[State-of-the-art trends in the treatment of immune-mediated inflammatory kidney diseases: Translation of the fundamental science into clinical practice. A review].

Immune-mediated kidney diseases like glomerulonephritis and tubulointerstitial nephritis are not the most common cause of chronic kidney disease in the population, however the difficulties in their management, as well as a more rapid deterioration of kidney function, compared to diabetes mellitus and hypertension, justify the importance of this problem for internal medicine. Due to the fundamental discoveries in pathology and to the introduction of various methods of laboratory and instrumental investigation in the second half of the XX century substantial progress was made in the diagnostic approaches and treatment of these conditions. State-of-the-art diagnostic approach requires complex evaluation of the clinical, laboratory and morphological data to identify the nosological form of the disease. The accumulation of knowledge in the field of diseases' pathogenesis led to the revision of the current classification of glomerulonephritis that should be based on the immunopathogenesis of these conditions. The following phenotypes were suggested: autoimmunity-related, autoinflammation-related, alloimmunity-related, infections-related, and monoclonal gammopathy-related. The assessment of disease activity and chronicity in the kidney tissue should be mandatory. Personalized selection of the optimal treatment modality on the basis of the diagnosis, severity, and individual features of the patient is currently possible. The leading trends include rational prescription of glucocorticoids (steroid-sparing regimens) and cytotoxic agents, e.g. cyclophosphamide, as well as the introduction of multitarget regimens that include biologic agents or small molecules selectively suppressing B-cells or various complement pathways. Another mandatory component of treatment on par with immune suppression is nephroprotective therapy, which currently comprises not only traditional renin-angiotensin-aldosterone antagonists, but also endothelin receptor antagonists and sodium-glucose cotransporter-2 inhibitors. Current guidelines emphasize the importance of the non-pharmacological interventions for the implementation of the nephroprotective strategy. Rational combination of the aforementioned approaches allows for the optimization of the management of patients with immune-mediated kidney diseases, although it requires high competencies and strict adherence to the principles of the evidence-based medicine from the healthcare providers.

[State-of-the-art paradigm of corticosteroid therapy for immune-mediated inflammatory kidney diseases].

Since 1950's corticosteroids (CS) have remained the cornerstone of immunosuppressive therapy for immune-mediated kidney diseases. However multiple adverse events, associated with the prolonged CS therapy, became the basis for the development of novel treatment approaches. Current evidence supports the implementation of the steroid-sparing regimens for the treatment of different types of glomerulonephritis. Randomised controlled trial PEXIVAS demonstrated the efficacy and safety of early steroid tapering, starting from the second week of therapy, in patients with ANCA-associated vasculitis with kidney involvement. Several trials showed the efficacy of oral prednisolone 0.3-0.5 mg/kg/daily as a part of multitarget therapy for severe proliferative lupus nephritis. A combination of calcineurin inhibitors and low-dose CS are effective for remission induction in membranous nephropathy, as well as the steroid-free rituximab regimen for the patients with moderate risk of disease progression. Medium dose CS showed promising effect in patients with IgA-nephropathy. Long-term high dose CS remain the standard-of-care for the treatment of minimal change disease and focal segmental glomerulosclerosis, however patients with steroid-dependent and relapsing disease tacrolimus and rituximab can help to achieve steroid-sparing effect. The role of CS pulse-therapy is currently debated, nevertheless it remains a compulsory treatment in several conditions. Thus, overall trend is directed towards the minimization of the maximal doses of CS and/or treatment duration. However, to implement this approach morphological verification of the diagnosis and personalized assessment of the potential risk and benefit are required.

[Study of urinary markers of different podocytopathies by proteomic analysis].

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a primary podocytopathy characterized by primary podocyte detection and high proteinuria. The search for biomarkers and factors associated with the progression of this disease is an important task nowdays. AIM: To assess the proteomic profile of urine in patients with FSGS and to isolate urinary biomarkers of podocytopathies. MATERIALS AND METHODS: The study included 41 patients diagnosed with chronic glomerulonephritis, 27 men and 14 women. According to the morphological study, 28 patients were diagnosed with FSGS, 9 with steroid-sensitive nephrotic syndrome and 14 with steroid-resistant nephrotic syndrome. The comparison group included 13 patients with membranous nephropathy. The study of the urinary proteome was carried out by targeted liquid chromatography-mass spectrometry using multiple reaction monitoring with synthetic stable isotope labelled peptide standards. RESULTS: The main differences in the protein profile of urine were found in the subgroups of steroid-sensitive (SS) and steroid-resistant (SR) FSGS. In the FSGS SR group, at the onset of the disease, there was a high concentration of proteins reflecting damage to the glomerular filter (apo-lipoprotein A-IV, orosomucoid, cadherin, hemopexin, vitronectin), as well as proteins associated with tubulo-interstitial inflammation and accumulation of extracellular matrix (retinol- and vitamin D-binding proteins, kininogen-1, lumican and neurophilin-2). Compared with the membranous nephropathy group, FSGS patients had significantly higher urinary concentrations of carnosinase, orosomucoid, cadherin-13, tenascin X, osteopontin, and zinc-alpha-2-glycoprotein. CONCLUSION: Thus, in patients with SR FSGS, the proteomic profile of urine includes more proteins at elevated concentrations, which reflects severe damage to various parts of the nephron compared with patients with SS FSGS and membranous nephropathy.

