Clinical Manifestations and Prognosis of Giant Cell Arteritis: A Retrospective Cohort Study.

The aim of the study was to evaluate the clinical manifestations and survival of patients with giant cell arteritis (GCA). MATERIALS AND METHODS: . A retrospective study included 166 patients with newly diagnosed GCA. Clinical, laboratory, and instrumental data and three sets of classification criteria were used to confirm the diagnosis: the American College of Rheumatology (ACR) 1990, the revised ACR criteria of 2016 and/or the new ACR and European Alliance of Rheumatologic Associations (EULAR) 2022 criteria. Some of the patients underwent instrumental investigations: temporal artery ultrasound Doppler (n = 61), contrast-enhanced computed tomography (n = 5), CT angiography (n = 6), magnetic resonance imaging (n = 4), MR angiography (n = 3), and 18F-FDG PET/CT (n = 47). Overall and recurrence-free survival rates were analyzed using survival tables and Kaplan-Meier method. RESULTS: . The most frequent first manifestations of GCA were headache (81.8%), weakness (64%), fever (63.8%), and symptoms of rheumatic polymyalgia (56.6%). Changes in temporal arteries in color duplex scanning were detected in 44 out of 61 patients. GCs therapy was performed in all patients who agreed to be treated (n = 158), methotrexate was used in 49 out of 158 patients, leflunomide in 9 patients. In 45 (28.5%) out of 158 patients, a stable remission was achieved as a result of GC monotherapy; in 120 (75.9%) patients, long-term maintenance therapy with GCs was required to prevent exacerbations, including 71 (44.9%) patients in combination with methotrexate or other immunosuppressive drugs. The follow-up period of patients with a history of relapses was 21.0 (8.0-54.0) months. Relapses developed in 73 (46.2%) patients. The overall one-year survival rate was 97.1% [95% CI 94.3; 99.9], and the five-year survival rate of patients was 94.6% [95% CI 90.2; 99.0]. The one-year relapse-free survival rate was 86.4% [95% CI 80.5; 92.3], and the five-year relapse-free survival rate was 52.4% [95% CI 42.0; 62.8]. Twelve (7.2%) of 166 patients died. The cause of death was myocardial infarction in two patients, stroke in two patients, and breast cancer in one patient; in the remaining seven cases, the cause of death was not determined. CONCLUSIONS: : Given the high frequency of disease exacerbation, patients with GCA require long-term follow-up, especially during the first year after diagnosis.

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

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

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

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

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

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

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

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

A new cognitive clock matching phenotypic and epigenetic ages.

Cognitive abilities decline with age, constituting a major manifestation of aging. The quantitative biomarkers of this process, as well as the correspondence to different biological clocks, remain largely an open problem. In this paper we employ the following cognitive tests: 1. differentiation of shades (campimetry); 2. evaluation of the arithmetic correctness and 3. detection of reversed letters and identify the most significant age-related cognitive indices. Based on their subsets we construct a machine learning-based Cognitive Clock that predicts chronological age with a mean absolute error of 8.62 years. Remarkably, epigenetic and phenotypic ages are predicted by Cognitive Clock with an even better accuracy. We also demonstrate the presence of correlations between cognitive, phenotypic and epigenetic age accelerations that suggests a deep connection between cognitive performance and aging status of an individual.

The alternative complement pathway in ANCA-associated vasculitis: further evidence and a meta-analysis.

