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Markers of transplantation tolerance in kidney transplantation
Krepsová, Eva ; Viklický, Ondřej (advisor) ; Krejčí, Karel (referee) ; Živný, Jan (referee)
Long-term renal graft acceptance still requires long-term immunosuppressive therapy, which is accompanied by many adverse effects. Contrarily insufficient immunosuppression could lead to graft rejection and its failure. Therefore, research continues for biomarkers that reflect a patient's immunological status and thus allowing for individualized immunosuppressive therapy. In our study we showed lower incidence of acute rejection in kidney transplant recipients treated with rabbit anti-thymocyte globulin (rATG) or basiliximab induction within the first three months after transplantation. The rATG induction caused profound decrease of recipient's peripheral blood T and NK cells, as well as transcripts that are exclusively expressed by these cell types together with expansion of regulatory T cells (Tregs) among CD4+ T cells. In rATG group the increase of two transcripts associated with rejection (MAN1A1 and TLR5) was also observed in early post-transplant period. After the basiliximab induction we transiently detected CD4+CD25low/-FoxP3+ cell population along with disappearance of CD4+CD25+FoxP3+ Tregs. Basiliximab induction resulted in a transient increase in CD4+FoxP3+ Tregs, accompanied by the highest peripheral expression levels of markers associated with operational tolerance (FOXP3 and TCAIM)....
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Role of BAFF cytokine in transplantation reactons
Sekerková, Zuzana ; Slavčev, Antonij (advisor) ; Krulová, Magdaléna (referee)
Current immunogenetic tests before organ transplantation include HLA typing and detection of HLA-specific antibodies. However, these tests do not provide information about the B cells participating in the humoral response against the transplanted organ. BAFF (B activating factor) plays an important role in the proliferation, maturation and differentiation of B cells. A soluble form of the cytokine arises after splicing the membrane form of BAFF. The soluble cytokine binds to three types of receptors - TACI, BCMA and BCMA. Some recent studies suggest that BAFF could serve as a marker or predictor of antibody-mediated (humoral) rejection in kidney transplant recipients. Our study consists of two parts. The first part is focused on the detection of soluble BAFF levels in patients after renal transplantation. The aim of our study was therefore to correlate levels of soluble BAFF cytokine in patients before and after transplantation with the clinical course and incidence of rejection after transplantation. The study included 92 kidney recipients. Humoral rejection was diagnosed on the basis of a positive finding of C4d deposits in peritubular capillaries (imunoflorescenční detection), and the presence of donor- specific antibodies. BAFF levels were determined using Xmap methodology by the Luminex method...
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Effect of physical activity Nordic Walking on body composition and cardiorespiratory parameters in individuals after kidney transplantation and dialysis individual.
Rousová, Martina ; Mahrová, Andrea (advisor) ; Horčic, Josef (referee)
Title: Effect of physical activity Nordic Walking on body composition and cardiorespiratory parameters in individuals after kidney transplantation and dialysis individual. Objective: The aim of the study was to determine the effect of physical activity Nordic Walking on body composition and cardiorespiratory parameters in individuals after kidney transplantation and dialysis individual. Method: This thesis has been prepared in the form of a qualitative case study. The study involved 9 probands at the beginning, but only 5 probands completed the study. It was done the input examination before the intervention. The intervention was made from 20 lessons of Nordic Walking which should take 60 minutes each of them. Then were probands tested again like the output examination. During these both examination were measured specific values of body composition, anthropometric values (height, weight, age, circuit level), as well as the distribution of muscle and fat mass in the body, the value of physical fitness, respectively. cardiorespiratory parameters of the individual, for which was used the spiroergometric test within a modified Balke's walking test. For to detect the quality of life was used before and after intervention standardized questionnaire assessing quality of life WHOQOL-BREF. Last but not...
