The article is devoted to controversial issues of autoimmune small vessel vasculitis with kidney and lung damage. Modern data on the features of pathogenesis, clinical manifestation, treatment, outcome, and prognosis of the disease with AT to GBM have presented: an idiopathic disease with AT of class IgG (IgG1 and IgG3) against non-collagen domain-1 (NC1) α3-chain of
collagen type IV GBM (Goodpasture autoantigen); with the simultaneous increase in AT to GBM and ANCA; "de novo" diseases with AT to the α5(IV) and α3(IV) chains of GBM type IV collagen in renal graft with Alport syndrome in pediatric patients.

   Atypical hemolytic uremic syndrome (aHUS) is a rare variant of thrombotic microangiopathy (TMA) associated with uncontrolled activation of alternative complement pathway due to mutations in complement regulatory protein genes or antibodies formation to regulators. Clinical manifestations of aHUS can be triggered by infections, sepsis, pregnancy, autoimmune diseases, organ transplantation, and other complement-activating conditions. Previously, the only treatment option for aHUS was plasma therapy – fresh frozen plasma infusions or plasma exchange, but its effectiveness was insufficient. Currently, targeted treatment available – recombinant monoclonal antibodies against complement C5 protein – eculizumab with high efficiency in achieving aHUS remission, renal function recovery, and preventing TMA at kidney transplantation. For a long time, the question of the optimal duration of treatment and the possibility of eculizumab discontinuing remained unresolved. It was shown that aHUS relapses developed in 20-35 % of patients after discontinuation of complement-blocking therapy. The article presents an overview of a large number of studies of eculizumab treatment outcomes and the possibility of its withdrawal, including a French prospective multicenter study that identified risk factors for aHUS relapse after eculizumab discontinuation: the presence of rare variants of complement genes, female gender, increased soluble C5b-9 plasma level. In patients who did not have rare genetic variants, the risk of relapse was less than 5 %. In general, eculizumab discontinuation after achieving complete remission of aHUS and renal function recovery in patients with low risk of recurrence can provide better tolerability of maintenance treatment, and decrease the incidence of infectious complications and the financial burden on the healthcare system.

   The review presents the main data on the problem of cryoglobulinemic vasculitis associated with HCV infection. The options for the course are considered, and modern diagnostic criteria, the choice of tactics, and the effectiveness of various treatment regimens are presented. The use of modern antiviral drugs makes it possible to achieve the eradication of the virus in 95 % of patients. However, in some patients, clinical and immunologic markers of vasculitis persist despite viral clearance. The article discusses the concept that the persistence of B-cell clones after achieving a sustained virological response may underlie the pathogenesis of HCV-independent CV reactivation.

   Modern scientific data and the emergence of new opportunities for the development of pediatrics and nephrology are inextricably linked with medical genetics, the role of which is especially important for understanding the etiology and pathogenesis of many diseases of the urinary system. In 35–80 % of children with diffuse connective tissue diseases, kidney damage is formed, which is one of the leading causes of comorbidity of pathology and mortality of patients. Modern genetic research will allow not only to decipher the nature of diseases but also to scientifically substantiate adequate therapy. The active development of methods for the molecular diagnosis of kidney diseases opens up a large section of medicine, which can be called "molecular nephropathology". Further study of kidney diseases from the standpoint of molecular biology will allow us to take a fresh look at the pathogenesis of many diseases and solve a number of problems from the standpoint of personalized therapy, which takes into account the genetic characteristics of the patient. The active development of genetic research in nephrology has led to an understanding of the role of genetic mutations and polymorphisms leading to the occurrence of nephropathies in children. Correct clarification of the causes of the development of the disease can radically change the tactics of managing a patient by a nephrologist and rheumatologist. Determination of the genetic cause of the development of nephropathy is important in children since it justifies the need to examine other family members, it will allow predicting the risk of developing kidney pathology in diffuse connective tissue diseases, which is very important, predicting the response to immunosuppressive therapy. The development of molecular diagnostic methods is increasingly opening up prospects for a personalized approach to the study of pathology at various levels of interaction; these achievements provide a qualitative assessment of DNA, RNA, proteins, and their metabolites, which makes it possible to determine new biomarkers. The article deals with gene polymorphisms in secondary nephropathies in children with diffuse connective tissue diseases (systemic lupus erythematosus, systemic microthrombovasculitis, rheumatoid arthritis).

