[The analysis of secondary AA-amyloidosis current etiology and its influence on the approaches for diagnosis and treatment].

AIM: To investigate an influence of the currently changed etiologic structure of AA-amyloidosis on the diagnosis and treatment tactics. MATERIALS AND METHODS: In 110 patients with АА-amyloidosis followed during full disease duration (1 month 29 years) etiology, clinical manyfestations and approaches to diagnose and treatment of AA-amyloidosis were evaluated. With ELISA levels of amyloid precursor acute phase inflammation reactant SAA and neutrophil activity marker S100A12 were measured. RESULTS: Among the most common causes of AA-amyloidosis at the present stage, in addition to RA (40.3%), a significant place is occupied by a group of diseases with a predominantly autoinflammatory mechanism (53.73%). To confirm the autoinflammatory mechanism of the predisposing disease it is recommended to study a highly sensitive parameter serum protein S100A12. An effective marker of the risk of AA-amyloidosis progression, especially in patients with subclinical activity of inflammatory disease, is a high level of production of amyloidogenic protein-a precursor of SAA.

[Monoclonal gammopathy of renal significance: consensus of hematologists and nephrologists of Russia on the establishment of nosology, diagnostic approach and rationale for clone specific treatment].

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.

[Monoclonal gammapathy of renal significance (MGRS) at the current state: terminology, diagnosis and treatment].

In this article we discussed the current state of monoclonal gammapathy of renal significance (Monoclonal Gammopathy of Renal Significance MGRS) and revealed problems of B-cell clone secreting nephrotoxic monoclonal immunoglobulin identification. We followed 276 patients with monoclonal gammapathy including patients with non-amyloid nephropathy. The majority of patients had systemic AL-amyloidosis. We established better survival of the treated patients with systemic AL-amyloidosis in comparison with retrospective untreated cohort. We considered current treatment of patients with non-amyloid nephropathy and focused on the crucial role of multidisciplinary approach in management of these patients.

[Low serum Klotho level as a predictor of calcification of the heart and blood vessels in patients with CKD stages 2-5D].

Cardiovascular calcification (CVC) makes a significant contribution to the manifestation of cardiovascular complications in patients with chronic kidney disease. Early CVC markers are currently being actively studied to optimize cardio-renoprotective strategies. We performed a prospective comparative analysis of the following factors: FGF-23, a-Klotho, sclecrostin, phosphate, parathyroid hormone, the estimated glomerular filtration rate (eGFR), central systolic pressure as an independent determinant of CVC. MATERIALS AND METHODS: The study included 131 patients with chronic kidney disease 25D st. Serum levels of FGF-23, Klotho, and sclerostin were evaluated using the ELISA method. Vascular augmentation (stiffness) indices, central arterial pressure (using the SphygmoCor device), calcification of heart valves and the degree of aortic calcification (aortic radiography) were also investigated. The observation period was 2 years. RESULTS: According to the Spearman correlation analysis, the percent of calcification increase and the change in Klotho level are most related. According to ROC analysis, a decrease in serum levels of Klotho by 50 units or more is a significant predictor of an increase in aortic calcification of 50% or more with a sensitivity of 86% and a specificity of 77%. Using logistic regression analysis, it was found that a serum Klotho level 632 pg/L predicts an eGFR below a median level of 48 ml/min/1.73 m2 with a sensitivity of 85.5% and a specificity of 78.5%. Wherein OR 17.477 (CI 95% 8.04637.962; p0.001). CONCLUSION: The factor most associated with CVC is Klotho. Decreased serum level of Klotho is a predictor of aortic calcification. In addition, the initial serum level of Klotho is a predictor of eGFR after 2 years.

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.

HCV-associated mixed cryoglobulinemia and b-cell non-Hodgkin's lymphoma - pathogenetically related problems.

