SARS-CoV-2 infection continues to be relevant for healthcare systems because it is widespread and characterized by systemic lesions. Complications of the disease primarily affect the respiratory, cardiovascular and urinary systems. In severe cases, secondary infection may join and acute distress syndrome may develop. The most formidable complication, with a high frequency leading to the death of patients, is multiple organ failure. Undoubtedly, the presence of concomitant pathology in the patient has a negative impact on the course of COVID-19 and affects the prognosis of the disease, which requires special attention in clinical practice for their detection and rapid response in order to optimize therapy. The spectrum of complications is very wide. From the cardiovascular system, these are myocarditis, acute myocardial infarction, thromboembolic events. Acute kidney injury and/or worsening of the course of chronic kidney disease also often develops. This review examines several issues related to the defeat of vital organs, various clinical variants of the course of the disease. Particular attention is paid to the damage of the kidneys and cardiovascular system, as the most vulnerable systems for the SARS-CoV-2 virus.

Violations of the interaction between the host and the microbiota are pathophysiologically significant in patients with chronic kidney disease (CKD). At the same time, the effect is bi-directional: on the one hand, uremia affects both the composition and metabolism of the intestinal microbiota, and on the other hand, uremic toxins arise and are removed as a result of microbial metabolism. Therefore, probiotic drugs can be an effective correction tool. There are three known positive mechanisms of the effect of probiotics: elimination of uremic retaining solutes (URVS), in which there is a decrease in the conversion of amino acids into trimethylamine n-oxide, p-cresyl sulfate or indoxyl sulfate; an increase in the content of short-chain fatty acids in blood plasma; increased hydrolysis of urea. CKD is one of the frequent complications of diabetes mellitus. However, with this disease, not every method of administration of probiotics can be effective. Thus, no significant effect was observed when using probiotic yogurt. The use of encapsulated probiotics gives promising results: metabolic profiles in 11 out of 24 biomarkers were positive. Probiotic therapy can be successfully used in renal replacement therapy.

THE AIM: to analyze the state of the left heart in patients with chronic kidney disease (CKD) at stages C4 and C5 of the disease who do not receive renal replacement therapy. PATIENTS AND METHODS. 123 men and 81 women aged 16 to 74 years with CKD C4-C5 not receiving renal replacement therapy were examined. Patients underwent general clinical examination, electro- and echocardiography. The excretory function of the kidneys was evaluated by the formula CKD-EPI. results. Among the examined patients, 35 (28.4 %) men and 22 (27.1 %) women were found to be overweight. Arterial hypertension (AH) was recorded in 92 (74.7 %) men and 58 (71.6 %) women. An increase in the content of C-reactive protein in blood serum was observed in 28 men (22.7 %) and 19 women (23.4 %). 88.6 % of men and 91.3 % of women showed signs of anemia. Among the surveyed men and women, iron deficiency was observed in 17.8 and 18.5 %, respectively. Hypercholesterolemia was detected in 25.2 % of men and 23.4 % of women. Nephrotic proteinuria was significantly more common among males compared to women (21.1 % and 14.8 %, p<0.05). The prevalence of hyperuricemia was significantly higher in the examined women than in men (41.9 and 18.6 %, respectively, p<0.05). Cardiac conduction and/or excitability disorders were significantly more frequently reported among female patients compared to men (9.8 % and 4.8 %, p<0.05). Signs of subendocardial or subepicardial myocardial damage were detected in 2.4 % of men and 4.9 % of women. An increase in the size of the left atrium was significantly more often recorded in men (25.2 %) compared with women (16.0 %, p<0.05). A decrease in the left ventricular ejection fraction (LV) was recorded in 8.9 % of cases in men and 6.1 % in women. Men had a statistically significant increase in LP size (p<0.05) compared to female patients. In the subgroup of males, the final systolic and diastolic dimensions, LV wall thickness values, and LV myocardial mass index (LVMMI) were significantly higher (p<0.05) compared with female patients. In the studied subgroups of men and women, the most common type of LV structural adjustment was eccentric LV hypertrophy (69.9 % and 74.1 %, respectively), and concentric LV hypertrophy in the 1st and 2nd subgroups was detected in 30.1 % and 25.9 % of cases, respectively. In the subgroup of men, the level of systolic blood pressure (BP) (R2=24 %, β=0.449, p=0.003) and the concentration of hemoglobin (Hb) (R2=24 %, β = – 0.310, p=0.003) had a statistically significant effect on the value of LVH. In female patients, the level of diastolic blood pressure (R2=49 %, β=0.364, p=0.001) and the concentration of g (R2=49 %, β = –0.315, p=0.001) significantly influenced the LVMMI index. CONCLUSION. In patients with CKD at stages C4 and C5 of the disease, structural and functional changes of the heart are associated with hypertension, anemia, hyperuricemia and nephrotic proteinuria. The change in LV geometry is mainly represented by an eccentric type of hypertrophy. A more pronounced structural restructuring of the left parts of the heart is observed in males. The level of systolic blood pressure in men and diastolic blood pressure in women has a significant impact on the development of LV hypertrophy. The Hb concentration was a factor independent of gender, which had a significant effect on the value of LVMMI. 

