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Measurement of Circulating 1,25-Dihydroxyvitamin D and Vitamin D–Binding Protein in Chronic Kidney Diseases

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Vitamin D in Chronic Kidney Disease

Abstract

After providing a short reminder on the physiopathology of vitamin D, we will discuss the potential interest to analyze the different metabolites of vitamin D. Undoubtly, measuring 25(OH) vitamin D is one of the most relevant and frequent dosage in daily clinical practice. Indeed, this is the most interesting measurement to assess global vitamin D status. The number of 25(OH)D determinations has dramatically increased over the last 10 years. This fact has led most of the clinical laboratories to move from the DiaSorin RIA, the most widely used method before twenties, to automated immunoassays or liquid chromatographs coupled with two mass spectrometers in tandem (LC-MS/MS). Anyway, one has to remember that analytical 25(OH)D determination is far from an easy task. Indeed, several important problems have to be overcome to correctly assess this parameter. Among them, the very high lipophilic nature of the molecule and its strong association with vitamin D–binding protein (VDBP) and, to a lesser extent, albumin, necessitates a thorough separation step and, for the one-phase immunoassays, a good equilibrium between the analyte and the antibodies used in the kits. We will also discuss the performance of this measurement in very specific population like pregnant women and chronic kidney diseases patients treated by dialysis among others.

In this chapter, we will also describe potential indications and methods available to measure other vitamin D metabolites like cholecalciferol, 1,25 and 24,25 vitamin D. Finally, we will critically focus on vitamin D binding protein (VDBP) and on the new concept of “free” or “bioavailable” vitamin D.

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References

  1. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266–81.

    Article  CAS  PubMed  Google Scholar 

  2. Zhu JG, Ochalek JT, Kaufmann M, Jones G, Deluca HF. CYP2R1 is a major, but not exclusive, contributor to 25-hydroxyvitamin D production in vivo. Proc Natl Acad Sci USA. 2013;110:15650–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Nemere I, Schwartz Z. Identification of a membrane receptor for 1, 25 dihydroxyvitamin D3 which mediates rapid activation of protein kinase C. J Bone Miner Res. 1998;13:1353–9.

    Article  CAS  PubMed  Google Scholar 

  4. Schlingmann KP, Kaufmann M, Weber S, Irwin A, Goos C, John U, Misselwitz J, Klaus G, Kuwertz-Bröking E, Fehrenbach H, Wingen AM, Güran T, Bindels RJ, David E, Jones G, Konrad M. Mutations in CYP24A1 and idiopathic infantile hypercalcemia. N Engl J Med. 2011;365:410–21.

    Article  CAS  PubMed  Google Scholar 

  5. Matsuoka LY, Wortsman J, Hollis BW. Use of topical sunscreen for the evaluation of regional synthesis of vitamin D3. J Am Acad Dermatol. 1990;22:772–5.

    Article  CAS  PubMed  Google Scholar 

  6. Zhu J, Deluca HF. Vitamin D 25-hydroxylase - four decades of searching, are we there yet? Arch Biochem Biophys. 2012;523:30–6.

    Article  CAS  PubMed  Google Scholar 

  7. Binkley N, Lappe J, Singh RJ, Khosla S, Krueger D, Drezner MK, Blank RD. Can vitamin D metabolite measurements facilitate a “treat-to-target” paradigm to guide vitamin D supplementation? Osteoporos Int. 2015;26:1655–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Wallace AM, Gibson S, de la Hunty A, Lamberg-Allardt C, Ashwell M. Measurement of 25-hydroxyvitamin D in the clinical laboratory: current procedures, performance characteristics and limitations. Steroids. 2010;75:477–88.

    Article  CAS  PubMed  Google Scholar 

  9. Powe CE, Evans MK, Wenger J, Zonderman AB, Berg AH, Nalls M, Tamez H, Zhang D, Bhan I, Karumanchi SA, Powe NR, Thadhani R. Vitamin D-binding protein and vitamin D status of black Americans and white Americans. N Engl J Med. 2013;369:1991–2000.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. 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.

