszanecka-Glinianowicz M, Chudek J. Fibroblast Growth Factor 23--structure, Function and Role in Kidney Diseases. Adv Clin Exp Med. 2012 May-Jun;21(3):391-401. PubMed PMID: 23214203.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fibroblast growth factor 23--structure, function and role in kidney diseases. AU - Kocełak,Piotr, AU - Olszanecka-Glinianowicz,Magdalena, AU - Chudek,Jerzy, PY - 2012/12/11/entrez PY - 2012/12/12/pubmed PY - 2013/1/5/medline SP - 391 EP - 401 JF - Advances in clinical and experimental medicine : official organ Wroclaw Medical University JO - Adv Clin Exp Med VL - 21 IS - 3 N2 - The fibroblast growth factor (FGF) family comprises a number of polypeptides which share a common homology core region. FGF-23, produced by osteoblasts and osteocytes, belongs to the FGF-19 subfamily and serves as the main phosphatonine. Two forms of circulating FGF-23 are detectable in serum: full-length FGF-23--intact FGF-23 (iFGF-23), which is biologically active, and the inactive C-terminal FGF-23 (cFGF-23). FGF-23 with a coreceptor (Klotho protein) inhibits renal phosphate reabsorption and synthesis of calcitriol by reducing 1alpha-hydroxylase (CYP27B1) activity, reducing vitamin D-dependent phosphate intestinal absorption. High phosphorus intake, 1,25-dihydroxyvitamin D3 and PTH are the main stimuli for FGF-23 secretion. Impaired FGF-23 metabolism is involved in phosphate disturbances manifesting as rickets or osteomalacia or increased tissue calcinosis. FGF-23 may be also produced by some tumors leading to hypophosphatemia. Both cFGF-23 and iFGF-23 concentrations start to increase with mild impairment of the glomerular filtration rate in stage 2 or 3 of chronic kidney disease (CKD) as a consequence of the increased FGF-23 production. It seems that enhanced FGF-23 secretion may constitute a protective mechanism against enhanced phosphate accumulation in the early stages of CKD. However, it may lead to calcitriol deficiency and escalation of secondary hyperparathyroidism. Increased FGF-23 level is supposed to be an independent factor increasing mortality of CKD patients. There is ambiguous data if FGF-23 only reflects disturbances in calcium-phosphate metabolism or if it exerts a detrimental effect itself by diminishing calcitriol synthesis, inducing cell proliferation or acting through low-affinity, Klotho-independent receptors in the heart and endothelium. So far, little evidence supports direct FGF-23 toxicity. SN - 1899-5276 UR - https://www.unboundmedicine.com/medline/citation/23214203/Fibroblast_growth_factor_23__structure_function_and_role_in_kidney_diseases_ L2 - http://www.advances.am.wroc.pl/pdf/2012/21/3/391.pdf DB - PRIME DP - Unbound Medicine ER -