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Biochemical and structural mechanisms of kidney and vascular damage in children with renal disease
Zieg, Jakub ; Matoušovic, Karel (advisor) ; Doležel, Zdeněk (referee) ; Skálová, Sylva (referee)
11 English Summary The objective of my PhD. thesis was to examine the pathophysiology of renal damage in patients with chronic kidney disease, defined by Kidney Disease Improving Global Outcomes (KDIGO) as a persistent renal damage or lowering the kidney function at least for 3 months. In the study Urinary TGF beta 1 in children with hydronephrosis we dealt with renal damage in children with obstructive uropathy. We focused on the identification of non- invasive marker transforming growth factor (TGF) beta 1 of this disease and its correlation with laboratory indications of renal parenchymal damage. Cytokine TGF beta 1 belongs among the main mediators of fibrogenesis in kidney diseases. A higher urinary concentration of TGF beta1 in patients suffering from obstructive hydronephrosis has been found in several studies before, but it has not been confirmed by other authors. In our study we are the first to describe the correlation of urinary concentrations TGF beta1 with laboratory markers of kidney damage. In the study Premature atherosclerosis in children with chronic kidney disease we dealt with the chronic kidney disease (CKD), its consequences and its impact on the origin of atherosclerosis. Patients in end-stage renal disease are many times over in danger of cardiovascular complications than the rest of...
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Signalling of protein kinase B and expression of cyclooxygenase in early phases of diabetic nephropathy
Ždychová, Jana ; Komers, Radko (advisor) ; Haluzík, Martin (referee) ; Matoušovic, Karel (referee) ; Škrha, Jan (referee)
Introduction: Renal hypertrophy, extracellular matrix accumulation, aItered apoptosis as well as changes in regional hemodynamics have been implicated in the pathophysiology of nephropathy in diabetes mellitus (DM). On the molecular level the detailed mechanisms for development of diabetic nephropathy (DN) have becn intensively studied. Insulin induces a variety of biologicaI effects in a number of cell types via phosphatidylinositol-3 kinase (PI3K)/Akt kinase signaling pathway. Considering multiple function of Akt that incIude potentiaIly hannful pro-growth effects mediated by mTOR and cyclooxygenas-2 (COX-2), as well as protective effects mediated by endotheliaI nitric oxide synthase (eNOS), it is possible that aIterations in activities of Akt may play role in the pathophysiology ofDN. Renal corticaI activity and expression of Akt, its down-strearn effectors mTOR, eNOS, and "C<JIX-:Z. as well as PTEN, an endogenous Akt inhibitor, were investigated in streptozotocin (STZ): diabetic rats as a model of Type 1 DM with different levels of glycenůc control, and in Zucker ~d.iabetic fatty rats, a model ofDM2, and in nondiabetic rats as controls. Methods: Akt activity was measured by kinase assay. Protein expressions were measured by .immunoblotting and immunohistochemistry in renal cortex of 4- and 12- week old...
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Infectious complications in chronic renal failure
Kielberger, Lukáš ; Eiselt, Jaromír (advisor) ; Dusilová Sulková, Sylvie (referee) ; Matoušovic, Karel (referee)
INFECTIOUS COMPLICATIONS IN CHRONIC RENAL FAILURE Infections represent a serious problem in chronic kidney disease (cohort and they are) associated with signifficant morbidity and mortality. The thesis originated in the nephrology division of the Department of Internal Medicine I., Charles University Teaching Hospital and Medical Faculty in Pilsen, an institution with a long standing research activity in the field. In the theoretical part of this work, a general summary of infectious complications in chronic kidney disease population is presented. The other part of this work presents results of our research dealing with pharmacoeconomical aspects of cytomegalovirus infection and finally our results in the field of influenza vaccination. The Aim of the first presented work was to evaluate the cost impact of four different strategies for prevention of cytomegalovirus infection after renal transplantation. We provide post hoc analysis of 2 randomized studies performed in our department and calculating direct CMV-related expenses using valacyclovir prophylaxis, ganciclovir prophylaxis, preemptive vlaganciclovir treatment and deferred therapy. To simulate ihe impact of varying prices of prharmacotherapy or diagnostic procedures, a sensitivity analysis was performed. With respect to our results, valacyclovir...