    Article  CAS  PubMed  Google Scholar 

  11. Depreter B, Heijboer AC, Langlois MR. Accuracy of three automated 25-hydroxyvitamin D assays in hemodialysis patients. Clin Chim Acta. 2013;415:255–60.

    Article  CAS  PubMed  Google Scholar 

  12. Cavalier E, Wallace AM, Carlisi A, Chapelle J-P, Delanaye P, Souberbielle J-C. 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.

    CAS  PubMed  Google Scholar 

  13. Kobold U. Approaches to measurement of vitamin D concentrations – mass spectrometry. Scand J Clin Lab Invest Suppl. 2012;243:54–9.

    PubMed  Google Scholar 

  14. Cavalier E, Carlisi A, Bekaert A-C, Rousselle O, Chapelle JP. Human anti-animal interference in DiaSorin Liaison total 25(OH)-vitamin D assay: towards the end of a strange story? Clin Chim Acta. 2012;413:527–8.

    Article  CAS  PubMed  Google Scholar 

  15. Sempos CT, Vesper HW, Phinney KW, Thienpont LM, Coates PM. Vitamin D status as an international issue: national surveys and the problem of standardization. Scand J Clin Lab Invest Suppl. 2012;243:32–40.

    PubMed  Google Scholar 

  16. Cavalier E, Lukas P, Crine Y, Peeters S, Carlisi A, Le Goff C, Gadisseur R, Delanaye P, Souberbielle JC. Evaluation of automated immunoassays for 25(OH)-vitamin D determination in different critical populations before and after standardization of the assays. Clin Chim Acta. 2014;431:60–5.

    Article  CAS  PubMed  Google Scholar 

  17. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM. Guidelines for preventing and treating vitamin D deficiency and insufficiency revisited. J Clin Endocrinol Metab. 2012;97:1153–8.

    Article  CAS  PubMed  Google Scholar 

  18. Kallas M, Green F, Hewison M, White C, Kline G. Rare causes of calcitriol-mediated hypercalcemia: a case report and literature review. J Clin Endocrinol Metab. 2010;95:3111–7.

    Article  CAS  PubMed  Google Scholar 

  19. Malloy PJ, Feldman D. Genetic disorders and deficits in vitamin D action. Endocrinol Metab Clin N Am. 2010;39:333–46.

    Article  CAS  Google Scholar 

  20. Hawkes C, Schnellbacher S, Singh R, Levine M. 25-hydroxyvitamin D can interfere with a common assay for 1,25-dihydroxyvitamin D in vitamin D intoxication. J Clin Endocrinol Metab. 2015;100:2883–9.

    Google Scholar 

  21. Van Helden J, Weiskirchen R. Experience with the first fully automated chemiluminescence immunoassay for the quantification of 1α, 25-dihydroxy-vitamin D. Clin Chem Lab Med. 2015;53:761–70.

    PubMed  Google Scholar 

  22. Delanaye P, Weekers L, Warling X, Moonen M, Smelten N, Médart L, Krzesinski J-M, Cavalier E. Cholecalciferol in haemodialysis patients: a randomized, double-blind, proof-of-concept and safety study. Nephrol Dial Transplant. 2013;28:1779–86.

