Differences in 25-Hydroxyvitamin D Clearance by eGFR and Race: A Pharmacokinetic Study
Hsu S, Hsu S, Zelnick LR, Lin YS, Best CM, Kestenbaum B, Thummel KE, Rose LM, Hoofnagle AN, de Boer IH
Journal of the American Society of Nephrology : JASN · 19 citations
How it was studied
- Design
- Controlled clinical trial (classified by our AI screen)
- Studied in
- People
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Possibly industry funded
- Nonprofit
- Karst Waters Institute
- Company
- Northwest Kidney Centers
- Government
- National Institutes of Health
- Government
- National Heart, Lung, and Blood Institute
- Government
- National Institute of General Medical Sciences
- Government
- National Institute of Diabetes and Digestive and Kidney Diseases
- Government
- National Center for Advancing Translational Sciences
- Government
- NIDDK NIH HHS
- Government
- NHLBI NIH HHS
- Government
- NCATS NIH HHS
- Government
- NIGMS NIH HHS
- Grants
- National Institute of Diabetes and Digestive and Kidney Diseases (P30 DK 040561); National Institute of Diabetes and Digestive and Kidney Diseases (R01DK099199-S1); National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK099199); National Heart, Lung, and Blood Institute (T32HL007028); National Institute of General Medical Sciences (R01 GM 063666); National Institute of General Medical Sciences (R01GM63666); National Institute of Diabetes and Digestive and Kidney Diseases (P30‐DK‐017047); National Institute of Diabetes and Digestive and Kidney Diseases (P30 DK-035816); National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007467); National Center for Advancing Translational Sciences (UL 1 TR002319); National Institute of Diabetes and Digestive and Kidney Diseases (2T32DK007467-36)
Based on 11 listed funder(s).
Publication
- Published
- 2020-10-28 · J Am Soc Nephrol · vol. 32 · issue 1 · pp. 188–198
- Publisher
- American Society of Nephrology
- Cited
- 26 citations · more than 90% of similar papers · 2.4× the field average
- Impact
- Top 10% most cited in its field
- References
- 65 works
- Access
- Open access (repository copy)
- Research areas
- Vitamin D Research Studies · Parathyroid Disorders and Treatments · Thyroid Disorders and Treatments
- Keywords
- Renal function, Pharmacokinetics, Vitamin D and neurology, Medicine, Kidney disease, Internal medicine, Hemodialysis, Endocrinology, Urology
- MeSH
- humans, kidney failure, chronic, calcifediol, vitamin d, glomerular filtration rate, renal dialysis, adult, aged, middle aged, female, male, administration, intravenous, ethnicity, white people, black or african american, black people
9 authors
From US
- Simon HsuUniversity of Washington
- Leila R. ZelnickUniversity of Washington
- Yvonne S. LinUniversity of Washington
- Cora M. BestUniversity of Washington
- Bryan R. KestenbaumUniversity of Washington
- Kenneth E. ThummelUniversity of Washington
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.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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