Laminines are high weighted glycosylated proteins that communicate with each other and forming at least 15 heterotrimeric macromolecules. Laminin-521 is one of the key molecules in the glomerular basal membrane and is synthesized by podocytes and endothelial cells. The majority of laminins form a cruciform structure, short globular processes of which (LN-domains) are responsible for laminin interaction in the extracellular environment. This interaction leads to polymerization of laminin, underlying the formation of the basal membrane. Polymerization of laminins forms a mesh crystalloid structure. Moreover, the polymerization of laminins in vivo does not occur in liquids, this process requires the connection of laminins with cellular receptors. Domains LG1-3 laminine are associated primarily with integrins, and LG4-5 - with α-dystroglycan (a-DG), heparan sulfate and sulfated glycolipids (sulfatide). The research of laminin mutations in the laboratory allows to study in details its probable role in the development of glomerulopathy and glomerular membrane remodeling in pathological processes.

THE AIM. Clarify the possible pathogenic relationship between markers of bone and mineral metabolism and markers of cardiovascular diseases, characterizing the state of the myocardium and aorta vessel wall in patients on renal replacement therapy. PATIENTS AND METHODS: We examined 95 patients with chronic kidney disease (CKD) VD stage: 45 men and 50 women aged from 25 to 68 years (mean age 54 ± 2,4). Levels of calcium, phosphorus, parathyroid hormone (PTH), morphogenetic protein FGF-23, cardiospecific proteins - troponin were estimated I. We studied the morphological and functional characteristics of the left ventricle (LV) and the aorta. Determined the LV myocardium mass index (LVMMI), blood flow peak systolic velocity in the aortic arch (Vps). Echocardiography with Doppler was performed on “ALOKA 4000”. RESULTS. Changes in bone and mineral metabolism, including an increase of the FGF- 23 level in patients with end-stage renal failure, were closely related to the increase in LVMMI, decrease of ejection fraction (EF) of the left ventricle and increased troponin I levels. CONCLUSION. In patients with end-stage renal failure revealed changes in bone and mineral metabolism, including increased FGF-23 levels from moderate to very high numbers, which indicates a high risk of remodeling processes in the cardiovascular system (CVS ), even when the initial absence EHO CT signs of myocardial hypertrophy and aortic lesions. It is necessary to take it into account when determing cardioprotective therapy tactics.

THE AIM: To estimate the effectiveness of nephroprotective properties of methylethylpiridinol in patients with type I diabetes mellitus (DM). PATIENTS AND METHODS. We examined 34 patients with type I DM with signs of diabetic nephropathy. All patients were treated by methylethylpiridinol. Before and after the course of therapy we determined albuminuria levels, vWF activity, adhesion and aggregation of platelets. RESULTS. Prior to treatment in patients with diabetes was diagnosed microalbuminuria MA (91.2%), increase of vWF activity, platelet adhesion and aggregation. Glomerular filtration rate decrease revealed in 60.6% of patients, and hyperfiltration in 9.1% of patients. Revealed decrease of the peak and end-diastolic flow velocity in right segmental renal artery. After treatment was detected the positive dynamics in patients. Decreased adhesion and aggregation of platelets to level of control group. Decreased vWF activity. Increased the number of patients with normal glomerular filtration rate. An improvement of blood flow in segmental renal artery. CONCLUSIONS. In patients with type I diabetes noticed the platelets functional activity increase and development of endothelial dysfunction. Therapy by methylethylpiridinol normalized these factors which provided inclusion of methylethylpiridinol in complex diabetic nephropathy treatment.

THE AIM. To estimate contribution of renin and aldosteron in development of the arterial hypertension (AH) in children with congenital vesicoureteral reflux (VUR) and a reflux nephropathy without structural and functional changes. MATERIALS AND METHODS. 75 patients with VUR aged from 3 to 18 years were examined. Depending on existence of structural and functional changes 3 groups were allocated. The 1st group - 23 children with VUR without structural and functional changes; the 2nd group of - 29 children with reflux nephropathy without AH syndrome, the 3rd group - 23 patients with a reflux nephropathy and AH. Renin and aldosterone production was estimated on the basis of determination of renin and aldosterone levels in blood plasma (supine) by enzyme linked immunoadsorbent assay. RESULTS. Renin-aldosterone system activation in 68% of 51 patients with congenital VUR is revealed. Significantly higher concentrations of a renin and aldosterone, glomerular filtration rate reduction are established in patients with reflux nephropathy with AH, AH at 56,5% of patients is followed by a hypernatremia. CONCLUSION. Reflux nephropathy is associated with high concentrations of renin and aldosterone, as the pathogenic mechanisms of the nephrosclerosis and AH formation.

