The review summarized recent data on the causes of chronic tissue hypoxia that occurs in kidneys in CKD and the mechanisms of development and progression of hypoxic glomerulosclerosis and tubulointerstitial fibrosis. Causes of chronic renal hypoxia are associated with the failure of the oxygen delivery, consumption, and arteriovenous shunting in renal cortical layer. The leading role among them have hypoperfusion of postglomerular capillary network due to the sclerotic glomerular injury and postglomerular capillaries loss, and local oxidative/nitrozative stress development, which increases oxygen consumption by kidney tissue cells. Additional risk factors which contribute to chronic renal hypoxia are anemia and hypoxemia, which are included in the mechanism of nephropathy formation in CKD patients with severe CHF. Nuclear transcription factor HIF-1a is expressed in podocytes and epithelial cells of proximal tubules influenced by chronic tissue hypoxia. This factor initiates intracellular signal pathways leading to epithelial-mesenchymal transformation of these cells into profibrotic phenotype cells and accelerating the processes of glomeruli and tubulointerstitial tissue sclerotic injure of. Elucidation of the causes of chronic renal hypoxia and the mechanisms underlying the development and progression of hypoxic glomerulosclerosis and tubulointerstitial fibrosis will go to development new approaches to CKD renoprotective therapy.

THE AIM: to select adaptation mechanisms of bone structures reorganization which are involved in mineral and bone metabolism disorders in CKD following the own data and literature analysis. It is showed that one of the reasons for high sensitivity of bone tissue in particular and mineral metabolism in general to regulatory-metabolic shift in renal function disorder is the incorporation of osteocytes in lacunary-tubular system (LTS). This incorporation significantly limits cells nutrients delivery and metabolites removal. Therefore, during phylogeny in osteocytes formed a complex system of bone structures mechanical properties adaptive correction and LTS capacity which allows carrying out environmental parameters continuous optimization. As a result, osteocytes become one of the main mineral metabolism regulators of the body. Therefore, cells functioning adaptive shifts cause systemic effects associated also with mineral homeostasis parameters deviation outside the physiological limits. According to authors, it has become a clinical need to develop a non-invasive method for assessing the functional state of osteocytes. Proposed solutions to this problem using chronobiological method.

This review summarizes data on the idiopathic hypercalciuria aetiology and pathogenesis. The basic types of hypercalciuria are considered. The different causes and mechanisms of this metabolic disorder are discussed.

THE AIM: to evaluate the association of pretransplant immunological risk (IR) factors and rejection type with the long-term prognosis of renal allografts (RA). PATIENTS AND METHODS: Among all patients being transplanted in two kidney transplant centers between 2000 and 2013, ninety-three renal allograft recipients with pretransplant panel-reactive antibody (PRA) >0% and 195 patients without PRA were enrolled into the case-control study in a ratio of 1:2 with matching for age, gender, HLA mismatch (HLAMM), and year of transplantation. In both groups, pretransplant IR factors (number of previous transplants and), clinical data, episodes of kidney allograft rejection, and outcomes were recorded. Kaplan-Meier method was used for kidney allograft survival analysis. Multivariate Cox regression analysis was used to estimate the relation of investigated parameters, including IR, to the risk of kidney allograft loss. RESULTS: According to the number of pretransplant immunological factors (previous kidney transplants, PRA level, HLAMM) and its relations to kidney allograft survival in univariate regression all patients were divided into two groups: low IR (0-1 risk factor) (n=191) and high IR (2-3 risk factors) (n=97). Kidney allograft survival in high IR (HR) group was significantly worse than in low IR (LR) group (p log-rank<0,001). Antibody-mediated rejection (AMR) occurred more frequently in HR group than in LR group (p<0,001). In the Cox regression model adjusted for other potential confounders the HR group was associated with twofold increase of relative risk of the allograft loss (p=0,015). AMR (Exp(B)=10,72 (95% CI 4,46-25,74; p<0,001), T-cell mediated rejection (Exp(B)=4,29 (95% CI 1,64-11,22; p=0,003), and donor age (Exp(B)=1,03 (95% CI 1,01-1,05; p=0,002) were independent predictors of allograft survival after adjustment the multivariate model for the rejection type while IR grouping lost its independent prognostic significance. CONCLUSION: Based on the analysis of allograft survival, a simplified approach to the stratification of pretransplant immunological risk is suggested. HR was associated with the allograft failure; however, it was not independently predictive of graft prognosis and seemed to be triggered by AMR occurrence. Therefore, the allograft prognosis assessment in clinical practice should consider pretransplant immunological risks, but high attention has to be paid to post-transplant morphological evaluation of the allograft and monitoring of donor-specific antibodies.

