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Genetic factors of progression of selected forms of chronicnephropathies.
Šafaříková, Markéta ; Reiterová, Jana (advisor) ; Brdička, Radim (referee) ; Gaillyová, Renata (referee)
Nephrotic syndrome is characterized by proteinuria, hypoproteinemia, edemas and hyperlipidemia. It occurs in primary (e.g. focal segmental glomerulosclerosis, FSGS or minimal change disease, MCD) and in secondary glomerulopathies (e.g. kidney amyloidosis). In primary forms, great attention is paid to the potential genetic background of the disease and due to new molecular genetic methods genes, whose mutations cause different nephropathies (e.g. ACTN4 or INF2) were identified. The aims of presented doctoral thesis were following. Firstly, to continue the mutational analysis of ACTN4 that was described in the author's diploma thesis in other glomerulopathies. Secondly, to implement the mutational analysis of INF2 and subsequently analyse this gene in patients with FSGS/MCD and in patients from special group characterized by positive family history for end stage renal disease (ESRD) in combination with advanced chronic kidney disease (CKD) or already developed ESRD at the time of diagnosis. Thirdly, mutational analysis of NPHS2 and TRPC6 (methods implemented in laboratory earlier) in selected patients from the special group. Finally, expression analyses of genes important for podocyte function or connected with human immune system. This part also verifies the applicability of NPHS2/SYNPO expression...
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Genetic factors of progression of selected forms of chronicnephropathies.
Šafaříková, Markéta ; Reiterová, Jana (advisor) ; Brdička, Radim (referee) ; Gaillyová, Renata (referee)
Nephrotic syndrome is characterized by proteinuria, hypoproteinemia, edemas and hyperlipidemia. It occurs in primary (e.g. focal segmental glomerulosclerosis, FSGS or minimal change disease, MCD) and in secondary glomerulopathies (e.g. kidney amyloidosis). In primary forms, great attention is paid to the potential genetic background of the disease and due to new molecular genetic methods genes, whose mutations cause different nephropathies (e.g. ACTN4 or INF2) were identified. The aims of presented doctoral thesis were following. Firstly, to continue the mutational analysis of ACTN4 that was described in the author's diploma thesis in other glomerulopathies. Secondly, to implement the mutational analysis of INF2 and subsequently analyse this gene in patients with FSGS/MCD and in patients from special group characterized by positive family history for end stage renal disease (ESRD) in combination with advanced chronic kidney disease (CKD) or already developed ESRD at the time of diagnosis. Thirdly, mutational analysis of NPHS2 and TRPC6 (methods implemented in laboratory earlier) in selected patients from the special group. Finally, expression analyses of genes important for podocyte function or connected with human immune system. This part also verifies the applicability of NPHS2/SYNPO expression...
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Markers influencing the course of IgA nephropathy.
Neprašová, Michaela ; Maixnerová, Dita (advisor) ; Dusilová Sulková, Sylvie (referee) ; Rychlík, Ivan (referee)
IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide with a very severe prognosis, causing kidney failure in up to 50 % of patients in a period of 30 years. For the diagnosis of IgAN it is necessary to perform a renal biopsy, this is an invasive examination that carries number of risks for the patients (the most common is bleeding and others). The aim of our work was to identify markers that could facilitate diagnosis and might help in determining the disease activity with an estimate of prognosis and consequently optimal use of effective therapy. In the pilot project on 19 patients with different types of glomerulonephritides (IgAN, diabetic nephropathy, membranous glomerulonephritis, lupus nephritis, ANCA associated vasculitis) and 19 healthy subjects we demonstrated a panel of 7 biomarkers (8-hydroxyguanosine, dodecanal, leukotriene C4, alpha1-antitrypsin, heparan sulfate , IgA-uromodulin, Gd-IgA1) that were able to completely differentiate patients with IgAN from other types of glomerulonephritides or healthy controls. In a group of 93 Czech patients with IgAN we confirmed the influence of clinical factors (PU, HT, eGFR) on the progression of renal function. Using LDA and logistic regression modelling we found that serum Gd-IgA1 (native without pre-treatment with...
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