SP085
DUALITY OF CALCITRIOL-BASED INHIBITION OR PROPAGATION OF VASCULAR CALCIFICATION IN VITRO IS DEPENDENT ON NORMAL OR HIGH CALCIUM LEVELS, RESPECTIVELY Free

Introduction and Aims: Calcitriol (1, 25-dihydroxyvitamin D₃) is used to mitigate secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD). However, the use of calcitriol has been found in vitro and in vivo to paradoxically both inhibit and increase vascular calcification (VC), a risk factor for cardiovascular disease (CVD).

Methods: The study’s objective was to examine the impact of calcitriol on aortic calcification in vitro when exposed to different medium concentrations of Ca²⁺ and PO₄^3-. Aortic tissue was harvested from 16 week-old Sprague Dawley rats (n = 12), with whole rings incubated in Dulbecco’s Modified Eagles Medium (DMEM) for 4 days. Incubation treatments consisted of control (Group 1, 0.9mM PO₄^3- & 1.6mM Ca²⁺), high Ca²⁺ and low PO₄^3- (Group 2, 0.9mM PO₄^3- & 3.2mM Ca²⁺), normal Ca²⁺ and high PO₄^3- (Group 3, 3.8mM PO₄^3- & 1.6mM Ca²⁺), and high Ca²⁺ and high PO₄^3- (Group 4, 3.8mM PO₄^3- & 1.6mM Ca²⁺). Calcitriol (0nM, 1nM, 10nM, or 100nM) was added to different DMEM treatments. Media was switched every 48hours.

Results: In the normal Ca²⁺ and high PO₄^3- treatment (Group 3), there was a dose-dependent decrease in Ca²⁺ and PO₄^3- accrual with calcitriol. Mineral accrual in the 10nM calcitriol group was significantly lower than controls (p<0.05) and mineral accrual in the 100nM calcitriol groups was significantly lower than all groups (p<0.05); reaching control levels. In contrast, with aortic rings in high Ca²⁺ and high PO₄^3- media (Group 4) there was a significant increase in both Ca²⁺ and PO₄^3- in the 100nM calcitriol group compared to all groups (p<0.0001). Further, in normal PO₄^3- and high Ca²⁺ conditions (Groups 2), an increase in mineral accrual with calcitriol was similarly observed; where the 10nM group was significantly elevated compared to control (p<0.05) and 100nM group was significantly elevated compared to all groups (p<0.05).

Conclusions: These findings in vitro suggest that the dose-dependent ability of calcitriol to inhibit or promote VC is dependent on Ca²⁺. Where aortic rings in media with high PO₄^3- and normal Ca²⁺ show a dose-dependent inhibition of mineral accrual, a significant rise in mineral accrual occurs with an increase to media [Ca²⁺]. These findings suggest an optimal in vivo strategy to ameliorate SHPT in CKD while mitigating impact to vascular health is required, but possible.