[Obesity-related glomerulopathy: Mechanisms of development, clinical course]. / Glomerulopatiia, assotsiirovannaia s ozhireniem: mekhanizmy razvitiia, klinicheskoe techenie.

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.

[Risk factors for pulmonary hypertension at the predialysis stage of chronic kidney disease].

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 (ß=0.34; р=0.008) and RV dimension index (ß=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.

[Clinical value of TNF, IL-6, and IL-10 gene polymorphic markers in chronic glomerulonephritis].

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.

[Cystatin C is a new marker for left ventricular hypertrophy in patients with chronic kidney disease].

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; p = 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.

[Risk factors for cardiovascular system damage in chronic kidney disease].

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.

[Role of circulating angiogenic factors in diabetic kidney disease].

This original article contains the authors own data on homeostasis of angiogenic growth factors (vascular endothelial growth factor - VEGF, angiopoietin 1 and 2 - Ang-1, Ang-2) in diabetic kidney disease. The aims of study were evaluation of alteration on serum concentration of circulating VEGF, Ang-l and Ang-2, and of their association with markers of renal damage (albuminuria, glomerular filtration rate) and anemia in patients with diabetes mellitus. We studied 78 patients type I diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Among this group 37patients had chronic kidney disease. The serum level of VEGF was elevated in T1DM patients and was associated with degree of proteinuria. The serum concentration of Ang-2 was higher in patients with chronic kidney disease (T1DM and T2DM), renal failure (T1DM), proteinuria and anemia (T2DM). Ang-2 strongly associated with albuminuria (T1DM and T2DM), glomerular filtration rate (T1DM) and hemoglobin (T2DM). Obtained results demonstrate that levels of VEGF and Ang-2 (but not Ang-1) are raised in patients with diabetic kidney disease and associated with markers of renal damage and anemia. These data indicate the presence of the disturbance of angiogenic growth factors (VEGF, Ang-2) homeostasis and activity in diabetic patients with chronic kidney disease.

[Early erythropoietin deficiency in diabetic kidney lesion].

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.

[Risk factors for myocardial remodeling at stage II-IV of chronic kidney disease].

AIM: To evaluate frequency and risk factors of development of left ventricular hypertrophy (LVH) of the heart in patients with chronic kidney disease (CKD) of stage II-IV. MATERIAL AND METHODS: The trial enrolled 83 patients (42 - 51% males, 41 - 49% females, mean age 46.7 years) with stage II-IV CKD of non-diabetic origin. Glomerular filtration rate (GFR) estimated according to Cockroft-Goult formula was 37,7 ml/min (95% confidence interval from 33,9 do 41,4). Chronic renal failure duration averaged 2,7 years (95 % CI from 2.0 to 3.3). Arterial hypertension (AH) was diagnosed in 96% patients, hereditary predisposition to cardiovascular diseases - in 54%, obesity - in 60%. lipid disbolism - in 66%, anemia - in 34 % and hyperphosphatemia - in 45%; 40% patients smoked. Echocardiography was performed in all the patients. RESULTS: LVH was detected in 31 (37.3%) of 83 patients. With progression of renal failure, frequency of registration of LVH increased LVH onset was associated with conventional (age, AH, high level of total cholesterol) and renal (lowering of GFR, anemia, hyperphosphatemia) factors. Concentric remodeling, concentric LVH, eccentric LVH were detected in 31.3, 19.3 and 18.1% patients, respectively. Eccentric LVH developed more frequently under the influence of factors associated with renal failure (GFR, anemia, hyperphosphatemia, hypocalcemia). Concentric LVH was characterized with the highest systolic blood pressure. CONCLUSION: Patients with renal dysfunction develop LVH of different geometric model associated with both conventional and renal risk factors even at early stages of CKD.

[The role of hyperinsulinemia and insulin resistance in development of chronic kidney disease in patients with metabolic syndrome].

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.

[The role of lipid metabolism disorders in kidney disease in metabolic syndrome associated with obesity].

