Prediction of features of the course of chronic hepatitis C using Bayesian networks.

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

Clinical significance of the determination of surfactant proteins A and D in assessing the activity of lung sarcoidosis.

AIM: To study the clinical significance of SP-A, SP-D in assessing the activity of idiopathic pulmonary fibrosis and sarcoidosis. We examined 81 patients with morphologically confirmed diagnoses of idiopathic pulmonary fibrosis (ILF) and sarcoidosis, a control group of 20 healthy individuals. The MSCT of the thoracic organs of the chest was performed, the diffusivity of the lungs was examined, oxygen saturation was determined. In the serum, the surfactant proteins SP-A and SP-D were determined by the enzyme-linked immunosorbent assay. RESULTS: A significant increase in SP-A and SP-D (p<0.05) was observed in patients compared with patients in the control group, a direct correlation was found with signs of activity: SP-A with alveolitis (p<0.05), SP- D with progressive fibrosis (p<0.05), inverse correlation of surfactant proteins with respiratory function indices (p<0.05). CONCLUSION: Serological parameters of SP-A and SP-D reflect the activity of alveolitis and the progression of pulmonary fibrosis in patients with ILF and sarcoidosis.

[Giant cell arteritis: Genetic and epigenetic aspects]. / Gigantokletochnyi arteriit: geneticheskie i épigeneticheskie aspekty.

The paper describes clinical cases in 2 patients (brothers) with giant cell arteritis. It analyzes the genetic and epigenetic aspects of the disease. The data available in the Russian and foreign literature are given.

[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.

[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.

[Role of neutrophil dysfunction in the pathogenesis of systemic lupus erythematosus]. / Rol' disfunktsii neitrofilov v patogeneze sistemnoi krasnoi volchanki.

Neutrophil dysfunction plays a considerable role.in systemic lupus erythematosus (SLE) The protective function of neutrophils is carried out through various mechanisms: isolation of granular antimicrobial peptides (gAMP), microbial phagocytosis with subsequent degradation via reactive oxygen species inside the phagolysosomes; as well as bactericidal action due to the release of networks from chromatin and gAMP, also called neutrophil extracellular traps (NECTs). The development of neutropenia in SLE has multiple causes, including the formation of antibodies directly to leukocytes; that of neutralizing autoantibodies to the growth factors of neutrophils and cells - myeloid precursors; bone marrow suppression; involvement of neutrophils in the processes of apoptosis and NETosis. Neutrophils in SLE are characterized by reduced phagocytic ability and pathological oxidative activity. In SLE, there is a decrease in the ability to remove the products of neutrophil apoptosis, which is correlated with disease activity. SLE patients are noted to have a higher expression level of the genes specific for low-density granulocytes, an abnormal immature neutrophil population. The impaired processes of formation of NECTs and removal NETosis products play a substantial role in the pathogenesis of SLE. It is shown that the abnormal formation of NECTs also causes endothelial injury and increases the risk of thromboses. The design of novel drugs that act on the specific parts of the formation of NECTs or contribute to their removal from the extracellular environment can propel therapy for SLE and other autoimmune diseases to new heights. There is evidence for further investigations of neutrophil-mediated pathogenetic processes in SLE in order to identify potential therapeutic targets and to understand the mechanisms of action of drugs used in clinical practice.

[Role of polymorphic markers for the genes of hemostasis and platelet receptors in liver fibrosis progression in patients with chronic hepatitis C]. / Rol' polimorfnykh markerov genov gemostaza i trombotsitarnykh retseptorov v progressirovanii fibroza pecheni u bol'nykh khronicheskim gepatitom S.

AIM: to estimate the clinical and prognostic value of the carriage of different allele variants of the gene polymorphisms of the coagulation system and platelet receptors in the progression of liver fibrosis (LF) in patient with chronic hepatitis C (CHC). SUBJECTS AND METHODS: The investigation enrolled 177 patients with CHC and liver cirrhosis at its outcome who were divided into 2 groups according to the rate of LF progression: 1) 89 patients with rapid (rapid fibrosis) and 2) 88 patients with slow (slow fibrosis) progression. The polymorphism of the study genes was studied using a real-time polymerase chain reaction and a melting curve analysis. RESULTS: In CHC patients, the FV 1691G/A genotype was more often in the rapid progressors than that in the slow progressors (10.11% vs 1.14%; p=0.011). The A allele of the 1691 G/A FV gene was more common in the rapid fibrosis group than that in the slow fibrosis group (1.7% vs 5.56%, odd ratio 9.787; p=0.139). In our investigation, the polymorphic marker GA in the FII 20210 G/A gene, as well as the 4G allele (5G4G + 4G4G genotypes) and the 4G allele of PAI-I -675 5G/4G were more often seen in the rapid fibrosis group than that in the slow fibrosis group; the detection rate was only at the trend level (p=0.118, p=0.112, and p=0.117 respectively). There were no significant differences between the groups in the spread of variant genotypes and alleles of other study genes. Integral model construction by coding «profibrogenic¼ genotypes (FV 1691 G/A, FII 20210 G/A, PAI-I -675 5G/4G) showed that the fibrosis progression rate expressed as fibrosis units annually also increased with higher total scores (p=0.039), indicating the combined effect of these genes. CONCLUSION: The carriage of mutant genotypes of FV 1691 G/A, FII 20210 G/A, and PAI-I -675 5G/4G genes is a prognostic factor for rapid CHC progression.

