Background
25-hydroxyvitamin D can undergo C-3 epimerization to produce 3-epi-25(OH)D3. 3-epi-25(OH)D3 levels decline in chronic kidney disease (CKD), but its role in regulating the cardiovascular system is unknown. Herein, we examined the relationship between 3-epi-25(OH)D3 and cardiovascular functional and structural endpoints in patients with CKD.
Methods
We examined n = 165 patients with advanced CKD from the Cardiopulmonary Exercise Testing in Renal Failure (CAPER) study cohort, including those who underwent kidney transplant (KTR, n = 76) and waitlisted patients who did not (NTWC, n = 89). All patients underwent cardiopulmonary exercise testing and echocardiography at baseline, 2 months, and 12 months. Serum 3-epi-25(OH)D3 was analyzed by liquid chromatography-tandem mass spectrometry.
Results
Patients were stratified into quartiles of baseline 3-epi-25(OH)D3 (Q1: <0.4 ng·mL–1, n = 51; Q2: 0.4 ng·mL–1, n = 26; Q3: 0.5–0.7 ng·mL–1, n = 47; Q4: ≥0.8 ng·mL–1, n = 41). Patients in Q1 exhibited lower peak oxygen uptake (VO2Peak = 18.4 [16.2–20.8] mL·min–1·kg–1) compared to Q4 (20.8 [18.6–23.2] mL·min–1·kg–1; P = 0.009). Linear mixed regression model showed that 3-epi-25(OH)D3 levels increased in KTR (from 0.47 [0.30] ng·mL–1 to 0.90 [0.45] ng·mL–1) and declined in NTWC (from 0.61 [0.32] ng·mL–1 to 0.45 [0.29] ng·mL–1; P < 0.001). Serum 3-epi-25(OH)D3 was associated with VO2Peak longitudinally in both groups (KTR: ß [SE] =2.53 [0.56], P < 0.001; NTWC: 2.73 [0.70], P < 0.001), but was not with left ventricular mass or arterial stiffness. Non-epimeric 25(OH)D3, 24,25(OH)2D3, and 25(OH)D3:24,25(OH)2D3 ratio were not associated with any cardiovascular outcome (p's > 0.05).
Conclusions
Changes in 3-epi-25(OH)D3 levels may regulate cardiovascular functional capacity in patients with advanced CKD.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.