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Materials and methods. 253 patients with chronic hepatitis C (CHC) and liver cirrhosis were included in the study. Assessment of gene polymorphisms of genes involved in inflammatory reactions and antiviral immunity (IL-1β-511C/T, IL-10 -1082G/A, IL28B C/T, IL28B T/G, TNF-α -238G/A, TGF-β -915G/C, IL-6 -174G/C), activators of local hepatic fibrosis (AGT G-6A, AGT 235 M/T, ATR1 1166 A/C), hemochromatosis (HFE C282Y, HFE H63D), platelet receptors (ITGA2 807 C/T, ITGB3 1565 T/C), coagulation proteins and endothelial dysfunction (FII 20210 G/A, FV 1691G/A, FVII 10976 G/A, FXIII 103 G/T, eNOS 894 G/T, CYBA 242 C/T, FBG -455 G/A, PAI-675 5G/4G, MTHFR 677 C/T) was carried. Using Bayesian networks we studied the predictor value of clinical and laboratory factors for the following conditions - end points (EP): development of cirrhosis (EP1), fibrosis rate (EP2), presence of portal hypertension (EP3) and cryoglobulins (EP4). Results and discussion. In addition to traditional factors we have shown the contribution of the following mutations. Predicting EP1- liver cirrhosis - HFE H63D, C282Y, CYBA 242 C/T, AGT G-6G, ITGB31565 T/C gene mutations were significant. We also found a link between the rate of progression of liver fibrosis and gene polymorphisms of AGT G-6G, AGT M235T, FV 1691G/A, ITGB31565 T/C. Among the genetic factors associated with portal hypertension there are gene polymorphisms of PAI-I-675 5G/4G, FII 20210 G/A, CYBA 242 C/T, HFE H63D and Il-6 174GC. Cryoglobulins and cryoglobuliemic vasculitis (EP4) are associated with gene mutations MTHFR C677T, ATR A1166C and HFE H63D. Conclusion. The results obtained allow to detect the major pathophysiological and genetic factors which determine the status of the patient and the outcome of the disease, to clarify their contribution, and to reveal the significance of point mutations of genes that control the main routes of HCV course and progression.

Microscopic polyangiitis (MPA) is the form of ANCA-associated vasculitis, characterized by pulmonary and kidney damage. This article discusses a case of severe MPA in a young patient and is focused on the modern diagnostic and treatment approaches. The authors also review different clinical courses and outcomes of MPA.

Cardiac sarcoidosis is of predictive value, but its diagnostics is difficult in view of the lack of pathognomonic clinical signs and the high frequency of cases with subclinical course. In this article, we present an algorithm of clinical examination and treatment strategy using combined immunosuppressive therapy of cardiac sarcoidosis in a young women whose only symptom was frequent premature ventricular beats. In this clinical case cardiac sarcoidosis was diagnosed practically at the onset of the disease and the use of massive immunosuppressive therapy allowed to reach considerable positive dynamics even before development of irreversible changes both in myocardium and lungs.

Neutrophil dysfunction plays a considerable role.in systemic lupus erythematosus (SLE) The protective function of neutrophils is carried out through various mechanisms: isolation of granular antimicrobial peptides (gAMP), microbial phagocytosis with subsequent degradation via reactive oxygen species inside the phagolysosomes; as well as bactericidal action due to the release of networks from chromatin and gAMP, also called neutrophil extracellular traps (NECTs). The development of neutropenia in SLE has multiple causes, including the formation of antibodies directly to leukocytes; that of neutralizing autoantibodies to the growth factors of neutrophils and cells - myeloid precursors; bone marrow suppression; involvement of neutrophils in the processes of apoptosis and NETosis. Neutrophils in SLE are characterized by reduced phagocytic ability and pathological oxidative activity. In SLE, there is a decrease in the ability to remove the products of neutrophil apoptosis, which is correlated with disease activity. SLE patients are noted to have a higher expression level of the genes specific for low-density granulocytes, an abnormal immature neutrophil population. The impaired processes of formation of NECTs and removal NETosis products play a substantial role in the pathogenesis of SLE. It is shown that the abnormal formation of NECTs also causes endothelial injury and increases the risk of thromboses. The design of novel drugs that act on the specific parts of the formation of NECTs or contribute to their removal from the extracellular environment can propel therapy for SLE and other autoimmune diseases to new heights. There is evidence for further investigations of neutrophil-mediated pathogenetic processes in SLE in order to identify potential therapeutic targets and to understand the mechanisms of action of drugs used in clinical practice.Нарушение функции нейтрофилов при системной красной волчанке (СКВ) играет значительную роль. Защитная функция нейтрофилов осуществляется через различные механизмы: выделение гранулярных антимикробных пептидов (ГАМП), фагоцитоз микроорганизмов с последующей деградацией с помощью активных форм кислорода внутри фаголизосом, а также осуществление бактерицидного действия за счет выброса сетей из хроматина и ГАМП, называемых также нейтрофильными внеклеточными ловушками (НВЛ). Развитие нейтропении при СКВ имеет множество причин, включающих образование антител непосредственно к лейкоцитам, образование нейтрализующих аутоантител к факторам роста нейтрофилов и клеток - предшественников миелоидного ряда, супрессию костного мозга, участие нейтрофилов в процессах апоптоза и нетоза. Для нейтрофилов при СКВ характерны сниженная фагоцитарная способность и патологическая оксидативная активность. При СКВ происходит снижение способности к удалению продуктов апоптоза нейтрофилов, коррелирующее с активностью заболевания. У больных СКВ отмечают повышение уровня экспрессии генов, специфичных для гранулоцитов низкой плотности, патологической незрелой популяции нейтрофилов. В патогенезе СКВ значительную роль играет нарушение процесса образования НВЛ, а также удаления продуктов нетоза. Показано, что патология формирования НВЛ вызывает также повреждение эндотелия и повышает вероятность тромбозов. Создание новых лекарственных препаратов, действующих на определенные звенья процесса образования НВЛ или способствующих их удалению из внеклеточной среды, может вывести терапию СКВ и других аутоиммунных заболеваний на новый уровень. Оправдано дальнейшее изучение патогенетических процессов при СКВ, опосредованных нейтрофилами, с целью поиска потенциальных терапевтических мишеней, а также понимания механизмов действия лекарственных средств, применяемых в клинической практике.