[Chronic kidney disease and atrial fibrillation as components of the cardiorenal continuum].

The paper discusses the present-day idea on a relationship between atrial fibrillation and chronic kidney dis~ase, the specific features of therapeutic policy, and the place of antithrombotic therapy in particular."Based on the results of population-based studies,the authors set forth the specific features of cardiac arrhythmias concurrent with kidney injury, as well as promising directions to optimize management schemes for this category of patients.

[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.

[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).

[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.

[NODULAR POLYARTERITIS ASSOCIATED WITH HEPATITIS B VIRUS (A CASE STUDY)].

This study is focused on a case of nodular polyarteritis associated with hepatitis B virus successfully treated by immunosuppressive and antiviral agents.

[Acute glomerulonephritis in the 21-st century].

The paper discusses the specific features of the current course of acute glomerulonephritis, the spectrum of its etiological factors, and clinical manifestations. The factors influencing the course and outcomes of acute glomerulonephritis, including the risk of its progression to chronic kidney disease, are specially depicted.

[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.

[Impact of interleukin-10 and interleukin-28 gene polymorphisms on the development and course of lupus nephritis].

AIM: To assess the relationship of the carriage of IL-10-1080 G/A and IL-28 rs8099917 C/T polymorphisms to the course of lupus nephritis (LN). SUBJECTS AND METHODS: Ninety-nine patients with systemic lupus erythematosus (SLE), including 68 with LN, were examined. Gene polymorphisms were analyzed using standard molecular genetic techniques. The frequency of the clinical manifestations of LN was analyzed; renal survival (RS) was estimated by the Kaplan-Meier method. RESULTS: Ten-year RS rates were 80 and 86% of the patients with and without the mutant IL-10 allele, respectively (p = 0.78). The 10-year RS was lower (75%) in carriers of the mutant IL-28 rsl2979860 allele than in patients without this mutant allele (83%; p = 0.049) and in those of the mutant IL28 rs8099917 allele than in patients without the above mutant allele (67 and 88%, respectively; p = 0.047). LN patients, carriers of the mutant IL-10-1028 G/A allele, were observed to have higher-grade proteinuria in the presence of nephritic syndrome (mean 6.1 g/l) than those without the mutant allele of this gene (mean 2.9 g/l; p = 0.034). However, the mutant allele carriers responded to treatment better (p = 0.050). The mutant IL-10 and IL-28 alleles were unassociated with the development of rapidly progressive nephritis, the activity of a renal lupus process, and the rate of onset of SLE and LN. CONCLUSION: In the LN patients, the carriage of the mutant IL-10 allele A is associated with a better response to treatment and that of the mutant IL-28 allele is linked to the severe course of the disease.

[Urinary excretion of angiogenesis regulatory factors and renal injury markers in chronic glomerulonephritis: Significance in the assessment of progression].