We compared the common pathway components C3a, C5a and membrane attack complex (MAC), also known as C5b-9, and the alternative pathway components factor B and properdin in patients with ANCA-associated vasculitis (AAV) and healthy controls, and conducted a meta-analysis of the available clinical evidence for the role of complement activation in the pathogenesis of AAV. Complement components were evaluated in 59 patients with newly diagnosed or relapsing granulomatosis with polyangiitis or microscopic polyangiitis and 36 healthy volunteers. In 28 patients, testing was repeated in remission. Next, we performed a meta-analysis by searching databases to identify studies comparing complement levels in AAV patients and controls. A random-effects model was used for statistical analyses. The median concentrations of MAC, C5a, C3a and factor B were higher in active AAV patients (P < 0·001). Achievement of remission was associated with reductions in C3a (P = 0·005), C5a (P = 0·035) and factor B levels (P = 0·045), whereas MAC and properdin levels did not change. In active AAV, there were no effects of ANCA specificity, disease phenotype, previous immunosuppression or disease severity on complement levels. A total of 1122 articles were screened, and five studies, including this report, were entered into the meta-analysis. Plasma MAC, C5a and factor B in patients with active AAV were increased compared to patients in remission (excluding factor B) and controls. Changes in C3a were of borderline significance. Our findings and the results of the meta-analysis support activation of the complement system predominantly via the alternative pathway in AAV patients.

[Risk factors for the early development of septic shock in patients with severe COVID-19].

AIM: In a retrospective study, we evaluated factors associated with the early development of septic shock in patients with severe COVID-19. MATERIALS AND METHODS: We collected medical records of the intensive care unit patients submitted by the local COVID-19 hospitals across Russia to the Federal Center for the Critical Care at the Sechenov First Moscow State Medical University (Sechenov University). Septic shock in crticially ill patients requiring mechanical ventilation was defined as a need in vasopressors to maintain blood pressure. RESULTS: We studied 1078 patients with severe COVID-19 who were admitted to the intensive care units for respiratory support. There were 611 males and 467 females. The mean age was 61.013.7 years. Five hundred twenty five medical records (48.7%) were received from the Moscow hospitals, 159 (14.7%) from the Moscow region, and 394 (36.5%) from the hospitals located in 58 regions of the Russian Federation. In 613 (56.9%) patients, diagnosis of SARS-CoV-2 infection was confirmed by PCR, and in the other cases it was established on the basis of the clinical picture and the results of the chest CT scan. Septic shock developed in 214 (19.9%) of 1078 patients. In the logistic regression model, the risk of septic shock in patients older than 50 years was higher than in patients of a younger age (OR 2.34; 95% CI 1.533.67; p0.0001). In patients with more severe SARS-CoV-2 infection, there was an increase in the prevalence of cardiovascular diseases, including coronary heart disease and atrial fibrillation, type 2 diabetes and malignant tumors. The risk of septic shock in patients with three or more concomitant diseases was higher than in patients without any concomitant chronic diseases (OR 1.76; 95% CI 1.762.70). CONCLUSION: The risk of septic shock in patients with acute respiratory distress syndrome induced by SARS-CoV-2 is higher in patients older than 50 years with concomitant diseases, although a severe course of the disease is also possible in younger patients without any concomitant disorders.

[Predictors of clinical events in patients with Fabry disease: the role of chronic kidney disease].

Fabry disease is a rare disorder characterized by high frequency of severe organ manifestations in young patients. Aim. To determine predictors of clinical events in patients with Fabry disease. Materials and methods. We recruited 100 adult (over 18 years) patients with Fabry disease that was confirmed by enzymatic and genetic studies. The main outcome was a composite of end - stage renal disease, cardiac (arrhythmia and cardioverter/pacemaker implantation) and cerebrovascular (transient ischemic attack, stroke) events. Kaplan-Meier analysis was performed for event - free survival. Cox regression model was used to examine the risk of composite endpoint. Results and disscussion. Forty - seven of the 100 patients (38 males and 9 females) experienced clinical events. The median age of the first event was 39 [32; 49] years. In Kaplan-Meier analysis, the age of the first event was significantly lower among men than women, (p.

Relationship between serologic profile (ANCA type) and clinical features of renal involvement in ANCA-associated vasculitides.

