Vol 84, No 6 (2012)

Editorial
PERSONIFICATED MEDICINE IN CLINICAL NEPHROLOGY
Mukhin N.A., Fomin V.V.
Abstract
Prospects of introduction of personification medicine principles into clinical nephrology are discussed with a special emphasis on prognosis of the course of chronic kidney diseases and response of the latter to pathogenetic therapy.
Terapevticheskii arkhiv. 2012;84(6):5-9
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ENDOTHELIAL DYSFUNCTION AND APOPTOSIS AT EARLY STAGE OF CHRONIC KIDNEY DISEASE
Smirnov A.V., Petrischev N.N., Mnuskina M.M., Panina I.Y., Pumyantsev A.S., Vasina E.Y., Achkasova V.V., Menshutina M.A.
Abstract
Aim. To study changes in apoptosis and endothelial function in patients with chronic kidney disease (CKD) stage I-IIIb (CKDsI-IIIb). Material and methods. A complex of biochemical, enzyme immunoassay and device investigations was used to examine 128 patients with CKDsI-IIIb. Results. In CKD stage I reduction of endothelium-dependent vasodilation (EDV) was detected in 34% patients, in stage II — in 52 %, in stage IIIa — у 52 %, in stage IIIb — in 70 %. An EDV decrease was associated with glomerular filtration rate (GFR), a homocysteine level and hemodynamic factors. Elevation of endothelin-1 (ET-1) level was seen in CKDsI in 41 %, in CKDsII — in 54 %, in CKDsIIIa — in 70 %, in stage IIIb — in 83 % patients. A negative correlation was observed between the level of ET-1 and GFR and positive — with diurnal proteinuria. A significant rise of annexin A 5 concentration versus normal was detected as early as in CKDsI (1,14 ± 0,68 ng/ml). In CKDsII annexin A 5 was 2,61 ± 0,75 ng/ml, in CKDsIIIa — 3,75±0,93 ng/ml and in CKDsIIIb — 5,16±1,01 ng/ml. Negative correlations were found between annexin A 5 level and GFR, a maximal growth of volumetric blood flow rate in skin vessels in the acetylcholine test, positive correlations with systolic blood pressure, body mass index. Conclusion. The levels of ET-1 and annexin A5 are factors having an independent impact on EDV in patients with CKDsI-II.
Terapevticheskii arkhiv. 2012;84(6):9-15
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CLINICOPATHOGENETIC CHARACTERISTICS OF CARDIORENAL SYNDROME IN NON-ALCOHOLIC FATTY DISEASE OF THE LIVER
Severova M.M., Saginova E.A., Gallyamov M.G., Ermakov N.V., Rodina A.V., Fomin V.V., Mukhin N.A.
Abstract
To study clinicopathogenetic characteristics of cardiorenal syndrome (CRS) in non-alcoholic fatty disease of the liver (nAFDL). Material and methods. Insulin resistance markers, plasma ієрtin and serum adiponectin concentrations, albuminuria, intima-media thickness (IMT) of the common carotid artery (CCA) were assessed in 80 patients with metabolic syndrome (60 males and 20 females, mean age 44+-11 years) and NAFDL. Results. With increasing signs of affection of target organs in NAFDL there was a trend to a significant rise in detection of chronic kidney disease (CKD) and carotid artery atherosclerosis, aggravation of albuminuria and CCA IMT, lowering of glomerular filtration rate. Leptinemia was maximal in CKD patients and directly correlated with albuminuria. Patients with CCA atherosclerosis had a significant fall of serum adiponectin which negatively correlated with CCA IMT. The latter positively correlated with insulinemia, a C-peptide plasma level and HOMA index. Serum concentration of adiponectin positively correlated with DeRitis index. Conclusion. CRS in NAFDL is characterized with frequent development of CKD and CCA atherosclerosis defined also by unbalance of adiponectin and leptin production.
Terapevticheskii arkhiv. 2012;84(6):15-20
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MYOCARDIAL REMODELING RISK FACTORS AT STAGE II-IV CHRONIC KIDNEY DISEASE
Rudenko T.E., Kutyrina I.M., Shvetsov M.Y.