THE AIM: to study the urine microbiota of healthy women during daytime. PATIENTS AND METHODS. We performed bacteriological examination of urine samples from 20 healthy sexually active women taken at different time (at 8:00, 12:00, and 16:00). Examination of the urine was performed using an extended set of culture media for facultative anaerobic and non-clostridial anaerobic bacteria. 10 culture media were used. HiAnaerobic System - Mark VI or AnaeroHiGas Pak were used to create anaerobic conditions. Calculations were performed in R software environment for statistical computing and graphics. RESULTS. Bacteriological examination of 60 urine specimens revealed no sterile samples. In the facultative anaerobic bacteria group, coagulase-negative staphylococci and Corynebacterium spp. were detected with high frequency (>60,0%) throughout the day. In the nonclostridial anaerobic bacteria group, Eubacterium spp., Peptococcus spp., Propionibacterium spp., and Lactobacillus spp. demonstrated stable association. Bacteriuria level for all microorganisms verified in the urine of healthy women in the overwhelming majority of cases was <10³ CFU/ml. Cochran’s test established the absence of significant variations in the detection frequency of different bacterial genera during the day. Except for 3 genera, no significant differences in the bacteriuria levels were revealed. Dendrograms indicate high level of similarity between the presence frequency and concentration of microorganisms at different points in time. CONCLUSION. Typical spectrum of the urine is identified in healthy women irrespectively of the time of the day.

THE AIM. To study the renal function and the severity of insulin resistance (IR), followed by evaluation of the combined risk of progression of chronic kidney disease (CKD) and cardiovascular complications in patients with obesity and existing cardiovascular disease (CVD). PATIENTS AND METHODS. The study included 140 patients with CVD between the ages of 45 to 70 years. Patients were divided into four comparable in age, sex, smoking, presence / absence of arterial hypertension (AH) and chronic heart failure (CHF), duration of hypertension, functional class (FC) of CHF, the level of office systolic blood pressure (SBP) and diastolic blood pressure (DBP) groups depending on the body mass index (BMI). We assessed the general condition, the clini- cal measurement of the heart rate (HR), and office BP in both arms according to standard procedure, the definition of CHF FC on 6-minute walk test, anthropometry with BMI calculation, measurement of waist circumference (OT) and hip circumference (ON) and body composition by the bioelectric impedance analysis. We also determined proteinuria (PU), albuminuria (AU), calculated glomerular filtration rate (GFR). We analyzed the combined risk of CKD progression and cardiovascular complications, depending on the GFR and the AU. To assess the current IR we used index HOMA-IR, triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) ratio and the metabolic index (MI) with the use of carbohydrate and lipid parameters. RESULTS. There was a significant increase in the level of PU among patients group 4 compared to group 1 (560,19 ± 454,59 mg / g vs 330,8 ± 85,0 mg / g) and a statistically significant decrease in GFR in patients 3 and 4 groups compared with patients of group 1 (65,83 ± 13,39 and 64,06 ± 14,52 ml / min / 1.73 m 2, respectively, vs 74,94 ± 13,68 ml / min / 1.73 m2). Reliable average power detected correlation between the severity of visceral obesity and AU (r = 0,452), PU (r = 0,360), and GFR (r = -0,491). Analysis of the combined risk of CKD progression and cardiovascular complications showed a significant increase in very high-risk patients in the comparison group and 4 patients 1, 2 and 3 groups (68,6% vs 25, 39.8 and 40%, respectively). In assessing the indices that characterize the severity of IR, a statistically significant increase in HOMA-IR, TG / HSLPVP, MI with increasing BMI from group 1 to group 4 was established. We noted a high fidelity direct strong correlation between the level of visceral fat in the body, and HOMA-IR (r = 0,821), TG / HSLPVP (r = 0,806), MI (r = 0,812). CONCLUSION. The study showed a statistically significant progressive deterioration of renal function and an increase in the severity of IR as well as the increase in the combined risk of progression of CKD and cardiovascular events in patients with CVD with an increase in obesity during the comparable values of SBP office, DBP office and CHF FC among the studied groups. There were significant correlations between parameters of renal function and visceral obesity.

THE AIM: to study features of ferrokinetic in hemodialysis patients according to the level of soluble receptors of transferrin and ferritin index. PATIENTS AND METHODS. Research included 100 patients with chronic kidney disease 5D stage receiving hemodialysis, among them 51 women and 49 men, mean age was 53,4±15,8 years. All patients were performed complex clinical and laboratory tests. RESULTS. The increasing concentration of soluble transferrin receptors was observed in 44% of patients that can be caused by iron deficiency and increased erythropoiesis in response to therapy with erythropoietin. The level of hemoglobin is not varied depending on the concentration of soluble transferrin receptors. The estimation of genesis of anemia based on the ferritin index allowed to identify a higher frequency of anemia of chronic disease (92,5%) than using the traditional approach based on the level of ferritin and transferrin saturation (functional iron deficiency in 9% of patients). The combination of anemia in chronic disease with iron deficiency associated with low iron concentration and a high level of hepcidin. The negative role of hypoalbuminemia on the iron level, transferrin saturation and soluble receptor of transferrin was demonstrated (p<0.05). CONCLUSION. In dialysis patients for a comprehensive evaluation of iron metabolism, it is advisable to perform a study of soluble transferrin receptors and the calculation of ferritin index, which allow to assess the anemic syndrome formation pathogenetic mechanisms.

