Numerous studies have shown the critical role of sirtuin-1 deacetylase (SIRT1) in the protection of renal cells from endogenous and exogenous stresses. A protective role for SIRT1 has been established in both podocytes and renal tubular cells in many kidney diseases, including diabetic nephropathy (DN). SIRT1 has also been shown to have nephroprotective effects in DN, in part through the deacetylation of transcription factors involved in disease pathogenesis, such as p53, FOXO, RelA / p65NF-KB, STAT3, and PGC1a / PPARy. Recently, it was found that podocyte-specific overexpression of SIRT1 attenuates proteinuria and kidney damage in an experimental model of DN, suggesting the possibility of using SIRT1 as a potential target for the treatment of kidney disease. In addition, SIRT1 agonists such as resveratrol and BF175 have been shown to reduce diabetic kidney damage in several experimental animal models. It has also been shown that puerarin, a Chinese herbal medicine, activates SIRT1, providing nephroprotection in a mouse model of DN. In addition to SIRT1 agonists, inhibitors of bromodomain, in particular, MS417, also have a nephroprotective effect. These results suggest that SIRT1 agonists and bromodomain inhibitors may be new potential therapeutic agents that slow the progression of DN.

Hypophosphatasia (HPP) ORPHA 436 is a rare disease with an autosomal recessive/autosomal dominant mode of inheritance due to mutations in the ALPL gene mapped on chromosome 1p36.12, encoding a nonspecific tissue isoenzyme alkaline phosphate (TNSALP). Currently, there are more than 400 known mutations in the ALPL gene. HPF is characterized by variability of manifestations from a mild course with minor damage to bones and teeth to severe forms with damage to the nervous system, lungs, and kidneys. In different countries, data on the prevalence of HPP differ, the average prevalence of severe forms is ~ 3.3 cases per 1 million newborns. In Europe, the prevalence of severe forms is 1: 300000 and moderately severe 1: 63701. The prevalence of mild HPP is thought to be much higher. The expected prevalence of severe forms in the Russian Federation is 1: 100000. GPP is diagnosed in patients of any age (with manifestation in utero, in childhood, or in adulthood).

HPP is an orphan disease, occurring in patients with damage to many organs and systems: bone (osteoporosis, rickets, fractures, growth retardation), lungs (hypoplasia of the lungs, respiratory failure), central nervous system (vitamin B-dependent convulsions), kidney (calciuria, nephrocalcinosis, chronic kidney disease). In the absence of timely enzyme replacement therapy for severe forms of HPP, characterized by a progressive course, the prognosis for life is unfavorable. The only effective treatment for patients is enzyme replacement therapy in combination with symptomatic therapy. The article presents the features of the phenotype and genotype, clinical forms of HPP (perinatal severe, lethal, perinatal benign, infant, pediatric, adult, and odontohypophosphatasia), methods of early diagnosis, the strategy of pathogenetic enzyme replacement therapy of severe and moderate forms in pediatric and adult patients. In the absence of a timely diagnosis, pathogenetic treatment of GFF, there is a high risk of progression with disability and death.

Free light chains (FLC) of immunoglobulins have been of interest to researchers in various branches of medicine since their discovery in the late 19^th and early 20^th centuries. In addition to hematology, where the role of monoclonal FLC (mFLC) produced by the clone of the B-cell line is being actively studied, other specialties are no exception. Thus, in modern neurology and rheumatology, polyclonal FLC (pFLC), produced by B-lymphocytes during their excessive immune/autoimmune stimulation, are being actively studied. In the pathogenesis of kidney disease, both mFLC and pFLC can be involved. The importance of mFLC for nephrology is associated, firstly, with various variants of kidney damage in monoclonal gammopathies - cylinder nephropathy, AL-amyloidosis, etc., and secondly, with the initiation of the epithelial-mesenchymal transition and the progression of sclerotic changes in the renal tubulointerstitium. With regard to pFLC, their increased level in kidney pathology of various origins is associated with an unfavorable prognosis not only in relation to the progression of chronic kidney disease but also in life. This allows us to reasonably assume the participation of PSLC in the initiation of profibrotic processes in the kidney. Currently, it is believed that the mechanism of epithelial-mesenchymal transition, which underlies the formation of fibrosis of the renal parenchyma, can be mediated not only by mFLC, but also by pFLC, which has been demonstrated in a limited number of studies in some glomerulopathies. The review outlines the current understanding of FLC, as well as the role of mFLC and pFLC in renal pathology.

