Therapeutic apheresis is a cornerstone of therapy for several conditions in transplantation medicine and is available in different technical variants. In the setting of kidney transplantation, immunological barriers s...Therapeutic apheresis is a cornerstone of therapy for several conditions in transplantation medicine and is available in different technical variants. In the setting of kidney transplantation, immunological barriers such as ABO blood group incompatibility and preformed donor-specific antibodies can complicate the outcome of deceased-or living-donor transplantation. Postoperatively,additional problems such as antibody-mediated rejection and a recurrence of primary focal segmental glomerulosclerosis can limit therapeutic success and decrease graft survival. Therapeutic apheresis techniques find application in these issues by separating and selectively removing exchanging or modifying pathogenic material from the patient by an extracorporeal aphaeresis system. The purpose of this review is to describe the available techniques of therapeutic aphaeresis with their specific advantages and disadvantages and examine the evidence supporting the application of therapeutic aphaeresis as an adjunctive therapeutic option to immunosuppressive agents in protocols before and after kidney transplantation.展开更多
Renal transplantation is a well established treatment for end-stage renal disease, allowing most patients to return to a satisfactory quality of life. Studies have identified many problems that may affect adaptation t...Renal transplantation is a well established treatment for end-stage renal disease, allowing most patients to return to a satisfactory quality of life. Studies have identified many problems that may affect adaptation to the transplanted condition and postoperative compliance. The psychological implications of transplantation have important consequences even on strictly physical aspects. Organ transplantation is very challenging for the patient and acts as an intense stressor stimulus to which the patient reacts with neurotransmitter and endocrine-metabolic changes. Transplantation can result in a psychosomatic crisis that requires the patient to mobilize all bio-psychosocial resources during the process of adaptation to the new foreign organ which may result in an alteration in self-representation and identity, with possible psychopathologic repercussions. These reactions are feasible in mental disorders, e.g., post-traumatic stress disorder, adjustment disorder, and psychosomatic disorders. In organ transplantation, the fruitful collaboration between professionals with diverse scientific expertise, calls for both a guarantee for mental health and greater effectiveness in challenging treatments for a viable association between patients, family members and doctors. Integrated and multidisciplinary care should include uniform criteria and procedures for standard assessments, for patient autonomy, adherence to therapy, new coping strategies and the adoption of more appropriate lifestyles.展开更多
BACKGROUND Tacrolimus extended-release tablets have been Food and Drug Administrationapproved for use in the de novo kidney transplant population.Dosing requirements often vary for tacrolimus based on several factors ...BACKGROUND Tacrolimus extended-release tablets have been Food and Drug Administrationapproved for use in the de novo kidney transplant population.Dosing requirements often vary for tacrolimus based on several factors including variation in metabolism based on CYP3A5 expression.Patients who express CYP3A5 often require higher dosing of immediate-release tacrolimus,but this has not been established for tacrolimus extended-release tablets in the de novo setting.AIM To obtain target trough concentrations of extended-release tacrolimus in de novo kidney transplant recipients according to CYP3A5 genotype.METHODS Single-arm,prospective,single-center,open-label,observational study(ClinicalTrials.gov:NCT037-13645).Life cycle pharma tacrolimus(LCPT)orally once daily at a starting dose of 0.13 mg/kg/day based on actual body weight.If weight is more than 120%of ideal body weight,an adjusted body weight was used.LCPT dose was adjusted to maintain tacrolimus trough concentrations of 8-10 ng/mL.Pharmacogenetic analysis of CYP3A5 genotype was performed at study conclusion.RESULTS Mean time to therapeutic tacrolimus trough concentration was longer in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers(6 d vs 13.5 d vs 4.5 d;P=0.025).Mean tacrolimus doses and weight-based doses to achieve therapeutic concentration were higher in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers(16 mg vs 16 mg vs 12 mg;P=0.010)(0.20 mg/kg vs 0.19 mg/kg vs 0.13 mg/kg;P=0.018).CYP3A5 extensive metabolizers experienced lower mean tacrolimus trough concentrations throughout the study period compared to CYP3A5 intermediate metabolizers and non-expressers(7.98 ng/mL vs 9.18 ng/mL vs 10.78 ng/mL;P=00.008).No differences were identified with regards to kidney graft function at 30-d post-transplant.Serious adverse events were reported for 13(36%)patients.CONCLUSION Expression of CYP3A5 leads to higher starting doses and incremental dosage titration of extended-release tacrolimus to achieve target trough concentrations.We suggest a higher starting dose of 0.2 mg/kg/d for CYP3A5 expressers.展开更多
During post-transplant evolution, adolescents may present problems with adherence to treatment, becoming a high-risk group for graft loss. Here, we report a case which describes an adolescent patient who lost a graft ...During post-transplant evolution, adolescents may present problems with adherence to treatment, becoming a high-risk group for graft loss. Here, we report a case which describes an adolescent patient who lost a graft due to humoral rejection associated with lack of adherence to treatment. During chronic peritoneal dialysis therapy, the patient developed pain and increased volume in the graft area, fever, gross hematuria and leukocyturia upon urine examination. The patient was diagnosed with graft immune intolerance syndrome and transplantectomy was suggested. Finally, a graft embolization was performed. A decrease in symptoms was observed until the patient became asymptomatic.展开更多
文摘Therapeutic apheresis is a cornerstone of therapy for several conditions in transplantation medicine and is available in different technical variants. In the setting of kidney transplantation, immunological barriers such as ABO blood group incompatibility and preformed donor-specific antibodies can complicate the outcome of deceased-or living-donor transplantation. Postoperatively,additional problems such as antibody-mediated rejection and a recurrence of primary focal segmental glomerulosclerosis can limit therapeutic success and decrease graft survival. Therapeutic apheresis techniques find application in these issues by separating and selectively removing exchanging or modifying pathogenic material from the patient by an extracorporeal aphaeresis system. The purpose of this review is to describe the available techniques of therapeutic aphaeresis with their specific advantages and disadvantages and examine the evidence supporting the application of therapeutic aphaeresis as an adjunctive therapeutic option to immunosuppressive agents in protocols before and after kidney transplantation.
