The literature review is devoted to methods of extracorporeal hemocorrection, such as plasma exchange, cascade plasma filtration and immunosorption in kidney diseases, including glomerulonephritis associated with antibodies to the glomerular basement membrane, antineutrophil cytoplasmic antibodies-associated glomerulonephritis, focal segmental glomerulosclerosis, systemic lupus erythematosus, atypical hemolytic-uremic syndrome in adults

This is a review of the literature on the problem of nephrotoxicity of antitumor drugs. Clinical manifestations of nephrotoxicity are considered, including acute/chronic tubulointerstitial nephritis (due to infection, hyperuricemia, calciuria, drug effects, etc.); thrombotic microangiopathy with kidney damage; acute tubular necrosis; acute cortical necrosis; thrombosis of the renal artery and its branches; thrombosis of the renal vein, its branches, inferior vena cava; glomerulonephritis (nephritic syndrome, nephrotic syndrome, isolated urinary syndrome; morphological patterns of IgA nephropathy, membranous nephropathy, disease of minimal changes, focal segmental glomerulosclerosis, C3 dominant nephropathy, etc.); hempigmental nephropathy (a consequence of acute intravascular hemolysis, less often – rhabdomyolysis); nephrocalcinosis, urolithiasis; pyelonephritis, etc. The classification of antitumor drugs is given. Since different classes of drugs have different mechanisms for the development of nephrotoxicity, the article discusses the main ones with examples. The article also presents well-known and promising approaches to the prevention and treatment of nephrotoxicity of antitumor drugs.

The successful application of messenger RNA (mRNA)-based vaccines for the prevention of COVID-19 infection has drawn the attention of the scientific community to the potential clinical applications of these molecules as innovative and alternative therapeutic approaches in various fields of medicine. As therapeutic agents, mRNAs may be advantageous due to their unique biological properties – the ability to target virtually any genetic component of the cell and encode any proteins and peptides without the need to transfer them to the nuclei of target cells. In addition, these molecules can be rapidly designed/produced and clinically tested. Once the RNA chemistry and delivery system are optimized, the cost of developing new variants of these drugs for newly selected clinical diseases is greatly reduced. However, despite their potential value as novel therapeutic weapons against several kidney diseases, the complex kidney architecture and the inability of oligonucleotide-containing nanoparticles to cross the integral glomerular filtration barrier have greatly reduced their potential application in nephrology. Nevertheless, technical improvements in mRNAs that increase translation efficiency, modulate innate and adaptive immunogenicity, and improve their selective delivery to the site of action are expected to overcome these limitations and the potential for kidneytargeted therapies will greatly expand over the next few years. This is all the more important given that chronic kidney disease (CKD) affects just over 10 % of the world's adult population to some degree, and CKD is projected to become the fifth leading cause of death by 2040, with about half of patients dying from cardiovascular disease. The purpose of this mini-review is to provide a summary of the main benefits of RNAi-based therapies and illustrate the potential future directions and challenges of this promising technology for widespread therapeutic use in nephrology.

Impaired renal function is characteristic of systemic lupus erythematosus (SLE) and other autoimmune diseases. Given the availability of various diagnostic methods and the potential for etiopathogenetic treatment, it is crucial for rheumatologists and nephrologists to promptly suspect kidney disease in patients with SLE and take necessary measures for diagnosis and treatment. Modern strategies for classifying and treating SLE guidelines have been updated to incorporate findings from kidney biopsies., significantly improving the prognosis for this disease. On the other hand, it should be remembered that long-term use of immunosuppressants, as well as concomitant diseases such as diabetes mellitus, hypertension, and cardiovascular complications, might be the main causes of kidney damage in patients with SLE. In this review, we discuss renal dysfunction due to underlying diseases, the side effects of medications, and the importance of making timely decisions.

BACKGROUND. Cardiovascular complications (CVС) are the leading cause of death in a cohort of CKD patients, including young working age people. The search for a prognostic marker that allows predicting and preventing the risk of CVС is an important not only medical but also socioeconomic task.

THE AIM OF THE STUDY: To determine the predictive value of baseline serum Klotho levels in assessing cardiovascular risk, risk of developing end-stage renal disease (ESRD), and overall survival among patients with stage 3-4 CKD, during an 8-year follow-up period.

