Evaluation of a New Automated Chemiluminescence Immunoassay for FGF23

Overview

Journal J Bone Miner Metab

Specialty Endocrinology

Date 2011 Sep 8

PMID 21898178

Citations 16

Authors

Yuichiro Shimizu

Seiji Fukumoto

Toshiro Fujita

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Intact FGF23 concentration in healthy infants, children, and adolescents, and diagnostic usefulness in patients with X-linked hypophosphatemic rickets.

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Normocalcemic primary hyperparathyroidism is an early stage of primary hyperparathyroidism according to fibroblast growth factor 23 level.

Chertok Shacham E, Maman N, Lazareva T, Masalha R, Mahagna L, Sela G Front Endocrinol (Lausanne). 2023; 14:1152464.

PMID: 37065752 PMC: 10098304. DOI: 10.3389/fendo.2023.1152464.

Clinical performance of a new intact FGF23 immunoassay in healthy individuals and patients with chronic hypophosphatemia.

Kato H, Miyazaki H, Kimura T, Hoshino Y, Hidaka N, Koga M Bone Rep. 2023; 18:101659.

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Determination of iFGF23 Upper Reference Limits (URL) in healthy pediatric population, for its better correct use.

Brescia V, Fontana A, Lovero R, Capobianco C, Marsico S, De Chirico T Front Endocrinol (Lausanne). 2022; 13:1018523.

PMID: 36440231 PMC: 9681906. DOI: 10.3389/fendo.2022.1018523.

Determination of FGF23 Levels for the Diagnosis of FGF23-Mediated Hypophosphatemia.

Hartley I, Gafni R, Roszko K, Brown S, de Castro L, Saikali A J Bone Miner Res. 2022; 37(11):2174-2185.

PMID: 36093861 PMC: 9712269. DOI: 10.1002/jbmr.4702.

References

Fukumoto S, Martin T . Bone as an endocrine organ. Trends Endocrinol Metab. 2009; 20(5):230-6. DOI: 10.1016/j.tem.2009.02.001. View

Mirza M, Hansen T, Johansson L, Ahlstrom H, Larsson A, Lind L . Relationship between circulating FGF23 and total body atherosclerosis in the community. Nephrol Dial Transplant. 2009; 24(10):3125-31. DOI: 10.1093/ndt/gfp205. View

Yamazaki Y, Okazaki R, Shibata M, Hasegawa Y, Satoh K, Tajima T . Increased circulatory level of biologically active full-length FGF-23 in patients with hypophosphatemic rickets/osteomalacia. J Clin Endocrinol Metab. 2002; 87(11):4957-60. DOI: 10.1210/jc.2002-021105. View

Gutierrez O, Mannstadt M, Isakova T, Rauh-Hain J, Tamez H, Shah A . Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med. 2008; 359(6):584-92. PMC: 2890264. DOI: 10.1056/NEJMoa0706130. View

Ito N, Shimizu Y, Suzuki H, Saito T, Okamoto T, Hori M . Clinical utility of systemic venous sampling of FGF23 for identifying tumours responsible for tumour-induced osteomalacia. J Intern Med. 2010; 268(4):390-4. DOI: 10.1111/j.1365-2796.2010.02262.x. View

Tanaka R, Takemura M, Sato M, Yamada Y, Nakagawa T, Horibe T . Comparison of chemiluminescence enzyme immunoassay (CLEIA) with ELISA for the determination of anti-cyclic citrullinated peptide antibodies. Clin Chim Acta. 2009; 411(1-2):22-5. DOI: 10.1016/j.cca.2009.09.032. View

Titan S, Zatz R, Graciolli F, Dos Reis L, Barros R, Jorgetti V . FGF-23 as a predictor of renal outcome in diabetic nephropathy. Clin J Am Soc Nephrol. 2010; 6(2):241-7. PMC: 3052212. DOI: 10.2215/CJN.04250510. View

Jonsson K, Zahradnik R, Larsson T, White K, Sugimoto T, Imanishi Y . Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia. N Engl J Med. 2003; 348(17):1656-63. DOI: 10.1056/NEJMoa020881. View

Urakawa I, Yamazaki Y, Shimada T, Iijima K, Hasegawa H, Okawa K . Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature. 2006; 444(7120):770-4. DOI: 10.1038/nature05315. View

10.

