Vol 82, No 6 (2010)


Evidence-based medicine in nephrology

Mukhin N.A.


The paper describes the specific features and perspective for introducing the principles of evidence-based medicine into Russian clinical nephrology
Terapevticheskii arkhiv. 2010;82(6):5-8
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Diabetes mellitus: renal osmoregulating function

Natochin Y.V., Shestakova M.V., Kuznetsova A.A., Klefortova I.I., Trubitsyna N.P., Dedov I.I.


Aim. To evaluate the kidney status from osmotic urine concentration in different stages of diabetes mellitus (DM) to define whether not only glomeruli and proximal tubules, but also renal medullary substance structures are involved into the pathological process, as well as their reaction to endogenous vasopressin production. Subjects and methods. Forty patients with a 1-to-28-year history of DM, including 18 with diabetic nephropathy, 10 with chronic renal failure, and 22 without diabetic nephropathy, were examined. Urine and blood osmolality were determined and renal osmoregulating function was estimated. Results. Decreased glomerular filtration rate was found in relation to the duration of DM. The osmolality of nocturnal urine samples tended to diminish during short-term deprivation depending on the duration of DM. Increased diuresis in DM was shown to correlate with the higher reabsorption of osmotically free water. Conclusion. Diminished renal concentrating capacity in DM appears to depend on evolving renal failure rather than vasopressin resistance. The application of a new approach, by calculating the clearance of sodium-free water, suggests that its increased reabsorption favors normalization of serum osmolality in hyperglycemia.
Terapevticheskii arkhiv. 2010;82(6):9-14
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Renal artery stenosis in patients with type 2 diabetes mellitus: clinical signs, diagnosis, prognostic value

Shamkhalova M.S., Klefortova I.I., Shestakova M.V., Remizov O.V., Bukhman A.I., Alpenidze V.A., Tugeeva E.F., Sharia M.A., Ustyuzhanin D.V., Buziashvili Y.I., Dedov I.I.


Aim. To define the prevalence, clinical features, risk factors, and prognostic value of atherosclerotic renal artery stenosis (RAS) in patients with type 2 diabetes mellitus (T2DM). Subects and methods. One hundred and fifty-seven T2DM patients (63 males and 94 females) aged over 50 years were examined. Screening for RAS was carried out by duplex ultrasound scanning (DUSS); the diagnosis was verified by multispiral computed tomography and magnetic resonance imaging. Moreover, the detection rate of RAS was analyzed from the selective angiographic readings of 30 patients with T2DM and 26 coronary angiography patients without DM who had undergone coronary angiography (CA). Results. In the total group of T2DM patients, the RAS detection rate was 36.9%, as evidenced by DUSS and 43.3% by selective renal artery angiography in the patients who had undergone CA. The factors associated with the development of RAS were smoking (relative risk (RR) = 3.3; p < 0.001); atherosclerosis of coronary (RR = 4.28; p < 0.001) and peripheral (RR = 3.38; p < 0.02) arteries, isolated systolic hypertension (RR = 3.9; p < 0.01), and anemia (RR = 6.4; p < 0.001). In patients with T2DM, RAS was one of the important factors of progressive renal and cardiac diseases and increased mortality determined by the combined end point: death, emergency hospitalization for heart failure, myocardial infarction, double creatinine, and end-stage renal failure (RR = 6.28; p < 0.001). Conclusion. The optimization of prognosis in T2DM patients with RAS requires its timely clinical identification in combination with other types of renal lesion, aggressive correction of the mechanisms of the progressive process, and development of medical and endovascular therapies.
Terapevticheskii arkhiv. 2010;82(6):15-21
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Contribution of obesity to renal lesion in patients with type 2 diabetes mellitus

Kutyrina I.M., Savelyeva S.A., Kryachkova A.A., Shestakova M.V.


