Vol 81, No 8 (2009)


Renin as a target of direct pharmacological block in arterial hypertension

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


Renin is a basic component of renin-angiotensin-aldosteron system which contributes much to the activity of this system. Renin and its precursor prorenin can interact with prorenin receptors thus inducing hypertrophy and fibrogenesis in target tissues. Many variants of arterial hypertension are associated with plasmic renin activation suggesting high efficacy of direct renin inhibitors. Large controlled clinical trials demonstrated that one of such inhibitors, aliskiren, reduces high blood pressure and damage to target organs.
Terapevticheskii arkhiv. 2009;81(8):5-9
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Clinical implications of urine matrix metalloproteinases assay in patients with chronic glomerulonephritis

Li O.A., Bobkova I.N., Kozlovskaya L.V., Lee O.A., Bobkova I.N., Kozlovskaya L.V.


Aim. Estimation of urinary excretion of matrix metalloproteinases (MMP) and their inhibitors in patients with chronic glomerulonephritis (CGN), specification of the role of MMP and inhibitors as criteria of CGN activity and prognosis. Material and methods. ELISA was used for measurement of urinary levels of basic proteolysis system components (MMP-2 and MMP-9), tissue inhibitor TIMP-2 and plasminogen activator inhibitor PAI-1 in four groups of patients. Patients of group 1 (n = 23) had CGN with manifest urinary syndrome (US), of group 2 (n = 26) - CGN with nephritic syndrome (NS), of group 3 (n = 22) - CGN with marked proteinuria (PU) and transient renal failure (RF), group 4 (n = 15) - CGN with high PU and persistent RF. Results. Patients with enhancing CGN activity (marked US, developing NS, acute nephritic syndrome) had balanced elevation of urinary levels of MMP, TIMP and PAI-1. Development of persistent RF in CGN occurred with imbalance between components of proteolysis system - low urine excretion of MMP and elevation of PAI-1. Urine excretion of MMP and TIMP in patients with progressive CGN directly correlated with 24-h PU and negatively correlated with blood serum creatinine. PAI-1 correlated with severity of RF and fibrosis in renal tissue. Conclusion. Correlation of changes in urinary excretion of MMP, TIMP and PAI-1 with CGN activity, RF and fibrosis in the kidney confirm the importance of the above urinary tests for estimation of local renal proteolysis and validity of their use for monitoring of extracellulary matrix accumulation (fibrosis) in the kidney and for CGN prognosis.
Terapevticheskii arkhiv. 2009;81(8):10-14
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Molecular factors of angiogenesis in renal tissue of patients with chronic glomerulonephritis: association with nephrosclerosis and anemia

Shvetsov M.Y., Ivanov A.A., Kuznetsova A.V., Popova O.P., Rameeva A.S., Shvetsov M.Y., Ivanov A.A., Kuznetsova A.V., Popova O.P., Rameeva A.S.


