The review is devoted to the consideration of the nephroprotective effect and its mechanisms in new hypoglycemic drugs gliflozins, identified in largescale randomized placebo-controlled trials and experimental studies. It was found that inhibition of sodium-glucose co-transporter 2 (SGLT2) in the proximal tubules of the kidneys when using these drugs not only leads to a decrease in blood glucose levels, a decrease in blood pressure, body weight, and uric acid content in blood plasma but also delays the progression of chronic kidney disease, inhibiting the development of diabetic nephropathy. This beneficial effect is multifactorial. It is caused by the diuretic and natriuretic effects, a decrease in albuminuria, a decrease in glucotoxicity in the cells of the renal tubules, a hemodynamic effect on kidney function, and a direct anti-inflammatory effect. It is discussed why the use of SGLT2 inhibitors restores tubuloglomerular feedback, which is disrupted in the initial period of diabetic nephropathy and leads to hyperfiltration in the remaining nephrons. Information is provided on the restoration of impaired mitochon drial function due to the positive effect of drugs on the ionic composition of renal tubule cells. This greatly contributes to the enhancement of autophagy, the lysosome-mediated pathway of degradation and removal of damaged organelles, and normalizes intracellular homeostasis. The probable mechanism of autophagy enhancement through increased activity of energy deprivation sensors of AMPK and SIRT1 cells is considered. Possible mechanisms of development of anti-inflammatory and antioxidant action of SGLT2 inhibitors through inhibition of inflammasome activity are discussed. The question of the possible use of gliflozins in chronic kidney disease, the pathogenesis of which is not associated with diabetes mellitus, is considered.

Inhibitors of renal sodium-glucose cotransporter type 2 (SGLT2) are a new class of antidiabetic drugs that have recently been introduced into clinical practice for the treatment of patients with type 2 diabetes mellitus. According to CREDENCE study, the inclusion of canagliflozin in drug therapy for patients with type 2 diabetes mellitus not only provides adequate control of blood glucose but also has a pronounced nephroprotective effect, which manifests in a significant reduction in the risk of progression of renal dysfunction in patients with stages 2, 3a and 3b CKD. The identification of nephroprotective effects in SGLT2 inhibitors, which is not related to their antihyperglycemic effect, suggests the possibility of using drugs of this class for drug therapy of patients with CKD of non-diabetic etiology. The review presents the data of clinical studies devoted to elucidating the participation of diuretic action and the associated decrease in blood pressure and venous stasis in the kidneys, improving glomerular hemodynamics and inhibiting the activity of intrarenal RAS in the mechanism of nephroprotective action of these drugs. Large-scale DAPA-CKD and EMPA-KIDNEY studies are currently underway, the results of which will provide information on the clinical efficacy and safety of dapagliflozin and empagliflozin in non-diabetic patients with the impaired renal function of varying severity, including those with stage 4 CKD. Initial data obtained in the DAPA-CKD trial indicated that dapagliflozin, when added to nephroprotective therapy, significantly improves renal outcomes not only in patients with type 2 diabetes but also in patients with CKD of non-diabetic origin, including those with glomerulonephritis, hypertensive nephropathy, and other kidney damage.

