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Monoclonal gammopathy of renal significance (MGRS) is a new nosology in modern nephrology and oncohematology. MGRS is defined as kidney injury due to nephrotoxic monoclonal immunoglobulin produced by the B-cell line clone which does not reach the hematological criteria for specific treatment initiation. Monoclonal proteins pathological effects on kidney parenchyma result in irreversible decline of kidney function till the end stage renal disease that in line with the position of International Consensus of hematologists and nephrologists determinates critical necessity for clone specific treatment in patients with MGRS despite the absence of hematological indications for treatment initiation. Main challenge of MGRS in Russian Federation is an inaccessibility of an in-time diagnostic and appropriate treatment for the great majority of patients due to the following reasons: 1) limited knowledge about the MGRS among hematologists and nephrologists; 2) lack of necessary diagnostic resources in most health-care facilities; 3) lack of approved clinical recommendations and medical economic standards for treatment of this pathological entity. Consensus document comprises the opinion of experts leading nephrologists and hematologists of Russian Federation on the problem of MGRS including the incoherence in nosology classification, diagnostics approach and rationale for clone specific treatment. Consensus document is based on conclusions and agreements reached during the conference of leading nephrologists and hematologists of Russia which was held in the framework of symposia Plasma cell dyscrasias and lymphoproliferative diseases: modern approaches to therapy, 1516 of March 2019, Pavlov First Saint Petersburg State Medical University. The present Consensus is intended to define the principal practical steps to resolve the problem of MGRS in Russian Federation that are summarized as final clauses.Моноклональная гаммапатия ренального значения (МГРЗ) представляет собой новую нозологическую группу в современной нефрологии и онкогематологии. Под МГРЗ понимают поражение почек, обусловленное действием нефротоксичного моноклонального иммуноглобулина, продуцируемого клоном В-клеточной линии, который не достигает критериев, необходимых для начала противоопухолевой терапии по онкогематологическим показаниям. Результатом воздействия моноклонального белка на почечную паренхиму является неуклонное прогрессирование дисфункции почек вплоть до утраты функции органа, что в соответствии с единой позицией международного консенсуса гематологов и нефрологов определенно указывает на необходимость клон-ориентированного лечения МГРЗ, несмотря на отсутствие критериальных онкогематологических показаний. Основной проблемой МГРЗ в Российской Федерации является недоступность для большинства пациентов своевременной диагностики и лечения данной патологии, что обусловлено, во-первых, недостаточной осведомленностью гематологов и нефрологов страны в отношении МГРЗ, во-вторых, отсутствием в большинстве медицинских учреждений необходимых диагностических ресурсов, в-третьих, отсутствием утвержденных рекомендаций и медико-экономических стандартов лечения этой болезни. Текст настоящего консенсуса заключает в себе мнение специалистов РФ в отношении нозологической классификации, диагностики и подходов к терапии МГРЗ и основан на итогах проведенного совместного совещания ведущих гематологов и нефрологов страны. Совещание состоялось 1516 марта 2019 г. в рамках симпозиума Плазмоклеточные дискразии и лимфопролиферативные заболевания: новые подходы к терапии, проведенного в ФГБОУ ВО Первый СПбГМУ им. акад. И.П. Павлова. Настоящий консенсус гематологов и нефрологов призван наметить основные практические пути решения проблемы МГРЗ в РФ, которые кратко сформулированы в виде заключительных положений.