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The role of B cells in transplantation reactions
Brožová, Jitka ; Slavčev, Antonij (advisor) ; Stříž, Ilja (referee)
Kidney transplantation is the best treatment for patients with end-stage renal failure. The main problem of kidney transplantation is however the development of a cellular and antibody-mediated (humoral) rejection. During the last decade, thanks to the advanced immunosuppression, prognosis of survival and function of transplanted organs has significantly improved. Nevertheless, humoral rejection remains very serious obstacle in high-risk patients, because it can permanently damage the graft. Therefore, before transplantation it is necessary to stratify patients into high and low risk groups for development of antibody-mediated rejection. Current immunogenetic tests performed before transplantation include, in addition to HLA typing, detection of panel-reactive antibodies. However, this test does not provide information about B cells which participate in the humoral response of the kidney recipient. Therefore, in the presented thesis we studied B cell reactivity and its regulation in transplanted patients. In this retrospective analysis we measured levels of the B cell activating factor, a cytokine regulating the function of B lymphocytes (BAFF). Current reports suggest that BAFF could serve as a marker of humoral rejection. Furthermore, we focused on B lymphocytes and their capacity to produce...
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Prediction of graft function development and rejection of transplanted kidney
Wohlfahrtová, Mariana ; Viklický, Ondřej (advisor) ; Zadražil, Josef (referee) ; Reischig, Tomáš (referee)
Improving the short-term results of kidney transplantation did not result in improving the long-term function and survival of kidney allograft. Organ shortage and increasing number of marginal donors remains the key problem in transplant today. The quality of donor organ is critical for graft function development and survival. The aim is to improve understanding to ischemia/reperfusion injury and its consequences, predict delayed graft function and rejection, improve organ allocation strategy and identify patients suitable for safe drug minimization or complete withdrawal of immunosuppressive therapy. Analysis of donor kidneys identified poor tubular cell quality and low survival factor, Netrin-1 expression levels, to be associated with delayed graft function. We confirmed that reperfusion phase of ischemia/reperfusion injury leads to minimal morphological but significant molecular abnormalities. Dissociation observed in histology and molecular pathology finding calls for an integrated approach in donor quality organ evaluation and allocation for transplantation. Significant heterogeneity within donors with expanded criteria was shown and subgroup of organs at low risk of delayed graft function was identified. We suggested donor biopsies to be performed as a routine praxis in all kidneys...
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The effect of physical activity and nutrition interventions on physical fitness and quality of life during the first year after kidney transplantation
Švagrová, Klára ; Bunc, Václav (advisor) ; Brandejský, Petr (referee) ; Adámková, Věra (referee)
UNIVERZITA KARLOVA V PRAZE FAKULTA TĚLESNÉ VÝCHOVY A SPORTU The effect of physical activity and nutrition interventions on physical fitness and quality of life during the first year after kidney transplantation Abstract of disertation Zpracovala: Mgr. Klára Švagrová Školitel: Prof. Ing. Václav Bunc, CSc. Školící pracoviště: Laboratoř sportovní motoriky Praha, 2012 ABSTRACT Kidney transplantation is the best known treatment of chronic kidney failure. However, it is often accompanied by a number of health complications. The transplantation itself positively affects both physical fitness and quality of life during the first year after the transplant surgery which are seriously diminished when compared to the healthy population. This improvement can be even enhanced by appropriate physical activity and nutrition interventions otherwise both the physical fitness and quality of life would start declining after the first post-transplant year again. The aim of this study was to confirm a positive effect of a long-term physical activity and nutrition interventions on health-related physical fitness and health-related quality of life in a representative sample of individuals in the first year after the kidney transplantation. At the same time it was fundamental to verify that the experimental trial can be...
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Quality of life of hemodialysis patients
Kycltová, Pavlína ; Tomová, Šárka (advisor) ; Hlaváčová, Marie (referee)
Throughout the introduction to this bachelor thesis I would like to narrate the issue of a chronic kidney failure. The causes, symptoms, diagnosis, cure as well as the quality of life of patients diagnosed with this condition, will be mentioned. We will learn what principle hemodialysis is based on, what its complications might be and what requirements have to be met, in order for the patient to undergo a hemodialysis treatment. My aim will be to depict the problems caused by this illness in a family, work place and one's social life. The assessment of this issue will be based on information gathered from a survey conducted by myself at the hemodialysis center. My thesis will be concluded, with the use of a graphic and verbal description, by an analysis of the survey questionnaire and a disclosure of the data and final results about the quality of life of hemodialysis patients which participated in the research.
