Congenital anomalies of kidney and urinary tract (CAKUT) constitute an average of 25 % of the total number of all genetic anomalies diagnosed in utero and include both individual anomalies of kidney or urinary tract and a combination of such. One of the important problems of pediatric nephrology is the early diagnosis of congenital anomalies of kidney and urinary tract, since untimely detected pathologies lead to a decrease in renal function. The cause of such violations can be genetic factors, environmental factors affecting the woman's body before or during pregnancy. Genetic factor contributes significantly to the formation of CAKUT based on the proven role of mutations in more than 200 genes associated with the development of these anomalies. Since the classical methods of molecular diagnostics do not allow in 90 % of cases to determine occurring mutations, there is a need to apply new genetic testing technologies to identify mutations of genes associated with this group of diseases. Next generation sequencing allows to detect rare genetic variants and concurrently test a large number of genes within a short period of time for the presence of clinically important mutations in them. In addition, the use of next-generation sequencing expands the search for new candidate genes of CAKUT. There are ethnic differences regarding genes involved in the development of congenital anomalies of kidney and urinary tract. The most promising present-day strategy is based on the study of the specific region of patient’s whole exome and the subsequent development of a diagnostic panel.

Literature data indicate that as a result of achievements in medical genetics, the pathogenesis of the development of hormone-resistant isolated and syndromal nephrotic syndrome in pediatric and adult patients has been established. Clinical and genetic features of hereditary isolated or syndromal nephrotic syndrome in pediatric and adult patients are caused by mutations of genes encoding the main components of the glomerular basal membrane, slit diaphragm, structural and functional proteins of the podocyte. Clinical manifestations of hereditary nephrotic syndrome in pediatric and adult patients aged 0 to 70 years, progression to terminal renal failure from 5 months to 75–80 years, depending on genetic and clinical and morphological features, are established. Molecular Genetic testing in steroid-resistant isolated and syndromal nephrotic syndrome conducted before the start of cytostatic therapy and kidney biopsy in pediatric and adult patients is of important clinical significance for making decisions about the feasibility of kidney biopsy and immunosuppressive therapy evaluating the rate of progression to terminal renal failure, and choosing immunosuppressive therapy before kidney transplantation. The problem of early diagnosis of hereditary isolated and syndromal nephrotic syndrome in paediatric and adult patients facing domestic nephrology should be solved by the introduction of molecular genetic testing in nephrological practice.

The article presents an analysis of fundamental data on the problem of stress and its role in the development of stressful diseases. Scientific evidence on the role of stress in childhood pathology indicates the extreme pathogenetic significance of stress. It is proved that stress has three interconnected faces: stress as a link in the adaptation mechanism, stress as a link in the pathogenesis of diseases and adaptation to stressful situations as a natural prevention of stressful diseases. The scientific substantiation of the main evolutionarily determined role of stress as an adaptation link indicates the possibility of acquiring some degree of resistance to stressful situations. Prevention of reducing the excess of stress reactions and reducing the possibility of its transformation into a link in the pathogenesis of diseases limits the complex of mechanisms designated as a stress-limiting system. Important information is the development and coordination of the stress response, which is provided by a complex set of mechanisms of neuroendocrine regulation, united by the concept of “stress-implementing system”. The most common forms of stress are fetal hypoxia, metabolic disturbances, and toxic effects leading to uncontrolled oxidative stress at the cellular and tissue levels with the development of pregnancy complications, intrauterine growth retardation syndrome (IUGR), persistent changes and pathological conditions. As the fetus grows, the flow of oxygen and nutrients from the mother through the placenta increases, which is accompanied by an increased risk of the formation of pathologies of the brain, heart, liver and kidneys with the development of a multi-organ pathology in the subsequent life. It has been proven that oxidative stress combined with stress of malnutrition in the prenatal period increases the risk of endocrinopathies, kidney diseases, and a number of other chronic diseases in the adult state. In practical terms, the negative effects of stress are of particular interest. Early detection of psychosocial and sympathomimetic factors causing stress is the basis for the prevention of childhood pathology.

Molecular genetic research has led to the discovery of new genes encoding proteins – transporters, cotransporters and exchangers involved in the transport of sodium, potassium and chlorine in the thick ascending part of the Henle loop and in the distal convoluted tubule. The article presents modern literature data on the genetic types of tubulopathy with the leading syndrome of hypokalemia and alkalosis – Bartter and Gitelman syndromes in children. The clinical and genetic features of the six types of Bartter syndrome with autosomal recessive and X-linked inheritance, classification approaches, diagnosis, and modern treatment methods are described. Since the first description of Bartter syndrome, 6 clinical genetic options have been known, including antenatal I, II, IVa, IVb, V types, which are potentially life-threatening diseases. Bartter type III syndrome is characterized by the manifestation of hypokalemic alkalosis in children at an early and preschool age. Treatment of Bartter syndrome in children includes the correction of water – electrolyte disturbances, the use of non-steroidal anti-inflammatory drugs (NSAIDs) to inhibit the excessive formation of renal prostaglandin PgE 2. Gitelman syndrome with an autosomal recessive type of inheritance manifests itself in children at school age, later on in adolescents and adults there is an increase in clinical manifestations (with severe hypomagnesemic seizures of the upper and lower extremities, arterial hypertension) requiring correction. The review presents the clinical and genetic features of the rare, atypical form of the autosomal recessive Gitelman syndrome with a manifestation in school age, which is characterized by progressive bilateral calcifications of the subcortical parts of the cerebral hemispheres, calcifications in the basal ganglia and subcortical cerebellum. Unlike Bartter syndrome, with more severe clinical manifestations in newborns, infants and young children, Gitelman syndrome tends to increase clinical manifestations in adolescents and adults. Treatment of Gitelman syndrome in children and adolescents includes the correction of water – electrolyte disturbances, the use of magnesium preparations and salt subsidy.

