Abstract
Patients with chronic kidney disease (CKD) have a considerably higher risk of death due to cardiovascular causes. Using an iTRAQ MS/MS approach, we investigated the alterations in plasma protein accumulation in patients with CKD and classical cardiovascular disease (CVD) without CKD. The proteomic analysis led to the identification of 130 differentially expressed proteins among CVD and CKD patients and healthy volunteers. Bioinformatics analysis revealed that 29 differentially expressed proteins were involved in lipid metabolism and atherosclerosis, 20 of which were apolipoproteins and constituents of high-density lipoprotein (HDL) and low-density lipoprotein (LDL). Although dyslipidemia is common in CKD patients, we found that significant changes in apolipoproteins were not strictly associated with changes in plasma lipid levels. A lack of correlation between apoB and LDL concentration and an inverse relationship of some proteins with the HDL level were revealed. An increased level of apolipoprotein AIV, adiponectin, or apolipoprotein C, despite their anti-atherogenic properties, was not associated with a decrease in cardiovascular event risk in CKD patients. The presence of the distinctive pattern of apolipoproteins demonstrated in this study may suggest that lipid abnormalities in CKD are characterized by more qualitative abnormalities and may be related to HDL function rather than HDL deficiency.
Highlights
Identified apolipoproteins are anti-atherogenic or atherogenic factors; our results showed that this simple division did not explain the higher incidence of atherosclerosis and cardiac events in Chronic kidney disease (CKD) patients
In our earlier studies we performed 2DE/MS analyses of plasma samples of patients with diagnosed CKD and cardiovascular disease (CVD) as well as in healthy volunteers (HVs) and we have shown that CKD-related atherosclerosis (CKD-A) is more accelerated by inflammatory processes compared with nonrenal classical CVD14
We have demonstrated that apoAIV displays an anti-atherogenic effect only in the case of classical CVD and is not efficient in CKD-A
Summary
CKD is frequently accompanied by reduced plasma HDL concentrations and normal or even low serum total cholesterol and LDL concentrations[6,7]. In CKD patients, higher total cholesterol and LDL values may even be associated with greater survival and a lower risk of CVD8,9. Lowering LDL cholesterol with statin therapy is effective in reducing the risk of cardiovascular morbidity and mortality only among people with mild degrees of renal impairment but not in patients at the most advanced CKD stages, i.e., ESRD10. The association between low serum cholesterol concentrations and higher mortality, especially in ESRD patients, is probably related to systemic inflammation or malnutrition, both of which have a cholesterol-lowering effect[11]. The question of whether atherosclerosis in patients with CKD is a different process than that in patients with classical CVD persists. This article focuses on the alterations in abundance of proteins involved in lipid transport, metabolism and atherosclerotic plaque formation in patients with different stage of CKD as well as patients with “classical” CVD
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