Hantavirus nephropathy (CVI) is considered to be acute kidney injury (AKI) associated with hantavirus infection (CVI). This infection in the countries of the European and Asian continents causes hemorrhagic fever with renal syndrome (HFRS). However, up to 60% of kidney damage is manifested by pathological changes in urinary sediment without signs of AKI, in connection with which the problems of terminology and diagnosis of kidney damage in HFRS were discussed. A review of the world literature of recent years, devoted to the study of modern data on the pathogenesis of CVI, is presented. The data were revealed that explain the organ specificity of the pathological process in different variants of CVI. The data were revealed that explain the organ specificity of the pathological process in different variants of CVI. The mechanisms related to various aspects of the pathogenesis of hantavirus nephropathy are considered. The factors that alter the functional activity of target cells through the direct action of the virus and the factors mediated by the immune response of the biological host to viral proteins in the form of the action of cytokines ("cytokine storm") causing damage to target organs (indirect factors) are listed. The influence of the hantavirus serotype, genetic factors, and the nature of the immune response of the biological host organism on the severity of renal dysfunction was shown. The concept of "acute damage to podocytes" is disclosed, which explains massive protein uria at the onset of the disease. The molecular and cellular mechanisms of damage to the main compartments of the kidney during hantavirus infection are presented. Disorders of hemostasis and mechanisms of hypercoagulation were demonstrated that underlie glomerular AKI due to acute microvascular syndrome, which is realized in the form of disseminated intravascular coagulation (DIC), hemolytic uremic syndrome (HUS), and thrombotic microangiopathy (TMA). The results of experimental data obtained on a laboratory model of infection and in cell culture, histological studies of autopsy material, and nephrobiopsy specimens from patients with hantavirus nephropathy are demonstrated.

BACKGROUND. The survival of dialysis patients remains unsatisfactory. A number of observational studies have shown that the conditions of initiation of dialysis can influence long-term outcomes, including mortality.

THE AIM. To compare the mortality of patients under predefined conditions of optimal (planned) and suboptimal (unplanned) dialysis initiation.

METHODS. Using the MEDLINE and EMBASE databases from inception to June 2020, we conducted a systematic search for studies that examined the overall mortality of patients who met or did not meet the predefined conditions for an “optimal” start of renal replacement therapy (RRT): planned vs. unplanned onset; initiation of substitution therapy on permanent access vs. temporary; with priorobservation of the nephrologist vs. without it. As a result of a systematic search, subsequent analysis and selection of publica tions, 8 studies were included in the meta-analysis (total number of incident patients was 22755; 13680 patients met the conditions of the optimal dialysis start).

RESULTS. All-cause mortality among patients with the conditions of suboptimal dialysis start was higher than in those with the optimal start (34.4 % vs. 46.6 %, p<0,001) with the increase in the relative risk (RR) of fatal outcome by 35.1 % (95 % confidence interval (CI) 30.8 %-39.4 %, p<0.0001). Estimated number of patients needed to start dialysis in the optimal conditions to prevent 1 death was 8 (95 % CI 7-9).

CONCLUSION. The meta-analysis demonstrated the relationship between the urgent initiation of RRT, the use of temporary access for dialysis, and the lack of timely prior follow-up by a nephrologist with an increase in mortality. Prevention of dialysis initiation in these suboptimal conditions in real-world clinical practice can be an effective tool for improving patient-centered outcomes.

BACKGROUND. The course and outcomes of primary IgA nephropathy in children are variable. Early therapy for high-risk individuals can help to delay the development of end-stage renal disease.

THE AIM: to analysis of risk factors for progression and outcomes in children with IgA nephropathy, taking into account clinical and morphological data at the onset and during follow-up.

PATIENTS AND METHODS. A retrospective study of 75 children was carried out; the median follow-up was 28 months. The median age of onset was 9.1 years. Patients were divided into 2 groups: 1st – patients with idiopathic IgA nephropathy (n= 53), 2nd – patients with Shenlein-Henoch purpura (n = 22). The diagnosis of primary IgA nephropathy was morphologically confirmed in all patients. Nephrobiopsy data were classified according to the Oxford scale (MEST-C score). The age of onset and first-time admission, the level of proteinuria and glomerular filtration rate (GFR) at the onset, at 12 months, at the end of follow-up, mean arterial blood pressure, MEST-C score, medication before nephrobiopsy were investigated. Progression was determined as a decrease in GFR less than 60 ml/min/1.73 m². Outcomes were assessed by absence/presence of remission. We provided a search for factors influencing GFR at the end of the follow-up. Data analysis was performed using Student's t-test, Mann-Whitney, χ^2, Fisher, linear regression model, binary logistic regression.