AIM: To study the role of lipid metabolism impairment in renal disease in patients with metabolic syndrome associated with obesity. MATERIAL AND METHODS: Lipid metabolism was studied in 77 patients with metabolic syndrome (MS) aged from 17 to 63 years (mean age 48 +/- 9 years). Lipid abnormalities were analysed in groups of patients with different degree of obesity: group 1 - body mass index (BMI) 25-29.9 kg/m2 (n = 13), group 2 - BMI 30-39.9 kg/m2 (n = 49), group 3 - BMI > 40 kg/m2 (n = 15), and in groups of patients with different insulin resistance (IR) : group 1 - HOMA-IR < 2; n = 12; group 2 - HOMA-IR 2 - 4; n = 27; group 3 HOMA-IR > 4; n = 32). Correlation between plasma lipid composition abnormalities and markers of renal disease were studied with correlation analysis. RESULTS: Lipid disbolism in MS patients was characterized with elevated level of triglycerides, total cholesterol (TC), VLDLP cholesterol, low level of HDLP cholesterol. A significant relationship was detected between defective blood lipid composition and renal dysfunction: rise of microalbuminuria, proteinuria, creatinin, inhibition ofglomerular filtration rate. CONCLUSION: The changes found characterize lipid metabolism disorder as an independent factor of kidney disease in patients with MS.

[Association of gene TP53 polymorphic marker Pro72Arg with clinical characteristics of chronic glomerulonephritis].

AIM: To study association of gene TP53 polymorphic marker Pro72Arg coding synthesis of p53 protein with onset, course and progress of chronic glomerulonephritis (CGN). MATERIAL AND METHODS: We examined 126 patients (63 males and 63 females, mean age 38.8 +/- 13.2 years) with CGN duration 13.0 +/- 9.1 years. When analyzing genetic predisposition to CGN, we compared incidence rate of alleles/genotypes of polymorphic marker Pro72Arg of gene TP53 in CGN patients and 69 controls free of renal disease. CGN clinical features were assessed retrospectively including analysis of nephritis onset, clinical and morphological variants. The course of CGN was analysed by changes in severity of hypertension, persistence of proteinuria > 3 g/day during 6 months and longer, conduction of immunosuppressive therapy and response to it. In analysis of progression rate, doubling of blood creatinine was considered as an end point. We used polymerase chain reaction with analysis of restriction fragment length for identification of alleles of Pro 72Arg polymorphic marker of TP53 gene. RESULTS: Distribution of the genotypes of the above polymorphic marker in CGN patients and in controls did not significantly differ. Depending on Pro allele carriage, CGN patients were divided into two groups: Arg/Arg group (59 carriers of genotype Arg/Arg) and Pro group (63 patients with genotype Arg/Pro and 4 with genotype Pro/Pro). Carriage of Pro allele of gene TP53 was associated with high CGN activity at onset, presence of arteriolosclerosis and IgA deposits in kidney biopsy. Patients with genotype Arg/Arg more frequently developed nephritic syndrome without renal dysfunction syndrome. CONCLUSION: We have discovered association of gene TP53 polymorphic marker Pro72Arg with clinical manifestations of CGN. Carriers of Pro allele more often have signs of active glomerular inflammation and vascular impairment with renal dysfunction while carriers of Arg/Arg genotype more frequently demonstrate isolated nephritic syndrome.

[Contribution of obesity to renal lesions in patients with type 2 diabetes mellitus].