Monoclonal gammopathy of renal significance (MGRS) is a new nosology in modern nephrology and oncohematology. MGRS is defined as kidney injury due to nephrotoxic monoclonal immunoglobulin produced by the B-cell line clone which does not reach the hematological criteria for specific treatment initiation. Monoclonal protein’s pathological effects on kidney parenchyma result in irreversible decline of kidney function till the end stage renal disease that in line with the position of International Consensus of hematologists and nephrologists determinates critical necessity for clone specific treatment in patients with MGRS despite the absence of hematological indications for treatment initiation. Main challenge of MGRS in Russian Federation is an inaccessibility of an in-time diagnostic and appropriate treatment for the great majority of patients due to the following reasons: i) limited knowledge about the MGRS among hematologists and nephrologists; ii) lack of necessary diagnostic resources in most health-care facilities; iii) lack of approved clinical recommendations and medical economic standards for treatment of this pathological entity. Consensus document comprises the opinion of experts – leading nephrologists and hematologists of Russian Federation – on the problem of MGRS including the incoherence in nosology classification, diagnostics approach and rationale for clone specific treatment. Consensus document is based on conclusions and agreements reached during the conference of leading nephrologists and hematologists of Russia which was held in the framework of symposia «Plasma cell dyscrasias and lymphoproliferative diseases: modern approaches to therapy», 15-16 of March 2019, Pavlov First St-Petersburg State Medical University, St-Petersburg, Russia. The present Consensus is intended to define the principal practical steps to resolve the problem of MGRS in Russian Federation that are summarized as final clauses.

BACKGROUND. Мonoclonal gammopathy (MG) is not only the state preceding of hematological neoplasms, but also associated with non- hematological diseases, in particular damage of kidneys. Earlier diagnosis of MG represents an important area in treating patients with renal diseases associated with MG. THE AIM: To determine the frequency of MG among therapeutic and nephrological patients for optimization of methods of their diagnosis and treatment. PATIENTS AND METHODS: In common, 11392 patients were analyzed within 4 years (2013-2016). The standard clinical examination was conducted. Method of an electrophoresis of proteins of serum of blood and the 24-hour urine, method of immunofixation of proteins of serum and urine, and method of free light chains definition in serum (Freelite) were used for MG identification. RESULTS: MG is diagnosed in 174 of 11392 patients: 49 % of men and 51 % of women aged from 18 up to 85 years. MG was found 2.1 times more often in nephrological patient than in patients of therapeutic departments. Among patients of this group, AL-amyloidosis with kidney involvement was diagnosed in 41 %, cryoglobulinemic glomerulonephritis – in 18 %, chronic glomerulonephritis – in 35 %, also there was small number of patients with light chain disease and cast-nephropathy. 86 % of nephrological patients had less than 5 g/l of monoclonal protein that corresponds oligo secretory MG, and at 46 % from them – less than 1 g/l, other 10 % had MG of 5-10 g/l, and only in 4.42 % of patients MG more 10g/l was defined. CONCLUSION: We conclude that MG, especially oligo secretory form, play a significant role in pathogenesis of renal damage. It is important to apply sensitive methods – immunofixation of proteins and method «Freelite» for nephrological patients.

