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Cardiovascular complications in patients with end-stage renal disease.
Valeriánová, Anna ; Malík, Jan (advisor) ; Zemánek, David (referee) ; Piťha, Jan (referee)
Patients with end-stage renal disease frequently suffer from cardiovascular complications. Many factors contribute to their development: hyperkinetic circulation caused by anaemia, fluid retention and by presence of dialysis arteriovenous access; metabolic changes leading to acceleration of atherosclerosis and increase of vascular stiffness and also fluctuation of blood pressure and organ perfusion during haemodialysis, that cause repeated tissue hypoxia. We performed our research on patients in chronic haemodialysis programme. The project studying long-term patency of dialysis access showed that dialysis graft patency is negatively influenced by presence of coronary artery disease and low serum concentrations of cholesterol. In our studies about tissue hypoxia we proved that haemodialysis patients suffer from hypoxia of cerebral tissue and muscle tissue of the dialysis access arm, and that the hypoxia worsens during dialysis. Factors associated with brain hypoxia are presence of heart failure, higher BNP levels and higher erythrocyte distribution width. One of the serious consequences of brain hypoxia is development of cognitive deficit. Among the negative impact of haemodialysis on the heart, we observed left atrial dysfunction, which is a consequence of long-term remodelling and cannot be...
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Contribution of particular vasoactive systems in the development of chronic kidney disease
Drábková, Natálie ; Vaněčková, Ivana (advisor) ; Vaňourková, Zdeňka (referee)
Chronic kidney disease (CKD) is a life-threating disease which arises as a frequent consequence of diabetes and hypertension. Since it is going on silently, CKD often progresses to the end-stage renal disease. It is therefore necessary to combat this disease especially due to the fact that the world population is growing old. The aim of this work was to determine the contribution of selected vasoactive systems contributing to the maintenance of high blood pressure in the developmental and established phase of CKD. Two models of CKD were used: 5/6 nephrectomy in Ren-2 transgenic rats (TGR) and stenosis of renal artery (2K1C) in Wistar rats. We demonstrated that renin-angiotensin system does not play so important role in blood pressure maintenance in both CKD models. By contrast, a more important role has sympathetic nervous system. During both the developmental and established phase of CKD, vasoconstrictor systems prevail above vasodilator NO-synthase effects. In fact, the role of NO-dependent vasodilation gradually decreased in nephrectomized TGR rats, while it was unchanged in Wistar rats with 2K1C hypertension.
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Biomarkers of early renal injury
Fořtová, Magdaléna ; Průša, Richard (advisor) ; Kalousová, Marta (referee) ; Ryšavá, Romana (referee)
Aims: The thesis deals with the biomarkers of early renal injury, namely albuminuria and neutrophil gelatinase-associated lipocalin (NGAL). The aims in the case of albuminuria were the implementation of HPLC method, comparing HPLC with immunoturbidimetric (IT) method and monitoring the relationship to the diagnosis of diabetes mellitus. The aim of urinary NGAL (and eventually other markers) examination was to verify its reliability in the prediction of acute kidney injury (AKI). Methods: We investigated albuminuria in fresh urine samples in the groups of 636 diabetics and 456 nondiabetics using the HPLC method (Agilent 1200, Agilent Technologies, USA) and immunoturbidimetrically (Cobas Integra 400, Roche Diagnostics); we studied the correlations and relationships between albuminuria and glycated hemoglobin HbA1c. We investigated urinary NGAL by chemiluminescent microparticle immunoassay (Architect i4000, Abbott) in children's groups: 1) after renal transplantation (N = 15), 2) with acute or chronic kidney disease (N = 28); and in adult patient's groups: 1) after cardiac surgery (N = 10) and 2) post angiography (N = 41). Results: Albuminuria determined by HPLC was statistically significantly higher than albuminuria determined by IT. We excluded nonspecificity of the HPLC method. Results indicate...
