Abstract
Background: Owing to a growing interest in vitamin D, there has been an increasing demand for 25-hydroxyvitamin D (25[OH]D) measurements over the past few years warranting a critical evaluation of laboratory methods for 25(OH)D determinations. Therefore, the aim of this study was to compare four of the most frequently used routine assays for 25(OH)D.
Methods: In 106 hypertensive patients (53±14 years; 59% females), derived from the Graz Endocrine Causes of Hypertension (GECOH) study, we measured 25(OH)D in serum and plasma by means of four automated immunoassays (DiaSorin Liaison, IDS iSYS, Abbott ARCHITECT, and Roche Cobas).
Results: We observed a poor comparability between assay results with Pearson correlation coefficients between the different methods ranging from 0.57 to 0.85. Using a value of ≤20 ng/mL (50 nmol/L) as the cut-off for vitamin D deficiency, the percentages of vitamin D deficient patients was significantly different depending on the assay method: 79.2% (Abbott ARCHITECT), 50.0% (DiaSorin Liaison), 28.3% (IDS iSYS), and 23.6% (Roche Cobas).
Conclusions: By comparing four frequently used automated immunoassays for 25(OH)D, we observed remarkable differences with a significant impact on vitamin D status classification. Clinicians and researchers must be aware of these assay differences and must aim for standardization of 25(OH)D measurements.
Zusammenfassung
Einleitung: Aufgrund eines steigenden Interesses am Vitamin D kam es in den letzten Jahren zu einer zunehmenden Nachfrage nach Bestimmungen des 25-Hydroxyvitamin D (25[OH]D). Dies erfordert auch eine kritische Evaluierung der Labormethodik, weswegen wir 4 der am häufigsten verwendeten Immuno-assays für das 25(OH)D miteinander verglichen haben.
Methoden: Bei 106 hypertensiven PatientInnen (53±14 Jahren; 59% Frauen) der Graz Endocrine Causes of Hypertension (GECOH) Studie, wurde 25(OH)D im Serum und Plasma mit 4 automatisierten Immuno-Assays gemessen (DiaSorin Liaison, IDS iSYS, Abbott ARCHITECT, and Roche Cobas).
Ergebnisse: Es zeigte sich eine schlechte Vergleichbarkeit zwischen den unterschiedlichen Assays mit Pearson Korrelationskoeffizienten zwischen den unterschiedlichen Methoden von 0,57 bis 0,85. Bei Verwendung eines cut-offs von ≤20 ng/mL (50 nmol/L) für die Definition eines Vitamin D Mangels, schwankte die Prävalenz des Vitamin D Mangels je nach verwendetem Assay: 79.2% (Abbott ARCHITECT), 50.0% (DiaSorin Liaison), 28.3% (IDS iSYS) und 23.6% (Roche Cobas).
Schlussfolgerungen: Bei einem Vergleich von 4 häufig verwendeten automatisierten Immuno-Assays für das 25(OH)D fanden wir signifikante Unterschiede mit deutlichen Auswirkungen auf die Klassifikation des Vitamin D Status. Ärzte und Forscher müssen sich dieser Assay-Unterschiede bewusst sein und man muss unbedingt eine Standardisierung der 25(OH)D Messungen anstreben.
Reviewed Publication:
März W.
We are grateful for all the support by the laboratory staff at the Department of Endocrinology and Metabolism and at the Clinical Institute of Medical and Chemical Laboratory Diagnostics at the Medical University of Graz. We are grateful for Abbott Diagnostics, Roche Diagnostics and DiaSorin for providing 25(OH)D reagents free of charge.
Conflict of interest statement
Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article. Research support played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
Research funding: The GECOH study is supported by the province of Styria. Katharina Kienreich is supported by funding from the Austrian National Bank (Jubilaeumsfond: project numbers: 13878 and 13905). Nicolas Verheyen is supported by funding from the Austrian National Bank (Jubilaeumsfond: project number: 14621). Stefan Pilz is supported by the EFSD Albert Renold Travel Fellowship grant.
Employment or leadership: None declared.
Honorarium: None declared.