Aim. To study correlations between accumulation of angiogenesis molecular factors (hypoxia-inducible factor-1alpha - HIF-1α, vascular endothelial growth factor - VEGF, thrombospondin -TSP-1) in kidney biopsy tissue from chronic glomerulonephritis (CGN) patients and severity of nephrosclerosis, obliteration of renal capillary bed, filtration dysfunction and anemia. Material and methods. We examined 22 patients with marked proteinuria (2.7; 5.7, mean 4.2 g/day). Half of the patients had nephrotic syndrome. Glomerular filtration rate (GFR) by Cochroft-Golt formula was 68 (53;84) ml/min/1.73 m2. According to renal biopsy findings, CGN was detected in 19 patients, 2 patients had lupus nephritis (LN), 1 patient had renal amyloidosis. Nineteen CGN patients were divided into two groups by nephrosclerosis severity: group 1-7 patients with moderate nephrosclerosis, group 2-12 patients with severe nephrosclerosis. Cryostate sections of renal biopsy tissue samples were studied immunohistochemically using monoclonal antibodies to HIF-1α, VEGF, TSP-1, CD34. The reaction intensity was assessed by 6-point scale semuquantitative method. Results. Response to HIF-1a was stronger in the tubular epithelium than in glomeruli. No correlation was observed between accumulation of HIF-1a in the glomeruli and tubular epithelium. Intensity of glomerular staining correlated with severity of proteinuria (Rs = 0.63, p < 0.05), intensity of HIF-1α accumulation in tubular epithelium correlated with duration of the kidney disease (Rs = 0.74, p < 0.001), duration of persistent arterial hypertension (Rs = 0.68, p < 0.05) and severity of nephrosclerosis. VEGF and TSP-1 were found in equal quantity both in the glomeruli and renal interstitium. CGN patients with marked nephrosclerosis had lower accumulation of VEGF and higher TSP-1 in the interstitium. No correlation was found between intensity of tubular epithelium response to HIF-1α and accumulation of VEGF in the interstitium. Patients with severe nephrosclerosis demonstrated weaker staining of tubulointerstitium to CD34, reflecting the degree of its vascularisation. Significant correlation between CD34 and expression of HIF-1α, VEGF, TSP-1 was not registered. In patients with low intensity of tubular epithelial staining to HIF-1α (less than 2 points) anemia was detected in 63% versus 18% in patients with more intensive accumulation. Conclusion. CGN progression is associated with development of renal tubulointerstitial ischemia. High tubular production of HIF-1α was not accompanied with activation of VEGF accumulation in renal interstitium but was associated with reduced risk of anemia in CGN patients with manifest nephrosclerosis.
Terapevticheskii arkhiv. 2009;81(8):14-19
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Correlations between heart rate variability, renin activity and plasma aldosteron concentration in chronic glomerulonephritis with intact function of the kidneys

Borovkova N.Y., Borovkov N.N., Sidnev B.N., Obukhova E.O., Borovkova N.Y., Borovkov N.N., Sidnev B.N., Obukhova E.O.


Aim. To study correlations between heart rate variability (HRV), renin activity and blood aldosteron in chronic glomerulonephritis (CGN) with intact renal function. Material and methods. A total of 136 CGN patients with intact renal function were examined (100 hypertensive and 36 normotensive patients). HRV was studied with 24-h ECG monitoring. Active renin (AR) and aldosteron in blood plasma was studied with radioimmunoassay. Results. The analysis of HRV detected a progressive attenuation of vegetative impacts on the cardiovascular system with aggravation of hypertension in CGN patients with intact renal function. In hypertension of the second and third degree AR and aldosteron levels increased. Conclusion. With arterial hypertension progression in CGN patients with intact renal function, vegetative impacts on the cardiovascular system diminished while the levels of active renin and aldosterone rose.
Terapevticheskii arkhiv. 2009;81(8):20-23
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Hyperfiltration in hypertensive patients: results of epidemiological studies

Arutyunov G.P., Oganezova L.G., Arutyunov G.P., Oganezova L.G.


Aim. To evaluate prevalence of hyperfiltration (HF) in hypertensive patients, to estimate HF correlation with main demographic, clinical and laboratory data. Material and methods. A retrospective analysis was made by a proposed algorithm of 1160 case histories of outpatients and 1070 case histories of inpatients with hypertension. Glomerular filtration rate (GFR) was calculated by Mayo formula. 100 hypertensive patients with HF participated in telephone questionnaire survey. Also, 100 healthy medical students were examined. Results. HF was found in 15.83% examinees with hypertension and in no healthy subjects. HF patients had a shorter history of hypertension (4.64 ± 0.97 years), less frequent affection of target organs, type 2 diabetes mellitus, circulatory insufficiency. Most of the patients were males (82.35%, p < 0.05), they were significantly younger (mean age 51.93 ± 9.85 years) than the controls. Out of HF patients, 44.48, 26.35, 27.76% had arterial hypertension of the first degree, high normal pressure and hypertension of the second degree, respectively; 37.96% hypertensive patients with hyperfiltration received no treatment. In the absence of treatment for 2 years this group of patients exhibited a 12.12% fall in GFR, a 17.85 mm Hg rise of systolic and 7.4 mm Hg of diastolic pressure, a 10-fold increase of microalbuminuria. Overweight (body mass index in HF patients 31.51 ± 16.2 kg/m2) and smoking (68%) were among factors promoting GFR acceleration. Conclusion. Hyperfiltration develops at early stages of arterial hypertension in young patients and deteriorates prognosis. Therefore, preventive and therapeutic measures should be taken early with a focus on modification of the risk factors, first of all, obesity and smoking.
Terapevticheskii arkhiv. 2009;81(8):24-30
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Clinicomorphological characteristics of renal disorders in patients with genetic thrombophilia

Kozlovskaya N.L., Bobrova L.A., Shkarupo V.V., Varshavskiy V.A., Miroshnichenko N.G., Kozlovskaya N.L., Bobrova L.A., Shkarupo V.V., Varshavsky V.A., Miroshnichenko N.G.


