Hyperhomocysteinemia in patients with chronic kidney disease and its relationship with the functional status of the cardiovascular system

Abstract

Chronic kidney disease (CKD) is an important medical, social and economic problem nowadays. Patients with CKD are known to have an increased risk of development and progression of cardiovascular diseases. However, the causes and pathogenesis of cardiovascular complications are not well understood. One of the recently recognized “non-traditional” risk factors for the increased development of cardiovascular pathology in severe stages of CKD is hyperhomocysteinemia (HHC). The article presents the results of study of HHC frequency in patients with different stages of CKD as well as the relationship between HHC and endothelial dysfunction and structural-functional status of the heart. The study involved 148 persons with different stages of CKD who underwent immunoenzyme determination of total plasma homocysteine (HC), echocardiography, carotid ultrasonograghy, endothelial function was assessed as well. It was found that among the patients with CKD, 26 (21.1%) had normal and 34 (27.7%) had subnormal HC levels, mild HHC was observed in 30 (24.4%) and moderate HHC – in 33 (26.8%) cases, i.e. the total number of patients with elevated HC level was 88.9%. It should be noted that no patients with normal HC level were found among those with stage four CKD as well as in dialysis patients. The increase of blood plasma HC level was actually proportional to the severity of renal failure, which in its turn led to the shift in the number of cases towards higher rank indices of HHC level. In particular, while there were no patients with HHC among those with CKD-I, more than 50% of such patients were found in the group with CKD-V. Reduced myocardial contractility and echocardiographic markers of left ventricular hypertrophy in patients with CKD were found to be closely associated with HC concentrations in blood plasma. The data presented clearly demonstrate strong inverse correlation between endothelial dysfunction indices and HC level. So, the endothelium-dependent brachial artery vasodilation in patients with CKD-IV was lower by 3.8 and 1.5 times compared with control group and CKD-III group, respectively, and endothelium-independent vasodilation of the brachial artery – by 2.4 and 1.9 times, respectively. Correlation analysis also confirmed that impaired endothelium-dependent and endothelium-independent dilation with high statistical significance inversely correlated with the level of HC in blood plasma. Thus, the population of patients with CKD is characterized by high HHC frequency, which is closely associated with cardiovascular disorders (endothelial dysfunction, structural and functional remodelling of the myocardium) and can be an important risk factor for the development of vascular lesions. We believe that adequate correction of HHC, including administration of folic acid preparations could reduce the progression of vascular lesions in patients with CKD.

Keywords

• homocysteine
• renal failure
• left ventricular hypertrophy
• myocardial contractile function
• endothelial dysfunction