Calcified Tissue International

, Volume 101, Issue 5, pp 510–518 | Cite as

Evaluation of a New Fully Automated Assay for Plasma Intact FGF23

  • Jean-Claude Souberbielle
  • Dominique Prié
  • Marie-Liesse Piketty
  • Anya Rothenbuhler
  • Pierre Delanaye
  • Philippe Chanson
  • Etienne Cavalier
Original Research

Abstract

Several FGF23 immunoassays are available. However, they are reserved for research purposes as none have been approved for clinical use. We evaluated the performances of a new automated assay for intact FGF23 on the DiaSorin Liaison platform which is approved for clinical use. We established reference values in 908 healthy French subjects aged 18–89 years, and measured iFGF23 in patients with disorders of phosphate metabolism and in patients with chronic kidney disease (CKD). Intra-assay CV was 1.04–2.86% and inter-assay CV was 4.01–6.3%. The limit of quantification was <10 ng/L. Serum iFGF23 concentrations were considerably lower than EDTA values highlighting the importance of using exclusively EDTA plasma. Liaison iFGF23 values were approximately 25% higher than Immutopics values. In the 908 healthy subjects, distribution of the Liaison iFGF23 values was Gaussian with a mean ± 2SD interval of 22.7–93.1 ng/L. Men had a slightly higher level than women (60.3 ± 17.6 and 55.2 ± 17.2 ng/L, respectively). Plasma iFGF23 concentration in 11 patients with tumour-induced osteomalacia, 8 patients with X-linked hypophosphatemic rickets, 43 stage 3a, 43 stage 3b, 43 stage 4, 44 stage 5 CKD patients, and 44 dialysis patients were 217.2 ± 144.0, 150.9 ± 28.6, 98.5 ± 42.0, 130.8 ± 88.6, 130.8 ± 88.6, 331.7 ± 468.2, 788.8 ± 1306.6 and 6103.9 ± 11,178.8 ng/L, respectively. This new iFGF23 assay available on a platform that already allows the measurement of other important parameters of the mineral metabolism is a real improvement for the laboratories and clinicians/researchers involved in this field.

Keywords

FGF23 Reference values Vitamin D Chronic kidney disease Hypophosphatemia Hyperphosphatemia 

Notes

Compliance with Ethical Standards

Conflict of interest

JCS reports lecture fees and/or travel/hotel expenses from DiaSorin, Roche Diagnostics, Abbott, Amgen, Shire, MSD, Lilly and Rottapharm; EC is a consultant for IDS and DiaSorin and has received lecture fees from IDS, DiaSorin, Roche, Abbott and Amgen; PD is a consultant for IDS and has received lecture fees and/or travel expenses from DiaSorin, Amgen, Shire, Fresenius, Menarini and Sanofi; DP, M-LP, AR and PC have nothing to disclose.

Human and Animal Rights and Informed Consent

All procedures performed in our patients/healthy subjects were in accordance with the ethical standards of the national research committee and with the 1964 Helsinki declaration and its latter amendments or comparable ethical standards. All healthy subjects and patients gave informed consent to have their blood sample tested.