Aim. To study of the contribution of obesity to renal lesion in patients with type 2 diabetes mellitus (T2DM). Subects and methods. One hundred and fifty-four patients (62 males and 92 females) with T2DM (mean age 58±8 years) were examined. The study excluded patients with significant stages of diabetic nephropathy (glomerular filtration rate (GFR) < 60 ml/min; proteinuria more than 2 g/day). Anthropometric indicators, such as body mass index (BMI), were estimated. The serum levels of creatinine, uric acid (UA), lipid composition, and the adipose tissue hormones leptin and adiponectin were measured. Renal lesion was evaluated from GFR and urine albumin excretion level. Groups of patients with a less and more than 5-year history and subgroups of a MBI of less and more than 30 kg/m2 were identified. Results. In patients with a more than 5-year history of T2DM, the detection rate of microalbuminuria and proteinuria increased as obesity progressed. This regularity was not found in those with a less than 5-year history of T2DM. Diabetic patients with a BMI of l 30 kg/m2 were more frequently found to have intrarenal hemodynamic disorders (hyperfiltration) elevated blood pressure, increased UA, and decreased high-density lipoproteins, as compared with those with a BMI of < 30 kg/m2. With a higher BMI, leptin levels increased; its highest values were found in a group of patients with proteinuria. Hypoadiponectinemia was detected in most patients with T2DM. Adiponectin was decreased in early-stage nephropathy; its increase was further increased. Conclusion. There was a greater prevalence of renal lesion in obese (BMI l 30 kg/m2) patients with a more than 5-year history of T2DM than in non-obese patients. Obesity has an impact on renal function due to its hemodynamic, metabolic, and hormonal effects.
Terapevticheskii arkhiv. 2010;82(6):21-25
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Phosphorus and calcium metabolism and the cardiovascular system in patients with early-stage chronic renal disease

Smirnov A.V., Volkov M.M., Dobronravov V.A., Rafrafi H.


Aim. To define the impact of phosphorus and calcium metabolic disturbances in patients with early-stage chronic renal disease (CRD) on the cardiovascular system. Subects and methods. The levels of phosphate (P), calcium, parathyroid hormone (PTH), 25(OH) vitamin D and 1,25(OH)2 vitamin D, serum lipidogram, carotid artery intima-media thickness (IMT), and X-ray degree of abdominal artery calcification (AAC) were determined and echocardiography, electrocardiography and blood pressure monitoring were made in 465 patients with Stages I-V CRD who did not receive renal replacement therapy (of them, 73.5% of the patients had early (I to III) stages). Results. Blood 1,25(OH)2D was related inversely to left ventricular (LV) posterior wall thickness, blood pressure (BP), triglycerides, and the degree of AAC and correlated directly to the severity of LV diastolic dysfunction and inversely to IMT, the presence of coronary heart disease and heart failure (HF). ACC, LV hypertrophy, and arterial hypertension (AH) were more significant in patients with higher serum levels PTH and P. Conclusion. In patients with early-stage CRD, phosphorus and calcium metabolic disturbances promote the development of AH, vascular and cardiac valvular calcification, myocardial hypertrophy, and HF.
Terapevticheskii arkhiv. 2010;82(6):25-28
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New capacities of the diagnosis and monitoring of the course of AL-amyloidosis

Rameyev V.V., Kozlovskaya L.V., Kogarko I.N., Kogarko B.S.