PATIENTS AND METHODS: The study included 75 patients with CKD C3-4, mean age 54+9 years. The initial serum Klotho level was divided into quartiles (1 quartile Klotho – 148-336 pg/ml; 2-3 quartile – 337-580 pg/ml; 4 quartile – 580-812 pg/ml). The overall survival of patients over a period of 8 years, the cause of death, and the achievement of ESRD, depending on the Klotho quartile, were assessed. RESULTS: During the observation period, 22 patients died, of which 12 (54.5 %) died from CVC, 7 (31.8 %) from covid infection, 3 (13.6 %) from other causes. When assessed by quartiles, patients with the 1st quartile prevailed among the deceased patients, including those from CVC: the 1st quartile was – 9 (75.0 %), the 2nd-3rd quartile -3 (25.0 %), the 4th quartile – 0 ( 0 %), (chi-square = 8.2, p=0.023). Among patients who achieved ESRD and started dialysis (n=30), patients with 1 quartile were 12 (63.2 %), 2-3 quartile -16 (43.2 %), 4 quartile – 2 (10.5 % ), (chi-square = 11.3, p = 0.01). Among the surviving patients (n=53) with CVC on the moment of end study (n=28), patients with 1 quartile were 19 (67.9 %), 2-3 quartile 9 (32.1 %), 4 quartile – 0 % (chisquare=19.9, p<0.001). At the same time, among the entire sample of patients, there was no correlation of the Klotho level with age (r=-0.067, p=0.570), CKD stage (r=-0.281, p=0.06). In the same time, there was a statistically significant correlation of Klotho level with the achievement of ESRD by the patient and the beginning of dialysis (r=-0.465, p<0.001), the development of CVC (r=-0.512, p<0.001), overall survival (r=-0.368, p=0.001).

CONCLUSION: According to our data, the serum level of Klotho did not depend on the age of patients or the stage of CKD (in the sample of patients with 3-4 stages of CKD), however, it was clearly associated with the risk of cardiovascular events, the risk of progression of CKD to ESRD, overall survival of patients and can be considered as prognostic marker in patients with pre-dialysis stages of CKD.

BACKGROUND. The achievement and maintenance of euhydration are the key components of dialysis effectiveness, particularly in reducing the risk of cardiovascular events. Sodium loading during the session is one of causes of excessive sodium and water intake. THE AIM: was to evaluate the effectiveness and safety of an individualized approach to the prescription of dialysate sodium based on the serum sodium. PATIENTS AND METHODS. After retrospective analysis of previous serum sodium (1049 patients-months), interdialytic weight gain (IDWG), blood pressure(BP) and dialysate sodium(NaD), we prescribed the NaD at the sodium setpoint (n=45). RESULTS. The stability of predialysis serum sodium was high, and five monthly samples were sufficient to accurately assess the sodium setpoint. After six-month, there was a reduction in IDWG from 2.51±0.86 to 2.26±0.87 kg in the entire group (p=0.003), the result was achieved in both subgroups, with a decrease in NaD (2.63±0.81→2.37±0.82 kg; p=0.021), and with an increase in NaD (2.39±0.90→2.15±0.88 kg; p=0.049). Baseline IDWGs were higher in the first subgroup (p=0.041); but after NaD individualizing they were almost the same. Individualization of NaD was accompanied by a gradual reduction in systolic BP (-0.76±0.14 mmHg/month, p=0.005), but not diastolic BP (-0.13±0.13 mmol/l/month). After bidirectional change in NaD the dynamics of systolic BP didn`t differ between groups with a decrease or increase in NaD: (-0.80±0.13 vs. -0.72±0.11 mmHg/month; p=0.052). CONCLUSION. Individualization of dialysate sodium to set point leads to a decrease in IDWG and BP even while NaD increases, without increasing in the frequency of intradialysis hypotension. The effectiveness and safety of the approach require confirmation in large-scale interventional studies.

THE AIM OF THE STUDY: to identify risk factors associated with the course of chronic kidney disease (CKD), as the main manifestation of damage to the target organ – the kidney, in patients with chronic heart failure (CHF) infected with the human immunodeficiency virus (HIV).

PATIENTS AND METHODS. In a multidisciplinary hospital for 28 months in 2019-2022, a one-stage screening clinical study was conducted, which included 240 patients with HIV infection. Of these, 160 people were diagnosed with CHF. Depending on the presence of CKD with a glomerular filtration rate (GFR) <60 mm/min/m2, patients with CHF were divided into 2 groups. The first group consisted of patients with CKD (46 people), and the second group – without signs of CKD (114 people). All patients within the framework of the study underwent the determination of cystatin C in blood serum, the Nterminal fragment of the brain natriuretic peptide (NT-proBNP) in blood plasma, C-reactive protein (CRP) in blood serum, and the quantitative determination of protein in urine.

