Free 25-hydroxyvitamin-D concentrations are lower in children with renal transplant compared with chronic kidney disease

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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 ² = 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 ² = 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.

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Most cited references 48

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Measuring agreement in method comparison studies.

Elliot Bland, Michael Altman (1999)

Agreement between two methods of clinical measurement can be quantified using the differences between observations made using the two methods on the same subjects. The 95% limits of agreement, estimated by mean difference +/- 1.96 standard deviation of the differences, provide an interval within which 95% of differences between measurements by the two methods are expected to lie. We describe how graphical methods can be used to investigate the assumptions of the method and we also give confidence intervals. We extend the basic approach to data where there is a relationship between difference and magnitude, both with a simple logarithmic transformation approach and a new, more general, regression approach. We discuss the importance of the repeatability of each method separately and compare an estimate of this to the limits of agreement. We extend the limits of agreement approach to data with repeated measurements, proposing new estimates for equal numbers of replicates by each method on each subject, for unequal numbers of replicates, and for replicated data collected in pairs, where the underlying value of the quantity being measured is changing. Finally, we describe a nonparametric approach to comparing methods.

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Vitamin D levels and patient outcome in chronic kidney disease.

Patrizia Pizzini, Giovanni Tripepi, Pietro Ravani … (2008)

Vitamin D deficiency has been linked to cardiovascular disease and early mortality in patients on hemodialysis; however, it is not known if the same association exists at earlier stages of chronic kidney disease. To determine this we enrolled 168 consecutive new referrals to a chronic kidney disease clinic over a 2 year period and followed them for up to 6 years. All patients were clinically stable and had an estimated glomerular filtration rate (eGFR) at stage 2 or less and were without an imminent need for dialysis. Baseline 25-hydroxyvitamin D levels directly and significantly correlated with eGFR. After an average follow-up of 48 months, 48 patients started dialysis and 78 had died. In crude analyses, 25-hydroxyvitamin D predicted both time to death and end-stage renal disease. A dual-event Cox's model confirmed 25-hydroxyvitamin D as an independent predictor of study outcomes when adjusted for age, heart failure, smoking, C-reactive protein, albumin, phosphate, use of converting enzyme inhibitors or angiotensin receptor blockers, and eGFR. Our study shows that plasma 25-hydroxyvitamin D is an independent inverse predictor of disease progression and death in patients with stage 2-5 chronic kidney disease.

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Affinity differences for vitamin D metabolites associated with the genetic isoforms of the human serum carrier protein (DBP).

J. Arnaud, J. M. Constans (1993)

Human vitamin D binding protein (DBP) displays considerable polymorphism with 120 described alleles. Among these, three alleles are frequently observed, Gc 1F (pI 4.94-4.84), Gc 1S (pI 4.95-4.85) and Gc 2 (pI 5.1). Differences between these genetic forms of the protein in affinity for vitamin D metabolites have been detected by electrophoretic methods. The constant affinity (Ka) values determined in this study confirm these differences. The affinities of six rare variants were also examine. Those of the DBP genetic forms to the vitamin D derivatives 25-OH-D3 and 1,25-(OH)2-D3 seem to be related to the isoelectric point of the proteins: a high affinity corresponding to a low isoelectric point. The Gc 1A9 and 1A11 mutants were associated with higher affinity for the vitamin D derivatives and the Gc 1C1 and 1C21 mutants were deficient.

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Author and article information

Contributors

Mandy Wan:

ORCID: https://orcid.org/0000-0001-8802-0425

mandy.wan@kcl.ac.uk

Journal

Journal ID (nlm-ta): Pediatr Nephrol

Journal ID (iso-abbrev): Pediatr. Nephrol

Title: Pediatric Nephrology (Berlin, Germany)

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 0931-041X

ISSN (Electronic): 1432-198X

Publication date (Electronic): 22 January 2020

Publication date PMC-release: 22 January 2020

Publication date (Print): 2020

Volume: 35

Issue: 6

Pages: 1069-1079

Affiliations

[1 ]GRID grid.424537.3, ISNI 0000 0004 5902 9895, Renal Unit, , Great Ormond Street Hospital for Children NHS Foundation Trust, ; London, UK

[2 ]GRID grid.83440.3b, ISNI 0000000121901201, Developmental Biology and Cancer Programme, , UCL Great Ormond Street Institute of Child Health, ; London, UK

[3 ]GRID grid.13097.3c, ISNI 0000 0001 2322 6764, Institute of Pharmaceutical Science, King’s College London, ; London, UK

[4 ]GRID grid.420468.c, Department of Chemical Pathology, , Great Ormond Street Hospital NHS Foundation Trust, ; London, UK

Author information

Evgenia Preka https://orcid.org/0000-0001-7130-0439

Mandy Wan https://orcid.org/0000-0001-8802-0425

Karen L Price https://orcid.org/0000-0002-8113-1461

David A Long http://orcid.org/0000-0001-6580-3435

Helen Aitkenhead https://orcid.org/0000-0002-1787-9467

Rukshana Shroff https://orcid.org/0000-0001-8501-1072

Article

Publisher ID: 4472

DOI: 10.1007/s00467-020-04472-z

PMC ID: 7184055

PubMed ID: 31970483

SO-VID: 0d13d77e-6447-4683-b22c-e23846e1bf83

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 8 November 2019

Date revision received : 19 December 2019

Date accepted : 2 January 2020

Funding

Funded by: National Institute for Health Research

Award ID: ICA-CDRF-2016-02-057

Award ID: CDF-2016-09-038

Award Recipient : Mandy Wan Rukshana Shroff

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ScienceOpen disciplines: Nephrology

Keywords: 25-hydroxyvitamin d,chronic kidney disease,pediatric renal transplantation,children

Data availability:

ScienceOpen disciplines: Nephrology

Keywords: 25-hydroxyvitamin d, chronic kidney disease, pediatric renal transplantation, children

Free 25-hydroxyvitamin-D concentrations are lower in children with renal transplant compared with chronic kidney disease

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Karger: Nephrology

Most cited references 48

Measuring agreement in method comparison studies.

Vitamin D levels and patient outcome in chronic kidney disease.

Affinity differences for vitamin D metabolites associated with the genetic isoforms of the human serum carrier protein (DBP).

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