The article presents current literature data on clinical phenotypes and variants of ALPL gene mutations, the effectiveness of enzyme replacement therapy with asfotase alfa in children with hypophosphatasia (HPP). HPP is inherited disease ORPHA (436). The OMIM catalog contains forms of HPP: perinatal (lethal), infantile; hypophosphatasia of childhood; hypophosphatasia in adults; odontohypophosphatasia. M.E. Nunes (2023) considers 7 forms of HPP, taking into account the age and severity of the clinical manifestation. As a result of worldwide molecular genetic studies, fundamental information has been obtained on the phenotypic features of the manifestation and severity of HFF in pediatric patients, depending on the variants of the ALPL gene mutations. Molecular genetics diagnosis and enzyme replacement therapy with Asfotase alfa in our country are guaranteed for children with HPP at the expense of the «Krug Dobra Foundation», the founder of the foundation is the Ministry of Health of the Russian Federation. The article presents a clinical observation of a proband with hypophosphatasia receiving Asfotase alfa.

Excessive uncontrolled inflammatory and immune reactions often lead to the development of acute and chronic forms of damage to various organs, including the kidneys. Neutrophils are the cells of the innate immune system, which are the first cellular effectors in protecting the host from a variety of pathogens, including bacteria, fungi and protozoa. As the most numerous leukocytes present in human blood, neutrophils migrate early to the foci of inflammation or tissue damage, where they play a significant role in the development of inflammation, recruitment of immune cells, removal of pathogens and tissue repair. Neutrophils also produce pro-inflammatory cytokines and release, in a process called netosis, a network of DNA and granular proteins known as neutrophil extracellular traps (NETs). NETs are potentially toxic, contribute to glomerular damage, activate autoimmune processes, cause vascular damage, and promote renal fibrosis. Numerous studies show that an imbalance between NET production and clearance is detrimental to kidney function. Therefore, strategies aimed at modulating the processes associated with NET may have a favorable prognostic effect. The review discusses the role of the netosis in the pathogenesis of kidney diseases, describes the mechanisms of tissue damage associated with NET, and the therapeutic potential of NET regulatory therapy.

Adrenoleukodystrophy (ALD) is the most common peroxisomal disease of X-linked recessive inheritance caused by a mutation in the ABCD 1 gene located on chromosome Xq28. A characteristic feature of ALD is the lack of correlation between genotype and phenotype. Depending on the time of onset, the main manifestations, and the rate of symptom progression, there are 6 main forms of the disease, but the most common is adrenomyeloneuropathy (AMN). When carefully examining patients with AMI, in most cases it is possible to identify urological pathology manifested by overactive bladder in both sexes and hypogonadism in men, which are hidden behind other numerous neurological symptoms and often remain undiagnosed. To date, there are few works devoted to the peculiarities of pathogenesis, clinical course, diagnosis and treatment of this pathology in ALD. In this article, we reviewed the current literature data on neurogenic bladder dysfunction and hypogonadism in ALD.

The accumulation of glycation end products (AGEs) is closely related to chronic inflammation, oxidative stress and can affect muscle function. An increase of the concentration of AGEs in the serum can be observed in patients already at the initial stages of the formation of chronic kidney disease (CKD). At the same time, there is no need for a violation of carbohydrate tolerance or diabetes mellitus. Sarcopenia is one of the complications of CKD. Its development in CKD can be considered not only as a result of endogenous intoxication, but also as one of the variants of premature aging. This literature review is devoted to the analysis of the mechanisms of the influence of AGEs on the occurrence and progression of sarcopenia in CKD.

BACKGROUND. Hemodialysis patients are characterized by a wide range of concomitant diseases, including cardiovascular, bone mineral, nutritional, cognitive, various metabolic disorders and anemia. Meanwhile, gastrointestinal tract disorders in these patients remains largely unexplored. Patients receiving treatment with programmed hemodialysis are characterized by a wide range of concomitant diseases, including cardiovascular, bone mineral, nutritional, cognitive, various metabolic disorders and anemia. Meanwhile, the pathology of the gastrointestinal tract in this category of patients remains largely unexplored.

