[Clinical significance of the determination of antibodies to thrombospondin type 1 containing domain 7A (THSD7A) in membranous nephropathy].

BACKGROUND: Membranous nephropathy (MN) is an immunocomplex glomerular disease, which is the most common cause of nephrotic syndrome in adults. Numerous studies have established that autoantibodies against the target podocyte autoantigens, including the thrombospondin type 1 domain containing 7A (THSD7A), play a leading role in the development of idiopathic MN. AIM: To evaluate the prevalence of anti-THSD7A autoantibodies (anti-THSD7A AB) in a group of Russian patients with MN. MATERIALS AND METHODS: Serum titers of anti-THSD7A AB were tested in 61 patients with biopsy-proven MN and 12 healthy controls. RESULTS: The prevalence of anti-THSD7A AB was not differing significantly in patients with MN and in the control group (110.9 [71.63; 210.62] and 159.25 [125.64; 231.97] pg/ml, respectively; p=0.111). When comparing subgroups of anti-PLA2R-negative patients and patients who did not receive immunosuppressive therapy with the control group, there were also no statistically significant differences in the Anti-THSD7A AB levels (p>0.05). In the MN group, 1 (1.6%) patient was anti-THSD7A-positive: a 60-year-old man with anti-PLA2R-negative MN and the presence of hormonally inactive adenomas of both adrenal glands and colon polyps (villous adenoma with focal moderate dysplasia, tubulo-villous and tubular adenoma with focal moderate severe dysplasia). CONCLUSION: THSD7-associated MN is a rare variant of MN and is usually detected in PLA2R-negative patients. Screening for malignancies in THSD7A-positive MN patients is proposed.

[Frailty and chronic kidney disease - the real problem of modern nephrology: A review].

The article deals with the syndrome of frailty or senile asthenia in patients with chronic kidney disease. The questions of prevalence, diagnosis, pathogenesis of this syndrome and its clinical consequences in chronic kidney disease are discussed.

[Modern approaches to conservative therapy of polycystic kidney disease].

Polycystic kidney disease (PKD) is a genetically determined pathological process associated with the formation and growth of cysts originating from the epithelial cells of the tubules and/or collecting tubes. PBP is represented by two main types - autosomal dominant (ADPKD) and autosomal recessive PKD (ARPKD), which are different diseases. The main causes of ADPKD are mutations of the PKD1 and PKD2 genes, which encode the formation of polycystin-1 and polycystin-2 proteins. ARPKD-linked mutation in the gene PKHD1, leads to total absence or defective synthesis of receptor protein primary cilia - fibrocystin. There are relationships between the structural and functional defects in the primary cilia and PBP. Mechanisms of cysts formation and growth include a) mutations of polycystines genes located on the cilia; b) increased activity of renal intracellular cAMP; c) vasopressin V2 receptors activation; d) violation of the tubular epithelium polarity (translocation of Na,K-ATPasa from basolateral to apical membrane); e) increased mTOR activity in epithelial cells lining renal cyst. The most promising directions of ADPKD therapy are blockade of vasopressin V2 receptors activation, inhibition of mTOR signaling pathways and reduction of intracellular cAMP level. The review presents clinical studies that assessed the effectiveness of named drugs in ADPKD.

Risk factors for diastolic left ventricular myocardial dysfunction in patients with chronic kidney disease.

AIM: To examine the frequency and risk factors for the development of diastolic dysfunction (DD) of the left ventricle (LV) of the heart in patients with chronic kidney disease (CKD). MATERIALS AND METHODS: The study included 225 patients with stage I-CKD of non-diabetic etiology (median age 47.0 years, 50.2% of women). Depending on the degree of decrease in the glomerular filtration rate (GFR), all patients were divided into 3 groups. Group 1 (n=70) consisted of patients with GFR 89-45 ml / min / 1.73 m2, group 2 (n=120) - patients with GFR 44-15 ml / min / 1.73 m2, group 3 (n=35) - patients with GFR <15 mL / min / 1.73 m2. The control group includes persons without CKD. All patients underwent general clinical examination and transthoracic echocardiography; in 86 patients the level of cystatin C in the blood serum was determined. RESULTS: Hypertrophy of the left ventricle (LVH) of the heart was detected in 87 (38.7%) of 225 patients with CKD. Hypertrophic type (type I) of myocardial DD is diagnosed in 90 (41.4%) of 225 patients with CKD. The incidence of myocardial left ventricular dysfunction of the 1st type increased with a decrease in GFR, amounting to 30, 40 and 60% in groups 1, 2 and 3, respectively. The systolic function of the left ventricular myocardium was preserved. Patients with DD were older, they had a higher body mass index (BMI), a more pronounced decrease in GFR, a higher level of fibrinogen. They were more likely to have LVH. The level of cystatin C as the kidney function worsened, but when comparing the mean levels of cystatin C in patients with the presence / absence of DD in the groups isolated depending on the stage of CKD, no statistically significant differences were found. According to the multivariate analysis, the independent predictor of DD was the age (odds ratio 1.106, 95% confidence interval 1.051-1.157, p=0.00001). CONCLUSION: DD of the myocardium of the LV is detected on average in 40% of patients with CKD, the frequency of its development increases with the progression of renal dysfunction. The development of DD is influenced by traditional factors of cardiovascular risk (age, BMI), as well as the decline in GFR and closely related structural remodeling of LV myocardium.