Aim. To evaluate the results of immunosuppressive and/or antiviral treatment of patients with hepatitis C virus (HCV)-induced mixed cryoglobulinemic (MC) vasculitis. Material and methods. This prospective study included 60 patients (m/f - 23/49, age - 45,9±11,1) with HCV-MC vasculitis. The Birmingham vasculitis activity score (BVAS) was used before the treatment and during follow-up (3,5±4,1 years). The rate of clinical and immunological responses to the treatment, the frequency of relapses and the influence of different treatment approaches on the prognosis of the disease were evaluated. Logistic regression analysis was used to assess factors influencing the effectiveness of treatment. Results. 23 (38%) patients had liver cirrhosis. BVAS scores before treatment ranged from 2 to 36. 25 (41,6%) patients had BVAS≥15. 6 (10%) patients presented with B-cell non-Hodgkin lymphomas. The antiviral treatment resulted in the elimination of the virus in 48.0% of the cases, complete clinical and immunological responses were achieved in 68,0% and 32,0% respectively. It had an advantage over immunosuppressive therapy in terms of long-term results of the treatment. We established the superiority of anti-CD monoclonal antibodies (rituximab) over conventional immunosuppressive drugs: complete clinical response 73% vs 13% (p=0,001). Combined therapy (rituximab and antiviral treatment) was more effective in patients with severe vasculitis (BVAS≥15). A case of successful treatment using direct-acting antivirals (DAAs) is reported. Causes of MC-vasculitis relapses after achieving sustained viral response are discussed. Conclusion. Antiviral therapy is the treatment of choice in all patients with HCV- HCV-MC vasculitis. Preference should be given to highly effective and safe modern therapy regimens with the use of DAAs. The antiviral treatment of severe forms of vasculitis must be combined with rituximab therapy.

The aim of the study was to explore the Klotho protein significance in patients with different stages of chronic kidney disease (CKD) and to assess the influence of antihypertensive therapy on Klotho protein serum levels. Materials and methods. 130 patients with stage 5 CKD1 were included in the study. Serum PTH, calcium and phosphorus were measured. ELISA was used to determine serum soluble alpha Klotho. Blood pressure including brachial and central (aortic) pressure was measured in all patients together with pulse wave velocity (using a «Sfigmokor» device); in addition, echocardiography (EchoCG), and X-ray examination of the abdominal aorta by Kauppila method were performed. Results. The dynamic study of serum Klotho level showed that it changes with decreasing glomerular filtration rate faster than a rise in phosphate and PTH levels starting from stage 3A of CKD. The two later variables increased at stages 4-5.According to the ROC analysis, the values of serum Klotho below 387 pg /ml suggested enhanced risk of myocardial calcification with 80% sensitivity and 76% specificity. In addition, the highest Klotho serum levels were observed in patients whose target BP values were achieved with angiotensin receptor blockers (ARB) compared to those who used other drugs [р

ObjectiveTo assess the safety and efficacy of rituximab in systemic sclerosis (SSc) in clinical practice.MethodsWe performed a prospective study including patients with SSc from the European Scleroderma Trials and Research (EUSTAR) network treated with rituximab and matched with untreated patients with SSc. The main outcomes measures were adverse events, skin fibrosis improvement, lung fibrosis worsening and steroids use among propensity score-matched patients treated or not with rituximab.Results254 patients were treated with rituximab, in 58% for lung and in 32% for skin involvement. After a median follow-up of 2 years, about 70% of the patients had no side effect. Comparison of treated patients with 9575 propensity-score matched patients showed that patients treated with rituximab were more likely to have skin fibrosis improvement (22.7 vs 14.03 events per 100 person-years; OR: 2.79 [1.47–5.32]; p=0.002). Treated patients did not have significantly different rates of decrease in forced vital capacity (FVC)>10% (OR: 1.03 [0.55–1.94]; p=0.93) nor in carbon monoxide diffusing capacity (DLCO) decrease. Patients having received rituximab were more prone to stop or decrease steroids (OR: 2.34 [1.56–3.53], pConclusionRituximab use was associated with a good safety profile in this large SSc-cohort. Significant change was observed on skin fibrosis, but not on lung. However, the limitation is the observational design. The potential stabilisation of lung fibrosis by rituximab has to be addressed by a randomised trial.

Objective: to determine the role of serum Klotho (s-Klotho) protein levels changes in patients with different stages of chronic kidney disease (CKD). Methods: The study involved 130 patients with CKD stages 1–5D (mean age ― 41±6.7 years). Serum levels of parathyroid hormone (PTH), calcium, phosphorus and s-Klotho protein (ELISA method) at baseline and after 1 year of follow-up were examined in all the patients so as the blood pressure (BP), including central (aortic), pulse wave velocity ― with the help of «Sphygmоcor» (Australia), echocardiography, radiography of the abdominal aorta in a lateral projection were also performed. Results: when comparing the s-Klotho levels in patients with different CKD stages, it was found that the level change associated with the reduction of glomerular filtration rate (GFR) ahead of phosphorus and PTH increase in serum, stared at 3A CKD, whereas hyperphosphatemia and PTH increase started at 4–5 CKD stages. According to ROC analysis, decreasing of s-Klotho levels below 387 pg/ml was indicated a calcification risk of abdominal aorta increased with an 80% sensitivity and 75% specificity. In addition, a strong negative relationship of low s-Klotho levels and heart remodeling was found. When comparing the patients with hypertension who were receiving antihypertensive monotherapy, the highest serum levels of Klotho protein were observed in those of them whose target blood pressure level was achieved primarily through Angiotensin II Receptors Blockers (ARB), compared to those who was administered another drug group (p

The paper discusses the present-day idea on a relationship between atrial fibrillation and chronic kidney dis~ase, the specific features of therapeutic policy, and the place of antithrombotic therapy in particular."Based on the results of population-based studies,the authors set forth the specific features of cardiac arrhythmias concurrent with kidney injury, as well as promising directions to optimize management schemes for this category of patients.В статье обсуждаются современные представления о взаимосвязи фибрилляции предсердий и хронической болезни почек, особенности терапевтической тактики, в частности место антитромботической терапии. На основании результатов популяционных исследований излагаются особенности сочетания нарушений ритма сердца с поражением почек, а также перспективные направления оптимизации схем ведения пациентов данной категории.

The paper describes clinical cases in 2 patients (brothers) with giant cell arteritis. It analyzes the genetic and epigenetic aspects of the disease. The data available in the Russian and foreign literature are given.Представлены клинические наблюдения 2 больных (родные братья) с гигантоклеточным артериитом. Анализируются генетические и эпигенетические аспекты заболевания. Приводятся данные отечественной и зарубежной литературы.

Autoinflammatory disease (AID) is a new concept formulated from the results of studying the pathogenesis of familial periodic fevers, a heterogeneous group of genetically determined diseases characterized by causelessly recurrent exacerbations of the inflammatory process due to genetically determined disorders of innate immunity and accompanied by uncontrolled hypersecretion of interleukin-1 (IL-1). These mechanisms were a basic model for understanding a wide range of rheumatologic and other inflammatory diseases of the internal organs. The late diagnosis of AIDs and their ineffective treatment increase the risk for the development and progression of secondary AA amyloidosis. Elaboration of both clinical and effective laboratory criteria for diagnosing autoinflammation is of great importance for determining the tactics of anti-inflammatory therapy and prevention of complications.Аутовоспалительные заболевания (АВЗ) - новое понятие, сформулированное по результатам изучения патогенеза семейных периодических лихорадок - гетерогенной группы генетически детерминированных заболеваний, характеризующихся беспричинно повторяющимися обострениями воспалительного процесса вследствие генетически детерминированных нарушений врожденного иммунитета и сопровождающихся бесконтрольной гиперсекрецией интерлейкина-1 (IL-1). Эти механизмы оказались базовой моделью для понимания широкого круга ревматологических и других воспалительных заболеваний внутренних органов. Поздняя диагностика АВЗ и их неэффективное лечение увеличивают риск развития и прогрессирования вторичного АА-амилоидоза. Для определения тактики противовоспалительной терапии, предотвращения осложнений большое значение имеет разработка как клинических, так и эффективных лабораторных критериев диагностики аутовоспаления.