Monoclonal gammopathy (MG) is not only the state preceding of hematological neoplasms, but also associated with non - hematological diseases, in particular kidney damage.To assess the diagnostic value of "Freelite" methods in addition to electrophoresis (EF) and immunofixation (IF) of serum and urine proteins for detecting MG in patients with kidney diseases.87 patients with kidney damage, in which MG was established using the method of electrophoresis of serum proteins (EF), immunofixation (IF) and the method of free light chains determination - FLC "Freelite" were selected. The diagnostic value of three - component serum panel was compared with EF and IF.AL-amyloidosis with kidney involvement was diagnosed in 41% patients, cryoglobulinemic glomerulonephritis (cryo GN) - in 18%, chronic glomerulonephritis (CGN) - in 35%, also there was small number of patients with light chain disease and cast - nephropathy. Determination of MG using EP was possible only in 38 (44%). Adding to the serum electrophoretic methods instead of the "Freelite" method, the urine EF and IF reduced the number of missed patients with monoclonal gammopathy from 24 (27%) to 11 (13%), including in the subgroup of patients with AL-amyloidosis but did not reach the sensitivity of the three - component serum screening panel. In 10 (11.5%) MG was represented only by intact mIg with one type of light chain, either κ or λ. Most often - in 25% of patients, intact monoclonal gammopathy was observed in HCV (+) cryo GN. A combination of intact mIgM, mIgG or mIgA with mFLC, was detected in 37 (42.5%). In almost half (46%) of the patients, only mFLC was detected - an abnormal κ/λ ratio.The serum screening panel EF + IF + "Freelite" spreads the low - grade monoclonal gammopathy recognition (MGUS) and should be included in the algorithm of examining patients with kidney disease.Моноклональная гаммапатия (МГ) неопределенного значения (MGUS) является не только предопухолевым состоянием, предшествующим развитию множественной миеломы (ММ) и других секретирующих опухолей, но и возможной причиной заболеваний неопухолевой природы, в том числе поражения почек Цель исследования. Оценить информативность методов «Freelite», в добавление к электрофорезу (ЭФ) и иммунофиксации (ИФ) белков сыворотки и мочи, для выявления МГ у больных с поражением почек. Материалы и методы. Из 113 больных с МГ было отобрано 87 больных с поражением почек, у которых МГ установлена при использовании метода ЭФ белков сыворотки, ИФ и метода определения свободных легких цепей - FLC «Freelite». Проведена оценка эффективности в диагностике МГ этой трехкомпонентной сывороточной панели. Результаты и обсуждение. Из 87 больных с поражением почек МГ была определена у 39 (45%) пациентов с AL-амилоидозом, 16 (18%) - с (HCV+) криоглобулинемическим гломерулонефритом (крио-ГН), 28 (32%) - с хроническим ГН (ХГН), 4 (4%) - с болезнью отложения легких цепей (БОЛЦ) с помощью трехкомпонентной скрининговой панели. Определение МГ с помощью ЭФ было возможным только у 38 (44%) больных. Добавление к сывороточным электрофоретическим методам вместо метода «Freelite» ЭФ и ИФ мочи уменьшило число пропущенных больных с моноклональной гаммапатией - в целом с 24 (27%) до 11 (13%), но не достигло чувствительности трехкомпонентной сывороточной скрининговой панели. У 10 (11,5%) пациентов МГ была представлена только интактными mIg с одним типом легких цепей - либо κ, либо λ. Наиболее часто - у 25% больных - интактная МГ наблюдалась при HCV(+) крио-ГН. У 37 (42,5%) пациентов выявлена комбинация интактных mIgM, mIgG или mIgA с mFLC. Почти у половины (46%) больных обнаружены только mFLC - анормальное отношение κ/λ. Заключение. Трехкомпонентная сывороточная скрининговая панель ЭФ+ИФ+«Freelite» расширяет возможности распознавания МГ малого объема (MGUS) и должна быть введена в алгоритм обследования больных нефрологического профиля.

Peripheral nervous system involvement may be a main manifestation of systemic amyloidosis or occur in the later stages of the disease in the presence of multiple organ pathology. Focal, multiple mononeuropathy, radiculopathy, polyneuropathy, autonomic nervous system dysfunction, and myopathy develop depending on the localization of amyloid deposits in the peripheral nervous system. The most characteristic symptom in systemic amyloidosis is sensorimotor polyneuropathy accompanied in most cases by the involvement of autonomic nerve fibers in the pathological process. In cases of systemic amyloidosis, peripheral nervous system involvement is progressive, leading to disability, which makes the early diagnosis of the disease and its neurological manifestations and subsequent pathogenetic therapy relevant.

The term «monoclonal gammopathies of undetermined significance» (MGUS) was introduced by R. Kyle in 1978 to designate the condition characterized by the presence ofsmall amounts ofM-protein in the serum. In some patients, such condition remains benign for a long time but predetermines for the development of multiple myeloma and other B-lymphocytic tumours. Also, it can provoke non-cancerous diseases due to the toxic action of monoclonal proteins (immunoglobulins and free light chains) on various organs, especially kidneys. MGUS-associated renal lesions include glomerulopathies with organized deposits, such as AL-amyloidosis (amyloid light chain of immunoglobulin), cryoglobulinic and immunotactoid glomerulonephritis, and with unorganized deposits (light chain deposition and proliferative forms of idiopathic glomerulonephritis. The available experimental data throw light on the possible mechanisms of renal lesions. We summarized the literature data and original observations to describe methods for differential diagnostics of MGUS-associated renal lesions including the highly sensitive test for free light chine identification (Freelite method) and principles of pathogenetic treatment by the impact on the pathological B-cell clone.