Abstract
Aim. To evaluate frequency and risk factors of development of left ventricular hypertrophy (LVH) of the heart in patients with chronic kidney disease (CKD) of stage II-IV Material and methods. The trial enrolled 83 patients (42 - 51% males, 41 - 49% females, mean age 46.7 years) with stage II-IV CKD of non-diabetic origin. Glomerular filtration rate (GFR) estimated according to Cockroft-Goult formula was 37,7 ml/min (95% confidence interval from 33,9 до 41,4). Chronic renal failure duration averaged 2,7 years (95 % CI from 2.0 to 3.3). Arterial hypertension (AH) was diagnosed in 96% patients, hereditary predisposition to cardiovascular diseases - in 54 %, obesity — in 60 %, lipid disbolism - in 66%, anemia — in 34 % and hyperphosphatemia — in 45 %; 40% patients smoked. Echocardiography was performed in all the patients. Results. LVH was detected in 31 (37.3%) of 83 patients. With progression of renalfailure, frequency of registration of LVH increased. LVH onset was associated with conventional (age, AH, high level of total cholesterol) and renal (lowering of GFR, anemia, hyperphosphatemia) factors. Concentric remodeling, concentric LVH, eccentric LVH were detected in 31.3, 19.3 and 18.1% patients, respectively. Eccentric LVH developed more frequently under the influence of factors associated with renal failure (GFR, anemia, hyperphosphatemia, hypocalciemia). Concentric LVH was characterized with the highest systolic blood pressure. Conclusion. Patients with renal dysfunction develop LVH of different geometric model associated with both conventional and renal risk factors even at early stages of CKD.
Terapevticheskii arkhiv. 2012;84(6):21-26
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REMODELING OF CARDIOVASCULAR SYSTEM AND DEVELOPMENT OF CHRONIC KIDNEY DISEASE IN PATIENTS WITH METABOLIC SYNDROME AND OBESITY: ROLE OF GENES ENOS, SUBUNIT P22-PHOX OF NADPH-OXIDASE AND MTHFR
Saginova E.A., Gallyamov M.G., Balatsky A.V., Kolotvin A.V., Severova M.V., Samokhodskaya L.M., Fomin V.V., Krasnova T.N., Mukhin N.A.
Abstract
Aim. To examine contribution of polymorphisms of genes of endothelial NO-synthase (eNOS), NADPH-oxidase and methylenetetrahydrofolate reductase (mTHFR) to development of remodeling of cardiovascular system and chronic disease of the kidneys (CDK) in patients with metabolic syndrome (mS) and obesity. Material and methods. Standard clinical and device examinations were made and polymorphisms C242T of gene of subunit p22-phox of NADPH-oxidase, G894T of gene of eNOS and C677T of gene of MTHFR were studied in 66 MS patients (49 males and 17 females, age 19-62 years. Results. The presence of even one prognostically poor allele variants of the genes studied was registered in 83 examinees. The genotype 242TT p22-phox of NADPH-oxidase subunit was associated with the highest insulin resistance, allele 894T of gene eNOS - with reduced glomerular filtration rate and progression of left ventricular hypertrophy. Conclusion. Polymorphism of the genes the products of which modulate endothelial function can be considered as potential predictors of severity of MS target organs impairment.
Terapevticheskii arkhiv. 2012;84(6):26-31
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THE ROLE OF HYPERINSULINEMIA AND INSULIN RESISTANCE IN DEVELOPMENT OF CHRONIC KIDNEY DISEASE IN PATIENTS WITH METABOLIC SYNDROME
Kutyrina I.M., Kryachkova A.A., Savelieva S.A.
Abstract
Aim. To examine relations between hyperinsulinemia, insulin resistance (IR), components of metabolic syndrome (MS) and predisposition to renal damage. Material and methods. A total of 94 MS patients (64 males and 30 females, age 30-67 years, mean age 52±9 years) entered the study. The examination included measurement of waist and hip circumference, body mass index (BMI), HOMA index, estimation of lipids and immunoreactive insulin concentrations. Renal damage was assessed by glomerular filtration rate and urinary excretion of albumin. The patients were divided into groups by IR and BMI. Results. A strong correlation was found between IR markers and lipid metabolism disorders, hemodynamic parameters. Statistics show that IR is an independent unfavourable factor of renal damage in MS patients. Conclusion. IR is an essential component of MS and an independent factor of development of chronic kidney disease in MS patients.
Terapevticheskii arkhiv. 2012;84(6):32-36
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URINARY EXCRETION OF PROFIBROTIC AND ANTIFIBROTIC GROWTH FACTORS IN TYPE 1 DIABETIC PATIENTS: THE RELATION WITH DIABETIC NEPHROPATHY
Bondar I.A., Klimontov V.V., Parfentieva E.M., Romanov V.V., Nadeev A.P.
