The review is devoted to the consideration of the most common drugs currently used in the treatment of primary nephrotic syndrome. Mechanisms of pharmacological activity of glucocorticosteroids, ACTH, calcineurin inhibitors cyclosporine A and tacrolimus, alkylating compounds cyclophosphamide and chlorambucil, mycophenolate mofetil, levamisole, abatacept, rituximab and a number of other recently created monoclonal antibodies. An attempt is made to separate the immune and non-immune mechanisms of action of the most common drugs, concerning both the impact on the immunogenetics of the noted diseases and the direct impact on the podocytes that provide permeability of the glomerular filtration barrier and the development of proteinuria. It is shown that the immune mechanisms of corticosteroids are caused by interaction with glucocorticoid receptors of lymphocytes, and nonimmune – with stimulation of the same receptors in podocytes. It was found that the activation of adrenocorticotropic hormone melanocortin receptors contributes to the beneficial effect of the drug in nephrotic syndrome. It is discussed that the immune mechanism of calcineurin inhibitors is provided by the suppression of tissue and humoral immunity, and the non-immune mechanism is largely due to the preservation of the activity of podocyte proteins such as synaptopodin and cofilin. Evidence is presented to show that the beneficial effect of rituximab in glomerulopathies is related to the interaction of the drug with the protein SMPDL-3b in lymphocytes and podocytes. The mechanisms of action of mycophenolate mofetil, inhibiting the activity of the enzyme inosine 5-monophosphate dehydrogenase, which causes the suppression of the synthesis of guanosine nucleotides in both lymphocytes and glomerular mesangium cells, are considered. It is emphasized that the effect of levamisole in nephrotic syndrome is probably associated with the normalization of the ratio of cytokines produced by various T-helpers, as well as with an increase in the expression and activity of glucocorticoid receptors. The mechanisms of pharmacological activity of a number of monoclonal antibodies, as well as galactose, the beneficial effect of which may be provided by binding to the supposed permeability factor produced by lymphocytes, are considered.

Glomerular filtration rate (GFR) is a recognized indicator of the functional status of the kidneys. In medical practice, there are various approaches for measuring GFR. However, despite the nearly 100-year history, not all methodological problems of evaluating GFR in clinical practice have been solved. The most physiologically justified (“reference”) methods are not acceptable in routine practice because of the complexity and high cost. Therefore, clinicians have to rely mainly on the results of surrogate methods, most of which use endogenous creatinine as a glomerulotropic test agent. Therefore, the accuracy of determining the concentration of this metabolite in biological media (especially in serum) is often crucially determined by the reliability of the GFR assessment. Manufacturers of creatinine reagent kits should take into account current requirements for accuracy and traceability of measurement results and ensure that their products comply with international standards.

THE AIM. Assessment of factors associated with cardiopulmonary bypass (CPB) in acute renal dysfunction in patients in the early postoperative period after cardiac surgery.
PATIENTS AND METHODS. Monocentric observational study in patients (n = 97) who underwent elective open-heart cardiac surgery (coronary artery bypass grafting -50.44 %, aortic valve prosthetics – 31.04 %, mitral valve prosthetics – 12.61 %) using cardiopulmonary bypass. Inclusion criteria: the study included patients not younger than 18 years old, undergoing cardiac surgery with CPB lasting up to 95 minutes (coronary bypass surgery, valve replacement), without signs of end-stage renal disease. Using nonparametric correlation analysis, we evaluated the effect on the development of acute kidney injury (AKI) of the following extracorporeal circulation factors: duration of CPB, aortic cross-clamp, mean arterial pressure (MAP), cardiac index (CI), perfusion flow rate (PFR), transport, consumption, and oxygen extraction variables. The diagnosis of AKI was made on the basis of the KDIGO classification, the studied parameters were recorded initially (before the operation), 15 minutes after the start of general anesthesia, 30 minutes after the start of cardiopulmonary bypass and 15 minutes after the end of general anesthesia.
RESULTS. The frequency of AKI in 24 hours after surgery was 56.3 % (58 cases): including stage 1 in 37 (35.9 %), stage 2 in 17 (16.5 %) , stage 3 – in 4 (3.9 %) patients. In the 48th hour of the postoperative period, signs of AKI regressed and were presented in only 26 people (25.2 %), including the stage 1 in 18 (17.5 %), the stage 2 – in 5 (4.8 %), stage 3 – in 3 (2.9 %). Among the risk factors for AKI in cardiac surgery with CPB, the main effect of the anemia was revealed, especially a decrease in hemoglobin levels of less than 90 g / l and hematocrit of less than 25 %.
CONCLUSION. Hemodilution below the "threshold" values of hemoglobin and hematocrit during the CPB provoke acute
kidney injury in patients undergoing open-heart surgery.