References

  1. 1.
    Liu S, Quarles LD (2007) How fibroblast growth factor 23 works. J Am Soc Nephrol 18:1637–1647. doi: 10.1681/ASN.2007010068 CrossRefPubMedGoogle Scholar
  2. 2.
    Kurosu H, Ogawa Y, Miyoshi M et al (2006) Regulation of fibroblast growth factor-23 signaling by Klotho. J Biol Chem 281:6120–6123. doi: 10.1074/jbc.C500457200 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Chong WH, Molinolo AA, Chen CC, Collins MT (2011) Tumor-induced osteomalacia. Endocr Relat Cancer 18:53–77. doi: 10.1016/B978-0-12-373884-4.00079-3 CrossRefGoogle Scholar
  4. 4.
    Carpenter TO, Imel EA, Holm IA et al (2001) A clinician’s guide to X-linked hypophosphatemia. J Bone Miner Res 26:1381–1388. doi: 10.1002/jbmr.340.A CrossRefGoogle Scholar
  5. 5.
    Chefetz I, Heller R, Galli-Tsinopoulou A et al (2005) A novel homozygous missense mutation in FGF23 causes familial tumoral calcinosis associated with disseminated visceral calcification. Hum Genet 118:261–266. doi: 10.1007/s00439-005-0026-8 CrossRefPubMedGoogle Scholar
  6. 6.
    Ichikawa S, Imel EA, Kreiter ML et al (2007) A homozygous missense mutation in human Klotho causes severe tumoral calcinosis. J Clin Investig 117:2684–2691. doi: 10.1172/JCI31330 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Bergwitz C, Jüppner H (2010) Regulation of phosphate homeostasis by PTH, vitamin D, and FGF23. Annu Rev Med 61:91–104. doi: 10.1146/annurev.med.051308.111339 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Kovesdy CP, Quarles LD (2013) Fibroblast growth factor-23: what we know, what we don’t know, and what we need to know. Nephrol Dial Transplant 28:2228–2236. doi: 10.1093/ndt/gft065 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    David V, Martin A, Isakova T et al (2015) Inflammation and functional iron deficiency regulate fibroblast growth factor 23 production. Kidney Int. doi: 10.1038/ki.2015.290 PubMedPubMedCentralGoogle Scholar
  10. 10.
    Ramnitz MS, Gourh P, Goldbach-Mansky R et al (2016) Phenotypic and genotypic characterization and treatment of a cohort with familial tumoral calcinosis/hyperostosis-hyperphosphatemia syndrome. J Bone Miner Res 31:1845–1854. doi: 10.1002/jbmr.2870 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Isakova T, Wahl P, Vargas GS et al (2011) Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease. Kidney Int 79:1370–1378. doi: 10.1038/ki.2011.47 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Shimada T, Urakawa I, Isakova T et al (2010) Circulating fibroblast growth factor 23 in patients with end-stage renal disease treated by peritoneal dialysis is intact and biologically active. J Clin Endocrinol Metab 95:578–585. doi: 10.1210/jc.2009-1603 CrossRefPubMedGoogle Scholar
  13. 13.
    Donate-Correa J, De Fuentes MM, Mora-Fernández C, Navarro-González JF (2014) Pathophysiological implications of fibroblast growth factor-23 and Klotho and their potential role as clinical biomarkers. Clin Chem 60:933–940. doi: 10.1373/clinchem.2013.206649 CrossRefPubMedGoogle Scholar
  14. 14.
    Shimizu Y, Fukumoto S, Fujita T (2012) Evaluation of a new automated chemiluminescence immunoassay for FGF23. J Bone Miner Metab 30:217–221. doi: 10.1007/s00774-011-0306-4 CrossRefPubMedGoogle Scholar
  15. 15.
    Chanson P, Arnoux A, Mavromati M et al (2016) Reference values for IGF-I serum concentrations: comparison of six immunoassays. J Clin Endocrinol Metab 101:3450–3458. doi: 10.1210/jc.2016-1257 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Souberbielle J-CC, Massart C, Brailly-Tabard S et al (2016) Prevalence and determinants of vitamin D deficiency in healthy French adults: the VARIETE study. Endocrine. doi: 10.1007/s12020-016-0960-3 PubMedGoogle Scholar
  17. 17.
    Smith ER, McMahon LP, Holt SG (2013) Method-specific differences in plasma fibroblast growth factor 23 measurement using four commercial ELISAs. Clin Chem Lab Med 51:1971–1981. doi: 10.1515/cclm-2013-0208 CrossRefPubMedGoogle Scholar
  18. 18.
    El-Maouche D, Dumitrescu CE, Andreopoulou P et al (2016) Stability and degradation of fibroblast growth factor 23 (FGF23): the effect of time and temperature and assay type. Osteoporos Int 27:2345–2353. doi: 10.1007/s00198-016-3543-5 CrossRefPubMedGoogle Scholar
  19. 19.
    Yuen SN, Holly K, Luke A et al (2016) Fibroblast growth factor-23 (FGF-23) levels differ across populations by degree of industrialization. J Clin Endocrinol Metab 101:2246–2253. doi: 10.1210/jc.2015-3558 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Smith ER, Cai MM, McMahon LP, Holt SG (2012) Biological variability of plasma intact and C-terminal FGF23 measurements. J Clin Endocrinol Metab 97:3357–3365. doi: 10.1210/jc.2012-1811 CrossRefPubMedGoogle Scholar
  21. 21.
    Ix JH, Chonchol M, Laughlin GA et al (2011) Relation of sex and estrogen therapy to serum fibroblast growth factor 23, serum phosphorus, and urine phosphorus: the heart and soul study. Am J Kidney Dis 58:737–745. doi: 10.1053/j.ajkd.2011.06.011 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Dhayat NA, Ackermann D, Pruijm M et al (2016) Fibroblast growth factor 23 and markers of mineral metabolism in individuals with preserved renal function. Kidney Int 90:648–657. doi: 10.1016/j.kint.2016.04.024 CrossRefPubMedGoogle Scholar
