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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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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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Oxidative and carbonyl stress,microinflammation and cardiovascular risk in patiens with chronic kidney disease
Peiskerová, Martina ; Kalousová, Marta (advisor) ; Teplan, Vladimír (referee) ; Racek, Jaroslav (referee)
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...
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Pathophysiology of cardiorenal interaction in patients with type 2 diabetes mellitus
Pecková, Marie ; Horáčková, Miroslava (advisor) ; Teplan, Vladimír (referee) ; Linhart, Aleš (referee)
Patients with type 2 diabetes mellitus (DM) suffer often from cardirenal syndrome because of high prevalence of cardiac and renal insufficiency. Functional deterioration of both organs depends on the compensation of DM, arterial hypertension and other metabolic parameters. We asked a question when did the cardiorenal interaction develop and which factors influenced its development. We examined 82 patients with type 2 DM with optimally corrected arterial hypertension, with well compensated diabetic metabolic disorder, without any clinical signs of heart disease and with normal or mild-to-moderate decrease in glomerular filtration rate according to MDRD equation (eGFR). We analysed the associations between eGFR and echocardiographic parameters of left ventricular (LV) diastolic function E' and E/E' on the basis of linear regression and multivariate analysis. According to multivariate analysis eGFR was significantly associated with E' and E/E' either. We assessed the association between E' and GFR by cluster analysis that divided whole cohort into two subgroups on the basis of the value E' = 7.1 cm s-1 . We analysed the associations between the parameters of LV diastolic function, eGFR and other parameters separately in both subgroups. We found out, that cardiorenal interaction (significant association...
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Lupus nephritis-novel diagnostic and therapeutic approaches
Pešičková, Satu ; Tesař, Vladimír (advisor) ; Teplan, Vladimír (referee) ; Krejčí, Karel (referee)
Key words: anti-mCRP antibodies, cyclophosphamide, cyclosporine A, lupus nephritis, systemic lupus erythematosus Systemic lupus erythematosus (SLE) is a systemic autoimmune disease. Circulating autoantibodies against the body's own nuclear and cytoplasmic structures and creation of immune complexes play a key role in the pathogenesis of SLE. Antibodies against monomeric C-reactive protein (anti-mCRP) might play role in pathogenesis of lupus nephritis (LN). The aim of this study was to find relation between anti-mCRP and activity of LN and response to therapy. Methods: The study was performed on 57 patients (M/F 0.21, median age 32 years) with LN. In a subanalysis, we focused on 29 patients with newly diagnosed active LN and we followed them up for a median of 5.9 years. Levels of anti-CRP were measured by in house ELISA. Disease activity was measured by SLEDAI. Results: Levels of anti-mCRP were significantly higher in patients with active lupus nephritis (26.78 versus 7.5 AU, p=0.009) and levels of anti-mCRP positively correlated with the activity of SLE as assessed by the SLEDAI score (Spearman's r=0.406, p= 0.002). We found negative prediction of anti-mCRP for worse outcome after two years of standard therapy, OR (95% CI)=13.7 (1.22-770.87); p=0.014. Conclusion: Serum levels of anti-mCRP seem to...
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Cytokines and adipocytokines in surgically ill patients: the role of fat tissue
Teplan, Vladimír ; Gürlich, Robert (advisor) ; Adamec, Miloš (referee) ; Herget, Jan (referee)
Cytokines and adipocytokines have major effect on post-operative prognosis of patients. In obese patients, we find significantly higher expression of proinflammatory mediators. In first part of our project we focus on cytokine expresion after elective abdominal surgery. Abdominal surgery was choosen as model of stress reaction to organism. Our results show, that proinflammatory cytokine expresion was significantly higher in obese patients and especially early elevation of visfatin could be a new marker in diagnosis of postoperative inflammatory complications. Related publications describe methods, design and results of trials. Second part of our poject is focused on patients after kidney transplanation, considering obesity, type of previous dialysis, early postoperative movement a nutrition. Our results show, that there is higher proinflammatory expresion after kidney transplanation with no effect of previous type of dialysis. On the other side early exercise have positive effect on cytokine expresion and decreases ADMA. Related publicatons describe methods, details and results of trials.
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Determinants of premature atherosclerosis in children with end-stage renal disease
Dvořáková, Hana Marie ; Piťha, Jan (advisor) ; Teplan, Vladimír (referee) ; Vaverková, Helena (referee)
Children with chronic renal failure are at extremely high risk of premature cardiovascular disease. In our work, we have shown that the measurement of carotis intima- media thickness (CIMT) with high resolution ultrasound is a suitable method for the diagnosis of early atherosclerotic changes especially in younger children. In contrast, flow mediated dilatation (FMD) according to our experience is not very suitable method for investigations in pediatrics because of its high variability. In our group of patients we did not find correlation of preclinical atherosclerosis measured by CIMT with any of the traditional cardiovascular risk factors (hypertension, dyslipidemia, overweight expressed as body mass index). In contrast, a significant negative correlation was found in the ESRD patients between the CIMT and serum bilirubin and albumin. On the one hand, these findings could indicate an impaired defending mechanisms against oxidative stress, which are considered one of the key factors in the development of atherosclerotic process, on the other hand they indicated an important role played by nutritional status in children with ESRD. In addition, we found strong evidence for significant correlations between CIMT and proteinuria as another discussed cardiovascular risk factor in boys, but not in girls. To our...