The relevance of the study of glycemic variability in patients with diabetes mellitus and diabetic nephropathy is due to disability of the able-bodied population and high mortality against the background of the almost irreversible progression of diabetic nephropathy. The article highlights modern ideas about the influence of various factors on the occurrence of diabetic nephropathy and its course. The article is devoted to a review of current recommendations on diabetes mellitus and diabetic nephropathy; the etiopathogenesis of diabetic nephropathy was described in detail. The role of the kidneys in glucose homeostasis, renal gluconeogenesis, and glucose reabsorption by the kidneys in healthy and in pathology is described. Detailed expositions of glycemic variability parameters, their changes in patients with diabetes mellitus depending on the stage of diabetic kidney damage are presented. The role of the kidneys in maintaining energy homeostasis, impaired glucose homeostasis in conditions of chronic kidney disease is described. We analyzed different options for insulin therapy, their advantages, and disadvantages in patients with diabetes mellitus with diabetic nephropathy. The presented material is extremely relevant for the development and implementation in the clinical practice of glycemic control methods to optimize treatment tactics, prevent the formation of microvascular complications, and early disability of patients with diabetes mellitus.

INTRODUCTION. We have previously postulated the similarity of molecular pathogenetic mechanisms in bronchial asthma (BA) and chronic kidney disease (CKD). Understanding these mechanisms in such a comorbidity pathology is of interest to the clinicians. In recent years, the attention of BA pathogenesis researchers has attracted low-investigated adipokine – apelin. On the other hand, apelin is considered as a renoprotective adipokine that can prevent the progression of CKD.
THE AIM of the study is to identify the relationship between apelin/APJ signaling system and glomerular filtration rate in different BA variants.
PATIENTS AND METHODS. The 12 of practically healthy persons and 36 bronchial asthma patients were examined. Levels of apelin-12, apelin-36, and APJ receptor of apelines on peripheral blood lymphocytes were determined, as well as levels of TNF-α, IL-6 IL-4 by immunoenzyme method according to standard protocol. Glomerular filtration rate (eGFR) by CKD-EPI was calculated.
RESULTS. With the help of factor analysis, it was revealed that the glomerular filtration rate in bronchial asthma is associated with the level of apelin-36. A high level of glomerular filtration rate corresponds to a high level of apelin-36. In bronchial asthma, the negative association of pro-inflammatory adipokines TNF-α and IL-6 with the glomerular filtration rate was revealed. On the other hand, the IL-4 was found to be directly related to the glomerular filtration rate according to the factorial analysis.
CONCLUSION. The obtained data suggest a possible renoprotective effect of apelin-36 in bronchial asthma.

