COVID-19 is a severe acute respiratory disease caused by the SARS-CoV-2 virus. Although COVID-19 is characterized mainly by diffuse alveolar damage and acute respiratory failure, in some cases COVID-19 may acquire extra-respiratory features, including renal dysfunction that has existed earlier or developed de novo. The reasons for the extra-respiratory manifestations are biological properties of SARS-CoV-2 based on its multiple organ tropism. It has been shown that at least 50% of patients hospitalized for COVID-19 have proteinuria, hematuria, and signs of renal dysfunction, which in some cases reaches the degree of acute kidney injury (AKI). Here we present a review that discusses the clinical aspects and possible pathophysiological mechanisms of kidney damage in COVID-19. It is believed that renal damage observed in this disease is the result of a complex mechanism induced directly or indirectly by SARS-CoV-2 with the development of acute kidney injury. Two main pathophysiological mechanisms of kidney damage in COVID-19 are discussed. The first of them is the direct cytopathic effect of SARS-CoV-2 on the renal epithelium with the development of acute tubulonecrosis. The second mechanism is the cytokine storm syndrome that results from hyperactivation of the immune system with the development of acute renal and multiorgan inflammatory damage accompanied by hypoxia, persistent hypotension, rhabdomyolysis, hyperactivation of the coagulation cascade, and microcirculation disorders. From a clinical point of view, it should be noted that signs of kidney damage are associated with an increase in the severity of COVID-19 and a poor outcome of the disease, and the prognosis becomes the worst with the development of AKI (the risk of death may increase by 5.3 times). The incidence of COVID-19 in patients with ESRD is higher than in the general population. The most typical for these patients is a severe course of the disease, which determines the increased mortality in comparison with the general population, caused by a respiratory failure with hyperactive inflammation, cytokine storm, hemodynamic, and multiple organ failures.

Introduction: primary focal segmental glomerulosclerosis is a morphological variant of chronic nephropathy based on podocyte damage. The pathogenesis of primary FSGS has been studied since the 90s but has not been fully understood until now. At the same time, a large amount of data has been accumulated allowing one to build a certain concept of the disease. The review aimed to present a modern view on the pathogenesis and approaches to the treatment of primary FSGS in adults. Main information: the review presents current view on the pathogenesis of primary focal segmental glomerulosclerosis. The role of podocytes and parietal epithelial cells in the formation of sclerosis foci and disease progression is discussed. The possible candidate molecules of circulating permeability factors and mechanisms of their action are reviewed: soluble plasminogen activator receptor (suPAR), cardiotrophin-like factor-1 (CLCF-1), CD80 (B7-1). An increased level of these factors was detected in the serum and on the surface of podocytes in FSGS patients. According to the modern concept, the pathogenesis of primary FSGS is associated with the adaptive immune response. The imbalance of certain T-cell subclasses plays a role in the pathogenesis of the disease. In particular, an increase in Th17 lymphocytes and a decrease in the number of T regulatory cells are believed to be crucial for the development of primary FSGS. The activation of B cells is also important, as evidenced by the direct effect of B lymphocytes on proteinuria, the detection of circulating antibodies, and the success of rituximab in FSGS patients. The possible role of anti-CD40 antibodies and ubiquitin carboxyl hydrolase L1 antibodies in primary FSGS is discussed. These mechanisms lead to damage to podocytes directly or through the production of permeability factors. A separate section describes the algorithm of immunosuppressive therapy: glucocorticosteroids and cytostatics, as well as future treatment approaches in FSGS patients.