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Acid-base balance in peritoneal dialysis Patients: Stewart-Fencl Analysis
Klaboch, Jan ; Matoušovic, Karel (advisor) ; Kazda, Antonín (referee) ; Jabor, Antonín (referee)
Background: Evaluation of acid-base disorders using Stewart-Fencl principle is based on assessment of independent factors: strong ion difference (SID) and the concentration of non- volatile weak acids (Atot-). This approach allows for a more detailed evaluation of the cause of acid-base imbalance than the conventional bicarbonate-centered approach based on the Henderson-Hasselbalch principle. Studies with lactate-based peritoneal dialysis fluid (PDF) demonstrated an effect of peritoneal membrane transport characteristics on acid-base status. The "A" aim of our study was to assess acid-base disorders in peritoneal dialysis (PD) patients using both of these principles. The "T" aims were to determine whether or not peritoneal membrane transport characteristics, i.e., dialysate-to-plasma creatinine ratio (D/Pcreat) and creatinine mass transfer area coefficient (MTACcreat) have an effect on base influx when using a PDF with a combination of bicarbonate (bic-25mmol/L) and lactate (lac-15 mmol/L), and whether or not base influx differ between patients using icodextrin- or glucose-based PDF in night-time exchange. Methods: Two groups of patients with chronic renal failure treated with peritoneal dialysis "A" 17 patients and "T" 21 patients and group of healthy volunteers with normal renal function were...
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Association Between Echocardiogrtaphic Markers and Glomerular and Tubular Kidney Functions in Cardiologic Patients
Opatrný, Jan ; Matoušovic, Karel (advisor) ; Dusilová Sulková, Sylvie (referee) ; Pařenica, Jiří (referee)
A close relation between the kidneys and the heart functions is a long lasting clinical experience. In the second half of the XXth century, many studies documented a role of the kidneys in blood pressure regulation. Since the beginning of the XXI century, many findings have highlighted a role of a damaged kidney function as a risk factor for the heart injury. A close link between the heart and kidney functions is mediated by many common pathophysiologic mechanisms. It is surprising, that terms cardio-renal and renocardiac syndromes have got in a common awareness of clinicians only in the last 15 years. Some links between echocardiopgraphic signs of the systolic and diastolic heart dysfunction and the glomerular kidney function has already been described. Relations between the cardiorenal syndrome and echocardiographic findings versus the renal concentrating capacity are unknown. It is well established, that even mild renal insufficiency increases the mortality risk in ischemic heart disease patients. A question arises, if only a transient decrease of the renal function influences a mortality risk in ischemic heart disease patients. The aim of our study was to find out: A) The associations between the echocardiographic signs of systolic and diastolic heart dysfunction, the eGFR and the kidney...
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Relationship between pH and strong ion difference (SID) in predialysis patients with chronic kidney disease and in patients on chronic haemodialysis
Havlín, Jan ; Matoušovic, Karel (advisor) ; Žabka, Jiří (referee) ; Zadražil, Josef (referee)
SUMMARY: Metabolic acidosis (MAC) is a constant symptom of chronic kidney diesease (CKD) in advanced stages. The Siggaard-Andersen analysis is a traditional method of acid-base balance (ABB) assessment, assessing the metabolic component by means of the base excess and the anion gap (AG). Modern methods of ABB assessment draw upon the theory proposed by Stewart, which is based on the electric neutrality principle. Stewart distinguishes three independent variables determining plasmatic pH: pCO2, strong ion difference (SID) and 3) the total charge of non-volatile weak acids [Atot-]. The aim of this study was to assess the relationship between pH and plasma ion changes associated with ABB disorders in patients with chronic kidney disease using both methods of analysis, and subsequently compare both approaches. The cohort of patients consisted of three groups: 1) the "CKD" group, 60 patients with CKD stage 3 to 4 according to the KDOQI; 2) the "HD" group, 68 patients on chronic hemodiafiltration using dialysate bicarbonate concentration of 32 mmol/L; 3) a control group, 19 healthy volunteers. In all patients we measured parameters necessary for both approaches, in the HD group before and after dialysis treatment. We have found that MAC was present in two thirds of patients in the CKD group. A decrease of...
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Infectious complications in chronic renal failure
Kielberger, Lukáš ; Eiselt, Jaromír (advisor) ; Dusilová Sulková, Sylvie (referee) ; Matoušovic, Karel (referee)
INFECTIOUS COMPLICATIONS IN CHRONIC RENAL FAILURE Infections represent a serious problem in chronic kidney disease (cohort and they are) associated with signifficant morbidity and mortality. The thesis originated in the nephrology division of the Department of Internal Medicine I., Charles University Teaching Hospital and Medical Faculty in Pilsen, an institution with a long standing research activity in the field. In the theoretical part of this work, a general summary of infectious complications in chronic kidney disease population is presented. The other part of this work presents results of our research dealing with pharmacoeconomical aspects of cytomegalovirus infection and finally our results in the field of influenza vaccination. The Aim of the first presented work was to evaluate the cost impact of four different strategies for prevention of cytomegalovirus infection after renal transplantation. We provide post hoc analysis of 2 randomized studies performed in our department and calculating direct CMV-related expenses using valacyclovir prophylaxis, ganciclovir prophylaxis, preemptive vlaganciclovir treatment and deferred therapy. To simulate ihe impact of varying prices of prharmacotherapy or diagnostic procedures, a sensitivity analysis was performed. With respect to our results, valacyclovir...
