Associations between fibroblast growth factor 23 and cardiac characteristics in pediatric heart failure
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In adults with heart failure, elevated levels of fibroblast growth factor 23 (FGF23) are associated with mortality. Data on FGF23 levels in pediatric heart failure are lacking.
Patients and methods
We conducted a cross-sectional study of 17 healthy children (mean age 13 years) and 20 pediatric patients with heart failure (mean age 12 years) who underwent echocardiography and for whom the following measurements were taken: plasma FGF23 and parathyroid hormone (PTH) and serum phosphate, creatinine and N-terminal prohormone brain natriuretic peptide (NT-proBNP). Symptom severity was assessed with the New York Heart Association and the Ross classification systems.
Of the 20 patients, 11 had dilated cardiomyopathy, four had congenital heart disease, three had hypertrophic cardiomyopathy, one had a failing heart transplant and one had pulmonary hypertension. Mean phosphate levels in these patients were within the reported reference range for healthy children. Median PTH levels were in the normal range in patients and controls. The median FGF23 level was higher in patients versus controls (110.9 vs. 66.4 RU/ml; P = 0.03) and higher in patients on diuretics versus other patients (222.4 vs. 82.1 RU/ml; P = 0.01). Levels of FGF23 and NT-proBNP were directly correlated (r = 0.47, P = 0.04), and patients with greater physical functional impairment had higher FGF23 levels (142.5 in those with moderate-severe limitation vs. 92.8 RU/ml in those with no limitation; P = 0.05). Among patients with dilated cardiomyopathy, higher FGF23 levels were associated with a greater left ventricular end-diastolic diameter (r = 0.63, P = 0.04).
FGF23 levels are elevated in children with heart failure and are associated with diuretic use, severity of heart failure and left ventricular dilation.
KeywordsHeart failure Fibroblast growth factor 23 Parathyroid hormone Diuretics N-terminal prohormone brain natriuretic peptide
This study was supported by grants from the National Institute of Health: K23DK087858 (TI), R01HL111459, R01HL109090, R01HL053392, R01HL087000 (SEL) and R01HL095127 (TLM), and the Children’s Cardiomyopathy Foundation (SEL).
- 7.Isakova T, Xie H, Barchi-Chung A, Vargas G, Sowden N, Houston J, Wahl P, Lundquist A, Epstein M, Smith K, Contreras G, Ortega L, Lenz O, Briones P, Egbert P, Ikizler TA, Jueppner H, Wolf M (2011) Fibroblast growth factor 23 in patients undergoing peritoneal dialysis. Clin J Am Soc Nephrol 6:2688–2695CrossRefPubMedGoogle Scholar
- 8.Parker BD, Schurgers LJ, Brandenburg VM, Christenson RH, Vermeer C, Ketteler M, Shlipak MG, Whooley MA, Ix JH (2010) The associations of fibroblast growth factor 23 and uncarboxylated matrix Gla protein with mortality in coronary artery disease: the Heart and Soul Study. Ann Intern Med 152:640–648CrossRefPubMedGoogle Scholar
- 9.Isakova T, Xie H, Yang W, Xie D, Anderson AH, Scialla J, Wahl P, Gutierrez OM, Steigerwalt S, He J, Schwartz S, Lo J, Ojo A, Sondheimer J, Hsu CY, Lash J, Leonard M, Kusek JW, Feldman HI, Wolf M (2011) Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. JAMA 305:2432–2439CrossRefPubMedGoogle Scholar
- 14.Seeherunvong W, Abitbol CL, Chandar J, Rusconi P, Zilleruelo GE, Freundlich M (2012) Fibroblast growth factor 23 and left ventricular hypertrophy in children on dialysis. Pediatr Nephrol 27:2129–2136Google Scholar