The study aimed to assess the clinical course and risk factors for adverse outcomes, as well as the treatment options for COVID-19 in renal transplant recipient (RTR). Patients and methods: a retrospective study included 279 RTRs (M 60.9%, age 49.9±10.9 years), infected with SARS-CoV-2 from 01.04.2020 to 30.11.2020. After confirmation of COVID-19 by PCR and chest СТ, MMF/Аza were canceled. In severe cases, the CNI dose was minimized while that of CS was increased. Observation endpoints: hospital discharge/recovery or death. Results: SARS-CoV-2 was identified in 84.2% of RTRs. In almost 90% of patients, the COVID-19 was confirmed by CT data. Duration after transplantation at the time of infection was 54.0 (14.0; 108.0) months, in 17.6% of cases it was 6 months or less. 223/79.9% RTRs were treated in the hospital. The period from the onset of the disease to the hospitalization was 6.8±4.5 days. Severe lung damage (>50%) occurred in 43.1% RTRs; 45.3% of patients required respiratory support. Hospital mortality was 13.9%, overall mortality was 11.1%. The most common cause of death (93.5%) was acute respiratory distress syndrome (ARDS). The risk factors associated with an unfavorable outcome were a high comorbidity index, the severity of the pulmonary lesion, the degree of graft dysfunction at the onset of the disease, decreased SpO2 and the use of mechanical ventilation, as well as anemia, leukocytosis, lymphocytopenia, and hypoalbuminemia, increased levels of creatinine, AST, CRP, LDH, and D-dimer, interleukin-6 and procalcitonin. Scr during the course of the disease increased from 171.6±78.0 μM to 221.5±121.3 μM (p<0.01) with no signs of acute rejection. In 2 recipients with severe graft failure at the time of infection with SARS-CoV-2, HD was resumed from the moment of hospitalization. We were unable to identify the effect of hydroxychloroquine on the outcome of COVID-19. At the same time, mortality in patients with hydroxychloroquine use was higher than in recipients treated with immunobiological drugs: 25.6% and 11.4%, respectively, p<0.02. When immunomodulators were combined with dexamethasone, mortality decreased to 4.8%. The independent factors of adverse outcome were high levels of procalcitonin (p<0.019) and mechanical ventilation (p<0.001). Conclusion: COVID-19 in RTRs is characterized by a severe course and high mortality, which necessitates hospitalization of the majority of infected patients. An increase in procalcitonin levels and the need for mechanical ventilation were independent predictors of an unfavorable outcome of COVID-19.

The study aimed to reveal the nature of the relationship between morphofunctional changes in the heart and blood vessels, indicators of renal dysfunction, and vascular wall stiffness in patients at the initial stages of essential arterial hypertension. A one-stage cohort sample study included 137 patients with essential hypertension stage 1-2, 1-2 degrees. was carried out. A group of 60 healthy people of similar age and gender distributions was used for control. The glomerular filtration rate eGFR (formula CKD-ERI) and the level of albuminuria were determined. Arterial blood pressure was monitored for 24-h, the calculation of the stiffness of the vascular wall using the Vasotens Office application package was carried out. The mean daytime, nighttime, and daily values of time (RWIT) and pulse wave velocity in the aorta (PWVAo), augmentation index (ALo), and central aortic pressure (CAP) were calculated. Based on the ultrasound examination of the heart and blood vessels, the main indicators of cardiovascular remodeling were calculated - the left ventricular mass index with the frequency of left ventricular hypertrophy (LVH), the left atrial index (LAI), the wall thickness of the common carotid artery, the frequency of atherosclerotic plaques in the common and internal carotid arteries. Results: in patients with essential arterial hypertension, there was a decrease in eGFR and an increase in the level of albuminuria compared with the control group, associated with remodeling of the heart (an increase in the left atrium, the frequency of left ventricular hypertrophy) and blood vessels (an increase in atherosclerotic plaques). A decrease in eGFR to 89-60 ml/min/1.73 m2 was associated with higher level of indicators of vascular wall stiffness during 24-hour monitoring. Conclusion: albuminuria in patients with stage 1-2 arterial hypertension is directly associated with the level of office systolic blood pressure, and eGFR was inversely associated with the size of the left atrium, IMT, and aortic augmentation index.

