Obesity and overweight are recognized as epidemics of non-communicable diseases in the 21st century. The kidneys are a target organ for obesity, damage to which is considered to be an independent risk factor for the development of renal failure. Obesity-related glomerulopathy (OGP) is one of the types of renal injury in obesity, which is characterized by the development of proteinuria in patients with a body mass index (BMI) of >30 kg/m2 in the absence of other causes of kidney damage. The pathogenesis of OGP is multifactorial. It is associated with intrarenal hemodynamic disorders - the development of renal hyperfiltration, the damaging action of adipose tissue hormones (hyperleptinemia, activation of the renin-angiotensin-aldosterone system, decreased production of adiponectin); with ectopic lipid accumulation in the kidney. The morphological pattern of OGP is characterized by a low glomerular density (oligonephronia) that leads to glomerular and tubular hypertrophy; by the development of perihilar focal segmental glomerulosclerosis (FSGS), obvious podocyte damages, and the development of a fatty kidney. The clinical picture of OGP is characterized by the slow and gradual development of albuminuria, not exceeding Stage A3 (300-1999 mg/day). Approximately one-third of patients develop partial nephrotic syndrome with massive proteinuria, but without edema and hypoproteinemia. Complete nephrotic syndrome is observed in not more than 6% of patients with OGP. In the course of the disease, 50% of patients develop hypertension and more than 80% do dyslipidemia. Stages IV-V chronic kidney disease may develop 20-30 years after the disease occurs.

AIM:To study the association of the polymorphic markers (PMs) G(-238)A of the TNF gene, G(-174)C of the IL-6 gene, and G(-1082)A of the IL-10 gene with the clinical characteristics of chronic glomerulonephritis (CGN) and a response to immunosuppressive therapy (IST).SUBJECTS AND METHODS:Clinical syndromes at the time of diagnosis, the morphological types of nephritis, and a response to IST were analyzed in relation to the carriage of the examined PMs of the TNF, IL-6, and IL-10 genes in 102 patients with CGN.RESULTS:No association was found between the PM G(-238)A of the TNF gene and the clinical features of CGN. The carriers of the C allele of the PM G(-174) C of the IL-6 gene versus the homozygous individuals were observed to have more frequently kidney dysfunction at the time of diagnosis (р=0.014). Hypertension was more common in the carriers of the AA genotype of the PM G(-1082)A of the IL-10 gene (p=0.023); moreover, they tended to have a more frequent concurrence of nephrotic syndrome and hypertension (p=0.082). Analysis of the distribution of the morphological types of CGN disclosed that the proliferative variants were more common in the patients with the GG genotype (the TNF gene) as compared to the A allele carriers (p=0.067); and the nonproliferative forms were in the individuals homozygous for GG (the IL-6 gene) as compared to the C allele carriers (p=0.067). Examination of an IST response showed that a complete response at 12 months of treatment occurred more frequently in the carriers of the C allele of the IL-6 gene (p=0.045) and in those of the GG genotypes of the IL-10 gene (p=0.030).CONCLUSION:There was an association of the PMs G(-174)C of the IL-6 gene and G(-1082)A of the IL-10 gene with the clinical features of CGN and a response to IST.

Investigation data presented revealed association between pulmonary hypertension and the stage of chronic renal disease. It was shown that development of pulmonary hypertension was noted at the earliest stages of the chronic renal disease (when glomerular filtration rate decreased to < 80 ml/min) and the rate of hypertension development increased with the progression of the disease.

Development of risk factors of the common carotrid and femoral arteries stiffness was assessed in patients with pre-dialysis chronic renal disease of non-diabetic etiology. It was shown that vascular remodeling was affected by the conventional risk factors such as patients'' age, hypertension, and smoking. A trend to existence of dependence between renal risk factors (hypercreatinemia and disturbances of phosphor-calcium metabolism) and rigidity of the common carotid arteries is also noted.

Association of polymorphic ADPRT1 gene Val762Ala marker, encoding poly(ADP-ribose)polymerase-l, with the development, course and progress of chronic glomerulonephritis was revealed during investigation. The risk of the chronic glomerulonephritis development is higher in patients-carriers of Val-allele and Val/Val-genotype and lower in those with Ala-allele and Ala/Ala-genotype.