AIM: To compare the frequency, clinical features and outcomes of renal involvement in ANCA-associated vasculitides (AAV) in patients with antibodies against proteinase-3 (pr3-ANCA) and myeloperoxidase (MPO-ANCA). MATERIALS AND METHODS: In our retrospective study we enrolled 264 patients, 94 males and 170 females, median age 53 [36; 62] years. Among them 157 were pr3-ANCA positive and 107 were MPO-ANCA positive. AAV was diagnosed according to ACR criteria and Chapel Hill consensus conference definition (2012). Median follow up was 44 [18; 93] months. We assessed baseline BVAS and VDI by the end of the follow up. Serum creatinine (sCr), estimated glomerular filtration rate (eGFR), hematuria and daily proteinuria were estimated. Diagnosis and stage of chronic kidney disease (CKD) and acute kidney injury (AKI) were established according to KDIGO guidelines (2012) and Scientific Society of Russian Nephrologists (2016). RESULTS: Renal involvement was present in 181 (68.6%) patients, and its frequency was similar in pr3-ANCA and MPO-ANCA subgroups. Patients with MPO-ANCA developed rapidly progressive glomerulonephritis and hypertension significantly more often than patients with pr3-ANCA: 50.7% vs 35.6% (p=0.049) and 46.1% vs 29.8% (p=0.029) respectively. At disease onset, median sCr was significantly higher and eGFR was significantly lower in patients with MPO-ANCA (p<0.05). 1-year and 5-year renal survival rates were similar in pr3-ANCA-positive (93.9% and 87.4% respectively) and MPO-ANCA positive patients (87.4% and 83.1% respectively). Median BVAS and VDI scores were significantly higher in pr3-ANCA subgroup. The number of patients who developed AAV relapse during 1-year follow up was also significantly higher in pr3-ANCA subgroup. The frequency of eye and ENT involvement was significantly higher in pr3-ANCA positive patients than in MPO-ANCA-positive patients. CONCLUSION: The frequency of extrarenal manifestations, clinical features of renal involvement and relapse rate are associated with AAV serotype.

Clinical features of kidney involvement in microscopic microscopic polyangiitis.

AIM: To evaluate clinical features and outcomes of renal involvement in patients with microscopic polyangiitis (MPA). MATERIALS AND METHODS: We enrolled 99 patients with MPA, diagnosed in accordance with the algorithm of the European Medicines Evaluation Agency (EMEA) and the Chapel Hill consensus conference definition (2012). Serum creatinine (sCr), estimated glomerular filtration rate (eGFR), hematuria and proteinuria were estimated. Frequency of rapidly progressive renal failure (a twofold increase in the sCr level in ≤3 months) was regarded as the clinical equivalent of rapidly progressive glomerulonephritis (RPGN). RESULTS: Renal involvement was present in 92 (92.9%) patients. RPGN developed in 51 (55,4%) patients. The most common features of kidney involvement were hematuria and subnephrotic proteinuria. Arterial hypertension was revealed in 32 (34.7%) patients and was associated with RPGN (p<0.004). End-stage renal disease (ESRD) developed in 11 (11.9%) patients. Despite effective induction therapy disease relapses occurred in 20 (21.1%) patients during the 1st year, including renal relapses in 12 (13.3%) cases. During 5-year follow up 34 (37.1%) patients developed disease relapses, including renal relapses in 22 (24.4%) patients. CONCLUSION: Renal involvement is one of the most common manifestations of MPA with a high frequency of RPGN. More than one third of patients develop disease relapses despite adequate therapy.

Atypical Goodpasture's disease: a clinical case report and literature review.

Goodpasture's disease (anti-GBM disease) is a rare small vessels vasculitis characterized by the presence of autoantibodies directed against the glomerular basement membrane (GBM) and alveolar basement membrane. Common feature of anti-GBM disease is a combination of rapidly progressive glomerulonephritis and alveolar hemorrhage (pulmonary-renal syndrome). We present a case of atypical disease course in a young male patient who developed alveolar hemorrhage without renal failure. The only symptom of renal involvement was isolated hematuria. Plasmapheresis combined with immunosuppression (cyclophosphamide and corticosteroids) was effective. We present a review of state-of-art data on the pathogenesis and disease course of anti-GBM disease.