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Changes in the iron metabolism and its regulation in patients with end-stage renal disease treated by hemodialysis and kidney transplantion
Turková Sedláčková, Terezie ; Racek, Jaroslav (advisor) ; Zima, Tomáš (referee) ; Teplan, Vladimír (referee)
Iron is a very important biogenous trace element, which is involved in many of cell processes in organism. For its character iron can be also involved in Fenton reaction, where a toxic hydroxyl radical is produced. The iron metabolism is very carefully regulated in order to avoid formation of hydroxyl radical. Iron Responsive Proteins-Iron Responsive Elements (IRPs-IREs) system is involved in the regulation of iron metabolism on cell level, small peptide hormon hepcidin is involved in the regulation on systemic level. Hepcidin was discovered in 2000 as a peptide with antimicrobial properties. It is a key regulator of iron metabolism, as was discovered later. The target of hepcidin is ferroportin-the only known iron cell exporter. The expression of hepcidin is downregulated by hypoxia and anemia and upregulated by iron overload and inflammation. Hemodialyzed patients suffer from anemia very often. This anemia is caused by many factors, e.g. inadequate production of erythropoietin, chronic inflammation, chronic oxidative stress, blood loss during hemodialysis process or lower lifetime of red blood cells. We realized three studies on the patients with end-stage renal disease in our laboratories. Our aim was to find a relationship of hepcidin and other parameters of iron metabolism, inflammation and...
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Genetic basis of selected chronic nephropathies
Šafránková, Hana ; Merta, Miroslav (advisor) ; Otová, Berta (referee) ; Teplan, Vladimír (referee)
Keywords: nephrotic syndrome, FSGS, MCD, podocin, NPHS2, VEGF polymorphisms Nephrotic syndrome (NS), caused by minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) has about 20% of the genetic background caused by mutations in the NPHS2 gene encoding protein podocin that plays an important role in the kidney filtration barrier. The aim of this work is to introduce mutation analysis of the NPHS2 gene and to examine the sample of Czech patients with NS. We examined 71 patients with FSGS/MCD and subsequently, on the basis of these data we tested two common polymorphisms in NPHS2 (p.R229Q and p.P20L) in the group of patients with different glomerulonephritides (GN): IgA nephropathy (IGAN) (n = 169), membranous GN (MGN) (n = 46) and control group (n = 300). We also examined two polymorphisms located in the promoter of vascular endothelial growth factor (VEGF) (-2578 A/C, -1154 A/G) and influencing the level of its expression. VEGF is produced by specialized kidney cells called podocytes and has a function in the formation of blood vessels and capillary fenestration. The sample included 56 patients (pts) with FSGS/MCD, 113 pts with IGAN, 44 pts with MGN and 311 controls. No mutation in NPHS2 gene was found in patients with FSGS/MCD arising in adulthood. We detected one homozygous...
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31P MR Spectroscopy of Human Kidney Grafts Monitoring of MR parameters of human grafts and their comparison with clinical parameters of patients
Vyhnanovská, Pavlína ; Hájek, Milan (advisor) ; Teplan, Vladimír (referee) ; Mechl, Marek (referee)
The aim of this work was to evaluate the possibility of using in vivo phosphorus magnetic resonance spectroscopy (31P MRS) for diagnosis of kidney graft dysfunction after transplantation. In vivo 31P MRS is noninvasive imaging method which make possible to assess energy metabolism. A total of 68 patients with kidney grafts were examined on a 1.5T MR scanner. 31P MRS was performed using the 2D-chemical shift imaging method. The patients were divided into four groups: acute rejection; acute tubular necrosis; late graft dysfunction; and patients with good renal function after transplantation. We measured the signal intensities of phosphomonoesters (PME), inorganic phosphate (Pi), phosphodiesters (PDE) and -, -- adenosine triphosphate (with contribution of -, -adenosine diphosphate) and their ratios. Patients with acute rejection episodes showed significantly elevated PME/ß-ATP, PME/Pi and PDE/Pi signal ratios compared to the control group. The group with acute tubular necrosis has decreased these ratios: PDE/-ATP a PDE/Pi compared to the control group. Patients with late graft dysfunction revealed only significant decrease of PME/Pi ratio. The group of AR patients display higher ratios of PME/Pi and PDE/Pi compared to the group of ATN patients and display higher ratios of PME/Pi compared to the group of LGD....
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