18-year change in serum intact fibroblast growth factor 23 from midlife to late life and risk of mortality: the ARIC Study

in European Journal of Endocrinology
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  • 1 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
  • | 2 Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA
  • | 3 Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota, USA

Correspondence should be addressed to K Matsushita; Email: kmatsus5@jhmi.edu
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Objective

Fibroblast growth factor 23 (FGF23) concentration increases in response to declining kidney function to preserve normal phosphate concentrations. However, the etiological association of change in FGF23 concentration with mortality has not been examined in the general population.

Design and methods

We analyzed 5458 participants of the Atherosclerosis Risk in Communities Study who had intact FGF23 and estimated glomerular filtration rate (eGFR) assessed during midlife (visit 3, 1993–1995, mean age: 58 years) and late life (visit 5, 2011–2013, 76 years) to examine the association of FGF23 change over 18 years from mid-life to late life with the subsequent risk of mortality in late life using Cox regression models.

Results

The median 18-year change in intact FGF23 was +17.3 pg/mL. During a median follow-up of 7.2 years following visit 5, 1176 participants died. In multivariable Cox models, elevated mortality was seen in the highest quartile of FGF23 change (ΔFGF23: ≥31.3 pg/mL) (adjusted hazard ratio (aHR): 1.61 (95%CI: 1.36–1.90), or 1.37 (1.15–1.64) after additionally adjusting for eGFR change, compared with the lowest quartile (≤6.4 pg/mL)). When both FGF23 change and FGF23 in late life were simultaneously entered into the Cox model, FGF23 in late life, but not FGF23 change, was an independent predictor of mortality; however, we observed a high correlation between FGF23 change from midlife to late life and FGF23 in late life (r = 0.77).

Conclusions

Serum intact FGF23 change from midlife to late life was associated with subsequent risk of mortality independent of decline in kidney function. Our findings further support the implications of FGF23 beyond its association with kidney function.

 

     European Society of Endocrinology

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  • 1

    Vervloet M Renal and extrarenal effects of fibroblast growth factor 23. Nature Reviews: Nephrology 2019 15 109120. (https://doi.org/10.1038/s41581-018-0087-2)

    • Search Google Scholar
    • Export Citation
  • 2

    Isakova T, Wahl P, Vargas GS, Gutierrez OM, Scialla J, Xie H, Appleby D, Nessel L, Bellovich K & Chen J et al.Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease. Kidney International 2011 79 13701378. (https://doi.org/10.1038/ki.2011.47)

    • Search Google Scholar
    • Export Citation
  • 3

    Ishigami J, Jaar BG, Rebholz CM, Grams ME, Michos ED, Wolf M, Kovesdy CP, Uchida S, Coresh J & Lutsey PL et al.Biomarkers of mineral and bone metabolism and 20-year risk of hospitalization with infection: the atherosclerosis risk in communities study. Journal of Clinical Endocrinology and Metabolism 2017 102 46484657. (https://doi.org/10.1210/jc.2017-01868)

    • Search Google Scholar
    • Export Citation
  • 4

    Isakova T, Xie H, Yang W, Xie D, Anderson AH, Scialla J, Wahl P, Gutierrez OM, Steigerwalt S & He J et al.Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. JAMA 2011 305 24322439. (https://doi.org/10.1001/jama.2011.826)

    • Search Google Scholar
    • Export Citation
  • 5

    Ishigami J, Taliercio JT, Feldman HI, Srivastava A, Townsend RR, Cohen DL, Horwitz EJ, Rao P, Charleston J & Fink JC et al.Fibroblast growth factor 23 and risk of hospitalization with infection in chronic kidney disease: the chronic renal insufficiency cohort (CRIC) study. Journal of the American Society of Nephrology 2020 31 18361846. (https://doi.org/10.1681/ASN.2019101106)

