Clinical and pathogenetic features of the development of endothelial dysfunction in patients with chronic kidney disease and its contribution to the development of cognitive impairments

THE AIM: to study the clinical and pathogenetic features of the development of endothelial dysfunction (ED) in patients with chronic kidney disease stages 3A-5D and its contribution to the development of cognitive impairment.

PATIENTS AND METHODS: The study included 80 patients with CKD stages 3A-5D aged from 26 to 79 years (average age 58.9 ± 1.4 years): 43 women (average age 60.1 ± 1.9 years) and 37 men (average age 57.4±2.3 years). The patients were divided into 2 groups: group 1 included 40 patients with CKD 3A-5 (average age 59.9 ± 2.1 years), group 2 included 40 patients with CKD 5D (average age 58.1 ± 2 years). All patients underwent common and biochemical blood tests, the levels of endothelial nitric oxide synthase 3 (eNOS-3) and endothelin-1 (END-1) were determined, an endothelium-dependent vasodilation test (EDVD) was performed, testing for the presence and severity of cognitive disorders using the Montreal Cognitive Assessment Scale (MoCA) and the Mini Mental State Examination (MMSE).

RESULTS: The prevalence of ED in the overall cohort of patients based on the results of a positive test with EDVD was 55 % of cases. ED was statistically significantly more often detected in the group of patients receiving hemodialysis treatment compared to patients in group 1: 70  % versus 40 %, respectively (p=0.007). The level of eNOS-3 in group 1 was higher compared to group 2 and amounted to 1.01±0.5 ng/ml versus 0.76±0.3 ng/ml (p=0.008). While the level of END-1 was statistically significantly lower in patients of group 1 compared to group 2 and amounted to 45.4±9.1 pg/ml versus 54.9±4.7 pg/ml (p<0.001). Cognitive impairments were identified in the general cohort: according to MMSE – in 67.5 % of cases, according to MoCA – in 71.3 %, and were more common in group 2. There were no statistically significant relationships between the results of the EDVD test and testing on the MoCA and MMSE scales. The level of eNOS-3 was lower in the subgroup of patients with cognitive impairment according to MoCA compared to the subgroup without it: 0.73±0.1 ng/ ml versus 0.94±0.2 ng/ml (p=0.127). The content of END-1 was statistically significantly higher in the subgroup of patients with cognitive impairment according to MoCA – 52.98±1.2 pg/ml compared to the subgroup without it – 47.67±1.5 pg/ml (p=0.043). When assessing the relationship between the levels of eNOS-3 and END-1 and the results of the EDVD test, it was found that in patients with a positive test in group 1, the level of eNOS-3 was statistically significantly higher compared to group 2 (p=0.01). An inverse relationship was observed for END-1; its level was lower in patients of group 1 compared to group 2 (p<0.01).

CONCLUSION. Thus, the study revealed a high prevalence of endothelial dysfunction in patients with CKD stages 3A-5D. Progressive loss of renal function leads to dysregulation of the molecular mechanisms controlling vascular tone and the development of ED. eNOS-3 and END-1 have demonstrated high sensitivity for ED verification, and their detection improves the quality of the EDVD test. The development and progression of ED in patients with CKD is a multifactorial process that leads to hemodynamic disturbances in various organs and tissues, their damage and has a negative impact on the patient’s quality of life, his cognitive status and life expectancy.

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