Vitamin D bioavailability and catabolism in pediatric chronic kidney disease |
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Authors: | Michelle R. Denburg Heidi J. Kalkwarf Ian H. de Boer Martin Hewison Justine Shults Babette S. Zemel David Stokes Debbie Foerster Benjamin Laskin Anthony Ramirez Mary B. Leonard |
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Affiliation: | 1. The Children’s Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA 7. Division of Nephrology, The Children’s Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA, 19104, USA 2. Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA 3. Kidney Research Institute, University of Washington, Seattle, WA, USA 4. UCLA Orthopaedic Hospital, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA 6. Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA 5. The Children’s Hospital of Philadelphia, Philadelphia, PA, USA
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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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