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Humoral rejection after kidney transplantation and monitoring antibodies against HLA and non-HLA antigens.
Valhová, Šárka ; Slavčev, Antonij (advisor) ; Mrázek, František (referee)
Kidney transplantation is the treatment of choice for patients with end stage renal failure and is associated with prolonged survival of patients and better quality of life than long-term dialysis. Simultaneously, however, transplantation carries the risk of immunological complications leading to graft rejection. A serious problem in patients after organ transplantation is the development of humoral rejection, which is most often associated with the presence of antibodies specific to HLA antigens, particularly against mismatched HLA antigens of the organ donor. In certain cases antibodies may be specific to antigens expressed on endothelial cells, not on lymphocytes, like MICA, MICB, ICAM, and up till now unidentified tissue-specific antigens. Humoral rejection has significantly worse prognosis for the transplanted kidney than cellular rejection, and therefore its timely diagnosis is of great importance for the subsequent choice of appropriate therapy. The diagnosis of humoral rejection is based on the simultaneous detection of C4d deposits in the peritubular capillaries of the transplanted kidney and the finding of antibodies specific to the mismatched antigens of the donor (donor specific antibodies, DSA). The aim of our retrospective study was to contribute to improvement of the diagnosis of acute and...
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Functional disorders of the musculoskeletal system on individuals after kindey transplantation
Školová, Lucie ; Mahrová, Andrea (advisor) ; El Ali, Zaher (referee)
Title: Functional disorders of the musculoskeletal system on individuals after kindey transplantation Defining of the problem: Renal transplantation is a method to treat patients with renal failure,which is associated to a prolonged survival of patients compared to a dialysis method (Viklický et al., 2008). After a successful renal transplantation the renal function is restored and complications caused by dialysis treatment disappear . However, complications due to the transplant, not only in terms of surgical intervention, but also from the point of a lifelong immunosuppressive therapy remain at risk. Functional changes on the locomotor system can occur as a concequence of a long-term renal disease or kidney transplant. This could further reduce the quality of life on patients due to self-sufficiency, being the main role of the locomotor system. Objectives: The aim of this study is to valuate functional disorders of the musculoskeletal system on individuals after kindey transplantation up to one year after a transplant. Methods: This thesis is elaborated in the form of an analytical - experimental study in which 2 groups of selected individuals were tested. Testing was conducted by using suitable tests focused on functional disorders of the locomotor system and parameters in each group and time...
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The role of T regulatory cells in kidney transplantation
Urbanová, Anna ; Stříž, Ilja (advisor) ; Zajícová, Alena (referee)
T regulatory lymphocytes (Treg) belong to the CD4+ cell group. They are an essential part of the immunity system. Treg cells prevent from excessive activation of effector T cells and they keep the tolerance to the tissues of the body. They have high expression of CD25 and the transcription factor Foxp3. We distinguish two basic populations of Treg cells: natural Treg cells (nTreg) created in the thym and representing 5-10 % of all CD4+ cells, and induced Treg cells (iTreg), created from naive CD4+ cells in the periphery.Their regulatory effect is well-known, therefore using of Treg cells could bring about a huge treatment potential for patients with a transplantated kidney. Healthy people and patients tolerant to the transplantated kidney show higher occurance of circulating Treg cells and the Treg cells present in the graft unlike patients with chronical rejection. The tolerance is cancelled with the damage of CD4+ CD25+ cells.For a graft acceptance it is necessary to treat the patient after the transplantation with immunosuppressive medicaments resulting in suppression of immunity reaction against the graft. Their disadvantages are side effects often resulting in the patient's death. Moreover they often have a negative impact on survival and expansion of Treg cells. The analysis of flow cytometry has...
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