Mirza M, Karlsson M, Mellstrom D, Orwoll E, Ohlsson C, Ljunggren O . Serum fibroblast growth factor-23 (FGF-23) and fracture risk in elderly men. J Bone Miner Res. 2010; 26(4):857-64. DOI: 10.1002/jbmr.263. View

11.

Frishberg Y, Ito N, Rinat C, Yamazaki Y, Feinstein S, Urakawa I . Hyperostosis-hyperphosphatemia syndrome: a congenital disorder of O-glycosylation associated with augmented processing of fibroblast growth factor 23. J Bone Miner Res. 2006; 22(2):235-42. DOI: 10.1359/jbmr.061105. View

12.

Shimada T, Muto T, Urakawa I, Yoneya T, Yamazaki Y, Okawa K . Mutant FGF-23 responsible for autosomal dominant hypophosphatemic rickets is resistant to proteolytic cleavage and causes hypophosphatemia in vivo. Endocrinology. 2002; 143(8):3179-82. DOI: 10.1210/endo.143.8.8795. View

13.

Heijboer A, Levitus M, Vervloet M, Lips P, Ter Wee P, Dijstelbloem H . Determination of fibroblast growth factor 23. Ann Clin Biochem. 2009; 46(Pt 4):338-40. DOI: 10.1258/acb.2009.009066. View

14.

Endo I, Fukumoto S, Ozono K, Namba N, Tanaka H, Inoue D . Clinical usefulness of measurement of fibroblast growth factor 23 (FGF23) in hypophosphatemic patients: proposal of diagnostic criteria using FGF23 measurement. Bone. 2008; 42(6):1235-9. DOI: 10.1016/j.bone.2008.02.014. View

15.

Araya K, Fukumoto S, Backenroth R, Takeuchi Y, Nakayama K, Ito N . A novel mutation in fibroblast growth factor 23 gene as a cause of tumoral calcinosis. J Clin Endocrinol Metab. 2005; 90(10):5523-7. DOI: 10.1210/jc.2005-0301. View

16.

Ito N, Fukumoto S, Takeuchi Y, Yasuda T, Hasegawa Y, Takemoto F . Comparison of two assays for fibroblast growth factor (FGF)-23. J Bone Miner Metab. 2005; 23(6):435-40. DOI: 10.1007/s00774-005-0625-4. View

17.

Gutierrez O, Januzzi J, Isakova T, Laliberte K, Smith K, Collerone G . Fibroblast growth factor 23 and left ventricular hypertrophy in chronic kidney disease. Circulation. 2009; 119(19):2545-52. PMC: 2740903. DOI: 10.1161/CIRCULATIONAHA.108.844506. View

18.

Goetz R, Nakada Y, Hu M, Kurosu H, Wang L, Nakatani T . Isolated C-terminal tail of FGF23 alleviates hypophosphatemia by inhibiting FGF23-FGFR-Klotho complex formation. Proc Natl Acad Sci U S A. 2009; 107(1):407-12. PMC: 2806769. DOI: 10.1073/pnas.0902006107. View

19.

Shimada T, Hasegawa H, Yamazaki Y, Muto T, Hino R, Takeuchi Y . FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. J Bone Miner Res. 2004; 19(3):429-35. DOI: 10.1359/JBMR.0301264. View

20.

Kazama J, Sato F, Omori K, Hama H, Yamamoto S, Maruyama H . Pretreatment serum FGF-23 levels predict the efficacy of calcitriol therapy in dialysis patients. Kidney Int. 2005; 67(3):1120-5. DOI: 10.1111/j.1523-1755.2005.00178.x. View