Current Opinion in Organ Transplantation最新文献

Purpose of review: Highly sensitized kidney transplant candidates, particularly those with calculated panel reactive antibody (CPRA) ≥99.9%, face significant immunologic barriers to transplantation. This review highlights recent clinical strategies that have improved transplant access and outcomes in this population, with a focus on allocation policy, kidney-paired donation, and desensitization.

Recent findings: Updates from national allocation systems and kidney-paired donation programs have demonstrated substantial gains in transplant access for many highly sensitized candidates. However, those with CPRA at least 99.9% remain difficult to match. Novel desensitization approaches, such as imlifidase, proteasome inhibitors, anti-CD38 mAbs, and early-phase CAR T-cell therapies have shown promise in selected patients. Increasingly, immunologic phenotyping or gene expression profiling may help tailor desensitization strategies to individual recipients.

Summary: Most highly sensitized candidates now achieve transplant through allocation policy or paired donation. For those with CPRA at least 99.9%, desensitization will likely remain an important tool to facilitate transplantation. Emerging therapies and immunologic profiling may help individualize treatment and expand transplant access for this challenging group.

Purpose of review: Machine perfusion has emerged as a transformative technique in organ transplantation, helping to address the persistent organ shortage while mitigating ischemia-reperfusion injury. Since the 2010s, its implementation in Europe has expanded access to life-saving transplants. This review examines the impact of hypothermic oxygenated perfusion (HOPE) on liver transplantation, with a focus on viability assessment, posttransplant complications, oncologic outcomes, organ utilization, and cost-effectiveness.

Findings: HOPE offers significant advantages over traditional cold storage preservation including enhanced mitochondrial protection, reduced oxidative stress, and improved posttransplant recovery. Studies have demonstrated its effectiveness in lowering the incidence of graft dysfunction, biliary complications, and overall transplant-related issues. Additionally, HOPE provides viability assessment by incorporating biomarkers such as flavin mononucleotide (FMN) and syndecan-1 (Sdc-1), which may aid in graft selection and predicting posttransplant outcomes. This review explores the cellular mechanisms underlying HOPE, its influence on graft function and transplant success, and its role in enhancing viability assessment and cost-effectiveness.

Summary: HOPE represents a significant advancement in liver transplantation, offering a safer, more efficient alternative to traditional preservation methods. By improving both clinical outcomes and being cost efficient, this technique has the potential to become a standard of care in liver transplantation. Further research should focus on refining viability assessment protocols, optimizing logistical implementation, and expanding clinical adoption to maximize organ utilization and improve patient survival.

Purpose of review: Current immune risk criteria for selecting induction therapy lack precision. Here, we examined the relationship of human leukocyte antigen (HLA) and molecular matching with outcomes in patients treated with different induction regimens and immunosuppressive minimization protocols to inform their potential utility in guiding therapy.

Recent findings: Initial studies evaluating induction therapy suggest the role of HLA matching in immune risk-stratification. However, criteria based on antigen level matching and panel-reactive antibodies are imprecise and risk over-assigning patients to treatment with T-cell-depleting agents. Molecularly defined low-risk patients comprise 19-61% of study cohorts. Across heterogenous induction regimens and immunosuppressive minimization studies, these patients consistently demonstrated low immune event rates, providing the basis for prospective trials to test its utility in guiding the choice of induction regimens.

Summary: Granular assessment of immune compatibility using molecular mismatch methods coupled with rapid genotyping technologies may help improve the selection of immunosuppressive regimens but will require prospective confirmation.

Purpose of review: This paper explores the ethical complexities of surgical buy-in within the context of organ transplantation. Surgical buy-in refers to an implicit agreement in which transplant recipients consent not only to the surgery itself, but also to the necessary postoperative care in the context of scarce donor organs. Ethical tensions arise when patients choose to deviate from suggested care pathways after receiving organ transplantation, challenging the balance between respecting individual autonomy and ensuring just stewardship of finite donor organs.