To summarize the experience of a multidisciplinary therapy hospital in treating patients with hepatitis C virus (HCV)-associated cryoglobulinemic vasculitis (CV).Seventy-two patients (mean age, 49.4±10.3 years) with HCV-associated CV were examined and followed up for an average period of 2.8±3.6 years. The efficiency of traditional (corticosteroids ± cyclophosphamide) and selective (rituximab) immunosuppressive therapy (IST) was estimated in 31 and 15 observations, respectively, and that of antiviral therapy (AVT) in 25. Vasculitis activity was assessed using the Birmingham vasculitis activity score (BVAS). The patients' survival was studied; multivariate logistic regression analysis was carried out.24 (33.4%) of the 72 patients had a stage of liver cirrhosis (LC). The pretreatment mean BVAS was 11.9±7.2 (range 2 to 36). Severe CV (BVAS ≥15) was present in 30.6% of the patients. AVT was accompanied by achievement of sustained virologic response in 48% of the patients, clinical remission in 68% and had an advantage over IST in relation to long-term treatment results. Rituximab was significantly more effective than traditional immunosuppressants (remission rates of 73 and 13%, respectively). Combined therapy (rituximab and AVT) was most effective in patients with severe forms of vasculitis. Sixteen patients died from complications of vasculitis (37.5%), infection (37.5%), and LC (25%). The factors adversely affecting prognosis were age55 years (odds ratio (OR), 4.49), the presence of LC (OR, 3.68), renal failure (OR, 4.66) and the use of glucocorticosteroids (OR, 3.91).HCV-associated CV can determine the prognosis of chronic HСV infection. AVT is the treatment of choice in all patients with HСV-associated CV. AVT must be combined with rituximab therapy in patients with severe forms of vasculitis.Цель исследования. Обобщить опыт многопрофильного терапевтического стационара в лечении больных криоглобулинемическим васкулитом (КВ), ассоциированным с вирусом гепатита С (HСV). Материалы и методы. Обследовали и наблюдали в среднем 2,8±3,6 года 72 больных хроническим гепатитом С (ХГС) с ассоциированным с HСV КВ (средний возраст 49,4±10,3 года). Эффективность традиционной (глюкокортикостероиды ± циклофосфамид) и селективной (ритуксимаб) иммуносупрессивной терапии (ИСТ) оценена в 31 и 15 наблюдениях соответственно, противовирусной терапии (ПВТ) - в 25. Активность васкулита оценивали с помощью BVAS (Birmingham vasculitis activity score). Изучали выживаемость больных, проводили многофакторный логистический регрессионный анализ. Результаты. У 24 (33,4%) из 72 больных имелась стадия цирроза печени (ЦП). Средняя оценка по BVAS до лечения составила 11,9±7,2 балла (от 2 до 36 баллов). Тяжелая форма КВ (BVAS ≥15 баллов) имелась у 30,6% больных. ПВТ сопровождалась достижением устойчивого вирусологического ответа у 48%, клинической ремиссии - у 68% больных и имела преимущество перед ИСТ в отношении отдаленных результатов лечения. Ритуксимаб оказался статистически значимо эффективнее традиционных иммуносупрессоров (ремиссия 73 и 13% соответственно). У больных с тяжелыми формами васкулита наиболее эффективна сочетанная терапия (ритуксимаб и ПВТ). Умерли 16 больных: от осложнений васкулита 37,5%, инфекции 37,5%, осложнений ЦП 25%. Факторами, негативно влияющими на прогноз, явились возраст55 лет (отношение шансов - ОШ 4,49), наличие ЦП (ОШ 3,68), почечной недостаточности (ОШ 4,66) и применение глюкокортикостероидов (ОШ 3,91). Заключение. КВ, ассоциированный с HСV, может определять прогноз хронической инфекции HСV. ПВТ является терапией выбора у всех больных HСV КВ. У больных с тяжелыми формами васкулита ПВТ должна сочетаться с терапией ритуксимабом.

Systemic AA amyloidosis is a relatively rare complication of chronic inflammatory disorders, e.g. rheumatoid arthritis, ankylosing spondylitis, familial Mediterranean fever and other autoinflammatory syndromes, Crohn’s disease, malignancies and recurrent infections. Isolated case of AA amyloidosis have been reported in many other chronic diseases, including systemic vasculitides, diffuse connective tissue diseases, sarcoidosis, chronic hepatitis, etc. In the past ten years the incidence of AA amyloidosis decreased significantly due to earlier and more aggressive treatment of underlying conditions such as rheumatoid arthritis or infections. In the recent series of 474 patients with renal amyloidosis from Mayo clinic there were only 7% cases of AA amyloidosis while 86% patients presented with AL form of disease. Nevertheless, AA amyloidosis remains a life-threatening complication of immune-mediated and inflammatory conditions and deserves effective prevention and treatment. Takayasu’s arteritis (TAK) is a rare largevessel vasculitis of unknown etiology that more frequently affects women of childbearing age and is defined as "granulomatous inflammation of the aorta and its major branches" by the revised Chapel Hill Consensus Conference. The search in Pubmed database revealed only a dozen reports of AA amyloidosis in patients with TAK. The objective of our study was to evaluate the incidence of AA amyloidosis in a cohort of consecutive TAK patients.

