Abstract
BackgroundCardiovascular events are frequent and vascular endothelial function is abnormal in patients with chronic kidney disease (CKD). We demonstrated endothelial dysfunction with vitamin D deficiency in CKD patients; however the impact of cholecalciferol supplementation on vascular stiffness and vasomotor function, endothelial and bone biomarkers in CKD patients with low 25-hydroxy vitamin D [25(OH)D] is unknown, which this study investigated.MethodsWe assessed non-diabetic patients with CKD stage 3/4, age 17–80 years and serum 25(OH)D <75 nmol/L. Brachial artery Flow Mediated Dilation (FMD), Pulse Wave Velocity (PWV), Augmentation Index (AI) and circulating blood biomarkers were evaluated at baseline and at 16 weeks. Oral 300,000 units cholecalciferol was administered at baseline and 8-weeks.ResultsClinical characteristics of 26 patients were: age 50±14 (mean±1SD) years, eGFR 41±11 ml/min/1.73 m2, males 73%, dyslipidaemia 36%, smokers 23% and hypertensives 87%.At 16-week serum 25(OH)D and calcium increased (43±16 to 84±29 nmol/L, p<0.001 and 2.37±0.09 to 2.42±0.09 mmol/L; p = 0.004, respectively) and parathyroid hormone decreased (10.8±8.6 to 7.4±4.4; p = 0.001). FMD improved from 3.1±3.3% to 6.1±3.7%, p = 0.001.Endothelial biomarker concentrations decreased: E-Selectin from 5666±2123 to 5256±2058 pg/mL; p = 0.032, ICAM-1, 3.45±0.01 to 3.10±1.04 ng/mL; p = 0.038 and VCAM-1, 54±33 to 42±33 ng/mL; p = 0.006. eGFR, BP, PWV, AI, hsCRP, von Willebrand factor and Fibroblast Growth Factor-23, remained unchanged.ConclusionThis study demonstrates for the first time improvement of endothelial vasomotor and secretory functions with vitamin D in CKD patients without significant adverse effects on arterial stiffness, serum calcium or FGF-23.Trial RegistrationClinicalTrials.gov NCT02005718
Highlights
Patients with chronic kidney disease (CKD) have up to 3.5 fold increased risk of cardiovascular (CV) events and cardiovascular disease (CVD) is the most common cause of mortality and morbidity [1]
Brachial artery Flow mediated dilatation (FMD) is a surrogate for CV disease, as it correlates with coronary atherosclerosis [7]
We have previously reported an association between reduced vitamin D levels and impaired brachial artery FMD in CKD patients [14]
Summary
Patients with chronic kidney disease (CKD) have up to 3.5 fold increased risk of cardiovascular (CV) events and cardiovascular disease (CVD) is the most common cause of mortality and morbidity [1]. Evidence from general population surveys has shown that CKD is an independent risk factor for CVD [2]. Endothelial dysfunction is the final common pathway of vascular injury mediated by both traditional and non-traditional risk factors of CVD [5]. Flow mediated dilatation (FMD) of the brachial artery in response to distal ischaemia, has been validated for assessment of endothelial function in-vivo [6]. FMD has been shown to predict future CV events and mortality in the general population and in patients with mild to moderate CKD [8,9]. We demonstrated endothelial dysfunction with vitamin D deficiency in CKD patients; the impact of cholecalciferol supplementation on vascular stiffness and vasomotor function, endothelial and bone biomarkers in CKD patients with low 25-hydroxy vitamin D [25(OH)D] is unknown, which this study investigated
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