Free 25-hydroxyvitamin-D Concentrations Are Lower in Children with Renal Transplant Compared with Chronic Kidney Disease

Overview

Journal Pediatr Nephrol

Specialties Nephrology
Pediatrics

Date 2020 Jan 24

PMID 31970483

Citations 3

Authors

Evgenia Preka

Mandy Wan

Karen L Price

David A Long

Helen Aitkenhead

Rukshana Shroff

Affiliations

Soon will be listed here.

Abstract

Background: Total serum 25-hydroxyvitamin D [25(OH)D] is considered the best marker of vitamin D status and used routinely in clinical practice. However, 25(OH)D is predominantly bound to vitamin D-binding protein (VDBP), and it has been reported that the free-25(OH)D and 25(OH)D loosely bound to albumin fraction correlates better with clinical outcomes.

Methods: We assessed total-25(OH)D, measured free-25(OH)D, and calculated free-25(OH)D and their relationship with VDBP and biomarkers of mineral metabolism in 61 children (22 CKD 2-3, 18 dialysis, and 21 post-transplant).

Results: Total-25(OH)D concentrations were comparable across the three groups (p = 0.09), but free- and bioavailable-25(OH)D (free- and albumin-25(OH)D) were significantly lower in the transplant group (both: p = 0.01). Compared to CKD and dialysis patients, the transplant group had significantly higher VDBP concentrations (p = 0.03). In all three groups, total-25(OH)D concentrations were positively associated with measured free-, calculated free-, and bioavailable-25(OH)D. Multivariable regression analysis showed that total-25(OH)D was the only predictor of measured free-25(OH)D concentrations in the dialysis group (β = 0.9; R = 90%). In the transplant group, measured free-25(OH)D concentrations were predicted by both total-25(OH)D and VDBP concentrations (β = 0.6, - 0.6, respectively; R = 80%). Correlations between parathyroid hormone with total-25(OH)D and measured and calculated free-25(OH)D were only observed in the transplant group (all: p < 0.001).

Conclusions: In transplanted patients, VDBP concentrations were significantly higher compared to CKD and dialysis patients, and consequently, free-25(OH)D concentrations were lower, despite a comparable total-25(OH)D concentration. We suggest that free-25(OH)D measures may be required in children with CKD, dialysis, and transplant, with further research required to understand its association with markers of mineral metabolism.

Citing Articles

Vitamin D levels in the pre- and post-COVID-19 pandemic periods in pediatric patients with chronic kidney disease.

Parra-Ortega I, Zurita-Cruz J, Ortiz-Flores I, Romero-Navarro B, Villasis-Keever M, Martinez B Front Nutr. 2023; 10:1268347.

PMID: 38024354 PMC: 10654788. DOI: 10.3389/fnut.2023.1268347.

Development of free 25-hydroxyvitamin D3 assay method using liquid chromatography-tandem mass spectrometry.

Ishimine N, Wu S, Ota R, Takahashi K, Takiwaki M, Sugano M Biosci Rep. 2022; 42(10).

PMID: 36107130 PMC: 9547169. DOI: 10.1042/BSR20221326.

Body mass index is associated with hyperparathyroidism in pediatric kidney transplant recipients.

Vanderstraeten K, De Pauw R, Knops N, Bouts A, Cransberg K, El Amouri A Pediatr Nephrol. 2020; 36(4):977-986.

PMID: 33034742 DOI: 10.1007/s00467-020-04796-w.

References

de Boer I, Katz R, Chonchol M, Ix J, Sarnak M, Shlipak M . Serum 25-hydroxyvitamin D and change in estimated glomerular filtration rate. Clin J Am Soc Nephrol. 2011; 6(9):2141-9. PMC: 3359004. DOI: 10.2215/CJN.02640311. View

Prytula A, Wells D, Mclean T, Balona F, Gullett A, Knott C . Urinary and dialysate losses of vitamin D-binding protein in children on chronic peritoneal dialysis. Pediatr Nephrol. 2011; 27(4):643-9. DOI: 10.1007/s00467-011-2045-0. View

Powe C, Ricciardi C, Berg A, Erdenesanaa D, Collerone G, Ankers E . Vitamin D-binding protein modifies the vitamin D-bone mineral density relationship. J Bone Miner Res. 2011; 26(7):1609-16. PMC: 3351032. DOI: 10.1002/jbmr.387. View

Metzger M, Houillier P, Gauci C, Haymann J, Flamant M, Thervet E . Relation between circulating levels of 25(OH) vitamin D and parathyroid hormone in chronic kidney disease: quest for a threshold. J Clin Endocrinol Metab. 2013; 98(7):2922-8. DOI: 10.1210/jc.2013-1294. View

Ali F, Arguelles L, Langman C, Price H . Vitamin D deficiency in children with chronic kidney disease: uncovering an epidemic. Pediatrics. 2009; 123(3):791-6. DOI: 10.1542/peds.2008-0634. View