The article deals with the so-called monoclonal gammopathy of undetermined significance (MGUS), which is being actively explored in the world and has been recently investigated in Russia. It indicates the principles of identifying the phenotypes of MGUS and criteria for assessing the risk of its progression to cancer. There is an update on the possible involvement of monoclonal proteins in the pathogenesis of certain non-neoplastic kidney diseases, renal injuries in particular. The paper gives their classification and enumerates differential diagnostic techniques, including the Freelite method, a highly sensitive one to determine free light chains (FLC), prognostic criteria, and approaches to treating each separate form in relation to the phenotype of a monoclonal protein. The authors present their own data on detection rates for MGUS at a multidisciplinary hospital and a clinical case of MGUS-associated membranoproliferative glomerulonephritis, by justifying a treatment regimen containing bortezomib (velcade).Статья посвящена активно изучаемой в мире и последние годы в России так называемой моноклональной гаммапатии неопределенного значения (MGUS). Указаны принципы выделения фенотипов MGUS, критерии оценки риска ее прогрессирования в злокачественную опухоль. Представлены современные данные о возможности участия моноклональных белков в патогенезе некоторых заболеваний неопухолевой природы, в частности поражений почек. Дана их классификация, перечислены методы дифференциальной диагностики, в том числе высокочувствительный метод определения свободных легких цепей (FLC) - Freelite, критерии прогноза, подходы к лечению каждой отдельной формы в зависимости от фенотипа моноклонального белка. Приведены собственные данные о частоте выявления MGUS в многопрофильном стационаре и клиническое наблюдение мембранопролиферативного гломерулонефрита, ассоциированного с MGUS, с обоснованием схемы терапии, содержащей бортезомиб (вилкейд).Аннотация Статья посвящена активно изучаемой в мире и последние годы в России так называемой моноклональной гаммапатии неопределенного значения (MGUS). Указаны принципы выделения фенотипов MGUS, критерии оценки риска ее прогрессирования в злокачественную опухоль. Представлены современные данные о возможности участия моноклональных белков в патогенезе некоторых заболеваний неопухолевой природы, в частности поражений почек. Дана их классификация, перечислены методы дифференциальной диагностики, в том числе высокочувствительный метод определения свободных легких цепей (FLC) — Freelite, критерии прогноза, подходы к лечению каждой отдельной формы в зависимости от фенотипа моноклонального белка. Приведены собственные данные о частоте выявления MGUS в многопрофильном стационаре и клиническое наблюдение мембранопролиферативного гломерулонефрита, ассоциированного с MGUS, с обоснованием схемы терапии, содержащей бортезомиб (вилкейд).