  23. 23.
    Prié D, Friedlander G (2010) Reciprocal control of 1,25-dihydroxyvitamin D and FGF23 formation involving the FGF23/Klotho system. Clin J Am Soc Nephrol 5:1717–1722. doi: 10.2215/CJN.02680310 CrossRefPubMedGoogle Scholar
  24. 24.
    Imel EA, DiMeglio LA, Hui SL et al (2010) Treatment of X-linked hypophosphatemia with calcitriol and phosphate increases circulating fibroblast growth factor 23 concentrations. J Clin Endocrinol Metab 95:1846–1850. doi: 10.1210/jc.2009-1671 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Jonsson KB, Zahradnik R, Larsson T et al (2003) Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia. N Engl J Med 348:1656–1663. doi: 10.1056/NEJMoa020881 CrossRefPubMedGoogle Scholar
  26. 26.
    Imel EA, Peacock M, Pitukcheewanont P et al (2006) Sensitivity of fibroblast growth factor 23 measurements in tumor-induced osteomalacia. J Clin Endocrinol Metab 91:2055–2061. doi: 10.1210/jc.2005-2105 CrossRefPubMedGoogle Scholar
  27. 27.
    Yu WJ, He JW, Fu WZ et al (2016) Reports of 17 Chinese patients with tumor-induced osteomalacia. J Bone Miner Metab. doi: 10.1007/s00774-016-0756-9 PubMedGoogle Scholar
  28. 28.
    Goetz R, Nakada Y, Hu MC et al (2010) Isolated C-terminal tail of FGF23 alleviates hypophosphatemia by inhibiting FGF23-FGFR-Klotho complex formation. Proc Natl Acad Sci 107:407–412. doi: 10.1073/pnas.0902006107 CrossRefPubMedGoogle Scholar
  29. 29.
    Gutiérrez OM, Mannstadt M, Isakova T et al (2008) Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med 359:584–592. doi: 10.1056/NEJMoa0706130 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Jean G, Terrat J-C, Vanel T et al (2009) High levels of serum fibroblast growth factor (FGF)-23 are associated with increased mortality in long haemodialysis patients. Nephrol Dial Transplant 24:2792–2796. doi: 10.1093/ndt/gfp191 CrossRefPubMedGoogle Scholar
  31. 31.
    Isakova T, Xie H, Yang W et al (2011) Fibroblast growth factor 23 and risks of mortality and end- stage renal disease in patients with chronic kidney disease. JAMA 305:2432–2439. doi: 10.1001/jama.2011.826 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Seiler S, Reichart B, Roth D et al (2010) FGF-23 and future cardiovascular events in patients with chronic kidney disease before initiation of dialysis treatment. Nephrol Dial Transplant 25:3983–3989. doi: 10.1093/ndt/gfq309 CrossRefPubMedGoogle Scholar
  33. 33.
    Kendrick J, Cheung AK, Kaufman JS et al (2011) FGF-23 associates with death, cardiovascular events, and initiation of chronic dialysis. J Am Soc Nephrol 22:1913–1922. doi: 10.1681/ASN.2010121224 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Wolf M, Molnar MZ, Amaral AP et al (2011) Elevated fibroblast growth factor 23 is a risk factor for kidney transplant loss and mortality. J Am Soc Nephrol 22:956–966. doi: 10.1681/ASN.2010080894 CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Baia LC, Humalda JK, Vervloet MG et al (2013) Fibroblast growth factor 23 and cardiovascular mortality after kidney transplantation. Clin J Am Soc Nephrol 8:1968–1978. doi: 10.2215/CJN.01880213 CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Oliveira RB, Cancela ALE, Graciolli FG et al (2010) Early control of PTH and FGF23 in normophosphatemic CKD patients: a new target in CKD-MBD therapy? Clin J Am Soc Nephrol 5:286–291. doi: 10.2215/CJN.05420709 CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Faul C, Amaral AP, Oskouei B et al (2011) FGF23 induces left ventricular hypertrophy. J Clin Investig 121:4393–4408. doi: 10.1172/JCI46122 CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Shalhoub V, Shatzen EM, Ward SC et al (2012) FGF23 neutralization improves chronic kidney disease—associated hyperparathyroidism yet increases mortality. J Clin Investig 122:2543–2553. doi: 10.1172/JCI61405 CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Moe SM, Chertow GM, Parfrey PS et al (2015) 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. doi: 10.1161/CIRCULATIONAHA.114.013876 CrossRefPubMedGoogle Scholar
  40. 40.
    Moe SM, Drueke TB, Group for the KW (2009) KDIGO clinical practice guideline for the diagnosis, evaluation, prevention and treatment of chronic kidney disease mineral and bone disorder (CKD-MBD). Kidney Int 76:S1–S128. doi: 10.1038/ki.2009.188 Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Service des Explorations FonctionnellesG.H. Necker Enfants MaladesParis cedex 15France
  2. 2.Service d’Endocrinologie pédiatrique, French Reference Center for Rare Disorders of the Mineral Metabolism, Department of Endocrinology and Diabetology for ChildrenHôpital Bicêtre, Assistance Publique-Hôpitaux de ParisLe Kremlin BicêtreFrance
  3. 3.Department of Nephrology-Dialysis-TransplantationUniversity of LiègeLiègeBelgium
  4. 4.Service d’Endocrinologie et des Maladies de la ReproductionAssistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Hôpital de BicêtreLe Kremlin BicêtreFrance
  5. 5.INSERM 1185, Fac Med Paris SudUniv Paris-Sud, Université Paris-SaclayLe Kremlin BicêtreFrance
  6. 6.Department of Clinical ChemistryUniversity of LiègeLiègeBelgium

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