Hepatitis C virus (HCV) is a global population problem due to its high prevalence, usually late diagnosis, the difficulties of treatment. In the prognosis of patients with HCV not only hepatic, but increasingly frequent of extrahepatic HCV manifestations, such as mixed cryoglobulinemia (CG), are important. Mixed CG is currently considered as a B-cell benign lymphoproliferative disorders. The role of HCV virus in the pathogenesis of lymphoproliferative diseases is confirmed by a large number of epidemiological studies, as well as by the effectiveness of antiviral therapy in patients with non-Hodgkin's lymphoma (NHL). The purpose of the review was to provide an overview of recent literature data and the meta-analysis of epidemiological data explaining the role of HCV in the development of NHL. The review also discusses the treatment for HCV-associated NHL by antiviral therapy or other therapeutic options, such as chemotherapy.

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.

[Autoinflammatory diseases and kidney involvement]. / Autovospalitel'nye zabolevaniia i porazhenie pochek.

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.

[Risk factors for anemia in the early stages of chronic kidney disease]. / Faktory riska razvitiia anemii na rannikh stadiiakh khronicheskoi bolezni pochek.

AIM: To identify the early markers of anemia in chronic kidney disease (CKD) in patients with chronic glomerulonephritis (CGN) and glomerulonephritis (GN) in systemic diseases. SUBJECTS AND METHODS: Seventy-nine patients with some male preponderance who were aged 21 to 65 years (45.3±11.1 years) and had CKD (CGN and GN) in systemic diseases (systemic lupus erythematosus and Wegener's granulomatosis) in the early stages (Stages I-II) of CKD were examined. GN was diagnosed by a lifetime renal biopsy. Systemic diseases were diagnosed according to the criteria for each nosological entity. The stages of CKD were defined according to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) criteria; the glomerular filtration rate (GFR) was calculated using the CKD EPI equation (2012). According to the presence or absence of anemia, all the patients included in the study were divided into 2 groups: 1) 43 (54.4%) anemic patients; 2) 36 (45.6%) non-anemic patients (a control group). In addition to general clinical examination adopted for a nephrology department, special studies, such as determination of the serum levels of hepcidin, interferon-γ (IFN-γ), soluble Klotho protein (s-Klotho), as well as iron, ferritin, and transferrin saturation (TSAT) ratio, were performed to solve the set tasks. RESULTS: Forty-three anemic patients who had a hemoglobin level of 110 (100; 119) g/l and 36 control patients who had the similar values were noted to have statistically significantly (p<0.001) higher levels of IFN-γ (11 (10; 14) and 0.2 (0.09; 0.6) ng/ml), hepcidin (26 (25; 27) and 5.1 (3.8; 5.9) ng/ml) and C-reactive protein (1.5 (1.1; 2.1) and 0.3 (0.2; 0.6) mg/dl), and lower levels of s-Klotho protein (12 (10; 18) pg/ml) and TSAT (18 (14; 19)%. Forty-three patients with anemia were also found to have a statistically significantly (p<0.01) lower GFR (65 (62; 87) and 80.5 (62; 90) ml/min) and higher systolic blood pressure (145 (125; 160) and 120 (115; 16) mm Hg) as compared with those in 36 control patients. At the same time, the compared groups displayed no statistically significant differences in serum ferritin levels (123 (110; 150) and 115 (100; 140) µg/l). Among 43 CKD patients with anemia, its detection rate in the presence of systemic diseases was 3.2 times higher than that in CGN patients (41.7 and 12.7%). ROC analysis revealed that in the CKD patients with CGN and GN, the serum hepcidin level ≥ 25 ng/ml, with the sensitivity and specificity being of 89.7% and 74%, respectively (p > 0.001), was associated with the development of anemia. Moreover, the hemoglobin level of<120 g/ l was found to have an independent impact on the risk of reducing serum s-Klotho production. CONCLUSION: In Stage I-II CKD patients with CGN and GN in the presence of systemic diseases, elevated serum hepcidin levels should be regarded as a predictor for anemia of chronic disease (ACD). Herewith, the decrease in hemoglobin levels <120 g/l is associated with the reduced production of the nephroprotective factor s-Klotho. The treatment of ACD for Stages I-II CKD should encompass intravenous administration of iron in order to increase its content and availability for erythropoiesis.