AIM: To study the urinary excretion of the molecular factors regulating angiogenesis, such as vascular endothelial growth factor type A (VEGF-A), thrombospondin 1 (THBS1), and angiopoietin 2 (ANGPT2), versus that of the urinary markers of renal injury and fibrogenesis, such as neutrophil gelatinase-associated lipocalin (NGAL), type IV collagen (COL4), and known clinical risk factors for accelerated disease progression to estimate the prognostic value of urinary excretion in patients with chronic glomerulonephritis (CGN). SUBJECTS AND METHODS: Eighty-two patients (45% men, 55% women; mean age, 36.5 years) with a clinical diagnosis of CGN were examined. 31.7% of the examinees presented with nephrotic syndrome; 31.7% had a glomerular filtration rate (GFR) of less than 60 ml/min/1.73 m2. Morning urine samples were analyzed by Elisa to determine the urinary excretion of biomarkers (VEGF-A, THBS1, ANGPT2, NGAL, and COL4). The results were adjusted to urinary creatinine concentrations. RESULTS: The urinary excretion of the angiogenesis regulators VEGF-A, THBS1, and ANGPT2 correlated between them, with that of the renal injury markers NGAL and COL4, with the level of proteinuria. That was found to be unassociated with blood pressure and GFR. In the presence and absence of nephrotic syndrome, high (> 75th percentile) urinary excretion rates were 46.2 and 14.8% for VEGF-A (p < 0.01); 50 and 13% for THBS1 (p < 0.001); and 46.2 and 14.8% for ANGPT2 (p < 0.01), respectively. That for ANGPT2 was also high in the presence of anemia (63.2 versus 11.7%; p < 0.001). CONCLUSION: The finding of the high urinary excretion of the angiogenesis regulators VEGF-A, THBS1, and ANGPT2 and its association with that of kidney injury markers in the patients with the proteinuric forms of CGN suggest that this excretion may be considered as an integral index that displays glomerular injury and indicates tubulointerstitial proteinuric/hypoxic remodeling.

[Clinical value of surfactant protein D as a biomarker of pulmonary fibrosis in patients with scleroderma systematica in relation to the presence of gastroesophageal reflux].

AIM: To study the role of serum surfactant protein D (SP-D) as a biomarker of lung injury in scleroderma systematica (SDS) in relation to the presence of gastroesophageal reflux (GER). SUBJECTS AND METHODS: Fifty-six patients (mean age 46±14 years) with diffuse and circumscribed SDS were examined and underwent pulmonary functional tests, X-ray and, if lung injury was present, high-resolution computed tomography of the lung, echocardiography, gastroduodenoscopy, and barium X-ray of the esophagus; an enzyme-linked immunosorbent assay was used to determine serum SP-D levels. RESULTS: SP-D concentrations significantly correlate with the presence of lung injury in SDS and are significantly higher in the presence of pulmonary fibrosis and the signs of frosted glass and honeycomb lung patterns. SP-D levels were higher in the patients with lung injury and SDS in the group of those with pulmonary fibrosis and GER than in the group of pulmonary fibrosis patients without the latter. CONCLUSION: Serum SP-D may be considered in a number of biomarkers for the severity of lung injury in SDS, including GER-associated lung injury.

[Better diagnosis is an obligatory condition for improving medical care quality].

The paper discusses current approaches to organizing a diagnostic process in health care facilities. It describes approaches to improving patient examinations in multidisciplinary hospitals.

[Mathematic Model for Prediction of Liver Fibrosis Progression Rate in Patients with Chronic Hepatitis C Based on Combination of Genomic Markers].

AIM OF STUDY: To evaluate clinical significance of different combinations of gene polymorphisms IL-1b, IL-6, IL-10, TNF, HFE, TGF-b, ATR1, N0S3894, CYBA, AGT, MTHFR, FII, FV, FVII, FXIII, ITGA2, ITGB3, FBG, PAI and their prognostic value for prediction of liver fibrosis progression rate in patients with chronic hepatitis C (CHC). SUBJECTS AND METHODS: 118 patients with CHC were divided into "fast" and "slow" (fibrosis rate progression ≥ 0.13 and < 0.13 fibrosis units/yr; n = 64 and n = 54) fibrosis groups. Gene polymorphisms were determined. Statistical analysis was performed using Statistica 10. RESULTS: A allele (p = 0.012) and genotype AA (p = 0.024) of AGT G-6T gene, as well as T allele (p = 0.013) and MT+TT genotypes (p = 0.005) of AGT 235 M/T gene were significantly more common in "fast fibrosers" than in "slow fibrosers". Patients with genotype TT of CYBA 242 C/T had a higher fibrosis progression rate than patients with CC+CT genotype (p = 0.02). Our analysis showed a protective effect of TTgenotype of ITGA2 807 C/T on fibrosis progression rate (p = 0.03). There was a trend (p < 0.15) to higher fibrosis progression rate in patients with mutant alleles and genotypes of TGFb +915 G/C, FXIII 103 G/T, PAI-675 5G/4G genes. Other gene polymorphisms were not associated with enhanced liver fibrosis. To build a mathematical modelfor prediction of liverfibrosis progression rate we performed coding with scores for genotypes and virus genotype. Total score correlated with the fibrosis progression rate (R = 0.39, p = 0.000). CONCLUSION: Determination of genetic profile of the patient and virus genotype allows to predict the course of CHC.