to estimate the clinical and prognostic value of the carriage of different allele variants of the gene polymorphisms of the coagulation system and platelet receptors in the progression of liver fibrosis (LF) in patient with chronic hepatitis C (CHC).The investigation enrolled 177 patients with CHC and liver cirrhosis at its outcome who were divided into 2 groups according to the rate of LF progression: 1) 89 patients with rapid (rapid fibrosis) and 2) 88 patients with slow (slow fibrosis) progression. The polymorphism of the study genes was studied using a real-time polymerase chain reaction and a melting curve analysis.In CHC patients, the FV 1691G/A genotype was more often in the rapid progressors than that in the slow progressors (10.11% vs 1.14%; p=0.011). The A allele of the 1691 G/A FV gene was more common in the rapid fibrosis group than that in the slow fibrosis group (1.7% vs 5.56%, odd ratio 9.787; p=0.139). In our investigation, the polymorphic marker GA in the FII 20210 G/A gene, as well as the 4G allele (5G4G + 4G4G genotypes) and the 4G allele of PAI-I -675 5G/4G were more often seen in the rapid fibrosis group than that in the slow fibrosis group; the detection rate was only at the trend level (p=0.118, p=0.112, and p=0.117 respectively). There were no significant differences between the groups in the spread of variant genotypes and alleles of other study genes. Integral model construction by coding «profibrogenic» genotypes (FV 1691 G/A, FII 20210 G/A, PAI-I -675 5G/4G) showed that the fibrosis progression rate expressed as fibrosis units annually also increased with higher total scores (p=0.039), indicating the combined effect of these genes.The carriage of mutant genotypes of FV 1691 G/A, FII 20210 G/A, and PAI-I -675 5G/4G genes is a prognostic factor for rapid CHC progression.Цель исследования. Оценка клинической и прогностической значимости носительства различных аллельных вариантов генов системы свертывания и тромбоцитарных рецепторов в прогрессировании фиброза печени у больных хроническим гепатитом С (ХГС). Материалы и методы. В исследование включили 177 больных ХГС и циррозом печени в его исходе, по темпу нарастания фиброза печени разделенных на 2 группы: с быстро ('быстрый фиброз') и медленно ('медленный фиброз') прогрессирующим течением заболевания (89 и 88 пациентов соответственно). Полиморфизм исследуемых генов изучали методом полимеразной цепной реакции (ПЦР) в реальном времени с анализом кривых плавления. Результаты. У больных ХГС в группе 'быстрого фиброза' генотип GA гена FV 1691G/A встречался достоверно чаще, чем у пациентов из группы 'медленного фиброза' (10,11% против 1,14%; р=0,011). Аллель А гена FV 1691G/A чаще выявлялась в группе 'быстрого фиброза' (1,7% против 5,56%, отношение шансов 9,787; р=0,139). Полиморфный маркер GA гена FII 20210 G/A, а также генотипы с 4G аллелью (5G4G+4G4G) и аллель 4G PAI-I -675 5G/4G чаще встречались в группе с 'быстрым фиброзом' по сравнению с группой с 'медленным фиброзом', частота выявления различалась лишь на уровне тенденции (р=0,118 и p=0,112 и p=0,117 соответственно). Достоверных различий между группами по распространении вариантных генотипов и аллелей других изучаемых генов не выявлено. При построении интегральной модели с кодированием генотипов с 'профиброгенной' направленностью (FV 1691 G/A, FII 20210 G/A, PAI-I -675 5G/4G) отмечено, что с повышением суммарной оценки скорость фиброза, выраженная в единицах фиброза в год, также возрастала (р=0,039), свидетельствуя о сочетанном влиянии данных генов. Заключение. Носительство мутантных генотипов гена FV 1691 G/A, FII 20210 G/A, PAI-I -675 5G/4G является прогностическим фактором быстрого течения ХГС.

Aim of study. To evaluate clinical significance of different combinations of gene polymorphisms IL-1b, IL-6, IL-10, TNF, HFE, TGF-b, ATR1, NOS3894, CYBA, AGT, MTHFR, FII, FV, FVII, FXIII, ITGA2, ITGB3, FBG, PAI and their prognostic value for prediction of liver fibrosis progression rate in patients with chronic hepatitis C (CHC).Subjects and methods: 118 patients with CHC were divided into «fast» and «slow» (fibrosis rate progression ≥0,13 and 0,13 fibrosis units/yr; n =64 and n =54) fibrosis groups. Gene polymorphisms were determined. Statistical analysis was performed using Statistica 10.Results. A allele (p =0,012) and genotype AA (p =0,024) of AGT G-6T gene, as well as T allele (p =0,013) and MT+TT genotypes (p =0,005) of AGT 235 M/T gene were significantly more common in «fast fibrosers» than in «slow fibrosers». Patients with genotype TT of CYBA 242 C/T had a higher fibrosis progression rate than patients with CC+CT genotype (p =0,02). Our analysis showed a protective effect of TT genotype of ITGA2 807 C/T on fibrosis progression rate (p =0,03). There was a trend (p 0,15) to higher fibrosis progression rate in patients with mutant alleles and genotypes of TGFb +915 G/C, FXIII 103 G/T, PAI -675 5G/4G genes. Other gene polymorphisms were not associated with enhanced liver fibrosis. To build a mathematical model for prediction of liver fibrosis progression rate we performed coding with scores for genotypes and virus genotype. Total score correlated with the fibrosis progression rate (R =0,39, p =0,000).Conclusion: Determination of genetic profile of the patient and virus genotype allows to predict the course of CHC.

Problems of diagnostics and treatment of ischemic renal disease (atherosclerotic stenosis of renal arteries) at patients with diabetes mellitus are discussed.

The paper discusses the specific features of the current course of acute glomerulonephritis, the spectrum of its etiological factors, and clinical manifestations. The factors influencing the course and outcomes of acute glomerulonephritis, including the risk of its progression to chronic kidney disease, are specially depicted.Обсуждаются особенности современного течения острого гломерулонефрита, спектр его этиологических факторов и клинических проявлений. Специально представлены факторы, влияющие на течение и исходы острого гломерулонефрита, в том числе на риск его трансформации в хроническую болезнь почек.

The paper discusses current approaches to organizing a diagnostic process in health care facilities. It describes approaches to improving patient examinations in multidisciplinary hospitals.Обсуждаются современные подходы к организации диагностического процесса в медицинских организациях. Представлены подходы к совершенствованию организации обследования пациентов в условиях многопрофильных стационарных медицинских организаций.

To study the role of serum surfactant protein D (SP-D) as a biomarker of lung injury in scleroderma systematica (SDS) in relation to the presence of gastroesophageal reflux (GER).Fifty-six patients (mean age 46±14 years) with diffuse and circumscribed SDS were examined and underwent pulmonary functional tests, X-ray and, if lung injury was present, high-resolution computed tomography of the lung, echocardiography, gastroduodenoscopy, and barium X-ray of the esophagus; an enzyme-linked immunosorbent assay was used to determine serum SP-D levels.SP-D concentrations significantly correlate with the presence of lung injury in SDS and are significantly higher in the presence of pulmonary fibrosis and the signs of frosted glass and honeycomb lung patterns. SP-D levels were higher in the patients with lung injury and SDS in the group of those with pulmonary fibrosis and GER than in the group of pulmonary fibrosis patients without the latter.Serum SP-D may be considered in a number of biomarkers for the severity of lung injury in SDS, including GER-associated lung injury.Цель исследования. Изучить роль сывороточного сурфактантного белка D (SP-D) как биомаркера поражения легких при системной склеродермии (ССД) в зависимости от наличия гастроэзофагеального рефлюкса (ГЭР). Материалы и методы. Обследовали 56 пациентов (средний возраст 46±14 лет) с диффузной и ограниченной формой ССД, провели легочные функциональные тесты, рентгенографию легких, при наличии поражения легких компьютерную томографию легких в режиме высокого разрешения, эхокардиографию, гастродуоденоскопию, рентгенографию пищевода с барием, методом иммуноферментного анализа (ELISA) исследовали содержание в сыворотке крови SP-D. Результаты. Концентрация SP-D достоверно коррелирует с наличием поражения легких при ССД и достоверно выше при наличии легочного фиброза, признаков 'матового стекла' и 'сотового легкого'. Уровень SP-D у пациентов с поражением легких при ССД в группе пациентов с фиброзом легких и ГЭР выше, чем в группе пациентов с фиброзом легких без ГЭР. Заключение. Сывороточный SP-D может рассматриваться в ряду биомаркеров тяжести поражения легких при ССД, в том числе ассоциированного с ГЭР.