INTRODUCTION. In patients with CKD stage 5 receiving hemodialysis as the main method of renal replacement therapy (RRT), the endocrine system organs, including the thyroid gland, are affected over time. The study of changes in the thyroid status is an urgent task.
AIM OF STUDY. Study of functional and gender characteristics of the thyroid status, depending on the duration of patients stay on hemodialysis.
PATIENTS AND METHODS. The thyroid status was measured in 108 patients (44 women and 64 men, average age 51.7±15.4 years) undergoing hemodialysis. Patients were divided into quartiles according to the duration of stay on the RRT: group 1 4 – 25 months (28 people), group 2 41 – 59 months (26 people), group 3 68 – 97 months (26 people) and the fourth more than 100 months (28 people). We performed correlation analysis and comparison between groups on the level of free T 4, TSH, the ratio of fT4 to TSH. RESULTS. The average value of fT4 was 11.95±2.07 pmol / ml and TSH 1.5± 0.94 mcME/ml. Significant differences in thyroid status were obtained between the first and second groups in terms of TSH level and ratio fT 4 to TSH (P<0.01) – the level of TSH in the second group is higher (0.74 to 2.1 mсME/ml) and the ratio of fT4 to TSH is lower (13.09 to 4.91). In total, thyroid dysfunction was detected in 20.3% of the examined patients.
CONCLUSION. Thus, deviations in the thyroid status occur after 2 years of being on RRT by hemodialysis. In patients who have been on RRT for more than 5 years, the thyroid status stabilizes. The reasons for this phenomenon are completely incomprehensible.

THE AIM. Compare cognitive performance in patients with CKD not receiving HD and patients on HD.
PATIENTS AND METHODS. The study included patients of young and middle age (from 18 to 60 years) (n = 40) who have stage 5 of chronic kidney disease (CKD) and 40 patients on hemodialysis of comparable age (from 18 to 58 years) who make up the comparison group. The exclusion criteria for both groups were: a history of diseases of the central nervous system; brain injury; episodes of cerebral circulation of varying severity; coronary heart disease; chronic heart failure; pregnancy; alcohol abuse; refusal to participate in the study. Cognitive impairments were assessed using the Status PF software package.
RESULTS. All patients were examined with software package Status PF. They demonstrated light cognitive dysfunctions in neurodynamics, memory, and attention indices. The differences in indices were statistically significant with the experimental group.
CONCLUSION. In patients of young and middle age with 5 stages of CKD, the use of modern software complex Status PF allows us to diagnose mild cognitive impairment. After dialysis, patients showed greater response time and psychomotor slowdown. The average exposure level of SHER in the group without HD was 359.4 ± 48.84 msec, in the group of HD – 381.1 ± 63.34 msec (p = 0.04). The average exposure to CHER in patients before the procedure was 515.57 ± 83.89 ms, after HD, this figure was lower – 498.87 ± 80.8 (p = 0.036).

INTRODUCTION. The registration of late-stage chronic kidney disease (CKD) has increased significantly worldwide in recent years. At the same time, the quality of life of patients has become important. AIM: to determine the features of the quality of life of patients on hemodialysis program, living in the North (on the example of the city of Surgut).
PATIENTS AND METHODS. The annual prospective study included 64 patients aged 33 to 68 years treated with hemodialysis for at least 3 months. The quality of life was determined using the Sydney Disease Quality of Life Short Form (KDQOL-SF) questionnaire.
RESULTS. Patients on hemodialysis also have low rates of renal-specific scales, as well as additional scales: “General perception of health”. A sharp decrease in the quality of life in patients with dialysis experience of up to 1 year and more than 10 years was revealed. Clusters of the leading scales of the KDQOL-SF questionnaire, determining the quality of life of patients on hemodialysis in Surgut, were identified.
 CONCLUSION. In patients with programmed hemodialysis, living in the Northern latitudes, there is a comparable with the General data decrease in the General quality of life. In patients of all groups, regardless of gender, age and dialysis experience, the decline in quality of life is mainly due to the physical component. The high level of «Support for dialysis staff» and «Feeling of social support» in patients of Surgut, regardless of the length of dialysis therapy, were determined by the level of economic development of the region.