   The term "microbiota" refers to a group of bacteria, as well as viruses, protozoa, fungi, and archaea associated with a specific niche of macroorganism. In recent years, interest in the viral component of the microbiota, virome, has increased. The gut microbiome is best studied. The study of the microbiome and urine virome and urinary organs has just begun. The review presents data on eukaryotic viruses and bacteriophages in the urinary system organs under physiological and pathological conditions. In the future, the study of urobiome and urovirome will allow revising approaches to therapy of nephro-urological pathology.

   THE AIM: to evaluate the functional reserve of the kidneys (FRK), and the effectiveness of empagliflozin (EMPA), a selective reversible inhibitor of sodium-glucose cotransporter type 2 (SGLT 2), in patients with chronic heart failure who have had COVID-19 infection.

   PATIENTS AND METHODS: To assess the state of renal function in patients with coronary heart disease (CHF), the most accessible and convenient method for determining FRK using 0.45 % saline was chosen. The study involved 110 patients with CHF developed as a result of coronary artery disease and hypertension. The first group consisted of 40 patients
with CHF who have had COVID-19 infection (16 (40 %) men and 24 (60 %) women, mean age 63.2 ± 1.2 years). They received EMPA in addition to standard therapy. The second group consisted of 40 patients with CHF who have also had COVID-19 (24 (60 %) men and 16 (40 %) women, mean age 64.1 ± 1.2 years). They received only standard therapy (ACE inhibitors or ARB,
beta-blockers, AMCR). The control group consisted of 30 CHF patients who haven’t had COVID-19 infection (16 (53.33 %) men and 14 (46.67 %) women, mean age 61.8 ± 1.2 years). They received only standard therapy.

   RESULTS. In patients of the first group (standard treatment+ EMPA) the FRK was 2.9 ± 0.2 % before and 8.1 ± 0.2 % after the treatment, which indicates a significant increase (p<0.001). The creatinine level before the treatment and exercise was 147.7±2.7 μmol/l, and after the exercise, it decreased to 144.7±2.5 μmol/l. After the standard therapy, a decrease in its index by 102.5±1.4 μmol/l and 99.7 ± 1.3 μmol/l, respectively, was established. The glomerular filtration rate before treatment and exercise was 56.8 ± 1.5 ml/min, and after exercise, it increased to 54.3 ± 1.6 ml/min. After the treatment, these values were 60.3 ± 2.01 ml/min and 62.7±2.08 ml/min, respectively. In patients of the second group (standard treatment), FRK was 4.4 ± 0.1 % before and 3.0 ± 0.2 % after treatment.

   CONCLUSION: Thus, in patients of the first group, who received EMPA along with standard CHF treatment, an increase in FRK by 2.8 times was found (p < 0.01). In the group of patients with CHF who did not receive an inhibitor of sodium-glucose transporter type 2 EMPA in combination with standard therapy, a decrease in FRK by 1.3 times was found (p > 0.05). While in the control group, FRK increased by 1.1 times (p > 0.05). Thus, the results show that in the first group, the FRK index was 2.9 %, which indicates the absence of a reserve, while after complex therapy in combination with EMPA, this increased to 8.1 %, which indicates the presence of a reserve. However, in the second group, the decrease in these indicators from 4.4 % to 3.3 %, respectively, suggests the absence of FRK. In the control group, this figure increased from 6.7 % before treatment to 7.1 % after.
This indicates a decrease in FRK in this group of patients. Thus, the decrease in the FRK in patients of the first group compared with the control indicates an adverse effect of COVID-19 on the kidneys. It is confirmed in numerous studies, which makes us think about its long-term effect not only in the acute period of infection but also after the clinical convalescence.

   BACKGROUND. Among the causes of death in patients with chronic kidney disease (CKD) on dialysis, cardiovascular complications play a leading role. One of them is acute incidences of cerebral circulation (AICC). The assessment of the impact of mineral and bone disorders on the risk of developing AICC is interesting and on par with the assessment of the impact of traditional risk factors.