References
1. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab 2011;96:53–8.10.1210/jc.2010-2704Search in Google Scholar PubMed PubMed Central
2. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011;96:1911–30.10.1210/jc.2011-0385Search in Google Scholar PubMed
3. Souberbielle JC, Body JJ, Lappe JM, Plebani M, Shoenfeld Y, Wang TJ, et al. Vitamin D and musculoskeletal health, cardiovascular disease, autoimmunity and cancer: Recommendations for clinical practice. Autoimmun Rev 2010;9:709–15.10.1016/j.autrev.2010.06.009Search in Google Scholar PubMed
4. Muscogiuri G, Sorice GP, Ajjan R, Mezza T, Pilz S, Prioletta A, et al. Can vitamin D deficiency cause diabetes and cardiovascular diseases? Present evidence and future perspectives. Nutr Metab Cardiovasc Dis 2012;22:81–7.10.1016/j.numecd.2011.11.001Search in Google Scholar PubMed
5. Pilz S, Tomaschitz A, Drechsler C, Zittermann A, Dekker JM, März W. Vitamin D supplementation: a promising approach for the prevention and treatment of strokes. Curr Drug Targets 2011;12:88–96.10.2174/138945011793591563Search in Google Scholar PubMed
6. Herrmann M. The measurement of 25-hydroxy vitamin D – an analytical challenge. Clin Chem Lab Med 2012;50:1873–5.10.1515/cclm-2012-0526Search in Google Scholar PubMed
7. Pilz S, Maerz W. Vitamin D and cardiovascular diseases: where do we stand in 2012? J Lab Med 2012;36:281–9.10.1515/labmed-2011-0029Search in Google Scholar
8. Pilz S, Tomaschitz A, Pieber T, Lafer I, Drechsler C, Meinitzer A, et al. Vitamin D: clinical implications beyond musculoskeletal diseases. J Lab Med 2011;35:211–6.Search in Google Scholar
9. Farrell C, Soldo J, Williams P, Herrmann M. 25-Hydroxyvitamin D testing: challenging the performance of current automated immunoassays. Clin Chem Lab Med 2012;50:1953–63.10.1515/cclm-2012-0522Search in Google Scholar PubMed
10. Farrell CJ, Martin S, McWhinney B, Straub I, Williams P, Herrmann M. State-of-the-art vitamin D assays: a comparison of automated immunoassays with liquid chromatography-tandem mass spectrometry methods. Clin Chem 2012;58:531–42.10.1373/clinchem.2011.172155Search in Google Scholar PubMed
11. Janssen MJ, Wielders JP, Bekker CC, Boesten LS, Buijs MM, Heijboer AC, et al. Multicenter comparison study of current methods to measure 25-hydroxyvitamin D in serum. Steroids 2012;77:1366–72.10.1016/j.steroids.2012.07.013Search in Google Scholar PubMed
12. Heijboer AC, Blankenstein MA, Kema IP, Buijs MM. Accuracy of 6 routine 25-hydroxyvitamin D assays: influence of vitamin D binding protein concentration. Clin Chem 2012;58:543–8.10.1373/clinchem.2011.176545Search in Google Scholar PubMed
13. Lips P, Chapuy MC, Dawson-Hughes B, Pols HA, Holick MF. An international comparison of serum 25-hydroxyvitamin D measurements. Osteoporos Int 1999;9:394–7.10.1007/s001980050162Search in Google Scholar PubMed
14. Carter GD. 25-Hydroxyvitamin D: a difficult analyte. Clin Chem 2012;58:486–8.10.1373/clinchem.2011.180562Search in Google Scholar PubMed
15. Carter GD, Berry JL, Gunter E, Jones G, Jones JC, Makin HL, et al. Proficiency testing of 25-hydroxyvitamin D (25-OHD) assays. J Steroid Biochem Mol Biol 2010;121:176–9.10.1016/j.jsbmb.2010.03.033Search in Google Scholar PubMed
16. Carter GD. Accuracy of 25-hydroxyvitamin D assays: confronting the issues. Curr Drug Targets 2011;12:19–28.10.2174/138945011793591608Search in Google Scholar PubMed
17. Binkley N, Krueger D, Cowgill CS, Plum L, Lake E, Hansen KE, et al. Assay variation confounds the diagnosis of hypovitaminosis D: a call for standardization. J Clin Endocrinol Metab 2004;89:3152–7.10.1210/jc.2003-031979Search in Google Scholar PubMed