RESULTS. The prevalence of CKD among patients with CHF and HIV infection is 58.82 %, which is 4 times more common than in patients with HIV infection without CHF. Risk factors for the development of CKD in patients with CHF and HIV infection are smoking, alcohol and drug use, a history of chronic and acute forms of coronary artery disease, atrial fibrillation, ventricular arrhythmias, diabetes mellitus, chronic viral hepatitis C, anemia, and thrombocytopenia. Patients with CHF and CKD have a more rigid arterial wall – there is a significant excess of the stiffness indices of the aorta and peripheral arteries. Long-term use of antiplatelet agents and antiretroviral therapy aggravates the course of CHF in HIV-infected people with CKD manifestations. The concentration of NT-proBNP in the blood plasma of patients with CHF equal to or greater than 683.65 pg/ml can be considered as a diagnostic criterion for the development of CKD in HIV-infected people with a sensitivity of the method of 75.0 % and a specificity of 75.4 %, respectively. It has been proven that GFR depends on three main factors that reflect damage to the heart muscle – the concentration of NT-proBNP in blood plasma, the values of LVEF % and LVMI, which together, being included in the regression model, determine 42.2 % of the dispersion of GFR values and are decisive in the development of CKD in patients with CHF on the background of HIV infection.

BACKGROUND. Nephrogenic anemia is a serious problem in patients with chronic kidney disease, requiring a careful approach and adequate treatment. This condition manifests at the first stage and steadily progresses as GFR decreases. Therefore, timely correction of renal anemia with iron supplements and erythropoiesis stimulate agents (ESA) in CKD C5 is an integral component of therapy to reach target Hb values.

THE AIM. This paper provides an analysis of the effectiveness of erythropoiesis-stimulating therapy among patients with end-stage CKD (C5d) receiving treatment with program hemodialysis on the basis of the Republican hospital named V.A. Baranov.

PATIENTS AND METHODS. During the year 2022, 107 patients with end-stage CKD were observed. All of them had been receiving renal replacement therapy through a hemodialysis program (1284 patientmonths) and erythropoiesis-stimulating therapy with monthly monitoring of hemoglobin levels, following the clinical guidelines «Anemia in chronic kidney disease – 2020-2021-2022».

RESULTS. The median hemoglobin level for 2022 was 107.8 g/L. The average annual increase was 8.9 g/l. Overall, the hemoglobin level in patients who did not receive EPO was 115.5 g/l. Patients receiving EPO who did not reach the target hemoglobin level (IR: 100-120 g/L) had a median hemoglobin of 92.5 g/L. To achieve the presented levels of anemia correction, the average weekly dose was 6,785 IU when calculated for the entire year 2022, including those patient months when EPO was not used.

CONCLUSIONS. During treatment with EPO drugs, an increase in hemoglobin levels is observed, patients' quality of life improves, the risks of cardiovascular complications decrease, performance and physical endurance increase, the frequency and duration of hospitalizations decrease, and the need for blood transfusions decreases. The main challenges in solving the problem of refractory anemia involve individualizing treatment, considering drug response, and identifying additional factors.

THE AIM: to evaluate the morphological picture and its relationship with markers of acute kidney injury and other prognostic parameters in patients with severe fatal acute decompensation of heart failure (ADHF).

PATIENTS AND METHODS: material obtained from 62 patients 47–82 years old (mean age 72.8±2.1 years) with severe acute decompensation of chronic heart failure resulting in death. The red cell distribution width, erythrocyte sedimentation rate haemoglobin, creatinine, total bilirubin, C-reactive protein content in blood at admission and shortly before death were determined. Autopsy with subsequent detailed examination of renal tissue was performed in all cases.

RESULTS: The average duration of hospitalization of deceased patients with ADHF was 6,9±1,1 days. The main cause of death in 25 patients (40,3%) was pulmonary oedema due to pulmonary embolism, or against the background of heart failure, its acute decompensation developed – 37 patients (59,7%). On autopsy acute tubular injury was found in 36 patients (58.1%), with its direct strong correlation with the red cell distribution width, creatinine level, C-reactive protein; medium strength correlation with erythrocytes, total bilirubin; weak strength correlation – with transaminases was revealed.

CONCLUSION: In fatal ADHF, AKI occurred with high frequency and was characterized mainly by acute tubular epithelial injury of varying severity. Acute kidney injury in fatal ADHF was strongly associated with elevated levels of CRP, RDW, and creatinine, increased heart weight, and the presence of hydrothorax. There was a correlation of medium strength with decreased red blood cell count and increased total bilirubin levels, and a weak correlation with elevated transaminase concentrations. Acute kidney injury is one of the components of thanatogenesis associated with the combined effect of inflammatory factors.

BACKGROUND: Hemophagocytic lymphohistiocytosis is an uncommon disease with a high mortality rate due to ineffective overactivation of the immune system. THE AIM: to assess the effect and prediction of elevated serum soluble interleukin-2 alpha level on kidney outcomes in hemophagocytic lymphohistiocytosis.