Aim: to define the clinical value of various concentrations of immunoglobulin light chains (ILCs) in patients with AL amyloidosis. Subjects and methods. The content of free ILCs was studied by a nephelometric technique after their fixation in the blood of 31 patients with AL amyloidosis; monoclonal gammapathy was associated with the hyperproduction of monoclonal ILCs of λ- and κ-type in 14 and 17 patients, respectively. The obtained value was compared with the data of physical examination and laboratory and instrumental studies indicating lesions to target organs and with the course of the disease. Results. In patients with the good course of AL amyloidosis, the average level of free ILCs was 1.8 (range 0.77-3) times greater than the normal values (the range of ILCs of λ and k-type was 20.24 to 67.4 and 20.14 to 81.38 mg/l, respectively); in those with the poor course, the excess of ILCs was 5.8 (range 3.7-13) times higher than the normal values (the range of ILCs of λ and κ-type was 54.32 to 286.7 and 117.06 to 2606.0 mg/l, respectively). The optimal range of diagnostic sensitivity (75%) and specificity (75%) in the estimation of prognosis was determined at the ILC levels that were three times greater (64.5 mg/l for κ-ILCs and 80 mg/l for λ-ILCs). Among the patients with a blood free ILC level of m 3 times more than the normal values, the good and poor courses of AL amyloidosis were noted in 13 and 4 cases, respectively. Conclusion. The determination of serum ILC concentration by the Freelite method may be used to diagnose AL amyloidosis and to specify the presence of appropriate organ dysfunction; this study over time makes it possible to monitor the course of the disease and to estimate its response to therapy.
Terapevticheskii arkhiv. 2010;82(6):29-32
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Impact of lipid free radical oxidation on renal functional status in patients with alcohol withdrawal syndrome

Sibireva O.F., Khitrinskaya E.Y., Kalyuzhin V.V., Kalyuzhina E.V.


Aim: to study the activity of free radical processes in patients with alcoholism and renal lesion (A+RL) and the implication of depressed efficiency of the regulatory mechanisms limiting the accumulation of highly toxic products of lipid free radical oxidation (LFRO) in the development of secondary nephropathy. Subjects and methods. Fifty-seven patients (mean age 31±2.8 years) with a 5-10 history of alcoholism who had been admitted to hospital for uncomplicated alcohol withdrawal syndrome were examined. Alcoholic renal lesion was detected in 17 (29.8%) patients. A control group comprised 20 healthy individuals. The activity of LFRO and antioxidative defense (AOD) was studied. Results. In patients with alcoholism, the study indicators reflecting the activity of LFRO statistically significantly exceeded those in the group of healthy individuals. These patients were found to have also suppressed mechanisms of first- and second-line AOD in the A+RL group. Conclusion. LFRO activation developing in the presence of suppressed AOD seems to contribute to the development of secondary nephropathy in patients with alcoholism.
Terapevticheskii arkhiv. 2010;82(6):32-34
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Association of obstructive sleep apnea syndrome with the signs of non-alcoholic fatty liver disease and calculated glomerular filtration rate in metabolic syndrome

Severova M.M., Fomin V.V., Lebedeva M.V., Sorokin Y.D., Saginova E.A., Minakova E.G., Gallyamov M.G., Mukhin N.A.


Aim: to assess a relationship between obstructive sleep apnea syndrome (OSAS) and the signs of non-alcoholic fatty liver disease (NAFLD) in patients with metabolic syndrome (MS). Material and methods. Serum total cholesterol, triglycerides, high-density lipoprotein cholesterol concentrations, fasting blood glucose, ASAT, ALAT, γ-glutamyl transpeptidase (γ-GT), alkaline phosphatase (AP), total bilirubin, uricemia, and creatininemia were determined in 32 patients (mean age 47.6±9.7 years) with MS. The authors also measured fasting blood insulin levels with the further calculation of the homeostatic model assessment (HOMA) index, as well as plasma C-peptide concentration. Abdominal ultrasound study and OSAS diagnosis by the routine scheme were made in all the patients. Results. OSAS was associated with the significant increase in the body mass index (40.5±9.4 and 31.9±4.6 kg/m2; p = 0.001), waist circumference (130.0±22.5 and 107.5±11.0 cm; p = 0.001), and C-peptide levels (1611.0±614.0 pmol/l; p = 0.019), and the serum activities of γ-GT (117.0±57.0 and 42.0±14.0 IU/ml; p = 0.05) and AP (80.0±53.0 and 74.0±48.0 UI/ml; p = 0.05). The patients with OSAS had also a significantly lower glomerular filtration rate (GFR) estimated using the modification of diet in renal disease (MDRD) formula (66.0±19.0 and 82.0±21.0 ml/min/1.73 m2; p < 0.05). Conclusion. The presence of OSAS in patients with MS is associated with the increase in laboratory signs of NAFLD and the decrease in the GFR calculated by the MDRD formula.
Terapevticheskii arkhiv. 2010;82(6):35-39
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Effect of TT genotype of the vitamin D receptor gene on bone mineral density in dialysis patients

Shishkin A.N., Mazurenko S.O., Aseyev M.V.


