Generating reactive oxygen species (ROS) is necessary for both physiology and pathology. An imbalance between endogenous oxidants and antioxidants causes oxidative stress, contributing to vascular dysfunction. The ROS-induced activation of transcription factors and proinflammatory genes increases inflammation. This phenomenon is of crucial importance in patients with chronic kidney disease (CKD), because atherosclerosis is one of the critical factors of their cardiovascular disease (CVD) and increased mortality. The effect of ROS disrupts the excretory function of each section of the nephron. It prevents the maintenance of intra-systemic homeostasis and leads to the accumulation of metabolic products. Renal regulatory mechanisms, such as tubular glomerular feedback, myogenic reflex in the supplying arteriole, and the renin–angiotensin–aldosterone system, are also affected. It makes it impossible for the kidney to compensate for water–electrolyte and acid–base disturbances, which progress further in the mechanism of positive feedback, leading to a further intensification of oxidative stress. As a result, the progression of CKD is observed, with a spectrum of complications such as malnutrition, calcium phosphate abnormalities, atherosclerosis, and anemia. This review aimed to show the role of oxidative stress and inflammation in renal impairment, with a particular emphasis on its influence on the most common disturbances that accompany CKD.
Objectives The main question of this study was to evaluate the intensity of oxidative protein modification shown as advanced oxidation protein products (AOPP) and carbonylated proteins, expressed as protein carbonyl content (C=O) in abdominal aortic aneurysms (AAA), aortoiliac occlusive disease (AIOD), and chronic kidney disease (CKD). Design and Methods The study was carried out in a group of 35 AAA patients and 13 AIOD patients. However, CKD patients were divided into two groups: predialysis (PRE) included 50 patients or hemodialysis (HD) consisted of 34 patients. AOPP and C=O were measured using colorimetric assay kit, while C-reactive protein concentration was measured by high-sensitivity assay (hsCRP). Results The concentration of AOPP in both AAA and AIOD groups was higher than in PRE and HD groups according to descending order: AAA~AIOD > HD > PRE. The content of C=O was higher in the PRE group in comparison to AIOD and AAA according to the descending order: PRE~HD > AAA~AIOD. Conclusions AAA, AIOD, and CKD-related atherosclerosis (PRE and HD) contribute to the changes in the formation of AOPP and C=O. They may promote modification of proteins in a different way, probably due to the various factors that influence oxidative stress here.
BackgroundAtherosclerosis is considered the major cause of the dramatic increase in cardiovascular mortality among patients suffering from chronic kidney disease (CKD). Although the close connection between atherosclerosis and kidney dysfunction is undeniable, factors enhancing CKD-mediated plaque formation are still not well recognized.ResultsTo increase our knowledge of this process we carried out a comparative proteomic analysis of blood plasma proteins isolated from 75 patients in various stages of renal dysfunction (CKD group), 25 patients with advanced cardiovascular disease (CVD group) and 25 healthy volunteers (HV group). The collected samples were subjected to 2D electrophoresis. Then, individual proteins were identified by mass spectrometry. The comparative analysis involving CKD and HV groups showed a differential accumulation of α-1-microglobulin, apolipoprotein A-IV, γ-fibrinogen and haptoglobin in patients with kidney disease. Exactly the same proteins were identified as differentially expressed when proteomes of CVD patients and HV were compared. However, a direct comparison of CKD and CVD groups revealed significant differences in the accumulation of two proteins: α-1-microglobulin and apolipoprotein A-IV.ConclusionsThe obtained results indicate that at least two processes differentially contribute to the plaque formation in CKD- and CVD-mediated atherosclerosis. It seems that the inflammatory process is more intense in CKD patients. On the other hand, the down- and up-regulation of apolipoprotein A-IV in CVD and CKD groups, respectively, suggests that substantial differences exist in the efficacy of cholesterol transport in both groups of patients.
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.
