Mo741tumor Necrosis Factor Alpha and Magnesium Are Linked to Cardiac Valve Calcification in Diabetic Hemodialysis Patients

Abstract

Background and Aims The processes of cardiac valve calcification (CVC) in diabetic hemodialysis (HD) patients are not fully understood. In this context, it is reasonable to complex and comprehensively research the activity of chronic inflammation and magnesium (Mg) imbalance as cardiovascular risk factors in end-stage renal disease (ESRD). The main purpose of the current study was to determine the relationship of tumor necrosis factor alpha (TNF-α) and Mg levels with the presence and severity of CVC in diabetic patients with ESRD. Method We enrolled 136 patients undergoing HD (male/female, 78/58;age, 53.9±1.0 years; HD duration, 47.6±4.2 month) in this observational cross-sectional study. The study was performed in accordance with the provisions of the Declaration of Helsinki last revision. Depending on the presence of type 2 diabetes mellitus (T2DM) all subjects were divided into two groups: the 1st one – non-diabetic patients (n=88); the 2nd one – diabetic patients (n=48). Presence of CVC was detected by ultrasound. The mitral (MVC) and aortic (AVC) valve calcification degree were scored as follows: 1, no calcification; 2, valve thickening without calcification; 3, valve annulus or cusps calcification. Serum content of TNF-α as one of the key proinflammatory cytokine was determined by enzyme-linked immunosorbent assay. Serum Mg concentration was estimated by biochemical method. Data are expressed as means±SEM. Used nonparametric statistics methods: Mann-Whitney U-test, χ2-test, Spearman’s rank R correlations. Results In diabetic HD patients TNF-α content was higher (13.86±1.34 vs. 8.73±0.60 ng/L; Z=3.04, p=0.002) whereas Mg concentration (0.87±0.02 vs. 1.00±0.02 mmol/L; Z=4.91, p<0.001) – lower compared to non-diabetic ones, and in 2nd group indices of TNF-α and Mg were related (Rs=-0.68, p<0.001). CVC was detected in 66.6% of T2DM patients with predominance of calcification of both valves (35.4%) over isolated MVC (20.8%) and AVC (10.4%). Combined MVC and AVC in the 2nd group was observed 2.6 times more often (χ2=8.78, p=0.003) than in the 1st one. For the first time it was established that in diabetic patients with ESRD the presence of CVC closely associated with indices of TNF-α (Rs=0.51, p<0.001) and Mg (Rs=-0.57, p<0.001). The MVC as well as AVC degree were related with the content of TNF-α (Rs=0.49, p<0.001; Rs=0.52, p<0.001) and Mg concentration (Rs=-0.47, p<0.001; Rs=-0.50, p<0.001) respectively. Conclusion (1) T2DM in HD patients is characterized with an increase of serum TNF-α activity and simultaneous decreased of Mg content. (2) In diabetic patients with ESRD, both MVC and AVC are closely linked with the TNF-α accumulation and hypomagnesemia. (3) Chronic inflammation and Mg deficiency can be important factors of CVC progression and very high cardiovascular risk in diabetic HD patients.

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].…”