Background:Schnitzler’s syndrome (SchS) is a rare non-monogenic auto-inflammatory disease (AID) which manifests in adults and is characterized by recurrent urticarial lesions, monoclonal gammopathy, and other manifestations of a systemic inflammatory response (fever, muscle / joint / bone pains, leukocytosis, increased ESR, CRP). Off-label treatment with IL-1 inhibitors (anakinra, canakinumab) was shown to be highly effective and well tolerated in pts with SchS based on a few multicenter studies and practical experience.Objectives:To analyze a real-life experience of the treatment with IL-1 inhibitors in pts with SchS in the rheumatology tertiary care settings.Methods:The study included 7 pts (3 women, 4 men) with treated with IL-1 inhibitors (anakinra, canakinumab). A median age at the diagnosis was 44 years old (25 – 68). Age at the disease onset ranged from 22 to 66. All pts met the Strasbourg diagnostic criteria. 7 pts received canakinumab, while 3 pts were first treated with anakinra followed by a switch to canakinumab. Anakinra was administered subcutaneously 100 mg per day. Canakinumab was given subcutaneously at a dosage of 150 mg every 8 weeks. The treatment duration with anakinra ranged from 1 week to 2.5 months with further switching to canakinumab. The duration of canakinumab treatment by the time of analysis ranged from 2 months to 5.5 years.Results:All pts at the inclusion into the study suffered from urticarial rash, pains in bones and joints, fatigue, fever (6), increased acute phase marker levels (ESR, CRP), monoclonal gammopathy, mainly IgMk (4.7 – 9 g/l). An average period between the disease onset and the treatment initiation was 3 years (2 to 4). In all pts lymphoproliferative diseases and monogenic AIDs (CAPS, TRAPS) were excluded. Before the treatment with IL-1 inhibitors, all pts had received NSAIDs and/or GCs, methotrexate - 2, plaquenil-2. During the treatment with IL-1 inhibitors, 6 out of 7 pts had a complete response as demonstrated by a symptom resolution within several days and a rapid decrease in ESR and CRP levels. In 3 pts, who responded anakinra, the treatment was switched to canakinumab. In one patient with a partial response to anakinra, there was a loss of the effect upon switching to canakinumab, In one patient, the interval between canakinumab injections was increased up to 5 months without a symptom relapse. This patient fathered a healthy child whilst on treatment with canakinumab. The therapy was well tolerated in all pts, no SAE were noted.Table 1.Clinical and demographic characteristics of patients with SchSPatients1234567SexMFMFFMMAge (y)44325668255149Age of disease onset (y)40295366223947Urticarial rash+++++++Fever+-+++++Fatigue+++++++Bone pain+++++++Arthralgia/arthritis+++++++ESR(normal 3114010049815356CRP (normal 10744192963697641,82IgM kappa (g/l)7,1-5,24,7-7,87,6--5,29IgM lambda(g/l)--1,36----IgG kappa (g/l)---5,1---IgG lambda (g/l)----10,7--Conclusion:SchS is a rare disease that occurs in the practice of a rheumatologist. Short and long acting IL-1 inhibitors are highly efficient and safe treatment options for pts with SchS. A switching from short to long acting IL-1 inhibitors can be effective in SchS pts.References:[1]Krause K, Tsianakas A, Wagner N, Fischer J, Weller K, Metz M, et al. Efficacy and safety of canakinumab in Schnitzler syndrome: a multicenter randomized placebo-controlled study. J Allergy Clin Immunol 2017;139:1311-20.[2]Betrains A., Staelsa F, Vanderschueren S. Efficacy and safety of canakinumab treatment in schnitzler syndrome: A systematic literature review Seminars in Arthritis and Rheumatism 50 (2020) 636-642.Disclosure of Interests:None declared

