Vol 85, No 6 (2013)


Nephropathy in Fabry disease: possibilities for the radical improvement of prognosis for orphan diseases

Fomin V.V., Pulin A.A., Mukhin N.A.


The paper discusses the specific features of the diagnosis and treatment of kidney involvement in patients with Fabry disease.
Terapevticheskii arkhiv. 2013;85(6):4-9
pages 4-9 views

Diagnostic value of cystatin C and neutrophil gelatinase-associated lipocalin in primary glomerulopathies

Proletov I.I., Saganova E.S., Galkina O.V., Zubina I.M., Bogdanova E.O., Sipovskiĭ V.G., Smirnov A.V.


AIM: To study an association between clinical and morphological evidence and the serum and daily urinary levels of cystatin C (CysC) and neutrophil gelatinase-associated lipocalin (NGAL) in patients with primary glomerulopathies/MATERIAL AND METHODS: The investigation included 104 patients; morphological examination showed minimal change disease in 15 (14.4%) patients, focal segmental glomerulosclerosis in 24 (23.1%), membrane nephropathy in 32 (30.8%), and IgA nephropathy (mesangioproliferative glomerulonephritis) in 33 (31.7%). The investigators analyzed the clinical type of nephropathy, performed conventional laboratory and instrumental examinations, and determined the level of CysC (by immunoturbodimetry) and NGAL (by enzyme immunoassay) in the serum and daily urine taken before kidney biopsy. The degree of glomerulosclerosis, tubulointerstititial sclerosis, and tubular atrophy was semiquantitatively estimated/RESULTS: Urinary CysC and NGAL excretion correlated with the degree of glomerulosclerosis and proteinuria and the reduced glomerular filtration rate (GFR) regardless of the method of its determination. The urinary level of NGAL positively correlated with the degree of tubular atrophy. The GFR value determined from serum CysC and creatinine levels more precisely reflected the degree of glomerulosclerosis/CONCLUSION: The tubulointerstitial compartment in primary glomerulopathies should be determined not only by morphological changes, but also by tubular function parameters by estimating the urinary excretion of biomarkers. The urinary content of CysC reflects tubular epithelial dysfunction whereas that of NGAL also characterizes tubular atrophy. To estimate the degree of glomerulosclerosis, it is more preferable to use the GFR calculated from the blood concentrations of CysC and creatinine, by keeping in mind clinical findings (using Chronic Kidney Disease Epidemiology Collaboration formula, 2012).
Terapevticheskii arkhiv. 2013;85(6):10-16
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New markers of cardio-renal links in chronic kidney disease

Milovanova L.I., Milovanov I.S., Kozlovskaia L.V., Mukhin N.A.


AIM: To study the clinical significance of determining the serum concentration of phosphorus and calcium metabolism regulators - the morphogenetic proteins FGF-23 and Klotho in patients with different stages of chronic kidney disease (CKD)/MATERIAL AND METHODS: The serum levels of FGF-23 (a human FGF-23 ELISA kit with full-length anti-FGF-23 monoclonal antibodies) and Klotho (a human alpha-K1 ELISA with anti-Klotno antibodies) were investigated in 70 patients with Stages I-VD CKD (41 patients with chronic glomerulonephritis, including 10 with nephritis in systemic diseases, 22 with tubulointerstitial nephritis, and 7 with hypertensive nephroslerosis). The morphogenetic proteins were studied by the specialists of the LiTECH diagnostic laboratory according to the standard protocol/RESULTS: As CKD progressed from Stage I to VD, there were increased FGF-23 concentrations and decreased Klotho levels in the examinees' serum. The highest FGF-23 level and low Klotho concentration were noted in the group of patients on regular hemodialysis treatment (Stage VD). There was a strong inverse correlation between Klotho levels and proteinuria, C-reactive protein, and protein-energy insufficiency, which suggests that these factors influence the serum level of Klotho. The serum levels of FGF-23 and intact parathyroid hormone correlated with these values to a lesser degree. Analysis of the content of the morphogenetic proteins in patients with anemia versus those with CKD of the same stages and target hemoglobin values revealed low Klotho concentrations and high FGF-23 levels (r=0.602; p<0.01 and r=-0.450; p<0.01, respectively). Forty-nine hypertensive patients showed a direct strong relationship between elevated serum FGF-23 levels and an inverse strong one between the reduced serum Klotho levels and the increased posterior left ventricular wall (r=0.552; p<0.01 and r=-0,587; p<0.01, respectively). The same strong association was found between the higher serum level of FGF-23 (r=0.492; p<0.01) and the concentration of Klotho (r=-0.537; p<0.01) and peripheral vascular resistance index (as evidenced by Doppler ultrasound study)/CONCLUSION: Along with the active participation of the morphogenetic proteins (FGF-23 and Klotho) in mineral metabolism and its disturbances in CKD, their role is apparent in the development of cardiovascular events (in particular, through the involvement in the processes of vascular calcification and cardiac remodeling), anemia (through the possible effect on iron metabolism, enhanced ischemia of renal interstitial tissue with impaired Klotho production), and protein-energy insufficiency (through the participation in the processes of inflammation, oxidative stress, and protein synthesis).
Terapevticheskii arkhiv. 2013;85(6):17-24
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Specific features of cognitive impairments in patients with predialysis chronic kidney disease

