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.
CHU de Québec Research Center, L'Hôtel-Dieu de Québec Hospital, Québec, QC, Canada; Division of Nephrology, Faculty of Medicine, Université Laval, Québec, QC, Canada;
Catherine
C
Fortier
CHU de Québec Research Center, L'Hôtel-Dieu de Québec Hospital, Québec, QC, Canada; Division of Nephrology, Faculty of Medicine, Université Laval, Québec, QC, Canada;
Fabrice
F
Mac-Way
CHU de Québec Research Center, L'Hôtel-Dieu de Québec Hospital, Québec, QC, Canada; Division of Nephrology, Faculty of Medicine, Université Laval, Québec, QC, Canada;
Sacha A
SA
De Serres
CHU de Québec Research Center, L'Hôtel-Dieu de Québec Hospital, Québec, QC, Canada;
Karine
K
Marquis
Département de biologie moléculaire, de biochimie médicale et de pathologie, Faculty of Medicine, Université Laval, Québec, QC, Canada; Département de biologie médicale, CHU de Québec- L'Hôtel-Dieu de Québec Hospital, Québec, QC, Canada.
Pierre
P
Douville
CHU de Québec Research Center, L'Hôtel-Dieu de Québec Hospital, Québec, QC, Canada; Division of Nephrology, Faculty of Medicine, Université Laval, Québec, QC, Canada;
Simon
S
Desmeules
CHU de Québec Research Center, L'Hôtel-Dieu de Québec Hospital, Québec, QC, Canada; Division of Nephrology, Faculty of Medicine, Université Laval, Québec, QC, Canada;
Richard
R
Larivière
CHU de Québec Research Center, L'Hôtel-Dieu de Québec Hospital, Québec, QC, Canada; Division of Nephrology, Faculty of Medicine, Université Laval, Québec, QC, Canada; mohsen.aghrazii@crhdq.ulaval.ca.
Mohsen
M
Agharazii
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002112:Calcifediol / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D019587:Dietary Supplements / Q000009:adverse effects*; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood; D005966:Glucuronidase / Q000097:blood; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D000090265:Klotho Proteins; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010281:Parathyroid Hormone / Q000097:blood; D011792:Quebec; D006435:Renal Dialysis / Q000009:adverse effects; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000628:therapy*; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014652:Vascular Diseases / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology; D059289:Vascular Stiffness / Q000187:drug effects*; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
D015415:Biomarkers; C470125:PTH protein, human; D010281:Parathyroid Hormone; D014807:Vitamin D; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; C104450:25-hydroxyvitamin D; D005966:Glucuronidase; D000090265:Klotho Proteins; D002112:Calcifediol
aortic stiffness; blood pressure; chronic kidney disease; hemodialysis; hypertension; parathyroid hormone; vitamin D.; α-calcidol