THE AIM: to evaluate the effect of visceral obesity, adipokine status on the functional state of the kidneys in patients with arterial hypertension (AH), obesity, and chronic heart failure (CHF).

PATIENTS AND METHODS. 383 AH patients aged 45-70 years were divided into four groups: group 1 - persons with AH without obesity and CHF, group 2 - AH + obesity without CHF, group 3 - AH + obesity + CHF, group 4 - AH + CHF without obesity. A clinical examination was carried out, the indicators of visceral obesity, adipokine status, and functional state of the kidneys were assessed. In addition to descriptive statistics, comparison of groups with each other, and correlation analysis, multivariate regression analysis was used with the construction of regression equations.

RESULTS. Revealed statistically significant differences between 1 and 2, 1 and 3, 2 and 4, 3 and 4 groups not only in body mass index (BMI) - 23.9 [22.4; 24.3] vs 32.8 [31.1; 36.3], 23.9 [22.4; 24.3] vs 33.6 [30.8; 35.6], 32.8 [31.1; 36.3] vs 24.1 [23.1; 24.5], 33.6 [30.8; 35.6] vs 24.1 [23.1; 24.5] kg / m², respectively, but also by the percentage of visceral fat (7.0 [6.0; 8.0] vs 14.0 [11.0; 16.0] vs 18.0 [14.3; 22.0] vs 8.0 [5.0; 10.0] % in groups 1,2, 3 and 4, respectively - p_1-2, p_1-3, p_2-3, p2-4, p_3-4 less than 0,0001, p_1-4 = 0.022. The level of leptin in blood serum was significantly lower in group 1 in comparison with 2, 3, 4, and in group 4 in comparison with 3 (6.9 [6.6; 22.7] vs 64.8 [59.3; 70.3], 63.6 [42.0; 86.1], 58.7 [18.9; 73.5] and 58.7 [18.9; 73, 5] vs 63.6 [42.0; 86.1] ng / ml, respectively) The serum adiponectin concentration was statistically significantly higher in group 1 compared with group 2, 3 and in group 4 compared with group 3 (36.6 [29.2; 44.1] vs 18.9 [17.1; 20.6] vs 26.9 [22.2; 32.2] and 36.8 [20.2; 62.8] vs 26,9 [22.2; 32.2] ng / ml, respectively) Visceral obesity index (VAI) was 1.49 [1.24; 2.07] vs 2.58 [2.03; 3.37] vs 3.08 [2.59; 3.84] vs 2.36 [1.81; 3.13] c.u. in groups 1,2, 3, 4, respectively, p_1-2 = 0.0007, p_{1 -4} = 0.0001, p_2-3 = 0.017, p_1-3 and p_3-4 less than 0.00001. There was a significant decrease in the glomerular filtration rate (GFR) in groups 3 and 4 in comparison with group 1 (59.0 [53.0; 67.8] and 69.0 [62.0; 83.0] vs 75.0 [68.0; 96.0] ml / min / 1.73 m², respectively), as well as in group 3 in comparison with 2 and 4 (59.0 [53.0; 67.8] vs 71.0 [60.0; 86, 5] and 69.0 [62.0; 83.0] ml / min / 1.73 m², respectively). The level of albuminuria increased with adherence to hypertension of obesity and / or CHF (14.2 [3.7; 44.4] vs 36.9 [13.6; 118.2] vs 149.8 [92.2; 247, 6] vs 72.0 [36.2; 104.7] mg / g in groups 1,2, 3 and 4, respectively, the differences are statistically significant between 1 and 2, 1 and 3, 1 and 4, 2 and 3, 3 and 4 groups). The concentration of p2-microglobulins in urine was significantly lower in group 1 compared with groups 3 and 4 (0.10 [0.05; 0.42] vs 0.25 [0.20; 0.31] vs 0.27 [0,19; 0.31] pg / ml). Correlation analysis revealed the peculiarities of the influence of visceral obesity, adipokine status on the functional state of the kidneys in each of the studied groups.