Aim: to evaluate the effect of TaqI genotypes of vitamin D receptor (VDR) gene polymorphism on bone mineral density (BMD) and the risk for secondary osteoporosis (OP) in patients on programmed hemodialysis. Subjects and methods. Eighty-two patients treated with long-term hemodialysis were examined. Along with physical examination, osteodensitometry was carried out and VDR gene polymorphism was studied in all the patients. Results. OP in the study skeletal parts was more common in the TT-genotype group. The serum concentration of intact parathyroid hormone and the activity of alkaline phosphatase were also higher in the TT-genotype group. However, the differences were statistically insignificant between the TT-, Tt-, and tt- genotype groups. BMD was lowest in each study skeletal parts in the TT-genotype group and this difference was statistically significant in the proximal femur, which was estimated by the Z index (p = 0.02). Conclusion. The results of the present study confirm the hypothesis that the VRD gene is a genetic determinant of bone metabolism in patients with chronic renal disease who receive long-term hemodialysis.
Terapevticheskii arkhiv. 2010;82(6):39-43
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Antihypertensive therapy optimization and endothelial function in patients with gout and chronic urate tubulointerstitial nephritis

Lebedeva M.V., Stakhova T.Y., Zaitseva L.I., Selivanova O.Y., Severova M.M.


Aim: to characterize the markers of endothelial dysfunction and the effect of antihypertensive drugs on them in patients with chronic urate tubulointestinal nephritis (UTIN) and articular gout. Subjects and methods. The study enrolled 81 patients aged 39 to 59 years with gout and urate nephropathy. All the patients were diagnosed as having grade 1-2 arterial hypertension. A lower glomerular filtration rate (GFR) was noted in 49.9%; microalbuminuria (MAU) and elevated serum endothelin-1 (ET-1) levels were recorded in all the patients. Combination antihypertensive therapy based on the use of angiotensin-converting enzyme (ACE) inhibitors and/or an angiotensin II receptor blocker (ARB) in combination with calcium channel blockers was performed during 12 months. The time course of changes in blood pressure, the parameters of target organ lesion, and the markers of endothelial dysfunction were monitored. Results. Before the study, all the examinees were found to have MAU and increased serum ET-1, which are regarded simultaneously as signs of renal lesion and as markers of endothelial function. A combination of an ACE inhibitor or an ARB could diminish albuminuria and reduce ET-1 concentrations, lower systolic and diastolic blood pressure significantly, and increase GFR. Conclusion. The patients with articular gout and chronic UTIN are observed to have signs of endothelial dysfunction eliminated by combination antihypertensive therapy.
Terapevticheskii arkhiv. 2010;82(6):43-46
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Computer morphometry of lymphocytes in the diagnosis of chronic transplant nephropathy

Vatazin A.V., Valov A.L., Vasilenko I.A., Shcherbakova E.O., Metelin V.B.