BACKGROUND. 60 % of cases of acute poisoning are complicated by the occurrence of rhabdomyolysis. The most common and dangerous complication of rhabdomyolysis is acute kidney injury (AKI), which increases mortality by up to 10 %. One of the most promising directions of pathogenetic therapy of rhabdomyolysis complicated by AKI is extracorporeal removal of myoglobin and other factors of endogenous intoxication from the systemic bloodstream. THE AIM: to improve the results of treatment of patients with toxic rhabdomyolysis complicated by acute kidney injury by applying the most effective tactics of renal replacement therapy. PATIENTS AND METHODS. The prospective study included 81 patients with toxic rhabdomyolysis complicated by AKI. In the first group, standard basic intensive therapy was performed; in the second group, hemodiafiltration was performed at an early stage of AKI, in the third group, early application of hemodiafiltration with selective hemosorption was performed. The analysis of laboratory parameters of rhabdomyolysis, renal damage, as well as the outcomes of treatment of patients in groups was carried out. RESULTS. Early use of renal replacement therapy (RRT) increased the severity of reduction of myoglobin concentrations in blood and KIM-1 in urine during the first week of treatment from 26.3 % to 73.4 % and from 76.1 % to 96.8 %, respectively. The inclusion of RRT with selective hemosorption in the intensive therapy at an early stage of AKI allowed to increase these indicators to 88.0 % and 99.0 %, respectively. The most effective method is the use of a combination of RRT with selective hemosorption, which allows to increase the rate of recovery of kidney function and reduce the duration of the necessary use of RRT from 15 to 6 days, as well as to reduce hospital mortality from 14.3 % to 6.9 %.

Background. The current practice of patients with advanced CKD stages management is not optimal, as it leads to the risk of an emergency dialysis start with an unfavorable prognosis, does not utilize all the possibilities of nephroprotective therapy and does not provide optimal correction of the most important uremic syndromes before starting dialysis, which worsens the per spectives of long-term patient-oriented dialysis treatment. THE AIM. The obtained features of the standard practice will provide the possibility to assemble group carefully matched with intensive management group to compare outcomes in future prospective study and to assess the significance of the proposed program components of the intensive management of patients with advanced stages of chronic kidney disease in the "transition center". PATIENTS AND METHODS. A group with regular (at least 6 visits per year) follow-up of 540 patients with baseline CKD3B was retrospectively formed from the city nephrology center database (which included 7696 patients with CKD3 and higher) and was traced to the need for renal replacement therapy or to death. As part of the follow-up, patients underwent regular clinical and laboratory evaluation and received nephroprotective therapy, which were recorded in the database. RESULTS. The dynamics of an accelerating decrease in eGFR (according to CKD-EPICr) from median of -2.76 (-3.26÷-2.36) to -4.34 (-5.01÷-3.46) and further to -6.01 (-7.11÷-5.23) ml/min/1.73 m2/ year for the stages of CKD3B→CKD4→CKD5 in parallel with the dynamics of blood levels of hemoglobin (and iron), phosphate (and calcium), albumin, as well as proteinuria is described – factors that turned out to be significant in the multiple regression model with a dependent variable – the rate of eGFR reduction (the significance of the model F=2.864; p=0.015). CONCLUSION. The obtained detailed description of the progression of CKD in a typical regional population under standard management conditions will provide the possiblity to form a group from a cohort of regular monitoring in a nephrocenter, carefully compared with an intensive management group in the prototype of a transition center based on a large inpatient dialysis center to assess the significance of the components of the proposed control and interventions program.