RESULTS. Unlike adults, the predictive value of the MEST-C score in children has not been proven and is not associated with a decrease in GFR <60 ml/min/1.73 m². GFR at the end of follow-up was lower in the idiopathic IgA nephropathy group than in group 2. The use of multiple linear regression predicts GFR on average after 28 months of observation.

RESULTS. Unlike adults, the predictive value of the MEST-C scale in children has not been proven and is not associated with a decrease in GFR <60 ml/min/1.73 m². GFR at the end of follow-up was lower in the idiopathic IgA nephropathy group. The use of multiple linear regression predicts GFR on average after 28 months of observation.

CONCLUSIONS. The influence of morphological factors on the outcome and course of IgA nephropathy has not been proven. The level of GFR at the onset, mean blood pressure, and the age of the first-time admission turned out to be independent variables, which made it possible to identify children with an expected decrease in GFR less than 90 ml/min /1.73 m² to the group of specific outpatient follow-up.

INTRODUCTION. Previously, we postulated the common pathogenetic mechanisms in bronchial asthma (BA) and chronic kidney disease (CKD). The kidney injury molecule-1 (KIM-1) is considered as an early biomarker of the proximal renal tubules damage. In the available literature, there is only one clinical study of KIM-1 in children BA.

THE AIM of the study is to  assess KIM-1 levels in different variants of BA.

PATIENTS AND METHODS. The 24 BA patients were examined. Glomerular filtration rate (eGFR) by CKD-EPI was calculated. The concentration of the kidney injury molecule -1 (KIM-1) in urine was determined by enzyme immunoassay. Urinary albumin was determined by the immunoturbidimetric method. VEGF-A in serum was determined by enzyme immunoassay (sandwich variant).

RESULTS. In the urine of BA patients, KIM-1 was detected, and its level in patients with a non-allergic variant is significantly higher than in patients with an allergic variant of the disease. Factor analysis was carried out, the following was revealed: the KIM-1 component with a high positive factor load is associated with a key characteristic of BA such as the severity of the disease course, as well as with a high negative factor load – with a component of the glomerular filtration rate; the KIM-1 component with a high positive factor load is associated with the presence of drug intolerance in BA patients; the microalbuminuria component is negatively associated with the severity of BA disease course, as well as with the components KIM-1, VEGF-A, which seems to be associated with the use of systemic glucocorticoids in severe BA disease course; the KIM-1 component is positively associated with the VEGF-A component, which may indicate possible KIM-1 involvement in hypoxic kidney injury in BA.

CONCLUSION. The obtained data suggest that in BA, first of all, in a non-allergic variant of the disease and in a severe course of BA, kidney injure is formed, detected using kidney injure molecule-1 KIM-1.

BACKGROUND. Until recently there is no understanding of the clinical features and the reasons for the progression of complications of diabetes-associated nephrolithiasis (NLT) which limits the development of effective treatment for patients with this kidney pathology.

THE AIM was to investigate the molecular mechanisms of hematuria and leukocyturia in the comorbidity of nephrolithiasis with type 2 diabetes.

PATIENTS AND METHODS. The study analyzed the clinical, instrumental, and laboratory data of 196 patients with NLT; the study included 48 (24.5 %) patients with comorbidity of NLT with type 2 diabetes. All patients at the stage of hospitalization underwent a comprehensive clinical and laboratory examination according to the traditional scheme adopted for the diagnosis of NLT. ATP, PAF, and collagen (Sigma) agonists at EC50 concentrations causing aggregation at the 50 % level in healthy individuals were used to analyze the functional activity of platelet (PLT) receptors. PLT aggregation was assessed by the turbidimetric method using a ChronoLog analyzer (USA).

RESULTS. Microhematuria occurred in 27 (56.2 %) patients and gross hematuria in 21 (43.8 %) patients out of 48 patients with type 2 diabetes-associated NLT. Microscopy of urine in patients with comorbidity of NLT revealed a greater number of erythrocytes (P = 0.014); gross hematuria (P = 0.034) and leukocyturia (р=0,003) were more common in this cohort of patients. NLT complications occurred against the background of increased reactivity of P2X receptors, PAF receptor, and GPVI receptor (p <0.001) of PLT compared with that in patients with NLT without DM. The progression of leukocyturia was accompanied by increased severity of hematuria and was manifested by increased activity of GPVI receptors (p <0.001).

