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Abstract: PO0383

CKD and Vitamin D Status Alter Vitamin D Metabolism

Session Information

Category: Bone and Mineral Metabolism

  • 402 Bone and Mineral Metabolism: Clinical

Authors

  • Thompson, Lauren E., University of Colorado Denver Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado, United States
  • Tuey, Stacey M., University of Colorado Denver Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado, United States
  • Prebehalla, Linda, University of Pittsburgh Department of Pharmacy and Therapeutics, Pittsburgh, Pennsylvania, United States
  • West, Raymond E., University of Pittsburgh Department of Pharmacy and Therapeutics, Pittsburgh, Pennsylvania, United States
  • Chonchol, Michel, University of Colorado Denver Division of Renal Diseases and Hypertension, Aurora, Colorado, United States
  • Shah, Nirav A., University of Pittsburgh Renal-Electrolyte Division, Pittsburgh, Pennsylvania, United States
  • Nolin, Thomas D., University of Pittsburgh Department of Pharmacy and Therapeutics, Pittsburgh, Pennsylvania, United States
  • Joy, Melanie S., University of Colorado Denver Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado, United States
Background

Up to 90% of people with chronic kidney disease (CKD) are vitamin D (VitD) deficient. VitD is subsequently prescribed and has documented health benefits, including nephro-, cardio-, and immune- protection. This paired study sought to evaluate and compare VitD metabolism in CKD patients and healthy controls (HC) under both VitD deficiency and repletion.

Methods

VitD deficient (25[OH]D3 <30 ng/mL) CKD patients (n=30) and HC (n=11) were recruited (Phase 1). Participants were administered 5,000 I.U. oral D3 daily for 12 weeks. At week 12 (Phase 2), participants received their final dose of D3 after 25[OH]D3 was confirmed to be replete (≥30 ng/mL). Blood was collected at serial time points for up to 336 h at each phase for determination of D3, 25[OH]D3, 1,25[OH]2D3, and 24,25[OH]2D3. Metabolism ratios (MR) were defined by the area under the plasma concentration-time curve (AUC) of pre-cursor to a subsequent metabolite. Analyses for differences were assessed by ANOVA with a Tukey-Kramer post-hoc test.

Results

Metabolism was differentially altered by VitD status and CKD. Significant differences in assessment of MR were determined in both an immediate precursor to the next metabolite in the sequence and by the parent compound (D3) to the final metabolite in the metabolism sequence. The metabolism of D3 to 25[OH]D3 and of 25[OH]D3 to 1,25[OH]2D3 were significantly decreased by CKD severity, with differences more pronounced after VitD repletion.

Conclusion

CKD severity decreased metabolism by the cytochrome 2R1 and 27B1 sequential pathways resulting in reductions in the D3 to 25[OH]D3 and 25[OH]D3 to active VitD (1,25[OH]2D3), respectively. Daily dosing leading to repletion appears to decrease the overall conversion of cholecalciferol to its metabolites in HC and CKD patients, possibly due to saturation of metabolism pathways. Future research will evaluate the influence of daily vs. intermittent dosing on metabolism efficiency.

Data reported as mean ± SD (n); p-values calculated using one-way ANOVA.
a: p<0.05 vs. phase 1, HC.
b: p<0.05 vs. phase 1, CKD 1-3.
c: p<0.05 vs. phase 2, HC.

Funding

  • Other NIH Support