Cardiovascular Features of Chronic Inflammation and Endothelial Dysfunction in Patients with Diabetic Nephropathy on Programmed Hemodialysis

Abstract

Introduction and purpose: It is important today to determine the factors that form a very high cardiovascular risk in patients with type 2 diabetes mellitus (DM) with kidney damage on programmed hemodialysis (HD). The aim of the study has been to determine the cardiovascular features of chronic inflammation and endothelial dysfunction (ED) in HD patients with diabetic nephropathy (DN). Material and methods: The study has included 136 patients treated with HD (men, 78; age, 53.9±1.0 year, duration of HD, 47.6±4.2 months). Depending on the presence/absence of type 2 diabetes, they have been divided into two groups: the firstwithout DN (n=88); the secondwith DN (n=48). The intensity of inflammation has been assessed by the serum content of tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), fibrinogen (FG) and albumin. Vasomotor function of the brachial artery (BA) has been determined using a test with reactive hyperemia (endothelium-dependent vasodilation, (EDVD)). The content of nitrite anions (NO2-) and the number of circulating endothelial cells (CECs) in blood plasma have been measured. Results: In patients with DN, TNF-α (p=0.002), CRP (p<0.001) and FG (p=0.008) significantly exceeded those in non-diabetics. The average value of EDVD BA (p=0.001), NO2-(p=0.008) in patients of the second group has been lower, and the number of 145 CECshigher (p<0.001) compared with the first group. Vasoconstriction (EDVD<0%) and undilatation (EDVD=0%) reactions in the case of DN have been registered more often (52.1 vs. 19.1%, p<0.001). In patients with DN for the first time have been established correlations between CECs and TNF-α (Rs=0.73, p<0.001), CRP (Rs=0.53, p<0.001), FG (Rs=0.53, p<0.001), albumin (Rs=-0.43, p=0.002). Conclusions: Chronic inflammation in the constellation with endothelial damage in patients with DN in the case of HD is obviously an important factor in cardiovascular remodeling, a predictor of progression of cardiovascular complications.

The potential mechanisms of cardiovascular calcification in patients with chronic kidney disease

“…In addition, TNF-α is a chemoattractant of macrophages and Langerhans cells, a stimulant of angiogenesis, a potential activator of monocytes, adhesion molecules, enhances phagocytosis, the production of ROS, stimulates the production of proteins of the acute phase of inflammation [24]. The pro-inflammatory mediators, in particular TNF-α, promote cell degeneration, damage the endothelium, initiate inflammatory processes in the walls of arterial vessels and their calcification [5,6,20,22,24,[45][46][47]. It has been proven, that the multipotent cytokine TNF-α in CKD patients, affecting the endothelium, enhances the expression of cell adhesion molecules on it, significantly reduces the formation of basal NO and induces apoptosis and differentiation of endothelial cells [3,24,40,48].…”