Fibroblast Growth Factor-23 and Risks of Cardiovascular and Noncardiovascular Diseases: A Meta-Analysis

Journal of the American Society of Nephrology

Volumn 29, Issue 7, 2018, Pages 2000-2013

  Marthi, Amarnath ^a   Donovan, Killian ^b   Haynes, Richard ^b   Wheeler, David C ^c   Baigent, Colin ^b   Rooney, Christopher M ^a   Landray, Martin J ^b   Moe, Sharon M ^d   Yang, Jun ^e   Holland, Lisa ^b   Di Giuseppe, Romina ^f   Bouma de Krijger, Annet ^g   Mihaylova, Borislava ^a,h   Herrington, William G ^b  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b CLINICAL TRIAL SERVICE UNIT   (United Kingdom)

^c UNIVERSITY COLLEGE LONDON   (United Kingdom)

^d INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e AMGEN INC   (United States)

^f UNIVERSITY OF KIEL   (Germany)

^g VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^h QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

FIBROBLAST GROWTH FACTOR 23; FIBROBLAST GROWTH FACTOR;

ALL CAUSE MORTALITY; ARTICLE; ATHEROSCLEROSIS; CARDIOVASCULAR DISEASE; CARDIOVASCULAR MORTALITY; CARDIOVASCULAR RISK; CEREBROVASCULAR ACCIDENT; CHRONIC KIDNEY FAILURE; DIALYSIS; HEART FAILURE; HEART INFARCTION; HUMAN; PRIORITY JOURNAL; BLOOD; HEMODIALYSIS; META ANALYSIS; MORTALITY;

CARDIOVASCULAR DISEASES; FIBROBLAST GROWTH FACTORS; HEART FAILURE; HUMANS; MORTALITY; MYOCARDIAL INFARCTION; RENAL DIALYSIS; RENAL INSUFFICIENCY, CHRONIC; STROKE;

EID: 85049396542     PISSN: 10466673     EISSN: 15333450     Source Type: Journal    
DOI: 10.1681/ASN.2017121334     Document Type: Article

References (78)

1. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY: Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 351: 1296–1305, 2004
2. Herzog CA, Asinger RW, Berger AK, Charytan DM, Díez J, Hart RG, et al.: Cardiovascular disease in chronic kidney disease. A clinical update from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 80: 572–586, 2011
3. Matsushita K, van der Velde M, Astor BC, Woodward M, Levey AS, de Jong PE, et al.; Chronic Kidney Disease Prognosis Consortium: Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: A collaborative meta-analysis. Lancet 375: 2073–2081, 2010
4. Park M, Hsu CY, Li Y, Mishra RK, Keane M, Rosas SE, et al.; Chronic Renal Insufficiency Cohort (CRIC) Study Group: Associations between kidney function and subclinical cardiac abnormalities in CKD. J Am Soc Nephrol 23: 1725–1734, 2012
5. Foley RN, Parfrey PS, Kent GM, Harnett JD, Murray DC, Barre PE: Long-term evolution of cardiomyopathy in dialysis patients. Kidney Int 54: 1720–1725, 1998
6. Wheeler DC, London GM, Parfrey PS, Block GA, Correa-Rotter R, Dehmel B, et al.; EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) Trial Investigators: Effects of cina-calcet on atherosclerotic and nonatherosclerotic cardiovascular events in patients receiving hemodialysis: The EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) trial. J Am Heart Assoc 3: e001363, 2014
7. Palmer SC, Hayen A, Macaskill P, Pellegrini F, Craig JC, Elder GJ, et al.: Serum levels of phosphorus, parathyroid hormone, and calcium and risks of death and cardiovascular disease in individuals with chronic kidney disease: A systematic review and meta-analysis. JAMA 305: 1119–1127, 2011
8. Jono S, McKee MD, Murry CE, Shioi A, Nishizawa Y, Mori K, et al.: Phosphate regulation of vascular smooth muscle cell calcification. Circ Res 87: E10–E17, 2000
9. London GM, Guérin AP, Marchais SJ, Métivier F, Pannier B, Adda H: Arterial media calcification in end-stage renal disease: Impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant 18: 1731–1740, 2003
10. Isakova T, Wahl P, Vargas GS, Gutiérrez OM, Scialla J, Xie H, et al.: Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease. Kidney Int 79: 1370–1378, 2011
11. Shalhoub V, Ward SC, Sun B, Stevens J, Renshaw L, Hawkins N, et al.: Fibroblast growth factor 23 (FGF23) and alpha-klotho stimulate oste-oblastic MC3T3.E1 cell proliferation and inhibit mineralization. Calcif Tissue Int 89: 140–150, 2011
12. Wahl P, Wolf M:FGF23 in chronic kidney disease. In: Endocrine FGFs and Klothos, edited by Kuro-o M, Georgetown, TX, Landes Bioscience and Springer Science, 2012, pp 107–125
13. Faul C, Amaral AP, Oskouei B, Hu MC, Sloan A, Isakova T, et al.: FGF23 induces left ventricular hypertrophy. J Clin Invest 121: 4393–4408, 2011
14. Leifheit-Nestler M, Große Siemer R, Flasbart K, Richter B, Kirchhoff F, Ziegler WH, et al.: Induction of cardiac FGF23/FGFR4 expression is associated with left ventricular hypertrophy in patients with chronic kidney disease. Nephrol Dial Transplant 31: 1088–1099, 2016
15. Gutiérrez OM: Connecting the dots on fibroblast growth factor 23 and left ventricular hypertrophy. Nephrol Dial Transplant 31: 1031–1033, 2016
16. Wells GA, Shea B, O’Connell D, Peterson J, Welch V, Losos M, et al.: The Newcastle–Ottawa Scale (NOS) for assessing the quality of non-randomised studies in meta-analyses. Third Symposium on Systematic Reviews: Beyond the Basics. Oxford, July 2000. Available at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed April 30, 2018
17. Danesh J, Collins R, Appleby P, Peto R: Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: Meta-analyses of prospective studies. JAMA 279: 1477–1482, 1998
18. Mafham M, Emberson J, Landray MJ, Wen CP, Baigent C: Estimated glomerular filtration rate and the risk of major vascular events and all-cause mortality: A meta-analysis. PLoS One 6: e25920, 2011
19. Cooper H, Hedges LV, Valentine JC, editors: The Handbook of Research Synthesis and Meta-Analysis, New York, Russell Sage Foundation, 2009
20. Smith ER, Cai MM, McMahon LP, Holt SG: Biological variability of plasma intact and C-terminal FGF23 measurements. J Clin Endocrinol Metab 97: 3357–3365, 2012
