Short summary: Background: High cardiovascular risk in patients with chronic kidney disease is partly due to mineral dysbalance, microinflammation and oxidative stress. CKD patients accumulate traditional and non-traditional CV risk factors. FGF23, MMPs and PlGF belong among these non-traditional biomarkers of CV risk. FGF23 is a phosphaturic hormone and inhibitor of calcitriol synthesis. It is associated with vascular calcifications. Matrix-metalloproteinases (e.g. MMP-2, MMP-9) are proteolytic, proinflammatory enzymes, contributing to myocardial remodelation. Placental growth factor (PlGF) is a proangiogenic cytokine that is associated with LV hypertrophy in animal model. Plasmatic FGF23, MMPs and PlGF are elevated in CKD. Aim: We aimed to describe dynamic changes between several novel biomarkers of CV risk (FGF23, MMP-2, MMP-9 and PlGF) in CKD stages 1-5, to describe their mutual correlations and possible association with traditional CV risk markers. We studied possible association of laboratory and echocardiographic parameters in patients with CKD stages 2-4. Methods: In a cross-sectional study we evaluated 80 patiens with CKD 1-5 and 44 healthy controls. In a prospective study we evaluated echocardiographic and laboratory parameters in 62 patients with CKD 2-4 for an average study period of 36±10...

Detection of early pathophysiological changes of breathing in children with chronic respiratory disease MD. Vaclav Koucky - Ph.D. thesis Abstract Introduction: Currently, there are different methods for infant pulmonary function testing (iPFT) and morphological assessment of microscopic changes in endobronchial biopsy samples (EBB). In research setting, they allow detection of early pathophysiological changes of breathing in small children with chronic respiratory disease, respectively in risk of its development. Their clinical significance, however, is not fully acknowledged. The aim of this thesis is to evaluate the safety, feasibility and clinical significance of iPFT and EBB in infants younger than 2 years of age. In addition, the relationship between functional and morphological changes of respiratory tract and the function of peripheral chemoreceptors was studied in selected patients' subgroups. Methods: Fifty-five infants with cystic fibrosis (CF), 35 physician-confirmed recurrent wheezers (AB), 9 infants with congenital diaphragmatic hernia, 7 with interstitial lung disease (chILD) and 3 with primary ciliary dyskinesia (PCD) were enrolled. All infants underwent iPFT and relevant clinical history data were recorded. Based on patients' age, CF group was divided into CFmalí (< 6 months) and CFvelcí (>...

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...

Short summary: Background: High cardiovascular risk in patients with chronic kidney disease is partly due to mineral dysbalance, microinflammation and oxidative stress. CKD patients accumulate traditional and non-traditional CV risk factors. FGF23, MMPs and PlGF belong among these non-traditional biomarkers of CV risk. FGF23 is a phosphaturic hormone and inhibitor of calcitriol synthesis. It is associated with vascular calcifications. Matrix-metalloproteinases (e.g. MMP-2, MMP-9) are proteolytic, proinflammatory enzymes, contributing to myocardial remodelation. Placental growth factor (PlGF) is a proangiogenic cytokine that is associated with LV hypertrophy in animal model. Plasmatic FGF23, MMPs and PlGF are elevated in CKD. Aim: We aimed to describe dynamic changes between several novel biomarkers of CV risk (FGF23, MMP-2, MMP-9 and PlGF) in CKD stages 1-5, to describe their mutual correlations and possible association with traditional CV risk markers. We studied possible association of laboratory and echocardiographic parameters in patients with CKD stages 2-4. Methods: In a cross-sectional study we evaluated 80 patiens with CKD 1-5 and 44 healthy controls. In a prospective study we evaluated echocardiographic and laboratory parameters in 62 patients with CKD 2-4 for an average study period of 36±10...

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...

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...