Rogova I.V., Fomin V.V., Damulin I.V., Shashkova E.V.


AIM: To study the specific features of cognitive impairments (CI) in patients with predialysis chronic kidney disease (CKD)/MATERIAL AND METHODS: Examinations were made in 51 patients aged 52±10 years with CKD, including 20 patients with Stages I-II CKD (glomerular filtration rate (GFR) ≥60 ml/min/1.73 m2; signs of kidney lesion), 20 with Stage III (GFR 60-30 ml/min/1.73 m2), and 11 with Stage IV (GFR 30-15 ml/min/1.73 m2). GFR was estimated using the Modification of Diet in Renal Disease (DMRD) formula. The authors made a questionnaire survey to identify day-to-day activity limitations and depressions and performed neuropsychological tests using the mini-mental state examination (MMSE), a frontal assessment battery (FAB) for frontal lobe dysfunction, a short-term and delayed memory test (Luria's 10 words test), and a regulatory function assessment test (RFAT). Magnetic resonance imaging (MRI) was carried out to clarify the etiology of CI/RESULTS: CI was detected more frequently in the patients with chronic renal failure (CRF) (Stages III-IV CKD) than in those without CRF (Stages I-II CKD) (in 90.3 and 35%, respectively (p<0.001)). CI was statistically significantly more frequently found using MMSE (p<0.001), FAB (p=0.001), and RFAT (p<0.001). There was a statistically significant rise in the magnitude of CI with the higher stage of CKD, as shown by MMSE, FAB, and RFAT, other than the short-term and delayed memory test. Brain MRI in the patients with CI revealed focal changes in 9 (30%) patients, leukoaraiosis in 7 (23.3%), lateral cerebral ventricular dilatation in 15 (50%), and markedly dilated hemispheric sulci in 3 (10%)/CONCLUSION: The higher stage of CKD is associated with the increased incidence and magnitude of CI, as evidenced by MMSE, and with those of anterior brain dysfunctions. The comparisons of clinical and MRI findings suggest that cerebrovascular disorders underlie CI in CKD.
Terapevticheskii arkhiv. 2013;85(6):25-30
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Significance of the factors of hypoxia and endothelial dysfunction in kidney injury in the presence of obesity

Galliamov M.G., Saginova E.A., Severova M.M., Samokhodskaia L.M., Krasnova T.N., Sholomova V.I., Sorokin I.D., Mukhin N.A.


