Effect of regulated vitamin D increase on vascular markers in patients with chronic kidney disease: A systematic review and meta-analysis of randomized controlled trials

Aim The effect of increased vitamin D levels on vascular function in patients with chronic kidney disease(CKD) is controversial. This meta-analysis aimed to assess the effect of regulated vitamin D increase on vascular markers in patients with CKD. Data synthesis We searched PubMed, Web of Science, Embase and ClinicalTrials.gov from database inception up until July 21, 2023. We included randomized controlled trials assessing the effects of using vitamin D and its analogues on vascular function in patients with CKD. Fixed-effects and random-effects model analyses were performed using weighted mean difference effects for each trial by heterogeneity (I2) assessment. Primary outcomes encompassed blood flow-mediated dilation (FMD)、pulse wave velocity (PWV) and augmentation index (AIx). Findings From 1964 records we selected 12 trials, 5 (n=331) on FMD, 8 (n=626) on PWV and 4 (n=393) on AIx. Vitamin D and VDRA supplementation failed to significantly improve FMD (WMD 1.68%; 95% CI -0.18 to 3.53; P=0.08; I 2 =88%)、PWV (WMD -0.41m/s; 95%CI -0.95 to 0.13; P=0.14; I 2 =57%)and AIx (WMD -0.53%; 95%CI -1.69 to 0.63; P=0.37; I 2 =0%). Subgroup analysis revealed that 2 ug paricalcitol significantly improved FMD (WMD 2.09%; 95%CI 1.28 to 2.90; P<0.00001); I 2 =0%), as did cholecalciferol (WMD 5.49%; 95% CI 4.35 to 6.63; P<0.00001). Conclusion Supplementation vitamin D and VDRA are associated with improved vascular function as measured by FMD, but not arterial stiffness as measured by PWV and AIx, tentatively suggesting that regulating the increase of vitamin D could not potentially reduce the incidence of cardiovascular disease.