A Bimodal Association of Vitamin D Levels and Vascular Disease in Children on Dialysis

Abstract

In addition to its classical role in calcium-phosphate homeostasis, vitamin D has anti-inflammatory effects that may influence vascular disease. This study examined the impact of vitamin D levels on the vascular phenotype in 61 children who had been on dialysis for Ն3 mo and in 40 age-matched control subjects. All dialysis patients were prescribed daily oral 1-␣ hydroxyvitamin D 3 . 92% of patients were deficient in ,25(OH) 2 D] levels were low in 36% and high in 11% of patients. There was a weak correlation between 1␣-hydroxyvitamin D 3 dosage and 1,25(OH) 2 D levels. Both carotid intima-media thickness and calcification scores showed a U-shaped distribution across 1,25(OH) 2 D levels: patients with both low and high 1,25(OH) 2 D had significantly greater carotid intima-media thickness (P Ͻ 0.0001) and calcification (P ϭ 0.0002) than those with normal levels. Low 1,25(OH) 2 D levels were associated with higher high-sensitivity C-reactive protein (P Ͻ 0.0001). Calcification was most frequently observed in patients with the lowest 1,25(OH) 2 D and the highest highsensitivity C-reactive protein. In contrast, 25(OH)D levels did not correlate with any vascular measure. In conclusion, both low and high 1,25(OH) 2 D levels are associated with adverse morphologic changes in large arteries, and this may be mediated through the effects of 1,25(OH) 2 D on calcium-phosphate homeostasis and inflammation. For optimization of strategies to protect the vasculature of dialysis patients, careful monitoring of 1,25(OH) 2 D levels may be required.

Effects of Cholecalciferol on Functional, Biochemical, Vascular, and Quality of Life Outcomes in Hemodialysis Patients

“…In patients with CKD-5D, PWV may be increased by dosing with calcium, calcitriol, or its analogs and by phosphate exposure (30)(31)(32), although physiologic levels of 25(OH)D and 1,25(OH) 2 D may maintain stability of the vascular smooth muscle phenotype (33). In this study, baseline PWV values were directly associated with age and inversely to 25(OH)D levels.…”

Vitamin D Affects Survival Independently of Vascular Calcification in Chronic Kidney Disease

“…In this regard, Shroff et al have recently reported a bimodal association between vascular calcification and 1,25D levels in dialyzed children, but no association between 25D levels and the vascular measurements (22). London et al observed that in adult hemodialysis patients, 1,25D and 25D levels were negatively correlated with aortic stiffness but not with vascular calcification (13).…”

“…In animal models, exogenous administration of supraphysiological doses of VDR activators has been associated with both the incidence and progression of vascular calcification (19,20), whereas the administration of VDR activators at more physiologic doses (i.e., just enough to correct secondary hyperparathyroidism) protect against aortic calcification (21). In a CKD setting, a recent study in adult hemodialysis patients described an association between 25D deficiency and arterial stiffness (13), whereas dialyzed children showed a bimodal association between 1,25D levels and vascular calcification and stiffness (22).…”

Treatment of Secondary Hyperparathyroidism in CKD Patients with Cinacalcet and/or Vitamin D Derivatives

“…If not closely supervised, prolonged high-dose supplements of vitamin D or its active derivatives may lead to hypercalcemia and hyperphosphatemia and induce adverse effects such as vascular calcification (83)(84)(85). Of interest, both vitamin D deficiency and vitamin D excess have been shown to be associated with an increased prevalence of vascular calcification (63).…”