The Study aimed to describe the available clinical and demographic characteristics of patients with CKD, to assess its occurrence by primary referral, and to analyze the clinical outcomes and current treatment of CKD. Material and methods: a retrospective cohort clinical study (protocol identification number: EVS-20-01115) was carried out. Electronic databases of medical records of patients undergoing outpatient treatment in the city of Kirov were examined. The inclusion criteria were diagnosed CKD or the presence of one or more changes in the structure or function of the kidneys associated with the development of CKD, determined for more than 3 months. Results: the occurrence of CKD in a cohort of outpatients from three medical institutions in the city of Kirov was 8.7% of the total number of outpatients. The structure of CKD stages demonstrated a low degree of detectability of CKD stages 1-2; CKD C2 and C3 were the most common (76.5%), while the prevalence of C1 was only 10.2%. Proteinuria was observed in 25% of patients with CKD, i.e. 1.83% of the number of patients in the database. Albuminuria was found rarely, in 7.39% of the total number of patients with abnormalities of the kidneys structure or function and 11.91% of patients with an established diagnosis of CKD. As a decrease in GFR was observed in 89.8% of CKD cases, and proteinuria in 25% of cases a decrease in GFR was a more frequent sign of CKD than proteinuria in the registered CKD cases by primary referral. Arterial hypertension, cerebrovascular diseases, and diabetes mellitus were widespread in patients with CKD. The most commonly prescribed drugs for CKD were aCEI and ARBs prescribed in 81.8% of cases. Conclusion: the analysis made clear the need for earlier detection of CKD C1-C2 and such diseases as diabetes mellitus and hypertension, which are the main causes of CKD (Trial is funded by Astra Zeneca company (LLC "AstraZeneca pharmaceuticals"), protocol EVS-20-01115).

Goal: one of the most common complications of diabetes mellitus is diabetic nephropathy (DN). The central role in the pathogenesis of this complication plays the oxidative stress mediated by chronic hyperglycemia. Despite the existing methods of treatment, DN patients are characterized by a high risk of developing end-stage renal failure. In this regard, we carried out a comparative assessment of the therapeutic efficacy of combined treatment with melatonin and methylethylpiridinol hydrochloride that has antioxidant potential. Methods: the study involved 90 people with DN developing on the background of type 2 diabetes mellitus. The patients were divided into 3 groups of 30 people. The first group of patients was on basic treatment; the second group of the participants received 2 mg of melatonin in addition to the basic therapy; the third group of patients, in addition to the basic therapy, received 10 mg of methylethylpyridinol hydrochloride. The control group consisted of 65 healthy individuals with normal indicators of general and biochemical blood tests. In the course of the work, the analysis of clinical and biochemical indicators of the pathology development, parameters of biochemiluminescence (BCL), and the activity of superoxide dismutase (SOD) and catalase in DN patients of all three groups was carried out. Results: the results of the study showed that the level of glycaemia, concentration of creatinine and postprandial glucose were significantly decreased in all three groups of patients. The combined therapy with melatonin and methylethylpiridinol hydrochloride had a more significant effect on the SOD activity as compared with the basic treatment. In addition, the addition of melatonin to the treatment regimen led to a more significant decrease in the level of glycaemia and proteinuria, as well as a change in BCL parameters and catalase activity in the direction of their values in the control group. Conclusion: our results are probably associated with the high biological activity of melatonin, which has a regulatory activity in relation to carbohydrate metabolism and the functioning of the antioxidant system.

Introduction: the frequency and risk factors of contrast-induced acute kidney injury (CI AKI) after coronary angiography (CAG) or coronary stenting have been evaluated by several major studies. The purpose of this study: to determine the frequency and risk factors for the development of CI-AKI in patients with acute coronary syndrom (ACS) without ST-segment elevation after diagnostic coronary angiography. Material and methods: a retrospective analysis of 104 cases of patients admitted with the diagnosis of ACS without ST-segment elevation was performed, including 42 women (40%) and 62 men (60%). The average age of the patients was 66 (60; 73) years. Glomerular filtration rate before diagnostic coronary angiography was determined using the CKD-EPI formula (eGFR). CI-AKI was diagnosed when the serum creatinine (Scr) level increased by more than 26.5 μM within 48 hours compared to the baseline level. Results: the initial level of eGFR<60 ml/min/1.73 m2 was found in 25% of patients. In the subgroup of patients with eGFR<60 ml/min/1.73 m2, women of older age prevailed. In 6 patients (6%), the level of creatinine gain after CAG met the criteria for CI-AKI. In the subgroup of patients with eGFR ≥60 ml/min/1.73 m2, the relative number of patients with CI-AKI was 6.4%, in the subgroup of patients with eGFR<60 ml/min/1.73 m2 it was 3.8%. Statistically significant differences between patients with the development of CI-AKI and without CI-AKI were found for age and NYHA functional class III CHF. Conclusions: a quarter of patients with ACS without ST-segment elevation initially have eGFR <60 ml/min/1.73 m2. CI-AKI was developed in 6% of patients after the diagnostic CAG. The risk factors for CI-AKI in patients with ACS, according to the data obtained, were old age and chronic heart failure (CHF) of high functional class according to NYHA.

