Effect of Vitamin D Supplementation on Vascular Function and Inflammation in Patients with Chronic Kidney Disease: A Controversial Issue

Abstract

Vitamin D deficiency is common in patients with CKD and is associated with vascular dysfunction and inflammation. In recent years, some randomized controlled trials have revealed the effect of vitamin D supplementation on vascular function and inflammation in CKD patients, but the results are inconsistent. Thus, in light of the controversy, we performed a systematic review and meta-analysis of the effect of vitamin D in patients with CKD. We searched the literature in multiple databases for clinical trials from the date of inception to December 2018. The standardized mean difference (SMD) effect size was pooled using fixed and random effects models. A total of 10 randomized controlled trials involving 579 patients were included in the meta-analysis; among these, 313 patients were treated with vitamin D, and the control group included 266 who received a placebo. This meta-analysis revealed no statistical significance in the levels of flow-mediated dilatation (SMD, 0.94; 95% CI, −0.33 to 2.21; P = 0.15); pulse wave velocity (SMD, −0.13; 95% CI, −0.38 to 0.13; P = 0.33); systolic BP (SMD, −0.04; 95% CI, −0.29 to 0.22; P = 0.77); diastolic BP (SMD, 0.01; 95% CI, −0.26 to 0.27; P = 0.97); and CRP (SMD, −0.09; 95% CI, −0.44 to 0.26; P = 0.61) between the vitamin D group and controls for patients with CKD. Short-term intervention with vitamin D was not associated with improvements in vascular function and inflammation, as measured by flow-mediated dilatation, pulse wave velocity, systolic BP, diastolic BP and CRP. This suggested that there is insufficient evidence to conclude the benefit of vitamin D supplementation on vascular function and inflammation in CKD patients.

Inflammation and Premature Ageing in Chronic Kidney Disease

“…Meta-analyses demonstrating reduced circulating markers of inflammation in mostly non-CKD subjects on vitamin D supplementation [97,98], further supporting a significant role of vitamin D on the hallmarks of ageing. However, these associations were not seen in CKD patients on vitamin D supplementation [99]. Furthermore, two systematic reviews and meta-analyses did not find strong evidence for a beneficial effect of vitamin D supplementation on arterial stiffness [100] and endothelial function [101], two major components of EVA.…”

Εndothelial and microvascular function in CKD: Evaluation methods and associations with outcomes

“…46 A meta-analysis of studies examining the effect of vitamin D supplementation in patients with CKD confirmed the absence of vitamin D effects on FMD. 47 Finally, forearm FMD was significantly higher in patients undergoing highefficiency online haemodiafiltration compared with highflux haemodialysis. 48…”

“…In advanced diabetic kidney disease, treatment with paricalcitol (a vitamin D receptor activator used for secondary hyperparathyroidism treatment) was also not associated with FMD changes 46 . A meta‐analysis of studies examining the effect of vitamin D supplementation in patients with CKD confirmed the absence of vitamin D effects on FMD 47 . Finally, forearm FMD was significantly higher in patients undergoing high‐efficiency online haemodiafiltration compared with high‐flux haemodialysis 48 …”

Vitamin D, Cellular Senescence and Chronic Kidney Diseases: What Is Missing in the Equation?

“…The clinical impact of vitamin D supplementation on kidney or cardiovascular disease beyond CKD-MBD has been a topic of debate among researchers. A review conducted by Chun Hu et al [ 153 ] found that the evidence was insufficient to support the idea that vitamin D improves vascular function and reduces inflammation in such patients. On the other hand, Ding Dou et al [ 154 ] believed that the benefits of vitamin D supplementation could vary depending on the dose and the progression of the disease.…”