AIM:To investigate the incidence and risk factors of pulmonary hypertension (PH) in patients with chronic kidney disease (CKD). SUBJECTS AND METHODS:86 patients (53% men, 47% women; mean age, 45±13 years) with nondiabetic CKD were examined. According to the magnitude of glomerular filtration rate (GFR) decrease, all the patients were divided into 3 groups: 1) 33 patients with a GFR of 89--45 ml/min; 2) 33 with a GFR of 44--15 ml/min; 3) 20 with a GFR of <15 ml/min who were treated with hemodialysis. A control group consisted of 20 individuals with preserved kidney function (a GFR of >90 ml/min). Physical examination and transthoracic echocardiography were performed in all the patients. The serum concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNT) and cystatin C were determined. RESULTS:PH was detected in 21 (24.4%) of the 86 patients with CKD. As CKD progressed, its prevalence in Groups 1, 2, and 3 increased, amounting to 18.2, 24.2, and 35%, respectively. The most predictably significant risk factors for PH were hypertension (ρ=0.35; р=0.001) and kidney dysfunction (creatinine (ρ=0.23; р=0.02). Elevated pulmonary artery systolic pressure (PASP) correlated with right ventricular (RV) dimension index (ρ=0.45; р<0.0001), right atrial volume index (ρ=0.3; р=0.02), left atrial volume index (ρ=0.3; р=0.009), and left ventricular mass index (ρ=0.35; р=0.03). In all the patients with CKD in the presence of PH, the NT-proBNP level was significantly higher than in its absence: 37.43 (5.83; 59.84) and 8.54 (5.1; 20.43) fmol/ml, respectively (р=0.01). Positive correlations were found between the level of cystatin C and the presence of PH (ρ=0.32; р=0.003). Analysis of the ROC curve (AUC=0.718; р=0.03) in the predialysis-stage CKD groups (n=66) revealed that the cystatin C level of > 1045 ng/ml with a sensitivity of 71% and a specificity of 60% suggested that PH was present. Multivariate analysis showed that the factors correlating with the presence of PH were NT-proBNP (β=0.34; р=0.008) and RV dimension index (β=0.3; р=0.002). CONCLUSION:EchoCG reveals PH in almost 25% of the patients with CKD, which occurs at its predialysis stage. Elevated PASP is associated with myocardial structural changes. Traditional risk factors (hypertension) and diminished kidney function affect the development of PH.

Renal disorder is associated with high frequency of cardiovascular complications. The review summarizes data of a new entity of cardiorenal syndrome - pulmonary hypertension development in patients with chronic kidney disease (CKD). Its prevalence, potential pathogenic mechanisms, prognostic value and possible treatment in patients with CKD are discussed.

Aim. To estimate the diagnostic value of serum cystatin C in the development of left ventricular hypertrophy (LVH) in patients with chronic kidney disease (CKD).Subjects and methods. The investigation enrolled 86 patients (53% men, 47% women; mean age, 45+/-13 years) with nondiabetic CKD. According to the magnitude of glomerular filtration rate (GFR) decrease, the patents were divided into 3 groups: 1) 33 patients with a GFR of 89-45 ml/min; 2) 33 with a GFR of 15 ml/min; 3) 20 hemodialysis patients with a GFR of <15 ml/min. A control group included 20 individuals with a GFR of >90 ml/min. In all the patients, physical examination and transthoracic echocardiography were performed and serum cystatin C levels were measured.Results. In Groups 1, 2, and 3, LVH was detected in 42.4, 63.6, and 80% of cases, respectively. It was not found in the control group. In these groups, serum cystatin C levels were 1489.49+/-520.76, 2533.13+/-621.66, 5166.02+/-1586.61, and 820.08+/-224.54 ng/ml, respectively. An association was found between cystatin C and LVH (p=0.5; p<0.001). The level of cystatin C was shown to predict the development of LVH with a sensitivity of 78% and a specificity of 62% for predialysis CKD patients. Multivariate analysis of left ventricular mass index (LVMI), E-velocity/A-velocity, (E/A) ratio, and hypertension showed that the cystatin C levels were independently correlated with LVMI only (p<0.05; beta=0.3) in all the groups.Conclusion. Serum cystatin C levels may be regarded as an early LVH marker detectable in patients with the earliest stages of CKD.

