*4.3. Vitamin D*

Vitamin D deficiency and sHPT are common comorbidities in progressive CKD stages. Vitamin D application lowers PTH levels in the body. TheKidney Disease: Improving Global Outcomes KDIGO guideline from 2017 recommends vitamin D analogs for both CKD pre-dialysis patients stage 4 and 5 and dialysis patients with sHPT [11].

In a mouse model of CKD with electrocoagulation of the right renal cortex and left nephrectomy, treatment with the vitamin D receptor agonists calcitriol and paricalcitol prevented calcification (Table 2) [26]. A meta-analysis of 20 observational studies revealed an association of vitamin D supplementation in pre-dialysis and HD patients with decreased all-cause and CV mortality [84]. The association between vitamin D deficiency and endothelial dysfunction supports the hypothesis that vitamin D supplementation could attenuate vascular calcification in CKD patients [85]. Therefore, interventional studies investigated the effect of vitamin D analogs on arterial stiffness. A double-blind RCT compared the effect of calcifediol (25-hydroxyvitamin D3) and calcitriol (1,25-dihydroxyvitamin D3) to placebo by analyzing pulse wave velocity (PWV) as a parameter for vascular stiffness [86]. PWV was decreased in the calcifediol group, while it stagnated in the calcitriol group and was increased in the placebo control. Furthermore, cholecalciferol improved vascular stiffness in pre-dialysis patients compared to placebo, suggesting a beneficial effect of cholecalciferol on endothelial function [87]. However, treatment with cholecalciferol did not significantly attenuate CAC in CKD [88]. Evidence for a beneficial effect of vitamin D supplementation on CV calcification progression remains uncertain. The informative value is also limited by the use of different vitamin D analogs and dosages. Further RCT are necessary to evaluate the potential of vitamin D supplementation in CKD. Findings demonstrated a vitamin D level decline prior to the occurrence of changes in PTH and phosphate. Therefore, earlier vitamin D supplementation should be considered in patients without sHPT [89].