Aim. To characterize the course and clinicomorphological features of chronic glomerulonephritis (CGN) in patients with genetic thrombophilia. Material and methods. A clinical picture and evidence on renal biopsy from 25 patients (12 females, mean age 32 ± 12 years and 13 males, mean age 36 ± 8.8 years) admitted to hospital with diagnosis of chronic glomerulonephritis were analysed. Mean duration of renal problem to the moment of biopsy was 37.6 ± 39 months. Renal end point was stable rise of Scr > 1.4 mg/dl for 6 months. Polymerase chain reaction defined polymorphisms of the genes MTHFR C677T; PTG G20210A; FV Leiden G1691A; FGB G455A; ITGB3 T176C L33P; PAI-1 4G/5G 675. Results. Mutation in one gene was detected in 24% patients, a multigenic form of thrombophilia - in 76% patients. Morphologically, all the patients' renal tissue had the signs of thrombotic microangiopathy (TMA), 8 patients had a combination of acute and chronic TMA. TMA was the only histological sign of nephropathy in 3 (13%) patients, the rest patients showed TMA combination with different morphological variants of CGN. Sclerotic alterations were most severe in combined carriage of the alleles 4G PAI-1 and T MTHFR. A correlation was found between the renal end point and number of mutant alleles (r = 0.6, p < 0.05), the presence of allele 4G (r = 0.46, p = 0.05) and interstitial sclerosis (r = 0.5, p = 0.05). Conclusion. Hereditary thrombophilia promotes induction of nephrosclerosis leading to activation of intraglomerular blood clotting which contributes to CGN progression. Patients with genetic thrombophilia may develop acute TMA as the only variant of renal damage.
Terapevticheskii arkhiv. 2009;81(8):30-36
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Contrast-inducible nephropathy in coronarography in patients with type 2 diabetes mellitus: risk factors, prognostic significance, prophylactic approaches

Shamkhalova M.S., Zaytseva N.V., Kurumova K.O., Shestakova M.V., Deev A.D., Matskeplishvili S.T., Tugeeva E.F., Buziashvili Y.I., Shamkhalova M.S., Zaitseva N.V., Kurumova K.O., Shestakova M.V., Deev A.D., Matskeplishvili S.T., Tugeeva E.F., Buziashvili Y.I.


Aim. To determine risk factors, prognostic implications and prophylaxis of contrast-inducible nephropathy (CIN) during coronarography (CG) in patients with type 2 diabetes mellitus (DM). Material and methods. Records for 151 patients with type 2 DM and 50 non-diabetic patients examined with CG in A.N. Bakulev Research Center for Cardiovascular Surgery in 2000-2007 were analysed retrospectively. All the patients have undergone clinical examination including tests for blood serum creatinine before and after 48 hours after CG, standard ECG and echocardiography. Glomerular filtration rate was estimated by MDRD formula. Selective CG was made with application of contrast agent Omnipak-300 (iohexol). Results. CIN after CG more frequently developed in diabetics than in non-diabetic patients matched for age, renal function, dose of contrast medium and hydration regime (40.4 and 16%, respectively; p < 0.002). Risk of CIN in patients with type 2 DM was associated with cardiac failure of NYHA class III-IV, anemia, dose of the contrast agent, intake of diuretic drugs before and after the procedure, multiple affection of the coronary vessels, necessity of intervention. Patients with type 2 DM and CIN showed more rapid decline of the renal function, more frequently developed severe cardiovascular events, had worse 1-year survival. Conclusion. High probability of CIN and its prognostic significance in type 2 DM patients necessitates assessment of an individual risk for taking preventive measures during conduction of contrast diagnostic procedures.
Terapevticheskii arkhiv. 2009;81(8):36-42
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Left ventricular myocardial hypertrophy after transplantation of the kidney: risk factors and possible regress

Tomilina N.A., Gendlin G.E., Zhidkova D.A., Tronina O.A., Fedorova N.D., Tomilina N.A., Gendlin G.E., Zhidkova D.A., Tronina O.A., Fedorova N.D.