    Article  PubMed  Google Scholar 

  23. Lambert PW, Stern PH, Avioli RC, Brackett NC, Turner RT, Greene A, Fu IY, Bell NH. Evidence for extrarenal production of 1α,25-dihydroxyvitamin D in man. J Clin Invest. 1982;69:722–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Aronov PA, Hall LM, Dettmer K, Stephensen CB, Hammock BD. Metabolic profiling of major vitamin D metabolites using Diels-Alder derivatization and ultra-performance liquid chromatography-tandem mass spectrometry. Anal Bioanal Chem. 2008;391:1917–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. De Boer IH, Sachs MC, Chonchol M, Himmelfarb J, Hoofnagle AN, Ix JH, Kremsdorf RA, Lin YS, Mehrotra R, Robinson-Cohen C, Siscovick DS, Steffes MW, Thummel KE, Tracy RP, Wang Z, Kestenbaum B. Estimated GFR and circulating 24,25-dihydroxyvitamin D3 concentration: a participant-level analysis of 5 cohort studies and clinical trials. Am J Kidney Dis. 2014;64:187–97.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Kaufmann M, Gallagher JC, Peacock M, Schlingmann KP, Konrad M, DeLuca HF, Sigueiro R, Lopez B, Mourino A, Maestro M, St-Arnaud R, Finkelstein JS, Cooper DP, Jones G. Clinical utility of simultaneous quantitation of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D by LC-MS/MS involving derivatization with DMEQ-TAD. J Clin Endocrinol Metab. 2014;99:2567–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Bosworth CR, Levin G, Robinson-Cohen C, Hoofnagle AN, Ruzinski J, Young B, Schwartz SM, Himmelfarb J, Kestenbaum B, de Boer IH. The serum 24,25-dihydroxyvitamin D concentration, a marker of vitamin D catabolism, is reduced in chronic kidney disease. Kidney Int. 2012;82:693–700.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. De Boer IH, Sachs MC, Cleary PA, Hoofnagle AN, Lachin JM, Molitch ME, Steffes MW, Sun W, Zinman B, Brunzell JD. Circulating vitamin D metabolites and kidney disease in type 1 diabetes. J Clin Endocrinol Metab. 2012;97:4780–8.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Constans J, Gouaillard C, Bouissou C, Dugoujon JM. Polymorphism of the vitamin D binding protein (DBP) among primates: an evolutionary analysis. Am J Phys Anthropol. 1987;73:365–77.

    Article  CAS  PubMed  Google Scholar 

  30. Speeckaert M, Huang G, Delanghe JR, Taes YEC. Biological and clinical aspects of the vitamin D binding protein (Gc-globulin) and its polymorphism. Clin Chim Acta. 2006;372:33–42.

    Article  CAS  PubMed  Google Scholar 

  31. White P, Cooke N. The multifunctional properties and characteristics of vitamin D-binding protein. Trends Endocrinol Metab. 2000;11:320–7.

    Article  CAS  PubMed  Google Scholar 

  32. Chun RF, Peercy BE, Orwoll ES, Nielson CM, Adams JS, Hewison M. Vitamin D and DBP: the free hormone hypothesis revisited. J Steroid Biochem Mol Biol. 2013;144:132–7.

    Article  PubMed  Google Scholar 

  33. Bikle DD, Gee E, Halloran B, Kowalski MA, Ryzen E, Haddad JG. Assessment of the free fraction of 25-hydroxyvitamin D in serum and its regulation by albumin and the vitamin D-binding protein. J Clin Endocrinol Metab. 1986;63:954–9.

    Article  CAS  PubMed  Google Scholar 

  34. Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab. 1999;84:3666–72.

    Article  CAS  PubMed  Google Scholar 

  35. Powe CE, Ricciardi C, Berg AH, Erdenesanaa D, Collerone G, Ankers E, Wenger J, Karumanchi SA, Thadhani R, Bhan I. Vitamin D-binding protein modifies the vitamin D-bone mineral density relationship. J Bone Miner Res. 2011;26:1609–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Bhan I, Powe CE, Berg AH, Ankers E, Wenger JB, Karumanchi SA, Thadhani RI. Bioavailable vitamin D is more tightly linked to mineral metabolism than total vitamin D in incident hemodialysis patients. Kidney Int. 2012;82:84–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to Etienne Cavalier PhD .

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Cavalier, E., Delanaye, P. (2016). Measurement of Circulating 1,25-Dihydroxyvitamin D and Vitamin D–Binding Protein in Chronic Kidney Diseases. In: Ureña Torres, P., Cozzolino, M., Vervloet, M. (eds) Vitamin D in Chronic Kidney Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-32507-1_5

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  • DOI: https://doi.org/10.1007/978-3-319-32507-1_5

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