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

Abstract

Background 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. 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 2), 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. Results 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 (P=0.02). After adjustment for age, sex, race, and estimated blood volume, lower eGFR was associated with reduced 25(OH)D clearance (β=−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 (P for interaction=0.05). Clearance of 25(OH)D before versus after vitamin-D₃ supplementation did not differ. Conclusions Using direct pharmacokinetic measurements, we show that 25(OH)D clearance is reduced in CKD and may differ by race. Clinical Trial registry name and registration number Clearance of 25-hydroxyvitamin D in Chronic Kidney Disease (CLEAR), NCT02937350; Clearance of 25-hydroxyvitamin D3 During Vitamin D3 Supplementation (CLEAR-PLUS), NCT03576716