CONCLUSION. The study confirmed the negative effect of visceral obesity, hyperleptinemia, and hypoadiponectinemia on the progressive deterioration of the renal function in hypertensive patients with adherence to obesity and/or CHF.

BACKGROUND. The relevance of identifying new biomarkers of the cardio-renal syndrome in patients with coronary heart disease is beyond doubt. It is promising to study the indicators of tubular dysfunctions as predictors of the risk of cardiovascular complications in patients without primary kidney pathology.

THE AIM. Analysis of the effect of β₂-microglobulinuria on the prognosis of cardiovascular complications in patients with chronic ischemic heart disease in the long-term period after myocardial revascularization.

PATIENTS AND METHODS. The study included 90 patients with coronary artery disease and indications for myocardial revascularization. Coronary bypass surgery was performed in 64 people, coronary artery stenting - in 26. Clinical and anamnestic data were collected in all patients, standard laboratory and instrumental diagnostics were performed. In addition, the level of β₂-microglobulin (β₂-MG) in the first morning portion of urine was determined at different study dates. The endpoint was considered to be the presence of acute forms of coronary heart disease - myocardial infarction and unstable angina. Survival after 5.8 ±0.1 years after myocardial revascularization was 69 %.

RESULTS. A positive linear relationship of weak strength was established between the level of diastolic blood pressure (DBP) and β₂-MG of urine obtained before myocardial revascularization (r = 0.28, p = 0.03). Moreover, the Kaplan-Meyer survival analysis showed the effect of an increase in β₂-MG of urine over 0.2 ng/ml on the risk of AMI in the long-term period after myocardial revascularization (p = 0.025). It was found that an increase in the concentration of β₂-MG in urine determined before myocardial revascularization is a statistically significant risk factor for the development of unstable angina in the long-term period after RM (χ²-criterion = 7.17, p = 0.007).

CONCLUSION. It has been shown that an increase in the concentration of β₂-MG in urine, reflecting the presence of tubular dysfunctions, can be considered as a predictor of an unfavorable cardiovascular prognosis in patients in the long-term period after myocardial revascularization.

INTRODUCTION. The data obtained in clinical studies of recent years of the possible inhibitors of sodium-glucose cotransporter type 2 (SGLT2) nephroprotective effect in type 2 diabetes mellitus necessitate the further study of these drug's effect on kidney injury risk factors.

THE AIM: to study the effect of SGLT2 inhibitor empagliflozin as part of combination therapy on the main mechanisms of kidney damage in patients with type 2 diabetes.

PATIENTS AND METHODS. We have completed a clinical randomized study in parallel groups in patients with type 2 diabetes of nephroprotective effects of SGLT2 inhibitor empagliflozin during 2 years. The study included 244 patients with type 2 diabetes with a preserved glomerular filtration rate (GFR) and moderate arterial hypertension (AH), who had previously taken perindopril and indapamide, but did not reach target blood pressure (BP) values. Patients were randomized into 2 groups: Group I (n = 120) took Perindopril 10 mg per day, Indapamide retard 1.5 mg per day, β-blocker Carvedilol 12.5-25 mg 2 times a day; Group II (n = 124) was additionally prescribed empagliflozin 25 mg per day. The study endpoints were GFR changes, albuminuria, and renal blood flow as measured by Doppler imaging. Also studied the dynamics of blood pressure and glycemic control.

RESULTS. It was found that empagliflozin as part of complex therapy for type 2 diabetes is able to reduce albuminuria and prevent a decrease in GFR within a 2-year follow-up period. The use of empagliflozin promoted an increase in the rate of renal blood flow and a decrease in intrarenal vascular resistance and had a corrective effect on the daily dynamics of blood pressure and glycemic control.

CONCLUSION. Empagliflozin improves intrarenal and systemic hemodynamics, prevents a decrease in GFR, reduces albuminuria, and improves glycemic control in type 2 diabetes.

BACKGROUND. Cardiovascular complications caused by vascular calcification in chronic kidney disease (CKD) are closely related to disorders of bone and mineral metabolism, the mechanisms of which require further study.

