Abstract
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.
Association Between Classical and Emerging Risk Factors for Diabetic Kidney Disease and Albuminuria in a Cohort of Type 2 Diabetes Mellitus Patients