Aim: to assess the role of immunological mechanisms in the development and progression of chronic transplant nephropathy (CTN) and the prognostic value of rapid computer morphometry of lymphocytes in predicting the risk of renal allograft rejection. Subjects and methods. Thirty-seven renal graft recipients (29 males and 8 females; mean age 35.9±2.2 years; mean time after renal allografting 19.9±2.7 months). Twenty-three patients had satisfactory renal graft function; 14 patients were diagnosed as having CTN. A control group included 30 apparently healthy individuals. Along with physical examination, vital computer phase morphometry (CPM) of peripheral blood immunocompetent cells was carried out in all the patients. Results. Small and average cells were predominant in the T and B lymphocyte populations. In CTN, there were increases in diameter, perimeter, and area and decreases in the phase height and volume of B lymphocytes, which is indicative of their activation. There was a predominance of average B lymphocytes in CTN. Conclusion. Vital CPM of peripheral blood immunocompetent cells may be used for the early diagnosis and prediction of CTN development.
Terapevticheskii arkhiv. 2010;82(6):46-49
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Autonomic imbalance in patients with metabolic syndrome: role in the development of hyperfiltration, an early marker of renal lesion

Gornostayeva E.Y., Novikova M.S., Beloborodova A.V., Akarachkova E.S., Shilov E.M., Shvarkov S.B.


Aim: to study the impact of the autonomic nervous system on the development of renal lesion in patients with metabolic syndrome (MS). Subjects and methods. One hundred and nine patients (45 females and 54 males) aged 29 to 72 years who had MS were examined. Glomerular filtration rate (GFR) was estimated using the Cockroft-Gault formula, by correcting the obtained result on the body surface. According to the level of GFR, the patients were divided into 3 groups: 1) 30 MS patients with hyperfiltration (GFR > 110 ml/min/1.73 m2); 2) 55 patients with normal GFR (110-60 ml/min/1.73 m2); 3) 24 patients with lower GFR ( < 60 ml/min/1.73 m2). All the patients underwent physical examination; autonomic tonus was examined by 24-hour cardiac rhythm variability (CRV) study using the Holter monitoring system, by applying the time analysis. The presence of autonomic dystonia syndrome (ADS) and its degree were determined by a questionnaire to detect autonomic nervous system (ANS) dysfunction. Results. Each of 3 groups was found to have signs of autonomic imbalance with a preponderance of sympathetic activity with decreased parasympathetic activity, these impairments being more pronounced in Group 1. The obtained regulation reflects the entire decrease in autonomic actions on the cardiovascular system in patients with MS and suggests the maximum hyperactivation of the sympathetic ANS in early-stage renal lesion - hyperfiltration. Conclusion. When the first signs of renal lesion (hyperfiltration) occur in patients with MS, there is significant hypersympaticotonia that promotes the progression of target organs, including the kidneys.
Terapevticheskii arkhiv. 2010;82(6):49-53
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Severe Wegener's granulomatosis successfully treated with rituximab

Semenkova E.N., Krivosheyev O.G., Novikov P.I., Osipenko V.I., Nosova N.R., Parfenova S.A., Nikiforova N.V., Borodin O.O.


The paper discusses the problems of the diagnosis and treatment of Wegener's granulomatosis, the most common anti-neutrophil cytoplasmic antibody-associated systemic vasculitis. It describes a clinical case in which the administration of rituximab could achieve remission of severe Wegener's granulomatosis in a young man having numerous adverse reactions associated with the long-term use of high- and average-dose glucocorticoids and nonselective immunosuppressive agents. A place of rituximab in current drug therapy for Wegener's granulomatosis is shown.
Terapevticheskii arkhiv. 2010;82(6):53-55
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Severe disseminated constrictive polyserositis in a patient with rheumatoid arthritis

Blagova O.V., Tsaregorodtsev D.A., Nedostup A.V., Mayevskaya I.V., Petukhova N.V., Troitskaya M.P., Shadania Y.R.


