Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter May 9, 2022

Vitamin D metabolism in living kidney donors before and after organ donation

Dietmar Enko, Andreas Meinitzer, Sieglinde Zelzer, Markus Herrmann, Katharina Artinger, Alexander R. Rosenkranz and Sabine Zitta

Abstract

Objectives

Living kidney donors provide a unique setting to study functional and metabolic consequences after organ donation. Since the lack of data of the homoeostasis of numerous vitamin D metabolites in these healthy subjects, the aim of this study was to assess the vitamin D metabolism before and after kidney donation.

Methods

We investigated the 25-dihydroxyvitamin D2 (25[OH]D2), 25-dihydroxyvitamin D3 (25[OH]D3), 1,25-dihydroxyvitamin D3 (1,25[OH]2D3), 24,25-dihydroxyvitamin D3 (24,25[OH]2D3), 25,26-dihydroxyvitamin D3 (25,26[OH]2D3), and the native vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) in a well characterized study cohort of 32 healthy living kidney donors before and after organ donation.

Results

Thirty-two healthy subjects after kidney donation had significantly lower median (interquartile range) 1,25(OH)2D3 serum concentrations (88.6 [62.6–118.8] vs. 138.0 [102.6–152.4] pmol/L, p<0.001) and significantly higher median 25(OH)D2 serum levels (1.80 [1.19–2.19] vs. 1.11 [0.74–1.59] nmol/L, p=0.019) than before donation. Similar serum concentrations of 25(OH)D3 and 25,26(OH)2D3 were observed before and after donation. The 24,25(OH)2D3 blood levels distinctly decreased after organ donation (4.1 [2.3–5.3] vs. 5.3 [2.2–6.9] nmol/L, p=0.153). Native vitamin D2 (0.10 [0.08–0.14] vs. 0.08 [0.06–0.12] nmol/L, p=0.275) was slightly increased and vitamin D3 (1.6 [0.6–7.2] vs. 2.5 [0.9–8.6] nmol/L, p=0.957) decreased after kidney donation.

Conclusions

Living kidney donors were found with decreased 1,25(OH)2D3 and 24,25(OH)2D3, increased 25(OH)D2 and consistent 25(OH)D3 and 25,26(OH)2D3 serum concentrations after organ donation. The current study advances the understanding on vitamin D metabolism suggesting that altered hydroxylase-activities after donation is accompanied by compensatory elevated dietary-related 25(OH)D2 blood concentrations.


Corresponding author: Andreas Meinitzer, Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria, Phone: +43 316 385 145, Fax: +43 316 385 13430, E-mail:

  1. Research funding: None declared.

  2. Author contributions: All listed authors contributed to the study design. D.E. wrote the manuscript and S. Zitta supervised the study. S. Zitta, K.A., A.R.R., S. Zelzer and A.M. collected the data. D.E., A.M., and S. Zelzer analysed and interpreted the data. All authors provided critical feedback and finally approved the version to be published.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: The ethical approval was provided by the Ethical Committee of the Medial University of Graz (Graz, Austria) (approval number: 31-289 ex 18/19). The study was carried out in accordance with the Declaration of Helsinki.

References

1. Jenkinson, C. The vitamin D metabolome: an update on analysis and function. Cell Biochem Funct 2019;37:408–23. https://doi.org/10.1002/cbf.3421.Search in Google Scholar

2. Holick, MF. Vitamin D status: measurement, interpretation, and clinical application. Ann Epidemiol 2009;19:73–8. https://doi.org/10.1016/j.annepidem.2007.12.001.Search in Google Scholar

3. Armbrecht, HJ, Okuda, K, Wongsurawat, N, Nemani, RK, Chen, ML, Boltz, MA. Characterization and regulation of the vitamin D hydroxylases. J Steroid Biochem Mol Biol 1992;43:1073–81. https://doi.org/10.1016/0960-0760(92)90334-f.Search in Google Scholar

4. Armbrecht, HJ, Zenser, TV, Davis, BB. Conversion of 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 in renal slices from the rat. Endocrinology 1981;109:218–22. https://doi.org/10.1210/endo-109-1-218.Search in Google Scholar PubMed

5. Kawashima, H, Torikai, S, Kurokawa, K. Localization of 25-hydroxyvitamin D3 1 alpha-hydroxylase and 24-hydroxylase along the rat nephron. Proc Natl Acad Sci USA 1981;78:1199–203. https://doi.org/10.1073/pnas.78.2.1199.Search in Google Scholar PubMed PubMed Central

