Impact of Vitamin D Supplementation on Arterial Vasomotion, Stiffness and Endothelial Biomarkers in Chronic Kidney Disease Patients

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 50614 (mean61SD) years, eGFR 41611 ml/min/1.73 m2, males 73%, dyslipidaemia 36%, smokers 23% and hypertensives 87%. At 16-week serum 25(OH)D and calcium increased (43616 to 84629 nmol/L, p,0.001 and 2.3760.09 to 2.4260.09 mmol/L; p = 0.004, respectively) and parathyroid hormone decreased (10.868.6 to 7.464.4; p = 0.001). FMD improved from 3.163.3% to 6.163.7%, p = 0.001. Endothelial biomarker concentrations decreased: E-Selectin from 566662123 to 525662058 pg/mL; p = 0.032, ICAM-1, 3.4560.01 to 3.1061.04 ng/mL; p = 0.038 and VCAM-1, 54633 to 42633 ng/mL; p = 0.006. eGFR, BP, PWV, AI, hsCRP, von Willebrand factor and Fibroblast Growth Factor-23, remained unchanged. Conclusion: 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. Trial Registration: ClinicalTrials.gov NCT0200571

Analysis of baseline and follow up parameters after Cholecalciferol therapy.

<p><b>Legend:</b> MDRD eGFR: Abbreviated four variable Modified Diet of Renal Disease estimated Glomerular Filtration Rate (REF). Mean automated, sitting, clinic, blood pressure taken thrice using appropriate size cuff was recorded.</p><p>* denotes p<0.05.</p>†<p>Distribution non-parametric variable represented as median±IQR, Wilcoxon Signed Rank Test used to analyse the difference in distribution of baseline and follow up values.</p><p>ACE I- Angiotensin converting enzyme inhibitor, AT II RA- Angiotensin II receptor antagonist. NC: No Change.</p

Measure of endothelial function before and after Vitamin D Therapy.

<p>Legend: The endothelial function as measured by brachial artery flow mediated dilatation improves from 3.1±3.3% to 6.1±3.7%. Error bars show 95% CI, p<0.001.</p

Number of patients recruited into the study and completed the follow-up.

<p>Legend: Flow Diagram of the patient pathway recruited into the effects of oral vitamin D on endothelial function intervention study. Thirty five patients were recruited into the study after excluding twenty one patients. Twenty six patients completed the study.</p