Aim. To study structural-functional changes in left ventricular (LV) myocardium in recipients of renal allograft (RA) after different postoperative period and to specify factors promoting persistence, progression or regression of LV hypertrophy (LVH). Material and methods. The study included 240 recipients of primary RA (38% females and 62% males, age 16-69 years, mean age 42 ± 11 years). A prospective study covered 143 patients. Results. LVH was diagnosed in 52% patients. LVH incidence after renal transplantation (RT) had a wave-like dynamics: during 9 months after RT LVH presents in more than 50% patients; after 9-24 months after the operation it fell to 30% and after 3-7 years after the operation it affected at least 2/3 patients. After RT LVH risk factors were age, duration of chronic renal failure (CRF) and pretransplantation dialysis, reduced mass of the operating nephrons, arterial hypertension, anemia, functioning of arterio-venous fistula (AVF) and chronic inflammation syndrome. LVH was also associated with factors specific for RT: RA rejection crises, infections complicating massive immunosuppressive therapy. LVH is also associated with proteinuria which may indicate RA damage and can be considered as a marker of generalized endothelial dysfunction. 2-year and longer follow-up after RT confirmed complete LVH regression in 1/3 of the recipients. LVH regression was observed in normal RA function, normal blood pressure, the absence of proteinuria, hypoalbuminemia, anemia, AVF, infectious complications. Conclusion. LVH after RT is multifactorial and can completely regress in a favourable posttransplantation course.
Terapevticheskii arkhiv. 2009;81(8):42-48
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Correlations between the levels of vitamin D, parathormone, calcium, blood phosphates in patients with chronic disease of the kidneys untreated with replacement renal therapy

Smirnov A.V., Volkov M.M., Galkina O.V., Zhloba A.A., Emanuel' V.L., Smirnov A.V., Volkov M.M., Galkina O.V., Zhloba A.A., Emanel V.L.


Aim. To characterize correlations between the levels of vitamin D, parathormone, calcium, blood phosphates in patients with different stages of chronic disease of the kidney (CDK) given no therapy replacing renal function (TRRF). Material and methods. Serum levels of creatinine, electrolytes, parathormone (PTH), 25(OH)-vitamin D (calcidiol -CD), 1,25 (OH)2-vitamin D (calcitriol -CT), calcium (Ca) and phosphates (P) excretion with urine were studied in 465 patients aged 52.2 ± 15.5 years with CDK stage I-V given no TRRF having mean glomerular filtration rate (GFR) 51.8 ± 27.1 ml/min. Results. A CT level lowered with CDK progression and directly correlated with GFR, blood levels of Ca and CD. Correlation with PTH was not found. CD did not correlate with GFR. PTH rose from stage II CDK and its concentration in the blood correlated negatively with GFR, blood Ca (in lesser degree), directly correlated with P. Ca lowered at stage V of CDK, P - at stage II, increased at stage IV. In reduction of GFR 24-h excretions of P and Ca diminished in spite of growth of their excreted fractions and were related directly with CT. Conclusion. A rise of PTH and fall of CT occur at early CDK stages. P disbolism seems to play a key role in genesis of hyperparathyrosis. We are the first to show lowering of 24-hour Ca and P excretioin with CDK progression which may be caused by a progressive CT deficiency.
Terapevticheskii arkhiv. 2009;81(8):49-52
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The role of balanced low-protein diet in inhibition of progression of predialysis chronic disease of the kidneys in systemic diseases

Milovanov Y.S., Lysenko L.V., Milovanova L.Y., Dobrosmyslov I.A., Milovanov Y.S., Lysenko L.V., Milovanova L.Y., Dobrosmyslov I.A.