[Rheumatoid factor: study history and concept evolution].

Rheumatoid factor became the first laboratory marker of rheumatoid arthritis and one of the first serological markers used to recognize the major autoimmune diseases. Details of the discovery with special regard to contribution of E. Waaler and H. Rose are presented in this historical review. Same assays used to exam the rheumatoid factor, its frequency and modern view on diagnostic significance in different diseases are described in this article.

[Prevalence and risk factors of delirium in COVID-19]. / Rasprostranennost' i faktory riska deliriya pri COVID-19.

OBJECTIVE: To assess the frequency and risk factors of delirium in patients hospitalized with COVID-19. MATERIAL AND METHODS: Four hundred and forty patients admitted to the Infectious Diseases Hospital of the University Clinical Hospital No.3 of Sechenov University were included in the study. The Patient Health Questionnaire (PHQ-9), the Generalized Anxiety Disorder Screening Questionnaire-7 (GAD-7), the Insomnia Severity Index (ISI), the Delirium severity rating scale (DRS-R-98) were administered. RESULTS: Delirium was detected in 27.8% of patients. Significant risk factors were age (p=0.002), severity of respiratory failure (p=0.005), concomitant somatic disease (p=0.003), and respiratory therapy (p<0.001). There was an association between severe anxiety (p<0.001) and insomnia (p=0.07) observed at admission with the risk of developing delirium during the hospital stay. CONCLUSION: The study reveals a high prevalence of delirium in patients with COVID-19. In order to prevent delirium and/or reduce the risk, early diagnosis and identification of preclinical forms are of particular importance.

[Interstitial pneumonia with autoimmune features: monocentric prospective study].

AIM: To study demographic, clinical, serological and morphological features of interstitial pneumonia with autoimmune features (IPAF), compare survival in IPAF and interstitial lung disease in connective tissue diseases (CTD-ILD), and identify predictors of mortality and transformation to CTD in the IPAF group. MATERIALS AND METHODS: The IPAF group included 48 patients (75.0% women, median age 57.5 years), CTD-ILD - 49 patients (79.6% women, median age 60.0 years). The analysis of demographic, clinical, laboratory and instrumental data was performed, as well as comparison of survival with the Kaplan-Meier method and the log-rank test in the IPAF and CTD-ILD groups. In the IPAF group, predictors of mortality and the development of CTD were studied with multivariate regression analysis. RESULTS: Duration of observation period did not differ significantly in the IPAF and CTD-ILD groups (40.0 and 37.0 months, respectively). Clinical criteria of IPAF were observed in 25 (52.1%) patients, serological - in 44 (91.7%), morphological - in 44 (91.7%). Mortality in the IPAF group was significantly higher than in the CTD-ILD group (29.2 and 6.1%, respectively; p=0.023). The presence of diabetes mellitus, CT-pattern of usual interstitial pneumonia, and an initial low forced vital capacity value were independent predictors of mortality in the IPAF group. During the observation period, the development of CTD was noted in 4 (8.3%) patients with IPAF. The independent predictor of the CTD development was the increased C-reactive protein level. CONCLUSION: IPAF is characterized by a lower survival rate compared to CTD-ILD, and a relatively low risk of CTD transformation.

[Gout: from Hippocrates till the modern time].

Gout (podagra) is one of the most ancient articular diseases. Its accurate mechanisms and causes were delineated only during the last century. Major historical investigatory steps are described in relation to causality and pathogenesis of the disease from Hippocrates ages till the modern time. The newest genetic and epidemiologic aspects of the disease are presented in this article.

[Organizing pneumonia as a pulmonary manifestation of post-COVID syndrome: features of diagnosis and treatment].