THE AIM: to clarify the role of the regulatory proteins of bone metabolism of sclerostin and osteoprotegerin in the processes of vascular calcification and the development of cardiovascular complications in CKD.

PATIENTS AND METHODS. 110 patients with stage 3-5D CKD (67 men) were examined. Median age is 47.0 (23.0-68.0) years. Osteoprotegerin (OPG), sclerostin, intact parathyroid hormone (IPTG), troponin I in blood serum were determined using commercial kits "Enzyme-linked Immunosorbent Assay Kit for Sclerostin" ("Cloud-Clone Corp.", USA) and commercial kits "ELISA kit" ("Biomedica" (Austria) by enzyme immunoassay (ELISA). Echocardiography with Dopplerography was performed on the device "ALOKA 4000" ("Toshiba", Japan). The left ventricular myocardial mass index (LVMI) and peak systolic blood flow velocity in the aortic arch (Vps, peak systolic velocity) were determined to quantify hemodynamic changes indirectly indicating the state of the aortic vascular wall.

RESULTS. Analysis of the ratios of the calculated glomerular filtration rate (EGFR), IMLJ, Vps, OPG, and sclerostin showed that a decrease in excretory kidney function is accompanied by an increase in the concentrations of OPG and sclerostin in the blood serum. At the same time, there is an increase in IMLJ and Vps. During the correlation analysis, it was shown that the level of OPG was positively correlated with the level of sclerostin and negatively with the level of iPTG.

CONCLUSION. In our study, we obtained data confirming the interactive interaction between the vascular and bone systems. Morphogenetic proteins-inhibitors of bone metabolism (sclerostin and OPG) play a significant role in the defeat of the cardiovascular system in patients with CKD, as they promotes the development of vascular calcification.

BACKGROUND. In the modern era, COVID-19 is the biggest problem facing doctors and scientists around the world. SARSCоV-2 is a multisystem infection that is not limited to lung damage and has the immuno-mediated effect of negative effects on organs and systems, including the kidneys. To date, there is no precise understanding of the pathogenesis of nephrological disorders in patients with COVID-19. Patients with chronic kidney disease (CKD) are a group of particularly high risk of CO-VID-19 infection and high mortality in the development of the disease.

THE AIM: to evaluate the features of the course of a new coronavirus infection (COVID 19) in patients with acute kidney injury and terminal renal insufficiency.

PATIENTS AND METHODS. The study of clinical, laboratory and instrumental parameters was carried out in 119 patients (67 men and 52 women) diagnosed with COVID-19. The average age of the patients was 63.1±1.7 years. All patients were divided into two groups: group 1 - patients with CKD and HD, group 2 - patients with newly diagnosed kidney damage against the background of coronavirus infection (COVID-19). Statistical data analysis was carried out using the software package "IBM SPSS Statistics 21.0" (USA) (Russified version).

RESULTS. As a result of the study, it was found that in the clinical picture of COVID-19 patients suffering from CKD and undergoing hemodialysis, such a symptom as myalgia was noted 2 times more often, the percentage of saturation of arterial blood hemoglobin with oxygen (SaO₂,%) was significantly lower compared to patients with newly diagnosed kidney damage on the background of infection. The duration of the temperature reaction during the disease was 5 times longer than in patients without CKD. Although the incidence of lung damage in patients of both groups was identical, mortality was significantly higher in the group of patients with CKD.

CONCLUSION. In the patients examined by us, proteinuria, an increase in the level of nitrogenous metabolites, as well as D-dimers in both groups, are associated with increased mortality. Mortality in patients with CKD and HD was several times higher than in those without pathology of the urinary system. The severity of the patients' condition was primarily due to the symptoms of damage to the respiratory system, but the degree of renal dysfunction is undoubtedly an important prognostic value. Thus, monitoring the state of individual nephron structures in patients with CO-VID-19 is of great importance, and emergency nephroprotective measures may be crucial in the fight against cytokine storm.

BACKGROUND. Currently, there is a stable deterioration in the somatic health of preschool-age girls, which creates a real threat to the realization of reproductive function in the future. The state of vaginal microbiocenosis in preschool girls suffering from recurrent urinary tract infections (UTIs) remains a little-studied problem.

THE AIM: to assess the state of the vaginal biotope in preschool girls suffering from recurrent UTIs.