Aim. To evaluate the effects of low-protein diet (LPD) balanced by addition of highly energetic mix and essential keto/amino acids on inhibition of renal failure in patients with systemic diseases with predialysis stages of chronic disease of the kidney (CDK). Material and methods. Forty six patients with stage III-IV of CDK in systemic diseases (33 SLE patients and 13 with systemic vasculitis) were randomized into three groups. Group 1 consisted of 18 patients with CDK (10 with stage III and 8 with stage IV). They received LPD (0.6 g/kg/day) with addition of essential keto/amino acids for 24-48 months. Group 2 of 18 CDK patients with the same stages received the same diet but greater amount of vegetable protein (highly purified soya protein) to 0.3 g/kg/day in highly energetic nutrient mixture. Group 3 - 10 CDK patients (7 with stage III and 3 with stage IV) received free diet. Group 1 and 2 patients received LPD irrespective of the nutrient status assessed basing on anthropometric and other data. Protein consumption and caloric value were estimated by 3-day food diary. Results. Before diet therapy, out of 46 examinees nutrient status was abnormal in 45.7% patients. Both variants of LPD were well tolerated and nutrient status was corrected while the rate of nutritive disorders in group 3 increased 1.5-fold (from 40 to 60%) with progression of renal failure. Intake of LPD diet for at least a year reduced glomerular filtration rate inhibition, especially in addition of highly energetic mixture. Conclusion. Early (predialysis) restriction of diet protein (0.6 g/kg/day) with addition of highly energetic mixture and essential keto/amino acids improves a nutritive status of CDK patients and inhibits GFR decline.
Terapevticheskii arkhiv. 2009;81(8):52-57
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Kharakter sutochnogo ritma arterial'nogo davleniya u bol'nykh s khronicheskoy pochechnoy nedostatochnost'yu, nakhodyashchikhsya na peritoneal'nom dialize

Vetchinnikova O.N., Agal'tsov M.V., Pronina V.P., Vatazin A.V., Fedorova S.I., Vetchinnikova O.N., Agaltsov M.V., Pronina V.P., Vatazin A.V., Fedorova S.I.


Aim. To analyse 24-h rhythm of blood pressure (BP) and its influence on the rate and severity of left ventricular hypertrophy (LVH) in patients with chronic renal failure (CRF) on replacement therapy (peritoneal dialysis - PD). Material and methods. 70 CRF patients on PD were studied. Their examination included clinical, biochemical tests, automatic 24-hour blood pressure monitoring, transthoracic echocardiography. Results. Non-dipper and night-peaker disorders of BP 24-hour pattern were registered in 81.4% patients irrespective on hypertension severity. Left ventricular myocardial hypertrophy was 87.7% in patients with disturbed 24-h BP rhythm and 53.8% (p = 0.015) in normal BP rhythm. LV myocardial mass index median was 223 and 129 g/cm2 (p = 0.026), respectively. Concentric and excentric models of LV hypertrophy occurred with the same rate in normal and disturbed 24-h rhythm of BP. Conclusion. CRF patients on PD are characterized by disorders of 24-h BP rhythm independent of hypertension severity. Night-peaker pattern of BP is a risk factor of development and/or progression of LV hypertrophy.
Terapevticheskii arkhiv. 2009;81(8):57-61
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Efficacy and safety of CSA withdrawal in children late after kidney transplantation

Kaabak M.M., Babenko N.N., Molchanova E.A., Zokoev A.K., Kurakina Z.I., Goryaynov V.A., Minina M.G., Akhmetshin R.B., Kaabak M.M., Babenko N.N., Molchanova E.A., Zokoev A.K., Kurakina L., Goryainov V.A., Minina M.G., Akhmetshin R.B.


Aim. Evaluation of cyclosporine (CSA) withdrawal safety and efficacy in children late after kidney transplantation. Material and methods. Graft and patient survival was analysed in 30 kidney recipients operated in the central children's hospital in 1991-1999. Fifteen of 30 patients came for follow-up to the Russian Research Center for Surgery where CsA was withdrawn 6.8 ± 2.7 after transplantation. The other 15 children continued immunosuppression with CsA. Results. Higher graft survival was observed in children in whom CsA was discontinued. Conclusion. Discontinuation of cyclosporine late after kidney transplantation results in improvement of graft survival in most of the patients.
Terapevticheskii arkhiv. 2009;81(8):62-64
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Clinical experience with infliximab administration in patients with rheumatoid arthritis by Russian register data

Lukina G.V., Sigidin Y.A., Nasonov E.L., Lukina G.V., Sigidin Y.A., Nasonov E.L.


