Effects of Vitamin D2 Supplementation on Vitamin D3 Metabolites in Patients with and without Chronic Kidney Disease
Presentation Number: SAT 326
Date of Presentation: April 2nd, 2016
Zona Batacchi*1, Cassianne Robinson-Cohen1, Andrew N Hoofnagle1, Tamara Isakova2, Bryan Kestenbaum3, Kevin J Martin4, Kelsey Smith5, Myles Wolf6 and Ian de Boer1
1University of Washington, Seattle, WA, 2Northwestern University Feinberg School of Medicine, Evanston, IL, 3University of Washington, 4Saint Louis University, Saint Louis, MO, 5University of Pennsylvania, 6Northwestern University, Chicago, IL
Background and aims:
Vitamin D deficiency, marked by low circulating concentrations of 25-hydroxyvitamin D (25(OH)D), is common in the general population. In patients with chronic kidney disease (CKD), impaired CYP27B1-mediated activation of 25(OH)D to 1,25(OH)2D exacerbates vitamin D deficiency. Vitamin D supplements are commonly prescribed to deficient patients, but the effects of supplementation on CYP24A1-mediated catabolism of 25(OH)D to 24,25(OH)2D and how these effects are modified by CKD are poorly understood. The vitamin D metabolic ratios (VDMR) offer functional estimates of CYP24A1 and CYP27B1 activity: 1,25(OH)2D3:25(OH)D3 estimates CYP27B1 activity, and 24,25(OH)2D3:25(OH)D3 estimates CYP24A1 activity.
Study Design and Methods:
In a prospective, multi-center trial of individuals with total 25(OH)D < 30ng/mL, we tested the effects of vitamin D2 supplementation on vitamin D3 metabolism among 23 individuals with CKD (eGFR<60 mL/min/1.73m2) and 46 without CKD (eGFR≥60 mL/min/1.73m2). Both groups received 50,000 IU of vitamin D2(ergocalciferol) orally, twice weekly for 5 weeks. We measured plasma mineral metabolism biomarkers before and after treatment, and used mass spectrometry to measure vitamin D metabolites.
In the control group, there were significant increases in plasma 25(OH)D2 (1.1 ± 1.2 to 29.9 ± 1.2 ng/mL) and total 25(OH)D (19.3 ± 1.5 to 39.2 ± 1.5 ng/mL) with treatment. Plasma 1,25(OH)2D2 also increased (2.6 ± 1.4 to 32.3 ± 1.4 pg/mL), whereas 1,25(OH)2D3 decreased (46.7 ± 1.8 to 14.6 ± 1.9 pg/mL), resulting in no change in total 1,25(OH)2D. The 1,25(OH)2D3:25(OH)D3 ratio decreased (3.1 ± 0.18 to 1.70 ± 0.18) while the 24,25(OH)2D3:25(OH) D3 ratio increased (0.117 ± 0.008 to 0.195 ± 0.008), consistent with decreased CYP27B1 and increased CYP24A1 activity.
In the CKD group, baseline concentrations and changes in 25(OH)D2 (2.0 ± 1.4 to 30.6 ± 1.4 ng/mL) and total 25(OH)D (18.9 ± 1.7 to 40.2 ± 1.8 ng/mL) were similar to the control group (treatment-group interaction, p>0.05). However, comparing the CKD to control groups, baseline levels were lower and changes were smaller in magnitude for 1,25(OH)2D2 (2.1 ± 1.6 to 23.6 ± 1.6 pg/mL, interaction p=0.006), 1,25(OH)2D3:25(OH)D3 ratio (1.84 ± 0.2 to 1.13 ± 0.2, interaction p= 0.013), and 24,25(OH)2D3:25(OH)D3 ratio ( 0.072 ± 0.009 to 0.109 ± 0.009, interaction p<0.001). No significant changes in parathyroid (PTH) or fibroblast growth factor (FGF23) concentration were observed in either group.
Vitamin D2 supplementation decreases conversion of 25(OH)D3 to 1,25(OH)2D3 and induces vitamin D3 catabolism, as evidenced by changes in plasma vitamin D3 metabolites and VDMRs. These effects are blunted in CKD and occur independently of significant changes in circulating PTH or FGF23 levels.
Disclosure: TI: Advisory Group Member, Ultragenyx, Consultant, Daiichi Sankyo, Consultant, GuidepointGlobal. KJM: Consultant, Amgen, Consultant, Diasorin, Consultant, OPKO. ID: Clinical Researcher, Abbvie. Nothing to Disclose: ZB, CR, ANH, BK, KS, MW