CONCLUSION. The influence of diabetes on the pathogenesis of NLT complications is associated with increased ischemia of kidney tissue, systemic inflammatory response, and vascular wall remodeling. The activity of P2X, PAF, and GPVI platelet receptors could be considered as a system of potential biomarkers and prognostic factors of complications in the comorbidity of NLT with type 2 diabetes.

INTRODUCTION. Magnesium is the second most common intracellular cation, is a cofactor for more than 300 enzymes, affects the functional state of the cardiovascular system through various mechanisms, in particular, through the action on the smooth muscle cells of the vessels, modulation of the renin-angiotensin-aldosterone system, regulation of sodium and calcium homeostasis. Therefore, maintaining a normal level of magnesium in the blood is an urgent task, and the consumption of drinking water enriched with magnesium can be considered as a method of correcting an insufficient intake of exogenous magnesium.

THE AIM. The purpose of the study was determined – to evaluate the effect of drinking water with different contents of magnesium ions and a complex of magnesium with calcium on the state of the cardiovascular system of rats with genetically determined arterial hypertension.

MATERIALS AND METHODS. From 6–7 weeks of age, male SHR rats received drinking water of various compositions for two months: in the first group (hCа+Mg) – with increased content of calcium and magnesium (120 mg/l Ca²⁺ and 45 mg/l Mg²⁺), the second (nCа+Mg) – drinking water normalized by mineral composition (60 mg/l Ca²⁺ and 25 mg/l Mg²⁺), in the third (hMg) – enriched Mg²⁺ (45 mg/l), the fourth (control) control group – St. Petersburg tap water with a low mineral content (8 mg/l Ca²⁺ and 3 mg/l Mg²⁺). WKY rats were divided into 2 groups: one group (hMg) received water enriched with Mg²⁺ (45 mg/l), the control WKY (control) group received water with a low mineral content (8 mg/l Ca²⁺ and 3 mg/l Mg²⁺). After 2 months, the blood pressure of rats on the tail was measured by the cuff method, the level of urea, cholesterol, total calcium, and albumin in the blood serum was analyzed, left ventricular mass index (LVMI) and myocardial mass index (MMI) were calculated. The spontaneous contractile activity of the portal vein (PV) was recorded by myography (in vitro) in isometric mode. The following were analyzed: frequency, total and maximum amplitude of phase-tonic contractions, the area under the contraction curve in 1 min, which characterizes the work performed by the vein. %). 

RESULTS. Enrichment of drinking water with Ca²⁺ and Mg²⁺ had a more pronounced antihypertensive effect in SHR rats compared with the hMg²⁺ group. In WKY rats, magnesium enrichment of water did not affect blood pressure. Modification of the mineral composition of drinking water did not affect MMI and LVMI in both SHR and WKY rats. Interlinear differences were found in the contractile activity of PV in control rats (the amplitude of PV contractions in SHR rats was greater than WKY. Consumption of water enriched with minerals decreased the amplitude of PV contractions, the largest decrease was in the hMg²⁺ group (in SHR, 2.6 times, in WKY, 1.5 times as compared to the control of the corresponding line). The value of the work performed by the PV in the control SHR rats was greater than in the control rats of the WKY line, and the enrichment of water with magnesium caused a decrease in the work performed by the PV only in rats SHR lines (by 55.6 %), but not for WKY. 

CONCLUSIONS. In rats, the consumption of drinking water enriched only with magnesium has an antihypertensive effect; however, it suppresses the spontaneous contractile activity of PV. It is advisable to use a complex of magnesium with calcium, which lowers blood pressure, but maintains an adequate level of contractile activity of the PV.

