Abstract
The major cause of mortality in patients with chronic kidney disease (CKD) is atherosclerosis related to traditional and non-traditional risk factors. However, the understanding of the molecular specificity that distinguishes the risk factors for classical cardiovascular disease (CVD) and CKD-related atherosclerosis (CKD-A) is far from complete. In this study we investigated the disease-related differences in the proteomes of patients with atherosclerosis related and non-related to CKD. Plasma collected from patients in various stages of CKD, CVD patients without symptoms of kidney dysfunction, and healthy volunteers (HVs), were analyzed by a coupled label-free and mass spectrometry approach. Dysregulated proteins were confirmed by an enzyme-linked immunosorbent assay (ELISA). All proteomic data were correlated with kidney disease development and were subjected to bioinformatics analysis. One hundred sixty-two differentially expressed proteins were identified. By directly comparing the plasma proteomes from HVs, CKD, and CVD patients in one study, we demonstrated that proteins involved in inflammation, blood coagulation, oxidative stress, vascular damage, and calcification process exhibited greater alterations in patients with atherosclerosis related with CKD. These data indicate that the above nontraditional risk factors are strongly specific for CKD-A and appear to be less essential for the development of “classical” CVD.
Highlights
Chronic kidney disease (CKD) is highly prevalent worldwide and is an important cause of morbidity, especially due to cardiovascular disease (CVD)
The plasma collected from five experimental groups, healthy volunteers (HVs), CKD1-2, CKD3-4, CKD5, and CVD, without any fractionation were digested in solution with trypsin and analyzed by nano LC-MS/MS in one batch
The reproducibility of the technical and biological replicates was assessed by scatter plotting and the correlation coefficient determined based on the label-free quantification (LFQ) intensities
Summary
Chronic kidney disease (CKD) is highly prevalent worldwide and is an important cause of morbidity, especially due to cardiovascular disease (CVD). In classical CVD, without renal dysfunction, most atherosclerosis is caused by traditional risk factors that can be controlled, treated or modified (such as hypertension, tobacco use, diabetes, lipid levels) or factors that cannot be changed (such as age, gender, and family history) [1] In these cases, atherosclerosis is the consequence of many years of exposure to atherogenic influences that lead to early lesions. Chronic kidney disease-related atherosclerosis (CKD-A) is more complex and is related to traditional and non-traditional risk factors, including inflammation, endothelial dysfunction, oxidative stress, vascular calcification, and volume overload All of these problems lead to hypertension, anemia, mineral and bone disorders, and vascular remodeling and damage [2]. We sought to determine which of these risk factors have a substantial role in and are specific for CKD-A
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