Differential effects of vitamin D receptor activators on vascular calcification in uremic rats

Vascular calcification is associated with cardiovascular disease, the most common cause of death in chronic kidney disease (CKD). Patients with CKD are treated with vitamin D receptor activators (VDRAs); therefore, we determined if this treatment affects vascular calcification. Uremic rats were given vehicle, calcitriol, paricalcitol, or doxercalciferol three times a week for 1 month. Calcitriol significantly increased the serum calcium-phosphate product and aortic calcium content. Paricalcitol had no effect but the same dose of doxercalciferol significantly increased the calcium-phosphate product and the aortic calcium content, the latter being confirmed by von Kossa staining. To see if the increased aortic calcium was due to an increased serum calcium-phosphate product or to a differential effect of the two VDRAs, we lowered the dose of doxercalciferol and increased the dose of paricalcitol. A lower doxercalciferol did not increase the calcium-phosphate product but increased the aortic calcium content. A higher dose of paricalcitol still had no effect. Doxercalciferol treatment increased the mRNA and protein expression of the bone-related markers Runx2 and osteocalcin in the aorta, whereas paricalcitol did not. Hence, different VDRAs have different effects on vascular calcification in uremic rats. The effects are independent of the serum calcium-phosphate product suggesting independent mechanisms.