INTRODUCTION. A high intake of sodium chloride from food is associated with damage not only to the cardiovascular system but also to the kidneys. The mechanisms of the negative effects of high-salt diets on the kidneys have not been established. One of the important links in this process can be microRNAs, which can modulate gene expression at the post-transcriptional level. It is also not known whether soy proteins can counter the kidney remodeling associated with increased salt intake.

THE AIM. To estimate the expression levels of miRNA-133 and 203 in blood serum and urine and miRNA-21 in the urine of cynomolgus macaques received diets for a long time with various table salt contents, including and not including soy proteins.

MATERIALS AND METHODS. Three groups (6 individuals in each) of male cynomolgus macaques at the age of 6–8 years were studied. The first group (control) received a standard diet, the second – a diet with a high content of table salt (8 g NaCl / kg feed), the third – a diet with high salt content in combination with SUPRO 760 soy protein (200 g protein/kg feed). Blood pressure was measured in animals 12 months later. In monkey urine, the relative expression levels of miRNA-21, miRNA-133, and miRNA-203 were determined, in blood serum – the expression levels of miRNA-133 and miRNA-203.

RESULTS. During the follow-up period in the control group, there were no significant changes in the studied parameters. In the groups that received high-salt diets throughout the year, blood pressure also did not change significantly. There was no change in the level of expression of miRNA-133 in the blood serum of monkeys fed a high-salt diet and a standard protein diet. However, in macaques fed a diet high in salt in combination with soy protein, the serum expression of this miRNA was significantly reduced. The expression of miRNA-203 in blood serum did not change significantly. In the control group, there were no changes in the expression of miRNA-21 in urine. In the other two samples, this parameter increased in comparison with the initial values. Both high-salt diets resulted in a significant increase in the relative level of miRNA-133 expression in urine compared to basal values. However, the increase in this indicator in the group of animals fed a high-salt diet in combination with soy isolate was significantly less than in monkeys fed only a high-salt diet. Expression of miRNA-203 in urine was significantly increased only in the group with a high content of table salt without added soy protein.

CONCLUSIONS. It is possible that the effects of high-salt diets on the kidney may be mediated by epigenomic mechanisms and partially modulated by the inclusion of isolated soy proteins in the diet.

Tuberous sclerosis is a polysystemic, genetically determined, autosomal dominant orphan disease that affects approximately 1 in 10,000 people worldwide. Kidney damage in tuberous sclerosis is the leading cause of death due to serious complications, the most common of which is angiomyolipoma bleeding. A feature of renal angiomyolipomas is that they begin to progress and increase in volume from an early age, leading to the progression of chronic kidney disease, while angiomyolipomas more than 30 mm in diameter are at risk of bleeding. Currently, pharmacotherapy of tuberous sclerosis with mTOR inhibitors is the most effective worldwide. In this article, a clinical case of targeted therapy of tuberous sclerosis is presented, the effectiveness is demonstrated, and the features of the course of tuberous sclerosis are also given on a specific example.

Viral epidemics of various scales have ceased to be something extraordinary. However, it is unlikely that the COVID-19 epidemic can be compared to any other, except the Spanish flu epidemic of 1918-1919. The review discusses the pathogenesis of the "cytokine storm" and possible extracorporeal methods of its correction. Following the "Third International Consensus on the definition of sepsis and septic shock (Sepsis-3)", sepsis is recommended to be understood as "life-threatening acute organ dysfunction resulting from a violation of the regulation of the response of the macroorganism to infection". Severe COVID-19 is practically a variant of viral sepsis. However, the disease is not coded as sepsis and is not treated as sepsis. Great hopes are pinned on vaccination, which, presumably, should significantly reduce the likelihood of adverse outcomes. However, while the epidemiological situation is far from ideal, there are no "golden" standards of drug therapy. Therefore, do not forget about direct methods of removing proinflammatory cytokines. Among them, hemofiltration, combined hemocorrection, plasma exchange, combined plasma filtration, and adsorption are discussed. We were not able to identify the ideal method. This is probably due to the difficulties of performing randomized clinical trials among patients with severe COVID-19. The reasons are also discussed in the review.