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Vitamin D bioavailability and catabolism in pediatric chronic kidney disease

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Abstract

Background

Vitamin D-binding protein (DBP) and catabolism have not been examined in the clinical setting of childhood chronic kidney disease (CKD).

Methods

The concentrations of serum vitamin D {25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D], 24,25-dihydroxyvitamin D [24,25(OH)2D]}, DBP, intact parathyroid hormone (iPTH), and fibroblast growth factor-23 (FGF23) were measured in 148 participants with CKD stages 2–5D secondary to congenital anomalies of the kidney/urinary tract (CAKUT), glomerulonephritis (GN), or focal segmental glomerulosclerosis (FSGS). Free and bioavailable 25(OH)D concentrations were calculated using total 25(OH)D, albumin, and DBP concentrations.

Results

The concentrations of all vitamin D metabolites were lower with more advanced CKD (p < 0.001) and glomerular diagnoses (p ≤ 0.002). Among non-dialysis participants, DBP was lower in FSGS versus other diagnoses (FSGS–dialysis interaction p = 0.02). Winter season, older age, FSGS and GN, and higher FGF23 concentrations were independently associated with lower concentrations of free and bioavailable 25(OH)D. Black race was associated with lower total 25(OH)D and DBP, but not free or bioavailable 25(OH)D. 24,25(OH)2D was the vitamin D metabolite most strongly associated with iPTH. Lower 25(OH)D and higher iPTH concentrations, black race, and greater CKD severity were independently associated with lower levels of 24,25(OH)2D, while higher FGF23 concentrations and GN were associated with higher levels of 24,25(OH)2D.

Conclusions

Children with CKD exhibit altered catabolism and concentrations of DBP and free and bioavailable 25(OH)D, and there is an important impact of their underlying disease.

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Acknowledgments

We would like to thank the study participants and their families for their time and dedication. We greatly appreciate the assistance of the Clinical Research Coordinators and the staff at the Clinical Translational Research Centers (CTRC) at CCHMC and CHOP in the conduct of this study, particularly Samir Sayed, B.Sc. in the CTRC Translational Core Laboratory at CHOP for his work on the DBP assay.

Funding Sources

This project was supported by NIH grants R01-DK060030 (MBL), R01-HD040714 (MBL), K24-DK076808 (MBL), and by the National Center for Research Resources, Grants UL1RR024134 and M01-RR-08084, which are now at the National Center for Advancing Translational Sciences, Grants UL1TR000003 and UL1TR000077. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr. Laskin was supported by a Career Development Award in Comparative Effectiveness Research (KM1CA156715-01). Dr. Denburg was funded by a National Kidney Foundation/Amgen KDOQI Research Fellowship, The Nephcure Foundation–American Society of Nephrology Research Grant, and Grant K23-DK093556.

Disclosure statement

Dr. de Boer receives research funding from Abbott Laboratories. The remaining authors have nothing to disclose.

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Authors and Affiliations

  1. The Children’s Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Michelle R. Denburg, Justine Shults, Babette S. Zemel, Benjamin Laskin & Mary B. Leonard

  2. Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Heidi J. Kalkwarf

  3. Kidney Research Institute, University of Washington, Seattle, WA, USA

    Ian H. de Boer

  4. UCLA Orthopaedic Hospital, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Martin Hewison

  5. The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    David Stokes, Debbie Foerster & Anthony Ramirez

  6. Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Justine Shults & Mary B. Leonard

  7. Division of Nephrology, The Children’s Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA, 19104, USA

    Michelle R. Denburg

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  1. Michelle R. Denburg
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Correspondence to Michelle R. Denburg.

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Denburg, M.R., Kalkwarf, H.J., de Boer, I.H. et al. Vitamin D bioavailability and catabolism in pediatric chronic kidney disease. Pediatr Nephrol 28, 1843–1853 (2013). https://doi.org/10.1007/s00467-013-2493-9

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  • DOI: https://doi.org/10.1007/s00467-013-2493-9

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