21. Burnett SM, Gunawardene SC, Bringhurst FR, Jüppner H, Lee H, Finkelstein JS: Regulation of C-terminal and intact FGF-23 by dietary phosphate in men and women. J Bone Miner Res 21: 1187–1196, 2006
22. di Giuseppe R, Kühn T, Hirche F, Buijsse B, Dierkes J, Fritsche A, et al.: Plasma fibroblast growth factor 23 and risk of cardiovascular disease: Results from the EPIC-Germany case-cohort study. Eur J Epidemiol 30: 131–141, 2015
23. Bouma-de Krijger A, Bots ML, Vervloet MG, Blankestijn PJ, Ter Wee PW, van Zuilen AD, et al.: Time-averaged level of fibroblast growth factor-23 and clinical events in chronic kidney disease. Nephrol Dial Transplant 29: 88–97, 2014
24. Moe SM, Chertow GM, Parfrey PS, Kubo Y, Block GA, Correa-Rotter R, et al.; Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial Investigators: Cinacalcet, fibroblast growth factor-23, and cardiovascular disease in hemodialysis: The Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) trial. Circulation 132: 27–39, 2015
25. MacMahon S, Peto R, Cutler J, Collins R, Sorlie P, Neaton J, et al.: Blood pressure, stroke, and coronary heart disease. Part 1, prolonged differences in blood pressure: Prospective observational studies corrected for the regression dilution bias. Lancet 335: 765–774, 1990
26. 2 tests. Biometrics 10: 417–451, 1954
27. Udell JA, Morrow DA, Jarolim P, Sloan S, Hoffman EB, O’Donnell TF, et al.: Fibroblast growth factor-23, cardiovascular prognosis, and benefit of angiotensin-converting enzyme inhibition in stable ischemic heart disease. J Am Coll Cardiol 63: 2421–2428, 2014
28. Nakano C, Hamano T, Fujii N, Obi Y, Matsui I, Tomida K, et al.: Intact fibroblast growth factor 23 levels predict incident cardiovascular event before but not after the start of dialysis. Bone 50: 1266–1274, 2012
29. Prié D, Forand A, Francoz C, Elie C, Cohen I, Courbebaisse M, et al.: Plasma fibroblast growth factor 23 concentration is increased and predicts mortality in patients on the liver-transplant waiting list. PLoS One 8: e66182, 2013
30. Gutiérrez OM, Mannstadt M, Isakova T, Rauh-Hain JA, Tamez H, Shah A, et al.: Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med 359: 584–592, 2008
31. Taylor EN, Rimm EB, Stampfer MJ, Curhan GC: Plasma fibroblast growth factor 23, parathyroid hormone, phosphorus, and risk of coronary heart disease. Am Heart J 161: 956–962, 2011
32. Semba RD, Fink JC, Sun K, Cappola AR, Dalal M, Crasto C, et al.: Serum fibroblast growth factor-23 and risk of incident chronic kidney disease in older community-dwelling women. Clin J Am Soc Nephrol 7: 85–91, 2012
33. Lee JE, Gohda T, Walker WH, Skupien J, Smiles AM, Holak RR, et al.: Risk of ESRD and all cause mortality in type 2 diabetes according to circulating levels of FGF-23 and TNFR1. PLoS One 8: e58007, 2013
34. Tuñón J, Cristóbal C, Tarín N, Aceña Á, González-Casaus ML, Huelmos A, et al.: Coexistence of low vitamin D and high fibroblast growth factor-23 plasma levels predicts an adverse outcome in patients with coronary artery disease. PLoS One 9: e95402, 2014
35. Söderholm M, Engström G: Fibroblast growth factor 23 and incidence of subarachnoid hemorrhage: Nested case-control study. Stroke 46: 3260–3262, 2015
36. Fyfe-Johnson AL, Alonso A, Selvin E, Bower JK, Pankow JS, Agarwal SK, et al.: Serum fibroblast growth factor-23 and incident hypertension: The Atherosclerosis Risk in Communities (ARIC) study. J Hypertens 34: 1266–1272, 2016
37. Langsford D, Tang M, Cheikh Hassan HI, Djurdjev O, Sood MM, Levin A: The Association between biomarker profiles, etiology of chronic kidney disease, and mortality. Am J Nephrol 45: 226–234, 2017
38. Ärnlöv J, Carlsson AC, Sundström J, Ingelsson E, Larsson A, Lind L, et al.: Serum FGF23 and risk of cardiovascular events in relation to mineral metabolism and cardiovascular pathology. Clin J Am Soc Nephrol 8: 781–786, 2013
39. Ärnlöv J, Carlsson AC, Sundström J, Ingelsson E, Larsson A, Lind L, et al.: Higher fibroblast growth factor-23 increases the risk of all-cause and cardiovascular mortality in the community. Kidney Int 83: 160–166, 2013
40. Brandenburg VM, Kleber ME, Vervloet MG, Tomaschitz A, Pilz S, Stojakovic T, et al.: Fibroblast growth factor 23 (FGF23) and mortality: The Ludwigshafen Risk and Cardiovascular Health Study. Atherosclerosis 237: 53–59, 2014