6. Zelzer, S, Le Goff, C, Peeters, S, Calaprice, C, Meinitzer, A, Enko, D, et al.. Comparison of two LC-MS/MS methods for the quantification of 24,25-dihydroxyvitamin D3 in patients and external quality assurance samples. Clin Chem Lab Med 2021;60:74–81. https://doi.org/10.1515/cclm-2021-0792.Search in Google Scholar PubMed

7. Napoli, JL, Okita, RT, Masters, BS, Horst, RL. Identification of 25,26-dihydroxyvitamin D3 as a rat renal 25-hydroxyvitamin D3 metabolite. Biochemistry 1981;20:5865–71. https://doi.org/10.1021/bi00523a033.Search in Google Scholar PubMed

8. Kaufmann, M, Schlingmann, KP, Berezin, L, Molin, A, Sheftel, J, Vig, M, et al.. Differential diagnosis of vitamin D-related hypercalcemia using serum vitamin D metabolite profiling. J Bone Miner Res 2021;36:1340–50. https://doi.org/10.1002/jbmr.4306.Search in Google Scholar PubMed

9. Ishimura, E, Nishizawa, Y, Inaba, M, Matsumoto, N, Emoto, M, Kawagishi, T, et al.. Serum levels of 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D, and 25-hydroxyvitamin D in nondialyzed patients with chronic renal failure. Kidney Int 1999;55:1019–27. https://doi.org/10.1046/j.1523-1755.1999.0550031019.x.Search in Google Scholar PubMed

10. Stubbs, JR, Zhang, S, Friedman, PA, Nolin, TD. Decreased conversion of 25-hydroxyvitamin D3 to 24,25-dihydroxyvitamin D3 following cholecalciferol therapy in patients with CKD. Clin J Am Soc Nephrol 2014;9:1965–73. https://doi.org/10.2215/cjn.03130314.Search in Google Scholar PubMed PubMed Central

11. Naylor, KL, Garg, AX. Bone health in living kidney donors. Curr Opin Urol 2014;24:624–8. https://doi.org/10.1097/mou.0000000000000107.Search in Google Scholar

12. Enko, D, Meinitzer, A, Scherberich, JE, März, W, Herrmann, M, Artinger, K, et al.. Individual uromodulin serum concentration is independent of glomerular filtration rate in healthy kidney donors. Clin Chem Lab Med 2020;59:563–70. https://doi.org/10.1515/cclm-2020-0894.Search in Google Scholar PubMed

13. Delmonico, F, Council of the Transplantation Society. A report of the Amsterdam Forum on the care of the live kidney donor: data and medical guidelines. Transplantation 2005;79:S53–66.10.1097/01.TP.0000157343.27949.9FSearch in Google Scholar

14. Zelzer, S, Meinitzer, A, Enko, D, Simstich, S, Le Goff, C, Cavalier, E, et al.. Simultaneous determination of 24,25- and 25,26-dihydroxyvitamin D3 in serum samples with liquid-chromatography mass spectrometry – a useful tool for the assessment of vitamin D metabolism. J Chromatogr B Anal Technol Biomed Life Sci 2020;1158:122394. https://doi.org/10.1016/j.jchromb.2020.122394.Search in Google Scholar PubMed

15. Zelzer, S, Meinitzer, A, Herrmann, M, Goessler, W, Enko, D. A novel method for the determination of vitamin D metabolites assessed at the blood-cerebrospinal fluid barrier. Biomolecules 2021;11:1288. https://doi.org/10.3390/biom11091288.Search in Google Scholar PubMed PubMed Central

16. Zitta, S, Schrabmair, W, Reibnegger, G, Meinitzer, A, Wagner, D, Estelberger, W, et al.. Glomerular filtration rate (GFR) determination via individual kinetics of the inulin-like polyfructosan sinistrin versus creatinine-based population-derived regression formulae. BMC Nephrol 2013;14:159. https://doi.org/10.1186/1471-2369-14-159.Search in Google Scholar PubMed PubMed Central

17. Levey, AS, Stevens, LA, Schmid, CH, Zhang, YL, Castro, AF3rd, Feldman, HI, et al.. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009;150:604–12. https://doi.org/10.7326/0003-4819-150-9-200905050-00006.Search in Google Scholar PubMed PubMed Central

18. Gossmann, J, Wilhelm, A, Kachel, HG, Jordan, J, Sann, U, Geiger, H, et al.. Long-term consequences of live kidney donation follow-up in 93% of living kidney donors in a single transplant center. Am J Transplant 2005;5:2417–24. https://doi.org/10.1111/j.1600-6143.2005.01037.x.Search in Google Scholar PubMed