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Effect of combined endothelin and renin-angiotensin systems blockade on blood pressure and chronic kidney disease regression in model of angiotensin II-dependent hypertension
Sedláková, Lenka ; Kopkan, Libor (advisor) ; Bürgelová, Marcela (referee)
and key words Enhanced activation of renin-angiotensin system (RAS) and endothelin system (ES) plays the key pathophysiological role in the progression of hypertension and the chronic kidney disease (CKD). The aim of this study was to verify wheter the combined inhibition RAS and selective inhibition ETA receptor for endothelin 1 (ET-1) will show additive renoprotective effects in experimental model CKD. This therapeutic aproach was tested on the transgenic rats with mouse renin gen (TGR), to whome ablation nephrectomy (5/6 NX) was done in the age of 6 weeks. After next 6 weeks the relevant treatment was given in drinking-water: dual RAS blockade (trandolapril 6mg/L + losartan 100mg/L) or the combination of dual RAS blockade + inhibitor of ETA receptor (atrasentan 25mg/L). Results of the first series show 100 % mortality in untreated rats with 5/6 NX to the 30th week. Both type of treatments increased the survival rate up to 30 % in 5/6 NX TGR after the 50th week. In the second series influence of treatments on the blood pressure (BP) was monitored in 5/6 NX TGR, which had systolic BP over 210 mmHg. Both treatments decreased BP to the level normotensive rats and reduced heart hypertrophy. In the third series the results showed that treatment significantly decreased renal level of angiotensin II...
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The role of endothelin system in the treatment of chronic renal failure
Drábková, Natálie ; Vaněčková, Ivana (advisor) ; Vebr, Pavel (referee)
Chronic kidney disease (CKD) is a life-threatening disease arising as a frequent consequence of diabetes and hypertension. Since it is silent for a long time, it often progresses to end-stage renal disease (ESRD). Managing chronic kidney disease, the prevalence of which is sharply increasing in the last decades due to the ageing of the world population, is thus major health problem. Apart from blockers of renin-angiotensin system, which are used as the "golden standard" in the treatment of CKD due to their antihypertensive and renoprotective effects, other strategies are also applied for the management of this disease. A relatively new class of therapeutics - blockers of endothelin system - seems to be very promising in this field.
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Oxidative and carbonyl stress in kidney diseases
Kratochvílová, Markéta ; Tesař, Vladimír (advisor) ; Průša, Richard (referee) ; Zadražil, Josef (referee)
Aims: 1. Determination of AGEs (Advanced Glycation End products) in patients with various types of nephropathy. 2. Association AGEs with nutritional parameters and anemia. 3. Influence of renal parameters on sRAGE (soluble form of Receptor for Advanced Glycation End products) levels. 4. Technics and proceeding methods of the podocytes cultivation. 5. Determination of urine podocytes. Methods: We determined fluorescent AGEs by spectrofluorometry, sRAGE by Enzyme-Linked ImmunoSorbent Assay (ELISA). Podocytes were passaged and identified immunocytochemically. Podocytes in urine were specified by flow cytometry method. Results: 1. We did not find significant differences in AGEs serum levels among various types of nephropathy, even though the pathogenesis differs. 2. The albumin and prealbumin levels positively and haemoglobin levels negatively correlate with AGEs in patients with CKD grade 1-5, without necessity of dialysis. 3. Serum sRAGE levels are increased in patients with decreased renal function independently on the course of renal disease. 4. We implemented the methods and technics of podocyte cultivation. 5. Urine podocytes observation and confirmation that podocyturia relates to disease activity. Conclusion: We confirmed that AGEs serum levels depend more on renal function than the type of...
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Novel biomarkers in patients with renal disease
Zakiyanov, Oskar ; Kalousová, Marta (advisor) ; Teplan, Vladimír (referee) ; Průša, Richard (referee)
Chronic kidney disease (CKD) and acute kidney injury (AKI) are major public health problems. It is important to be able to identify those at high risk of adverse outcome, CKD progression and associated cardiovascular disease. The aim of the thesis was to study novel promising biomarkers, their relationship to kidney function, chronic inflammation and/or cardiovascular risk - placental growth factor (PlGF), pregnancy associated plasma protein A (PAPP-A), matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9), soluble receptor for advanced glycation end products (sRAGE), calcium binding protein S100A12 or extracellular newly identified RAGE binding protein (EN-RAGE), and high mobility group box protein-1 (HMGB-1) in patients with renal diseases including CKD, haemodialysis (HD), AKI patients, and healthy controls for comparison. First study revealed that PlGF is elevated in patients with decreased renal function. Second study demonstrated the association of MMP-2 and PAPP-A with proteinuria in patients with CKD. Moreover, serum MMP-2, MMP-9 and PAPP-A levels significantly differed in patients with various nephropathies. EN-RAGE levels are not elevated in patients with CKD, but are related to inflammatory status. PAPP-A, EN-RAGE and HMGB-1 levels are significantly elevated, but sRAGE and PlGF...
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