PATIENTS AND METHODS. 92 girls aged 3-6 years were examined, of which: group 1 (n=32) - patients with recurrent UTI; group 2 (n=30) - patients with rare UTI; group 3 (n=30) - girls of 1,2 health groups. Vaginal microbiocenosis was assessed by quantitative PCR using the «Femoflor-17 test system». Statistical analysis was performed using the application program "Statistica 6.0 for Windows".

RESULTS. Facultative anaerobes predominate in the vaginal microbiocenosis of patients with UTI, the absolute content of which is significantly higher in patients with the recurrent course (p <0.05). The relative number of facultative anaerobes is significantly higher in patients with rare UTIs (p<0.05). In patients with recurrent UTI, the absolute and relative content of obligate anaerobes is lower than in patients with rare UTI and girls from the control group. The index of total bacterial mass in patients with UTI, compared with girls of the control group, is significantly higher (p<0.05). In patients with UTI, an increase in the colonies of the Enterobacteriacea family and a decrease in obligate anaerobes were determined in comparison with similar indicators of girls in the control group.

CONCLUSION. The presence of recurrent UTI in preschool girls is a risk factor for the development of the severe vaginal dysbiotic condition. Rare UTIs can also be a risk of developing vaginal dysbiosis. Real-time multi-dimensional PCR provides quantitative and qualitative characteristics of the conditionally pathogenic flora of the vaginal biotope.

BACKGROUND. Vitamin D has been known since 1928. The wide range of its metabolic effects paradoxically contrasts with the high prevalence of insufficiency and deficiency in the population of different regions of the world. A number of publications have demonstrated information about the relationship between vitamin D and insulin production by beta cells of the pancreas, as well as the excretory function of the kidneys.

THE AIM: to assess the level of vitamin D in patients with diabetes mellitus in combination with chronic kidney disease (CKD).

PATIENTS AND METHODS. A questionnaire and a study of the level of 25-hydroxyvitamin D, creatinine, urea, and glucose in the blood were conducted in 117 patients aged 18 to 84 years who gave voluntary consent. All patients were divided into three study groups: group 1 - patients with long-term DM, group 2 - patients with newly diagnosed DM, and 3 - control group. The glomerular filtration rate (GFR) is calculated by the formula CKD-EPI.

RESULTS. As a result of the study, it was found that patients with DM, regardless of the duration of its course, were more likely to suffer from vitamin D deficiency, compared with the control group, where D-deficiency and D-deficiency occurred with the same frequency. In addition, patients with DM were more likely to have stage 2-3A CKD, in contrast to the control group, where preserved kidney function prevailed. We also identified and confirmed the direct dependence of GFR on the level of vitamin D in the blood of patients with DM.

CONCLUSION. In the patients studied by us, a clear association was found between a lower vitamin D index in the blood serum and the presence of a history of diabetes. They also showed a tendency to decrease the excretory function of the kidneys and the formation of CKD. Consequently, a full-fledged diagnosis of vitamin D-deficient conditions and timely initiated therapy can prevent or at least slow down the progression of CKD in these patients, which will certainly improve their quality of life and reduce the costs of health services for renal replacement therapy and rehabilitation of this group of patients.

BACKGROUND. Natriuretic peptides have cardio- and renoprotective effects, inhibiting inflammatory and proliferative processes. The role of natriuretic peptides in the early diagnosis and characterization of chronic kidney disease (CKD) and cardiovascular complications as the disease development and progresses has not been studied.

TNEAIM: to study the level of natriuretic peptides in children depending on the stage of CKD development and to assess the significance of this indicator.

PATIENTS AND METHODS. The study involved 93 children with congenital diseases of the urinary system at the age from 3 to 18 years. Three groups were identified: group I - 54 patients with CKD stage I , group II - 29 patients with CKD stage II; Group III - 10 children with CKD stages IV-V (patients with CKD stages IV and V were combined due to their small amount). Control group - 10 clinically healthy children of the corresponding age. The N-terminal propeptide of natriuretic hormone (NT-proBNP) was determined in the blood by the enzyme-linked immunosorbent assay.

