REVIEWS AND LECTURES
In recent years, ideas about the pathogenesis of urinary tract infections have been changed significantly. Various pathogenetic factors of microorganisms and new defense mechanisms against them have been discovered. A significant part of pathogens is inactivated by the first line of defense - innate immunity which includes epithelial barriers (mucous membranes), cellular (phagocytes, dendritic cells, NK-cells) and humoral (chemokines, cytokines, complement) components, as well as antimicrobial proteins). The second and more specific line of defense is the acquired (adaptive) immune system - humoral (B-cells, antibodies) immunity and cellular (T-cells) immunity. However, epithelial cells play an important role in the immune response. These cells interact with the components of both innate immunity and acquired one. Antimicrobial proteins are one of the most ancient and primitive components of the immune system and they are very widely spread in nature. More than 800 antimicrobial proteins have been described and more than 100 of them have been found in the human body. The mechanism of these proteins is mainly connected with the violation of the bacterial membrane integrity. Nevertheless, some proteins can inhibit protein and/or DNA synthesis. The most common protein in the urine is uromodulin (Tamm-Horsfall protein), synthesized in the thick ascending section of the Henle loop. Uromodulin does not have direct antimicrobial activity, but it is involved in the pathogenesis of many inflammatory kidney diseases. In addition, uromodulin acting through the TLR4 signaling pathway pro
motes the maturation of dendritic cells, thereby further activating innate and acquired immunity. Currently, the role of antimicrobial proteins and dendritic cells in the pathogenesis of the infectious process is being actively studied. It will probably have a significant practical value. Thus, the development of urinary tract infections is the process of competing for the interaction of the uropathogenic and the macroorganism. The treatment of these diseases (especially chronic) should not be limited to the use of antibacterial drugs. An important component of the pathogen eradication is to increase the activity of its own protective mechanisms.
In chronic kidney disease (CKD), progressive decline in kidney function leads to disorders of mineral metabolism, which are usually called secondary hyperparathyroidism. An increase in the serum concentration of the parathyroid hormone is associated with a decrease in the level of calcium and calcitriol and/or an increase in the level of fibroblast growth factor-23 and inorganic phosphate in serum. CKD-related disorders of mineral and bone metabolism are associated with other metabolic disorders, such as acidosis, protein-energy wasting, inflammation, and accumulation of uremic toxins. This contributes to vascular calcification, which is a consequence of an imbalance between numerous inhibitors and promoters of soft tissue mineralization. Vascular calcification is a degenerative process characterized by the accumulation of calcium and phosphate salts in the artery wall. This is observed in almost all vascular areas and can develop in the media, intima, or both vascular layers of the arteries. Calcification of the intima usually occurs due to atherosclerosis and may be responsible for coronary ischemic events. Conversely, media calcification is non-exclusive and predominantly develops along elastic fibers. As a result, media calcification increases vascular stiffness, aortic pulse wave velocity, systolic and pulse blood pressure, contributing to the development of left ventricular hypertrophy and heart failure. This review examines the current understanding of the mechanisms that lead to the development of vascular calcification in CKD. The participation of factors such as inflammation, age glycation end products, indoxyl sulfate, and others in calcification processes is discussed. Promising therapeutic goals associated with a new understanding of the mechanisms of cardiovascular calcification in CKD are identified.
ORIGINAL ARTICLES. CLINICAL INVESTIGATIONS
THE AIM: to study the functional state ofthe kidneys in patientswith chronic heart failure (CHF)and obesity. PATIENTS AND METHODS. 116 patients with CHF l-lll functional class (FC) 45-65 years old are divided into three comparable groups depending on body mass index (BMI). A physical examination was performed, evaluated the renal function, the level of leptin and adiponectin, assessed the insulin resistance index, the combined risk of progression of chronic kidney disease (CKD), and the development of cardiovascular complications was analyzed. RESULTS. Among patients with CHF and obesity, a statistically significant decrease in glomerular filtration rate (GFR) was observed compared with patients of the 1st group (61.3 [46.2; 67.1] vs 73.2 [62.1; 86.3] ml/min / 1.73 m2), a clinically significant decrease in GFR <60 ml/min /1.73 m2 (CKD C3a-3b), high (A2) and very high (A3) albuminuria (AU) compared in patientswith normal and overweight. The leptin concentration significantly increased from the 1st to the 3rd group, while the adiponectin concentration decreased from the 1st to the 3rd group. Statistically significant correlations were established between the concentration of leptin and GFR (r = -0.52), AC (r = 0.36), between the concentration of adiponectin and GFR (r = 0.38), AC (r = -0.32). Significant associations were found among patientswith overweight and obesity between the severity of AU, GFR, and HOMA-IR, metabolic index. CONCLUSION. A significant deterioration in the functional parameters ofthe kidneys in patientswith CHF with increasing body weight, as well as an increase in the combined risk of CKD progression and the development of cardiovascular complications with comparable FC, was established. The revealed reliable relationships reflect the significant pathogenetic contribution of the hormonal activity of visceral adipose tissue and insulin resistance to the development and progression of renal dysfunction in patients with heart failure and obesity.