[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.

[Difficulties in the differential diagnosis of kidney injury in a patient with infective endocarditis associated with antineutrophil cytoplasmic antibodies]. / Trudnosti differentsial'noi diagnostiki porazheniia pochek u bol'nogo infektsionnym éndokarditom, assotsiirovannym s antineitrofil'nymi tsitoplazmaticheskimi antitelami.

Infective endocarditis (IE) may be accompanied by the production of a broad spectrum of autoantibodies, including antineutrophil cytoplasmic antibodies (ANCA). ANCA detection creates difficulties in the differential diagnosis of IE, especially in relation to kidney injury, the determination of the mechanism of which is important for choosing a treatment policy and estimating a prognosis. The paper describes a clinical case of a 57-year-old man who was found to have higher proteinase-3 (PR-3) ANCA titers along with the symptoms of anemia, purpura, and kidney injury during his hospitalization; echocardiography revealed vegetation on the aortic valve. IE was diagnosed; 2-week antibiotic therapy was ineffective; there was progressive aortic insufficiency necessitating aortic valve replacement. In the postoperative period, there was progression of renal failure and higher PR-3 ANCA titers, which made it possible to regard kidney injury as a manifestation of ANCA-associated glomerulonephritis. Intensive immunosuppressive therapy with intravenous and oral prednisolone was initiated, which showed positive effects in reducing proteinuria, erythrocyturia, serum creatinine levels, and simultaneously PR-3 ANCA titers. The paper gives the data available in the literature on the frequency of an association of IE with ANCA, the clinical features, diagnostic criteria, and treatment approaches. It discusses the mechanisms of ANCA formation in patients with IE.

[Hepatitis C virus-associated cryoglobulinemic vasculitis: A 20-year experience with treatment]. / Krioglobulinemicheskii vaskulit, assotsiirovannyi s virusom gepatita S: 20-letnii opyt lecheniia.

AIM: To summarize the experience of a multidisciplinary therapy hospital in treating patients with hepatitis C virus (HCV)-associated cryoglobulinemic vasculitis (CV). SUBJECTS AND METHODS: 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. RESULTS: 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 age >55 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). CONCLUSION: 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.

[EVALUATION OF CARDIOVASCULAR RISKS WITH THE USE OF MORPHOGENETIC KLOTHO PROTEIN IN PATIENTS WITH CHRONIC RENAL DISEASE].

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 «Sfigmokor¼ 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<0,01] or failed to reached target BP levels [p=0,008]. Conclusion: The study showed the possibility of practical use of Klotho protein as an early diagnostic marker of cardiovascular risk. Reduced serum Klotho was less pronounced in patients who used ARB for correction of high blood pressure. Normal Klotho protein levels in serum have been associated with a lower frequency of heart and vessels calcification in CKD patients.

[Impact of anemia correction on the production of the circulating morphogenetic protein α-Klotho in patients with Stages 3B-4 chronic kidney disease: A new direction of cardionephroprotection].

AIM: 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). SUBJECTS AND METHODS: 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. RESULTS: 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-ß + iron saccharate; anemia (the hemoglobin level of <110 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. CONCLUSION: 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.

[Significance of the determination of urinary excretion of kidney injury molecule-1 (KIM-1) in the assessment of the activity and prognosis of chronic glomerulonephritis].