AIM: to investigate the structure of digestive diseases in patients receiving hemodialysis treatment.

PATIENTS AND METHODS. This study included 180 hemodialysis patients. The median age was 60[47;68] years. Gastrointestinal Symptoms Questionnaire (GSQ) was used to evaluate gastrointestinal symptoms over the last month. The results of abdomen ultrasound, gastroscopy, colonoscopy, and complex laboratory examination were also analyzed.

RESULTS. The overall prevalence of gastrointestinal symptoms was 77.2 % (139/180). The most frequent complaints were constipation (46.8 %) and abdominal pain (41 %). The most common stool frequency was one bowel action per day. The third, fourth, fifth type of stool according to the Bristol Stool Form Scale were noted by the majority of participants. Abdominal ultrasound revealed diffuse liver changes in 115 (63.9 %), signs of cirrhosis – in 7(3.9 %) patients. Ultrasound pathology of the gallbladder was represented by anomalies of its shape in 11.1 %, signs of chronic cholecystitis – in 10 %, stones (sludge) – in 7.2 %, polyps – in 2.2 % of patients. Diffuse changes in pancreatic parenchyma, steatosis, pseudocysts and dilatation of the main pancreatic duct were diagnosed respectively in 39(21,7 %), 21(11,7 %), 10(5,6 %) and 3(1.7 %) hemodialysis patients. According to 154 gastroscopies, the most common endoscopic finding in the stomach was chronic gastritis, detected in 86(55.8 %) of the subjects. Erosive gastritis was diagnosed in 22(14.3 %), gastric ulcer – in 3(2.0 %) patients. Endoscopic duodenal pathology was represented by erythematous duodenitis in 53(34.4 %), erosive duodenitis in 15(9.7 %), ulcer in 2(1.3 %), duodenal bulb abnormalities in 23(14.9 %) patients. Combined gastric and duodenal lesions were found in 88(57.1 %) patients. Сolonoscopy was performed in 56 patients, of whom 15 (26.8 %) had signs of colitis (mainly sigmoiditis), 2(3.6 %) – diverticulitis, 10(17.9 %) – diverticulosis, 12(21.4 %) – colon polyps, 8(14.3 %) – angiodysplasia mucosa, in 3(5.4 %) – dolichocolon. Despite the abundance of gastrointestinal symptoms and instrumental findings, no significant deviations in laboratory parameters (including an increase in AST, ALT, total bilirubin, amylase, lipase) were found.

CONCLUSION. Hemodialysis patients are characterized by a high prevalence of gastrointestinal symptoms and various pathological changes in the gastrointestinal tract, the diagnosis and treatment of which require an individual multidisciplinary approach.

BACKGROUND. Patients with Diabetes Mellitus 2 (DM2) and Chronic Kidney Disease (CKD) are at a high risk for severe clinical course of COVID-19. The high mortality rate due to COVID-19 and widespread distribution of DM2 and CKD all over the world make it necessary to determine the predictors of adverse outcome of novel coronavirus infection (NCI).

AIM. The identification of predictors of NCI adverse outcome in patients with DM2 and CKD stage 3 due to diabetic kidney disease.

Patients and Methods. The patients with NCI and CKD stage 3 were included in observational retrospective uncontrolled study during the follow-up period from 04.01. to 10.30.2020. The study endpoints were the outcome of NCI (survivors/nonsurvivors). Data were collected from electronic versions of case records. Demographic, DM2-related, CKD-related and NCI-related baseline parameters/signs were studied as independent variables.

RESULTS. 90 patients with DM2 and CKD stages 3 (Me GFR 43[37; 49] ml/ min/1,73m²) were included, mean age 70 [69; 78] y, females – 56 %, the mortality rate – 21 %. The independent predictors of NCI adverse outcome were detected using a single factor analysis (odds ratio). Among them are: initial prandial glycemia ≥ 10 mmol/l (ОR 11,8; 95 % CI 3,13–44,9; р <0,001), albuminemia at admission ≤ 35 g/l (ОR 5,52; 95 % CI 1,85–16,55; р = 0,012), initial proteinuria ≥ 1 g/л (ОR 6,69; 95 % CI 1,95–23,00; р = 0,002), News2 ≥ 5 at admission (ОR 14,7; 95 % CI 3,15–48,8; р <0,001), lung damage CT 3–4 at admission (ОR 31,7; 95 % CI 6,59–52,85; р = 0,04). A prognostic model was constructed to determine the risk of lethal outcome using logistic regression method. The detected risk factors were used as variables. The predictive value of the model was 93 % according to ROC-analyses data.