To determine the possibility of using the serum proinflammatory calcium-binding protein, or calgranulin C (S100A12), to assess activity and therapeutic efficiency in patients with periodic disease (PD) and other familial periodic fevers (FPFs).Thirty-five patients with PD and other FPDs, which were verified by molecular genetic study, were examined. In accordance with the disease activity, the patients were divided into 2 groups. The investigators determined the concentration of S100A12 by solid-phase enzyme immunoassay and that of other acute-phase inflammatory markers (erythrocyte sedimentation rate (ERT), neutrophil counts, and fibrinogen and C-reactive protein (CRP) concentrations).The serum concentration of S100A12 in the stage of disease activity was 466.7 (265.22--851.7) ng/ml, which was significantly higher than in remission (244.29 (118.93--409.85) ng/ml (p=0.000002). The highest S100A12 concentrations were noted in the patients with PD; these were 758.95 (434.80--1035.95) ng/ml; the S100A12 level in the majority of PD patients even during remission remained moderately higher. An investigation of the relationship of A100A12 to genetic variants found no differences between the patients homozygous for M694V and those with other genotypes (p=0.37). Estimation of the time course of therapy-induced changes in the serum S100A12 concentration revealed its considerable reduction (р=0.0018). However, normalization of S100A12 levels was not achieved in PD. The remaining increased S100A12 concentration in these patients may be suggestive of the activity of PD despite the absence of its clinical manifestations. S100A12 as a highly sensitive marker allows more exact evaluation of the anti-inflammatory effect of therapy. The S100A12 identification of the subclinical activity of autoinflammatory diseases made all the more important since traditional inflammatory markers, such as ERT, CRP, fibrinogen, and leukocyte counts, are less sensitive for these purposes. In our study, these markers were within the reference range in remission. No differences were found in the S100A12 levels between the groups with and without amyloidosis (p=0.62).S100A12 is a highly sensitive marker for the activity of autoinflammatory diseases and the efficiency of their therapy. The serum level of S100A12 in PD may be used to diagnose the subclinical activity of inflammation, which is of importance in monitoring the risk of amyloidosis.Цель исследования. Определение возможности использования сывороточного провоспалительного белка, связывающего кальций, или кальгранулина С (S100A12), для оценки активности и эффективности лечения пациентов с периодической болезнью (ПБ) и другими семейными периодическими лихорадками (СПЛ). Материалы и методы. Обследовали 35 больных ПБ и другими СПЛ, подтвержденными молекулярно-генетическим методом. В зависимости от активности заболевания больных разделили на 2 группы. Определяли концентрацию белка S100A12 (методом твердофазового иммуноферментного анализа) и других острофазовых маркеров воспаления (скорость оседания эритроцитов - СОЭ, количество нейтрофилов, концентрация фибриногена и С-реактивного белка - СРБ). Результаты. Концентрация S100A12 в сыворотке крови в стадию активности заболевания составила 466,7 (265,22; 851,7) нг/мл, что достоверно выше, чем в ремиссию, - 244,29 (118,93; 409,85) нг/мл (p=0,000002). Самые высокие концентрации S100A12 отмечены нами у больных ПБ - 758,95 (434,80; 1035,95) нг/мл, даже во время ремиссии уровень S100A12 у большинства больных ПБ сохранялся умеренно повышенным. При исследовании зависимости концентрации S100A12 от генетического варианта различий между гомозиготами M694V и больными с другими генотипами не выявлено (р=0,37). При оценке динамики концентрации S100A12 в сыворотке в результате лечения выявлено значительное снижение его уровня (р=0,0018). Однако при ПБ нормализации уровня S100A12 не достигнуто. Сохраняющаяся повышенная концентрация S100A12 у этих больных может свидетельствовать об остаточной активности ПБ, несмотря на отсутствие ее клинических проявлений. S100A12, являясь высокочувствительным маркером, позволяет более точно оценивать противовоспалительный эффект терапии. Выявление субклинической активности аутовоспалительных заболеваний с помощью S100A12 тем более важно, что традиционные показатели воспаления (СОЭ, СРБ, фибриноген, уровень лейкоцитов) менее чувствительны для этих целей. В нашем исследовании в период ремиссии болезни эти показатели не выходили за референтные значения. Различий по уровню S100A12 между группами больных амилоидозом и без него не выявлено (p=0,62). Заключение. S100A12 является высокочувствительным маркером активности и эффективности терапии аутовоспалительных заболеваний. При ПБ уровень S100A12 в сыворотке может быть использован для диагностики субклинической активности воспаления, что важно для мониторирования риска развития амилоидоза.

Cardiac involvement is the major prognosis determinant in light chain (AL)-amyloidosis. Close relationship between renal failure and heart disease worsens prognosis and determinates prognostic valu...

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.

In a recent study, Deshayes et al used 16S ribosomal RNA gene sequencing to analyse the gut microbiome in patients with familial Mediterranean fever (FMF) complicated or not by AA amyloidosis and in patients with AA amyloidosis of another origin.1 Compared with healthy controls, FMF was associated with decreased α-diversity (ie, microbial richness and evenness) and altered composition of the gut microbiome. Certain operational taxonomy units (OTUs) belonging to the Clostridiales were associated with FMF, whereas two OTUs were overrepresented in AA amyloidosis among FMF patients. The authors suggested that intestinal microorganisms may play a role in the clinical expression and pathogenesis of these diseases. In a similar study, decreased species richness diversity was shown in the microbiome of patients with systemic lupus erythematosus (SLE). Moreover, SLE was associated with intestinal outgrowth of Ruminococcus gnavus of the Lachnospiraceae family that was most pronounced in those with lupus nephritis and correlated with disease activity.2 These and previous studies in spondyloarthritis and rheumatoid arthritis reflect the growing interest of researchers to the role …

The paper gives current general data on the structure of amyloid fibril and the principles in the classification of amyloidosis, information on the clinical course of cardiac and renal involvements in systemic AL and AA amyloidosis, and that on diagnostic and prognostic criteria and the specific features of cardiorenal links. The authors draw the conclusion that the identification of acute and chronic cardiorenal links is of practical value for systemic amyloidosis. Cardiorenal and renocardiac syndromes are not always differentiated clearly in the systemacy of involvement.