AIM: To define the clinical significance of asymmetric dimethylarginine (ADMA) and that of methylenetetrahydrofolate reductase (MTHFR) gene polymorphism as factors of endothelial dysfunction (ED) in the development of early kidney injury in obese patients/MATERIAL AND METHODS: The investigation included 86 patients (64 men and 22 women aged 44±11 years) with abdominal obesity. Along with physical examination, the authors determined albuminuria, calculated glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease (MDRD) formula, estimated insulin resistance markers (fasting plasma insulin and C-peptide concentrations and homeostatic model assessment (HOMA) index), as well as serum ADMA levels by enzyme immunoassay in all the patients. C677T polymorphism in the MTHFR gene was studied by allele-specific polymerase chain reaction and restriction fragment length polymorphism analysis. Kidney injury (chronic kidney disease (CKD)) was diagnosed using the Kidney Disease Outcomes Quality Initiative (KDOQI) criteria. Early vascular remodeling was determined from the increased intima-media thickness (IMT) of the common carotid artery (CCA)/RESULTS: CKD was diagnosed in 27 (31%) patients. The latter, unlike the patients with CKD, were observed to have more pronounced obesity (body mass index (BMI) 36.8±8.0 and 32.0±4.7 kg/m2, respectively (p<0.001)), waist circumference (119±18 and 109±11 cm (p=0.002)), higher levels of C-peptide (1348±363 and 1028±363 pmol/l; p<0.001), insulin (16.9±7.3 and 11.7±5.5 µU/ml; p<0.001), and НОМА index (4.3±1.7 and 2.9±1.5; p<0.001). In the patients with Stage IIIa CKD, ADMA concentrations (0.77±0.19 µmol/l) was higher than in those with Stages I (0.58±0.11 µmol/l; р=0.048) and II (0.61±0.13 µmol/l; р=0.071). An association between ADMA concentrations, CCA IMT, and estimated GFR was revealed in the patients with CKD. The predictors of an estimated GFR reduction in obesity were elevated serum concentrations of ADMA, uric acid, insulin, and HOMA index. The combination of obstructive sleep apnea syndrome and metabolic syndrome increased the risk of CKD by 2.1-fold (95% confidence interval, 1.06-3.14). Evaluation of the impact of MTHFR gene polymorphism on kidney injury in obesity disclosed that the patients with homozygous carriage of the abnormal T allele of the MTHFR gene had a higher risk for Stages I-IIIa CKD (2.60 with 95% confidence interval, 1.32-3.88), more marked obesity and hyperinsulinemia, and increased serum ADMA concentrations/CONCLUSION: Insulin resistance and ED hold a central position in the pathogenesis of CKD in obese patients. The mechanisms of the atherosclerotic vascular remodeling associated with elevated serum ADMA concentrations are of paramount importance in the progression of early-stage CKD. The homozygous carriage of the abnormal T allele of the MTHFR gene increases the risk of Stages I-IIIa by more than twice.
Terapevticheskii arkhiv. 2013;85(6):31-37
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Test strip evaluation of albuminuria for the early detection of chronic kidney disease in persons at different risks (the experience of the Health Centers of the Moscow Region)

Nagaĭtseva S.S., Shaliagin I.D., Shvetsov M.I., Piagaĭ N.L., Ivanova E.S., Shilov E.M.


AIM: To evaluate albuminuria (AU) in the Moscow Region's dwellers visiting the health centers and to clarify its association with the proven and discussed risk factors (RF) of chronic kidney disease (CKD)/MATERIAL AND METHODS: A total of 1623 patients (390 (24%) men and 1233 (76%) women; mean age 46±16 years) were examined. Urinalysis using test strips was performed in all the examinees. AU was estimated by the following scale: normal AU (NAU) (<10 mg/l), an initial increase (11-30 mg/l), a pronounced increase (31-300 mg/ml), very high AU (>300 mg/ml). A questionnaire covering gender, age, patients' anthropometric data, comorbidities, healthy lifestyle adherence, and smoking was designed to assess possible RFs for CKD. Body mass index (BMI) was calculated. Medical history examination showed metabolic disturbances and cardiovascular diseases/RESULTS: The detection rate of NAU was 18%; the initial and pronounced increases were found in 40 and 41% of the examinees, respectively; the very high AU was in 1%. The first questionnaire items associated with AU >30 mg/ml were complaints of edema, sternal pain, poor appetite, meat aversion, and constant thirst. The detection rate of AU >30 mg/l in hypertensive persons was 51%. If the patients had diabetes mellitus or a history of increased blood glucose episodes, the detection rate of AU >30 mg/l amounted to as much as 65.5%. Estimation of overweight and obesity indicated that AU of >30 mg/l was found in 44 and 49% of cases, respectively (p<0.001). Analgesic abusers, long-term smokers, and sedentary people were statistically significantly more frequently found to have AU of >30 mg/l/CONCLUSION: The pronounced and very high AU was noted in more than 40% of those who had visited the health centers. A questionnaire survey makes it possible to reveal a variety of AU increase-associated factors that primarily reflect metabolic disturbances and cardiovascular diseases and to identify a risk group in order to study AU first. Particular emphasis should be placed on the examinees' lifestyle. Healthy lifestyle non-adherence is closely correlated with increased AU and may be regarded as a RF for CKD.
Terapevticheskii arkhiv. 2013;85(6):38-43
pages 38-43 views

Diastolic dysfunction in different types of left ventricular hypertrophy in patients with end- stage renal failure: Impact of long-term erythropoietin therapy

Dzgoeva F.U., Gatagonova T.M., Kadzaeva Z.K., Khamitsaeva O.V., Kochisova Z.K., Dzutseva A.T., Bazaeva B.G., Bestaeva T.L.