Treatment of patients with long-term persistent symptoms after COVID-19 is an urgent problem for clinicians around the world. One of the most significant manifestations of post-COVID-19 syndrome is organizing pneumonia that is usually treat with corticosteroids. The paper presents a clinical case of typical course of post-COVID-19 organizing pneumonia in a patient without previous lung disease. Risk factors, diagnostic methods and treatment options in this group of patients are also discuss.

[Lupus nephritis in the XXI century].

Lupus nephritis (LN) is the most common organ lesion in systemic lupus erythematosus (SLE), developing in 4050% of patients. Due to immunosuppressive therapy, the survival of patients with SLE has increased significantly over the past 50 years, and the proportion of severe kidney damage in the death structure has decreased. However, LN relapses and complications of immunosuppression, accelerated atherogenesis, concomitant diseases lead to the accumulation of organ damage and an increased risk of death. The article consideres the place of kidney damage in the SLE, the risk factors for LN development, the main renal histopathological changes, it identifies a number of issues that need to be addressed to optimize treatment and improve LN long-term outcomes, including, the revision of pathogenetic therapy regimens with restriction of glucocorticosteroids and prescribing drugs with steroid-sparing activity, the integration of new drugs for LN treatment, wider use of modern nephroprotection capabilities.

[Evaluation of hemostasis disorders using the thrombodynamic test in patients with chronic glomerulonephritis with nephrotic syndrome].

BACKGROUND: Nephrotic syndrome (NS) is accompanied by a risk of thrombotic complications due to hypercoagulability. Routine laboratory tests are not sensitive enough to detect these disorders, and therefore the use of integral coagulation tests, including a new thrombodynamic test (TT) in patients with NS, is of high relevance. AIM: Using a TT to determine hemostasis disorders in patients with chronic glomerulonephritis (CGN) with NS. MATERIALS AND METHODS: The study included 49 patients with CGN, mean age 37 years, of which 25 (51%) women and 24 (49%) men. Of all the examined patients, 20 (40.8%) of people had NS, 29 (59.2%) had no NS. The process of clot formation was assessed by TT. RESULTS: According to TT, 30% (6/20) of patients with NS and 13.7% (4/29) of patients without NS have hypercoagulation with changes in parameters that go beyond the reference values. In patients with NS, an increase in clot density (D), clot formation rate (V) and clot size (CS) was found, especially when albumin decreased below 25 g/l. Negative correlations were found between the levels of albumin, creatinine and clot density (D), which reflects the level of hyperfibrinogenemia, the rate of clot formation (V) and the integral index of coagulation (CS). The results indicate mainly the activation of the plasma hemostasis due to the internal coagulation pathway. However, the correlation of Tlag (delay time for the onset of clot formation after contact of blood plasma with the insert-activator) with serum cholesterol levels may also indicate activation of the extrinsic coagulation pathway. CONCLUSION: In CGN patients with NS, activation of the plasma hemostasis is noted, as evidenced by an increase in the rate of formation (V) and size of the clot (CS) after 30 minutes, as well as the density of the formed clot (D).

[Risk factors of kidney injury in patients with COVID-19].

AIM: To determine the incidence and risk factors of acute kidney injury (AKI) in Russian cohort of patients with COVID-19. MATERIALS AND METHODS: We included 315 patients, who were hospitalized with COVID-19 from October 2020 till February 2021. The diagnosis was established on the basis of the positive SARS-CoV-2 swab test and/or typical radiologic findings on CT scans. RESULTS: AKI complicated the clinical course in 92 (29.21%) cases. The independent risk factors of AKI were female sex, underline chronic kidney disease and the highest level of C-reactive protein during hospitalization. In the general group of patients were 41 (13%) lethal cases, in the group with AKI 32 (34.8%). Compared with those without AKI, patients with AKI had 4.065 (95% confidence interval 2.154 to 7.671) times the odds of death. Respiratory support, the highest serum creatinine and glucose levels appeared to be the risk factors of death among patients with AKI in the multivariable Cox regression. CONCLUSION: The clinical course of COVID-19 was complicated by AKI in 29% cases. The independent risk factors of AKI in patients with COVID-19 are underline chronic kidney disease, circulatory disorder and the highest level of C-reactive protein during hospitalization.

[Impact of kidney biopsy on the management of patients in the rheumatology department: retrospective study].

