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.

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.

Purpose of the study. 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

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.

METHODS: During living-donor renal transplantation procedure, subcutaneous fat biopsies were obtained from the abdominal wall at the incision site from donors and recipients for isolation of arteries (Ø230 mm) used to assess endothelial and smooth muscle function using wire myography.In vivo RHI was measured using the EndoPAT.RESULTS: Recipient and donor groups were of similar age (mean 6 SEM; years: 46615; n=28 vs. 50612; n=28).During in vitro isometric force measurements, arteries from recipients (n=11) demonstrated similar contractions to those obtained in arteries from donors (n=12) after single stimulation with KCl at 119 mM (mN/mm: 5.364 vs. 6.064) and agonists phenylephrine at 10 mM (% of max KCl contraction: 8265 vs. 8866).The concentration response curves to norepinephrine were similar between the groups (e.g. at 10mM: 109610; n=11 vs. 10667; n=12) and the basal tension did not differ either.The endothelium-dependent dilatation to bradykinin (BK) did not differ between groups (% max dilatation at 1mmol: 7764, n=9 vs. 7364; n=12) and sodium nitroprusside-induced relaxation was also similar (at 100 mmol: 7964 n=11; vs. 7965; n=12).There were no differences between the responses studied in the subgroup of recipients on RRT or not.Nitric oxide synthase and cyclooxygenase inhibition had no effect on any functional parameter in arteries from any group.RHI reflecting endothelial function in vivo did not differ between recipients and donors (2.260.5;n=20 vs. 2.460.6;n=23).There was a tendency towards positive correlation between RHI and BK relaxation, but it did not reach significance (rho=0,44; p=0,08; n=17).RHI did not correlate with any of other functional parameters studied.CONCLUSIONS: The present study found no differences between uremic and control arteries regarding peripheral vasomotor function in resistance arteries.The tendency towards a positive correlation between endothelial function in vitro and RHI in vivo requires further experimental investigations including additional subjects.

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.

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.

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.

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.