Impact of vitamin D supplementation on arterial vasomotion, stiffness and endothelial biomarkers in chronic kidney disease patients

Nihil Chitalia, Tuan Ismail, Laura Tooth, Frances Boa, Geeta Hampson, David Goldsmith, Juan Carlos Kaski, Debasish Banerjee, Nihil Chitalia, Tuan Ismail, Laura Tooth, Frances Boa, Geeta Hampson, David Goldsmith, Juan Carlos Kaski, Debasish Banerjee

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.

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 NCT02005718.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Number of patients recruited into…
Figure 1. Number of patients recruited into the study and completed the follow-up.
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.
Figure 2. Measure of endothelial function before…
Figure 2. Measure of endothelial function before and after Vitamin D Therapy.
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

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