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.

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&lt;0.001), CRP (9.94±1.12 vs. 7.07±1.09 mg/L, Z=3.47, p&lt;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&lt;0.001), NO2– (Rs=-0.56, p&lt;0.001), СECs (Rs=0.63, p&lt;0.001) and СRP (Rs=0.54, p&lt;0.001). The MVC as well as AVC degree were related with the level of FMD (Rs=-0.47, p&lt;0.001; Rs=-0.43, p=0.003), content of NO2– (Rs=-0.40, p=0.005; Rs=-0.62, p&lt;0.001), СECs (Rs=0.47, p&lt;0.001; Rs=0.62, p&lt;0.001) and СRP (Rs=0.48, p&lt;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&lt;0.001) – lower compared to non-diabetic ones, and in 2nd group indices of TNF-α and Mg were related (Rs=-0.68, p&lt;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&lt;0.001) and Mg (Rs=-0.57, p&lt;0.001). The MVC as well as AVC degree were related with the content of TNF-α (Rs=0.49, p&lt;0.001; Rs=0.52, p&lt;0.001) and Mg concentration (Rs=-0.47, p&lt;0.001; Rs=-0.50, p&lt;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.

Background and Aims According to population registries, the survival of diabetic patients with end-stage-renal disease (ESRD) remains low today. In this context, it is reasonable to develop new therapeutic strategies based on advances in science of the important role of magnesium (Mg) and L-carnitine deficiency (via inflammation and endothelial dysfunction) in mechanisms of cardiovascular remodeling, high morbidity and mortality rates. Thus, the purpose of the present study was to evaluate the effect of Mg and L-carnitine supplementation on 3-year survival and development of the cardiovascular complications in diabetic hemodialysis (HD) patients. Method 48 type 2 diabetic ESRD patients were included in this prospective cohort study (male/female, 29/19; age, 59.9±0.6 years; HD duration, 34.8±4.8 month; diabetes mellitus duration, 174.7±7.1 month). The study was performed in accordance with the provisions of the Declaration of Helsinki last revision. Depending on the treatment programme, patients were divided into two groups: the 1st (main) group (n=24) in addition to basic treatment (hypoglycemic, antihypertensive therapy, according to indications - correction of anemia, hyperparathyroidism, hyperphosphatemia) was treated by combination of magnesium aspartate (0.5 g/day orally) and L-carnitine (1 g/day parenterally after each HD session (three times weekly); the 2nd (comparison) group (n=24) was only on the basic therapy. Complex treatment lasted 12-months; administration of L-carnitine was performed continuously throughout the year, while magnesium aspartate – by three 2-months’ courses/year. The follow up period in both groups was 36 months. Quantitative data are expressed as means±SEM, qualitative ones – as %. Kaplan-Meier method and Log-rank test were used to estimate survival of HD patients, χ2-test – to compare the frequency values. Results The cumulative proportion of survivors at the end of follow-up was 60.4%; however, after 36 months, the survival rate of diabetic HD patients who received a combination of magnesium aspartate and L-carnitine as part of their modified treatment was significantly higher (75 vs. 45.8%; Log-rank=2.07, p=0.038) compared to patients who were on basic therapy (Figure). Survival time in main and comparison groups was 31.9±1.7 and 26.4±2.2 months respectively. It is noteworthy, that throughout the year (from 10 to 22 months), no completed events were recorded in subjects who underwent Mg and L-carnitine supplementation. Conclusion (1) The combined use of magnesium aspartate and L-carnitine in addition to the basic 12-month treatment provides an effective reduction of cardiovascular complications and promotes 3-year survival of diabetic HD patients. (2) The results obtained substantiate the advisability of using repeated courses of Mg and L-carnitine administration 1 years after the end of the primary modified treatment to improve the prognosis in these ESRD patients.

Systematic analysis of cardiac remodeling peculiarities in patients with V D stage of chronic kidney disease (CKD VD)  caused by diabetes mellitus is important both in the stratification of cardiovascular risk and in the choice of adequate treatment strategies. The purpose of the study was to determine the character of structural and functional reconstruction of myocardium in patients with diabetic nephropathy (DN) on maintenance hemodialysis (HD) by identifying left ventricular hypertrophy (LVH), its geometric types, assessment of the severity of heart dysfunction, pulmonary hypertension (PH), as well as determination of frequency of cardiac valve calcification (CVC), development of defects of mitral (MV) and aortic (AV) valves. Materials and methods. The study included 136 patients on chronic HD (men, 78, age, (53,9±1,0) years, duration of HD, (47,6±4,2) months). Depending on the presence/absence of type 2 diabetes mellitus (DM) with kidney damage, they were divided into two groups: the first one – without DN (n=88); the second one – with DN (n=48). All patients were followed up by standard echocardiography (EchoCG) examination by standard procedure. Results. LVH was diagnosed in 84.6% of patients with CKD VD stage, significantly more often (93.8 vs. 78.4%, p=0.020) in patients with DN, with the incidence of eccentric LVH in the second group being higher (47.9 vs. 28.4%, p=0.023) than in the first one. Prevalence of pseudonormal and restrictive types of LV diastolic dysfunction (62.5 vs. 28.4%, p<0.001), LV systolic dysfunction (27.1 vs. 9.1%, p=0.006) and PH (64.6 vs 35.2%, p=0.001) were significant in HD patients with DN. CVC was detected in 66.6% of patients with type 2 DM with renal injury with a predominance of calcification of both valves (35.4%) over isolated calcification of MV (MVC) (20.8%) and AV (AVC) (10.4 %). Combined valve calcification in the HD patients of the second group was observed 2.6 times more often (p=0.003) than in the first one. Patients with DN, unlike those without diabetes, were associated with a higher prevalence of stenoses of MV (16.7 vs. 3.4%, p=0.007) and AV (39.6 vs. 15.9%, p=0.004), and insufficiency of MV (66.7 vs. 44.3%, p=0.013) and AV (35.4 vs. 14.8%, p=0.006). The most significant EchoCG parameters that distinguished groups of HD patients with the presence of DN were: left atrial diameter (p<0.001), end-diastolic LV dimension (p<0.001), thickness of interventricular septum (p=0.001), LV myocardial mass index (p=0.001), ratio of transmitral flows in early and late diastole (p=0.009), time of deceleration of early diastolic transmitral blood flow (p<0.001), LV ejection fraction (p=0.009), diameter of the right ventricle (RV) (p=0.003), diameter (p=0.007) and mean pulmonary artery pressure (p<0.001). Conclusions. In patients with CKD VD stage with DN the maladaptive cardiac remodeling with predominance of unfavorable types (eccentric (to a greater extent) and concentric) LV hypertrophy, RV dilatation, PH, expressive of LV diastolic and systolic dysfunction, large-scale combined MVC and AVC occurs, which, in turn, leads to the formation of valve defects, can contribute to the progression of diastolic myocardial stiffness and heart failure.