Introduction: indoxyl sulfate is a uremic toxin considered as one of the sources of muscle failure (cachexia) in patients with renal failure; this category of patients has a poor prognosis. Objective: an examination of the possibilities of exogenous regulation of the influence of indoxyl sulfate on myoblasts in vitro. Material and methods: the culture of primary mouse myoblasts was obtained according to the standard method. The cells were cultured in DMEM medium with 10% fetal calf serum (FST) (Gibco) at 37 °C and 6% CO2. The study of the effect of indoxyl sulfate on the proliferation rate of myoblasts was carried out by measuring the rate of reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT, Sigma). To measure the expression of myostatin, RNA was isolated from mouse myoblasts using the Trizol reagent (Thermo Fisher Scientific). Reverse transcription was performed using a set of reagents from Silex. To compare the expression of myostatin mRNA in myoblasts, a real-time polymerase chain reaction was used. Ethylmethylhydroxypyridine malate was used at a physiological concentration of 70 μg/ml. Results: we have shown that indoxyl sulfate has a significant cytostatic effect on myoblasts in vitro, suppressing their proliferation. Ethyl methyl hydroxypyridine malate showed a statistically significant protective effect for myoblasts treated with the toxicant. In experiments where the expression of myostatin mRNA was studied, indoxyl sulfate did activate the expression for euther 48 hours or 72 hours. However, the expression of myostatin mRNA increased with the combined use of indoxyl sulfate and ethylmethylhydroxypyridine malate for 48 hours and persisted after 72 hours. Conclusion: ethylmethylhydroxypyridine malate, leveling the toxic effect of indoxyl sulfate, has a protective effect on myoblasts in vitro. The mechanism of joint activation of mRNA expression of myostatin indoxyl sulfate and ethylmethylhydroxypyridine malate remains unclear and requires further study.

Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disorder caused by defects in the AGXT gene that encodes the hepatic peroxisomal enzyme alanine glyoxylate aminotransferase (AGT), which leads to increased production of oxalates. PH1 is characterized by the development of nephrocalcinosis/urolithiasis with rapid progression to end-stage renal disease (ESRD) in childhood. Combined liver-kidney transplantation (CLKT) is one of the methods to save the life of a patient with PH1 and ESRD, and/or significantly improve his quality of life. CLKT is a rarely performed complex surgical intervention in children (no more than 30 operations in the world per year). It includes the simultaneous transplantation of a part or whole of the liver and kidney from one donor to one recipient. The paper presents clinical cases of 2 children from the same family with an identical homozygous mutation in the AGXT gene (NM_000030.2: c.1 -? _ 358+? Del in exons 1_2 encoding the NP_000021.1: EX1_EX2del protein). The phenotypic manifestations of the disease were different: in an older child - severe nephrocalcinosis/urolithiasis with access to hemodialysis at the age of 9.5 years, in a younger child - recurrent urolithiasis (from 5 years old) with stable kidney function. The first child, after being for 2 years on programmed hemodialysis, underwent CLKT from a deceased donor. In the early postoperative period, the child required hemodialysis due to a delayed renal graft function. Despite several surgical complications (on the 11th day - intraabdominal bleeding, on the 12th day - stenosis by 80-90% in hepatic artery anastomosis), which were successfully eliminated, the function of the transplanted kidney recovered on the 14th day, and on the 30th day the child was discharged from the hospital. For the last 3.5 years after the operation, the child has a satisfactory function of the transplanted organs. This clinical case confirms the possibility of a successful simultaneous liver and kidney transplantation in a child with end-stage renal disease. In the second child, since the diagnosis of PH1 at the age of 7.7 years and the beginning of conservative therapy, there is a regular discharge of calculi with episodes of renal colic and obstruction of the urinary tract. Despite this, stable kidney function has been maintained over the past 5 years.