The strengths of our study are its double blind randomised placebo control design, replacement of vitamin D in line with international guidelines that was standardised for all patients and commensurate with baseline serum concentrations of 25 D as well as the use of techniques that specifically assessed both conduit artery and microcirculatory BMN673 endothelial function. At the time of designing this study, microcirculatory endothelial function had not previously been evaluated in patients with CKD and concomitant VDD in a clinical trial setting. Iontophoresis has been used in the setting of clinical trials to evaluate endothelial function. The experimental conditions and iontophoretic protocol in the present study were standardised and changes in endothelial function were compared with baseline prior to treatment with ergocalciferol. The use of a low current iontophoresis protocol will have reduced the direct galvanic effect from the iontophoretic process on the endothelium seen when a higher current is used. Therefore, any change seen in LDF after iontophoresis must be due to the direct effect of ergocalciferol itself on microvascular endothelial function. Limitations of this study include the short follow up time and small sample size. The study duration is insufficient to detect significant differences between treatment groups in key outcome measures including CV events. Excluding patients with diabetes mellitus has limited the external validity but improved the internal validity and precision of the present study. Human aortic endothelial cells were not cultured in media consistent with the degree of CKD in the clinical trial subjects due to the complexity of establishing a culture medium that accurately reflects the earlier rather than more advanced stages of CKD. Consequently, the results from the in vitro experiments cannot be directly generalised to the uraemic milieu associated with CKD stage 3–4. The current study did not assess the effect of ergocalciferol on endothelial progenitor cells which are important mediators of endothelial repair and function and are reduced in patients at high risk of CVD. Additional studies are required to address the effect of ergocalciferol on endothelial cells cultured in a medium more representative of the earlier stages of CKD as well as the effect of ergocalciferol on EPC number and function in CKD stage 3–4. However, this frequency may differ among different ethnic groups. Despite intense treatment, the prognosis in young BC patients, particularly in black women, is worse than that in their older counterparts. This fact has been partially attributed to the high frequency of unfavorable tumor characteristics. The influence of genetic factors may contribute to the poor prognosis, but familial history of cancer explains only 10%–37% of the cases, of which 10%–25% were attributable to BRCA1/2 mutations, which are currently known as the 2 major BC predisposing genes. In sporadic cases, this frequency is still smaller, ranging from 3%–10%.