Cornea verticillata in Fabry disease.

AIM: To study the frequency of cornea verticillata in patients with Fabry disease and it's relation to the severity of the disease and the types of mutation in the GLA gene. MATERIALS AND METHODS: We studied 69 adult (over 18 years) patients with a classic form of Fabry disease that was confirmed by enzymatic and molecular genetic studies. There were 39 males and 30 females. The median age was 39 years [30.0; 50.0]. The severity of Fabry disease was assessed using the Mainz Severity Score Index (MSSI) with a maximum value of 76 points. Depending on the MSSI score, patients were classified into mild (<20), moderate (20-40), and severe (>40) clinical categories. RESULTS: At least one classic symptom of Fabry disease was present in 88.4% of patients. The majority of patients had the missense mutations of the GLA gene. Cornea verticillata was found in 65.2% of patients and occurred with a similar frequency in males (56.4%) and females (76.7%; p=0.07). Cornea verticillata was the single classic symptom of Fabry disease in only 4.9% of cases, while the rest of the patients presented with angiokeratoma, neuropathic pain and/or hypohidrosis. The frequency of classic symptoms of Fabry disease, as well as renal disease (with the exception of terminal chronic renal failure), brain and heart damage was similar in patients with and without cornea verticillata. Median MSSI scores were also similar in patienths with and without cornea verticillata (20.0 and 18.5 points, respectively; p=0.92). Similar results were obtained in males (26.5 and 30.0 points, p=0.97) and females (16.0 and 16.0 points, p=0.45). The frequency of cornea verticillata did not differ in patients with different types of mutations in the GLA gene. CONCLUSION: Cornea verticillata occured in 65% of adult patients with Fabry disease, was usually accompanied by the other classic symptoms of the disease, and was not associated with the severity of the disease.

[Kidney injury molecules (KIM-1, MCP-1) and type IV collagen in the assessment of activity of antineutrophil cytoplasmic antibody-associated glomerulonephritis]. / Molekuly povrezhdeniia pochechnoi tkani (KIM-1, MCP-1) i kollagen IV tipa v otsenke aktivnosti assotsiirovannogo s antineitrofil'nymi tsitoplazmaticheskimi antitelami glomerulonefrita.

AIM: To assess the significance of determining the serum and urinary concentrations of monocyte chemotactic protein-1 (MCP-1), kidney injury molecule-1 (KIM-1), and type IV collagen in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) to estimate the activity of renal involvement in AAV. SUBJECTS AND METHODS: 78 patients (32 men and 46 women) (median age 55 (45; 61) years) with AAV were examined. The patients were divided into 3 groups according to the AAV activity estimated using the Birmingham vasculitis activity Score (BVAS): 1) 25 patients with active ANCA-associated glomerulonephritis (GN); 2) 26 patients with active AAV without renal involvement; 3) 27 patients in sustained AAV remission. The serum and urinary concentrations of the markers were measured by enzyme immunoassay. RESULTS: The urinary concentration of all 3 biomarkers was higher in patients with renal involvement (Group 1); the differences in the levels of MCP-1 and type IV collagen were statistically significant as compared to Groups 2 and 3 (p<0.01), while that in KIM-1 level was only in Group 2. There were statistically significant correlations between the urinary concentration of these biomarkers and the traditional GN activity indices (erythrocyturia, daily proteinuria (DPU), total BVAS scores that reflect renal involvement, as well as serum creatinine levels and estimated glomerular filtration rate (p<0.05). ROC curve analysis showed that the urinary MCP-1 excretion of ≥159 pg/ml had the highest (92%) sensitivity and urinary type IV collagen excretion of ≥3.09 µg/l had the highest (86%) specificity in assessing the activity of ANCA-associated GN. At the same time, their diagnostic value increased in terms of a combination of DPU and ESR (96% sensitivity, 84.9% specificity). CONCLUSION: The urinary excretion of MCP-1, KIM-1, and type IV collagen reflects the severity of local renal inflammation in AAV patients and a study of these indicators is a promising diagnostic tool for assessing the activity of ANCA-associated GN.

