Endothelium-Dependent and -Independent Vascular Function in Advanced Chronic Kidney Disease

Background and objectives CKD is associated with increased cardiovascular risk not fully attributable to traditional risk factors. We compared endothelium-dependent and -independent vascular function among individuals with advanced CKD with function in those with vascular disease but preserved kidney function. Design, setting, participants, & measurements Matched cohort analysis randomly selected from 1259 participants at a single center with measurements of brachial artery flow–mediated dilation, an endothelium-dependent process, and nitroglycerin-mediated dilation, an endothelium-independent process. Patients with advanced CKD ( n =70) were matched 1:1 to controls with preserved kidney function and ( 1 ) no overt vascular disease, ( 2 ) hypertension, and ( 3 ) coronary artery disease. Results The trend toward lower flow-mediated dilation (mean±SEM) in advanced CKD (5.4%±0.5%) compared with no overt vascular disease (7.3%±0.6%), hypertension (6.2%±0.5%), and coronary artery disease (5.8%±0.5%) did not reach statistical significance in adjusted analyses ( P =0.05). Nitroglycerin-mediated dilation was lower in advanced CKD compared with in the other groups (adjusted nitroglycerin-mediated dilation: 6.9%±0.8%, 11.8%±0.9%, 11.0%±0.7%, and 10.5%±0.7% in advanced CKD, no overt vascular disease, hypertension, and coronary artery disease groups, respectively; P <0.001). Using tertiles generated from the full cohort and no overt vascular disease as the reference, the adjusted odds of flow-mediated dilation falling within the lowest tertile was higher in both the advanced CKD (odds ratio, 4.84; 95% confidence interval, 2.09 to 11.25) and coronary artery disease (odds ratio, 4.17; 95% confidence interval, 1.76 to 9.87) groups. In contrast, the adjusted odds of lowest tertile nitroglycerin-mediated dilation was higher in advanced CKD (odds ratio, 24.25; 95% confidence interval, 7.16 to 82.13) but not in the hypertension (odds ratio, 0.79; 95% confidence interval, 0.23 to 2.77) or coronary artery disease (odds ratio, 2.34; 95% confidence interval, 0.74 to 7.40) group. Conclusions Impairment in endothelium-dependent vascular function is present in patients with CKD and those with clinically evident vascular disease but preserved kidney function. In contrast, substantial reduction in endothelium-independent function was observed only in the CKD group, suggesting differences in severity and pathophysiology of vascular dysfunction between CKD and other disease states.