19. Kasiske, BL, Kumar, R, Kimmel, PL, Pesavento, TE, Kalil, RS, Kraus, ES, et al.. Abnormalities in biomarkers of mineral and bone metabolism in kidney donors. Kidney Int 2016;90:861–8. https://doi.org/10.1016/j.kint.2016.05.012.Search in Google Scholar PubMed PubMed Central

20. Kasiske, BL, Anderson-Haag, T, Ibrahim, HN, Pesavento, TE, Weir, MR, Nogueira, JM, et al.. A prospective controlled study of kidney donors: baseline and 6-month follow-up. Am J Kidney Dis 2013;62:577–86. https://doi.org/10.1053/j.ajkd.2013.01.027.Search in Google Scholar PubMed PubMed Central

21. Ponte, B, Trombetti, A, Hadaya, K, Ernandez, T, Fumeaux, D, Iselin, C, et al.. Acute and long term mineral metabolism adaptation in living kidney donors: a prospective study. Bone 2014;62:36–42. https://doi.org/10.1016/j.bone.2014.01.020.Search in Google Scholar

22. Young, A, Hodsman, AB, Boudville, N, Geddes, C, Gill, J, Goltzman, D, et al.. Bone and mineral metabolism and fibroblast growth factor 23 levels after kidney donation. Am J Kidney Dis 2012;59:761–9. https://doi.org/10.1053/j.ajkd.2011.09.019.Search in Google Scholar

23. Bieniasz, M, Kwiatkowski, A, Domagala, P, Gozdowska, J, Kieszek, R, Ostrowski, K, et al.. Serum concentration of vitamin D and parathyroid hormone after living kidney donation. Transplant Proc 2009;41:3067–8. https://doi.org/10.1016/j.transproceed.2009.09.039.Search in Google Scholar

24. Kim, HK, Chung, HJ, Lê, HG, Na, BK, Cho, MC. Serum 24,25-dihydroxyvitamin D level in general Korean population and its relationship with other vitamin D biomarkers. PLoS One 2021;16:e0246541. https://doi.org/10.1371/journal.pone.0246541.Search in Google Scholar

25. Ahmed, LHM, Butler, AE, Dargham, SR, Latif, A, Chidiac, OM, Atkin, SL, et al.. Vitamin D3 metabolite ratio as an indicator of vitamin D status and its association with diabetes complications. BMC Endocr Disord 2020;20:161. https://doi.org/10.1186/s12902-020-00641-1.Search in Google Scholar

26. Horst, RL, Littledike, ET, Gray, RW, Napoli, JL. Impaired 24,25-dihydroxyvitamin D production in anephric human and pig. J Clin Invest 1981;67:274–80. https://doi.org/10.1172/jci110023.Search in Google Scholar

27. Graeff-Armas, LA, Kaufmann, M, Lyden, E, Jones, G. Serum 24,25-dihydroxyvitamin D3 response to native vitamin D2 and D3 supplementation in patients with chronic kidney disease on hemodialysis. Clin Nutr 2018;37:1041–5. https://doi.org/10.1016/j.clnu.2017.04.020.Search in Google Scholar

28. Napoli, JL, Pramanik, BC, Partridge, JJ, Uskoković, MR, Horst23S, RL. 25-dihydroxyvitamin D3 as a circulating metabolite of vitamin D3. Its role in 25-hydroxyvitamin D3-26,23-lactone biosynthesis. J Biol Chem 1982;257:9634–9. https://doi.org/10.1016/s0021-9258(18)34119-x.Search in Google Scholar

29. Shepard, RM, Horst, RL, Hamstra, AJ, DeLuca, HF. Determination of vitamin D and its metabolites in plasma from normal and anephric man. Biochem J 1979;182:55–69. https://doi.org/10.1042/bj1820055.Search in Google Scholar PubMed PubMed Central

30. Zerwekh, JE, Harvey, JA, Pak, CY. Administration of pharmacological amounts of 25(s),26-dihydroxyvitamin D3 reduces serum 1,25-dihydroxyvitamin D3 levels in rats. Endocrinology 1987;121:1671–7. https://doi.org/10.1210/endo-121-5-1671.Search in Google Scholar PubMed

Received: 2022-02-17
Accepted: 2022-04-29
Published Online: 2022-05-09
Published in Print: 2022-07-26

© 2022 Walter de Gruyter GmbH, Berlin/Boston

Scroll Up Arrow