Epimeric Vitamin D is Not Associated With Arterial Stiffness or Cardiovascular Outcomes in Patients With Advanced CKD.
10 affiliations
- 1Division of Nephrology & Hypertension, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN.
- 2Department of Geriatric and Gerontology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
- 3Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
- 4Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, IN.
- 5Department of Biostatistics and Health Data Science and Richard M. Fairbanks School of Public Health, Indiana University School of Medicine, Indianapolis, IN.
- 6Renal Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
- 7Department of Biomedical and Molecular Sciences and Medicine, Queen's University, Kingston, Ontario, Canada.
- 8Department of Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
- 9Department of Nephrology and Department of Acute Medicine, North Cumbria University Hospital NHS Trust, Carlisle, UK.
- 10Cambridge Clinical Trials Unit and School of Clinical Medicine, University of Cambridge, Cambridge, UK.
Abstract
Rationale & objective
3-epi-25(OH)D₃, an epimeric form of 25(OH)D₃ generated by C-3 epimerization, declines with advancing chronic kidney disease (CKD), yet its role in vascular health and related outcomes remains largely unknown. We aimed to determine whether circulating 3-epi-25(OH)D₃ levels are associated with arterial stiffness and longitudinal cardiovascular (CV) outcomes in advanced CKD (stages 5 and 5D).Study design
A prospective observational study.Setting & participants
A total of 270 patients with advanced CKD using the Cambridge Coventry Vascular cohort.Exposure s or predictor s
Baseline 3-epi-25(OH)D₃ measured by liquid chromatography-tandem mass spectrometry.Outcome s
Arterial stiffness was assessed by carotid-femoral pulse wave velocity (PWV) and augmentation index (AIx75). Longitudinal outcomes included a composite of major CV events and all-cause mortality.Analytical approach
Baseline 3-epi-25(OH)D₃ was categorized into quartiles. Associations were assessed using multivariable regression adjusted for age, race, and dialysis status. Kaplan-Meier and Cox models assessed longitudinal outcomes.Results
Among 270 participants, quartiles were Q1 < 0.30 ng/mL (n = 64), Q2: 0.30-0.456 ng/mL (n = 71), Q3: 0.457-0.729 ng/mL (n = 68), and Q4 ≥ 0.73 ng/mL (n = 67). Strata were similar in age (44.9 years), sex, and BMI (all P > 0.05). Race differed by quartile (P < 0.001); 87.4% were White. 24.8% were pre-dialytic, 61.1% treated with hemodialysis, and 14.1% treated with peritoneal dialysis. Arterial stiffness was similar across quartiles (AIx75 ∼20-21%, P = 0.99; PWV: 7.8-8.0 m/s, P = 0.94). 3-epi-25(OH)D₃ showed no association with AIx75 or PWV before or after adjustment using multiple regression modeling. Over 9.3 years, 115 composite events occurred (97 CV events, 18 deaths). Kaplan-Meier analysis did not discriminate risk across 3-epi-25(OH)D₃ quartiles for the composite outcome (log-rank P = 0.23), and adjusted Cox models showed no association.Limitations
Observational design with possible residual confounding.Conclusion
In advanced CKD, 3-epi-25(OH)D₃ showed no independent association with arterial stiffness or CV events and mortality. Further studies are needed to determine the role of epimeric vitamin D in patients with CKD.
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BibTeX
@article{campos2026epimeric,
title = {{Epimeric Vitamin D is Not Associated With Arterial Stiffness or Cardiovascular Outcomes in Patients With Advanced CKD.}},
author = {Monique O Campos and Chien-Yao Sun and Heather N Burney and Yang Li and Gayatri Narayanan and Olivia Carlton and Tzong-Shi Lu and Glenville Jones and Martin Kaufmann and Stephen M S Ting and Daniel Zehnder and Thomas Hiemstra and Kenneth Lim},
journal = {Kidney medicine},
year = {2026},
month = sep,
doi = {10.1016/j.xkme.2026.101519},
url = {https://europepmc.org/article/MED/42894851},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Epimeric Vitamin D is Not Associated With Arterial Stiffness or Cardiovascular Outcomes in Patients With Advanced CKD.
AU - Monique O Campos
AU - Chien-Yao Sun
AU - Heather N Burney
AU - Yang Li
AU - Gayatri Narayanan
AU - Olivia Carlton
AU - Tzong-Shi Lu
AU - Glenville Jones
AU - Martin Kaufmann
AU - Stephen M S Ting
AU - Daniel Zehnder
AU - Thomas Hiemstra
AU - Kenneth Lim
PY - 2026
DA - 2026/09/09
JO - Kidney medicine
DO - 10.1016/j.xkme.2026.101519
UR - https://europepmc.org/article/MED/42894851
AB - Rationale & objective 3-epi-25(OH)D₃, an epimeric form of 25(OH)D₃ generated by C-3 epimerization, declines with advancing chronic kidney disease (CKD), yet its role in vascular health and related outcomes remains largely unknown. We aimed to determine whether circulating 3-epi-25(OH)D₃ levels are associated with arterial stiffness and longitudinal cardiovascular (CV) outcomes in advanced CKD (stages 5 and 5D).Study design A prospective observational study.Setting & participants A total of 270 patients with advanced CKD using the Cambridge Coventry Vascular cohort.Exposure s or predictor s Baseline 3-epi-25(OH)D₃ measured by liquid chromatography-tandem mass spectrometry.Outcome s Arterial stiffness was assessed by carotid-femoral pulse wave velocity (PWV) and augmentation index (AIx75). Longitudinal outcomes included a composite of major CV events and all-cause mortality.Analytical approach Baseline 3-epi-25(OH)D₃ was categorized into quartiles. Associations were assessed using multivariable regression adjusted for age, race, and dialysis status. Kaplan-Meier and Cox models assessed longitudinal outcomes.Results Among 270 participants, quartiles were Q1 < 0.30 ng/mL (n = 64), Q2: 0.30-0.456 ng/mL (n = 71), Q3: 0.457-0.729 ng/mL (n = 68), and Q4 ≥ 0.73 ng/mL (n = 67). Strata were similar in age (44.9 years), sex, and BMI (all P > 0.05). Race differed by quartile (P < 0.001); 87.4% were White. 24.8% were pre-dialytic, 61.1% treated with hemodialysis, and 14.1% treated with peritoneal dialysis. Arterial stiffness was similar across quartiles (AIx75 ∼20-21%, P = 0.99; PWV: 7.8-8.0 m/s, P = 0.94). 3-epi-25(OH)D₃ showed no association with AIx75 or PWV before or after adjustment using multiple regression modeling. Over 9.3 years, 115 composite events occurred (97 CV events, 18 deaths). Kaplan-Meier analysis did not discriminate risk across 3-epi-25(OH)D₃ quartiles for the composite outcome (log-rank P = 0.23), and adjusted Cox models showed no association.Limitations Observational design with possible residual confounding.Conclusion In advanced CKD, 3-epi-25(OH)D₃ showed no independent association with arterial stiffness or CV events and mortality. Further studies are needed to determine the role of epimeric vitamin D in patients with CKD.
SN - 2590-0595
ER -