Markers of vascular disease in plasma from patients with chronic kidney disease identified by proteomic analysis.

ABSTRACT

OBJECTIVES: Chronic kidney disease (CKD) patients belong to the group of patients with a high prevalence of cardiovascular disease (CVD). Arterial calcification and aortic stiffness are currently used as surrogates for vascular alterations. However, still little is known about prediction and the patho-physiologic mechanisms leading to CVD. METHODS: We applied capillary electrophoresis coupled mass spectrometry profiling to blood specimens collected from 34 CKD stage 5D patients suffering from vascular alterations to allow insights into the molecular pathology of the disease. RESULTS: Statistical comparison of plasma profiles from mild and severe CVD cases according to either arterial calcification or aortic stiffness unveiled 13 novel biomarkers for vascular disease. Tandem mass spectrometry identified four of these as fragments of collagen alpha-1 type I and III and one as fragment of apolipoprotein CIII. Integrated in a distinct pattern the candidates were validated using the moderate CVD cases among the 34 CKD patients (N=11) and an additional independent blinded cohort of CKD stage 4-5 patients (N=21), who all had not been considered during biomarker discovery. The panel distinguished mild and severe CVD with sensitivity of 89% and specificity of 67% in this independent cohort. CONCLUSION: This diagnostic phase I/II study supports the notion that vascular alterations are reflected by distinct changes in plasma profiles of CKD patients.