BACKGROUND: Alport syndrome is a non-immune genetically determined glomerulopathy caused by mutation of genes encoding α3-5 chains of collagen type IV of the basement membranes. It manifests with hematuria and/or proteinuria, progressive renal functions decrease, often in combination with hearing and vision pathology. According to world statistics the incidence of Alport syndrome is less than 1:5000 people. THE AIM: We analyzed the effectiveness of combined Cyclosporine A and nephroprotective therapy in children with Alport syndrome in comparison with nephroprotectors only. PATIENTS AND METHODS: 35 patients were enrolled in retrospective controlled comparative non-randomized single-center longitudinal study: 9 girls (26 %) and 26 boys (74 %). The median age Me was 8,7 [5,4; 13,7] years old. The patients were divided into 2 groups. Group 1 (n=25) – patients receiving Cyclosporine A and nephroprotective therapy, group 2 (n=10) – patients receiving nephroprotective therapy only. The groups did not differ statistically significantly. The observation period was 24 months. The effectiveness of therapy was assessed by reducing proteinuria. RESULTS: In group 1, the level of proteinuria decreased significantly, especially in the first 6 months. Despite gradual increase in the level of proteinuria in this group, by 24 months of follow-up, there was statistically significant difference compared to baseline (1872.0 [1195.0; 2531.0] vs 805.0 [306.0; 1504.0]; p=0.0005). Use of nephroprotectors did not change significantly the dynamics of proteinuria. In general, after 2 years, the level of proteinuria remained practically the same (1812.0 [1508.0; 2093.0] vs 1080.0 [147.0; 3141.0]; p = 0.11). Glomerular filtration rate in two groups did not change significantly during the observation period: in group 1 – 133 [108; 146] vs 123 [106; 131]; p=0.1 and in group 2 – 124 [64; 133] vs 81 [40; 102]; p=0.18. CONCLUSION: The relative safety and efficacy of combined use of Cyclosporine A in low doses and nephroprotectors was shown in children with Alport syndrome with nephrotic proteinuria and glomerular filtration rate > 60 ml/min/1.73m2, if monocomponent nephroprotective therapy was ineffective.

BACKGROUND. The widespread use of genetic methods in clinical practice has shown that pathogenic variants in COL4A3, COL4A4, COL4A5 genes associated with Alport syndrome (AS) are detected in 10 % of sporadic and in 20 % of familial cases of IgA nephropathy (IgAN), which suggested a relationship between the two diseases. THE AIM was to determine the frequency and characteristics of the course of IgAN in children with AS. PATIENTS AND METHODS. A single-centre retrospective pilot study included 102 patients with AS. The inclusion criteria were: age 2-18 years, genetic and/or morphological confirmation of AS, availability of morphological data of pts. The comparison group included children and adolescents 2-18 years with morphologically confirmed primary IgAN; the exclusion criterion was the presence of AS-specific glomerular basement membrane changes. IgAN was classified according to the MESTC scale. Demographic (gender, age), clinical (arterial hypertension, AH) and laboratory data (proteinuria (Pr, mg/m2/day), (Schwartz eGFR, ml/min/1.73m2) at the time of the biopsy and at the last examination of patients were assessed. Arterial pressure ≥95‰ for sex, age, height was defined as AH. Pr >100 mg/m2/day, Pr≥500 mg/m2/day and Pr>1000 mg/m2/day were defined as proteinuria, high-level proteinuria and nephrotic level proteinuria, respectively. The statistic parametric and nonparametric methods were used ("Statistica 10", StatSoft Russia). RESULTS. IgAN was detected in 3 of 102 children with AS (q=0.03): 2 girls had heterozygous variants in COL4A3 and COL4A4, a boy had X-linked AS. Two patients had nephrotic proteinuria, 1 had SRNS at onset of IgAN. The comparison group included 25 children with IgAN (17M). Baseline patients age (9±4.2 vs 13±2.7 years), frequency of AH (q1=0.66 vs q2=0.28), eGFR decrease (q1=0.33 vs q2=0.44), eGFR level (91±24 vs 90.8±24 ml/ min/1.73 m2), morphological characteristics of IgAN did not differ significantly by groups; patients with AS were more likely to have nephrotic proteinuria (q1=1 vs q2=0.32, p=0.023). At follow-up (3.8±1.4 years), the groups were comparable in age (12.3±5.2 vs 15±1.8 years), AH frequency (q1=0.66 vs q2=0.5), eGFR level (87±16 vs 91±13 ml/min/1.73m2); children with AS had higher grade Pr (800[0;1150] vs 30[10;100] mg/m2/day, p=0.048) and more often had high-level Pr (q1=0.66 vs q2=0.06, p=0.006) at follow-up observation. The AS was associated with the development of nephrotic-level Pr at onset (r=0.41, p=0.008) and with high-level Pr (r=0.38, p=0.012) during follow-up. CONCLUSION. IgAN was detected in 3 % of children with AS. The presence of COL4A3, COL4A4, COL4A5 genes variants is associated with more pronounced proteinuria at the onset of IgAN and its preservation in the follow-up, and may be a risk factor for more severe course glomerulonephritis. The main limitations of the study: small sample size and duration of follow-up.