BACKGROUND. The study of the prognostic significance of markers of tubular dysfunction in patients with the acute coronary syndrome (ACS) and arterial hypertension (AH) is highly relevant, due to the unity of pathogenetic mechanisms and their consequences that develop during an acute coronary event. PURPOSE. Analysis of the influence of tubular dysfunction indicators on the risk of cardiovascular complications in patients with hypertension in the late period after ACS. PATIENTS AND
METHODS. The study included 103 patients with hypertension and ACS. All patients included in the study underwent coronary angiography (CAG) with stenting of the coronary arteries. Before CAG, clinical and anamnestic data were collected, laboratory (including creatinine and urea, potassium and sodium, plasma osmolarity), and instrumental diagnostic methods were used. The concentration of potassium and sodium in the daily urine, potassium and natriuresis, osmolarity of urine, and the calculated osmolar clearance index (ОС) were determined. Impedance spectrometry was performed to determine the water balance of the body's liquid media. After 17.0±0.51 months, the endpoints of the study were registered: AMI, NS, stable stress angina, repeated myocardial revascularization (RM), and death. RESULTS. It was found that an increase in ОС is associated with the risk of developing repeated RM in the late period after ACS (x2-criterion = 3.89, p = 0.04). Among the indicators of the electrolyte balance of urine, a statistically significant effect on the risk of repeated RM was found with an increase in the concentration of potassium in the urine (x2-criterion = 4.63, p = 0.03) and daily potassium urea (x2-criterion = 4.85, p = 0.03). The ОС index and an increase in the electrolyte balance of urine were considered and justified as markers of tubular dysfunction. The complex effect of increasing the ОС and reducing the volume of intracellular fluid from the proper values (x2-criterion = 6.16, p = 0.4) on the risk of repeated RM was established. It was found that when the balance of the volume of total fluid and CA is changed, the risk of developing repeated RM is potentiated. It is shown that with the excessive introduction of fluid volume into the body, mainly intravenously and an increase in ОС, the risk of developing repeated RM increases significantly. CONCLUSION. The study revealed that the presence of tubular dysfunction can be considered as a predictor of adverse cardiovascular prognosis in patients with ACS and hypertension. For a comprehensive analysis of the risk value, it is necessary to control homeostasis and individual selection of the volume of intravenous infusions.
BACKGROUND. The increasing prevalence of chronic kidney disease is a global trend as well in general as in terminal kidney failure in particular. Of great interest is the analysis of the impact of mineral and bone disorders on the risk of cardiovascular complications and, first of all, acute myocardial infarction (AMI ). THE AIM: to assess the impact of bone mineral disorders on the risk of AMI in patients with stage 5D chronic kidney disease. PATIENTS AND METHODS. It was conducted a prospective (three-year) cohort study of 85 patients with CKD S5D treated with programmed hemodialysis. At the first stage, it were registered the risk factors and clinical manifestations of CKD 5 St, as well as indicators that characterized bone mineral disorders (levels of blood inorganic phosphate, calcium, parathyroid hormone, 1,25(OH)D, fibroblast growth factor (FGF-23), a-Klotho). Signs of calcification of the heart valves and aortic wall were also determined. The second stage involved a re-examination of patients after 3.1±0.1 years, as well as registration of endpoints, which were identified as cases of fatal and non-fatal AMI. RESULTS. After 3 years of follow-up, the following endpoints were registered: nonfatal AMI - 6 cases, fatal AMI-4 cases. The risk of AMI increased in the presence of initial persistent hyperphosphatemia and 1,25(OH)D3 deficiency, as well as calcification of heart valves and high FGF-23 values, but only in combination with hyperphosphatemia and 1,25(OH)D3 deficiency. Hyperparathyroidism also increased the risk of AMI in conditions of a deficit of 1,25(OH)D3. The risk of nonfatal AMI cases was also increased by the presence of aortic calcification and its severity. The risk of AMI increases in the presence of initial persistent hyperphosphatemia and a deficit of 1.25 (OH)D3, as well as CCS, high FGF-23 values, but only in combination with hyperphosphatemia and a deficit of 1.25(OH)D3. Hyperparathyroidism also increases the risk of AMI in conditions of a deficit of 1.25(OH)D3. The risk of nonfatal cases of AMI also increases the presence of aortic calcification and its severity. CONCLUSION. The risk of AMI increases in the presence of initial persistent hyperphosphatemia and a deficit of 1,25(OH)D3, as well as calcification of the heart valves, high FGF-23 values, but only in combination with hyperphosphatemia and a deficit of 1,25(OH) D3. Hyperparathyroidism also increases the risk of AMI in conditions of a deficit of 1.25(OH)D3. The risk of nonfatal cases of AMI also increases the presence of aortic calcification.