BACKGROUND: a comparative analysis of laboratory and instrumental tests at patients with bronchial obstructive diseases seems very actual due to the wide prevalence of these diseases.
THE AIM: to evaluate characteristics of spirometry as well as allergic (total IgE, sputum eosinophils) and infectious (blood and sputum leucocytes, ESR, CRP, fibrinogen) inflammation markers at patients with bronchial obstructive diseases.
PATIENTS AND METHODS: 104 case histories of patients with bronchial asthma, chronic obstructive pulmonary disease and overlap were analyzed including age, duration of smoking (pack-years), laboratory (clinical blood test, biochemical blood test, general sputum analysis, sputum culture) and instrumental (spirometry, body plethysmography, echocardiography) tests. Data were processed statistically with non-parametric methods.
RESULTS: COPD patients were older than other groups’ patients, had the highest pack-years index. ACO patients were marked with maximal TLC and Raw, minimal FEV1, FEF25-75, FEV1/FVC. Patients with COPD had the highest inflammation markers (leucocyte count, CRP, fibrinogen).
CONCLUSION: high active inflammation may cause severe lower airways possibility disorders at patients with COPD. Data related to a possible role of K. pneumoniaе in the pathogenesis of eosinophilic inflammation in lower airways are of significant interest. Patients with ACO occupy an intermediate position between asthma and COPD patients based on clinical and functional features.

THE AIM. To find out if the level of regeneration of renal tissue after nephrectomy 5/6 kidney mass is sufficient to prevent pathological deterioration of microcirculation in the cerebral cortex.
MATERIAL AND METHODS. The method of intravital microscopy was used to study the density of the microvascular network of the pial sheath of the cerebral cortex in Wistar rats 4 months after the removal of 5/6 of the renal tissue mass. At the same time, the level of perfusion and oxygen saturation (SO2) were measured in the cortical tissue using laser Doppler flowmetry. To assess the degree of kidney regeneration after resection, a morphological study of kidney tissue was carried out when staining with hematoxylin-eosin and Masson.
RESULTS. It was shown that 4 months after nephrectomy in the pial membrane, the density of the microvascular network decreased by an average of 1.3 times compared with falsely operated animals, and the number of arterial vessels by 1.5 times. The level of tissue perfusion (on average by 20%) and SO2 (on average from 95 to 91%) decreased statistically significantly. On morphological preparations, there were no signs of true regeneration; revealed glomerular hypertrophy, the development of fibrosis, deformation of blood vessels, and tubular structures.
CONCLUSION. Renal regeneration 4 months after nephrectomy 5/6 kidney mass is insufficient to normalize its function, and therefore does not prevent the cerebrovascular accident. Significant microcirculation disorders are observed in rat cerebral cortex: a decrease in the density of the microvascular network, a decrease in the rate of cerebral blood flow and tissue oxygen saturation, which are signs of the formation of lacunar strokes.

BACKGROUND. Klotho is a transmembrane and circulating protein primarily synthesized by the kidney. Klotho deficiency characterizes chronic kidney disease (CKD), as myocardial hypertrophy (GM). The cardioprotective effect of the Klotho protein is due to the negative regulation of a variety of stress signals, leading to the activation of the hypertrophic intracellular signaling pathway calcineurin (CaN) / NFAT in the myocardium. The effect of Klotho may presumably be mediated by the modulation of Ca2 + channels and / or Foxo factors essential for CaN signaling.
THE AIM: to study the activity of CaN/ NFAT signaling pathway in the myocardium and to determine the molecular mechanisms of its regulation in conditions of Klotho level decrease in spontaneous hypertensive rats (SHR) with experimental CKD.
MATERIAL AND METHODS. The experimental model of CKD was 3/4 or 5/6 nephrectomy (Nx) in SHR. Sham-operated (SO) SHR, and Wistar Kyoto rats (WKY) were used as controls. In all animals were measured systolic blood pressure, myocardial mass index – MMI, creatinine clearance, cardiomyocyte (CM) diameter, Klotho levels in serum (ELISA) and kidney (IHC), myocardial expression of calcineurin (IHC, PCR), transcription factor NFAT (IHC), TRPC6 (IHC), FOXO3A (PCR) and phosphor-Foxo1/3/4 (IHC). The tissue expressions of calcineurin, TRPC6, and Klotho were calculated as the IHC specific product area to the field of view ratio. NFAT expression was evaluated as the positively stained nuclei to the number of nuclei ratio in the field of view. Measurements were performed in 10 fields of view for each histology slide. RESULTS. The model has corresponded to the initial stages of CKD. The increase in MMI (p = 0.005) and CM diameter (p = 0.002) were observed compared in Nx rats to SO. Renal Klotho expression (p < 0.001), and serum Klotho level (p = 0.019) were lower in the Nx. In multiple linear regression analyzes, the values of MMI and CM thickness were independently associated with the level of renal Klotho protein (β = -0.38 ± 0.16, p = 0.026, β = -0.64 ± 0.14, p <0.001, respectively). Nx and systemic hypertension were accompanied by an increase in the expression of the calcineurin gene (p = 0.005) and cytoplasmic calcineurin in CM (p = 0.004), the number of NFAT-positive nuclei (p = 0.007), and an increase in the expression of the FOXO3A gene (p <0.001) in the absence of accumulation of phosphorylated Foxo1/3/4 in CM cytoplasm. SHR rats were characterized by positive IHC staining for TRPC6 compared to WKY (p = 0.004). The expression of calcineurin and TRPC6 varied co-directionally (r = 0.69, p <0.001), and both of these indicators were associated with the Klotho levels (calcineurin vs Klotho in the kidney, r = -0.73, p <0.001; TRPC6 vs Klotho in serum, r = -0.43, p = 0.025).
CONCLUSION. The development of Klotho deficiency on early-stage CKD is associated with the expression of transient Ca2+ channels TRPC6 and activation of the calcineurin / NFAT
hypertrophic signaling pathway in cardiomyocytes.

