Association of Vitamin D Metabolites With Arterial Function in the Hemodialysis Fistula Maturation Study

Abstract

Background: Disturbances in vitamin D metabolism are common in patients with end-stage renal disease and may contribute to vascular dysfunction.

Study design: Cross-sectional.

Setting & participants: We evaluated 558 of 602 participants at baseline of the Hemodialysis Fistula Maturation (HFM) Study, a 7-center prospective cohort study of a cohort of patients with chronic kidney disease awaiting arteriovenous fistula (AVF) creation surgery.

Factor: 4 vitamin D metabolites measured with liquid chromatography-tandem mass spectroscopy from samples obtained within 4 weeks prior to AVF surgery.

Outcomes: Vasodilator functions and measurements of arterial stiffness.

Measurements: Trained HFM Study personnel measured brachial artery flow-mediated dilation, nitroglycerin-mediated dilation, and carotid-femoral and carotid-radial pulse wave velocities (PWVs) prior to AVF creation. We evaluated associations after basic adjustment for sex, age, and clinical site and more fully adjusted additionally for baseline education, smoking, body mass index, diabetes, dialysis status, and medication use.

Results: Mean participant age was 55±13 (SD) years and 65% were receiving maintenance dialysis. None of the vitamin D metabolites were significantly associated with flow-mediated dilation, carotid-femoral PWV, or carotid-radial PWV in basic or fully adjusted analyses. Higher serum concentrations of bioavailable vitamin D and 1,25-dihydroxyvitamin D were associated with 0.62% and 0.58% greater nitroglycerin-mediated dilation values, respectively, in basic models; however, these associations were no longer statistically significant with full adjustment. There were no significant associations of vitamin D metabolites with carotid-femoral or carotid-radial PWV in fully adjusted analyses.

Limitations: Cross-sectional ascertainment of vitamin D metabolites and vascular functions late during the course of kidney disease.

Conclusions: Serum concentrations of vitamin D metabolites are not associated with vasodilator functions or vascular stiffness at baseline in a cohort study of patients with chronic kidney disease awaiting AVF creation surgery. Laboratory measurements of vitamin D metabolites are unlikely to provide useful information regarding vascular functions in this setting.

Keywords: Vascular function; arterial function; arteriovenous fistula (AVF); calcitriol; end-stage renal disease (ESRD); endothelial function; epidemiology; flow mediated dilation (FMD); hemodialysis; nitroglycerine-mediated dilation (NMD); pulse wave velocities (PWV); stiffness; vasodilation; vitamin D metabolites.

Figure 1

Associations of continuous serum mineral metabolism concentrations with vascular functions stratified by dialysis status. BAVD = bioavailable vitamin D, FMD = flow mediated vasodilation, NMD = nitroglycerine mediated vasodilation, PWV CF = Carotid femoral pulse wave velocity, PWV CR = Carotid radial pulse wave velocity. Analyses adjusted for age, sex, race, study site, diabetes, BMI, current smoking, education, use of vitamin D medications, use of ACE inhibitors, use of ARBs, and use of calcium channel blockers X-axes depict the adjusted difference in each vascular function measurement per standard deviation increment in each vitamin D metabolism marker. The solid circles represent estimated adjusted differences and the solid horizontal bars represent 95% confidence intervals. The dashed vertical line indicates the null association (adjusted difference of 0).