AIM: To study of the contribution of obesity to renal lesion in patients with type 2 diabetes mellitus (T2DM). SUBJECTS AND METHODS: One hundred and fifty-four patients (62 males and 92 females) with T2DM (mean age 58 +/- 8 years) were examined. The study excluded patients with significant stages of diabetic nephropathy (glomerular filtration rate (GFR) < 60 ml/min; proteinuria more than 2 g/day). Anthropometric indicators, such as body mass index (BMI), were estimated. The serum levels of creatinine, uric acid (UA), lipid composition, and the adipose tissue hormones leptin and adiponectin were measured. Renal lesion was evaluated from GFR and urine albumin excretion level. Groups of patients with a less and more than 5-year history and subgroups of a MBI of less and more than 30 kg/mi were identified. RESULTS: In patients with a more than 5-year history of T2DM, the detection rate of microalbuminuria and proteinuria increased as obesity progressed. This regularity was not found in those with a less than 5-year history of T2DM. Diabetic patients with a BMI of > 30 kg/m2 were more frequently found to have intrarenal hemodynamic disorders (hyperfiltration) elevated blood pressure, increased UA, and decreased high-density lipoproteins, as compared with those with a BMI of < 30 kg/m2. With a higher BMI, leptin levels increased; its highest values were found in a group of patients with proteinuria. Hypoadiponectinemia was detected in most patients with T2DM. Adiponectin was decreased in early-stage nephropathy; its increase was further increased. CONCLUSION: There was a greater prevalence of renal lesion in obese (BMI > 30 kg/m2) patients with a more than 5-year history of T2DM than in non-obese patients. Obesity has an impact on renal function due to its hemodynamic, metabolic, and hormonal effects.

[Current methods for measuring the glomerular filtration rate in persons with normal weight and overweight].

A steady increase in glomerular filtration rate is considered to be one of the first stages of renal lesion in essential hypertension, metabolic syndrome, and type 2 diabetes mellitus. The paper discusses methods for detection of hyperfiltration and gives their comparative characterization and indications for their use.

[Cardiorenal syndrome in ischemic renal disease (atherosclerotic renovascular hypertension)].

AIM: To characterize cardiorenal syndrome in ischemic renal disease (IRD). MATERIAL AND METHODS: In examination of 105 IRD patients (63 males and 42 females, mean age 63.8 +/- 5.1 years) we estimated body mass index (BMI), indices of peripheral blood and urine, blood biochemistry, glomerular filtration rate (GFR). Plasmic homocystein concentration was measured in 30 patients. We also studied incidence of some cardiovascular risk factors, clinical variants of atherosclerosis and their correlation with GFR. RESULTS: IRD patients most frequently had hypertriglyceridemia (67.6%), hypercholesterinemia (53.3%), smoking (47.1%), obesity (41.9%), metabolic syndrome (38.1%), type 2 diabetes mellitus, arterial hypertension of the third degree (70.6%), isolated systolic arterial hypertension (46.7%). GFR was significantly lower in smokers (p < 0.001), arterial hypertension of the third degree (p < 0.05), isolated systolic arterial hypertension (p < 0.001) and type 2 diabetes mellitus (p < 0.05). In GFR < 40 ml/min homocysteinemia increased significantly (p < 0.01). Coronary artery disease in IRD occurred in 52.4%, cerebrovascular diseases (brain stroke, transitory ischemic attacks)--in 29.5%, intermittent claudication--in 19.0%, aneurism of the abdominal aorta--in 7.6%, documented atherosclerotic affection of the upper limb arteries--in 2.8%. Patients with intermittent claudication were characterized by significantly less GFR compared to that in patients without clinical symptoms of affected arteries of the lower limbs (38.6 +/- 8.2 and 44.6 +/- 7.3 ml/min, respectively; p < 0.01). CONCLUSION: Basic symptoms of cardiorenal syndrome in IRD are high rate of cardiovascular risk factors, some of them provoke aggravation of glomerular endotheliocyte dysfunction and deterioration of intrarenal hemodynamics leading to GFR reduction underlying appearance of new endothelium-tropic risk factors (hyperhomocysteinemia), and progression of atherosclerotic process with formation of its special clinical forms (intermittent claudication).

[The role of major vessels remodeling in development of left ventricular hypertrophy in patients with a predialysis stage of chronic renal failure].