Mantecon L, Alonso M, Moya V, Andres A, Avello N, Martinez-Morillo E . Marker of vitamin D status in healthy children: Free or total 25-hydroxyvitamin D?. PLoS One. 2018; 13(8):e0202237. PMC: 6107142. DOI: 10.1371/journal.pone.0202237. View

Querfeld U, Anarat A, Bayazit A, Bakkaloglu A, Bilginer Y, Caliskan S . The Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) study: objectives, design, and methodology. Clin J Am Soc Nephrol. 2010; 5(9):1642-8. PMC: 2974406. DOI: 10.2215/CJN.08791209. View

Melamed M, Astor B, Michos E, Hostetter T, Powe N, Muntner P . 25-hydroxyvitamin D levels, race, and the progression of kidney disease. J Am Soc Nephrol. 2009; 20(12):2631-9. PMC: 2794237. DOI: 10.1681/ASN.2009030283. View

Lee Y, Kim J, Roh Y, Choi H, Rhee Y, Kang D . The combination of vitamin D deficiency and mild to moderate chronic kidney disease is associated with low bone mineral density and deteriorated femoral microarchitecture: results from the KNHANES 2008-2011. J Clin Endocrinol Metab. 2014; 99(10):3879-88. DOI: 10.1210/jc.2013-3764. View

10.

Kalousova M, Dusilova-Sulkova S, Zakiyanov O, Kostirova M, Safranek R, Tesar V . Vitamin D Binding Protein Is Not Involved in Vitamin D Deficiency in Patients with Chronic Kidney Disease. Biomed Res Int. 2015; 2015:492365. PMC: 4434169. DOI: 10.1155/2015/492365. View

11.

Drechsler C, Verduijn M, Pilz S, Dekker F, Krediet R, Ritz E . Vitamin D status and clinical outcomes in incident dialysis patients: results from the NECOSAD study. Nephrol Dial Transplant. 2010; 26(3):1024-32. DOI: 10.1093/ndt/gfq606. View

12.

Hollis B, Bikle D . Vitamin D-binding protein and vitamin D in blacks and whites. N Engl J Med. 2014; 370(9):879-80. PMC: 4165606. DOI: 10.1056/NEJMc1315850. View

13.

Shieh A, Chun R, Ma C, Witzel S, Meyer B, Rafison B . Effects of High-Dose Vitamin D2 Versus D3 on Total and Free 25-Hydroxyvitamin D and Markers of Calcium Balance. J Clin Endocrinol Metab. 2016; 101(8):3070-8. PMC: 4971338. DOI: 10.1210/jc.2016-1871. View

14.

Vermeulen A, Verdonck L, Kaufman J . A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab. 1999; 84(10):3666-72. DOI: 10.1210/jcem.84.10.6079. View

15.

Meijers B, Bammens B, Verbeke K, Evenepoel P . A review of albumin binding in CKD. Am J Kidney Dis. 2008; 51(5):839-50. DOI: 10.1053/j.ajkd.2007.12.035. View

16.

Dhawan P, Christakos S . Novel regulation of 25-hydroxyvitamin D3 24-hydroxylase (24(OH)ase) transcription by glucocorticoids: cooperative effects of the glucocorticoid receptor, C/EBP beta, and the Vitamin D receptor in 24(OH)ase transcription. J Cell Biochem. 2010; 110(6):1314-23. DOI: 10.1002/jcb.22645. View

17.

Pilz S, Iodice S, Zittermann A, Grant W, Gandini S . Vitamin D status and mortality risk in CKD: a meta-analysis of prospective studies. Am J Kidney Dis. 2011; 58(3):374-82. DOI: 10.1053/j.ajkd.2011.03.020. View

18.

Lopez-Molina M, Santillan C, Murillo M, Valls A, Bosch L, Bel J . Measured free 25-hydroxyvitamin D in healthy children and relationship to total 25-hydroxyvitamin D, calculated free 25-hydroxyvitamin D and vitamin D binding protein. Clin Biochem. 2018; 61:23-27. DOI: 10.1016/j.clinbiochem.2018.08.007. View

19.

Johnsen M, Grimnes G, Figenschau Y, Torjesen P, Almas B, Jorde R . Serum free and bio-available 25-hydroxyvitamin D correlate better with bone density than serum total 25-hydroxyvitamin D. Scand J Clin Lab Invest. 2014; 74(3):177-83. DOI: 10.3109/00365513.2013.869701. View

20.

Ravani P, Malberti F, Tripepi G, Pecchini P, Cutrupi S, Pizzini P . Vitamin D levels and patient outcome in chronic kidney disease. Kidney Int. 2008; 75(1):88-95. DOI: 10.1038/ki.2008.501. View