Renal physiology is one of the fundamental branches of nephrology. It encompasses a number of complex issues that require discussion and consensus within the nephrology community. These include the question of partial renal functions, obligate reabsorption in the proximal tubule, key transformations in the kidney during its evolution, and their significance for human adaptation in pathological conditions. This article substantiates controversial terms and provides a modern understanding of the kidney's main functions. It outlines the mechanisms underlying urine formation and explains why they operate as they do. This relates to the enormous arterial blood flow of the kidneys, the mechanism of regulation of obligate proximal reabsorption, the replacement of the renal renoportal system with a higher arterial blood supply, and the importance of the kidneys in human homeostasis.

Acute ischemic-reperfusion injury (IRI) is the primary cause of acute kidney injury. Experimental studies have shown that the severity of IRI in renal tissue can be reduced through various pharmacological interventions. However, these data have not been successfully transferred into clinical practice, partly due to the suboptimal pharmacokinetic parameters of the drugs, their low bioavailability, and the occurrence of side effects with systemic administration. To address these issues, systems for the targeted delivery of drugs to the kidneys during IRI using nanoscale carriers have been developed in recent years. Binding to nanoparticles enables preferential accumulation of the active substance in the kidneys, followed by controlled release. For active targeted drug delivery to the kidneys during IRI, platforms containing specific guiding ligands and groups sensitive to local environmental conditions are being used. Most studies related to the development of targeted drug delivery systems for kidney tissue focus on antioxidants and anti-inflammatory agents. Improving targeted delivery systems is linked to actively targeting damaged kidney tissue, including using bio-like coatings on drug nanoparticles based on blood cell membranes.

Since 2010, studies have been published that have found expression of bitter taste receptors Tas2R (the so-called extralingual or ectopic) on bronchial smooth muscle cells, and then on many other cells outside their canonical localization, in particular, on inflammatory cells. It was found that activation of Tas2R receptors, contrary to the bronchoconstrictor effect initially expected by the authors, led to more pronounced (3 times) bronchodilation than activation by β₂ -agonists. Over the past 15 years since the discovery of ectopic expression of Tas2R receptors in the respiratory system, a number of research areas have emerged and are developing in this new field of bronchial asthma research. These areas include: I – study of the expression of Tas2R receptor subtypes on bronchial smooth muscle; II – studies of the molecular mechanisms of Tas2R-signaling; III – studies of Tas2R receptor expression on respiratory system cells (ciliated epithelium) and on cells involved in allergic inflammation (lymphocytes, mast cells, macrophages, etc.); IV – studies of Tas2R gene polymorphisms and their association with predisposition to bronchial asthma; V – studies of the role of soluble Tas2R receptors in bronchial asthma; VI – search for opportunities to use Tas2R receptor activation for targeted therapy of bronchial asthma. The review examines the main positions of research areas in the field of Tas2R-signaling in bronchial asthma and provides the main literature in this area. Despite the achievements in the treatment of bronchial asthma, it is known that control over the disease cannot always be achieved completely. It is concluded that, given the versatility of the effects of tas2r receptors in bronchial asthma (bronchodilation, decreased activity of allergic inflammation and bronchial hyperreactivity, effects on remodeling), these receptors are a promising candidate for the development of comprehensive therapy for bronchial asthma.

BACKGROUND. The relevance of the pediatric problem of hereditary podocytopathy in children is due to the peculiarities of the age at which the clinical phenotype of NS manifests with typical histology of focal segmental glomerulosclerosis (FSGS) or diffuse mesangial sclerosis (DMS), less often minimal changes (MC) due to variants of gene mutations and pathogenesis, with a high frequency of steroid resistance and the risk of progression to the end-stage chronic kidney disease (CKD) already in childhood. THE AIM: to identify the characteristics of the clinical phenotype, genotype, and pathogenesis of nephrotic syndrome (NS) in podocytopathies caused by mutations in genes encoding structural and functional proteins of epithelial podocyte cells of the glomerular filtration barrier.