A significant progress in the field of molecular-biological investigations resulted in definition of a new group of systemic diseases referred to as autoinflammatory. This group comprises familial periodic fevers: periodic disease (mediterranean fever), Muckle-Wells syndrome, others cryopirinopathy, TRAPS-syndrome. As shown by case reports, Muckle-Wells syndrome is not a rare disease, its sporadic forms are encountered as well as a less severe variant of cryopirinopathy — nonallergic cold urticaria. Awareness of the physicians in respect of this pathology is essential especially because early diagnosis enables control of this disease with use of biological preparations the spectrum of which tends to expansion. Moreover, arrest of inflammation is necessary for prevention of development and progression of such prognostically poor complication as AA-amyloidosis.

Aim. To determine clinical significance of measuring blood levels of protein precursors of AA- and AL-amyloidosis - SAA and immunoglobulin free light chains (ILC), respectively. Material and methods. SAA concentrations were studied with ELISA in 43 rheumatoid arthritis (RA) patients including complicated with reactive AA-amyloidosis (n = 31). Inflammation activity and its severity were studied (indices Li, richi, HAQ, DAS4). A modern quantitative nephelometric method Freelite estimated ILC levels in 31 patients with AL-amyloidosis. Results. Patients with RA complicated with AA-amyloidosis and free of it had a strong correlation between blood serum SAA concentration and activity of joint disease. Elevated SAA concentrations to 160 mg/l (normal 10 mg/l) were detected in many patients with clinical remission of the joint syndrome. Significal inhibition of AA-amyloidosis progression was seen only in SAA concentration drop under 60 mg/l. For AL-amyloidosis patients ILC fall by less than 3 normal value means a 6-time increase in chances of a favourable outcome. Conclusion. Monitoring of blood levels of proteins precursors of AA- and AL-amyloidosis is a key factor in prognosis of the disease and treatment efficacy.

Aim. To determine clinical significance of urinary biomarkers of proteolysis/fibrinolysis and fibroangiogenesis in essential hypertension (EH). Material and methods. Examination of the kidneys was made in 71 patients with EH degree 1-3. Renal function was assessed by 24-h albuminuria, calculated glomerular filtration rate (GFR) by Cockroft-Golt. Early signs of renal damage were microalbuminuria - MAU (diurnal albuminuria 30-300 mg/day), reduction of GFR ( < 90 ml/min/1.73 m2). EH patients with hypercreatininemia and GFR under 60 ml/min/1.73m2 corresponding to stage III of chronic kidney disease were not included in the study. An additional nephropathy marker was an elevated index of resistance of interlobular renal arteries (RI > 0.65) as shown by dopplerometry. ELISA examined urinary biomarkers of intercellular and cell-matrix interactions in the kidney in EH patients and healthy controls (n = 12). Results. MAU was detected in 54 (76%) of 71 EH patients, elevated RI > 0.65 - in 37 (52%) patients. Urinary biomarkers of proteolysis/fibrinolysis and fibroangiogenesis were higher in EH patients then in the controls. Urinary excretion of PAI-1, TGF-beta1, VEGF and collagen of type IV in EH patients with MAU was significantly higher than in patients with normoalbuminuria. A strong direct correlation between MAU and the rest above urinary biomarkers was found as well as between urinary excretion of collagen IV and RI. An inverse negative relationship was seen between RI and GFR. Conclusion. Renal impairment in EH patients is a progressive disorder. Each stage of this process has its own clinicodiagnostic markers. Urinary biomarkers of proteolysis/fibrinolysis and fibroangiogenesis in the kidney are informative for monitoring of early HNP.

The paper describes a clinical case of congenital cardiomyopathy (left ventricular noncompaction) concurrent with secondary amyloidosis and renal involvement that develops at the outcome of long existing brochoectatic disease.