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Acid-base balance in peritoneal dialysis Patients: Stewart-Fencl Analysis
Klaboch, Jan ; Matoušovic, Karel (advisor) ; Kazda, Antonín (referee) ; Jabor, Antonín (referee)
Background: Evaluation of acid-base disorders using Stewart-Fencl principle is based on assessment of independent factors: strong ion difference (SID) and the concentration of non- volatile weak acids (Atot-). This approach allows for a more detailed evaluation of the cause of acid-base imbalance than the conventional bicarbonate-centered approach based on the Henderson-Hasselbalch principle. Studies with lactate-based peritoneal dialysis fluid (PDF) demonstrated an effect of peritoneal membrane transport characteristics on acid-base status. The "A" aim of our study was to assess acid-base disorders in peritoneal dialysis (PD) patients using both of these principles. The "T" aims were to determine whether or not peritoneal membrane transport characteristics, i.e., dialysate-to-plasma creatinine ratio (D/Pcreat) and creatinine mass transfer area coefficient (MTACcreat) have an effect on base influx when using a PDF with a combination of bicarbonate (bic-25mmol/L) and lactate (lac-15 mmol/L), and whether or not base influx differ between patients using icodextrin- or glucose-based PDF in night-time exchange. Methods: Two groups of patients with chronic renal failure treated with peritoneal dialysis "A" 17 patients and "T" 21 patients and group of healthy volunteers with normal renal function were...
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Biochemical and structural mechanisms of kidney and vascular damage in children with renal disease
Zieg, Jakub ; Matoušovic, Karel (advisor) ; Doležel, Zdeněk (referee) ; Skálová, Sylva (referee)
11 English Summary The objective of my PhD. thesis was to examine the pathophysiology of renal damage in patients with chronic kidney disease, defined by Kidney Disease Improving Global Outcomes (KDIGO) as a persistent renal damage or lowering the kidney function at least for 3 months. In the study Urinary TGF beta 1 in children with hydronephrosis we dealt with renal damage in children with obstructive uropathy. We focused on the identification of non- invasive marker transforming growth factor (TGF) beta 1 of this disease and its correlation with laboratory indications of renal parenchymal damage. Cytokine TGF beta 1 belongs among the main mediators of fibrogenesis in kidney diseases. A higher urinary concentration of TGF beta1 in patients suffering from obstructive hydronephrosis has been found in several studies before, but it has not been confirmed by other authors. In our study we are the first to describe the correlation of urinary concentrations TGF beta1 with laboratory markers of kidney damage. In the study Premature atherosclerosis in children with chronic kidney disease we dealt with the chronic kidney disease (CKD), its consequences and its impact on the origin of atherosclerosis. Patients in end-stage renal disease are many times over in danger of cardiovascular complications than the rest of...
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Signalling of protein kinase B and expression of cyclooxygenase in early phases of diabetic nephropathy
Ždychová, Jana ; Komers, Radko (advisor) ; Haluzík, Martin (referee) ; Matoušovic, Karel (referee) ; Škrha, Jan (referee)
Introduction: Renal hypertrophy, extracellular matrix accumulation, aItered apoptosis as well as changes in regional hemodynamics have been implicated in the pathophysiology of nephropathy in diabetes mellitus (DM). On the molecular level the detailed mechanisms for development of diabetic nephropathy (DN) have becn intensively studied. Insulin induces a variety of biologicaI effects in a number of cell types via phosphatidylinositol-3 kinase (PI3K)/Akt kinase signaling pathway. Considering multiple function of Akt that incIude potentiaIly hannful pro-growth effects mediated by mTOR and cyclooxygenas-2 (COX-2), as well as protective effects mediated by endotheliaI nitric oxide synthase (eNOS), it is possible that aIterations in activities of Akt may play role in the pathophysiology ofDN. Renal corticaI activity and expression of Akt, its down-strearn effectors mTOR, eNOS, and "C<JIX-:Z. as well as PTEN, an endogenous Akt inhibitor, were investigated in streptozotocin (STZ): diabetic rats as a model of Type 1 DM with different levels of glycenůc control, and in Zucker ~d.iabetic fatty rats, a model ofDM2, and in nondiabetic rats as controls. Methods: Akt activity was measured by kinase assay. Protein expressions were measured by .immunoblotting and immunohistochemistry in renal cortex of 4- and 12- week old...
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