Evaluation of a new automated chemiluminescence immunoassay for FGF23
- 340 Downloads
Fibroblast growth factor 23 (FGF23) is a hormone regulating phosphate and vitamin D metabolism. We have previously established a sandwich enzyme-linked immunosorbent assay (ELISA) for FGF23 and reported that FGF23 values are useful for the differential diagnosis of chronic hypophosphatemia. However, this ELISA has a rather narrow assay range of 3–800 pg/ml, and it was pointed out that the assay performance is not satisfactory when automatic washing is used. Here we evaluated a new automated chemiluminescence immunoassay for FGF23. This assay uses 10 μl sera or plasma samples and requires 20 min to obtain the first result. The assay was linear up to about 15,000 pg/ml and had a detection limit of 1 pg/ml. In addition, this assay showed coefficients of variation of less than 5% using samples with average FGF23 levels of 43.2–2,454.0 pg/ml. When FGF23 levels in 210 samples from chronic hypophosphatemic patients were evaluated by both the previous ELISA and this new assay, there was a good correlation of R 2 = 0.96. However, FGF23 levels by the new assay showed lower values, especially in samples with high FGF23 levels. Given that the lowest FGF23 level in patients with FGF23-related hypophosphatemia was 30.8 pg/ml and that the highest FGF23 levels in patients with non-FGF23-related hypophosphatemia was 20.8 pg/ml by this novel assay, the sensitivity and specificity were 100% when the cutoff was set between 20.8 and 30.8 pg/ml. From the aspect of convenience and the coefficients of variation of this assay, we propose that the cutoff be 25 pg/ml. There results indicate that this new assay is ideal for both clinical use and clinical studies, especially when measuring many samples with high FGF23 levels.
KeywordsFGF23 Hypophosphatemia Immunoassay
This study was supported in part by grants from the Ministry of Education, Culture, Sports, Science and Technology, and from the Ministry of Health, Labour and Welfare, Japan.
Conflict of interest
Dr. Fukumoto serves as a consultant for Kyowa-Hakko Kirin Co. Ltd.
- 4.Yamazaki Y, Okazaki R, Shibata M, Hasegawa Y, Satoh K, Tajima T, Takeuchi Y, Fujita T, Nakahara K, Yamashita T, Fukumoto S (2002) Increased circulatory level of biologically active full-length FGF-23 in patients with hypophosphatemic rickets/osteomalacia. J Clin Endocrinol Metab 87:4957–4960PubMedCrossRefGoogle Scholar
- 5.Shimada T, Muto T, Urakawa I, Yoneya T, Yamazaki Y, Okawa K, Takeuchi Y, Fujita T, Fukumoto S, Yamashita T (2002) Mutant FGF-23 responsible for autosomal dominant hypophosphatemic rickets is resistant to proteolytic cleavage and causes hypophosphatemia in vivo. Endocrinology 143:3179–3182PubMedCrossRefGoogle Scholar
- 6.Goetz R, Nakada Y, Hu MC, Kurosu H, Wang L, Nakatani T, Shi M, Eliseenkova AV, Razzaque MS, Moe OW, Kuro-o M, Mohammadi M (2009) Isolated C-terminal tail of FGF23 alleviates hypophosphatemia by inhibiting FGF23–FGFR–Klotho complex formation. Proc Natl Acad Sci USA 107:407–412PubMedCrossRefGoogle Scholar
- 7.Endo I, Fukumoto S, Ozono K, Namba N, Tanaka H, Inoue D, Minagawa M, Sugimoto T, Yamauchi M, Michigami T, Matsumoto T (2008) Clinical usefulness of measurement of fibroblast growth factor 23 (FGF23) in hypophosphatemic patients: proposal of diagnostic criteria using FGF23 measurement. Bone (NY) 42:1235–1239Google Scholar
- 9.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 119:2545–2552PubMedCrossRefGoogle Scholar
- 12.Tanaka R, Takemura M, Sato M, Yamada Y, Nakagawa T, Horibe T, Hoshi M, Otaki H, Ito H, Seishima M, Shimizu K (2010) Comparison of chemiluminescence enzyme immunoassay (CLEIA) with ELISA for the determination of anti-cyclic citrullinated peptide antibodies. Clin Chim Acta 411:22–25PubMedCrossRefGoogle Scholar
- 14.Jonsson KB, Zahradnik R, Larsson T, White KE, Sugimoto T, Imanishi Y, Yamamoto T, Hampson G, Koshiyama H, Ljunggren O, Oba K, Yang IM, Miyauchi A, Econs MJ, Lavigne J, Juppner H (2003) Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia. N Engl J Med 348:1656–1663PubMedCrossRefGoogle Scholar
- 17.Frishberg Y, Ito N, Rinat C, Yamazaki Y, Feinstein S, Urakawa I, Navon-Elkan P, Becher-Cohen R, Yamashita T, Araya K, Igarashi T, Fujita T, Fukumoto S (2007) Hyperostosis–hyperphosphatemia syndrome: a congenital disorder of O-glycosylation associated with augmented processing of fibroblast growth factor 23. J Bone Miner Res 22:235–242PubMedCrossRefGoogle Scholar