|
|
Cytomegalovirus infection after kidney transplantation
Reischig, Tomáš ; Třeška, Vladislav (advisor) ; Viklický, Ondřej (referee) ; Zadražil, Josef (referee) ; Pazdiora, Petr (referee)
1 SUMMARY Cytomegalovirus (CMV) disease is a common infectious complication in patients after solid organ transplantation. The last decade witnessed major advances in CMV disease prevention. Use of universal prophylaxis or preemptive therapy resulted in a decrease in the incidence of CMV disease from 20-60% to 5-20%. However, the efficacy of preventive approaches in terms of indirect effects of CMV occurrence is problematic. Association with allograft rejection belongs to well documented and clinically extremely important indirect effects of CMV with a prolonged adverse impact on graft survival. Potential mechanisms include overexpression of major histocompatibility complex molecules, growth factors and cytokines, and upregulation of adhesion molecules. A number of questions remain to be answered in evaluating CMV as a risk factor for acute rejection. While CMV disease is associated with an increased incidence of acute rejection, data regarding the role of asymptomatic CMV viremia are controversial. In our research we evaluated the role of CMV in pathogenesis of allograft rejection in the era of modern immunosuppression and CMV prophylaxis as well as optimal preventive strategy to minimize impact of CMV. In the first trial, renal transplant (RTx) recipients were followed prospectively for 12 months to...
|
|
|
Contextual analysis of medication adherence in patients after kidney transplantation
Košťálová, Barbora ; Malý, Josef (advisor) ; Reischig, Tomáš (referee) ; Vlček, Jiří (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Training Workplace Department of Social and Clinical Pharmacy Doctoral Degree Program Clinical and Social Pharmacy Candidate Mgr. Barbora Košťálová Supervisor doc. PharmDr. Josef Malý, Ph.D. Advisor Title of Doctoral Thesis Contextual analysis of medication adherence in patients after kidney transplantation Introduction: Strict adherence to immunosuppressive medication (IS) is essential for organ transplant patients to minimize the risk of graft rejection. Growing number of randomized controlled trials (RCTs) shows the effectiveness of interventions to enhance medication adherence in transplantation, however, the real-world implementation is still a major challenge. The objective of the thesis was to analyze medication adherence in the context of selected clinical and behavioral aspects in Czech kidney transplant outpatients and to evaluate the range of information available in RCTs to support real-world implementation of adherence-enhancing interventions. Methods: 1) The cross-sectional study was conducted between April and December 2019 in the Transplant clinic of the University Hospital Hradec Králové. All adult outpatients were approached during their scheduled visit at the clinic. Data was collected via patient-administered...
|
|
|
Contextual analysis of medication adherence in patients after kidney transplantation
Košťálová, Barbora ; Malý, Josef (advisor) ; Reischig, Tomáš (referee) ; Vlček, Jiří (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Training Workplace Department of Social and Clinical Pharmacy Doctoral Degree Program Clinical and Social Pharmacy Candidate Mgr. Barbora Košťálová Supervisor doc. PharmDr. Josef Malý, Ph.D. Advisor Title of Doctoral Thesis Contextual analysis of medication adherence in patients after kidney transplantation Introduction: Strict adherence to immunosuppressive medication (IS) is essential for organ transplant patients to minimize the risk of graft rejection. Growing number of randomized controlled trials (RCTs) shows the effectiveness of interventions to enhance medication adherence in transplantation, however, the real-world implementation is still a major challenge. The objective of the thesis was to analyze medication adherence in the context of selected clinical and behavioral aspects in Czech kidney transplant outpatients and to evaluate the range of information available in RCTs to support real-world implementation of adherence-enhancing interventions. Methods: 1) The cross-sectional study was conducted between April and December 2019 in the Transplant clinic of the University Hospital Hradec Králové. All adult outpatients were approached during their scheduled visit at the clinic. Data was collected via patient-administered...
|
|
|
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....
|
|
|
Infectious complications after kidney transplantation
Kačer, Martin ; Reischig, Tomáš (advisor) ; Pazdiora, Petr (referee) ; Seeman, Tomáš (referee)
3 Abstract Infectious complications after kidney transplantation In the general part of this work, the most common and typical infectious complications in renal transplant recipients are reviewed. The practical part presents results of our research on prevention of the most common infection in renal transplant recipients, cytomegalovirus infection. Globally, infection belongs amongst the main causes of morbidity of solid organ recipients and is the second leading cause of mortality in patients with a functioning kidney graft. In the first year post kidney transplant, approximately one half of recipients undergo a clinically apparent infectious complication and 20% of patients are hospitalized due to infection. Cytomegalovirus (CMV) is the most common viral infection in kidney transplant patients and its occurence is associated with serious negative consequences for both kidney and patient survival. Prevention of CMV is essential in renal transplant recipients. Valganciclovir, due to its efficacy and good bioavailability, is the most commonly used antiviral agent used in CMV prophylaxis. The only currently recommended alternative for the prevention of CMV in patients undergoing renal transplantation is valacyclovir. So far, studies comparing valacyclovir and valganciclovir for CMV prophylaxis in renal...
