title: Impact of vitamin D supplementation on arterial vasomotion, stiffness and endothelial biomarkers in chronic kidney disease patients.
abstract: BACKGROUND
  Cardiovascular 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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  Clinical 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.
  
  
  CONCLUSIONS
  This 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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT02005718.
authors.affiliation: Renal and Transplantation Unit, St George's Healthcare NHS Trust, London, United Kingdom; Cardiovascular Research Centre, St George's, University of London, London, United Kingdom.
authors.forename: Nihil
authors.initials: N
authors.lastname: Chitalia
authors.affiliation: Cardiovascular Research Centre, St George's, University of London, London, United Kingdom.
authors.forename: Tuan
authors.initials: T
authors.lastname: Ismail
authors.affiliation: Chemical Pathology, St George's Healthcare NHS Trust, London, United Kingdom.
authors.forename: Laura
authors.initials: L
authors.lastname: Tooth
authors.affiliation: Chemical Pathology, St George's Healthcare NHS Trust, London, United Kingdom.
authors.forename: Frances
authors.initials: F
authors.lastname: Boa
authors.affiliation: Renal and Clinical Chemistry Departments, Guy's and St Thomas, NHS Foundation Trust, London, United Kingdom.
authors.forename: Geeta
authors.initials: G
authors.lastname: Hampson
authors.affiliation: Renal and Clinical Chemistry Departments, Guy's and St Thomas, NHS Foundation Trust, London, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Goldsmith
authors.affiliation: Cardiovascular Research Centre, St George's, University of London, London, United Kingdom.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Kaski
authors.affiliation: Renal and Transplantation Unit, St George's Healthcare NHS Trust, London, United Kingdom; Cardiovascular Research Centre, St George's, University of London, London, United Kingdom.
authors.forename: Debasish
authors.initials: D
authors.lastname: Banerjee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002118:Calcium / Q000097:blood; D019587:Dietary Supplements; D019040:E-Selectin / Q000097:blood; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D063177:Pulse Wave Analysis; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications / Q000178:diet therapy* / Q000503:physiopathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D059289:Vascular Stiffness / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014807:Vitamin D / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood / Q000150:complications / Q000178:diet therapy* / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D019040:E-Selectin; C000717427:FGF23 protein, human; D010281:Parathyroid Hormone; C546936:SELE protein, human; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D014807:Vitamin D; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; C104450:25-hydroxyvitamin D; D002118:Calcium