This review presents the possibility of using serum creatinine as an endogenous indicator of the functional state of the kidneys. The results of scientific research are analyzed, which shows the information content of the use of this indicator for assessing glomerular filtration rate (GFR). The features of laboratory methods for determining serum creatinine are considered. Particular attention is paid to information about the errors and variability of measurements of standardized methods obtained in laboratories of different countries. In addition to the physiological reasons that make serum creatinine an imperfect marker for GFR, there are analytical measurement errors, which, in turn, can also distort true results. Since the relationship between serum creatinine and GFR is hyperbolic, analytical errors will affect not only the accuracy of the calculation equations based on it. The introduction of standardization of routine methods for measuring serum creatinine from a reference sample improved the assessment of GFR by reducing the bias of the results of measuring creatinine from its true value. To increase the accuracy and reliability of standardized methods, it is necessary to continue research in this direction. In real clinical practice, all the limitations and assumptions of a specific method of measuring creatinine should be taken into account in order to avoid incorrect interpretation of the results when assessing the functional ability and staging of chronic kidney disease. For prospective observation of a specific patient, the same GFR calculation formula and the same method for measuring serum creatinine should be used.

IgG4-related disease (IgG4-RD) currently is considered as a chronic fibroinflammatory immune-mediated multisystemic condition of unidentified etiology, which can imitate a wide range of malignant, infectious, rheumatologic, and other diseases. It can affect almost any organ system in the body synchronously or sequentially, but the most often affected are the pancreas, hepatobiliary tract, periorbital structures, salivary glands, kidneys, and lymph nodes. The most frequent renal manifestations of IgG4-RD is IgG4-related tubulointerstitial nephritis. Membranous nephropathy is the most common glomerular disease accompanied by IgG4-RD. Regardless of the organ localization, patients with IgG4-RD are characterized by elevated serum IgG4, but this laboratory abnormality is not specific and can be changed in other diseases. In all suspected cases of IgG4-RD the diagnosis should be confirmed by histological examination. Characteristic pathologic features include diffuse or focal lymphoplasmacytic infiltration with prominent IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. Patients with IgG4- RD usually have an excellent clinical response to glucocorticoids, but relapse rates after steroid withdrawal are high, which may require additional use of immunosuppressants or rituximab. Due to the low prevalence and multitude of clinical manifestations the disease often remains underdiagnosed on time. This case report describes middle-aged patients with a history of chronic recurrent pancreatitis complicated by the nephrotic syndrome. Kidney biopsy showed membranous nephropathy and diagnosis IgG4-RD with multiorgan involvement was made. Partial remission was achieved on corticosteroid therapy. The presented case clearly demonstrates the difficulties of diagnosis and treatment of IgG4-RD. IgG4-related membranous nephropathy should be included in the differential diagnosis for patients with nephrotic syndrome accompanied by multiorgan dysfunction.