Abstract 3482: Increased Arterial Stiffness and Medial Calcification in Dialyzed Chronic Kidney Disease Patients Correlate with Vasomotor Dysfunction in the Arterial Macro-Vasculature
Chronic kidney disease (CKD) is recognized as a risk factor for cardiovascular disease (CVD). Increased aortic stiffness and pulse wave velocity (PWV) have been shown to impact on CV mortality in CKD patients. We hypothesized that there was demonstrable deterioration in the vasomotor function which correlates with changes in structural integrity in the macro-vasculature in CKD patients, especially those on dialysis. During live donor kidney transplantation, inferior epigastric arteries (EGA) from recipients [non-dialysis (ND)= 10; dialysis (D)= 15] were harvested for assessing mechanical, histological, and functional characteristics. Stiffness coefficient, determined from the stress-strain relation curve, of the EGA-D was 30% greater than that of the EGA-ND, and positively correlated (r=0.811, p<0.001) with in vivo PWV measured by sphygamacor. In the Movat’s stained histology, elastic fiber fragmentation was more pronounced in the EGA-D, and elastin content was 20% less in the dialyzed group. Medial calcium/phosphate deposition demonstrated in the von Kossa staining strongly correlated with the increased stiffness coefficient in EGA-D (r=0.61, p<0.05). Both arterial stiffness and calcium deposition in the EGA-D were negatively correlated with the acetylcholine-stimulated endothelium-dependent relaxation (r=−0.72, r=−0.80, p<0.001, respectively) and phenylephrine-induced contraction (r=−0.65, r=−0.60, p<0.05, respectively) measured in the isometric force experiments. These correlations were present, though weaker, in the EGA-ND (r=−0.45, r=−0.41, p<0.05). This study describes vessel calcification which is associated with worsening structural integrity, and impaired vascular contraction and relaxation which is more apparent in the dialyzed as compared to the non-dialyzed group. The compromised vascular function in the dialyzed group correlated with composite measures of arterial stiffness, elastic fiber fragmentation, medial calcium deposition, and in vivo PWV measurement, all of which are factors which have been associated with adverse CV events in CKD patients. This unique translational study establishes structural and functional correlations in vivo and ex vivo.