The AIM: to determine the relationship between vitamin D status and cardiovascular system state in patients with CKD S5d. PATIENTS AND METHODS. 103 patients receiving hemodialysis treatment (53 men and 50 women, mean age 54.8±15.2 years) were examined. Conventional clinical and laboratory parameters, serum parathyroid hormone (PTH) and carotid arteries intimamedia complex thickness were determined. 24-hour simultaneous ECG and blood pressure monitoring and echocardiography were performed. Vitamin D status indicators were determined by ELISA in 79 patients. RESULTS. The average serum calcidol concentration was 33.3±13,8 nmol/,l calcitriol - 11.5±6.9 pmol/l. Serum PTH level was decreased in 38 patients, normal - in 25 and increased in 40 patients. Vitamin D deficiency was associated with 3.9 times increased risk of coronary heart disease. Blood pressure circadian rhythm disturbances were associated with the most significant serum calcitriol concentration decrease: at diper - 15.9±9.2 pmol/l, at non-dipper - 9.3±5.1 pmol/l, p=0.034. CONCLUSION. Calcidol and calcitriol concentration overtime determining is necessary for personalized supplemental vitamin D prescription for patients with CKD S5d stade.

THE AIM: to identify morphological criteria of kidney tissue changes in cases of sudden heart death from alcohol cardiomyopathy. MATERIALS AND METHODS. Retrospective analysis of forensic autopsies acts from Saint-Petersburg State Healthcare Institution Bureau of Forensic Medical Examination archives and histological investigation of kidney tissue in 130 patients (37 female and 93 male). RESULTS. Kidney gross appearance analysis no specific morphological changes revealed, which are indicative for sudden cardiac death from alcoholic cardiomiopathy. Severe kidney tubular epithelial parenhymatous degeneration which was revealed in histological examination most probably was due to ethanol and its metabolites toxic effect. Significant kidney parenchyma congestion progression is result of acute heart failure associated with alcohol myocardium disease. Whereas, dyscirculatory changes found in microcirculatory vessels are associated with kidney histochematic barrier vascular element hypoxic damage, which manifests by increased vascular penetration. CONCLUSION. Morphological kidney changes in case of sudden cardiac death from alcoholic cardiomyopathy are nonspecific.

THE AIM: to identify quality of life (QL) in patients on hemodialysis (HD) in the Udmurt Republic. PATIENTS AND METHODS: The quality of life of 145 patients with chronic kidney disease (CKD) S5d was analyzed in Udmurt Republic. The dialysis period duration - 6,6±5,1 years. The questionnaire Kidney Disease Quality of Life Short Form (KDQOL-SF™) translated into Russian and adapted by I.A.Vasilyeva in 2006 [1,2] was used for the QL estimation. RESULTS. It has been established that the physical component of all patients on routine hemodialysis is significantly lower in comparison with healthy people in general estimation scales. The degree of physical role limitation was 17,1±31,2, the degree of vitality - 42,4±18,8, the value of general health estimation - 32,7±17,0 and the value of general health perception - 44,1±14,5. Furthermore, the renal specific scales indicators were decreased such as working capacity (19,0±31,0), quality of sleeping (49,4±19,7), burden of kidney disease (28,3±22,0). Quality of life indicators have been shown to be low in patients whose dialysis vintage was less than a year: both total mental and physical components were established as 38,6±9,6 and 34,2±5,2 respectively. Later the mental component was increased up to ten years of dialysis vintage (43,2±11,4) but decreased afterwards (41,1±9,1). The physical component was increased up to six years of dialysis vintage (36,8±9,5) and decreased later (32,3±7,4). The negative correlation of life quality indicators and age was detected: burden of chronic kidney disease (r=-0,3; р<0,01), working capacity (r=-0,3; р<0,01), sexual functions (r=-0,5; р<0,05), physical functioning (r=-0,4; р<0,01), total physical component (r=-0,3; р<0,05). Diabetic nephropathy has been indicated as an etiological agent affecting the life quality negatively according to all scales in the questionnaire (both total mental and physical components were 34,7±9,3 and 30,7±6,7 respectively). CONCLUSION. It has been established that the indicators of these patients’ life quality are lower in all estimation scales. The life quality dependence on age, etiological agent and dialysis vintage has been ascertained.