AIM: To study the specific features of diastolic dysfunction (DD) in different types of left ventricular (LV) hypertrophy (LVH) in patients with end-stage renal failure (ESRF) and to estimate the cardioprotective effect of erythropoietin/MATERIAL AND METHODS: 107 patients (57 women and 50 men) aged 22 to 63 years with ESRF were examined. The follow-up was 18 months. LV ejection fraction, peak early diastolic filling rate, peak late diastolic filling rate, their ratio, LV isovolumic relaxation time, LV end-diastolic diameter, LV end-diastolic volume, LV end-diastolic diameter index (EDDI), LV posterior wall and ventricular septal thickness, and LV mass index were determined. J. Gottdiener's classification based on the calculation of EDDI and LV relative wall thickness was used to estimate LV geometry. Erythropoietin was given to patients with the baseline level of hemoglobin (Hb) <110 g/l or hematocrit (Ht) <33%; and iron (III) hydroxide sucrose complex was used to those with ferritin <100 µg/l or transferrin saturation <20%. The target level of blood pressure was 130/80 mm Hg; Hb was less than 110 g/l for women and 120 g/l for men; Ht, >33%/RESULTS: The patients with ESRF were found to have different types of DD and LVH, the severity of which correlated with the magnitude of renal anemia and arterial hypertension (AH). Adequate correction of anemia and AH promoted the transition of more to less severe DD and LVH and in a number of cases the recovery of LV structure and function/CONCLUSION: ESRF is characterized by different types of DD, which are pathogenetically closely related to different types of LVH. Adequate correction of renal anemia and AH may cause a significant reduction and, in a number of cases, alleviate VLH, and normalize LV systolic and diastolic functional values.
Terapevticheskii arkhiv. 2013;85(6):44-50
pages 44-50 views

Cardiorenal links in systemic amyloidosis

Rameev V.V., Kozlovskaia L.V., Zhdanova E.A., Gudkova K.V.


The paper gives current general data on the structure of amyloid fibril and the principles in the classification of amyloidosis, information on the clinical course of cardiac and renal involvements in systemic AL and AA amyloidosis, and that on diagnostic and prognostic criteria and the specific features of cardiorenal links. The authors draw the conclusion that the identification of acute and chronic cardiorenal links is of practical value for systemic amyloidosis. Cardiorenal and renocardiac syndromes are not always differentiated clearly in the systemacy of involvement.
Terapevticheskii arkhiv. 2013;85(6):51-59
pages 51-59 views

Time course of changes in iron metabolic and oxidative-antioxidative system parameters in patients with acute myeloid leukemia

Gritsaev S.V., Shikhbabaeva D.I., Rybakova L.P., Sergeev A.N., Kapustin S.I., Abdulkadyrov K.M.


AIM: To study an association between iron metabolism, free radical oxidation (FRO), and antioxidative system (AOS) in patients with acute myeloid leukemia (AML) during intensive chemotherapy/MATERIAL AND METHODS: AML patients (n=14) with a median age of 46 years received 7+3 courses (n=3) containing cytarabine ≥1 g/m2/introduction (n=8) and myeloablative conditioning regimen before hematopoietic stem cell transplantation (n=3). The concentrations of iron, ferritin, transferrin saturation (TFS), and malonic dialdehyde and the activity of superoxide dismutase (SOD), ceruloplasmin (CP), and catalase were investigated in their sera. The investigations were performed before and after chemotherapy and during hemopoietic recovery and rehospitalization/RESULTS: After therapy termination, there was a significant increase in TFS (6.8% vs 41.9%; p<0.0001), which gave way to its reduction during hemopoietic recovery (89.5% vs 96.8%; p=0.003). The activity of antioxidant enzymes was found to be altered at a time. That of catalase was enhanced throughout cytopenia (3.8 and 3.3 vs 5.7 conventional units (CU)/ml; р=0.028 and р=0.011). The lower activity of SOD (21.0 vs 41.0 CU/ml; p=0.018) and the higher activity of CP (1.1 vs 0.8 g/l) were ascertained when leukocyte count increased up to ≥1·109/l/CONCLUSION: After intensive cytostatic therapy, there was a phasic TFS increase accompanied by the compensatory change in AOS activity, which is aimed at neutralizing FRO products.
Terapevticheskii arkhiv. 2013;85(6):60-65
pages 60-65 views

General molecular and cellular mechanisms for renal and cardiac remodeling in chronic kidney disease: a target for nephrocardioprotection

Kozlovskaia L.V., Bobkova I.N., Nanchikeeva M.L., Chebotareva N.V., Li O.A., Plieva O.K.