CONCLUSION. The detected predictors of adverse outcome are the part of routine screening available in pre-hospital setting and at hospital admission. Early identification of predictors allows optimizing patient routing and selecting the best treatment strategy for each patient.

BACKGROUND. Coronary heart disease (CHD) and obesity are common pathologies in patients who have had COVID-19. Endothelial dysfunction (ED) markers determination has been important in such patients due to the high risk of cardiovascular diseases progression and complications development.

THE AIM Assessment of endothelial dysfunction severity in patients with CHD and obesity in the post-COVID-19 period to improve the management of these patients.

PATIENTS AND METHODS. 49 patients were examined, who had COVID-19 a year ago. The first group (n=24) included patients with coronary artery disease in the post-COVID period. The second group (n=25) included patients with CHD and obesity who had COVID-19. We evaluated data from an ultrasound examination of the kidneys with duplex scanning of the renal arteries (resistance index (RI), pulsation index (PI)). We also studied the medical history, performed an objective examination, the results of a biochemical blood test, albuminuria levels.

RESULTS. We demonstrated higher RI and PI of interlobar, segmental arteries in persons of the second group. An increase in RI and PI of segmental arteries accompanied by an increase in uric acid (p=0.001). The average level of microalbuminuria in the first group was 15,71± 4,51 μg/l, in the second group it was 24,38±5,38 μg/l (p=0.110). Increasing glucose levels accompanied by an elevation of C-reactive protein levels. Obesepatients had significantly higher levels of total cholesterol, triglycerides, low density lipoproteins than patients in the first group.

CONCLUSION. We observed changes in lipid metabolism, a higher incidence of diabetes mellitus in females, and changes in intrarenal hemodynamic parameters associated with uric acid levels in patients with coronary heart disease and obesity in the post-COVID-19 period.

BACKGROUND. Modeling of chronic kidney disease using nephrectomy of 5/6 kidney parenchyma is actively used in experimental nephrology. However, the remaining 17 % of the organ parenchyma is associated with severe renal fibrosis in humans. A high-salt diet has traditionally been considered as a systemic hemodynamic model for the development of chronic kidney disease.

THE AIM: to compare the functional disorders that occur in rats with nephrectomy of ¾ of the kidneys and when using only a high-salt diet.

MATERIAL AND METHODS. The study was performed on 30 male Wistar rats. The animals were randomly divided into 3 equal groups: control (falsely operated, L), high-salt diet (falsely operated, LVD), nephrectomy ¾ renal parenchyma (NE). The rats received a balanced laboratory feed daily, differing only in the content of sodium chloride (NaCl). In the L and NE groups, rats received a feed containing 0.34 % NaCl, and in the VD group – 4 % NaCl. The duration of follow-up was 16 weeks. Systolic blood pressure (SBP) was measured on the tail by the cuff method. The serum and urine concentrations of creatinine, urea, potassium, sodium, chlorine, as well as the degree of proteinuria and albuminuria were determined.