   THE AIM: to evaluate the effects of bone mineral disorders on the risk of acute cerebrovascular accident in patients with stage 5 D CKD.

   PATIENTS AND METHODS. A single-center cohort prospective (three-year) study of 85 patients with stage 5D CKD on program hemodialysis was conducted. In the first stage, we evaluated traditional risk factors (blood pressure, echocardiography parameters) and parameters that reflect bone mineral disorders (parathyroid hormone, blood phosphate, calcium levels, 1.25 (OH) D, fibroblast growth factor-FGF-23, a-klotho of blood). Signs of calcification of the heart valves (CHV) and the aortic wall (CAW) were also recorded. In the second stage, three years later, patients were re-examined with the registration of the endpoint, which was identified as cases of fatal and non-fatal AICC.

   RESULTS. Within three years, 10 cases of AICC were registered. Mineral and bone disorders in patients on hemodialysis, such as hyperphosphatemia, CKD and its severity are risk factors for the development of AICC. It is shown that the severity of CCS and pulse pressure levels determined before the dialysis procedure and intradialytic have a positive effect on the risk of AICC. Factors such as FGF-23 and α-Klotho of blood have not demonstrated their effect on the risk of AICC.

   BACKGROUND. The influence of female sex hormones on the regulation of the processes of formation and resorption of bone tissue, as well as the effect of excess or deficiency of sex hormones on renal function is associated with the development of cardiovascular complications in patients at different stages of chronic kidney disease.

   THE AIM: to study the relationship between estradiol deficiency and excess FSH content with disorders of mineral and bone metabolism and cardiovascular complications in postmenopausal women on hemodialysis.

   PATIENTS AND METHODS. 119 women from 34 to 57 years old on hemodialysis were examined. The concentration of follicle-stimulating hormone (FSH) and estradiol2, sclerostin, and fibroblast growth factor 23 (FGF-23) was determined using a sandwich-variant solid-phase ELISA on a «Multiscan EX analyzer» («ThermoFisher Scientific Inc.», Finland) with kits of «Alkor-Bio Company» (Russian Federation) and sets of "sandwich" type manufactured by Cloud-Clone Corp., USA. Echocardiography was performed using an «ALOKA 4000 Aplio» (Toshiba, Japan) in Doppler mode. Determined the left ventricular ejection fraction (LVEF), peak systolic velocity in the aortic arch (Vps – peak systolic velocity); LV myocardial mass index (LVMI). Left ventricular hypertrophy (LVH) was defined with LVMI greater than 95 g /m² in women.

   RESULTS. There was a direct correlation between high levels of FSH and high levels of sclerostin, FSH, and FGF23, an inverse correlation between low levels of estradiol2 and sclerostin, estradiol2 and FGF23, expressed in groups of patients with more severe changes in LVMI and Vps. CONCLUSION. In women on hemodialysis, bone mineral and cardiovascular abnormalities are associated with both renal failure proper and changes in the system of female sex hormones. A decrease in estradiol levels causes an increase in the nephrotoxic FSH and contributes to the excessive synthesis of sclerostin, a key factor in bone-mineral and cardiovascular complications in CKD.

   BACKGROUND. Steroid-dependent nephrotic syndrome (SDNS) treatment is still an important problem in pediatric nephrology since the proper use of steroid-sparing agents can reduce the frequency of relapses and avoid steroid toxicity.

   THE AIM of our study was to compare the efficacy of cyclosporine A (CsA) and mycophenolic acid (MPA) in children with SDNS.

   PATIENTS AND METHODS. We observed 91 children (30 girls, 61 boys) with SDNS in 2015-2020. Age at the disease debut was 3 years [2,1; 5,0]. The age at steroid-sparing therapy debut was 8 years [4,0; 16,0]. All children received standard clinical and laboratory examinations and kidney biopsy.