BACKGROUND. Alport syndrome is a rare hereditary kidney disease that causes progressive renal failure. There are significant differences in the progression of the disease between patients with Alport syndrome. Identifying patients with a high risk of rapid progression in order to optimally balance benefits and risks for prescribing therapy has become particularly important at this time. In this study, we wanted to assess whether the factors of proteolysis in blood and urine are associated with the nature of the course and to assess their prognostic value for children with Alport syndrome. THE AIM: To determine the level in blood serum and urinary excretion of MMP-2, MMP-3 and MMP-9 and their inhibitors TIMP-1 and 2, PAI-I, to show the relationship of their changes with the character of the course of Alport syndrome in children as an additional criterion for progression. PATIENTS AND METHODS. The study included 32 children with Alport syndrome. The level of MMP-2, MMP-3 and MMP-9 and their inhibitors TIMP-1 and 2, PAI-I, in blood serum and urine was determined by ELISA. A decrease in eGFR of ≥ 30 % at 2 years from baseline was chosen to indicate a progressive course of Alport syndrome. RESULTS. 28.1 % of children with Alport syndrome had a progressive course of the dis ease, 71.9 % had a slowly progressive course. The frequency of a decrease in MMP-9 and an increase in TIMP-1 both in blood (88.9 versus 43.5 % and 77.8 versus 21.7 %; p = 0.044 and 0.006, respectively) and in urine (100 versus 47, 8 % and 88.9 versus 30.4 %; 0.012 and 0.005, respectively) were statistically significantly more often detected in children with Alport syndrome with a progressive course of the disease than in a slowly progressive course. CONCLUSION. Type 9 matrix metalloproteinase and type 1 tissue matrix metalloproteinase inhibitor can be considered as risk factors for the progression of Alport syndrome in children.

BACKGROUND. Preterm birth is still associated with an increased risk of neonatal morbidity and mortality in the early neonatal period. There is strong evidence demonstrating an association between a decrease in the number of nephrons in preterm infants and an increase in blood pressure, the risk of developing chronic kidney disease, which undoubtedly negatively affects the quality of life. THE AIM: to assess the functional state of the kidneys in children with very low (VLBW) and extremely low body weight (ELBW) in the first 8 weeks of postnatal life. PATIENTS AND METHODS. The study involved 134 newborns less than 37 weeks of gestation, who were divided into three groups depending on birth weight. The levels of protein and fluid intake, serum creatinine concentration, GFR according to Schwartz were taken into account as evaluation parameters. The Python programming language, t-tests, ShapiroWilk and d'Agostino tests were used as statistical methods. A threshold level of 0.05 was chosen to interpret the value of p tests for normality testing. RESULTS. There were no differences in the amount of protein received by preterm infants in the study groups both in the first week and subsequent 2–8 weeks of life. The average level of incoming fluid in the first week of postnatal life increased from 1 to 7 days in all study groups. There was a trend towards a more significant decrease in serum creatinine in children born with a larger birth weight. Analyzing the level of glomerular filtration rate in the studied groups, there is a clear picture of a progressive increase in the rate with age. CONCLUSION. The values of diuresis, creatinine level and GFR in premature babies with birth weight less than 1500 grams in the first 2 months of life have been established, which can be used in practice for comparison in the study of various pathologies.

