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Abstract: PO0339

Differences in 25-Hydroxyvitamin D Clearance by eGFR and Race: A Pharmacokinetic Study

Session Information

Category: Bone and Mineral Metabolism

  • 402 Bone and Mineral Metabolism: Clinical

Authors

  • Hsu, Simon, University of Washington, Seattle, Washington, United States
  • Zelnick, Leila R., University of Washington, Seattle, Washington, United States
  • Lin, Yvonne S., University of Washington, Seattle, Washington, United States
  • Best, Cora M., University of Washington, Seattle, Washington, United States
  • Kestenbaum, Bryan R., University of Washington, Seattle, Washington, United States
  • Rose, Lynn M., University of Washington, Seattle, Washington, United States
  • Hoofnagle, Andrew N., University of Washington, Seattle, Washington, United States
  • de Boer, Ian H., University of Washington, Seattle, Washington, United States
Background

25-hydroxyvitamin D (25(OH)D) clearance is an essential yet often overlooked determinant of circulating 25(OH)D concentration, the prevailing marker of vitamin D status. Observational studies associate markers of low 25(OH)D clearance with poor clinical outcomes and suggest differences in 25(OH)D clearance by kidney function and race, but these potential variations have not been tested using gold-standard methods.

Methods

We administered intravenous deuterated 25(OH)D3 (d-25(OH)D3) in a pharmacokinetic study of 87 adults with a wide range of kidney function, including normal estimated glomerular filtration rate (eGFR ≥ 60 ml/min/1.73m2, n=43), non-dialysis chronic kidney disease (CKD; eGFR < 60 ml/min/1.73m2, n=24), and kidney failure treated with hemodialysis (n=20). We measured d-25(OH)D3 and deuterated 24,25-dihydroxyvitamin D3 concentrations 5 minutes, 4 hours, and 1, 4, 7, 14, 21, 28, 42 and 56 days post-administration. We calculated 25(OH)D clearance using non-compartmental analysis of d-25(OH)D3 concentrations over time. We re-measured 25(OH)D clearance in a subset of participants after 12-16 weeks of 2000 IU/day of oral vitamin D3 (n=18).

Results

The mean age of the study cohort was 64 ± 11 years; 41% were female and 30% were black. Mean 25(OH)D clearances were 360 ± 108, 313 ± 86 and 263 ± 163 mL/day in participants with normal eGFR, CKD and kidney failure respectively (p = 0.02). After adjustment, lower eGFR was associated with reduced 25(OH)D clearance (-17 mL/day per 10 ml/min/1.73m2 decrement, 95% CI: -21, -12). Black race was associated with higher 25(OH)D clearance in participants with normal eGFR (71 mL/day, 95% CI: 16, 125), but not in those with CKD or kidney failure (p-for-interaction = 0.052). 25(OH)D clearance did not differ after compared with before vitamin D3 supplementation, although lower 25(OH)D clearance was correlated with a larger increase in serum total 25(OH)D concentration following supplementation (r = -0.41).

Conclusion

Through direct pharmacokinetic measurements, these findings confirm impaired 25(OH)D clearance as a feature of disordered mineral metabolism in CKD, and may help understand racial differences in vitamin D metabolism. Surrogate measures of 25(OH)D clearance may allow clinicians to more accurately anticipate individual response to vitamin D supplementation.

Funding

  • NIDDK Support