THE AIM. Assessment of the relationship of renal tissue remodeling and small diameter arteries in patients with various forms of glomerulopathy. PATIENTS AND METHODS. The study included 30 patients with primary kidney disease. All investigated were performed kidney biopsy with the morphological assessment of structural changes in the kidney tissue (including morphometric analysis of interlobular artery) and morphological variant of glomerulonephritis. RESULTS. According to the results of the study revealed the presence of the direct proportional correlation between the restructuring of the interlobular artery walls and blood pressure value, as well as the severity of tubulointerstitial inflammation. The relationship between the decrease in lumen interlobular artery and different stages of glomerulosclerosis development (thickening of the glomerular capillary walls, fusion and obliteration of capillary loops, the formation of fibro-cellular crescents). Moreover, it was found that the fibrosis of interlobular arteries walls increases the risk of glomerulosclerosis. CONCLUSION. The findings testify that there is a single pathogenic process of remodeling of renal tissue and blood vessel walls of small diameter in patients with primary kidney diseases of different etiologies.

THE AIM: to identify cognitive dysfunctions relationship with arterial hypertension in young and middle aged patients with chronic kidney disease. PATIENTS AND METHODS. 108 young and middle aged patients with chronic glomerulonephritis of 1-3 stages chronic kidney disease were examined. 71 (65.7%) patients were diagnosed chronic glomerulonephritis which was proved morphologically. Cognitive dysfunctions were assessed with MMSE survey and software package Status PF. All the patients were performed 24-hour blood pressure monitoring tested. RESULTS. All the patients at the 1st stage were tested with MMSE survey, cognitive dysfunctions like pre-demension state were identified in 3 (2,7%) patients. These patients were excluded from the study. 65 patients (60,2%) were diagnosed arterial hypertension. The patients with chronic kidney disease demonstrated statistically significant positive correlation with neurodynamic indices and average systolic and diastolic blood pressure indices at day and night time. Positive correlation between average exposure dose of visual-motor coordination and morning systolic blood pressure level was identified (r=0,29 p=0,02). The analysis demonstrates the 24-hour blood pressure indices correlation with the reaction to the moving object. The research revealed statistically significant differences between minimum and average exposure dose of simple visual motor reaction; minimum and average exposure dose of complex visual motor reaction (p=0,012; p=0,024) by comparison of groups with AH and without AH. The mechanic memory span and the span of attention were significantly less in the group of patients with arterial hypertension comparing to the group without arterial hypertension. CONCLUSION. Patients with chronic kidney disease of 1-3 stages and concomitant arterial hypertension demonstrated lower neurodynamic, attention and memory indices comparing to the group without arterial hypertension.

INTRODUCTION. The epidemiology of diabetic nephropathy (DN) in type 2 diabetes mellitus (DM) is investigated insufficiently since precisely extremely difficult to determine the time of the DN beginning. THE AIM: to search of molecular prognostic markers of DN 1 stage in patients with type 2 DM. PATIENTS AND METHODS. We have verified DN 1 stage patients with type 2 DM (n=42) in study. Control group included 30 healthy persons. The duration of DM was 5,6 years. At the stage of data collection and screening are applied standard methods of DN identification. Qualitative and quantitative molecular phenotyping of urine processed with methods in proteomics (MALDI-TOF-MS/MS, Ultraflex II, «Bruker», USA). The data of the molecular interactions were received with STRING 10.0 database. Statistical analysis was performed using the software “Statistica 12.0” (Statsoft, Russia). RESULTS. We identified potentially new biomarkers of DN 1 stage which could be used to create a noninvasive, urine-based diagnostic tests. The research of signaling pathways and the molecules that influence expression, secretion and amassing of extracellular matrix may aid in strategies for the prophylaxis of DN