The aim of the study was to evaluate the clinical and genetic predictors of AA amyloidosis in patients with familial Mediterranean fever (FMF). We retrospectively studied 170 Armenian patients who were admitted to the two tertiary centers in 2003–2014. The diagnosis of amyloidosis that was suspected clinically (new proteinuria or nephrotic syndrome) was confirmed histologically. Screening for MEFV gene mutations was performed in 70 patients. The most common genotype was M694V/M694V (in 36 % of patients). Biopsy-proven AA amyloidosis was found in 102 (60 %) of 170 patients. AA amyloidosis was diagnosed in 17 (68 %) of 25 patients with homozygous M694V mutation, 17 (53 %) of 32 patients with heterozygous M694V allele and 4 (31 %) of 13 patients with other MEFV gene mutations. The M694V homozygosity and heterozygosity were associated with increased risk of AA amyloidosis, but this association did not reach statistical significance (odds ratio 2.43; 95 % CI 0.87–6.76, and 3.33; 0.91–12.1, respectively). Male gender, early onset of disease, severity of FMF, frequent attacks, peritonitis, pleuritis and erysipelas-like erythema also did not predict AA amyloidosis development. Recurrent arthritis was the only clinical finding that was significantly associated with AA amyloidosis (odds ratio 2.28; 95 % CI 1.17–4.42). Involvement of the joint synovial membrane, that is capable of active serum amyloid A production, is the main predictor of renal amyloidosis in FMF.

The aim of our study was to study the changes in the clinical picture and outcomes of granulomatosis with polyangiitis (Wegener’s) (GPA) over 40 years. Two hundred and forty-two consecutive patients with GPA were distributed into retrospective (1970–2003) and prospective (2004–2012) cohorts. Anti-neutrophil cytoplasmic antibodies were present in 82.6 % of patients. In 78.0 % of patients, diagnosis was confirmed histologically. We compared the clinical features of GPA and the incidence of the major and minor relapses and mortality in the two cohorts. The majority of patients in both cohorts had generalized GPA that involved upper respiratory tract (retrospective 89.5 % vs prospective 82.85 %), kidneys (60.5 vs 50.8 %) and lungs (64.0 vs 52.3 %). The total duration of follow-up in the retrospective and prospective cohorts was 468 and 397 patients-years, respectively. In the prospective cohort, we found trend to lower incidence of relapses (54.2 vs 66.2 per 100 patient-year; p = ns; odds ratio 0.82; 95 % CI 0.53–1.21) and significantly lower mortality (4.3 vs 7.9 per 100 patient-year; p = 0.04; odds ratio 0.54; 95 % CI 0.31–0.94). The leading causes of death in the retrospective cohort were lung disease (37.8 %), complications of immunosuppressive treatment (35.1 %) and kidney failure (13.5 %). In the prospective cohort, patients rarely died from terminal uraemia and pulmonary complications (0.0 and 17.6 %) while the proportion of cardiovascular events and complications of the immunosuppression as the causes of death increased (29.4 and 47.1 %). Modern treatment apparently reduced the incidence of relapses and mortality and modified the causes of death in the GPA patients.

Quantitative and qualitative compositions of microbiocenosis in the colon of healthy subjects and patients with various somatic diseases (infectious endocarditis, rheumatic heart disease, chronic renal insufficiency, and acute odontogenic phlegmons) are compared. It is concluded that disease is a powerful factor of the intestinal microbiocenosis variability. No changes in the colonic microflora specific for the diseases are detected.

We read with great interest the article by Saadoun et al 1 who investigated the efficacy and safety of a 24-week treatment with sofosbuvir and ribavirin in a small, open-label and uncontrolled study of patients with hepatitis C virus (HCV)-associated cryoglobulinemia vasculitis. However, the limitations of the VASCUVALDIC study diminish the validity of the conclusions, although we agree with the authors that it would be unethical to delay effective antiviral therapy given the established role of HCV in the development of cryoglobulinemia vasculitis and its unfavourable prognosis. As expected, the rate of sustained virological response (SVR) was higher (74%) than in previous trials of interferon-based antiviral treatment in patients with HCV-associated cryoglobulinemia vasculitis.2 ,3 However, this looks relatively moderate in light of the current efficacy of the interferon-free, all-oral antiviral regimens (up to 95%–100%). Nonetheless, the SVR rate was comparable with that identified in the previous phase III sofosbuvir plus ribavirin trial in patients with HCV infection.4 We can also assume that the proportion of virological responders among patients with HCV-associated cryoglobulinemia …

To study whether the excessive production of serum fibroblast growth factor 23 (FGF-23) may be reduced with phosphate-binding agents to treat hyperphosphatemia in patients with Stage VD chronic kidney disease (CKD).The investigation enrolled 25 patients with Stage VD CKD on regular hemodialysis (HD) (12 patients with chronic glomerulonephritis, 8 with tubulointerstitial nephritis, and 5 with hypertensive nephrosclerosis); among them there were 15 men and 10 women at the age of 21 to 65 years; their mean age at inclusion in the study was 43±4.5 years. The clinical, laboratory, and instrumental examination similar to that in patients with the early stages of CKD was done. Serum FGF-23 levels (Human FGF-23 ELISA kit using monoclonal antibodies to the full FGF-23 molecule) were investigated in all the 25 patients. A whole blood sample was taken 2 days after the last session of HD before initiation of its regular procedure.The elevated serum FGF-23 concentrations in the patients on regular HD correlated with their HD duration (r=0.508; p0.001). Along with this, a strong direct correlation (r=0.522; p0.001) was found between the concentration of FGF-23 in the serum and inorganic phosphorus; at the same time hyperphosphatemia was less significantly associated with higher serum intact parathyroid hormone (PTH) levels (r=0.398; p0.05). Lower FGF-23 and PHT levels were noted in a group of patients who could achieve and maintain the target serum inorganic phosphorus level (0.9-1.45 mmol/l) compared to that of patients with uncorrected hyperphosphatemia (1.45 mmol/l) (p0.01). A decrease in FGF-23 and PHT levels was achieved chiefly in the patients who had used phosphate-binders that contained no calcium (sevelamer hydrochloride).Lower FGF-23 levels were observed in the patients with CHD on regular HD who can achieve and maintain the target serum inorganic phosphorus level when using phosphate-binders that do not contain calcium than in those with uncorrected hyperphosphatemia (p0.01).Реферат Цель исследования. Изучить возможность снижения избыточной продукции фактора роста фибробластов 23-го типа (FGF-23) в сыворотке крови у больных хронической болезнью почек (ХБП) VD стадии путем воздействия на гиперфосфатемию связывающими фосфат препаратами. Материалы и методы. В исследование включили 25 пациентов с ХБП VD стадии, находящихся на регулярном гемодиализе (ГД), 12 - хроническим гломерулонефритом, 8 - тубулоинтерстициальным нефритом и 5 - гипертензивным нефросклерозом; среди них 15 мужчин и 10 женщин в возрасте от 21 года до 65 лет, средний возраст на момент включения в исследование 43±4,5 года. Проводили клиническое, лабораторное и инструментальное обследование, аналогичное таковому у больных с более ранними стадиями ХБП. У всех 25 больных изучен уровень FGF-23 в сыворотке крови (Human FGF-23 ELISA kit с использованием моноклональных антител к полной молекуле FGF-23). Забор цельной крови выполняли через 2 дня после последнего сеанса ГД перед началом очередной процедуры. Результаты. У находящихся на регулярном ГД пациентов увеличение концентрации FGF-23 в сыворотке коррелировало с длительностью их пребывания на ГД (r=0,508; p0,001). Наряду с этим выявлена сильная прямая корреляция (r=0,522; p0,001) между концентрацией FGF-23 в сыворотке и неорганического фосфора, при этом связь гиперфосфатемии с повышением уровня интактного паратгормона (ПТГ) в сыворотке крови оказалась менее значительной (r=0,398; p0,05). В группе больных, которым удалось достичь и поддерживать целевой уровень (0,9-1,45 ммоль/л) неорганического фосфора в сыворотке крови по сравнению с группой больных с некорригированной гиперфосфатемией (1,45 ммоль/л) отмечены более низкие уровни FGF-23 и ПТГ (p0,01). При этом преимущественно снижение уровня FGF-23 и ПТГ достигнуто у тех больных, которым для коррекции гиперфосфатемии назначали не содержащие кальцийсвязывающие фосфат препараты (севеламера гидрохлорид). Заключение. У больных ХБП, находящихся на регулярном ГД, которым удается достичь и поддерживать целевой уровень неорганического фосфора в сыворотке крови при использовании связывающих фосфат препаратов, не содержащих кальций, отмечены более низкие, чем у больных с некорригированной гиперфосфатемией, уровни FGF-23 (p0,01).