    • Search Google Scholar
    • Export Citation
  • 6

    Lutsey PL, Alonso A, Selvin E, Pankow JS, Michos ED, Agarwal SK, Loehr LR, Eckfeldt JH, Coresh J. Fibroblast growth factor-23 and incident coronary heart disease, heart failure, and cardiovascular mortality: the atherosclerosis risk in communities study. Journal of the American Heart Association 2014 3 e000936. (https://doi.org/10.1161/JAHA.114.000936)

    • Search Google Scholar
    • Export Citation
  • 7

    Arnlov J, Carlsson AC, Sundstrom J, Ingelsson E, Larsson A, Lind L, Larsson TE. Higher fibroblast growth factor-23 increases the risk of all-cause and cardiovascular mortality in the community. Kidney International 2013 83 160166. (https://doi.org/10.1038/ki.2012.327)

    • Search Google Scholar
    • Export Citation
  • 8

    Sharma S, Katz R, Bullen AL, Chaves PHM, de Leeuw PW, Kroon AA, Houben AJHM, Shlipak MG, Ix JH. Intact and C-terminal FGF23 assays-do kidney function, inflammation, and low iron influence relationships with outcomes? Journal of Clinical Endocrinology and Metabolism 2020 105 e4875e48 85. (https://doi.org/10.1210/clinem/dgaa665)

    • Search Google Scholar
    • Export Citation
  • 9

    Isakova T, Cai X, Lee J, Xie D, Wang X, Mehta R, Allen NB, Scialla JJ, Pencina MJ & Anderson AH et al.Longitudinal FGF23 trajectories and mortality in patients with CKD. Journal of the American Society of Nephrology 2018 29 579590. (https://doi.org/10.1681/ASN.2017070772)

    • Search Google Scholar
    • Export Citation
  • 10

    The Atherosclerosis Risk in Communities (ARIC) Study: design and objectives. The ARIC investigators. American Journal of Epidemiology 1989 129 687702. (https://doi.org/10.1093/oxfordjournals.aje.a115184)

    • Search Google Scholar
    • Export Citation
  • 11

    Ishigami J, Karger AB, Lutsey PL, Coresh J, Matsushita K. Stability of serum bone-mineral, kidney, and cardiac biomarkers after a freeze-thaw cycle: the ARIC study. American Journal of Epidemiology 2022 191 534537. (https://doi.org/10.1093/aje/kwab251)

    • Search Google Scholar
    • Export Citation
  • 12

    Inker LA, Schmid CH, Tighiouart H, Eckfeldt JH, Feldman HI, Greene T, Kusek JW, Manzi J, Van Lente F & Zhang YL et al.Estimating glomerular filtration rate from serum creatinine and cystatin C. New England Journal of Medicine 2012 367 2029. (https://doi.org/10.1056/NEJMoa1114248)

    • Search Google Scholar
    • Export Citation
  • 13

    Naimark DM, Grams ME, Matsushita K, Black C, Drion I, Fox CS, Inker LA, Ishani A, Jee SH & Kitamura A et al.Past decline versus current eGFR and subsequent mortality risk. Journal of the American Society of Nephrology 2016 27 24562466. (https://doi.org/10.1681/ASN.2015060688)

    • Search Google Scholar
    • Export Citation
  • 14

    Infante-Rivard C, Cusson A. Reflection on modern methods: selection bias-a review of recent developments. International Journal of Epidemiology 2018 47 17141722. (https://doi.org/10.1093/ije/dyy138)

    • Search Google Scholar
    • Export Citation
  • 15

    Schoppet M, Hofbauer LC, Brinskelle-Schmal N, Varennes A, Goudable J, Richard M, Hawa G, Chapurlat R, Szulc P. Serum level of the phosphaturic factor FGF23 is associated with abdominal aortic calcification in men: the STRAMBO study. Journal of Clinical Endocrinology and Metabolism 2012 97 E575E583. (https://doi.org/10.1210/jc.2011-2836)

