Fibroblast Growth Factor 23: Mineral Metabolism and Beyond

Overview

Journal Contrib Nephrol

Specialty Nephrology

Date 2017 May 24

PMID 28535521

Citations 20

Authors

Alexander Grabner

Sandro Mazzaferro

Giuseppe Cianciolo

Stefanie Krick

Irene Capelli

Silverio Rotondi

Claudio Ronco

Gaetano La Manna

Christian Faul

Affiliations

Soon will be listed here.

Abstract

Patients affected by chronic kidney disease (CKD) exhibit a high risk of cardiovascular mortality that is poorly explained by traditional risk factors. There is a growing awareness about the role of derangement of mineral metabolism that is currently accepted as a trigger and sustainer of cardiovascular disease (CVD) in CKD patients. The synthetic definition of CKD mineral and bone disorder (CKD-MBD) split the concept that the indexes of mineral metabolism extend their effects beyond the bone until the vascular wall and metabolic milieu of CKD patients through complex pathways. A better understanding of the biomarkers and mechanisms of left ventricular hypertrophy, CVD, inflammation, and chronic renal damage may help with the diagnosis and treatment of the systemic impairment that occurs secondary to CKD-MBD, thus slowing the progression of renal and CVD and improving patient survival. Recent insights into fibroblast growth factor (FGF) 23 have led to marked advancement in interpreting data on CVD and CKD progression ascribing to FGF23 a pivotal role in these pathologies independent of its co-receptor klotho and well beyond mineral metabolism. This review article will discuss the current experimental and clinical evidence regarding the role of FGF23 in physiology and pathophysiology of CKD and its associated complications with an emphasis on CVD.

Citing Articles

Coronary Artery Disease in Patients Undergoing Hemodialysis: A Problem that Sounds the Alarm.

Barbuto S, Hu L, Abenavoli C, Picotti M, La Manna G, De Nicola L Rev Cardiovasc Med. 2024; 25(6):200.

PMID: 39076335 PMC: 11270123. DOI: 10.31083/j.rcm2506200.

Is there a role in acute kidney injury for FGF23 and Klotho?.

Mattinzoli D, Molinari P, Romero-Gonzalez G, Bover J, Cicero E, Pesce F Clin Kidney J. 2023; 16(10):1555-1562.

PMID: 37779849 PMC: 10539225. DOI: 10.1093/ckj/sfad093.

Fibroblast Growth Factor 23 Signaling Does Not Increase Inflammation from Infection in the Cystic Fibrosis Bronchial Epithelium.

Hirsch M, Matthews E, Bollenbecker S, Easter M, Kiedrowski M, Barnes J Medicina (Kaunas). 2023; 59(9).

PMID: 37763754 PMC: 10538042. DOI: 10.3390/medicina59091635.

Fibroblast Growth Factor Signaling in Development and Disease.

Bollenbecker S, Barnes J, Krick S Int J Mol Sci. 2023; 24(11).

PMID: 37298683 PMC: 10253427. DOI: 10.3390/ijms24119734.

Serum Intact Fibroblast Growth Factor 23 Levels Are Negatively Associated with Bone Mineral Density in Chronic Hemodialysis Patients.

Lee W, Fang Y, Chen M, Liou H, Lee C, Tsai M J Clin Med. 2023; 12(4).

PMID: 36836085 PMC: 9964480. DOI: 10.3390/jcm12041550.

References

Leifheit-Nestler M, Siemer R, Flasbart K, Richter B, Kirchhoff F, Ziegler W . Induction of cardiac FGF23/FGFR4 expression is associated with left ventricular hypertrophy in patients with chronic kidney disease. Nephrol Dial Transplant. 2015; 31(7):1088-99. PMC: 6388939. DOI: 10.1093/ndt/gfv421. View

Olauson H, Lindberg K, Amin R, Sato T, Jia T, Goetz R . Parathyroid-specific deletion of Klotho unravels a novel calcineurin-dependent FGF23 signaling pathway that regulates PTH secretion. PLoS Genet. 2013; 9(12):e1003975. PMC: 3861040. DOI: 10.1371/journal.pgen.1003975. View

Cianciolo G, Galassi A, Capelli I, Angelini M, La Manna G, Cozzolino M . Vitamin D in Kidney Transplant Recipients: Mechanisms and Therapy. Am J Nephrol. 2016; 43(6):397-407. DOI: 10.1159/000446863. View

Evenepoel P, Meijers B, de Jonge H, Naesens M, Bammens B, Claes K . Recovery of hyperphosphatoninism and renal phosphorus wasting one year after successful renal transplantation. Clin J Am Soc Nephrol. 2008; 3(6):1829-36. PMC: 2572285. DOI: 10.2215/CJN.01310308. View