The lecture considers a number of molecular and cellular mechanisms underlying the structural and functional rearrangement and development of renal and cardiac fibrosis in chronic kidney disease (CKD). It details the key component of disadaptative organ remodeling (the formation of myofibroblasts via epithelial-mesenchymal and endothelial-mesenchymal transdifferentiation) and the role of leading angiofibrogenic mediators (angiotensin II, transforming growth factor-Β type 1, a plasminogen activator inhibitor type 1, etc.) in the regulation of these processes. Investigation of the molecular and cellular bases of organ fibrosis, including the factors of dysregulated activation, differentiation and survival of microfibroblasts, makes it possible to specify the mechanisms of action of traditional nephro- and cardioprotective agents, to offer a possibility for a goal-oriented (target) effect on individual fibrogenic components, and to expand the arsenal of medications suppressing renal and cardiac remodeling.
Terapevticheskii arkhiv. 2013;85(6):66-72
pages 66-72 views

Efficiency and safety of lipid-lowering therapy for chronic kidney disease

Kolina I.B., Stavrovskaia E.V.


The paper considers the problem of lipid-lowering therapy for chronic kidney disease, by using different groups of drugs, the expediency, efficiency, and safety of the therapy at different disease stages, including end-stage renal failure, and replacement treatments.
Terapevticheskii arkhiv. 2013;85(6):73-77
pages 73-77 views

Hepatitis C virus-related cryoglobulinemic vasculitis with renal involvement: current possibilities of treatment

Gordovskaia N.B., Kozlovskaia L.V., Milovanova S.I., Ignatova T.M., Korotchaeva I.V.


The paper considers the specific features of renal involvement developing in chronic infection caused by hepatitis C virus (HCV) and the current possibilities of treatment. It details the clinical and morphological manifestations of HCV-related cryoglobulinemic glomerulonephritis, and criteria for its diagnosis and prognosis. The author discuss new approaches to treating (severe cryoglobulinemic vasculitis with renal involvement in particular) - antiviral therapy (pegylated interferon-α/ribavirin) in combination with biological agents (anti-CD monoclonal antibodies, such as rituximab) to achieve clinical, virological, immunological remissions and a response at a molecular level - to eliminate oligo- and monoclonal B lymphocyte proliferation.
Terapevticheskii arkhiv. 2013;85(6):78-84
pages 78-84 views

Factors for the development and progression of cardiorenal complications in women

Chicherina E.N., Padyganova A.V.


The paper describes the state-of-the-art of risk factors for cardiorenal complications in women. It is shown that while managing women of reproductive, menopausal, and menopausal ages, great importance should be attached to the assessment of all risk factors for the development and progression of chronic renal and cardiovascular diseases. Investigations of the specific features of these factors in women, their enrollment along with men in large-scale randomized trials will serve as a basis for developing more effective programs for the prevention and therapy for cardiovascular and renal diseases and hence will be able to reduce disability rates, to increase quality of life, and to prolong its span.
Terapevticheskii arkhiv. 2013;85(6):85-89
pages 85-89 views

Contrast-induced nephropathy

Mironova O.I.


The increasing number of invasive procedures done with contrast agents makes the prevention of their induced nephropathy more urgent. At present, different methods are being developed to prevent contrast-induced nephropathy (CIN) with antioxidants, intrarenal vasodilators, hydration therapy, by accurately determining the amount of excreted fluid obtained from a urinary catheter and less toxic iodine-containing contrast agents are being put into practice. Unfortunately, the current guidelines for the prevention of CIN are inadequately followed in both Russia and foreign countries. This review covers the main components of the pathogenesis and risk factors of this pathology and its possible preventive measures.
Terapevticheskii arkhiv. 2013;85(6):90-95
pages 90-95 views

Phosphate binders in chronic kidney disease: The positions of sevelamer

Fomin V.V., Shilov E.M., Svistunov A.A., Milovanov I.S.


The paper shows the role of phosphate binders in the correction of phosphorus and calcium metabolic disturbances in chronic kidney disease. The results of clinical trials demonstrating the efficacy and safety of sevelamer are discussed.
Terapevticheskii arkhiv. 2013;85(6):96-99
pages 96-99 views

Hyperuricemia and the problem of chronic kidney disease

Shcherbak A.V., Kozlovskaia L.V., Bobkova I.N., Balkarov I.M., Lebedeva M.V., Stakhova T.I.


The paper reviews the literature on the role of hyperuricemia as a risk factor for chronic kidney disease and as one of the factors for the progression of existing kidney disease. It gives epidemiological information on a relationship between hyperuricemia and kidney lesion. The mechanisms for the damaging action of uric acid on kidney tissue, which have experimentally and clinically observed, are considered. The main areas of hyperuricemia correction and its place in the total nephroprotection strategy are defined.
Terapevticheskii arkhiv. 2013;85(6):100-104
pages 100-104 views

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