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Evaluation of a New Fully Automated Assay for Plasma Intact FGF23

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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.

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References

  1. Liu S, Quarles LD (2007) How fibroblast growth factor 23 works. J Am Soc Nephrol 18:1637–1647. doi:10.1681/ASN.2007010068

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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 

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Authors and Affiliations

  1. Service des Explorations Fonctionnelles, G.H. Necker Enfants Malades, 149 rue de Sèvres, 75743, Paris cedex 15, France

    Jean-Claude Souberbielle, Dominique Prié & Marie-Liesse Piketty

  2. Service d’Endocrinologie pédiatrique, French Reference Center for Rare Disorders of the Mineral Metabolism, Department of Endocrinology and Diabetology for Children, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, 78 rue du Général Leclerc, 94270, Le Kremlin Bicêtre, France

    Anya Rothenbuhler

  3. Department of Nephrology-Dialysis-Transplantation, University of Liège, CHU de Liège, 4000, Liège, Belgium

    Pierre Delanaye

  4. Service d’Endocrinologie et des Maladies de la Reproduction, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Hôpital de Bicêtre, 94275, Le Kremlin Bicêtre, France

    Philippe Chanson

  5. INSERM 1185, Fac Med Paris Sud, Univ Paris-Sud, Université Paris-Saclay, 94276, Le Kremlin Bicêtre, France

    Philippe Chanson

  6. Department of Clinical Chemistry, University of Liège, CHU de Liège, 4000, Liège, Belgium

    Etienne Cavalier

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  1. Jean-Claude Souberbielle
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Correspondence to Etienne Cavalier.

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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.

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Souberbielle, JC., Prié, D., Piketty, ML. et al. Evaluation of a New Fully Automated Assay for Plasma Intact FGF23. Calcif Tissue Int 101, 510–518 (2017). https://doi.org/10.1007/s00223-017-0307-y

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