   RESULTS: 25 children were treated with CsA, and 66 children were treated with MPA. The steroid-sparing therapy duration was 36 months [29; 44]. The frequency of relapses before the steroid-sparing therapy onset was 1,32 ± 0,62 (0,5; 4,3)/year, during steroid-sparing therapy it became 0,5 ± 0,58 (0; 2)/year (р < 0,05). Relapse rate in the MPA group was 0,36 ± 0,49 (0; 1,76)/year compared to 0,85 ± 0,66 (0; 2)/year in the CsA group (p < 0,05). Withdrawal of prednisolone was achieved in 44 (48,4 %) children. The relapse-free period during steroid-sparing therapy with steroid withdrawal was 25 months [6; 120]. 15 children (16,5 %) showed long–term stable remission with no immunosuppressive therapy. 14 of them were treated with MPA and only one with CsA (χ²=9,7, р = 0,0021). The remission duration was 7-32,9 months. There were no severe side effects of CsA and MPA requiring discontinuation of therapy.

   CONCLUSION: steroid-sparing therapy of SDNS with CsA and MPA significantly reduces relapse frequency. Relapse risk in patients treated with CsA was significantly higher than with MPA. So, it is justified to prescribe MPA as a first-choice immunosuppressive therapy in patients with SDNS.

   BACKGROUND. Chronic kidney disease (CKD) is accompanied by the development of endothelial dysfunction, leading to a decrease in arterial reactivity to vasoactive agents. Uremia causes a change in the dilatation of arteries in various vascular regions, incl. and arteries of the pial membrane of the brain. The action of hydrogen sulfide (H₂S), which can induce relaxation of smooth muscle cells of blood vessels, is currently considered a possible route of vasoprotection in various diseases, particularly, in CKD. THE AIM. To evaluate the role of calcium-activated potassium channels of large (BKCa) and intermediate (IKCa) conductance in H2S-induced dilatation of pial arteries in nephrectomized (NE) rats.

   MATERIAL AND METHODS. In Wistar rats nephrectomy (NE) was performed by resection of 5/6 of the renal tissue mass. Sham-operated (LO) animals served as control. The reaction of the pial arteries of the sensomotor cortex of NE and control SO rats to the application of H₂S under physiological conditions and against the background of the use of BKCa channel blockers – tetraethylammonium (TEA) and IKCa – channels – TRAM-34.

   RESULTS. 4 months after NE, the application of H2S led to the dilatation of a smaller number of pial arteries (1.4 – 1.7 times) compared with SO rats. The preliminary exposure to TEA led to a decrease in the number of pial arteries responding by dilatation to the action of H₂S in NE and SO rats. Against the background of the action of TRAM-34, the number of dilated arteries decreased under the action of H₂S in SO rats, while in NE rats it practically did not change.

   CONCLUSION. Under physiological conditions, dilatation of the pial arteries in rats under the action of H₂S is realized (at least in part) through the activation of the BKCa and IKCa channels of the membrane of endothelial and smooth muscle cells. Uremia, caused by nephrectomy, leads to impairment of the mechanism of dilatation of pial arteries, mediated by activation of calcium-activated potassium channels intermediate conductance apparently due to dysfunction of endothelial cells.

   Primary membranous nephropathy (PMN) typical cause of nephrotic syndrome in adults. The key point in its pathogenesis is the production of IgG4 subclass autoantibodies (IgG4) against podocytic transmembrane phospholipase A2 M-type receptor (anti-PLA2R), followed by the deposition of subepithelial immune complexes (IC) in situ. We present a case of a 37-year-old young man with PMN associated with demyelinating polyneuropathy and idiopathic inflammatory lesions of skeletal muscles demonstrating a possible variant of extrarenal effects of IgG4-anti-PLA2R with an extended analysis of diagnostics and probable mechanisms of imbalance of secreted and intracellular phospholipases.

   The presented material raises the most important question in practical nephrology – how to correctly assess kidney function to understand the prognosis and duration of the predialysis period in a particular patient with chronic kidney disease (CKD)? From the standpoint of onto- and phylogenesis, the hierarchy of kidney functions was assessed. It is noted that the existing approaches to such an assessment are convenient for practice, but do not sufficiently take into account individual characteristics and are devoid of a load component that can show kidney reserves. The authors focused on the functional renal reserve (FRR) and the possibility of its detection. The above technique with 0.45 % saline allows revealing the true functional capabilities of the kidneys and understanding the patient's capabilities in the pre-dialysis period. Conclusions are drawn about the convenient use of the KDIGO scale, a more individual approach when using the QxMD calculator, and the possibility of a personalized approach when assessing the FRR.