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Background and Aims The character of endothelial dysfunction (ED), especially of nitric oxide (NO) system, in patients with diabetic kidney disease (DKD) undergoing chronic hemodialysis (HD) was not asserted enough. In this condition not clearly established the relationship of structural and functional activity of endothelium with the presence and severity of cardiac valve calcification (CVC) as independent predictor of cardiovascular morbidity and mortality. The purpose of the current study was to determine the role of ED in mechanisms of mitral (MVC) and aortic (AVC) valve calcification in HD patients with DKD. 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. According to the study design, depending on the presence of type 2 diabetes mellitus with kidney injury patients were divided into two groups: the 1st one – without DKD (n=88); the 2nd one – with DKD (n=48). All subjects underwent echocardiographical examination for detection of CVC; the MVC and AVC degree were scored as follows: 1, no calcification; 2, valve thickening without calcification; 3, valve annulus or cusps calcification. Vasomotional function of endothelium was assessed using a test with reactive hyperemia (brachial artery flow-mediated dilatation (FMD)). Plasma content of nitrites (NO2), circulating endothelial cells (СECs) and serum concentration of C-reactive protein (CRP) were measured as markers of ED. Data are expressed as means±SEM. Used nonparametric statistics methods: Mann-Whitney U-test, χ2-test, Spearman’s rank R correlations. Results In group of HD patients with DKD indices of СECs (22.3±1.3 vs. 14.2±0.7 × 104/L, Z=4.98, p<0.001), CRP (9.94±1.12 vs. 7.07±1.09 mg/L, Z=3.47, p<0.001) were higher, and NO2 (4.16±0.41 vs. 9.01±1.37 umol/L, Z=3.15, p=0.002), FMD (2.27±0.66 vs. 5.13±0.52%, Z=3.26, p=0.001) – lower compared to the group without diabetes. CVC was detected in 66.6% of patients with DKD with predominance of calcification of both valves (35.4%) over isolated MVC (20.8%) and AVC (10.4 %). Combined valve calcification in the HD patients of 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 DKD the presence of CVC closely associated with indices of FMD (Rs=-0.59, p<0.001), NO2– (Rs=-0.56, p<0.001), СECs (Rs=0.63, p<0.001) and СRP (Rs=0.54, p<0.001). The MVC as well as AVC degree were related with the level of FMD (Rs=-0.47, p<0.001; Rs=-0.43, p=0.003), content of NO2– (Rs=-0.40, p=0.005; Rs=-0.62, p<0.001), СECs (Rs=0.47, p<0.001; Rs=0.62, p<0.001) and СRP (Rs=0.48, p<0.001; Rs=0.41, p=0.004) concentrations respectively. Conclusion (1) HD patients with DKD are combined with damaged endothelium, disturbance of vasoreactivity and lack of NO. (2) Type 2 diabetes mellitus with kidney injury is characterized by the large-scale combined MVC and AVC, which in turn are closely associated with the ED markers. (3) Complex estimation of the character of CVC and endothelium activity in HD patients with DKD permits a better identification of their cardiovascular risk.

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.

Purpose. To study the effect of a single hemodialysis (HD) session on the endothelial structure and function by analyzing the contents of nitric oxide (NO) stable metabolites and circulating endothelial cells (CECs) number, and to establish the interrelation between the oxidative stress (OS) marker malondialdehyde (MDA) and endothelial dysfunction indices in patients with end-stage renal disease (ESRD). Material and methods. The study included 20 chronic HD patients (9 men aged 41,0±3,0 years; HD duration, (40,4±4,8) months). Patients with chronic glomerulonephritis (65%) dominated. Plasma content of MDA, the activity of superoxide dismutase (SOD) and catalase (CT) in erythrocytes, blood content of SH-groups were measured before and after the HD session by standard methods. Plasma content of nitrite-( NO2-) and nitrate anion (NO3-) was estimated by the spectrophotometric method, and CEC amount in platelet-rich plasma ss described by Hladovec J. et al., 1978 in our modification. Results. After the HD session NO2- content decreased by 18,4% (p<0,001), NO3- by 13,4% (p=0,007), while CEC number did not significantly change (p=0,478). Due to HD the content of MDA increased by 10,5% (p=0,007), the activity of SOD, CT increased by 8,9% (p=0,005) and 16,2% (p=0,016) respectively, and the concentration of SH-groups decreased by 20,8% (p<0,001). Significant correlation between the content of MDA and NO2- (Rs=-0,56, p=0,010), CECs amount (Rs=0,52, p=0,018) was established; the CEC number was in turn related to the level of NO2- (Rs=-0,58, p=0,007). Conclusions. The HD session is associated with the development of OS, lack of NO and possibly endothelial damage which confirms practicability of endothelial protection, in particular modulation of the L-arginine-NO system, during HD session in patients with ESRD.