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Antibody-mediated rejection after kidney transplantation
Slatinská, Janka ; Viklický, Ondřej (advisor) ; Reischig, Tomáš (referee) ; Krejčí, Karel (referee)
Antibody-mediated rejection (AMR) is the main cause of the kidney graft dysfunction and its failure after transplantation. Antibodies lead to vascular damage that is either acute or chronic and manifests as sudden or progressive graft dysfunction. Risk factors for development of AMR are time spent on haemodialysis, retransplantation, previous sensitisation against HLA antigens, and persistence of panel-reactive antibodies. Diagnosis is based on detection of deposits of C4d component of complement in peritubular capilaries and presence of donor-specific antibodies (DSA). We can also observe injury caused by antibodies against non-HLA antigens without detection of anti-HLA DSA. Use of "molecular microscope" can be beneficial in diagnosis and stratification of the risk of graft failure. High expression of ENDAT (endothelial activation and injury transcript) improves prediction of kidney graft failure more than C4d staining. Based on gene expression, the AMR scoring system correlates with the diagnosis of AMR and predicts graft loss in the future. The main goal of our work was to recognize patients at risk of AMR. In our study, we confirmed the efficacy and safety of acute AMR therapy with plasmaphereses and administration of intravenous immunoglobulins for improving outcomes of kidney transplantation....
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Biocompatibility of Peritoneal Dialysis Solutions
Procházková Pöpperlová, Anna ; Opatrná, Sylvie (advisor) ; Krejčí, Karel (referee) ; Šebeková, Katarína (referee)
Peritoneal dialysis (PD) is a form of renal replacement therapy using the peritoneum as a dialysis membrane. PD solutions employed to remove nitrogen metabolites and excess plasma fluid, and to restore electrolyte and acid-base balance are being developed to minimize local and systemic inflammatory responses while maintaining peritoneal homeostasis and host defense. The effect of chronic action of PD solutions on the peritoneum results in its remodeling and, possibly, eventual loss of peritoneal ultrafiltration capacity. Factors most responsible for late complications and peritoneal remodeling include high glucose levels in PD solutions, and the presence and formation of glucose degradation products (GDP) and advanced glycation end - products (AGEs) in the peritoneal cavity. The aim of our study described in this dissertation was to test various PD solutions with different glucose content and GDP and, using AGEs receptor ligands, to define their systemic effects and identify PD solutions with highest biocompatibility. This part of the dissertation characterizes conventional glucose - based solutions, low - glucose and GDP load solutions as well as glucose polymer (icodextrin) - based PD solutions while determining the plasma and dialysate levels of soluble receptor for AGEs (s - RAGE) and its...
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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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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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BK virus infection in kidney transplant patients.
Girmanová, Eva ; Viklický, Ondřej (advisor) ; Stříž, Ilja (referee) ; Krejčí, Karel (referee)
Polyoma BK virus is associated with graft dysfunction leading to BK viral nephropathy (BKVN) in 1-10% of kidney transplant recipients, moreover 30-80% of kidney transplant recipients experience asymptomatic reactivation of the virus that does not result in BKV associated damage of the renal allograft. The first aim of this study was to introduce monitoring of BK virus replication in the blood and urine of patients within first year after transplantation. Risk factors were evaluated and limit values for viremia and viruria for BKVN development was established. Positive BK viruria >107 copies/ml and positive BK viremia >104 copies/ml occurred in 25.8% and 5%; respectively. 3 patients out of monitoring study developed BKVN. Using ROC analysis, limit values for the development of BKVN were set at 103 copies/ml serum for BK viremia and 6.7x107 copies/ml BK viruria. The second objective was to determine the expression profile of the immune genes in kidney biopsies in three groups of patients with varying degrees of reactivation of the BK virus (without virus reactivation, with asymptomatic viruria, BKVN). 90 genes of immune response were measured by the TaqMan® low density array RT-qPCR. The analysis of biopsies from patients with non-signalling viruses led to the identification of 5 differentially...
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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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Biocompatibility of Peritoneal Dialysis Solutions
Procházková Pöpperlová, Anna ; Opatrná, Sylvie (advisor) ; Krejčí, Karel (referee) ; Šebeková, Katarína (referee)
Peritoneal dialysis (PD) is a form of renal replacement therapy using the peritoneum as a dialysis membrane. PD solutions employed to remove nitrogen metabolites and excess plasma fluid, and to restore electrolyte and acid-base balance are being developed to minimize local and systemic inflammatory responses while maintaining peritoneal homeostasis and host defense. The effect of chronic action of PD solutions on the peritoneum results in its remodeling and, possibly, eventual loss of peritoneal ultrafiltration capacity. Factors most responsible for late complications and peritoneal remodeling include high glucose levels in PD solutions, and the presence and formation of glucose degradation products (GDP) and advanced glycation end - products (AGEs) in the peritoneal cavity. The aim of our study described in this dissertation was to test various PD solutions with different glucose content and GDP and, using AGEs receptor ligands, to define their systemic effects and identify PD solutions with highest biocompatibility. This part of the dissertation characterizes conventional glucose - based solutions, low - glucose and GDP load solutions as well as glucose polymer (icodextrin) - based PD solutions while determining the plasma and dialysate levels of soluble receptor for AGEs (s - RAGE) and its...
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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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