AIM: To study correlation between development of left ventricular hypertrophy (LVH) and remodeling of major arteries at a predialysis stage of chronic renal failure (CRF). MATERIAL AND METHODS: A total of 95 non-diabetic patients (48 males-51% and 47 females-49%) with stage I-III CRF entered the trial. A mean age of the patients was 46.7 years (95% CI 43.7-49.8 years). Glomerular filtration rate calculated by Cockrott-Gault formula was 37.7 ml/min (33.9-41.4 ml/min), blood creatinine level--2.9 mg/dl (2.6-3.2 mg/dl). Arterial hypertension (AH) was registered in 96% patients, smoking--in 40%, cardiovascular hereditary burden--in 54%, hyperlipidemia--in 66%, overweight--in 60%, anemia--in 34%, hyperphosphatemia--in 45%. Echocardiography, ultrasonic dopplerography of the common carotid arteries (CCA) and common femoral artery (CFA) were performed in 83 and 37 patients, respectively. RESULTS: LVH (LV myocardium mass index > 134 g/m2 for males and > 110 g/m2 for females) was detected in 37.3% patients. Concentric remodeling was recorded in 31.3%, concentric myocardial hypertrophy--in 19.1% patients, excentric hypertrophy--in 18.1%. Development of LVH was linked with age, high systolic and pulse blood pressure, marked renal dysfunction, anemia, elevated ESR and hyperphosphatemia. The presence of L VH correlated with increased thickness of intima-media complex (IMC) of CCA and CFA (r = 0.65, p < 0.01 and r = 0.51, p < 0.05, respectively). There was correlation between thickness of LV posterior wall and impairment of CCA elasticity (r = -0.42, p < 0.05). CONCLUSION: Patients with initial and moderate disorders of renal function frequently have LVH related to conventional and "renal" risk factors. A LV mass increase and structural-functional changes of major vessels strongly correlate.

[Ischemic renal disease (atherosclerotic renovascular hypertension), a clinical variant of disseminated atherosclerosis and a cause of chronic renal insufficiency].

The study included 105 patients (63 men and 42 women) aged 34-84 (mean 63.8 +/- 5.1) years with ischemic renal disease (IRD). All of them underwent routine medical examination, blood homocysteine was measured in 30 patients. IRD was always associated with other manifestations of disseminated atherosclerosis and cardiovascular risk factors. Plasma homocysteine increased with decreasing glomerular filtration rate (GFR) that was especially low in patients with isolated systolic arterial hypertension, smoking, and type 2 diabetes. In 34.3% of the patients, IRD associated with other chronic conditions and in 49% with cardiovascular complications and/or the development of terminal renal insufficiency. It is concluded that IRD is characterized by a large number of concomitant manifestations of disseminated atherosclerosis and a high probability of irreversible deterioration of renal functions related to cardiovascular risk factors. IRD may be associated with other chronic renal diseases and a high risk of cardiovascular complications and terminal renal insufficiency.

[Ischemic disease of the kidneys and combined chronic nephropaties: clinical and prognostic features].

AIM: To characterize clinical features and course of ischemic renal disease (IRD) combined with other chronic nephropathies. MATERIAL AND METHODS: We examined 102 patients with IRD treated in the E. M. Tareev clinic of the I. M. Sechenov Moscow Medical Academy in 2001-2006. We made a general clinical examination, clinical and biochemical blood tests. Glomerular filtration rate (GFR) was calculated according to Cockroft-Gault formula. Arterial hypertension was assessed according to ESH. RESULTS: IRD associated with other chronic nephropathies was detected in 35 (34.3%) patients. Association of atherosclerotic stenosis of the renal arteries (ASRA) with diabetic, urate nephropathies was diagnosed in 9 and 8 patients, respectively; chronic pyelonephritis--in 7 cases, chronic glomerulonephritis--in 4 patients. The age of IRD patients associated with other chronic renal diseases was younger than of those with isolated IRD. Systolic arterial pressure was significantly higher in patients with isolated IRD, body mass index and total cholesterol--in the groups of IRD association with other chronic nephropathies. Aggravation of renal failure in patients with CRD association with other chronic nephropathies was provoked by ACE inhibitors and blockers of angiotensin II receptors. Revascularization of the kidneys in IRD associated with other chronic nephropathies leads to significant lowering of systolic blood pressure and stabilization of creatininemia. CONCLUSION: Development of IRD is possible in the presence of other chronic nephropathies. Diagnosis of IRD arising in patients suffering from other chronic renal diseases often requires radical change of therapeutic policy, but renal revascularization is not contraindicated.