Constrictive polyserositis (pleuritis, pericarditis) is a syndrome within the underlying disease (tuberculosis, periodic disease, rheumatoid arthritis, systemic lupus erythematosus, asbestos, silicosis, uremia, some genetic diseases), a complication due to chest surgery or radiation or drug therapy, is occasionally idiopathic (fibrosing mediastinitis). There are frequently great difficulties in making its nosological diagnosis. The paper describes a patient in whom the onset of disease was exudative pleurisy with the signs of constriction, arthralgias; pleural punctures provided serous exudates with 80% lymphocytes. A year later there was ascitis and shin and foot edemas, which concurrent with hepatomegaly and cholestasis was regarded as cryptogenic liver cirrhosis. The signs of constrictive pericarditis were further revealed. The disease was complicated by the development of pulmonary artery thromboembolism (PATE) (which required the use of warfarin) and hemorrhagic vasculitis. Therapy with metipred in combination with isoniazid yielded a slight effect. The diagnoses of tuberculosis, liver cirrhosis, and autoimmune hepatitis, systemic vasculitis were consecutively rejected; the diagnosis of rheumatoid polyarthritis with systemic manifestations was made, by taking into account persistent arthalgias with the minimum signs of arthritis, noticeably increased C-reactive protein, rheumatoid factor, and cyclic citrullinated peptide antibodies (CCPA); plasmapheresis, therapy with metipred and methotrexate, and subtotal pericardectomy were performed. Constrictive polyserositis concurrent with PATE, hemorrhagic vasculitis (probably, drug-induced one), and hepatic lesion has been first described in a CCPA-positive patient with rheumatoid arthritis in the presence of moderate true arthritis (during steroid therapy).
Terapevticheskii arkhiv. 2010;82(6):56-61
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The first experience in using rituximab in Mikulicz's disease

Vasilyev V.I., Palshina S.G., Simonova M.V., Logvinenko O.A., Sedyshev S.K., Mitrikov B.V., Probatova N.A., Kokosadze N.V., Safonova T.N., Aleksandrova E.N., Nasonov E.L.


The paper describes a case of Mikulicz's disease (MD) in a young woman (aged 19 years) with symmetrical large salivary gland lesion concurrent with the enlarged lacrimal glands. Immunomorphological and molecular studies of parotid gland biopsy specimens revealed the formation of MALT tissue without signs of B-cell clonality of an infiltrate. The diagnosis of lacrimal sac lymphoma was ruled out. MD was diagnosed. The use of rituximab in therapy for MD has first demonstrated a positive result in Russian and worldwide practice.
Terapevticheskii arkhiv. 2010;82(6):62-66
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Mechanisms of phosphorus and calcium homeostatic disorders in the development of cardiovascular events in patients with chronic renal diseases. The role of fibroblast growth factor 23 and Klotho

Milovanova L.Y., Kozlovskaya L.V., Milovanov Y.S., Bobkova I.N., Dobrosmyslov I.A.


The paper deals with the analysis of studies of the role of the bone morphogenetic proteins fibroblast growth factor 23 (FGF-23) and Klothno in the development of vascular wall calcification in chronic renal disease (CRD). FGF-23 is shown to be an important phosphaturic hormone that inhibits hypercalcemic and hyperphosphatemic effects of elevated serum vitamin D concentrations. There is evidence that there is an association between high serum FGF-23 levels and vascular wall calcification irrespective of the content of phosphorus and parathyroid hormone. Most authors regard FGF-23 as a potential uremic toxin in patients with end-stage CRD. There are data that support the renoprotective value of the morphogenetic protein Klotho whose expression in CRD is decreased.
Terapevticheskii arkhiv. 2010;82(6):66-72
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Calcium antagonists: on the way to expanding the indications

Fomin V.V.


The paper discusses indications for the use of long-acting dihydropyridine calcium blockers, such as felodipine, as well as perspectives for using this class of drugs.
Terapevticheskii arkhiv. 2010;82(6):72-77
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Capacities of laboratory diagnosis in the assessment of the activity of the renin-angiotensin-aldosterone system

Maksimov M.L.


The renin-angiotensin-aldosterone system (RAAS) plays a substantial role in the regulation of many cardiovascular parameters and renal function, including the maintenance of blood pressure and water-salt exchange. The paper describes the most intensively used methods for determining the components of RAAS.
Terapevticheskii arkhiv. 2010;82(6):77-81
pages 77-81 views

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