Work

Epimeric Vitamin D is Not Associated With Arterial Stiffness or Cardiovascular Outcomes in Patients With Advanced CKD

Year: 2026

Type: article

Abstract: Rationale & Objective 3-epi-25(OH)D 3 , an epimeric form of 25(OH)D 3 generated by C-3 epimerization, declines with advancing CKD, yet its role in vascular health and related outcomes remains largely unknown. We aimed to determine whether circulating 3-epi-25(OH)D 3 levels are associated with arterial stiffness and longitudinal cardiovascular (CV) outcomes in advanced CKD (stages 5 and 5D). Study Design Prospective observational study. Setting & Participants 270 patients with advanced CKD using the Cambridge Coventry Vascular Cohort. Exposure (s) or Predictor (s) Baseline 3-epi-25(OH)D 3 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 3-epi-25(OH)D 3 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% on hemodialysis, and 14.1% on 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)D 3 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)D 3 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)D 3 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 CKD patients.

Source: Kidney Medicine

DOI: 10.1016/j.xkme.2026.101519