[Polymorphic markers Val762Ala and Leu54Phe of the ADPRT1 gene associated with chronic glomerulonephritis in Russian patients from the city of Moscow].

A comparative analysis of allelic and genotype distribution of polymorphic markers Val762Ala and Leu54Phe of ADPRT1 gene encoding poly(ADP-ribose)polymerase I has been performed in chronic glomerulonephritis patients compared to normal controls. This has shown a significant difference in the ADPRTI gene polymorphic marker Val762Ala allelic and genotype frequency distribution between chronic glomerulonephritis patients and healthy controls (according to Fisher's exact test). At the same time the allelic and genotype frequency for a polymorphic marker Leu54Phe distribution did not show significant difference between these groups. Therefore, we have concluded that the ADPRTI gene polymorphic marker Val762Ala is associated with the development of chronic glomerulonephritis in Russian patients of the Moscow region.

[Development of renal affection in obese patients].

AIM: To characterize mechanisms, early markers and clinical signs of renal damage in obesity. MATERIAL AND METHODS: The trial covered 29 males aged under 50 years (mean age 37.7+/-9.3 years) with abdominal obesity having neither carbohydrate metabolism disturbances nor chronic renal disease. All the patients were examined for microalbuminuria (MAU), serum level of leptin. Radionuclide scintigraphy of the kidneys with an acute captopril test, tests for serum concentrations of endothelin-1, homocistein, uric acid, ultrasound dopplerography of the brachial artery for assessment of endothelium-related vasodilation (ERVD) were made in 24 patients. In 9 patients MAU and ERVD were estimated after 3 months of valsartan treatment (80 mg/day). RESULTS: MAU was detected in 62% patients, its rate increasing with elevation of serum leptin and endothelin concentration. Under normal values of creatininemia and GFR, obese patients showed deletion of renal functional reserve (RFR). Patients with low RFR had maximal uricemia and homocysteinemia, serum endothelin-1. Such patients demonstrated also abnormal ERVD. 3-month valsartan intake led to elevation of ERVD and disappearance of MAU. CONCLUSION: Excessive leptin registered in obese patients provoked dysfunction of the endothelium of the intrarenal vessels manifesting with MAU, growth of endothelin-1 serum concentration and disorder of ERVD. This leads to unfavourable changes in filtrating function of the kidneys as seen from gradual deletion of RFR in the absence of hypercreatininemia. Elimination of MAU and ERVD disorders in obesity can be achieved by administration of angiotensin II receptor blockers.

[Risk factors of vascular complications in patients at a predialysis stage of chronic renal failure].

AIM: To specify risk factors of vascular complications at a predialysis stage of renal failure. MATERIAL AND METHODS: The trial enrolled 165 patients with chronic renal failure (CRF) aged 46 +/- 15 years, glomerular filtration rate (GFR) - 37.2 (35.02-40.83) and arterial hypertension (96%). The examination included ultrasound dopplerography of the common carotid arteries (CCA) and common femoral arteries (CFA) for detection of atherosclerotic plaques (AP), estimation of the thickness of arterial intima-media, elasticity and rigidity of the vascular wall. Factors of risk for atherosclerosis and cardiovascular complications were assessed. RESULTS: Aortic atherosclerosis was detected in 60 patients, that of cardiac vessels, brain, kidneys and lower limbs - in 35, 30, 23 and 8 patients, respectively. Acute cardiovascular complications occurred in 13 patients. Main atherosclerosis risk factors were age, body mass index, systolic and pulse arterial pressure, disturbances of phosphorus-calcium metabolism. Structure and function of CCA and CFA were studied with dopplerography in 37 CRF patients. Increased intima-media thickness was associated with age, male sex, overweight, hypercholesterinemia, systolic and pulse arterial pressure. Body mass index, GFR, creatinin level were independent factors of intima-media thickness. Abnormal elasticity of CCA was related to hypertension, CFA - to hypercholesterolemia.