Abstract
Aim. To assess the relation between urinary excretion of profibrotic and antifibrotic growth factors, albuminuria and glomerular fibrosis in type 1 diabetic patients. Materials and methods. 64 patients with diabetes were examined, including 25 ones with normal albumin excretion rate (AER), 30 microalbuminuric and 9 macroalbuminuric patients. Urinary excretion of type IV collagen, transforming growth factor-β1 (TGF-ß1), tumor necrosis factor-α (TNF-α), fibroblast growth factor-2 (FGF-2), hepatocyte growth factor (HGF) and bone morphogenetic protein-7 (BMP-7) was determined by ELISA and compared to control (10 healthy subjects). Renal biopsy specimens were assessed in 7 patients with normal AER and in 14 microalbuminuric patients. Results. Type IV collagen, TGF-β1 and TNF-α excretion was increased significantly in patients with micro- and macroalbuminuria as compared to control (all p<0.05). Excretion of FGF-2 was increased in macroalbuminuric patients only (p=0.003). No marked changes in excretion of antifibrotic growth factors (HGF and BMP-7) were observed. TNF-α and FGF-2 correlated positively with urinary type IV collagen (r=0.37 and r=0.31, respectively). The presence of glomerular fibrosis in renal biopsy specimens was associated with higher excretion of TGF-ß1, TNF-α and FGF-2 (all p<0.05). Conclusion. The results suggest that unbalance between profibrotic and antifibrotic growth factors in the kidneys plays an important role in pathogenesis of diabetic nephropathy. Urinary TGF-ß1, TNF-α and FGF-2 may offer new possibilities for detection of renal fibrosis in diabetic patients.
Terapevticheskii arkhiv. 2012;84(6):36-40
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CHANGES IN RHEOLOGICAL BLOOD PROPERTIES IN PATIENTS WITH LUPUS NEPHRITIS AND IGA-NEPHROPATHY
Krasnova T.N., Georginova O.A., Rykova S.Y., Sokolova I.A., Mukhin N.A.
Abstract
Aim. To compare changes of hemorheological parameters in patients with lupus nephritis (LN) and IgA-nephropathy (IgA-N). Material and methods. Kinetics of spontaneous aggregation, disaggregation of red cells in shearing flow, red cell deformability were studied in 73 patients with LN including 6 patients with active LN with nephrotic syndrome, 38 patients with active LN with urinary syndrome, 29 with inactive LN; in 24 patients with a hematuric form of IgA-nephritis (IgA-N); in 24 healthy volunteers (controls). Results. Patients with LN and a hematuric form of IgA-H were found to have disorders of microrheological blood characteristics (accelerated formation of erythrocytic aggregates —EA of high density) depending on the form and activity of the disease. All LN and IgA-N patients exhibited increased time of "coin columbs" formation and accelerated aggregation. The largest EA were detected in IgA-H patients. Flow deformation ability of the red cells was poor in all the examinees. LN patients showed a positive correlation between maximal EA size and hematuria severity even in cases of trace proteinuria. A correlation was demonstrated in IgA-N patients between IgA level and EA density, between inhibition of GFR and erythrocytic deformability index. Conclusion. The above findings show deteriorated process of aggregation-disaggregation resultant from deterioration of red cell physical properties. Severity of hemorheological disorders depends on LN activity. Hematuria associated with increased size of EA is an important marker of the disease activity. Hemorheological disorders in patients with active LN and IgA-N are an additional pathogenetic component of hematuria.
Terapevticheskii arkhiv. 2012;84(6):41-44
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SERUM LEVELS OF MYELOID-RELATED PROTEIN MRP 8/14 (CALPROTECTIN) IN ARMENIAN PATIENTS WITH FAMILIAL MEDITERRANEAN FEVER (FMF)
Dzhndoyan Z.T.
