Serum Vitamin D C3-epimer Levels Are Associated With Cardiorespiratory Fitness In Patients With Advanced Ckd

PURPOSE: Epimeric vitamin D levels decline in progressive chronic kidney disease (CKD). However, whether circulating levels of 3-epi-25-hydroxyvitamin D3 [3-epi-25(OH)D3] are associated with cardiorespiratory fitness (CRF) in patients with advanced CKD is unknown. The purpose of this study was therefore to examine the relationship between circulating vitamin D metabolites and cardiovascular functional and structural indices. METHODS: We studied two groups of patients with advanced CKD: patients who underwent kidney transplant (KTR group, n = 76) and patients on the transplant waitlist who did not undergo kidney transplant (NTWC group, n = 89). All patients underwent cardiopulmonary exercise testing (CPET) and echocardiography at baseline (BL), 2 mo, and 12 mo. RESULTS: The study cohort was stratified into quartiles of baseline 3-epi-25(OH)D3 serum levels (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). After adjusting for age, sex, body mass index, mean arterial pressure, dyslipidemia, and intact parathyroid hormone levels, patients with the lowest 3-epi-25(OH)D3 levels (Q1) exhibited a significantly impaired VO2Peak (median [IQR] = 18.4 [16.2-20.8] mL·min-1·kg-1) compared to patients in Q4 (20.8 [18.6-23.2] mL·min-1·kg-1; p = 0.009). Additionally, ventilatory threshold (VT) was lower in patients in Q1 (p = 0.015) and Q2 (p = 0.011) compared to Q4. No significant differences were observed between quartiles in LVMI (p = 0.72). The KTR group had lower levels of 3-epi-25(OH)D3 compared to NTWC at BL (p = 0.004), but these levels increased following kidney transplantation and were significantly higher than NTWC at 12 mo (p < 0.001). We also found that longitudinal changes in 3-epi-25(OH)D3 levels were significantly associated with changes in VO2Peak (KTR: ß [SE] =2.53 [0.56], p < 0.001; NTWC: 2.73 [0.70], p < 0.001) and VT (KTR: ß [SE] =1.58 [0.31], p < 0.001; NTWC: 1.37 [0.35], p < 0.001) in both groups after adjusting for baseline covariates. CONCLUSION: Decreases in vitamin D C3-epimer levels may play a role in the poor CRF seen in patients with advanced CKD. Further research is warranted to elucidate the mechanisms by which 3-epi-25(OH)D3 may regulate exercise capacity.