THE AIM: to determine the frequency of acute kidney injury (AKI) and its prognostic value in patients with type 2 diabetes mellitus (DM) underwent coronary artery bypass grafting (CABG) with regard to initial renal function. PATIENTS AND METHODS. 358 patients (195 men and 163 women) aged from 48 till 67 years (61.7±6.3 years) were examined before and after CABG. Glomerular filtration rate (GFR) before operation was upper than 60 ml/min/1.73 m2 in 225 patients (62.8%) in the 1st group and ranged from 59 to 45 ml/min/1.73 m2 in 133 patients (37.2%) in the 2nd group. AKI was diagnosed by level of sCr using criteria of AKIN. RESULTS. Postoperative AKI was diagnosed in 29.8% patients of the 1st group and in 48.9% patients of the 2nd group (p<0,001). Cardiovascular complications have developed significantly more frequently in the 2nd group than in the 1st group. In-hospital mortality in the 1st group accounted for 3.1%, including patients with AKI (5.8%), in the 1st group and 6.1 and 9.2% in the 2nd group respectively. In long-term period chronic kidney disease (CKD) manifested in 14.9% of the patients with postoperative AKI in the 1st group. In the 2nd group regress of chronic kidney disease (CKD) was revealed in 46.2% of patients with postoperative AKI and in 55.4% of patients without previous history of AKI (p>0.05), however progressing of CKD was revealed in 10.8 and 5.9% of cases respectively (p>0.05). Late cardiovascular events, requiring hemodialysis and mortality were more frequent in the 2nd group than in the 1st group. CONCLUSION. It was revealed that the early and long-term cardiorenal prognosis in patients with a diabetic nephropathy underwent CABG and with postoperative AKI is much worse.

THE AIM: to evaluate the full model Stewart-Figge-Fencl parameters information value in adult cardiac patients with acute kidney injury (AKI) receiving continuous renal replacement therapy (RRT) and their suitability for stratification of adverse renal outcomes risk. PATIENTS AND METHODS: A retrospective cohort study was performed in 161 cardiac surgery patients from 21 to 80 years with dialysis-dependent AKI treated with continuous RRT. The parameters of a full model Stewart-Figge-Fencl including anion gap (Anion Gap), apparent and effective strong ion difference (Strong Ion Difference, «apparent», «effective») and strong ion gap (SIG) were analyzed. Using ROC- analysis, unmeasured ions were investigated as potential significant predictor's of in-hospital mortality and requirement for intermittent RRT after the continuous method termination. RESULTS. It was found that adult cardiac surgery patients with AKI characterized by the development of latent metabolic acidosis with increased anion gap, with a consequent reduction unmeasured ions for 2 days on background CRRT Specific patterns in the dynamics of unmeasured ions common to survivors and dead patients with AKI were detected. CONCLUSION: The appropriate and timely correction of unmeasured ions in patients with AKI, not only can improve a short-term but also long-term prognosis through reducing the need for intermittent renal replacement therapy after continuous RRT

THE AIM: to study the features of intrarenal hemodynamics in patients with metabolic syndrome (MS) depending on the class of obesity. PATIENTS AND METHODS: 108 patients with MS with different classes of obesity were examined. Lipid panels parameters, homocysteine, plasma insulin, microalbuminuria level (MAU), intrarenal hemodynamics (pulsatility index and resistivity index) in interlobar and segmental kidney arteries were determined. RESULTS: with the increase of obesity class status of intrarenal hemodynamics decreases. CONCLUSION: Obesity have an effect on the intrarenal hemodynamics.