THE AIM: to study of the cardiorenal relationships in patients with metabolic syndrome (MS). PATIENTS AND METHODS. 100 examined patients were divided into 4 groups: group 1 of 35 patients with primary pathology of the cardiovascular system (control), group 2 - 17 patients with cardiorenal syndrome 2 type (CRS2), group 3 - 19 patients with MS, group 4 - 29 patients with combined MS and KRS2. RESULTS. Patients of the 4th group revealed the highest disease duration, comorbidity, dyslipidemia and renal dysfunction. Also, only in patients of this group the need to perform coronary stenting was increased 3.6 times. Glomerular filtration rate (GFR) negatively correlated with the index of left ventricle myocardial mass and the end-diastolic volume of the left ventricle, despite the fact that the last two indicators did not exceed normal values. In patients of all groups noted the lack of character of cardio/renal protection therapy. CONCLUSION. The development of metabolic disorders and decrease in GFR caused by inadequate treatment of the underlying disease of the cardiovascular system and the absence of lifestyle changes. It is necessary to perform GFR monitoring in all patients with a primary pathology of the cardiovascular system, since the age of 40 years. Increase age declining more than 1 ml/min/1,73m² per year requires correction of the treatment.

AIM: to examine the effect of diets with different contents of sodium chloride on blood pressure (BP), remodeling of the myocardium and the parameters of sodium homeostasis in spontaneously hypertensive rats (SHR). MATERIAL AND METHODS. We studied two groups of animals. First group received during 2 months diet containing 0.34% NaCl, second - high salt diet (8.0 %) NaCl. The blood pressure (BP) was recorded at the end of the observation period. In serum and in daily urine sodium concentration was determined. The study of morphological changes in the myocardium was performed on the light-optical level. RESULTS. The level of BP did not differ between groups, myocardial mass index, left ventricular mass index, sodium concentration in the urine, daily urine volume and sodium excretion were higher in animals fed a diet containing 8% NaCl. In rats from this group increase of cardiomyocytes fibers hypertrophy severity, mild perivascular fibrosis and moderate hypertrophy of smooth muscle cells of the vessel walls were revealed. CONCLUSION. Results of the study suggest that the high sodium chloride diet in SHR rats leads to a unique profile of myocardial remodeling, which is not determined exclusively by the increase of blood pressure.

THE AIM of the study was to explore some of the pathogenic mechanisms of renal function disturbances during long-term administration of cadmium sulfate and preventive effects of Acyzol - an antihypoxant and antioxidant drug. MATERIALS AND METHODS. The work was carried out on 60 male Wistar rats, divided into three groups: intact; control with insolated cadmium sulfate administration at a dose of 0.1 mg / kg body weight; studied - with prophylactic Acyzol administration on the background of cadmium salts intake at the same dosage. The urine-generatory renal function, sodium and urea concentration in kidney tissue layers and Na+/K+-ATPase activity were studied. RESULTS. In animals with cadmium sulphate introduction the increase in the spontaneous six-hour urine output and sodium excretion, caused by reducing of water and cation reabsorption, marked proteinuria were observed. These changes correlated with the reduce in sodium and urea concentrations in all the layers of the kidneys, which also corresponded to the decrease in activity of the enzyme - Na+/K+-ATPase in kidney tissue layers. Acyzol injections to the animals on the background of cadmium intoxication led to the decrease of the severity of tubular reabsorption disorders, some recovery in activity of Na+/K+-ATPase, marked reduction of proteinuria. In the histological picture the differences between the groups with the isolated administration of cadmium salts and combined administration of cadmium sulfate and Acyzol were presented by the decrease of the severity of all pathological processes manifestations. The number of the tubules with preserved lumen was increased. CONCLUSION. Thus, the positive effect of Acyzol, which led to the decrease of the severity of the structural and functional changes in the renal nephrons tubular unit became evident. In the basis of Acyzol protective effect, obviously, lied its antihypoxic effect, which decreased the tubular hypoxic damage, caused by heavy metals

THE AIM: to examine the effect of diets with different contents of sodium chloride on blood pressure (BP), remodeling of the myocardium and the parameters of sodium homeostasis in spontaneously hypertensive rats (SHR). MATERIAL AND METHODS. We studied two groups of animals. Firs group received 2 months diet containing 0.34% NaCl, second - high salt diet (8.0 %) NaCl. The blood pressure (BP) was recorded at the end of the observation period. In serum and in daily urine sodium concentration was determined. The study of morphological changes in the myocardium was performed on the light-optical level. RESULTS. The level of BP did not differ between groups, myocardial mass index, index of left ventricular mass, sodium concentration in the urine, daily urine volume and sodium excretion were higher in animals fed a diet containing 8 % NaCl. In rats from this group increasing of the severity of hypertrophy of cardiomyocytes fibers, mild perivascular fibrosis and moderate hypertrophy of smooth muscle cells of the vessel walls were revealed. CONCLUSION. Results of the study suggest that the high sodium chloride diet in SHR rats leads to a unique profile of myocardial remodeling, which is not determined exclusively by the increase of blood pressure.