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What would we like to know, and what do we not know about fibroblast growth factor 23?
J Nephrol. 2011 Nov-Dec; 24(6):696-706.JN

Abstract

Recently, a new view of the molecular mechanisms of phosphate homeostasis and secondary hyperparathyroidism pathogenesis has been proposed, with fibroblast growth factor 23 (FGF23) as a novel player in the field. FGF23 is a 32-kDa peptide secreted by the osteocytes involved in the control of phosphate homeostasis and calcitriol metabolism. FG23 is constantly elevated in advanced chronic kidney disease (CKD) patients, and recent studies have indicated that high levels are associated with the progression of CKD and with higher mortality rates in hemodialysis patients. In the CKD population, high serum FGF23 concentration seems to predict the occurrence of refractory secondary hyperparathyroidism, by inducing a resistance of the parathyroid glands to FGF23, and to be associated with higher mortality risk in incident hemodialysis patients. FGF23 appears to be involved in bone metabolism, but a direct effect of FGF23 on bone disease in humans has not yet been elucidated, even if the inhibitory effect of FGF23 on osteoblast activity that has been described in animal models and hereditary rickets is clearly connected with FGF23 deficiency. The association between altered levels of FGF23 and bone disease could be mainly due to the dysregulation of phosphate-handling and vitamin D metabolism, more than to a direct antiosteoblastic activity of FGF23. FGF23 appears to be a new biomarker, which is independently associated with several cardiovascular risk factors such as endothelial dysfunction, arterial stiffness and left ventricular hypertrophy, in the general population as well as in early CKD. All of the above have been related to cardiovascular and general mortality. Until now, we know that elevated FGF23 levels in dialysis patient are associated with several cardiovascular adverse outcomes mentioned above; the clinical relevance of high FGF23 values in dialysis patients remains unclear, because therapy with active vitamin D sterols further increases FGF23 levels but, on the other hand, is associated with a survival benefit in dialysis patients. This paradox highlights the need for future prospective randomized trials to evaluate the correlation between vitamin D therapy and FGF23 levels in dialysis patients. In the clinical setting, there are still different FGF23 actions that need investigation. In this sense, increased knowledge of mineral metabolism disorder alterations in CKD may be used to improve diagnostics and select future treatments.

Authors+Show Affiliations

Department of Medicine, Surgery, University of Milan, Milan, Italy. mario.cozzolino@unimi.itNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

21786227

Citation

Cozzolino, Mario, et al. "What Would We Like to Know, and what Do We Not Know About Fibroblast Growth Factor 23?" Journal of Nephrology, vol. 24, no. 6, 2011, pp. 696-706.
Cozzolino M, Galassi A, Apetrii M, et al. What would we like to know, and what do we not know about fibroblast growth factor 23? J Nephrol. 2011;24(6):696-706.
Cozzolino, M., Galassi, A., Apetrii, M., & Covic, A. (2011). What would we like to know, and what do we not know about fibroblast growth factor 23? Journal of Nephrology, 24(6), 696-706. https://doi.org/10.5301/jn.5000003
Cozzolino M, et al. What Would We Like to Know, and what Do We Not Know About Fibroblast Growth Factor 23. J Nephrol. 2011 Nov-Dec;24(6):696-706. PubMed PMID: 21786227.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - What would we like to know, and what do we not know about fibroblast growth factor 23? AU - Cozzolino,Mario, AU - Galassi,Andrea, AU - Apetrii,Mugurel, AU - Covic,Adrian, PY - 2011/05/27/accepted PY - 2011/7/26/entrez PY - 2011/7/26/pubmed PY - 2012/4/19/medline SP - 696 EP - 706 JF - Journal of nephrology JO - J Nephrol VL - 24 IS - 6 N2 - Recently, a new view of the molecular mechanisms of phosphate homeostasis and secondary hyperparathyroidism pathogenesis has been proposed, with fibroblast growth factor 23 (FGF23) as a novel player in the field. FGF23 is a 32-kDa peptide secreted by the osteocytes involved in the control of phosphate homeostasis and calcitriol metabolism. FG23 is constantly elevated in advanced chronic kidney disease (CKD) patients, and recent studies have indicated that high levels are associated with the progression of CKD and with higher mortality rates in hemodialysis patients. In the CKD population, high serum FGF23 concentration seems to predict the occurrence of refractory secondary hyperparathyroidism, by inducing a resistance of the parathyroid glands to FGF23, and to be associated with higher mortality risk in incident hemodialysis patients. FGF23 appears to be involved in bone metabolism, but a direct effect of FGF23 on bone disease in humans has not yet been elucidated, even if the inhibitory effect of FGF23 on osteoblast activity that has been described in animal models and hereditary rickets is clearly connected with FGF23 deficiency. The association between altered levels of FGF23 and bone disease could be mainly due to the dysregulation of phosphate-handling and vitamin D metabolism, more than to a direct antiosteoblastic activity of FGF23. FGF23 appears to be a new biomarker, which is independently associated with several cardiovascular risk factors such as endothelial dysfunction, arterial stiffness and left ventricular hypertrophy, in the general population as well as in early CKD. All of the above have been related to cardiovascular and general mortality. Until now, we know that elevated FGF23 levels in dialysis patient are associated with several cardiovascular adverse outcomes mentioned above; the clinical relevance of high FGF23 values in dialysis patients remains unclear, because therapy with active vitamin D sterols further increases FGF23 levels but, on the other hand, is associated with a survival benefit in dialysis patients. This paradox highlights the need for future prospective randomized trials to evaluate the correlation between vitamin D therapy and FGF23 levels in dialysis patients. In the clinical setting, there are still different FGF23 actions that need investigation. In this sense, increased knowledge of mineral metabolism disorder alterations in CKD may be used to improve diagnostics and select future treatments. SN - 1724-6059 UR - https://www.unboundmedicine.com/medline/citation/21786227/What_would_we_like_to_know_and_what_do_we_not_know_about_fibroblast_growth_factor_23 L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=21786227.ui DB - PRIME DP - Unbound Medicine ER -