Abstract
Aim. The determination of serum myeloid-related protein MRP 8/14 (calprotectin) in Armenian patients with FMF before and after treatment with colchicine (including colchicine-resistant patients who don’t respond to 2 mg of colchicine; it patients who don’t respond to 1,5 mg of colchicine, and also responders to different dose of colchicine) and estimation of the response to antiinflammatory therapy. Material and methods. MRP 8/14 serum levels were measured in 80 FMF patients before and after treatment with colchicine and in healthy individuals (n=11) and patients with rheumatoid arthritis RA (n=11) as a control group. Serum MRP 8/14 concentration was measured by ELISA (Enzyme Linked-Immuno-Sorbent-Assay) method using "Bühlmann" kit (Switzerland) in the laboratory with modern equipment. Results. Serum MRP 8/14 concentrations were within a normal ranges in healthy individuals and elevated in patients with FMF and RA. MRP 8/14 serum levels in FMF patients were higher than in RA patients. Serum MRP 8/14 concentrations in FMF patients before colchicines therapy were higher than after treatment. Conclusion. The findings of our study indicate that myeloid-related protein MRP 8/14 is a very sensitive marker of the disease activity and response to antiinflammatory therapy in FMF.
Terapevticheskii arkhiv. 2012;84(6):45-48
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LONG-ACTING ERYTHROPOETIN EFFICACY IN THE TREATMENT OF NEPHROGENIC ANEMIA IN PATIENTS WITH CHRONIC KIDNEY DISEASE AT A PREDIALYSIS STAGE
Milovanov Y.S., Milovanova L.Y.
Abstract
Aim. Comparison of efficacy of 12-month treatment of anemia in patients with chronic kidney disease (CKD) of stage III — IV with a long-acting drug darbepoetin alpha — aranesp and short-acting drug erythropoietin beta — recormon. Material and methods. A total of 44 patients with CKD of stage III-IV were divided into two groups. Of them, 24 had chronic glomerulonephritis and 20 had tubulointerstitial nephritis with verified nephrogenic anemia. Group 1 consisted of 22 patients given long-acting erythropoetin (darbepoetin alpha) in an initial dose 0,75 mcg/kg each 2 weeks subcutaneously. Group 2 consisted of 22 patients matched by age, gender, severity of anemia and renal failure with group 1 patients given short-acting erythropoietin (erythropoietin beta) in an initial 20 IU 3 times a week subcutaneously for 12 months. In the phase of anemia correction and supporting therapy, the levels of packed red blood cells, Hb, free serum ferrum, ferritin, percentage of iron in transferrin, serum albumin in blood serum, creatinin, glomerular filtration rate were examined monthly. The patients themselves daily measured blood pressure, diuresis, body mass. Results. The target level of Hb 110-120 g/l was achieved faster in group 2 than in group 1 (3 and 4 months, respectively), p < 0.05). In the phase of supporting a target Hb level, on the opposite, darbepoetin alpha provided more stable hemopoetin effect than erythropoietin beta, darbepoetin alpha median dose being constant in the course of the study.
Terapevticheskii arkhiv. 2012;84(6):48-52
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MUCKLE-WELLS SYNDROME CAUSED BY A NEW CRYOPIRIN MUTATION: EFFECTIVE TREATMENT WITH INTERLEUKIN-1 ANTAGONIST
Rameev V.V., Kozlovskaya L.V., Bogdanova M.V.
Abstract
A significant progress in the field of molecular-biological investigations resulted in definition of a new group of systemic diseases referred to as autoinflammatory. This group comprises familial periodic fevers: periodic disease (mediterranean fever), Muckle-Wells syndrome, others cryopirinopathy, TRAPS-syndrome. As shown by case reports, Muckle-Wells syndrome is not a rare disease, its sporadic forms are encountered as well as a less severe variant of cryopirinopathy — nonallergic cold urticaria. Awareness of the physicians in respect of this pathology is essential especially because early diagnosis enables control of this disease with use of biological preparations the spectrum of which tends to expansion. Moreover, arrest of inflammation is necessary for prevention of development and progression of such prognostically poor complication as AA-amyloidosis.
Terapevticheskii arkhiv. 2012;84(6):53-59
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EFFICACY OF COMBINED IMMUNOCORRECTION IN THE TREATMENT OF CHRONIC VIRAL HEPATITIS C
Frolov V.M., Sotskaya Y.A.
