Epimeric vitamin D and cardiovascular structure and function in advanced CKD and after kidney transplantation

Abstract

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.