Aim. To analyse the data on infliximab administration (efficacy, tolerance, toxicity) in patients with rheumatoid arthritis (RA) in Russia by clinical evidence provided by the multicenter observation trial. Material and methods. The register included 297 patients with a documented diagnosis of RA who had for the first time treated with infliximab. The efficacy of the drug was evaluated by EULAR criteria based on the dynamics of DAS28 index. Results. The results of infliximab treatment show good response of RA patients to standard courses of infliximab. A good/satisfactory effect by EULAR criteria was achieved in 80% patients to week 22 of therapy and in 85% to week 46. After 6-month (22 week) infliximab treatment a good effect was achieved in 15.7% patients, satisfactory - in 64.7%; 19.6% patients did not respond. Remission (DAS28 < 2.6 units) was achieved in 7% patients. Infliximab tolerance was satisfactory. Non-severe infusion reactions were most frequent unwanted effects. To treatment week 22, ten patients developed serious side effects causing the drug discontinuation. Conclusion. The results of the Russian register confirm a high therapeutic potential and satisfactory tolerance of infliximab observed in real rheumatological practice of the treatment of severe RA. These results agree with those of European registers of infliximab.
Terapevticheskii arkhiv. 2009;81(8):65-69
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New potentialities in symptom-modifying therapy of osteoarthrosis

Salikhov I.G., Lapshina S.A., Myasoutova L.I., Kirillova E.R., Shamsutdinova N.G., Salikhov I.G., Lapshina S.A., Myasoutova L.I., Kirillova E.R., Shamsutdinova N.T.


Aim. To examine efficacy and tolerance of the drug Bora-Bora in patients with osteoarthrosis. Material and methods. Bora-Bora and nimesulid were given to 20 patients with a verified diagnosis of osteoarthrosis (OA). 20 control patients received nimesulid alone. Treatment efficacy was evaluated by quantitative parameters of articular syndrome, indices of periarticular muscles affection estimated before the treatment, 2, 6 and 8 weeks after the start of the treatment. Ultrasonic investigation of the joints and periarticular tissues was conducted before and after the treatment course. Results. The response to Bora-Bora was seen on day 10 of therapy. Bora-Bora attenuated pain syndrome in the joints and periarticular tissues, improved joint function more effectively than nimesulid (p < 0.05). Bora-Bora is a good anelgetic. It is well tolerated and can be recommended for OA treatment.
Terapevticheskii arkhiv. 2009;81(8):70-72
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Renal affection in a patient with Sneddon's syndrome

Kirsanova T.V., Kozlovskaya N.L., Kalashnikova L.A., Smirnova T.V., Roshchupkina S.V., Khafizova E.Y., Kirsanova T.V., Kozlovskaya N.L., Kalashnikova L.A., Smirnova T.V., Roschupkina S.V., Khafizova E.Y.


This case report draws attention to renal damage in a young patient with Sneddon's syndrome, analyses a course of nephropathy and methods of its diagnosis, shows efficacy of anticoagulant therapy, demonstrates possible development of generalized affection of the microcirculatory bed with involvement not only of the skin and brain vessels suggesting that Sneddon's syndrome is a systemic ischemic pathology the manifestations of which in many cases mask polyorganic impairment.
Terapevticheskii arkhiv. 2009;81(8):73-77
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Phenomenon of synergism of immunodepressive drugs (addition of kempas to the protocol of immunodepression)

Goryaynov V.A., Kaabak M.M., Shishlo L.A., Marchenko A.L., Goryainov V.A., Kaabak M.M., Shishlo L.A., Marchenko A.L.


Aim. To determine kempas ability to potentiate the action of simulneously used daklizumab. Material and methods. Kempas was given to 7 patients twice: 18-21 days before transplantation and on the day of transplantation after plasmapheresis. The control group consisted of 9 patients who received induction immunodepression only with daklizumab. By demographic and clinico-laboratory parameters the groups were identical. The assessment was made by duration of the interval between administration of daklizumab. Results. Patients given kempas had longer intervals between daklizumab administration (the difference was significant). Conclusion. Kempas potentiates an immunodepressive action of daklizumab
Terapevticheskii arkhiv. 2009;81(8):78-80
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