The aim of this study was to check if serum interleukin-18 (IL-18) predicts 2-year cardiovascular mortality in patients at various stages of chronic kidney disease (CKD) and history of acute myocardial infarction (AMI) within the previous year. Diabetes mellitus was one of the key factors of exclusion. It was found that an increase in serum concentration of IL-18 above the cut-off point (1584.5 pg/mL) was characterized by 20.63-fold higher risk of cardiovascular deaths among studied patients. IL-18 serum concentration was found to be superior to the well-known cardiovascular risk parameters, like high sensitivity C-reactive protein (hsCRP), carotid intima media thickness (CIMT), glomerular filtration rate, albumins, ferritin, N-terminal prohormone of brain natriuretic peptide (NT-proBNP) in prognosis of cardiovascular mortality. The best predictive for IL-18 were 4 variables, such as CIMT, NT-proBNP, albumins and hsCRP, as they predicted its concentration at 89.5%. Concluding, IL-18 seems to be important indicator and predictor of cardiovascular death in two-year follow-up among non-diabetic patients suffering from CKD, with history of AMI in the previous year. The importance of IL-18 in the process of atherosclerotic plaque formation has been confirmed by systems analysis based on a formal model expressed in the language of Petri nets theory.
We propose a control-theoretic aggregate model of the progression of atherosclerosis plaque, a chronic inflammatory disease of the arterial wall, to study the basic features of this disease. In the model, we exploit the role of inflammation in the disease progression, and use statins—drugs commonly recommended in atherosclerosis—to control this progression. We use a logistic function to allow for constrained growth of plaque. In the model, both the patient’s age and overall health impact the plaque growth and its sensitivity to statins. The model parameters are estimated using original data, or calibrated using published research as well as our own clinical and laboratory studies. We contend that our model helps to gauge the statins’ impact on a patient’s plaque thickness, hence the disease’s progression and cardiovascular risk, without requiring artery scans.
BackgroundAtherosclerosis is a major cause of cardiac events and mortality in patients suffering from chronic kidney disease (CKD). Moreover, the risk of cardiovascular disease (CVD) development in patients with CKD increases as kidney function declines. Although the close connection between atherosclerosis and kidney dysfunction is undeniable, particular risk factors and specific mechanisms that promote CVD in patients with CKD remain unclear. To gain insight into better recognition of the mechanisms of accelerated atherosclerosis in patients with CKD, we performed a comparative proteomic analysis of blood plasma from patients in various stages of CKD and thus distinct progression of atherosclerosis (n = 90), patients with advanced CVD and normal renal function (n = 30) and healthy volunteers (n = 30).MethodsPlasma samples were depleted using affinity chromatography and divided into three fractions: high-abundant, low-abundant and low-molecular weight proteins. The first two fractions were analyzed by two-dimensional gel electrophoresis and mass spectrometry, the last one has been subjected to direct MS/MS analysis. A proteomic profiles for high-abundant, low-abundant and low-molecular weight proteins fractions were obtained. Differential accumulated proteins were confirmed by selected reaction monitoring analysis (SRM). The Gene Ontology (GO) function and the interaction networks of differentially expressed proteins were then analyzed.ResultsForty-nine proteins (13 high- and 36 low-molecular mass) showed differences in accumulation levels. For eleven of them differential expression were confirmed by selected reaction monitoring analysis. Bioinformatic analysis showed that identified differential proteins were related to three different processes: the blood coagulation cascade, the transport, binding and metabolism of lipoproteins and inflammatory processes.ConclusionsObtained data provide an additional line of evidence that different molecular mechanisms are involved in the development of CKD- and CVD-related atherosclerosis. The abundance of some anti-atherogenic factors revealed in patients with CKD suggests that these factors are not associated with the reduction of atherosclerosis progression in CKD that is typically observed in “classical” CVD. Moreover, obtained data also suggest that mechanism of CVD acceleration may be different in initial and advanced stages of CKD. Undoubtedly, in advanced stages of CKD inflammation is highly pronounced.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-014-0378-8) contains supplementary material, which is available to authorized users.
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