BACKGROUND: Kidney involvement is a common manifestation of the systemic autoimmune rheumatic diseases. Kidney biopsy is the gold standard for the diagnosis of kidney diseases, however this method has not yet become the standard-of-care in rheumatology practice. AIM: To assess the diagnostic value of kidney biopsy in the management of patients of the rheumatology department. MATERIALS AND METHODS: In this retrospective observational study we analyzed the medical documentation including kidney morphology findings in the patients of the Department of Rheumatology at Tareev Clinic of Internal Diseases. All patients included in the research had signs of kidney involvement and had undergone needle biopsy of the kidney or re-evaluation of the kidney tissue received previously. RESULTS: From June 2016 to October 2021, 3110 patients were admitted to the rheumatology department. Among them 63 (2%) underwent kidney biopsy and were included in the study. Twenty (32%) were male. Mean age was 42.513.9 years. The most common preliminary diagnoses before kidney biopsy were ANCA-associated vasculitis (n=17), systemic lupus erythematosus (n=12), and AA-amyloidosis associated with inflammatory joint diseases (n=7). In 14 (27%) patients diagnosis was unspecified at the time of biopsy. Among 49 patients with established preliminary diagnosis morphological findings were in line 38 (78%) with the pre-liminary diagnosis. However, in 11 (22%) patients morphological findings resulted in the change of the diagnosis. In all 14 patients with unspecified condition kidney biopsy helped to establish clinical diagnosis. Ultrasound evaluation demonstrated hematoma formation in 18 (31%) patients, and among them two required blood component transfusions. CONCLUSION: Our study demonstrates significant value and safety of kidney biopsy in the patients with autoimmune rheumatic conditions. We suggest that kidney biopsy should be implemented in the management of this category of patients.

[Classification of systemic vasculitis: evolution from eponyms to modern criteria].

Systemic vasculitis is a manifold group of systemic autoimmune diseases characterized by the inflammation of the blood vessels. The first clinical cases of systemic vasculitis were described in the Middle Ages, and most of the currently recognised nosological forms were reported in the first half of the 20th century. The first attempt to create a united classification of vasculitis was performed by P. Zeek in 1952. In the following decades accumulation of the data on the etiology and pathogenesis of different vasculitis guided researchers from different countries in their attempts to improve classification. The main principles of classification were the size of the affected blood vessels, disease etiology and pathogenesis. In 1990 American College of Rheumatology (ACR) published classification criteria for seven forms of the systemic vasculitis, that gave a significant contribution to the conduction of large-scale studies in this field. However, the first international nomenclature of vasculitis was developed only in 1994 during the Consensus Conference in Chapel Hill. Revised and augmented version of this nomenclature was created in 2012 and is still valid. An important step in the development of the classification of vasculitis was a joint project of ACR and EULAR aimed to develop new diagnostic and classification criteria for vasculitis (DCVAS). The first result of this project are the new classification criteria for granulomatosis with polyangiitis, microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis published in 2022. In general, the evolution of the classification of vasculitis occurs under the influence of the progress in the understanding of their etiology and pathogenesis.

Photon/spin echo in a Fabry-Perot cavity.

The pulse area theorem is a well-known versatile analytical tool for capturing the general nonlinear nature of light propagation in a two-level medium. Here we derive the pulse area theorem for the photon/spin echo signal generated in a one-side cavity. The obtained analytical solutions for primary and secondary echo pulse areas allow us to describe the nonlinear patterns of the photon/spin echo signals in an atomic ensemble in a cavity. The developed approach and the obtained results constitute an important step in the study of the general properties of the photon/spin echo in optical and microwave cavities expanding applications of the photon echo in coherent spectroscopy, quantum memory, and processing.

[Sarcoidosis and primary biliary cholangitis in a patient with cholestasis].

Primary biliary cholangitis and sarcoidosis are both cholestatic liver diseases. Currently, there are no established specific criteria for distinguishing the diseases from each other; diagnosis is based on the anamnesis, as well as the results of physical, laboratory and instrumental examination. The case report presents a female patient with a rare combination of histologically verified liver sarcoidosis and primary biliary cholangitis. Despite the similar clinical manifestations, the approaches to the treatment of these diseases are completely different, that underlines the importance of the differential diagnosis to exclude combined liver damage.

[Methotrexate-induced lung damage in a patient with rheumatoid arthritis].

We herein report a case of interstitial lung disease secondary to the use of methotrexate in a patient with rheumatoid arthritis. Differential diagnosis between pneumonitis caused by methotrexate in patients treated with basic methotrexate therapy and interstitial pulmonary disease associated with rheumatoid arthritis is based on the clinical examination and instrumental data. The main condition for favorable clinical outcome in all drug-induced lung disease is drug withdrawal, what was proven in our report.