RESULTS. During the observation, the SBP in group L did not change. In the LVD group, SBP increased from 120 [120; 125] mmHg to 130.0 [125.0; 140.0] mmHg, p=0.011. In the NE group, SBP also increased from 120 [120; 125] mmHg to 135.0 [132.5; 137.5] mmHg, p=0.011. In the LVD group, there was an increase in serum creatinine concentration compared to the control to 52.5 [50.0; 56.0] mmol/l, p=0.0001; urea to 6.0 [5.6; 6.6] mmol/l, p=0.0001; potassium to 5.6 [5.3; 5.8] mmol/l, p=0.0001; chlorine up to 87.5 [86.6; 87.9] mmol/l, p= 0.0001. At the same time, creatinine clearance decreased from 187.5 [160.0; 205.0] ml/min in the L group to 92.0 [81.2; 99.0] ml/min, p=0.0003 in the LVD group and to 83.9 [65.7; 85.9] ml/min p=0.0001 in the NE group. The value of albuminuria before the end of the experiment was statistically significantly higher compared to the control in both the LVD group of 12.12 [6.36;18.41] mg/g creatinine, p= 0.0001, and in the NE group of 72.5 [61.6; 92.9] mg/g creatinine, p= 0.0001. When conducting a nonparametric correlation analysis (all three observation groups were combined), a statistically significant relationship was noted between the level of SBP after 1 month from the start of the experiment and the amount of albuminuria at its completion (Rs=0.583 p=0.001). A statistically significant relationship between the value of SBP and creatinine clearance was revealed before the end of the experiment (Rs=-0.700 p=0.005). Also, before the end of the experiment, a statistically significant relationship between albuminuria and creatinine clearance was revealed (Rs=-0.671 p=0.006).

CONCLUSION. The NE model of the renal parenchyma is expected to be accompanied by the development of less severe functional changes compared to NE 5/6 of the renal parenchyma. In this regard, we assume that its use may be useful in studying the effectiveness of nephroprotective measures at the initial stages of CKD development. The negative effects of a high-salt diet are comparable in a number of indicators to nephrectomy of the renal parenchyma. Traditionally, an increase in salt intake is associated with an increase in blood pressure, which could result in an increase in albuminuria. However, we could not identify any relationships between albuminuria and the value of SAD. We assume that the model of a high-salt diet can be considered as a variant of a local, rather than a systemic hemodynamic model of the development of chronic kidney disease. In the future, we will present the results of nephrobiopsy in the experimental groups described above.

The article discusses the prerequisites, formation and development of nephrology as a science. The purpose of this review is to analyze the formation of basic ideas about nephrology, starting from the era of the Ancient World and ending with studies of the Modern period. The results of the process of formation and development of ideas about nephrology are presented. The causes and processes of the development of kidney diseases were of interest to the healers already in ancient times. In the Middle Ages, the accumulation of empirical knowledge in this field were continued. The understanding of methods and means of diagnosis and therapy of kidney diseases expanded and deepened. In Modern times, the idea of kidney diseases and their treatment has received a more complete description. The study began not only of the mechanisms of development of these diseases, but also of risk factors and. Nowadays, research in this area continues. The review presents the stages of the formation of nephrology at each stage of the development of medicine. The achievements of Russian nephrologists (Shumlyansky A.M., Tsybulsky N.O., Pasternatsky F.I., Zimnitsky S.S., Tareev E.M., Vovsi M.S.) are analyzed, their scientific priorities in world nephrology, contribution to the development of this scientific direction are presented.

BACKGROUND. One of the congenital anomalies of the kidneys and urinary tracts (CAKUT) is renal hypodysplasia/aplasia type 3 (PHDA3), caused by pathogenic variants in the GREB1L gene not associated with steroid-resistant nephrotic syndrome (SRNS). PGDA3 leads to chronic kidney disease (CKD). Variants in the UMOD gene associated with autosomal dominant tubulointerstitial kidney disease (ATKD-UMOD) also lead to CKD. The association of the GREB1L/UMOD genes with SRNS has not been previously described.

THE AIM: to demonstrate a rare clinical case of SRNS in a child with CAKUT-syndrome.

PATIENTS AND METHODS. A patient with CAKUT in the form of PGDA3 and ADTBP-UMOD is observed in the department of nephrology for 2 years. Post-infectious development of SRNS required a revision of the genetic screening.

RESULTS. On the whole-genome sequencing were found a variability in the genes that cause CAKUT, with no candidate genes for SRNS.

CONCLUSION. The described case stands out with clinical polymorphism of CAKUT and the variability of UMOD and GREB1L gene variants not associated with the development of SRNS. Infectious etiology of the development of SRNS is assumed. The patient has an intensive development of CKD stage 4, requiring a long-term follow-up in dynamics.