BACKGROUND. The role of inflammation and uremic intoxication in the development and progression of bone mineral disorders, including cardiovascular calcification, has been actively studied over the past decades. PATIENTS AND METHODS. A single-stage, cohort study of 85 patients with stage 5D CKD treated with programmatic hemodialysis was conducted. The blood concentrations of interleukin-3 (IL-3) and interleukin-6 (IL-6) were determined using the enzyme immunoassay, the level of fibrinogen - using the Rutberg method, and the level of p2-microglobulins - using the nephelometric method. The blood leukocyte shift index (ISLC) and the Glasgow Prognostic Score (GPS) risk index for systemic inflammation were also calculated, taking into account the level of C-reactive protein (CRP) and blood albumin. The presence of valvular calcification, its severity, and calcification of the abdominal aortic wall was recorded. Statistical analysis was performed using the program STATISTICA 12.6 ("StatSoft", USA). THE AIM: to evaluate the relationship between factors of systemic inflammation and cardiovascular calcification in patients with stage 5D chronic kidney disease. RESULTS. The risk of detecting calcification of the aorta and heart valves was influenced by the pro-inflammatory cytokines IL-3 and IL-6, as well as ISLK and GPS. However, inflammatory factors such as fibrinogen, p2-microglobulin, and CRP levels in the blood did not show a statistically significant effect. In the case when the predicted parameter was chosen not friendly calcification, but the presence of any of its components, the predictive significance of IL-3 decreased, but IL-6 remained. The 20% risk threshold was exceeded at IL-6 values of more than 33 pg/ml. The effect of ISLC on the probability of detection of calcification was shown both about friendly calcification and concerning isolated calcification of the aorta or valves. CONCLUSION. It was found that among the studied factors of inflammation, IL-6, ILK, and IL-3 demonstrate a relationship with the processes of cardiovascular calcification, GPS-only in relation to friendly calcification. Nomograms have been developed that allow predicting the detection of cardiovascular calcification in dialysis patients, depending on the state of the inflammatory circuit.
ORIGINAL ARTICLES. EXPERIMENTAL INVESTIGATION
BACKGROUND. Determining the pathogenetic mechanisms of small-caliber renal artery remodeling in chronic glomerulonephritis (GN) is an urgent task of nephrology, the implementation of which will allow establishing new diagnostic and therapeutic approaches to patients management. THE AIM: To evaluate the influence of hemodynamic, tubulointerstitial, and endothe- liotropic risk factors on the probability of remodeling of interlobular arteries in an experimental model of glomerulonephritis. MATERIALS AND METHODS. The experiment included 45 individuals of white mongrel rats, 3 of which were used to prepare an antigen suspension (AS), and 42 rats were divided into 4 groups: 9 individuals in the main groups (with the introduction of only AS, with the introduction of an incomplete Freund adjuvant, with AS and sodium chloride, with AS and perindopril) and 6 rats
in the control group. Glomerulonephritis was formed in the main groups of the experiment. Systolic blood pressure (SAD), the protein level in the urine, and the presence of edematous syndrome were monitored initially, on the 15th, 30th, and 60th day of the experiment. The size of the interlobular artery (MA) was determined by the morphological study, and the expression of VEGF and TGFp in the kidneys. RESULTS. Morphological signs of glomerulonephritis were obtained in all the main groups of the experiment as early as day 15. The greatest increase in SAD, protein in the urine, the presence of edematous syndrome in groups with the introduction of AS and AS with sodium chloride was found. The highest expression of VEGF and TGFp was found in these groups of rats. In the group with AS with perindopril, normotension was formed, the protein level was lower than in rats with AS with or without the use of sodium chloride, and there was no edematous syndrome. The expression of VEGF and TGFp was minimal. Interlobular artery remodeling in established groups of AS an AC with sodium chloride. In the remaining groups of rats, the size of the interlobular arteries was comparable to the control group. CONCLUSION. The leading role of systemic blood pressure in the remodeling of small-diameter kidney arteries in glomerulonephritis has been established. Despite the presence of active glomerulonephritis in rats, the structure of small arteries does not change during the formation of normotension.
