Application of Meldonium for the Treatment of Patients with Diabetic Nephropathy

Introduction. Today, the life expectancy of people with diabetes mellitus (DM) has increased by several times. Mortality due to the acute complications of diabetes, such as diabetic coma, does not exceed 1.0%. But simultaneously with an increase in the life expectancy of patients with diabetes, the problem of vascular complications intensified. Endothelial dysfunction present in the patients with DM leads to the formation of diabetic nephropathy (DN), the activation of the predominant components of the renin-angiotensin system (RAS), progression of arterial hypertension (AH) with the remodeling of the entire vascular system of the organism. Aim. To determine the effect of Meldonium on the exchange of nitric oxide (NO) and cardiac hemodynamics in the patients with DM using basic organoprotective treatment. Materials and methods. We examined 360 patients with diabetes and DN of I-IV stages by the classification of D. E. Mogensen (1983), mean age of patients 58.6 ± 6.1 years, comparison group – 80 patients with arterial hypertension (AH) of II-III stages of the corresponding age, control group – 20 practically healthy people (26.2 ± 3.4) years old. The state of NO exchange and the observation of cardiac hemodynamics have been determined. The content of nitrite in plasma of venous blood was determined by the photometric method by the P. Griess reaction, the content of NO metabolites – by the P. Griess reaction after the reduction of nitrate to nitrite by zinc dust. Cardiac hemodynamics was studied by quantitative echocardiography with the calculation of cardioghemodynamics parameters according to L. Teicholz et al. (1972) and synchronic recording of the electrocardiograms. Treatment of the patients using angiotensin-converting enzyme (ACE) inhibitors (lisinopril 10.0-20.0 mg/day) and calcium channel blockers (CCB) (lercanidipine 10.0-20.0 mg/day) were given to 146 patients. Combination treatment using CCB and Meldonium (Novofarm-Biosynthesis) received 68 patients. Meldonium was administered intravenously over 10.0 ml for 10 days, followed by oral administration of 1000.0 mg per day for a month. Results. The analysis of the obtained results showed that in patients with diabetic nephropathy the manifestation of endothelial dysfunction is progressing and a “diabetic heart” is being formed. These changes occur in the presence of proliferative processes and myocardial fibrosis. In the patients with DN, starting at stage III, there is a disorders of the systolic function of the heart, which subsequently leads to heart failure. Medications of the basic treatment (ACE inhibitors and CCB) have a positive effect both on endothelial dysfunction and on structural changes of the myocardium, protecting it from the further remodeling. The additional use of Meldonium promotes the further improvement of the morphological structure and contractile function of the myocardium through its complex effects on metabolic processes and the exchange of NO. Сonclusions. Application of Meldonium combined with the medicines of the basic therapy in the patients with the diabetic nephropathy leads to an improvement of the morphological structure and myocardial contractile function owing to the complex effects on the metabolic processes and the NO exchange.