|
|
|
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...
|
|
|
BK-polyomavirus infection in patients after simultaneous pancreas and kidney transplantation
Mindlová, Martina ; Saudek, František (advisor) ; Forstová, Jitka (referee) ; Reischig, Tomáš (referee)
Introduction. The aim of the study was to introduce a new BKV PCR protocol in our centre and to verify its accuracy as well as to assess the prevalence, risk factors of BK virus replication, course of BKV infection and therapeutic approaches in simultaneous pancreas and kidney (SPK) recipients in order to design a screening protocol. Methods. The results analysed by both Affigene® and Transplantation Virology, Basel PCR protocols were compared. Thereafter 183 SPK patients were examined to assess the prevalence of BK viremia, viruria and BKVN and to identify the risk factors of BKV replication. The cases of retransplantation after a graft loss due to BKVN were retrospectively described. Results. 100 of results were analysed according to the Affigene ® and Transplantation Virology, Basel PCR protocols with the accordance of 95%, Rho = 0,946, 95% CI: 0.920 - 0.963, P<0,0001, Bland-Altman plot analyses: bias Basel PCR protocol/Affigene® BKV trender: -0,1 (mean) *±1.96 SD: -1,6 - 1,3] for both methods. Point-prevalence was assessed in 183 patients; Viruria found in 17,3 %, viremia in 3.8% of patients. High-level viruria >107 copies/mL detected in 3,7% of patiets, high-level virémia >104 in 1,6% of patients simultaneously with high-level viruria. BKVN was found in 0,5% of patients. Diabetes duration...
|
|
|
Infectious complications after kidney transplantation
Kačer, Martin ; Reischig, Tomáš (advisor) ; Pazdiora, Petr (referee) ; Seeman, Tomáš (referee)
3 Abstract Infectious complications after kidney transplantation In the general part of this work, the most common and typical infectious complications in renal transplant recipients are reviewed. The practical part presents results of our research on prevention of the most common infection in renal transplant recipients, cytomegalovirus infection. Globally, infection belongs amongst the main causes of morbidity of solid organ recipients and is the second leading cause of mortality in patients with a functioning kidney graft. In the first year post kidney transplant, approximately one half of recipients undergo a clinically apparent infectious complication and 20% of patients are hospitalized due to infection. Cytomegalovirus (CMV) is the most common viral infection in kidney transplant patients and its occurence is associated with serious negative consequences for both kidney and patient survival. Prevention of CMV is essential in renal transplant recipients. Valganciclovir, due to its efficacy and good bioavailability, is the most commonly used antiviral agent used in CMV prophylaxis. The only currently recommended alternative for the prevention of CMV in patients undergoing renal transplantation is valacyclovir. So far, studies comparing valacyclovir and valganciclovir for CMV prophylaxis in renal...
|
|
|
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...
|
|
|
Selected candidate genes variants with respect to the renal transplantation outcomes
Bandúr, Štěpán ; Viklický, Ondřej (advisor) ; Zadražil, Josef (referee) ; Reischig, Tomáš (referee)
6 Abstract: Renal transplantation outcomes might be influenced by genetic determinants, genes encoding structural and regulatory proteins involved in respective pathophysiological and immunological pathways. CYP3A4/CYP3A5 and ABCB1/MDR1 genes encoding cytochrome P450IIIA and P-glycoprotein, proteins determining bioavailability of immunosuppressants- calcineurin inhibitors and mTOR inhibitors, play important role. Polymorphisms in these genes have been suggested to influence immunosuppressants pharmacokinetics and renal transplant outcomes. The association of CYP3A4 -288A>G, CYP3A5 +6986G>A, ABCB1/MDR1 +1236C>T, +2677G>T>A and +3435C>T polymorphisms with clinical and laboratory endpoints was assessed by using haplotype analysis approach in 1016 patients. Except of HLA-DR mismatch, delayed graft function and kidney graft donor age, [ABCB1/MDR1+1236C;+2677G;+3435T] haplotype was independent predictor of acute rejection, but did not influence kidney graft survival. Homozygotes for the [CYP3A4- 288A;CYP3A5+6986G] haplotype had higher bioavailability of tacrolimus at week one. ABCB1/MDR1 haplotypes did not influence pharmacokinetics, but modified the risk of acute rejection, suggesting that allelic arrangement of the genetic loci was a stronger regulator of P- glycoprotein activity than single polymorphisms....
|
guest ::