THE AIM of the study is to evaluate interrelation between levels of cystatin C and uric acid with left ventricular hypertrophy (LVH) in patients with chronic kidney disease (CKD). MATERIALS AND METHODS. The study included 86 patients with non-diabetic 2-5 stage CKD (53% male, 47% female, mean age 45±13 years). According to glomerular filtration rate (GFR) decrease they were divided into 3 groups: the 1 one with GFR (n = 33) 89 - 45 ml/min, the 2 (n = 33) - 44 - 15 ml/min and hemodialysis patients (n = 20) were included in the third group. Control group (n=20) included persons with GFR> 90 ml/min. All patients were performedclinical examination and transthoracic echrocardiography, cystatin C and uric acid levels in serum were measured. RESULTS. LVH was detected in 52% (48 form 86) patients with CkD (in 1 group - 42,4%, 2 group - 63,6%, 3 group - 80%). It was correlated with age (p = 0,23 р = 0,016), male gender (p = 0,29 р = 0,003), body mass index (p= 0,38 р 1150,6 ng/ml had sensitivity 78% and specificity 62% LVH in ROC-curve analysis. Hyperuricemia was found in 76,6% patients with CKD. It was directly correlated with arterial hypertension (p = 0,4 р 424,7 mkmol/l was detected LVH with sensitivity 84% and specificity 61%. CONCLUSION. In stage 3-5 CKD higher levels of cystatin C and uric acid may be associated with left ventricular hypertrophy.

AIM To study the prevalence of and risk factors (RF) associated with cardiovascular system damage in patients with predialysis diabetic and nondiabetic chronic kidney disease (CKD). SUBJECTS AND METHODS The investigation enrolled 317 patients with CKD of various etiologies. In Group 1 (165 patients with CKD: 54% of men, 46% of women; mean age 46 +/- 15 years), the glomerular filtration rate (GFR) was 37.2 ml/min; the serum creatinine level was 2.9 mg/dl. Group 2 included 152 (41%) patients with type 2 diabetes mellitus (DM) (41% of men and 59% of women; mean age 57.3 +/- 7.1 years). The duration of DM averaged 10.4 +/- 7.1 years. All the patients underwent physical examination; the levels of glycated hemoglobin and adipose tissue hormones, urinary albumin excretion were additionally determined in the diabetic patients. Echocardiography was performed in 172 patients. The influence of populationwide and renal failure-associated RFs on the cardiovascular system was evaluated in CKD. RESULTS Clinical and instrumental examinations of 165 patients with Stages II-IV nondiabetic CKD revealed atherosclerosis of the aorta and the vessels of the heart, brain, kidney, and lower extremities in 60 (37%), 35 (24%), 30 (18%), 23 (14%), and 8 (5%), respectively. As atherosclerotic vascular lesion progressed, the incidence of cardiovascular events (CVE) increased. Left ventricular hypertrophy (LVH) was diagnosed in 37.3% of the patients with nondiabetic CKD. Along with traditional cardiovascular RFs (age, smoking, gender, arterial hypertension), the renal dysfunction-related factors (anemia, diminished glomerular filtration rate, elevated creatitine levels, and abnormal phosphorus and calcium metabolism) are of importance. An association was found between LVH, atherosclerotic vascular lesion, and heart valve calcification. According to EchoCG data, 36% of the patients with type 2 DM were diagnosed as having LVH. The RFs of the latter were albuminuria, obesity, and abnormal carbohydrate and purine metabolisms. There was an association of diabetic nephropathy with left ventricular remodeling processes and a history of CVE. CONCLUSION The development of cardiorenal syndrome is observed in early-stage CKD and related to both traditional and renal RFs.

