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 citas
Cómo se estudió
- Diseño
- Ensayo clínico controlado (clasificado por nuestro filtro de IA)
- Estudiado en
- Personas
- Resultado principal
- Marcadores de salud y funcionamiento
Quién lo pagó
- Financiación
- Posiblemente financiado por la industria
- Organización sin fines de lucro
- Karst Waters Institute
- Empresa
- Northwest Kidney Centers
- Gobierno
- National Institutes of Health
- Gobierno
- National Heart, Lung, and Blood Institute
- Gobierno
- National Institute of General Medical Sciences
- Gobierno
- National Institute of Diabetes and Digestive and Kidney Diseases
- Gobierno
- National Center for Advancing Translational Sciences
- Gobierno
- NIDDK NIH HHS
- Gobierno
- NHLBI NIH HHS
- Gobierno
- NCATS NIH HHS
- Gobierno
- NIGMS NIH HHS
- Subvenciones
- 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)
Según 11 financiadores declarados.
Publicación
- Publicado
- 2020-10-28 · J Am Soc Nephrol · vol. 32 · número 1 · págs. 188–198
- Editorial
- American Society of Nephrology
- Citado
- 26 citas · más que el 90% de estudios similares · 2.4× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 65 trabajos
- Acceso
- Acceso abierto (copia en repositorio)
- Áreas de investigación
- Vitamin D Research Studies · Parathyroid Disorders and Treatments · Thyroid Disorders and Treatments
- Palabras clave
- 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 autores
- Simon Hsu🇺🇸University of Washington
- Leila R. Zelnick🇺🇸University of Washington
- Yvonne S. Lin🇺🇸University of Washington
- Cora M. Best🇺🇸University of Washington
- Bryan R. Kestenbaum🇺🇸University of Washington
- Kenneth E. Thummel🇺🇸University of Washington
- Lynn Massman Rose🇺🇸University of Washington
- Andrew N. Hoofnagle🇺🇸University of Washington
- Ian H. de Boer🇺🇸University of Washington; VA Puget Sound Health Care System
Resumen
El texto original del estudio, en el idioma en que se publicó.
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.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial.
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