[The frequency of ophthalmologic manifestations of granulomatosis with polyangiitis (Wegener's) and their relationship to systemic diseases]. / Chastota oftal'mologicheskikh proiavlenii granulematoza s poliangiitom (Vegenera) i ikh sviaz' s sistemnoi patologiei.

AIM: To estimate the frequency of lesions in the organ of vision in granulomatosis with polyangiitis (GPA) (Wegener's) and to determine their relationship to systemic diseases. SUBJECTS AND METHODS: The retrospective study enrolled 218 patients followed up at the E.M. Tareyev Clinic of Nephrology, Internal and Occupational Diseases, with a diagnosis of GPA. The frequency and association of ophthalmic manifestations with systemic involvement were statistically analyzed using PASW Statistics 18. RESULTS: The organ of vision was impaired in 48.1% of the patients with GPA. The most common manifestations were orbital space-occupying lesion (22.9%), conjunctivitis/episcleritis (14.7%), dacryocystitis (6.0%), and scleritis (4.6%). Orbital space-occupying lesions occurred more frequently in the local type of the disease (p=0.0003), and, on the contrary, the involvement of the conjunctiva and eyeball was seen in patients with the systemic types of GPA (p=0.02). CONCLUSION: The findings may suggest that the orbital lesion is an independent manifestation of GPA, which develops more commonly in its local type. Conjunctivitis/episcleritis is, on the contrary, more frequently seen in the active phase of the disease and generally in the involvement of other organs and systems.

[Combination therapy of refractory localized granulomatosis with polyangiitis and orbital involvement]. / Kombinirovannoe lechenie refrakternoĭ formy granulematoza s poliangiitom s porazheniem orbity.

Granulomatous orbital cellulitis is one of the most common ocular manifestations of granulomatosis with polyangiitis (Wegener's). The process is often refractory to conventional immunosuppressive therapy and requires a more radical treatment approach. However, surgical experience with this type of patients is limited. There have been just a few reported cases of orbital decompression in such patients and many authors have doubted the appropriateness of the procedure, since it is associated with a high risk of potentially fatal complications. Our experience demonstrates the feasibility and effectiveness of orbital mass removal as to pain relief and exophthalmos reduction.

[Severe adverse events from treatment with genetically engineered biological agents in patients with rheumatic diseases].

AIM: To assess the risk of severe adverse events (AEs) within 6 months after treatment with biological agents in patients with rheumatic diseases (RD). SUBJECTS AND METHODS: The 6-month open-label trial included 107 patients with rheumatoid arthritis, antineutrophil cytoplasmic antibody-associated vasculitides, systemic lupus erythematosus, and other RDs who received genetically engineered biological agents (GEBAs), primarily rituximab (n = 66) and infliximab (n = 31). RESULTS: The majority of patients were noted to have improvements, including complete and partial remission in 62 (57.9%) and 42 (39.3%), respectively. There were mild or moderate AEs in 22 (20.6%) of the 107 patients, severe AEs in 6 (5.6%): grade IV neutropenia in 2 patients (after the use of rituximab), severe infusion reactions in 2 (after the administration of infliximab and rituximab), and systemic infections in 2 (fatal nocardial sepsis after rituximab treatment and unspecified sepsis after infliximab treatment). CONCLUSION: The rate of serious AEs, mainly infusion AEs and infections during treatment with infliximab, rituximab, and other GEBAs proved to be relatively low in patients with different RDs. At the same time, the use of biological agents could lower RD activity in the presence of severe visceral injuries refractory to conventional immunosuppressive therapy.

[Determination of urinary markers of proteolysis/fibrinolysis and fibroangiogenesis in the kidney in hypertensive patients].

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 EHpatients 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 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.