AIM: Combination of cardiovascular and renal disease is currently viewed as a unified cardiorenal syndrome (CRS). The aim of our study was to assess the CRS prevalence and risk factors associated with left ventricular hypertrophy (LVH) in patients with pre-dialysis stages of chronic kidney disease (CKD) of various etiology. MATERIALS AND METHODS: We enrolled 172 patients with CKD to participate in this study. First group consisted of 83 patients with nondiabetic CKD at 2nd through 4th stage (mean age 46-15 years, 51% male and 29% female). Mean glomerular filtration rate (GFR) was 37.2 ml/min (33.9-41.4 with 95% CI); creatinine plasma clearance was 2.9 mg/dl (2.6-3.2). Second group consisted of 89 patients with type 2 diabetes mellitus (T2DM) and CKD at 1st?2nd stage (40% male and 60% female) with albuminuria (mean age 57.3-7.1 years). Duration of diabetes in this sampling was 10.4-7.1 years. All patients underwent standard clinical examination, supplemented with echocardiography to evaluate the influence of general and CKD-related risk factors for LVH. RESULTS: LVH was diagnosed in 37.3% of non-diabetic patients with CKD at 2nd through 4th stage. Aside from classic cardiovascular riskfactors (including age, gender, arterial hypertension, family history of cardiovascular diseases, hypercholesterolemia), we observed theimpact of kidney-related factors (anemia, plasma creatinine, disturbance of calcium-phosphorus metabolism). CKD progression wasassociated with elevation in the incidence of concentric and eccentric LVH). Patients with T2DM were diagnosed with LVH in 36% ofcases. Increased myocardial mass correlated with plasma levels of uric acid, HbA1c, obesity and albuminuria. There was also a firmassociation between diabetic nephropathy, left ventricular myocardial remodelling and a history of cardiovascular events. CONCLUSION: In patients with diabetes mellitus and CKD cardiorenal syndrome develops at pre-dialysis stages due to both classic and kidney-related cardiovascular risk factors.

AIM:To examine relations between hyperinsulinemia, insulin resistance (IR). components of metabolic syndrome (MS) and predisposition to renal damage,MATERIAL AND METHODS:A total of 94 MS patients (64 males and 30 females, age 30-67 years, mean age 52 +/- 9 years) entered the study. The examination included measurement of waist and hip circumference, body mass index (BMI), HOMA index, estimation of lipids and immunoreactive insulin concentrations. Renal damage was assessed by glomerular filtration rate and urinary excretion of albumin. The patients were divided into groups by IR and BMI.RESULTS:A strong correlation was found between IR markers and lipid metabolism disorders, hemodynamic parameters. Statistics show that IR is an independent unfavourable factor of renal damage in MS patients.CONCLUSION:IR is an essential component of MS and an independent factor of development of chronic kidney disease in MS patients.

AIM:To evaluate the renal production of erythropoietin (EPO) in relation to filtration function in patients with diabetic kidney lesion.SUBJECTS AND METHODS:The investigation enrolled 183 patients with types 1 and 2 diabetes mellitus (DM), of whom 128 were diagnosed as having diabetic kidney lesion. Serum EPO levels were measured by enzyme immunoassay. Patients who had a glomerular filtration rate (GFR) of below 15 ml/min/1.73 m2 and received erythropoiesis-stimulating agents were excluded from the investigation.RESULTS:The mean serum EPO levels in the patients with diabetic kidney lesion did not vary with the presence or absence of anemia, the degree of albuminuria, or GFR. A physiological inverse relationship was found between the level of EPO and that of hemoglobin in the blood of the patients with DM without kidney disease and in those with renal lesion and GFR > or = 60 ml/min/1.73 m2. The magnitude of the association of the values increased as GFR was higher. The level of EPO was found to be unassociated with hemoglobin in patients with GFR < 60 ml/min/1.73 m2.CONCLUSION:In the patients with diabetic kidney lesion, serum EPO concentrations did not depend on the stage of chronic kidney disease and the degree of albuminuria in spite of more severe anemia as renal failure progressed. These patients showed inadequate EPO production just in early diminished renal filtration function.