PATIENTS AND METHODS: The study included 24 pediatric patients (aged 6 months to 17 years) with hereditary podocytopathies accompanied by NS, including 15 boys (62.5 %) and 9 girls (37.5 %). Clinical, biochemical, imaging, and molecular genetic diagnostic methods were used. The severity of chronic kidney disease (CKD) was stratified according to the K/DOQI classification (2002). RESULTS: Among 24 patients with NS, monogenic mutations were identified in 19 (79.2 %), digenic mutations in 3 (12.5 %), and trigenic mutations in 2 (8.3 %). In 24 children with identified pathogenic variants in the genes NPHS2 (4), PLCE1 (3), WT (3), PTPRO (1), COQ6 (1), NUP93 (2), NUP205 (1), NUP85 (1), KANK2 (1), MYO1E (1), TRPC6 (3), PAX2 (1), SGPL1 (1), and DAAM2 (1), the features of pathogenesis, clinical phenotype, and renal function in hereditary podocytopathy-associated NS were characterized.

CONCLUSION: Distinct features of the clinical phenotype, gene mutation variants, pathogenesis, and renal prognosis of NS were identified in 24 children with podocytopathies. Among 21 patients older than 2 years with hereditary podocytopathy with NS (20) and without NS (1), CKD stage C1 with normal glomerular filtration rate was observed in 16 (76.2 %), while progression to CKD stage C5 occurred in 5 (23.8 %). Of these 5 patients, two are receiving maintenance hemodialysis, and three patients with mutations in NPHS2, PLCE1, and WT have a functioning renal transplant. Among three infants with congenital NS, preserved renal function was observed in one case, while acute kidney injury, multiple organ failure, and fatal outcome were reported in two cases.

The impact of COVID-19 on chronic kidney disease (CKD) has already been confirmed by researchers around the world. However, there is still insufficient data in the literature how the new coronavirus infection can affect kidney function without signs of CKD before. The aim of this study was to determine the relative risk of developing stages 4-5 CKD in patients who had COVID-19 and did not have signs of kidney damage before, depending on the severity of the coronavirus infection, the fact of hospitalization and the complication of acute kidney injury. The results of the study demonstrate that the development of late (4-5) stages of CKD can be directly associated with COVID-19, especially in patients with severe COVID-19, hospitalization or acute kidney injury, which is consistent with many studies in this area, in particular in patients without signs of CKD before.

BACKGROUND. High-dose immunosuppressive therapy (HDIT) with autologous hematopoietic stem cell transplantation (AHSCT) is an effective treatment for resistant autoimmune diseases. However, the use of high-dose cyclophosphamide (CP) is associated with the risk of developing cyclophosphamide-induced cardiomyopathy (CIC). Massive infusion therapy may potentiate CP cardiotoxicity, but its role remains insufficiently studied.

THE AIM: to assess the contribution of infusion load to the development of CP cardiomyopathy and to find an early signs of its development.

PATIENTS AND METHODS. A prospective study was conducted involving 74 patients with multiple sclerosis receiving HDIT-AHSCT and 6 healthy volunteers. Comprehensive clinical, laboratory, and echocardiographic examinations were performed before, on the 3rd, and on the 7th day of therapy. RESULTS. In healthy individuals, infusions caused a transient elevation of NT-proBNP (max. 533.9 pg/ml) accompanied by an increase in heart chamber volumes and a rise in E/e'. Patients developed specific signs of cardiotoxicity: thickening of the walls and an increase in left ventricular (LV) myocardial mass. An NT-proBNP level >533.9 pg/ml on day 3 was associated with myocardial remodeling (ΔLV mass 15.94±26.36 g vs. -0.33±12.70 g, p=0.046) and left ventricular diastolic dysfunction (Δ E/e’ 1.21±2.10 vs. -0.19±1.39, p=0.030). Factor analysis identified three key components of cardiotoxicity, explaining 66.9% of the total data variance.

CONCLUSION. Massive infusion therapy within the HDIT-AHSCT protocol is a significant factor potentiating CP cardiotoxicity. An NT-proBNP level >533.9 pg/ml and echocardiographic signs of remodeling on day 3 serve as early markers of cardiac damage. Awareness of the CF-induced cardiomyopathy early symptoms will help to accurate identification of high-risk patients for timely prevention.

BACKGROUND. Standard criteria allow diagnosing AKI within hours to days. The use of biomarkers is a promising approach for early diagnosis and prognosis of AKI.

THE AIM: to study the capabilities of serum cystatin C (CYS) in the early diagnosis and prognosis of AKI and associated hospital mortality, the risk of 30-day death in pulmonary embolism (PE).