[Role of the mechanisms of replicative cellular senescence in structural and functional changes of the vascular wall in chronic kidney disease]. / Rol' mekhanizmov replikativnogo kletochnogo stareniia v strukturno-funktsional'nykh izmeneniiakh sosudistoi stenki pri khronicheskoi bolezni pochek.

This review considers the mechanisms and risk factors for the development of replicative cellular senescence of the vascular wall in patients with CKD and discusses therapeutic approaches to slowing the accelerated vascular aging.

[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.

[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.

[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 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.

[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.

[Factors influencing the condition of the intima-media complex of carotid and femoral arteries at initial stages of chronic renal failure].

AIM: To examine changes in the structure of large (carotid and femoral) arteries at an early stage of chronic renal failure (CRF) and factors significant for their development. MATERIAL AND METHODS: Duplex ultrasonography of the common carotid arteries (CCA) and common femoral arteries (CFA), serum biochemical tests, echocardiography were made in 32 patients (15 males and 17 females) with chronic diffuse renal disease at an initial stage of CRF (creatinine 2.7 mg%, CRF duration 2.7 years). Increased thickness of the intima-media complex (IMC) in both vascular territories was found in 72% of the examinees. There was a close correlation between CCA and CFA IMC (chi-square = 14.05; p = 0.0002). Plaques in the carotid arteries correlated with smoking (chi-square = 4.60; p = 0.0320), in the femoral arteries--with male sex (chi-square = 5.18; p = 0.0228). IMC of both arteries correlated with age (r = 0.49 and r = 50, respectively, p < 0.05), body mass index (r = 0.50, p < 0.05), thickness of the left ventricular posterior wall and interventricular septum (r = 0.65 and r = 0.55, respectively, p < 0.05), CFA IMC correlated also with creatinine level (r = 0.39, p < 0.05), hypertriglyceridemia (chi-square = 10.33; p = 0.0013), systolic, pulse and mean arterial pressure (r = 0.45, r = 0.38, r = 0.36, respectively, p < 0.05), smoking (r = 0.48, r = 0.40, respectively, p < 0.05) and family history of cardiovascular diseases (chi-square = 7.16; p = 0.0075). A linear multifactorial regression analysis has detected that an independent factor of increased CCA and CFA IMC in patients under 50 years of age was creatinine, in patients over 50 years--age. CONCLUSION: Even at early stages of renal failure patients have thicker IMC associated with both standard risk factors (age, hypertension, smoking, lipid disbolism) and development of renal failure itself.

[Experience in the use of valsartan with the aim to inhibit progression of kidney failure in patients with chronic glomerulonephritis]. / Opyt primeneniia valsartana s tsel'iu tormozheniia progressirovaniia pochechnoi nedostatochnosti u bol'nykh khronicheskim glomerulonefritom.

AIM: To assess the effect of valsartan, angiotensin-II receptor blocker type 1, on key factors of progression of chronic renal failure (CRF)--arterial hypertension (AH), proteinuria (PU), sodium excretion (SE)--in patients with chronic glomerulonephritis (CGN) and initial affection of renal function. MATERIAL AND METHODS: 11 patients (mean age 33.7 +/- 13.3 years, mean duration of nephritis 8.6 +/- 6.4 years, male to female ratio 8:3) with AH (AP > 140/90 mm Hg) and marked PU (> 1 g/day) who had not received immunosuppressive drugs for at least 6 months before the trial were given valsartan. It was administered after the period of "washing out" at the initial dose 80 mg/day with further addition of diuretics or raising the dose twice (in hyperuricemia) to decrease AP under 140/90 mm Hg. The duration of the treatment was 3 months. RESULTS: After 3 months of valsartan therapy systolic arterial pressure fell from 162 +/- 18 to 138 +/- 20 mm Hg (p < 0.05), diastolic pressure from 100 +/- 8 to 92 +/- 15 mm Hg (single measurements). 24-h monitoring of AP showed a significant lowering of mean 24-h and night systolic and diastolic AP, day-time diastolic AP, 24-h time index of systolic and diastolic AP. Initial antiproteinuric effect was observed after 1 month of the treatment and after 3 months of therapy PU reduced significantly (from 5.7 +/- 6.0 g/day to 3.3 +/- 3.3 g/day). After 3 months sodium excretion significantly rose, while creatinine level and glomerular filtration rate did not. Potassium rose in one patient. CONCLUSION: In CGN with initial CRF valsartan in a dose 80-160 mg/day produces a pronounced antihypertensive and antiproteinuric actions, stimulates sodium excretion. No serious side effects were noted. It is necessary to continue studies on the ability of valsartan to inhibit progression of CRF.