Transplantation
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Review Meta Analysis
Alemtuzumab induction therapy in kidney transplantation: a systematic review and meta-analysis.
Alemtuzumab (MabCampath or Campath; Genzyme, Cambridge, MA) is a CD52-specific monoclonal antibody that causes profound and sustained lymphocyte depletion. Its use as an induction therapy in organ transplantation is increasing. Since our last systematic review in 2006, where we identified the need for good-quality randomized controlled trials (RCTs), several RCTs have been published that examine its efficacy and safety in kidney transplantation. The aim of this study was to evaluate the current evidence for alemtuzumab induction therapy in kidney transplantation. ⋯ Alemtuzumab induction reduces the risk of BPAR compared with IL-2RAs but not rATG. Because the incidence of other efficacy outcomes (graft loss, DGF, and patient death) was similar, if it is felt that an induction agent is necessary, then our analysis suggests that it is more acceptable to base the choice of induction agent on safety outcomes and/or costs.
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Editorial Review
Whose consent matters? Controlled donation after cardiac death and premortem organ-preserving measures.
The goal of this overview is to discuss the ethics of premortem organ-protective measures with the aim of improving donation outcome for the recipient. A literature review was undertaken to find out which such measures were implemented in published articles on controlled donation after cardiac death. We reviewed studies on controlled human organ donation after cardiac death that were published in PUBMED and EMBASE between 2000 and 2010. ⋯ The authors conclude that premortem measures have the potential to instrumentalize the organ donor and that they should be restricted to cases in which the donor wish is known-directly, through a donor card, or through a surrogate decision maker-and specific consent to premortem procedures has been given. This specific consent should be required at least until the general public is aware that premortem measures may be performed. If potential donors were informed about premortem measures as part of a community information effort, for example, school curricula, and again when they signed their donor card, one might consider their consent to be truly informed and valid.
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Review
Immunological issues in clinical composite tissue allotransplantation: where do we stand today?
Composite tissue allografts are made of histogenetically different tissues and although skin seems to be the most antigenic of them, it is unknown whether the dominant immune response is really directed against the skin or we have insufficient information on the involvement of the other components of these allografts. The first clinical signs of acute rejection manifest on the skin and microscopically the earliest lesions consist in a dermal perivascular lymphocytic infiltrate, predominantly made of CD3+/CD4+ T cells. On the basis of the histological changes, a specific score (Banff score 2007) has been established to assess the severity of rejection. ⋯ The complications in composite tissue allotransplantation are similar to those usually reported after solid organ transplantation and have prompted different strategies to minimize the maintenance immunosuppression or to induce donor-specific tolerance. Furthermore, to what extent the immunosuppression can be tapered is unknown, as well as the influence of donor bone-marrow infusion in tolerance and chronic rejection. The increasing number of patients and the longer follow-up hopefully will allow answering these questions.
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The introduction of generic immunosuppressant medications may present an opportunity for cost savings in solid organ transplantation if equivalent clinical outcomes to the branded counterparts can be achieved. An interprofessional working group of the Canadian Society of Transplantation was established to develop recommendations on the use of generic immunosuppression in solid organ transplant recipients (SOTR) based on a review of the available data. Under current Health Canada licensing requirements, a demonstration of bioequivalence with the branded formulation in healthy volunteers allows for bridging of clinical data. ⋯ The advent of generic immunosuppression will require new practices including more frequent therapeutic drug and clinical monitoring, and increased patient education. The additional workload placed on transplant centers without additional funding will create challenges and could ultimately jeopardize patient outcomes. Until more robust clinical data are available and adequate regulatory safeguards are instituted, caution in the use of generic immunosuppressive drugs in solid organ transplantation is warranted.
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Survival rates after lung transplantation are the lowest among solid organ transplantations. Long-term survival is limited by the development of chronic rejection, known as bronchiolitis obliterans syndrome (BOS). Risk factors, such as acute rejection and cytomegalovirus infection, contribute to the development of BOS. ⋯ This review shows that there may be involvement of genetic polymorphisms in the development of BOS. Genetic risk profiling of lung transplant recipients could be a promising approach for the future, enabling individualized risk stratification and personalized immunosuppressive treatment after transplantation. Further studies are needed to define risk alleles.