Mendoza J, Isakova T, Ricardo A, Xie H, Navaneethan S, Anderson A . Fibroblast growth factor 23 and Inflammation in CKD. Clin J Am Soc Nephrol. 2012; 7(7):1155-62. PMC: 3386678. DOI: 10.2215/CJN.13281211. View

Baia L, Humalda J, Vervloet M, Navis G, Bakker S, de Borst M . Fibroblast growth factor 23 and cardiovascular mortality after kidney transplantation. Clin J Am Soc Nephrol. 2013; 8(11):1968-78. PMC: 3817902. DOI: 10.2215/CJN.01880213. View

Ben-Dov I, Galitzer H, Lavi-Moshayoff V, Goetz R, Kuro-O M, Mohammadi M . The parathyroid is a target organ for FGF23 in rats. J Clin Invest. 2007; 117(12):4003-8. PMC: 2066196. DOI: 10.1172/JCI32409. View

Andrukhova O, Smorodchenko A, Egerbacher M, Streicher C, Zeitz U, Goetz R . FGF23 promotes renal calcium reabsorption through the TRPV5 channel. EMBO J. 2014; 33(3):229-46. PMC: 3983685. DOI: 10.1002/embj.201284188. View

Ravikumar P, Ye J, Zhang J, Pinch S, Hu M, Kuro-O M . α-Klotho protects against oxidative damage in pulmonary epithelia. Am J Physiol Lung Cell Mol Physiol. 2014; 307(7):L566-75. PMC: 4187038. DOI: 10.1152/ajplung.00306.2013. View

10.

Isakova T, Xie H, Yang W, Xie D, Anderson A, Scialla J . Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. JAMA. 2011; 305(23):2432-9. PMC: 3124770. DOI: 10.1001/jama.2011.826. View

11.

Chue C, Townend J, Moody W, Zehnder D, Wall N, Harper L . Cardiovascular effects of sevelamer in stage 3 CKD. J Am Soc Nephrol. 2013; 24(5):842-52. PMC: 3636795. DOI: 10.1681/ASN.2012070719. View

12.

Fliser D, Kollerits B, Neyer U, Ankerst D, Lhotta K, Lingenhel A . Fibroblast growth factor 23 (FGF23) predicts progression of chronic kidney disease: the Mild to Moderate Kidney Disease (MMKD) Study. J Am Soc Nephrol. 2007; 18(9):2600-8. DOI: 10.1681/ASN.2006080936. View

13.

Vervloet M, van Zuilen A, Heijboer A, Ter Wee P, Bots M, Blankestijn P . Fibroblast growth factor 23 is associated with proteinuria and smoking in chronic kidney disease: an analysis of the MASTERPLAN cohort. BMC Nephrol. 2012; 13:20. PMC: 3366907. DOI: 10.1186/1471-2369-13-20. View

14.

Block G, Bushinsky D, Cheng S, Cunningham J, Dehmel B, Drueke T . Effect of Etelcalcetide vs Cinacalcet on Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism: A Randomized Clinical Trial. JAMA. 2017; 317(2):156-164. DOI: 10.1001/jama.2016.19468. View

15.

Cianciolo G, La Manna G, Cappuccilli M, Lanci N, Della Bella E, Cuna V . VDR expression on circulating endothelial progenitor cells in dialysis patients is modulated by 25(OH)D serum levels and calcitriol therapy. Blood Purif. 2011; 32(3):161-73. DOI: 10.1159/000325459. View

16.

Scialla J, Lau W, Reilly M, Isakova T, Yang H, Crouthamel M . Fibroblast growth factor 23 is not associated with and does not induce arterial calcification. Kidney Int. 2013; 83(6):1159-68. PMC: 3672330. DOI: 10.1038/ki.2013.3. View

17.

Mazzaferro S, Pasquali M, Pirro G, Rotondi S, Tartaglione L . The bone and the kidney. Arch Biochem Biophys. 2010; 503(1):95-102. DOI: 10.1016/j.abb.2010.06.028. View

18.

Wolf M, Molnar M, Amaral A, Czira M, Rudas A, Ujszaszi A . Elevated fibroblast growth factor 23 is a risk factor for kidney transplant loss and mortality. J Am Soc Nephrol. 2011; 22(5):956-66. PMC: 3083317. DOI: 10.1681/ASN.2010080894. View

19.

Grabner A, Amaral A, Schramm K, Singh S, Sloan A, Yanucil C . Activation of Cardiac Fibroblast Growth Factor Receptor 4 Causes Left Ventricular Hypertrophy. Cell Metab. 2015; 22(6):1020-32. PMC: 4670583. DOI: 10.1016/j.cmet.2015.09.002. View

20.

Singh S, Grabner A, Yanucil C, Schramm K, Czaya B, Krick S . Fibroblast growth factor 23 directly targets hepatocytes to promote inflammation in chronic kidney disease. Kidney Int. 2016; 90(5):985-996. PMC: 5065745. DOI: 10.1016/j.kint.2016.05.019. View