BACKGROUND. Previously, we postulated the common pathogenetic mechanisms in bronchial asthma (BA) and chronic kidney disease (CKD). Given that both the glomerular filtration rate and the erythrocyte sedimentation rate directly depend on the rheological properties of the blood, it was of interest to compare these two important characteristics in different types of bronchial asthma. At the same time, we considered the erythrocyte sedimentation rate (ESR) not only as a factor in systemic inflammation, but also as a model of erythrocyte aggregation and hemorheology. THE AIM: to compare the level of glomerular filtration rate and erythrocyte sedimentation rate in different types of BA. PATIENTS AND METHODS. 215 BA patients with various BA variants were examined. The glomerular filtration rate (eGFR) was calculated using CKD-EPI. Erythrocyte sedimentation rate (ESR) was determined by the Panchenkov method. The integral eGFR/ESR index was used as the ratio of eGFR and ESR values in each individual patient. RESULTS. The glomerular filtration rate is significantly reduced, and the ESR values are significantly higher in non-allergic and hormone-dependent BA compared with the allergic variant of the disease. In the same groups of patients, a significant decrease in the eGFR/ESR index was revealed. Factor analysis revealed that Factor 1, which characterizes the non-allergic variant of BA, had the component of the eGFR/ESR index with a very high negative factor load along with a high negative factor load of the FEV1 component. Factor 2 reflects the features of endothelial dysfunction in the allergic variant of BA, the allergic variant of BA, and the component of the eGFR/ESR index has practically no factor load in this factor. Factor 3, reflecting the manifestations of an atopic state, with a positive factor load, includes a component of the eGFR/ESR index. CONCLUSION. The data obtained suggest that the development of CKD in bronchial asthma depends primarily on the variant of the disease. The decrease in the eGFR/ ESR index in non-allergic and hormone-dependent variants of BA compared with the allergic variant of the disease indicates the involvement of blood microrheological properties to the development of CKD in these two variants of the disease. On the contrary, in the allergic variant of BA, the development of CKD under these conditions can be restrained.

INTRODUCTION. Recent years clinical studies have shown that bone mineral disorders in chronic kidney disease (CKD) increase the risk of cardiovascular mortality. Factors involved in mineral metabolism, dysregulation of the synthesis of which increases the risk of cardiovascular calcification in CKD S5D include fetuin A. A decrease in the level of fetuin A can lead to the development and progression of processes of extraossal calcification and increased cardiovascular mortality in patients with CKD S5D. THE AIM: to determination of Fetuin A level n and assessment of its relationship with factors involved in mineral metabolism to identify the risk of cardiovascular calcification in patients with CKD S5D. PATIENTS AND METHODS. 84 patients with stage 5 CKD receiving hemodialysis treatment were examined, of which 40 are female and 44 are male. The average age of patients was 55.6±14.9 years. All patients underwent routine examinations, as well as echocardioscopy with an assessment of calcification of the heart valves, radiography of the abdominal organs in a lateral projection with aortic calcification assessment, an analysis of indicators characterizing phosphorus-calcium metabolism was carried out. The level of serum fetuin A was determined, along with the level of calcitriol (1.25 (OH)D), fibroblast growth factor -23 (FGF-23), parathyroid hormone (PTH), alpha-klotho (A-klotho), phosphorus (P) and calcium (Ca) of blood. Statistical analysis was carried out using the program «STATISTICA 12.6» («StatSoft Inc.», USA). RESULTS. It was found that the level of fetuin A in the blood of patients is 0.78± 0.11 ng/ml and ranges from 0.45 to 0.95 ng/ml, signs of calcification of the heart valves and/or aortic wall were noted in 51.2 % of patients. It was revealed that fetuin A has a positive correlation with albumin, its level decreases in patients with age, in patients with low values of "dry weight", indicating the presence of protein-energy deficiency in this category of patients. It has been shown that a decrease in fetuin A level is associated with an increase in FGF-23 and a decrease in A-klotho and indicates an increase in the potential of vascular calcification. The effect of a decrease in the level of fetuin A on the risk of detection of calcification of the aortic wall and heart valves was confirmed. It was revealed that a low level of fetuin A not only increases the probability of calcification itself, but also its severity. We have established that fetuin A is able to do this in conjunction with A-klotho. Since both factors have protective properties against calcification, their friendly reduction also contributes to its development. CONCLUSION. A decrease in the level of fetuin A in patients blood with CKD S5D contributes to an increased risk of calcification of the heart valves and the aortic wall, both independently and in combination with a decrease in the level of A-klotho. Low fetuin A values increase the severity of cardiovascular calcification.