PATIENTS AND METHODS: In this analytic (experimental) clinical studies type with randomized clinical trials design in meta-analysis article, two-hundred eighty-three patients with hemophagocytosis lymphohistiocytosis diagnosis and kidney impairment were investigated.

RESULTS: Relative risk and Odds ratio of elevated serum soluble interleukin-2 receptor alpha level on kidney failure progression to kidney replacement therapy was assessed 1.04 and 1.12 during 28 days and interquartile range of 35.5 days in hemophagocytic lymphohistiocytosis in this research. In prediction probability of death and chronic kidney disease progression to end-stage kidney disease led to kidney replacement therapy as outcome using high serum soluble interleukin-2 receptor alpha level was not significant statistically (p-value of 0.91 and p=0.56, respectively). There was strong negative correlation between soluble interleukin-2 receptor alpha levels and cumulative incidence of renal outcomes such as hyponatremia, proteinuria, acute kidney disease, elevated serum blood urea nitrogen and serum creatinine levels with rs of -0.7 and p-value of o.18. There was relationship between serum soluble interleukin-2 receptor alpha level and past medical history (p-value: 0.01) but overall this analysis did not show significant level statistically (p-value: 0.1).

CONCLUSION: There was a strong negative correlation between serum soluble interleukin-2 receptor alpha levels and cumulative incidence of renal outcomes. There wasn't a relationship between serum soluble interleukin-2 receptor alpha level and renal outcome after adjustment of confounding factors for renal function except for past medical history.

Sujpplement files (Tables) are located at: https://figshare.com/authors/Fateme_Shamekhi_Amiri/9040742  

BACKGROUND. Of particular scientific and practical importance are studies aimed at assessing the clinical features of the course and morphological signs of nephrotic and nephritic syndromes in children with chronic kidney diseases of the first and second stages. THE AIM: to assess the rate of progression of glomerulopathy in children depending on the treatment regimen.

PATIENTS AND METHODS. 238 children aged 1–18 years with an established nosological diagnosis of kidney damage at various stages of CKD were examined, hospitalized for treatment in the Department of nephrology at the clinic of the Tashkent  Pediatric Medical Institute in the period 2010-2022 and the National Children's Medical Center from 2021–2023.

RESULTS. Children with CKD were divided into two subgroups: 146 children with nephrotic syndrome (steroid-sensitive, steroid-resistant or often recurrent) and 92 children with nephritic syndrome. More than half of the children have glomerulonephritis with minimal changes. In 25.4 % of cases, they were insensitive to steroid therapy. Among patients with nephritic syndrome, 46 % had IgA nephropathy. In dynamics, the most unfavorable picture was formed in children with focal segmental glomerulosclerosis. After 12 years of follow-up, 41.7 % of them developed terminal renal failure. The least effective treatment was noted with the use of cyclophosphamide, the best with the combination of tacrolimus with mycophenolate mofetil.

CONCLUSION. Treatment regimens for children with glomerulopathy are still far from perfect.

IgG4-associated disease is a systemic disease. Kidney damage is often noted in the form of interstitial nephritis, obstructive nephropathy, less often -glomerulopathy (including membranous nephropathy). IgG4-associated disease was isolated as an independent nosological form in 2003, when signs of systemic damage (involvement of the biliary tract, salivary glands, retroperitoneal space) were found in patients with type 1 autoimmune pancreatitis, and in 2012 the first international nomenclature of the disease was proposed. The clinical manifestations of IgG4-associated disease are nonspecific and diverse, which determines the difficulties of differential diagnosis, including infections and tumors, and increases the period from the onset of the disease to diagnosis to an average of 2 years. In recent years, there has been a significant increase in the number of studies devoted to this pathology, and in 2019, experts from the European Antirheumatic League (EULAR) and the American College of Rheumatology (ACR) proposed classification criteria for IgG4-associated disease. IgG4-associated disease is more likely to develop in middle age and old age. The prevalence of the disease is higher among men than among women, although the frequency of various clinical forms may vary depending on age and gender. Thus, autoimmune pancreatitis type 1, retroperitoneal fibrosis, and tubulointerstitial nephritis are more common in men, and sialoadenitis, dacryoadenitis, and thyroiditis are more common in women. In this article, we present a clinical case of IgG4-associated systemic disease with a combined lesion of the tubulo-interstitial and glomerular compartments of kidney tissue with nephrotic syndrome as the only initial manifestation. Membranous nephropathy was confirmed by nephrobiopsy. The combination of IgG4 and tubulo-interstitial nephritis with membranous nephropathy is an extremely rare pathology. The nephrotic syndrome was completely resolved after treatment with immunosuppressants. Nephrobiopsy was crucial in the diagnosis of this condition, which allowed the patient to be prescribed proper and timely treatment.