- 19.Faul C, Amaral AP, Oskouei B, Hu MC, Sloan A, Isakova T, Gutierrez OM, Aguillon-Prada R, Lincoln J, Hare JM, Mundel P, Morales A, Scialla J, Fischer M, Soliman EZ, Chen J, Go AS, Rosas SE, Nessel L, Townsend RR, Feldman HI, St John Sutton M, Ojo A, Gadegbeku C, Di Marco GS, Reuter S, Kentrup D, Tiemann K, Brand M, Hill JA, Moe OW, Kuro OM, Kusek JW, Keane MG, Wolf M (2011) FGF23 induces left ventricular hypertrophy. J Clin Invest 121:4393–4408CrossRefPubMedGoogle Scholar
- 20.Rosenthal D, Chrisant MR, Edens E, Mahony L, Canter C, Colan S, Dubin A, Lamour J, Ross R, Shaddy R, Addonizio L, Beerman L, Berger S, Bernstein D, Blume E, Boucek M, Checchia P, Dipchand A, Drummond-Webb J, Fricker J, Friedman R, Hallowell S, Jaquiss R, Mital S, Pahl E, Pearce FB, Rhodes L, Rotondo K, Rusconi P, Scheel J, Pal Singh T, Towbin J (2004) International Society for Heart and Lung Transplantation: Practice guidelines for management of heart failure in children. J Heart Lung Transplant 23:1313–1333CrossRefPubMedGoogle Scholar
- 25.Lipshultz SE, Miller TL, Scully RE, Lipsitz SR, Rifai N, Silverman LB, Colan SD, Neuberg DS, Dahlberg SE, Henkel JM, Asselin BL, Athale UH, Clavell LA, Laverdiere C, Michon B, Schorin MA, Sallan SE (2012) Changes in cardiac biomarkers during doxorubicin treatment of pediatric patients with high-risk acute lymphoblastic leukemia: associations with long-term echocardiographic outcomes. J Clin Oncol 30:1042–1049CrossRefPubMedGoogle Scholar
- 28.Lipshultz SE, Easley KA, Orav EJ, Kaplan S, Starc TJ, Bricker JT, Lai WW, Moodie DS, McIntosh K, Schluchter MD, Colan SD (1998) Left ventricular structure and function in children infected with human immunodeficiency virus: the prospective P2C2 HIV Multicenter Study. Pediatric Pulmonary and Cardiac Complications of Vertically Transmitted HIV Infection (P2C2 HIV) Study Group. Circulation 97:1246–1256CrossRefPubMedGoogle Scholar
- 29.Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, Gutgesell H, Reichek N, Sahn D, Schnittger I (1989) Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr 2:358–367PubMedGoogle Scholar
- 33.Fischer DC, Mischek A, Wolf S, Rahn A, Salweski B, Kundt G, Haffner D (2012) Paediatric reference values for the C-terminal fragment of fibroblast-growth factor-23, sclerostin, bone-specific alkaline phosphatase and isoform 5b of tartrate-resistant acid phosphatase. Ann Clin Biochem 49:546–553CrossRefPubMedGoogle Scholar
- 34.Gutierrez OM, Januzzi JL, Isakova T, Laliberte K, Smith K, Collerone G, Sarwar A, Hoffmann U, Coglianese E, Christenson R, Wang TJ, deFilippi C, Wolf M (2009) Fibroblast growth factor 23 and left ventricular hypertrophy in chronic kidney disease. Circulation 119:2545–2552CrossRefPubMedGoogle Scholar
- 35.Scialla JJ, Ling Lau W, Reilly MP, Isakova T, Hsueh-Ying Y, Crouthamel MH, Chavkin NW, Rahman M, Wahl P, Amaral AP, Hamano T, Master SR, Nessel L, Chai B, Xie D, Kallem RR, Chen J, Lash J, Kusek J, Budoff M, Giachelli CM, Wolf M for the Chronic Renal Insufficiency Cohort Study (2013) Fibroblast growth factor 23 is not associated with and does not induce arterial calcification. Kidney Int. doi: 10.1038/ki.2013.3 Google Scholar
- 42.Thadhani R, Appelbaum E, Pritchett Y, Chang Y, Wenger J, Tamez H, Bhan I, Agarwal R, Zoccali C, Wanner C, Lloyd-Jones D, Cannata J, Thompson BT, Andress D, Zhang W, Packham D, Singh B, Zehnder D, Shah A, Pachika A, Manning WJ, Solomon SD (2012) Vitamin D therapy and cardiac structure and function in patients with chronic kidney disease: the PRIMO randomized controlled trial. JAMA 307:674–684CrossRefPubMedGoogle Scholar
- 43.Kantor PF, Rusconi P, Lipshultz S, Mital S, Wilkinson JD, Burch M (2011) Current applications and future needs for biomarkers in pediatric cardiomyopathy and heart failure: summary from the second international conference on pediatric cardiomyopathy. Prog Pediatr Cardiol 32:11–14CrossRefPubMedGoogle Scholar