文摘Renal transplantation is a well established treatment for end-stage renal disease, allowing most patients to return to a satisfactory quality of life. Studies have identified many problems that may affect adaptation to the transplanted condition and postoperative compliance. The psychological implications of transplantation have important consequences even on strictly physical aspects. Organ transplantation is very challenging for the patient and acts as an intense stressor stimulus to which the patient reacts with neurotransmitter and endocrine-metabolic changes. Transplantation can result in a psychosomatic crisis that requires the patient to mobilize all bio-psychosocial resources during the process of adaptation to the new foreign organ which may result in an alteration in self-representation and identity, with possible psychopathologic repercussions. These reactions are feasible in mental disorders, e.g., post-traumatic stress disorder, adjustment disorder, and psychosomatic disorders. In organ transplantation, the fruitful collaboration between professionals with diverse scientific expertise, calls for both a guarantee for mental health and greater effectiveness in challenging treatments for a viable association between patients, family members and doctors. Integrated and multidisciplinary care should include uniform criteria and procedures for standard assessments, for patient autonomy, adherence to therapy, new coping strategies and the adoption of more appropriate lifestyles.
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文摘BACKGROUND Tacrolimus extended-release tablets have been Food and Drug Administrationapproved for use in the de novo kidney transplant population.Dosing requirements often vary for tacrolimus based on several factors including variation in metabolism based on CYP3A5 expression.Patients who express CYP3A5 often require higher dosing of immediate-release tacrolimus,but this has not been established for tacrolimus extended-release tablets in the de novo setting.AIM To obtain target trough concentrations of extended-release tacrolimus in de novo kidney transplant recipients according to CYP3A5 genotype.METHODS Single-arm,prospective,single-center,open-label,observational study(ClinicalTrials.gov:NCT037-13645).Life cycle pharma tacrolimus(LCPT)orally once daily at a starting dose of 0.13 mg/kg/day based on actual body weight.If weight is more than 120%of ideal body weight,an adjusted body weight was used.LCPT dose was adjusted to maintain tacrolimus trough concentrations of 8-10 ng/mL.Pharmacogenetic analysis of CYP3A5 genotype was performed at study conclusion.RESULTS Mean time to therapeutic tacrolimus trough concentration was longer in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers(6 d vs 13.5 d vs 4.5 d;P=0.025).Mean tacrolimus doses and weight-based doses to achieve therapeutic concentration were higher in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers(16 mg vs 16 mg vs 12 mg;P=0.010)(0.20 mg/kg vs 0.19 mg/kg vs 0.13 mg/kg;P=0.018).CYP3A5 extensive metabolizers experienced lower mean tacrolimus trough concentrations throughout the study period compared to CYP3A5 intermediate metabolizers and non-expressers(7.98 ng/mL vs 9.18 ng/mL vs 10.78 ng/mL;P=00.008).No differences were identified with regards to kidney graft function at 30-d post-transplant.Serious adverse events were reported for 13(36%)patients.CONCLUSION Expression of CYP3A5 leads to higher starting doses and incremental dosage titration of extended-release tacrolimus to achieve target trough concentrations.We suggest a higher starting dose of 0.2 mg/kg/d for CYP3A5 expressers.
文摘During post-transplant evolution, adolescents may present problems with adherence to treatment, becoming a high-risk group for graft loss. Here, we report a case which describes an adolescent patient who lost a graft due to humoral rejection associated with lack of adherence to treatment. During chronic peritoneal dialysis therapy, the patient developed pain and increased volume in the graft area, fever, gross hematuria and leukocyturia upon urine examination. The patient was diagnosed with graft immune intolerance syndrome and transplantectomy was suggested. Finally, a graft embolization was performed. A decrease in symptoms was observed until the patient became asymptomatic.