THE AIM: to analyze of the polymorbidity structure using the Charlson comorbidity index (CCI), and evaluation of the impact of comorbid status on the life prognosis among hemodialysis (HD) patients. PATIENTS AND METHODS: The observational study with retrospective analysis was performed based on patients medical records data of five dialysis centers in St. Petersburg (N=505; 269 men, 236 women) with analyzes of the basic demographic and anamnestic data, as well as laboratory parameters. In order to determine the polymorbidity structure the CCI has been calculated. The survival analysis was performed based on data of the total mortality in corresponding dialysis centers. RESULTS: The average age of patients was 56,4±13,9 years (from 17 to 85 years). Elderly patients (over 59 years) amounted for 44% of the sample (N=221). The relative risk of death in patients older than 59 years was 2.51 (CI 1,45-4,32, P <0.001). The average value of the CCI was at the high level of comorbidity (>5 points) and was 6,3±3,1 points (from 2 to 15 points). The most common and have an impact on the life prognosis were following comorbidities: peripheral artery disease (N = 277, 55%), relative risk of death 2.33 (CI 1,04-5,22, p <0.05), cerebral atherosclerosis (N = 161, 32%), relative risk of death 2.19 (CI 1,11-4,29, p <0.05), moderate liver damage (N = 159, 31%), relative risk of death 2.11 (CI 1,02-4,51, p <0.05). Increasing of the HD treatment duration in high CCI group (>5 points) was associated with a sharp deterioration in the life prognosis (relative risk of death of 2.85 (CI 1,35-6,04), p <0.05). CONCLUSION: The polymorbidity in CKD, estimated using CCI, determined by a wide range of diseases that have a reciprocal influence on the prognosis for the patient’s life. The prognostically adverse impact of the polymorbidity for patients with complicated comorbid status (CCI>5 points) compounded with increasing of renal replacement therapy duration, which appears to be due to the involvement of specific for HD patients complications of the disease such as mineral and bone disorders, anemia, nutritional disorders, chronic inflammation

THE AIM: to study kidneys functional state in patients with diabetes mellitus 2 type with determination of renal functional reserve (RFR). PATIENTS AND METHODS. The research involved 39 patients, 15 male (38 %) and 24 female (62 %) aged from 38 to 78 years, which determined НВА1с level, microalbuminuria, urinary sediment persistent changes and serum creatinine concentration, glomerular filtration rate (GFR) with determination of RFR after water-salt loading with 0.5% NaCl. RESULTS. Diabetic nephropathy was set in all patients with passing to chronic kidney disease (CKD), at that, an urinary syndrome was observed in 14 patients (35 %), however the miсroalbuminuria at most of examinees within 3 months didn’t exceed 0.02 g \l, the hypercreatinaemia from 98 to 133 mmol \l was observed in 10 patients (26%). Kidney changes according to ultrasonography were observed in 15 patients (39%). HbA1c level was within 5.3% - 15.2%. GFRc varied from 39.1 to 140.2 ml\m, GFR60 after carrying out water-salt loading was from 53 to 543 ml \min. RFR was ranging from - 60 to + 402% in all patients, in most patients RFR was preserved and only in 6 patients (15% of the cases) no kidney reserve was observed with GFRp more than 90 ml \min in 5 of the 6 cases. RFR was kept in 6 patients with GFRp less than 60ml \min after carrying out water-salt loading, moreover, in 5 patients it made over 100% (maximum to 478%). RFR was also kept and varied from 26% to 468% in 9 of 10 cases in patients with hypercreatinemia. INCLUSION. It has been established that in patients with diabetic nephropathy RFR decrease is not always proportional to CKD stage and it has no direct dependence on extent of GFR decrease. The RFR index allows to differentiate GFR decrease mechanism because of both convertible nephron damage and their death, and also to reveal hidden violations on the stage of clinical and laboratory wellbeing.