The review provides historical information on the study of renal cystosis that occurs with glomerular cysts, discusses terminology issues and classification of diseases that occur with glomerulocystic kidney. The course features, diagnostic methods, treatment, and prognosis of renal glomerulocystosis in children, renal and extrarenal manifestations of two subtypes of hereditary glomerulocystic kidney disease: autosomal dominant glomerulocystic kidney disease associated with mutations of uromodulin (OMIM 609886) and familial hypoplastic glomerulocystic kidney disease associated with mutations of the HNF-1β (TCF2) gene (OMIM 137920). Diagnostic tetrad of familial hypoplastic glomerulocystic kidney disease, features of course and prognosis of HNF-1β-associated kidney disease with very early onset (VEO), MODY5 diabetes caused by HNF-1β mutation and 17q12 microdeletion syndrome in children were detected. According to the results of ultrasound examination (US), the fetus and newborn reveal hyperechogenicity of the kidney parenchyma, the volume of which is increased or corresponds to normal values. Renal cysts in glomerulocystic kidney are small, located in the cortical layer or subcapsularly, single or multiple, rarely diagnosed in the neonatal period. In young children, US shows a picture of increasing hyperechogenicity of the parenchyma with visualization of renal cysts in the cortical layer or subcapsularly, a decrease in the volume or asymmetry in the size of the kidneys. Urinary syndrome in glomerulocystic kidney in childhood is characterized by hematuria, microproteinuria, magniuria and uraturia in combination with hypostenuria and polyuria. Molecular genetic research reveals the mutation of genes responsible for the development of inherited diseases that occur with glomerulocystic kidney, and largely determines the prognosis and management tactics of the patient. A systematic approach is needed in the diagnosis and treatment of glomerulocystic kidney in children in order to slow the progression of chronic kidney disease and extrarenal manifestations, and to maintain continuity of observation of patients in pediatric and adult nephrological structures.

INTRODUCTION. Among systemic vasopathies in children, IgA vasculitis Henoch Schoenlein (HS) is the most common, according to various authors, kidney damage is noted in 25-80 % and usually determines the prognosis of the disease.

THE AIM of the study was to analyze clinical, laboratory, immunological, morphological characteristics, features of the course and treatment of nephritis associated with IgA vasculitis HS in children, as well as factors affecting the prognosis.

PATIENTS AND METHODS. The study included 31 patients with morphologically verified nephritis due to IgA vasculitis HS (18 – boys, 13 – girls) aged 3 to 17 years, who were monitored at the Nephrology Department of the "2nd Children's City Clinical Hospital" of the National Center for Pediatric Nephrology and Renal Replacement therapy in Minsk from 2010 to 2019 yrs.The following parameters were analyzed: the clinical variant of kidney damage, laboratory tests (including the study of BAFF, RANTES lymphocyte activation molecules, pro-inflammatory IL1β, caspase1, TNFα, growth factors VEGF, TGF), 24 hours monitoring and office blood pressure measurements, ECHO cardiography with indicescalculation, ultrasound of the carotid arteries with the thickness of intima-media complex, morphological changes in the renal tissue, as well as treatment regimens.

RESULTS. The contribution of deGal-IgA1, markers of T and B lymphocytes activation, pro-inflammatory and profibrotic molecules in the development of the disease is shown. Arterial hypertension was registered in 42 % of children, signs of heart remodeling according to the calculated indices in 19,3 %. Decrease level of adiponectin, vitamin D, leptin, increase concentration of obestatin, Pro-BNP, hs-CRP, and TSAT indicator classify patients with nephritis due to IgA vasculitis HS at moderate risk for the developmentof cardio-vascular disorders, which suggests the need for timely correction.

CONCLUSION. In most cases, nephritis with IgA vasculitis HS has a benign course with rare relapses and progression to the end stage of chronic kidney disease (6,5 %).

AIM. Evaluation in comparative study the efficiency of first choice cytostatic therapy with calcineurin inhibitor cyclosporine A and nucleotide synthesis inhibitormycophenolatemofetil (MMF)/mycophenolate sodium in children with relapsing and frequently relapsing steroid-dependent and steroid-sensitive nephrotic syndrome (NS) with steroid toxicity.