Abstract
Aim. To assess efficacy of combined immunocorrection in the treatment of patients with chronic viral hepatitis C (CVHC). Material and methods. Routine clinicobiochemical tests, examination of immunological homeostasis (cellular immunity, the level of circulating immune complexes - CIC and their molecular composition, macrophagal phagocyting system — MPS) were made in two groups of CVHC patients: the study group (n=68) and control group (n=66). The control patients received standard treatment, the study group received also cyclopheron in combination with reamberin. Cyclopheron was given per os in a single daily dose 600 mg 2 days, then 3 times a week in a dose 150 mg for 48 weeks. Reamberin infusions in a single daily dose 400 m l were made for 5 — 7 days. Results. CVHC in exacerbation phase is characterized by the presence of secondary immunodeficiency running with T-lymphopenia, low count of peripheral blood lymphocytes with CD4+ phenotype and low immunoregulatory index CD4/CD8, depression of functional activity of T-cells as evidenced by lymphocyte blasttransformation test with phytohemagglutinin, inhibition of phagocyting activity of monocytes and inhibition of dermal macrophages. This shows subnormal functional activity of MPS. CVHC runs with accumulation of CIC in blood serum primarily due to increased content of most pathogenic mid- and low-molecularfractions of immune complexes. Addition of cyclopheron and reamberin in combined treatment of CVHC patients promotes normalization of immunological homeostasis which clinically occurs in parallel with achievement of persistent and long-term CVHC remission. Conclusion. The results of the above investigation support pathogenetic validity and prospects of cyclopheron and reamberin inclusion into combined treatment of CVHC.
Terapevticheskii arkhiv. 2012;84(6):60-65
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MICROHEMOCIRCULATION DISORDERS IN PATIENTS WITH BRONCHOPULMONARY PATHOLOGY AND METHODS OF MICROHEMOCIRCULATION STUDY
Korzheva I.Y., Yakovlev V.N., Mumladze R.B., Rozikov Y.S., Duvansky V.A.
Abstract
Aim. To investigate microhemocirculation in patients with bronchopulmonary pathology with application of Doppler flowmetry (DFM). Material and methods. Videobronchoscopy (Olimpas or Pentax devices) was performed in 203 patients with bronchitis of different inflammation intensity. Functional activity of microhemocirculation in bronchial mucosa was studied with endobronchial laser Doppler flowmetry (LDF) which was also made in 20 healthy controls. Results. LDF-grams demonstrated that patients with chronic bronchitis and pneumonia have congestive regional microcirculation with low activity of components of microcirculatory bed, venous blood congestion, weak blood flow and tissue ischemia. High informative value of the method and its availability was shown by comparison of LDF-grams on treatment day 7 and 14. Conclusion. High informative value of LDF procedure is found in diagnosis of vascular and intravascular microcirculatory disorders in patients with bronchopulmonary pathology.
Terapevticheskii arkhiv. 2012;84(6):65-67
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NEPHROTIC CRISIS — AN URGENT CONDITION IN PATIENTS WITH NEPHROTIC SYNDROME
Kozlovskaya L.V., Bobkova I.N., Chebotareva N.V., Fomin V.V., Roschupkina S.V.
Abstract
The lecture considers mechanisms of potassium and water retention underlying nephrotic syndrome, clinical differences between hypo- and hypervolemic variants of nephrotic syndrome, risk factors of nephrotic crisis and its clinical symptoms, current approaches to its treatment.
Terapevticheskii arkhiv. 2012;84(6):68-73
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CURRENT ANTI-INFLAMMATORY TREATMENT IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE
Shmelev E.I., Shmeleva N.M.
Abstract
The lecture analyses current tools of anti-inflammatory treatment of patients with chronic obstructive pulmonary disease (COPD). Anti-inflammatory treatment is aimed at a key element of COPD pathogenesis. The results of treatment with main anti-inflammatory drugs and methods in COPD management are reviewed as well as efficacy of a new anti-inflammatory drug roflumilast in COPD patients.
Terapevticheskii arkhiv. 2012;84(6):73-76
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PHARMACOLOGICAL NEPHROPROTECTION IN CHRONIC KIDNEY DISEASE: CURRENT OPPORTUNITIES AND PERSPECTIVES (REVIEW OF FOREIGN LITERATURE)
Nikolaev A.Y.
Abstract
A brief literature review analyses pharmacoprotective strategy in most widespread forms of chronic kidney disease: metabolic syndrome, hypertensive angionephrosclerosis, diabetic and non-diabetic nephropathy. Nephroprotective properties of the blockers of rennin-angiotensin-aldosteron system and other antiadrenergic drugs, diuretics, hypolipidemic, antianemic and hypouricemic drugs, active metabolites of vitamin D, metphormine and glytasones are reviewed. The highest efficacy of combined pharmaconephroprotection is demonstrated.
Terapevticheskii arkhiv. 2012;84(6):76-80
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