THE AIM: to evaluate myocardial remodeling features in Wistar rats after long time (4 month) of experimental nephrectomy (4 month of rat life is about 10-12 years of human life). MATERIAL AND METHODS. Male Wistar rats after 5/6 nephrectomy were studied (NE; n=9). Sham operated rats (SO; n=8) used as control (C). Animals were taken out of the experiment four month after NE or sham operation. Blood pressure (BP, mm Hg) was measured, serum concentrations of creatinine (Cr, mmol/l), urea (Ur, mmol/l), total calcium (Ca, mmol/l), inorganic phosphorous (Pi, mmol/l) and triglycerides (Tg, mmol/l) were determined. Left ventricular mass index (LVMI) was calculated as the ratio: ventricular mass/body mass (mg/g). Morphological changes of the myocardium were evaluated by quantitative morphometry using the system VideoTest 5.2 In each preparation measurements were carried out in several fields of view. The number of measurements of each parameter is indicated as N. Results are presented as mean±SE. Unpaired Student t-test was used. RESULTS. In NE group Cr (0.072±0.009), Ur (17.8±2.0), Tg (2.04±0.07), BP (165.0±5.0), LVMI (2.72± 0.11) were significantly higher than in control group (0.030±0.004), p<0.01; 5.4± 0,8), p<0.001; 0.52±0.05, p<0.001; 130.0±5.0, p<0.01; 2.35±0.09, p<0.01, respectively). Ca in NE was significantly lower, than in SO rats (2.07±0.09 vs 2.35±0.09, respectively; p<0.01) and Pi - significantly higher (2.62±0.010 vs 2.05±0.05; p<0.01, respectively). Thickness of cardiomyocytes (14.19±0.08, μm, N=1433), area of the nucleus of cardiomyocytes (30.1±0.65, μ^ι², N=359) and area of fibrosis (6231±113.8, μm², N=359) in NE rats were significantly higher than in control group (11.77±0.08, μ^ι, N=1520); (28.06±0.58, μm², N=300); (2773±45.9, μm², N=300), respectively, p<0.001 in all cases. CONCLUSION. 4 months after kidney tissue mass reduction in rats revealed severe myocardial remodeling expressed both hypertrophy and fibrosis. However, the exact contribution of uremia and age in myocardial remodeling needs further investigation.

TheAIM: to clarify the clinical utility and optimal multiplicity and duration of repeated courses of prostatilen treatment in patients with benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: We observed 56 patients with BPH aged from 5l to 89 years. 22 of them had the 1st stage of the disease (according to the classification by F. Guyon) and 54 patients - 2nd stage. As a therapeutic agent we used prostatilen in rectal suppositories containing 50 mg with 90 mg Dimexidum (as a conductor). For the course of treatment 15 suppositories were given. Prostatilen treatment was performed every three months - all four courses in one year. The survey included DRE, prostate ultrasound, uroflowmetry with the assessment of the maximum urinary flow rate. Urination quality was evaluated using questionnaires and counted as a sum score by IPSS. RESULTS: During the first course of treatment in patients with decreased frequency of urination with 9,4 ± 1,4 to 5,5 ± 1,1 times a day (p <0.05), the amount of residual urine in the bladder was reduced by more than half, and maximum urinary flow rate increased from 7,9 ± 2,5 to 17,8 ± 1,7 ml/sec (p <0.001). After a year from start of the treatment the examined patients showed significantly increased maximum speed of urination, and residual urine volume decreased compared with baseline. CONCLUSIONS: The treatment of patients with BPH with prostate gland preparations should be considered the most efficient by using small unit doses (5-10 mg per injection or 50 mg rectal suppositories) in short courses of 5-15 days with intervals of 5-4-6 months.

OBJECTIVE: to evaluate the reasons of persisting dysuria after operative treatment benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: urological evaluation, including urodynamic study, were performed 91 patients (mean age 62,3±2,1 years) with persisting lower urinary tract symptoms after operative treatment BPH. Dysuria continued 4,3±0,5 years. Control group consists of 36 BPH patient with absence dysuria after operative treatment BPH. Middle age patients of the control group was 64,1±1,2 years. RESULTS: Persisting dysuria after BPH surgery commonly was caused by detrusor pathology: detrusor hyperactivity and impaired contractility. These conditions were diagnosed at 59 (64,9%) and at 32 (35,2%) patients. At 27 (29,7%) patients based on the results urodynamic study were diagnosed this both pathology : detrusor hyperactivity and impaired contractility as well. Less frequent reason for persisting dysuria was combination infravesical obstruction and detrusor hyperactivity, diagnosed at 6 (6,7%) patients. CONLUSION: Urodynamic study performed to patients with unsatisfactory results operative treatment BPH allows to find out reason of dysuria. At the majority patient persisting dysuria was caused by detrusor hyperactivity or/and impaired detrusor contractility.

Literary data about the basic anatomical structures for hemodialysis vascular access is presented. In the review the literature data given on key anatomic structures that are used in the formation of vascular access for hemodialysis procedure.