JOURNAL IN THE JOURNAL. ACTUAL PROBLEMS OF UROLOGY
BACKGROUND. The leading role in the development of vulvovaginitis in girls of pre-school age belongs to the extragenital diseases, including recurrent urinary tract infections. The study of medical and social factors that affect the development of reproductive health disorders is of urgent importance. THE AIM: to study the medical and social risk factors for recurrent vulvovaginitis in preschool girls suffering from urinary tract infections. PATIENTS AND METHODS. A prospective controlled study was conducted in 107 girls aged 3-6 years, including group 1 (n=45) - patients with vulvovaginitis against the background of recurrent uncomplicated urinary tract infection; group 2 (n=32) - patientswith an isolated form of vulvovaginitis; group 3(n=30) - girls of health groups 1 and 2. The main parameters of social and biological anamnesis are analyzed. Statistical analysis was performed using the program "SPSS Statistics V. 17.0" ("SPSS Inc. IBM Company", USA). RESULTS. Patients with a combined form of vulvovaginitis, in comparison with patients with isolated vulvovaginitis, more often lived in rural areas, were from large families, belonged to the group of preschool children who do not attend preschool educational institutions, in their families, the monetary income was lower than the subsistence minimum (p<0.001). The lowest level of hygiene was observed in patientswith isolated forms of vulvovaginitis. In patientswith combined forms of vulvovaginitis, in comparison with patientswith isolated vulvovaginitis, gestational complications were significantly higher: 22.2% had gestational pyelonephritis, 13.6% had a premature birth, and 22.2% had a cesarean section (p <0.05). CONCLUSION. Patients with vulvovaginitis and recurrent UTI have a burdened social and biological history. In dispensary management, an interdisciplinary approach is required, taking into account the identified medical and social risk factors.
PROGRAM ON CONTINUOUS POSTGRADUATE EDUCATION ON NEPHROLOGY
PRACTICAL NOTES
This article reviews the available literature on the SARS-Cov-2 virus and its similarities with its predecessors. The mechanisms of infection due to the structure and epidemiology of the virus are described. Based on these data, the pathogenesis of COVID- 19 infection is described. Based on this, the authors suggest probable extrapulmonary target cells and target organs for the virus depending on their expression ofthe vector protein, APF-2. The article describes a classic clinical picture of the disease, possible complications of its course, and the extrapulmonary (cardiac, immunological, renal) manifestations ofthe infection. The authors traced and described the chain of knowledge about the involvement of the kidneys in the pathological process at COVID-19. Based on numerous studies, we are looking at the site of acute renal injury, coagulopathy, systemic inflammatory response in the spectrum of manifestations of COVID-19 relative to kidneys in patients with COVID-19, including those with hemodialysis. The article builds clinical-morphological associations between lung and kidney damage at COVID-19. We present new data on the pathomorphological manifestations of COVID-19 in the lungs, including own autopsy data. Specific
signs of the effects of the virus on alveolocytes and its cytopathic effect are highlighted and described. The article focuses on kidney signs of infection. The authors give new results of their own observations obtained during an autopsy of patients with COVID-19. Detailed morphological changes in kidney structures have been described, proving that the human kidney is a specific target for SARS-Cov-2 infection, and can also serve as a viral reservoir for the pathogen, playing a role in its subsequent persistence.
ISSN 2541-9439 (Online)