To investigate the impact of anemia correction with erythropoiesis stimulants on the serum level of the circulating morphogenetic protein α-Klotho in patients with Stages 3B--4 chronic kidney disease (CKD).64 patients aged 42±8 years with Stages 3B--4 nondiabetic CKD were examined and divided into 2 groups: 1) 32 patients with anemia (the target hemoglobin levels could be achieved and kept with erythropoietin and iron saccharate in 20 patients (Group A) and those could not be done in 12 patients (Group 1B). A control group (Group 2) consisted of 32 non-anemic patients matched for gender, age, and degree of a glomerular filtration rate (GFR) reduction. Along with iron exchange indicators, the time course of changes in serum Klotho levels were examined in all the 64 patients during screening and one year after the end of the study. For correction of anemia, 32 patients with this condition (Groups 1A and 1B) took short-acting epoetin (hypodermic recormon 2,000 IU thrice per week + iron (intravenous venofer 5 ml of 100 mg once per week)) under control of hemoglobin levels and serum transferrin iron and ferritin saturation. After achieving the target hemoglobin level of 110-120 g/l, for its keeping, all the patients received, instead of short-acting epoetin, long-acting hypodermic darbepoetin-α 1.5 µg once every 2 months and intravenous iron saccharate 100 mg once every 2 weeks.Among the 32 anemic patients in Group 1, 20 (63%) (Group 1 A) could achieve the target hemoglobin level (110--120 g/l) and maintain it within this range, by performing therapy with epoitin-β + iron saccharate; anemia (the hemoglobin level of110 g/l) persisted in 12 (37%) patients (Group 1B) despite the fact that epoetin and iron saccharate had been administered. Group 1A was noted to have an increase in α-Klotho concentrations by an average of 100±11.6-pg/ml as compared to Group 1B (by only 72±4.2 pg/ml). At the same time, the α-Klotho levels in the control group by the end of the follow-up decreased by an average of 210±12.9 pg/ml as compared to the prescreening value. There was a direct correlation between hemoglobin and serum ferritin concentrations and iron ferritin saturation percentage and α-Klotho levels. It was ascertained that the hemoglobin concentration of ≥110 g/l with a sensitivity of 89% and a specificity of 75% could predict higher serum α-Klotho levels in CKD. The same patients were found to have an inverse relationship between the serum level of α-Klotho and the risk of cardiovascular events.The serum level of the protein Klotho is not only a marker for the severity of CKD and its complications (anemia, left ventricular hypertrophy, and heart failure), but also a pathogenetic factor of CKD progression. Anemia correction with erythropoiesis stimulants has been shown to enhance the renal and extrarenal production of α-Klotho.Цель исследования. Изучить влияние коррекции анемии препаратами, стимулирующими эритропоэз, на уровень в сыворотке крови циркулирующей формы морфогенетического белка α-Klotho у больных хронической болезнью почек (ХБП) 3Б-4 стадии. Материалы и методы. Обследовали 64 больных ХБП недиабетической этиологии 3Б-4 стадии в возрасте 42±8 лет, которых распределили в 2 группы: 1-я - 32 больных с анемией (у 20 с помощью эритропоэтина и железа сахарата удалось достичь и поддерживать целевой уровень гемоглобина - группа 1А, и 12, которым назначенная терапия не позволила достигнуть целевого уровня гемоглобина - группа 1Б). Группу контроля (2-я) составили 32 больных без анемии, сопоставимых с больными 1-й группы по полу, возрасту и степени снижения скорости клубочковой фильтрации (СКФ). У всех 64 больных во время скрининга и через 1 год после окончания исследования наряду с показателями обмена железа изучена динамика уровня Klotho в сыворотке. Для коррекции анемии 32 пациента с анемией (группы 1А и 1Б) получали эпоэтин короткого действия (рекормон по 2000 ЕД 3 раза в неделю подкожно) + железо (венофер 5 мл 100 мг 1 раз в неделю внутривенно) под контролем уровня гемоглобина, насыщения трансферрина железом и ферритина сыворотки. После достижения целевого уровня гемоглобина 110-120 г/л для его поддержания всем пациентам вместо эпоэтина короткого действия вводили эпоэтин длительного действия дабепоэтин-α 1,5 мкг на 1 кг 1 раз в 2 мес подкожно и железа сахарат 100 мг 1 раз в 2 нед внутривенно. Результаты. Среди 32 больных 1-й группы с анемией у 20 (63%) (группа 1А) терапия эпоэтином-β + железа сахаратом позволила достигнуть целевого уровня гемоглобина (110-120 г/л) и поддерживать его в этом диапазоне; у 12 (37%) больных (группа 1Б), несмотря на введение эпоэтина и железа сахарата, сохранялась анемия (уровень гемоглобина110 г/л). У больных группы 1А отмечено увеличение концентрации α-Klotho в среднем на 100±11,6 пг/мл по сравнению с таковой у больных группы 1Б (только на 72±4,2 пг/мл). В то же время в контрольной группе к концу наблюдения уровень α-Klotho уменьшился в среднем на 210±12,9 пг/мл по сравнению с таковой до скрининга. Отмечена прямая связь между концентрацией гемоглобина, ферритина в сыворотке крови и процентом насыщения железом трансферрина и уровнем α-Klotho. Выявлено, что концентрация гемоглобина ≥110 г/л с чувствительностью 89% и специфичностью 75% позволяет прогнозировать выявление более высокого уровня α-Klotho в сыворотке крови при ХБП. У тех же больных обнаружена обратная связь между уровнем α-Klotho в сыворотке крови и риском развития сердечно-сосудистых осложнений. Заключение. Концентрация белка Klotho в сыворотке является не только маркером тяжести ХБП и ее осложнений (анемия, гипертрофия левого желудочка сердца, сердечная недостаточность), но и патогенетическим фактором прогрессирования ХБП. Показана возможность усиления продукции α-Klotho в почках и внепочечно через коррекцию анемии средствами, стимулирующими эритропоэз.