RESULTS. An increase in the level of NT-proBNP by 28.7% takes place already in the early stages of CKD. With the progression of CKD, an increase in the level of NT-proBNP was noted from 57.4 % in children in the group of patients with stage I CKD to 80 % in children in group III patients. The maximum concentrations of NT-proBNP, many times higher than those in CKD stages I and II, were observed in children with CKD stages IV-V. The degree of increase in the level of NT-proBNP correlated with the severity of CKD.

CONCLUSION. In the diagnosis and characterization of CKD and cardiorenal syndrome in children, the determination of the level of natriuretic peptides is of great importance. A high level of natriuretic peptides characterizes the presence of cardiorenal relationships and can be used as an additional criterion for assessing the severity of CKD, including at the early stages of its development.

INTRODUCTION. СЗ-glomerulopathy (СЗ-GP) is a spectrum of diseases caused by dysregulation of the alternative complement pathway. The present study was carried out taking into account the limited number of foreign and the absence of original studies in the Russian population.

THE AIM. Analysis of clinical and morphological manifestations of СЗ-GP at the time of primary diagnosis.

PATIENTS AND METHODS. Retrospective analysis of the etiology, clinical data and morphology of СЗ-GP identified in the period 2006-2021.

RESULTS. The study included 60 cases. The average age of patients is 4З±17 years. Nephrotic syndrome was detected in 47 % of patients; in 58 % of cases the estimated glomerular filtration rate was <60 ml/ min/иЗ m². The dominant morphological pattern was membranoproliferative glomerulonephritis (75% cases). In 2 cases, СЗ-GP debuted with clinical and morphological manifestations of the disease of minimal changes, in which the identification of characteristic electron-dense deposits became obvious when performing a second biopsy. 4 cases had at the onset classical signs of complement-mediated thrombotic microangiopathy (atypical hemolytic uremic syndrome) in combination with C3-GP or its subsequent development.Ultrastructural examination was performed in 40 cases. 8 patients (20%) were diagnosed dense deposit disease, 32 patients - C3-glomerulonephritis. Primary C3-GP was detected in 87 % of patients, secondary - in 13 % (monoclonal gammopathies - 10 %, autoimmune diseases - 3 %).Increased level of antibodies to factor H was detected in 2 of 12 patients who underwent this study. Nucleotide variants of unknown clinical significance in complement genes were detected in 2 out of 6 patients during molecular genetic testing.

CONCLUSION. C3-GP is a severe variant of glomerular damage with a heterogeneous etiological structure, which requires the use of ultrastructural and molecular diagnostics, as well as clinical analysis and identification of pathogenetic mechanisms to determine approaches to therapy.

BACKGROUND. Anomalies in the development of the uterus and vagina in some cases are combined with defects of the urinary tract. Therefore, the analysis of clinical situations associated with combined urogenital pathology in girls is of current and practical importance.

THE AIM: to assess the state of reproductive health in girls with reproductive anomalies, renal agenesis, and other diseases of the urinary tract.

PATIENTS AND METHODS. The study was conducted in 5 adolescent girls, including 3 patients with kidney agenesis, 1 patient with dysmetabolic nephropathy and nephroptosis, and 1 patient with recurrent urinary tract infection. In the analysis of clinical cases, the anatomical and functional features of the reproductive system are presented.

RESULTS. The first 3 clinical cases are associated with the presence of kidney agenesis in the girl. In 1 clinical case, the clinic of the Mayer-Rokitansky-Kuester-Hauser syndrome (SMRKH) type II, including aplasia of the uterus and vagina and renal malformation, is presented. In clinical case 2, it was shown that modern transabdominal ultrasound examination of the pelvic organs, similar to MRI, can reveal the Herlin-Werner-Wunderlich syndrome. Agenesis of the kidney is one of the manifestations of trisomy of 22 pairs of chromosomes, which was noted in a patient from 3 clinical cases. 4 clinical cases is associated with the fact that kidney pathology, including nephroptosis, dysmetabolic nephropathy, can be combined with impaired sexual development. In 5 clinical case, type I SMRCC was described in a patient with recurrent urinary tract infection.

CONCLUSION. Congenital malformations of the female genital organs are a rare pathology that requires special attention. Due to insufficient data concerning the mechanism of development of malformations of the genitourinary system, this problem requires further detailed study.