    • Search Google Scholar
    • Export Citation
  • 16

    Block GA, Wheeler DC, Persky MS, Kestenbaum B, Ketteler M, Spiegel DM, Allison MA, Asplin J, Smits G & Hoofnagle AN et al.Effects of phosphate binders in moderate CKD. Journal of the American Society of Nephrology 2012 23 14071415. (https://doi.org/10.1681/ASN.2012030223)

    • Search Google Scholar
    • Export Citation
  • 17

    Isakova T, Gutierrez OM, Smith K, Epstein M, Keating LK, Juppner H, Wolf M. Pilot study of dietary phosphorus restriction and phosphorus binders to target fibroblast growth factor 23 in patients with chronic kidney disease. Nephrology, Dialysis, Transplantation 2011 26 584591. (https://doi.org/10.1093/ndt/gfq419)

    • Search Google Scholar
    • Export Citation
  • 18

    Isakova T, Barchi-Chung A, Enfield G, Smith K, Vargas G, Houston J, Xie H, Wahl P, Schiavenato E & Dosch A et al.Effects of dietary phosphate restriction and phosphate binders on FGF23 levels in CKD. Clinical Journal of the American Society of Nephrology 2013 8 10091018. (https://doi.org/10.2215/CJN.09250912)

    • Search Google Scholar
    • Export Citation
  • 19

    Sigrist M, Tang M, Beaulieu M, Espino-Hernandez G, Er L, Djurdjev O, Levin A. Responsiveness of FGF-23 and mineral metabolism to altered dietary phosphate intake in chronic kidney disease (CKD): results of a randomized trial. Nephrology, Dialysis, Transplantation 2013 28 161169. (https://doi.org/10.1093/ndt/gfs405)

    • Search Google Scholar
    • Export Citation
  • 20

    The United States Department of Agriculture. Nutrient intakes from food and beverages 2017–2018. (available at: https://www.ars.usda.gov/northeast-area/beltsville-md-bhnrc/beltsville-human-nutrition-research-center/food-surveys-research-group/docs/wweia-data-tables/). Accessed on 25 Mar 2021.

    • Search Google Scholar
    • Export Citation
  • 21

    The National Academies Collection: reports funded by National Institutes of Health. In Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington (DC), 1997.

    • Search Google Scholar
    • Export Citation
  • 22

    Edmonston D, Wolf M. FGF23 at the crossroads of phosphate, iron economy and erythropoiesis. Nature Reviews: Nephrology 2020 16 719. (https://doi.org/10.1038/s41581-019-0189-5)

    • Search Google Scholar
    • Export Citation
  • 23

    Fauconnier C, Roy T, Gillerot G, Roy C, Pouleur AC, Gruson D. FGF23: clinical usefulness and analytical evolution. Clinical Biochemistry 2019 66 112. (https://doi.org/10.1016/j.clinbiochem.2019.03.002)

    • Search Google Scholar
    • Export Citation
  • 24

    Smith ER, McMahon LP, Holt SG. Method-specific differences in plasma fibroblast growth factor 23 measurement using four commercial ELISAs. Clinical Chemistry and Laboratory Medicine 2013 51 19711981. (https://doi.org/10.1515/cclm-2013-0208)

    • Search Google Scholar
    • Export Citation
  • 25

    Tang R, Lu Y, Yin R, Zhu P, Zhu L, Zheng C. The effects of storage time and repeated freeze-thaw cycles on intact fibroblast growth factor 23 levels. Biopreservation and Biobanking 2021 19 4852. (https://doi.org/10.1089/bio.2020.0073)

    • Search Google Scholar
    • Export Citation
  • 26

    Dirks NF, Smith ER, van Schoor NM, Vervloet MG, Ackermans MT, de Jonge R, Heijboer AC. Pre-analytical stability of FGF23 with the contemporary immunoassays. Clinica Chimica Acta: International Journal of Clinical Chemistry 2019 493 104106. (https://doi.org/10.1016/j.cca.2019.02.032)

    • Search Google Scholar
    • Export Citation