PATIENTS (MATERILS) AND METHODS. 98 patients with suspected PE were included; patients were excluded if the diagnosis was not confirmed. CYS was determined on admission, the difference between the determined CYS and the estimated CYS corresponding to a glomerular filtration rate (GFR) of 75 ml/min/1.73 m2 (CYSdiff) and the difference between the GFR by CYS and the GFR by creatinine (eGFRdiff) were calculated. RESULTS. AKI was diagnosed in 13 of 63 patients with PE (men – 36(57 %), age – 67(12) years). In 7(54 %) cases, AKI was detected against the background of chronic kidney disease (CKD), in 6(46 %) – first-onset AKI. CYS>2.55 μg/ ml predicted AKI (sensitivity – 70 %, specificity – 62 %; AUC=0,70; p=0,01) and AKI in CKD patients (sensitivity – 86 %, specificity – 62 %; AUC=0,78; p=0,001). CYSdiff>1,62 μg/ml predicted AKI (sensitivity – 69 %, specificity – 68 %; AUC=0,70; p=0,01). 5 patients (9 %) died in hospital. Mortality was higher in AKI (χ2 =5.8; p=0,02). CYS, CYSdiff did not predict hospital mortality, while CYS>2,17 μg/ml (sensitivity – 70 %, specificity – 70 %; AUC=0,76; p=0,0001) and CYSdiff>1,22 μg/ml (sensitivity – 70 %, specificity – 70 %; AUC=0.77; p0,05).

CONCLUSION. The results of the study confirm the effectiveness of CYS in the early diagnosis and prediction of AKI, including cases associated with CKD. The accuracy of prediction can be improved using CYSdiff. CYS does not predict in-hospital mortality but is associated with a high risk of 30-day death in PE.

BACKGROUND. Atherosclerosis is the most common cause of cardiovascular diseases, leading to early disability and high mortality among the population of developed countries. Lipidemia control is the cornerstone of prevention and treatment of atherosclerosis complications. Meanwhile, adherence to statin treatment is critically low. One of the reasons of the low compliance is the fear of side effects. The safety and possibly the effectiveness of treatment with various statin drugs depend on the genetic characteristics of their metabolism.

THE AIM: to determine the benefits of pharmacogenetic research in the appointment of therapy with atorvastatin and rosuvastatin in patients with high and very high cardiovascular risk.

PATIENTS AND METHODS. A prospective study involving 2 groups of similar age, gender, and cardiovascular risk. The study group consisted of 43 patients each (47.9±10 years old, 67 % men), for whom pharmacogenetic study data were taken into account when prescribing or correcting statin therapy. The control group consisted of 43 patients (46.9± 11 years old, 70 % men) who were prescribed statins in accordance with the clinical recommendations, but did not take into account the genetic characteristics of metabolism. Both groups were followed for 12 months with an interval of 3 months. At each point, the following items were assessed: adverse cardiovascular events; the fact that LDL-C targets were reached, the presence of statin-associated adverse symptoms, and treatment adherence.

RESULTS. Normal function of SLCO1B1, ABCG2, and CYP2C9 was detected in 25 patients (58.1 %), delayed function in 15 subjects (34.8 %), and slow metabolism of rosuvastatin and atorvastatin in 3 patients (7.0 %). The frequency of achievement of LDL-C targets did not differ between the study and control groups (p>0.05), the proportion of cardiovascular events was higher in patients in the control group (the frequency of reaching the composite endpoint: 7 % and 20.9 %, respectively). However, the initial proportion of these events in the control was also higher, which does not allow us to draw unambiguous conclusions. Statin-associated muscle symptoms (SAMS) were significantly less common in study group patients than in the control (1 case (7 %) versus 9 cases (20.9 %), p=0.015), which corresponded to an 89 % reduction in relative risk. Compliance with statin therapy was low and amounted to 30 % in the study group and 25.6 % in the control group (p>0.05).

CONCLUSIONS. Pharmacogenetic testing of patients before prescribing statins can significantly reduce the risk of developing ACS.

Bacterial infections currently pose a threat to human health, and in some cases, life. Urinary tract infections are a significant threat among them. Chronic pyelonephritis (chrPN), as a common cause of chronic kidney disease (CKD), is of significant importance in this regard.

THE AIM: to study the clinical and functional effects of antihypertensive drugs in patients with symptomatic arterial hypertension (AH) in the early stages of CKD due to chrPN, using a comparative analysis using dynamic renal scintigraphy.