41. Deo R, Katz R, de Boer IH, Sotoodehnia N, Kestenbaum B, Mukamal KJ, et al.: Fibroblast growth factor 23 and sudden versus non-sudden cardiac death: The Cardiovascular Health Study. Am J Kidney Dis 66: 40–46, 2015
42. di Giuseppe R, Buijsse B, Hirche F, Wirth J, Arregui M, Westphal S, et al.: Plasma fibroblast growth factor 23, parathyroid hormone, 25-hydroxyvitamin D3, and risk of heart failure: A prospective, case-cohort study. J Clin Endocrinol Metab 99: 947–955, 2014
43. Garimella PS, Ix JH, Katz R, Chonchol MB, Kestenbaum BR, de Boer IH, et al.: Fibroblast growth factor 23, the ankle-brachial index, and incident peripheral artery disease in the Cardiovascular Health Study. Atherosclerosis 233: 91–96, 2014
44. Ix JH, Katz R, Kestenbaum BR, de Boer IH, Chonchol M, Mukamal KJ, et al.: Fibroblast growth factor-23 and death, heart failure, and cardiovascular events in community-living individuals: CHS (Cardiovascular Health Study). J Am Coll Cardiol 60: 200–207, 2012
45. Kestenbaum B, Sachs MC, Hoofnagle AN, Siscovick DS, Ix JH, Robinson-Cohen C, et al.: Fibroblast growth factor-23 and cardiovascular disease in the general population: The Multi-Ethnic Study of atherosclerosis. Circ Heart Fail 7: 409–417, 2014
46. Lutsey PL, Alonso A, Selvin E, Pankow JS, Michos ED, Agarwal SK, et al.: Fibroblast growth factor-23 and incident coronary heart disease, heart failure, and cardiovascular mortality: The Atherosclerosis Risk in Communities study. J Am Heart Assoc 3: e000936, 2014
47. Masson S, Agabiti N, Vago T, Miceli M, Mayer F, Letizia T, et al.; Investigators of the PREDICTOR study: The fibroblast growth factor-23 and Vitamin D emerge as nontraditional risk factors and may affect cardiovascular risk. J Intern Med 277: 318–330, 2015
48. Panwar B, Jenny NS, Howard VJ, Wadley VG, Muntner P, Kissela BM, et al.: Fibroblast growth factor 23 and risk of incident stroke in community-living adults. Stroke 46: 322–328, 2015
49. Parker BD, Schurgers LJ, Brandenburg VM, Christenson RH, Vermeer C, Ketteler M, et al.: 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: 640–648, 2010
50. Speer T, Groesdonk HV, Zapf B, Buescher V, Beyse M, Duerr L, et al.: A single preoperative FGF23 measurement is a strong predictor of outcome in patients undergoing elective cardiac surgery: A prospective observational study. Crit Care 19: 190, 2015
51. Westerberg PA, Tivesten Å, Karlsson MK, Mellström D, Orwoll E, Ohlsson C, et al.: Fibroblast growth factor 23, mineral metabolism and mortality among elderly men (Swedish MrOs). BMC Nephrol 14: 85, 2013
52. Wright CB, Dong C, Stark M, Silverberg S, Rundek T, Elkind MS, et al.: Plasma FGF23 and the risk of stroke: The Northern Manhattan Study (NOMAS). Neurology 82: 1700–1706, 2014
53. Souma N, Isakova T, Lipiszko D, Sacco RL, Elkind MS, DeRosa JT, et al.: Fibroblast growth factor 23 and cause-specific mortality in the general population: The Northern Manhattan study. J Clin Endocrinol Metab 101: 3779–3786, 2016
54. Baia LC, Humalda JK, Vervloet MG, Navis G, Bakker SJ, de Borst MH; NIGRAM Consortium: Fibroblast growth factor 23 and cardiovascular mortality after kidney transplantation. Clin J Am Soc Nephrol 8: 1968–1978, 2013
55. Isakova T, Xie H, Yang W, Xie D, Anderson AH, Scialla J, et al.; Chronic Renal Insufficiency Cohort (CRIC) Study Group: Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. JAMA 305: 2432–2439, 2011
56. Kendrick J, Cheung AK, Kaufman JS, Greene T, Roberts WL, Smits G, et al.; HOST Investigators: FGF-23 associates with death, cardiovascular events, and initiation of chronic dialysis. J Am Soc Nephrol 22: 1913–1922, 2011
57. Levin A, Rigatto C, Barrett B, Madore F, Muirhead N, Holmes D, et al.; CanPREDDICT Investigators: Biomarkers of inflammation, fibrosis, cardiac stretch and injury predict death but not renal replacement therapy at 1 year in a Canadian chronic kidney disease cohort. Nephrol Dial Transplant 29: 1037–1047, 2014
58. Scialla JJ, Xie H, Rahman M, Anderson AH, Isakova T, Ojo A, et al.; Chronic Renal Insufficiency Cohort (CRIC) Study Investigators: Fibroblast growth factor-23 and cardiovascular events in CKD. J Am Soc Nephrol 25: 349–360, 2014
