Active vitamin D and accelerated progression of aortic stiffness in hemodialysis patients: a longitudinal observational study.

BACKGROUND: We hypothesized that high-dose active vitamin D therapy in the form of alphacalcidol (α-calcidol), used to treat secondary hyperparathyroidism in chronic kidney disease, could lead to vascular calcification and accelerated progression of aortic stiffness.

METHODS: We conducted an observational study in 85 patients on chronic hemodialysis, among which 70 were taking a weekly dose of α-calcidol of <2 µg and 15 were taking a weekly dose of ≥2 µg (pharmacological dose). Parathyroid hormone, 25-hydroxyvitamin D, fibroblast growth factor 23, and α-klotho were determined. Aortic stiffness was assessed by determination of carotid-femoral pulse wave velocity (cf-PWV) at baseline and after a mean follow-up of 1.2 years. A multivariable regression model was used to evaluate the impact of pharmacological dose of α-calcidol on the progression of aortic stiffness.

RESULTS: At baseline, clinical, biological, and hemodynamic parameters were similar. At follow-up, cf-PWV increased more in patients with pharmacological dose of α-calcidol (0.583±2.291 m/s vs. 1.948±1.475 m/s; P = 0.04). After adjustment for changes in mean blood pressure and duration of follow-up, pharmacological dose of α-calcidol was associated with a higher rate of progression of cf-PWV (0.969 m/s; 95% confidence interval = 0.111-1.827; P = 0.03), and this association persisted after further adjustments for parameters of mineral metabolism.

CONCLUSIONS: In this study, pharmacological dose of α-calcidol was associated with accelerated progression of aortic stiffness. This study suggest that the vascular safety of active vitamin D posology may need to be specifically addressed in the treatment of chronic kidney disease-related bone mineral disorder.