18. Pilz S, Tomaschitz A, Stepan V, Obermayer-Pietsch B, Fahrleitner-Pammer A, Schweighofer N, et al. Graz Endocrine Causes of Hypertension (GECOH) study: a diagnostic accuracy study of aldosterone to active renin ratio in screening for primary aldosteronism. BMC Endocr Disord 2009;9:11.10.1186/1472-6823-9-11Search in Google Scholar PubMed PubMed Central
19. Pilz S, Kienreich K, Stückler D, Meinitzer A, Tomaschitz A. Associations of sun exposure with 25-hydroxyvitamin D and parathyroid hormone levels in a cohort of hypertensive patients: the Graz Endocrine Causes of Hypertension (GECOH) study. Int J Endocrinol 2012;2012:732636.10.1155/2012/732636Search in Google Scholar PubMed PubMed Central
20. Schöttker B, Jansen EH, Haug U, Schomburg L, Köhrle J, Brenner H. Standardization of misleading immunoassay based 25-hydroxyvitamin D levels with liquid chromatography tandem-mass spectrometry in a large cohort study. PLoS ONE 2012;7:e48774.10.1371/journal.pone.0048774Search in Google Scholar PubMed PubMed Central
21. Cavalier E, Wallace AM, Carlisi A, Chapelle JP, Delanaye P, Souberbielle JC. Cross-reactivity of 25-hydroxy vitamin D2 from different commercial immunoassays for 25-hydroxy vitamin D: an evaluation without spiked samples. Clin Chem Lab Med 2011;49:555–8.10.1515/CCLM.2011.072Search in Google Scholar PubMed
22. Sempos CT, Vesper HW, Phinney KW, Thienpont LM, Coates PM; Vitamin D Standardization Program (VDSP). Vitamin D status as an international issue: national surveys and the problem of standardization. Scand J Clin Lab Invest Suppl 2012;243: 32–40.Search in Google Scholar
23. Zittermann A, Iodice S, Pilz S, Grant WB, Bagnardi V, Gandini S. Vitamin D deficiency and mortality risk in the general population: a meta-analysis of prospective cohort studies. Am J Clin Nutr 2012;95:91–100.10.3945/ajcn.111.014779Search in Google Scholar PubMed
24. Pilz S, Iodice S, Zittermann A, Grant WB, Gandini S. Vitamin D status and mortality risk in CKD: a meta-analysis of prospective studies. Am J Kidney Dis 2011;58:374–82.10.1053/j.ajkd.2011.03.020Search in Google Scholar PubMed
25. Pilz S, Tomaschitz A, Friedl C, Amrein K, Drechsler C, Ritz E, et al. Vitamin D status and mortality in chronic kidney disease. Nephrol Dial Transplant 2011;26:3603–9.10.1093/ndt/gfr076Search in Google Scholar PubMed
26. Thomas GN, O Hartaigh B, Bosch JA, Pilz S, Loerbroks A, Kleber ME, et al. Vitamin D levels predict all-cause and cardiovascular disease mortality in subjects with the metabolic syndrome: the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. Diabetes Care 2012;35: 1158–64.10.2337/dc11-1714Search in Google Scholar PubMed PubMed Central
27. Putz-Bankuti C, Pilz S, Stojakovic T, Scharnagl H, Pieber TR, Trauner M, et al. Association of 25-hydroxyvitamin D levels with liver dysfunction and mortality in chronic liver disease. Liver Int 2012;32:845–51.10.1111/j.1478-3231.2011.02735.xSearch in Google Scholar PubMed
28. Pilz S, Dobnig H, Tomaschitz A, Kienreich K, Meinitzer A, Friedl C, et al. Low 25-hydroxyvitamin D is associated with increased mortality in female nursing home residents. J Clin Endocrinol Metab 2012;97:E653–7.10.1210/jc.2011-3043Search in Google Scholar PubMed
29. Bjelakovic G, Gluud LL, Nikolova D, Whitfield K, Wetterslev J, Simonetti RG, et al. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev 2011;7:CD007470.10.1002/14651858.CD007470.pub2Search in Google Scholar PubMed
30. Rejnmark L, Avenell A, Masud T, Anderson F, Meyer HE, Sanders KM, et al. Vitamin D with calcium reduces mortality: patient level pooled analysis of 70,528 patients from eight major vitamin D trials. J Clin Endocrinol Metab 2012;97:2670–81.10.1210/jc.2011-3328Search in Google Scholar PubMed PubMed Central
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