THE AIM: to evaluate the effect of low protein diet supplemented with ketosteril on morphological and epigenomic changes in the myocardium of Wistar rats with simulated kidney dysfunction. MATERIALS AND METHODS. The work was performed on male Wistar rats subjected to 5/6 nephrectomy (NE). The first group after NE received a standard diet (20.16% animal protein), the second – low protein diet (LPD), including 10% ketosteril. Control rats received a standard diet. After 4 months, blood pressure (BP) and left ventricular mass index (LVMI) were assessed in rats, and a histological examination of the myocardium was performed. In the myocardium, the relative expression levels of NF-kB, miRNA-21, miRNA-133, and miRNA-203 were determined. RESULTS. After 4 months in rats with NE on a standard diet, an increase in blood pressure, an increase in the mass index of the LV myocardium was recorded. MBD with the inclusion of 10% Ketosteril slowed down the growth of systolic blood pressure and the development of LV myocardial hypertrophy in rats with kidney dysfunction. At the histological level, the use of LPD provided a decrease in the degree of hypertrophy of cardiomyocytes and degenerative changes in cardiomyocytes. Animals treated with LPD had less pronounced diffuse and perivascular fibrosis compared with animals fed normal food. The use of MBD slowed down the increase in the relative level of expression of the NFκB gene and miRNA-21 in the myocardium of rats with NE and promoted an increase in the expression level of miRNA-133 and miRNA-203 compared to the indices of animals with NE that received standard food. CONCLUSION: long-term use of LPD with the use of ketoanalogues of essential amino acids can have a potential cardioprotective effect in CKD, slowing down the growth of blood pressure, an increase in LV myocardial mass and the formation of structural changes in the myocardium. It is possible that a decrease in the expression of NF-kB and miRNA-21, as well as an increase in the expression of miRNA-203 and 133 in the myocardium, can play a significant role in this. 

Spina bifida is a developmental defect of the spinal cord and/or spinal cord that results from abnormal closure of the embryonic neural tube. Many factors have been described to determine the risks of developing this pathology, but the incidence of the defect is still high. 61% of patients with spina bifida have neurogenic bladder dysfunction based on intravesical hypertension, which contributes to reverse urethral flow and vesico-uretero-renal reflux, associated with chronic inflammatory and obstructive diseases of the urinary tract. Between 25-50% of patients with spina bifida develop chronic kidney disease, significantly reducing their quality of life. In some types of Spina bifida, urological symptoms may be prominent and indicate the presence of this malformation. Therefore, early diagnosis of Spina bifida and timely prophylactic and therapeutic measures are particular importance. This article describes a clinical case of Spina bifida posterior L1-L2 with a closed L1-L2 meningocele in which urological symptoms were the dominant manifestation. The development of secondary complications of neurogenic bladder in the presented patient cannot be excluded, which requires closer monitoring.

The problem of studying the functional reserve of the kidneys attracted the attention of nephrologists about 40 years ago. However, to date, a single protocol for performing functional load tests has not been developed. When assessing the excretory function of the kidneys, nephrologists, as before, are guided by the value of the glomerular filtration rate. However, in two patients of the same age and gender, the same value of this indicator cannot be interpreted unambiguously. In this article, we consider the technical features of performing load tests using egg white, "red meat", a mixture of amino acids, 0.5 % sodium chloride solution. All of them require time and labor resources. This limits the possibilities of their use in outpatient settings. We believe that it is necessary to determine the functional reserve in patients without primary kidney pathology, that is, persons with an established diagnosis of diabetes mellitus or hypertension with a disease duration of at least 5 years. Serious nephroprotective measures in them are recommended to begin only at the stage of chronic kidney disease C3a. It is possible that such a late start of secondary prevention partly explains the increase in the proportion of such patients in hemodialysis centers.