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

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).

A prospective observational study.

A total of 270 patients with advanced CKD using the Cambridge Coventry Vascular cohort.

Baseline 3-epi-25(OH)D₃ measured by liquid chromatography-tandem mass spectrometry.

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.

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.

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.

Observational design with possible residual confounding.

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.