It is currently well justified that monoclonal gammopathies are the most important predictor for kidney diseases, including glomerulonephritis. To determine a correlation of nephropathy with oligosecretory gammopathy is of fundamental importance, as the treatment of these patients necessitates the use of special chemotherapy regimens to eliminate a pathological clone of lymphocytes or plasmocytes. If this clone is not eliminated, injury of the organ may recur to develop its failure. The principles of this therapy have been presently tried out by the example of AL-amyloidosis and showed its efficiency and relatively low toxicity.В настоящее время хорошо обосновано, что моноклональные гаммапатии являются важнейшим прогностически значимым фактором развития заболеваний почек, в том числе гломерулонефрита. Выявление связи нефропатии с олигосекреторной гаммапатией имеет принципиальное значение, так как лечение таких больных обусловливает необходимость применения особых схем химиотерапии, направленных на элиминацию патологического клона лимфоцитов или плазмоцитов. Без элиминации этого клона органное поражение будет рецидивировать с развитием органной недостаточности. Принципы такой терапии в настоящее время хорошо отработаны на примере AL-амилоидоза, показали свою эффективность и относительно низкую токсичность.

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.

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.

To determine clinical significance of urinary biomarkers of proteolysis/fibrinolysis and fibroangiogenesis in essential hypertension (EH).Examination of the kidneys was made in 71 patients with EH degree 1-3. Renal function was assessed by 24-h albuminuria, calculated glomerular filtration rate (GFR) by Cockroft-Golt. Early signs of renal damage were microalbuminuria--MAU (diurnal albuminuria 30-300 mg/day), reduction of GFR (90 ml/min/1.73 m2). EH patients with hypercreatininemia and GFR under 60 ml/min/1.73m2 corresponding to stage III of chronic kidney disease were not included in the study. An additional nephropathy marker was an elevated index of resistance of interlobular renal arteries (RI0.65) as shown by dopplerometry. ELISA examined urinary biomarkers of intercellular and cell-matrix interactions in the kidney in EHpatients and healthy controls (n = 12).MAU was detected in 54 (76%) of 71 EH patients, elevated RI0.65--in 37 (52%) patients. Urinary biomarkers of proteolysis/fibrinolysis and fibroangiogenesis were higher in EH patients then in the controls. Urinary excretion of PAI-1, TGF-beta1, VEGF and collagen of type IV in EH patients with MAU was significantly higher than in patients with normoalbuminuria. A strong direct correlation between MAU and the rest above urinary biomarkers was found as well as between urinary excretion of collagen IV and RI. An inverse negative relationship was seen between RI and GFR.Renal impairment in EHpatients is a progressive disorder. Each stage of this process has its own clinicodiagnostic markers. Urinary biomarkers ofproteolysis/fibrinolysis and fibroangiogenesis in the kidney are informative for monitoring of early HNP.

The paper describes a clinical case of congenital cardiomyopathy (left ventricular noncompaction) concurrent with secondary amyloidosis and renal involvement that develops at the outcome of long existing brochoectatic disease.

Tubulointerstitial fibrosis (TIF) is thought now to be a key factor in progression of renal failure in chronic nephropathies. A similar pattern of changes in glomerulonephritis and amyloidosis suggests common mechanisms operating in progression of renal failure in these nephropathies. Of importance in the process of interstitial inflammation is activation of the nuclear factor of transcription (NFkB) in tubular cells due to components of proteinuria and their secretion of some proinflammatory mediators, first of all chemokines with formation of inflammatory infiltrate and accumulation of interstitial myofibroblasts--the main source of extracellular matrix (ECM) components. Our findings are of interest in the light of current ideas that among ECM components the number of fibronectin deposites most of all reflects the severity of structural renal tissue damage including TIF and correlates with severity of renal failure.

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.

Here is an observation data on systemic AL-amiloidosis with primary lesion of lungs and vessels (a false hemorrhagic syndrome, ischemic insult in the region of middle cerebral artery). At the same time lesions of kidneys and heart became of minor significance. Amiloid lesion of lungs was characterized by unusual combination of symptoms: a galloping hydrothorax, a vast focus in the consolidation of pulmonary tissue with focuses of calcification, relapsing pneumothorax.