SP302
TEMPORAL PATTERN VASCULAR PATHOGENESIS IN CKD: REGIONAL HETEROGENEITY IN VASCULAR CALCIUM ACCRUAL Free

Introduction and Aims: Blood vessels have a differential susceptibility to calcification depending on anatomical location. Although vascular calcification (VC) is highly prevalent in patients with chronic kidney disease (CKD), the regional and temporal pattern of calcium deposition across the vasculature has not been elucidated. The study objective was to determine the time course and severity of VC pathology across vascular beds in experimental CKD.

Methods: Male Sprague-Dawley rats were maintained on a CKD diet (0.25% adenine) for 3 weeks (n=8, creatinine: 127 ± 66uM), 5 weeks (n=15, creatinine: 391 ± 66uM) and 7 weeks (n=40, creatinine: 268 ± 121 uM).

Results: 3 wks of CKD did not yield VC in any vascular bed assessed. However, after 5 and 7 wks on CKD diet respectively: 21% vs. 33% of animals developed VC in the thoracic aorta, 36% vs. 51% in the abdominal aorta, 31% vs. 42% in the carotid artery, and 72% vs. 65% in the internal pudendal artery. These data indicate substantial heterogeneity across vascular beds in their susceptibility to calcification in CKD. To further characterize the pathogenesis of VC, CKD rats (7 wks 0.25% adenine, SD rats) were placed on a low (20 ng/kg/day, n=24, creatinine: 211 ± 63uM) or a high dose of calcitriol (80ng/kg/day, n=24, creatinine: 201 ± 45 uM) to generate a range of VC severity. The animals were grouped into a single cohort and then stratified by the presence of VC in the thoracic aorta. When VC was not yet present in the thoracic aorta, calcium content was already significantly elevated above control levels in the iliac artery (45.9 fold), renal artery (12.6 fold), and internal pudendal artery (12.6 fold; p<0.05). However, when VC was present in the TA, the rank order for the capacity for calcium accumulation (nmol/mg tissue, fold increase above control) was from proximal to distal: thoracic aorta (400x), abdominal aorta (314x), iliac artery (214x), renal artery (118x), internal pudendal artery (64x; p<0.05).

Conclusions: Together these findings in experimental CKD indicate that there is substantial heterogeneity in both the regional susceptibility to VC, but also in the capacity for total calcium accumulation. Although the peripheral vasculature calcifies prior to vasculature, i.e. those proximal to the heart, the larger vessels (e.g. aorta and iliac) have a significantly greater capacity for calcification than the distal vessels. Differences in embryonic origin as well as the vessel structure (e.g. wall thickness, extracellular matrix composition) likely play a significant role in the variations in susceptibility.