AIM: To estimate the urinary excretion of KIM-1 in groups of patients with varying clinical activity of chronic glomerulonephritis (CGN) and to determine the possibility of using the urinary KIM-1 concentration as a criterion for predicting the course of CGN. SUBJECTS AND METHODS: A total of 47 patients with CGN were examined. Group 1 included 10 patients with nephrotic syndrome (NS) and decreased glomerular filtration rate (GFR); Group 2 consisted of 16 patients with NS and normal GFR; Group 3 comprised 10 patients with partial remission of NS; Group 4 included 11 patients with CGN, hematuria, moderate proteinuria, and normal GFR. A control group consisted of 9 healthy individuals. In the examined groups, urinary KIM-1 concentrations were estimated using an indirect immunoassay. RESULTS: The urinary KIM-1 excretion in the patients with CGN was higher than that in the healthy individuals (p <0.0001), at the same time, in the average the KIM-1 excretion was statistically significantly higher in the patients with proteinuria than in those with hematuria (p=0.01). The highest levels were registered in Group 1; Group 2 was intermediate in the level of KIM-1 excretion and the difference between Groups 3 and 4 proved to be statistically insignificant. The lowest levels were noted in Group 4 and in the controls; the differences between the groups were statistically insignificant. In the patients with CGN, the level of KIM-1 excretion was established to correlate with all indicators of NS severity. The value of the determination of KIM-1 as a risk factor of persistent/refractory NS was estimated. The results of constructing the ROC-curve indicate that KIM-1 levels higher than 2.34 ng/ml could predict NS persistence in CGN patients with a high sensitivity and specificity. CONCLUSION: Urinary KIM-1 levels may be used to estimate the activity of CGN with NS and to evaluate the efficiency of treatment. The results of the study substantiate the search for ways of pharmacological blockade of KIM-1 production in the kidney in order to optimize the methods that impact on the pathogenesis of CGN progression.

[Serum calgranulin C is a highly sensitive autoinflammation activity indicator in patients with familial periodic fevers].

AIM: 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). SUBJECTS AND METHODS: 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). RESULTS: 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). CONCLUSION: 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.

[The serum level of the morphogenetic protein fibroblast growth factor 23 (FGF-23) as a marker for the efficiency of hyperphosphatemia therapy with phosphate-binding agents in chronic kidney disease]. / Uroven' morfogeneticheskogo belka - faktora rosta fibroblastov 23-go tipa (FGF-23) v syvorotke krovi kak marker effektivnosti terapii giperfosfatemii svyazyvayushchimi fosfat preparatami pri khronicheskoi bolezni pochek.

AIM: 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). MATERIALS AND METHODS: 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. RESULTS: The elevated serum FGF-23 concentrations in the patients on regular HD correlated with their HD duration (r=0.508; p<0.001). Along with this, a strong direct correlation (r=0.522; p<0.001) 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; p<0.05). 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) (p<0.01). 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). CONCLUSION: 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 (p<0.01).

[Oligosecretory monoclonal gammopathy with renal involvement]. / Oligosekretornaya monoklonal'naya gammapatiya s porazheniem pochek.

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).

[Decreased Serum Levels of Klotho Protein in Chronic Kidney Disease Patients: Clinical Imortance].

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 1­5D (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 «Sphygmоcor¼ (Australia), echocardiography, radiography of the abdominal aorta in a lateral projection were also performed. Results: Ehen 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 4­5 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<0.01) or has not reached the target blood pressure level (p=0,008). Conclusion: The change of serum Klotho levels (decrease) in CKD progression is associated with the degree (increase) of cardiovascular calcification and remodeling (the development of left ventricular hypertrophy, and cardiomyopathy) and it can be seen as an early independent marker of the cardiovascular system lesions in CKD. Our preliminary data of the effect of blood pressure correction on s-Klotho levels may indicate the possibility of drug maintaining serum Klotho levels and it requires further research.

[Role of the morphogenetic proteins FGF-23 and Klotho and the glycoprotein sclerostin in the assessment of the risk of cardiovascular diseases and the prognosis of chronic kidney disease].

UNLABELLED: 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. SUBJECTS AND METHODS: 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 BPs > 140/80 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. RESULTS: 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. CONCLUSION: 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.