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

Abstract

Conversion of 25-hydroxyvitamin D (25[OH]D) to the active form of vitamin D occurs primarily in the kidney. Observational studies suggest 25(OH)D clearance from the circulation differs by kidney function and race. However, these potential variations have not been tested using gold-standard methods. We administered intravenous, deuterated 25(OH)D₃ (d-25[OH]D₃) in a pharmacokinetic study of 87 adults, including 43 with normal eGFR (≥60 ml/min per 1.73 m²), 24 with nondialysis CKD (eGFR <60 ml/min per 1.73 m²), and 20 with ESKD treated with hemodialysis. We measured concentrations of d-25(OH)D₃ and deuterated 24,25-dihydroxyvitamin D₃ at 5 minutes and 4 hours after administration, and at 1, 4, 7, 14, 21, 28, 42, and 56 days postadministration. We calculated 25(OH)D clearance using noncompartmental analysis of d-25(OH)D₃ concentrations over time. We remeasured 25(OH)D clearance in a subset of 18 participants after extended oral vitamin-D₃ supplementation. The mean age of the study cohort was 64 years; 41% were female, and 30% were Black. Mean 25(OH)D clearances were 360 ml/d, 313 ml/d, and 263 ml/d in participants with normal eGFR, CKD, and kidney failure, respectively (<i>P</i>=0.02). After adjustment for age, sex, race, and estimated blood volume, lower eGFR was associated with reduced 25(OH)D clearance (<i>β</i>=-17 ml/d per 10 ml/min per 1.73 m² lower eGFR; 95% CI, -21 to -12). Black race was associated with higher 25(OH)D clearance in participants with normal eGFR, but not in those with CKD or kidney failure (<i>P</i> for interaction=0.05). Clearance of 25(OH)D before versus after vitamin-D₃ supplementation did not differ. Using direct pharmacokinetic measurements, we show that 25(OH)D clearance is reduced in CKD and may differ by race. Clearance of 25-hydroxyvitamin D in Chronic Kidney Disease (CLEAR), NCT02937350; Clearance of 25-hydroxyvitamin D3 During Vitamin D3 Supplementation (CLEAR-PLUS), NCT03576716.