We studied the efficiency and safety of a new homeopathic preparation Artrofoon containing affinely purified antibodies to tumor necrosis factor-alpha in the therapy of patients with rheumatoid arthritis. Artrofoon produced a positive antiinflammatory effect on the course of rheumatoid arthritis. This preparation reduced the severity of arthralgia (indexes of Li and Ritchie) and morning stiffness and decreased the erythrocyte sedimentation rate and contents of rheumatoid factor and C-reactive protein. One-month therapy improved the state of patients. Artrofoon was well tolerable. The preparation did not cause the ulcerogenic and nephrotoxic effects. Artrofoon holds much promise for combination therapy of patients with rheumatoid arthritis (including severe articular-and-visceral forms) and complications after treatment with nonsteroid antiinflammatory preparations.

Background Serum surfact protein D (SP-D) levels are elevated in systemic sclerosis interstitial lung disease (SSc-ILD) (1). Gastroesophageal reflux disease (GERD) is suggested to be a risk factor for SSc-ILD (2). However, previous studies did not analyze SP-D by subgroups of SSc-ILD patients with and without GERD. Objectives Aim of our study was to evaluate SP-D as a biomarker of severity of SSc-ILD in the presence or absence of GERD. Methods 56 SSc patients underwent chest computertomography and lung function test to evaluate ILD, and gastroesophagoscopy for confirmation/exclusion of GERD. Extend of lung fibrosis >20%, presence of ground-glass opacity (GGO) and honey combing (HC) were compared between SSc-ILD patients with and without GERD by chi-square test. Serum samples were analyzed for SP-D by Enzyme Linked Immunosorbent Assay. Correlations were evaluated by Spearman rank correlation test. Kruskal-Wallis test or Mann–Whitney U test were used to compare SP-D levels between different patient groups (values in ng/ml, mean±SD). Results 49 patients (87.5%) were female, mean age was 46.5±14.4 years. 43 patients had limited and 13 patients diffuse cutaneous involvement. 27 patients had coexistent ILD and GERD (group 1), 16 patients had ILD but no GERD (group 2) and 13 patients had no ILD or GERD (group 3). All patients with GERD by gastroesophagoscopy had signs of ILD by computer tomography. SSc-ILD patients with vs without GERD had statistically significant more often an extend of lung fibrosis >20% (20/37 (74.1%) vs 6/16 (37.5%, p=0.018) and tendentially more often GGO (19/27 (70.4%) vs 7/16 (43.75%), p=0.084), but there was no difference in presence of HC. The levels of SP-D were not significant different between male and female (286±97 vs 227±170, p=0.169) neither between diffuse and limited cutaneous SSc patients (291±198 vs 218±150, p=0.218). In addition, SP-D did not correlate with age (r=0.221, p=0.102) or disease duration (r=-0.164, p=0.226). SP-D levels were higher in group 1 compared to group 2 and group 3 (316±156 ng/ml vs 237±134 ng/ml va 62±19 ng/ml, p SP-D levels were highly correlated with the extend of lung fibrosis (r=0.783, p Conclusions ILD-SSc patients with GERD have a more severe lung involvement and higher SP-D levels then ILD-SSc patients without GERD. Moreover, SP-D levels are much lower in SSc patients without ILD or GERD. Thus, our results suggest that GERD is linked with extend of lung fibrosis and may contribute to GGO, as SP-D was a valuable biomarker to monitor the severity of SSc-ILD. References Kumanovics et al.: Comprehensive investigation of novel serum markers of pulmonary fibrosis associated with systemic sclerosis and dermato/polymyositis. Clin Exp Rheumatol. 2008. Christmann et al.: Gastroesophageal reflux incites interstitial lung disease in systemic sclerosis: clinical, radiologic, histopathologic, and treatment evidence. Semin Arthritis Rheum. 2010. Disclosure of Interest None declared

To study the urinary excretion of the molecular factors regulating angiogenesis, such as vascular endothelial growth factor type A (VEGF-A), thrombospondin 1 (THBS1), and angiopoietin 2 (ANGPT2), versus that of the urinary markers of renal injury and fibrogenesis, such as neutrophil gelatinase-associated lipocalin (NGAL), type IV collagen (COL4), and known clinical risk factors for accelerated disease progression to estimate the prognostic value of urinary excretion in patients with chronic glomerulonephritis (CGN).Eighty-two patients (45% men, 55% women; mean age, 36.5 years) with a clinical diagnosis of CGN were examined. 31.7% of the examinees presented with nephrotic syndrome; 31.7% had a glomerular filtration rate (GFR) of less than 60 ml/min/1.73 m2. Morning urine samples were analyzed by Elisa to determine the urinary excretion of biomarkers (VEGF-A, THBS1, ANGPT2, NGAL, and COL4). The results were adjusted to urinary creatinine concentrations.The urinary excretion of the angiogenesis regulators VEGF-A, THBS1, and ANGPT2 correlated between them, with that of the renal injury markers NGAL and COL4, with the level of proteinuria. That was found to be unassociated with blood pressure and GFR. In the presence and absence of nephrotic syndrome, high (75th percentile) urinary excretion rates were 46.2 and 14.8% for VEGF-A (p0.01); 50 and 13% for THBS1 (p0.001); and 46.2 and 14.8% for ANGPT2 (p0.01), respectively. That for ANGPT2 was also high in the presence of anemia (63.2 versus 11.7%; p0.001).The finding of the high urinary excretion of the angiogenesis regulators VEGF-A, THBS1, and ANGPT2 and its association with that of kidney injury markers in the patients with the proteinuric forms of CGN suggest that this excretion may be considered as an integral index that displays glomerular injury and indicates tubulointerstitial proteinuric/hypoxic remodeling.Цель исследования. У больных хроническим гломерулонефритом (ХГН) изучить мочевую экскрецию молекулярных факторов, регулирующих ангиогенез - фактора роста эндотелия сосудов A типа (VEGF-A), тромбоспондина 1-го типа (THBS1) и ангиопоэтина 2-го типа (ANGPT2) по сравнению с мочевыми маркерами повреждения и фиброгенеза почек - липокалином, ассоциированным с желатиназой нейтрофилов (NGAL), коллагеном IV типа (COL4) и известными клиническими факторами риска ускоренного прогрессирования заболевания для оценки ее прогностического значения. Материалы и методы. Обследовали 82 больных с клиническим диагнозом ХГН, средний возраст 36,5 года, 45% мужчин, 55% женщин. У 31,7% обследованных имелся нефротический синдром, у 31,7% - скорость клубочковой фильтрации (СКФ) ниже 60 мл/мин/1,73 м2. Для определения мочевой экскреции биомаркеров (VEGF-A, THBS1, ANGPT2, NGAL, COL4) исследовали утреннюю пробу мочи методом ELISA. Результат стандартизовали на концентрацию креатинина в моче. Результаты. Уровни мочевой экскреции регуляторов ангиогенеза VEGF-A, THBS1, ANGPT2 коррелировали между собой, с уровнем мочевой экскреции маркеров повреждения почек NGAL и COL4, уровнем протеинурии. Связи с уровнем артериального давления и СКФ не отмечено. При наличии и отсутствии нефротического синдрома частота высокого (75-й процентиль) уровня мочевой экскреции регуляторов ангиогенеза соответственно составляла: для VEGF-A 46,2 и 14,8% (р0,01); THBS1 50 и 13% (р0,001); ANGPT2 46,2 и 14,8% (р0,01). Частота высокого уровня ANGPT2 также была выше при наличии анемии - 63,2% против 11,7% (р0,001). Заключение. Полученные данные о высокой экскреции с мочой у больных с протеинурическими формами ХГН регуляторов ангиогенеза VEGF-A, THBS1 и ANGPT2 и ее связи с экскрецией маркеров повреждения почек свидетельствуют, что такая экскреция может рассматриваться как интегральный показатель, отражающий повреждение почечных клубочков и свидетельствующий о протеинурическом/гипоксическом ремоделировании тубулоинтерстиция.