PATIENT AND METHODS. Our study included 100 patients with CPN and hypertension, CKD C1-C3a, in remission.

RESULTS. Target blood pressure was achieved with ACE inhibitors and ARBs for 2 months. Estimated glomerular filtration rate (eGFR) did not change significantly. Lisinopril therapy had no effect on Tmax and Tmax–T½ in both kidneys. Improvement in secretory and excretory function in both kidneys was observed with valsartan.

CONCLUSION. A positive effect of valsartan was observed, suggesting it as a more promising drug for renal protection in patients with chronic kidney disease and hypertension.

BACKGROUND. Congenital nephrotic syndrome (CNS) is a rare autosomal recessive kidney disorder that manifests within the first three months of life. It is characterized by massive proteinuria, hypoalbuminemia, hypercholesterolemia, edema, steroid resistance and inevitable progression to end-stage chronic kidney disease (ESCKD). In 85 % of cases CNS is a monogenic disease.

THE AIM: To present a clinical case of genetically confirmed CNS of the Finnish type in the Republic of Belarus.

PATIENTS AND METHODS. A male infant from the first pregnancy and first full-term birth was examined. On the third day after birth testicular hydrocele, proteinuria and hypoalbuminemia were diagnosed and persisted despite transfusions of 20 % albumin solution. Further examination revealed persistent arterial hypertension and elevated levels of thyroid-stimulating hormone. At the age of 5 months bilateral nephrectomy was performed, followed by various forms of renal replacement therapy (peritoneal dialysis, hemodialysis, and kidney transplantation from a deceased donor). Molecular genetic testing identified two mutations in the NPHS1 gene in a compound heterozygote.

RESULTS. Mutations of the NPHS1 gene are associated with CNS of the Finnish type (Nephrotic syndrome, type 1, OMIM 256300). The identified variants NM_004646: exon18:c.2335-1G>A and NM_004646:exon8:c.C847T:p.Q283* differ from the ‘Finnish mutations’ Fin-major and Fin-minor and are in trans. The patient was also found to be homozygous for the p.R229Q polymorphism at locus rs61747728 of the NPHS2 gene. Morphological examination of the nephrectomy materials revealed changes characteristic of CNS of the Finnish type.

CONCLUSIONS. In this clinical case a child with compound heterozygous mutation in the NPHS1 gene and a homozygous rare polymorphic variant in the NPHS2 gene exhibited a severe course of CNS of the Finnish type with rapid progression to ESCKD. Molecular genetic testing confirmed the diagnosis of CNS of the Finnish type and allowed avoiding the administration of immunosuppressive therapy. Additionally, the results of molecular genetic analysis of the parents should be taken into account when planning future pregnancies.

Almost half of the world's population suffers from obesity. The prevalence of obesity and excess body weight is steadily increasing. We want to be graceful and slim without making significant efforts. Therefore, new "miraculous" medical drugs for weight loss appear. But their active use, unfortunately, often without a doctor's prescription, can lead to the development of serious consequences. And the more widely the drugs are advertised and used uncontrollably, the more likely the occurrence of adverse reactions. We encountered one of such cases and describe it in the article.

Globally, the prevalence of chronic kidney disease (CKD) is approaching epidemic levels. Some CKD phenotypes of secondary etiology are characterized by slow progression with a prolonged period of asymptomatic progression, does not reach nephrotic levels. Assessing prognostic markers in the early stages of CKD is essential to reduce the risk of progression to kidney dysfunction and cardiovascular disease through timely pathogenetic correction. This should be addressed not only by nephrologists but also by other primary care practitioners. This article describes a 64-year-old male patient with obesity, episodes of hyperglycemia, and long-standing arterial hypertension. Biochemical analysis confirms hyperglycemia, hyperuricemia, and dyslipidemia. Morphological studies indicate the development of secondary segmental glomerulosclerosis, including in the vascular pole of the glomeruli. Autoimmune pathology has been excluded. Urinalysis revealed episodes of proteinuria up to 4.2 g per day. After adequate treatment of hypertension, dyslipidemia, hyperglycemia, and hyperuricemia, a decrease in proteinuria was observed. The evaluation and treatment of these patients requires a comprehensive approach, with the mandatory participation of nephrologists and endocrinologists.when proteinuria