PATIENTS AND METHODS. Follow-up study with analysis of onset, clinical course and treatment includes 48 children ((29 boys (60 %) и 19 girls (40 %)) with relapsing and frequently relapsing NS, developedsteroid dependence and/or steroid toxicity.The efficiency of first choice cytostatic therapy with calcineurin inhibitor cyclosporine Ain 17 patients and nucleotide synthesis inhibitormycophenolatemofetil (MMF)/mycophenolate sodium in 31 patients is estimated in comparative study by analysis of 6 month remission rate and one year remission rate after treatment.

RESULTS. Statistically significant differences in 6 month and one year remission rate after first choice cytostatic therapy with MMF/ mycophenolate sodium and cyclosporine in children are established. Remission of NS during 6 months after MMF/ mycophenolate sodium treatment was in 67,7 % (in 21 from 31 patients) unlike of that after cyclosporine – in 29,4 % (in 5 from 17 patients) (р<0,05). Remission of NS during one year after MMF/ mycophenolate sodium treatment was in 58,1 % (in 18 from 31 patients) unlike of that after cyclosporine – 23,5 % (in 4 from 17 patients) (р<0,05). Cyclosporine toxicity was diagnosed in 5 from 17patients: increased creatinine (1),arterial hypertension (3), gingival hyperplasia (3) in treatment more than 12 months with reverse development after cancel. Side-effects after nucleotide synthesis inhibitor therapy was dignosed only in 1 from 31 patients (3,2 %) – lymphopenic crisis.

CONCLUSION. Remission of relapsing and frequently relapsing steroid-dependent and steroid-sensitive with steroid toxicity NS during 6 months after first choice cytostatic therapy with MMF/ mycophenolate sodium and cyclosporine in children was in 67,7 % and 29,4 % respectively, during one year in 58,1 % and 23,5 % respectively. As the result of comparative study remission during 6 months and one year was statistically significant more often in children after first choice cytostatic therapy with MMF/ mycophenolate sodium.

INTRODUCTION. Study of physical development (PD) of children with idiopathic nephrotic syndrome (INS) includes mainly assessment of body height and weight during corticosteroid (CS) therapy; specifics of these criteria before and after the treatment are not sufficiently studied. THE AIM: to study PD of children with INS debut during CS therapy and upon its completion.

PATIENTS AND METHODS. A retrospective analysis of PD was performed in 89 patients with INS in Voronezh Regional Children's Clinical Hospital No.1 during 1998-2014 using method of Z-score of body height and weight in comparison with regional standards.

RESULTS. At the INS debut body height of 38.2% of the children and body weight of 41.2% accordingly were less than those of healthy children, p<0.001. Children with steroid-sensitive nephrotic syndrome (SSNS) had no difference in body height Z-score during CS therapy (0.17±1.06) and upon its completion (0.28±1.22), p=0.794. Body height was less in steroiddependent patients (SDNS) compared to SSNS patients. Z-score body weight values in children with SSNS were higher during maximum doses of CS (0.94±1.59) and returned to previous values after the therapy (-0.24±1.33), р=0,040. Patients with a frequent relapsing SSNS and SDNS had overweight and obesity remained after prednisone treatment (p=0.009).

CONCLUSION. Physical development of children with INS has differences associated with CS therapy. Since body height and weight of children with INS were different from the norms before CS therapy, this could be influenced by genetic factors, which to be studied further. The results can be used to prognose CS therapy influence on PD of patients and assess prognosis of INS.

INTRODUCTION. The basis of hemolytic-uremic syndrome (HUS) is the pathology of hemostasis with the development of a condition that threatens the patient's life. Violations of the hemostatic system are probably largely due to a hereditary predisposition to thrombophilia.

THE AIM. To study the characteristics of allelic polymorphism of genes associated with hereditary thrombophilia in 15 children with hemolytic-uremic syndrome.

PATIENTS AND METHODS. A study was conducted of 15 children with HUS from the age of 1 to 4 years who were treated in the nephrology department of the clinic of St. Petersburg State Medical University. A typical HUS was diagnosed in 14 children. One child was diagnosed with atypical HUS confirmed by laboratory tests (increased levels of antibodies to protein H). At the Research Institute of Hematology and Transfusiology of the FMBA of Russia, PCR for all 15 patients and two parents analyzed the polymorphism of genes associated with thrombophilia.

RESULTS. In all examined children, polymorphism of genes associated with various links of hemostasis was found. Two patients showed a mutation in the factor V gene (FV Leiden). In 7 patients out of 15 subjects, the homozygous state of the plasminogen activator inhibitor (PAI-1 - 675 4G / 5G) was revealed.

CONCLUSION. The FV Leiden mutation, as the main reason for the resistance of activation of protein C (an inhibitor of the formation of thrombin), was found in two children, one with a typical HUS, and one with an atypical HUS. In 7 children out of 15 subjects, a homozygous state of plasminogen activator inhibitor (PAI-1 - 675 4G / 5G) was revealed, which may indicate insufficient fibrinolytic activity in these children, as an important factor contributing to the development of TMA.

The work is dedicated to the 170th anniversary of the outstanding physiologist I.P. Pavlova. Reflected some points of his scientific activities and biographies. Particular attention is paid to the image of I.P. Pavlova in the works of Russian artists and sculptors – contemporaries of the scientist.