AIM. To analyze changes in the serum concentrations of the morphogenetic proteins fibroblast growth factor 23 (FGF-23) and Klotho, as well as sclerostin, an osteocyte-secreted glycoprotein, in relation to the degree of hypertension, left ventricular (LV) hypertrophy, and arterial stiffness in patients with chronic kidney disease (CKD) at its different stages.Sixty-five patients (33 men and 32 women) aged 20-65 years, including 25 with chronic glomerulonephritis, 15 with tubulointerstitial nephritis, and 25 with hypertensive nephrosclerosis, were examined. A control group consisted of 15 healthy volunteers matched to the study group patients for age and gender. Serum FGF-23 concentrations and blood pressure (BP) were measured in the all subjects. Patients with BPs140/80 mm Hg underwent echocardiography, followed by determination of LV mass (LVM) and calculation of LVM index. Vascular circulation, pulse wave velocity, cardiac and vascular calcifications, and vascular functional properties were estimated.There was a strong direct Correlation between the serum concentration of FGF-23 and the stage of CKD and an inverse correlation between the levels of Klotho and sclerostin and the stage of CKD. As the glomerular filtration rate became lower, the concentration of FGF-23 increased and that of Klotho and sclerostin decreased just in Stage III CKD while hyperphosphatemia and elevated parathyroid hormone levels were noted in Stages IV-V CKD. As CKD progressed, the serum concentrations of Klotho and sclerostin were inversely correlated with the levels of phosphorus and parathyroid hormone. The degree of blood pressure elevation correlated positively with serum FGF-23 concentrations and inversely with Klotho levels. There was no significant correlation of the level of sclerostin with the degree of BP increase. The direct correlation between higher FGF-23 level and higher VLM is most pronounced in hypertensive patients. There was a strong direct relationship between FGF-23 and Klotho levels and a strong inverse relationship between sclerostin levels and pulse wave velocity. Lower Klotho concentrations were associated with the detection rate of calcifications in the heart valves and large arteries (the abdominal aorta). The reduced serum levels of Klotho and sclerostin were also correlated with concentric LV remodeling.It was demonstrated that there was a clear link between increased serum FGF-23 and decreased Klotho concentration as CKD progressed, and that between arterial stiffness and calcification and myocardial remodelling regardless of traditional risk factors. More experimental and clinical studies are required to clarify the role of sclerostin in CKD.Цель исследования. Проанализировать изменения концентрации в сыворотке крови морфогенетических белков FGF-23 и Klotho, а также склеростина (гликопротеин, секретируемый остеоцитами) в зависимости от выраженности артериальной гипертонии, гипертрофии левого желудочка (ЛЖ) сердца и ригидности артерий у больных хронической болезнью почек (ХБП) на разных ее стадиях. Материалы и методы. Обследовали 65 пациентов: 25 с хроническим гломерулонефритом, 15 с тубулоинтерстициальным нефритом, 25 с гипертензивным нефросклерозом - всего 33 мужчины и 32 женщины в возрасте 20-65 лет. В контрольную группу вошли 15 здоровых волонтеров, сопоставимых по возрасту и полу с пациентами основной группы. У всех определяли концентрацию в сыворотке крови FGF-23, измеряли артериальное давление (АД). Больным с АД140/80 мм рт.ст. проводили эхокардиографию с последующим определением массы миокарда ЛЖ (ММЛЖ) и расчетом индекса ММЛЖ. Оценивали кровоток в сосудах, скорость пульсовой волны, наличие кальцификатов в сердце и сосудах и функциональные свойства сосудов. Результаты. Между концентрацией в сыворотке крови FGF-23 и стадией ХБП выявлена сильная прямая корреляция, между концентрацией Klotho, склеростином и стадией ХБП - обратная корреляция. По мере снижения скорости клубочковой фильтрации (СКФ) концентрация FGF-23 повышалась, а Klotho и склеростина - снижалась уже при ХБП III стадии, в то время как гиперфосфатемия и повышение концентрации паратиреоидного гормона отмечены с IV-V стадии ХБП. Концентрации в сыворотке крови Klotho и склеростина по мере прогрессирования ХБП обратно коррелировали с уровнем фосфора и паратиреоидного гормона. Степень повышения АД позитивно коррелировала с концентрацией FGF-23 и обратно - с уровнем Klotho. Существенной корреляции уровня склеростина со степенью повышения АД не получено. Прямая связь между повышенным уровнем FGF-23 и увеличением ММЛЖ наиболее выражена у пациентов с АГ. Выявлена сильная корреляция: прямая между уровнем FGF-23 и уровнем Klotho и обратная между уровнем склеростина и скоростью пульсовой волны. Сниженная концентрация Klotho ассоциирована с частотой обнаружения кальцификатов в клапанах сердца и крупных артериях (абдоминальная аорта). Снижение концентрации в сыворотке крови Klotho и склеростина также коррелировало с ремоделирования миокарда ЛЖ концентрического типа. Заключение. Продемонстрирована четкая взаимосвязь повышенной FGF-23 и сниженной концентрации в сыворотке крови Klotho по мере прогрессирования ХБП, а также жесткостью и кальцификацией артерий, ремоделированием миокарда, независимо от наличия традиционных факторов риска. Для верификации роли склеростина при ХБП требуются дополнительные экспериментальные и клинические исследования.