59. Seiler S, Rogacev KS, Roth HJ, Shafein P, Emrich I, Neuhaus S, et al.: Associations of FGF-23 and sKlotho with cardiovascular outcomes among patients with CKD stages 2-4. Clin J Am Soc Nephrol 9: 1049–1058, 2014
60. Alderson HV, Ritchie JP, Middleton R, Larsson A, Larsson TE, Kalra PA: FGF-23 and osteoprotegerin but not fetuin-A are associated with death and enhance risk prediction in non-dialysis chronic kidney disease stages 3-5. Nephrology (Carlton) 21: 566–573, 2016
61. Munoz Mendoza J, Isakova T, Cai X, Bayes LY, Faul C, Scialla JJ, et al.; CRIC Study Investigators: Inflammation and elevated levels of fibroblast growth factor 23 are independent risk factors for death in chronic kidney disease. Kidney Int 91: 711–719, 2017
62. Chonchol M, Greene T, Zhang Y, Hoofnagle AN, Cheung AK: Low vitamin D and high fibroblast growth factor 23 serum levels associate with infectious and cardiac deaths in the HEMO study. J Am Soc Nephrol 27: 227–237, 2016
63. Jean G, Terrat JC, Vanel T, Hurot JM, Lorriaux C, Mayor B, et al.: High levels of serum fibroblast growth factor (FGF)-23 are associated with increased mortality in long haemodialysis patients. Nephrol Dial Transplant 24: 2792–2796, 2009
64. Kim HJ, Park M, Park HC, Jeong JC, Kim DK, Joo KW, et al.: Baseline FGF23 is associated with cardiovascular outcome in incident PD patients. Perit Dial Int 36: 26–32, 2016
65. Montford JR, Chonchol M, Cheung AK, Kaufman JS, Greene T, Roberts WL, et al.; HOST Investigators: Low body mass index and dyslipidemia in dialysis patients linked to elevated plasma fibroblast growth factor 23. Am J Nephrol 37: 183–190, 2013
66. Nowak A, Friedrich B, Artunc F, Serra AL, Breidthardt T, Twerenbold R, et al.: Prognostic value and link to atrial fibrillation of soluble Klotho and FGF23 in hemodialysis patients. PLoS One 9: e100688, 2014
67. Olauson H, Qureshi AR, Miyamoto T, Barany P, Heimburger O, Lindholm B, et al.: Relation between serum fibroblast growth factor-23 level and mortality in incident dialysis patients: Are gender and cardiovascular disease confounding the relationship? Nephrol Dial Transplant 25: 3033–3038, 2010
68. Scialla JJ, Parekh RS, Eustace JA, Astor BC, Plantinga L, Jaar BG, et al.: Race, mineral homeostasis and mortality in patients with end-stage renal disease on dialysis. Am J Nephrol 42: 25–34, 2015
69. Hill AB: The environment and disease: Association or causation? Proc R Soc Med 58: 295–300, 1965
70. Brown JR, Katz R, Ix JH, de Boer IH, Siscovick DS, Grams ME, et al.: Fibroblast growth factor-23 and the long-term risk of hospital-associated AKI among community-dwelling older individuals. Clin J Am Soc Nephrol 9: 239–246, 2014
71. Mirza MA, Karlsson MK, Mellström D, Orwoll E, Ohlsson C, Ljunggren O, et al.: Serum fibroblast growth factor-23 (FGF-23) and fracture risk in elderly men. J Bone Miner Res 26: 857–864, 2011
72. Singh S, Grabner A, Yanucil C, Schramm K, Czaya B, Krick S, et al.: Fibroblast growth factor 23 directly targets hepatocytes to promote inflammation in chronic kidney disease. Kidney Int 90: 985–996, 2016
73. Nowak KL, Bartz TM, Dalrymple L, de Boer IH, Kestenbaum B, Shlipak MG, et al.: Fibroblast growth factor 23 and the risk of infection-related hospitalization in older adults. J Am Soc Nephrol 28: 1239–1246, 2017
74. Rossaint J, Unruh M, Zarbock A: Fibroblast growth factor 23 actions in inflammation: A key factor in CKD outcomes. Nephrol Dial Transplant 32: 1448–1453, 2017
75. Feng S, Wang J, Zhang Y, Creighton CJ, Ittmann M: FGF23 promotes prostate cancer progression. Oncotarget 6: 17291–17301, 2015
76. Lewington S, Whitlock G, Clarke R, Sherliker P, Emberson J, Halsey J, et al.; Prospective Studies Collaboration: Blood cholesterol and vascular mortality by age, sex, and blood pressure: A meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet 370: 1829–1839, 2007
77. Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, et al.; Cholesterol Treatment Trialists’ (CTT) Collaboration: Efficacy and safety of more intensive lowering of LDL cholesterol: A meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 376: 1670–1681, 2010
78. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R; Prospective Studies Collaboration: Age-specific relevance of usual blood pressure to vascular mortality: A meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 360: 1903–1913, 2002