Recent findings: Recent literature highlights the experience of transplant teams when patients withdraw from posttransplant care, a phenomenon termed "cashing out." Approximately 60% of surgeons performing high-risk surgeries expect postoperative compliance as a precondition to surgery. In transplant settings, this expectation is intensified by the communal impact of organ allocation, raising justice-based concerns when organ recipients withdraw from postoperative protocols.

Summary: This review proposes a modified informed consent process that explicitly delineates a recipient's ethical commitment when receiving an organ transplant. Improving transparency and aligning expectations with patients can help transplant teams better navigate the ethical tension between respecting patient autonomy and responsibly stewarding scarce public resources.

Purpose of review: Transplantation in candidates with psychotic disorders has been a controversial topic for over 40 years. Reviewing the outcomes of these candidates may inform decisions going forward, though it is unclear whether outcomes with kidney recipients is generalizable to other organs, which are life-sparing not mainly life-enhancing.

Recent findings: Outcomes in recipients with psychotic disorders after kidney transplants were described in three studies. Outcomes with heart, lung, pancreas, and small bowel or multivisceral transplants is sparse to nonexistent. There were 26 cases and 8 case series published, mostly highly selected patients, with small sample size, and the majority had less than 3-year follow-up. Guidelines were proposed for this population based on a survey of 12 centers.

Summary: More systematic study is needed on the risks and barriers to transplantation in these candidates. More data is needed regarding outcomes in those recipients with life-sparing transplants for whom there is not a rescue plan in case the graft is lost. Candidates should be evaluated on an individual basis based on known risk factors in accordance with the ethical principles of beneficence, justice, and utility in the face of scarce resources.

Purpose of review: This article will review the use of HLA molecular mismatch algorithms to predict the risk of de-novo DSA and rejection in pediatric heart transplant recipients. Here, we will focus on results obtained using the combined algorithm approach pairing HLAMatchmaker or HLA-EMMA with PIRCHE-II.

Recent findings: The combined algorithm approach was recently used to assess risk of de-novo DSA and rejection in a pediatric heart transplant cohort from Clinical Trials in Organ Transplant in Children 04/09. This approach to analyzing HLA molecular mismatch data allowed for a more granular assessment of de-novo DSA and rejection risk than any individual algorithm.

Summary: Advances in HLA molecular mismatch methods may enable personalized immunosuppression management that improves outcomes of pediatric heart transplant recipients.

Purpose of review: Normothermic regional perfusion (NRP) for the donation after circulatory death (DCD) increases the supply and function of organs. However, the procedures used have led to significant ethical controversies. Despite the numerous studies on the subject, moral issues are seldom analyzed comparatively. This article describes and identifies three ethical problems related to NRP, critiquing them with philosophical and ethical suggestions.

Recent findings: Current literature suggests that using oxygenated blood instead of cold perfusion enhances the function of transplanted organs, more pronounced in thoracic organs. The blood perfusion requires surgical maneuvers such as stimulating and restarting the heart while in the patient, leading to criticism based on ethical grounds, relating to declaration of death and violation of the dead donor rule (DDR).

Summary: These findings are a significant ethical quandary that threatens to eliminate the use of NRP and jeopardize the benefits mainly to recipients of hearts and lungs. The declaration of death, violation of the dead donor rule, informed consent, and public perception are the main moral criticisms of NRP. Neither the declaration of death nor the dead donor rule is violated, and justice is served through the provision of informed consent, thereby preserving public trust and the donors' wishes.

Purpose of review: Organ transplantation is a vital medical procedure that saves and extends lives. However, it requires a careful balance of resources, which are often limited by managed care constraints. Renal transplantation is the definitive treatment for patients with end-stage renal disease (ESRD). We share our experience with a managed care organization and how it upheld ethical principles while maintaining solvency and cost-effectiveness.

Recent findings: Managed care organizations are pervasive healthcare entities and highly regulated businesses. To remain solvent, patients must join them and be satisfied with the care, or they will switch to a competitor. Most programs currently use the comprehensive risk-based managed model, consistent with federal regulations.CareMore in California, established in 1992, provided care to patients with ESRD. Services were based on ethical principles and alignment of incentives. An unsuccessful program or one fraught with complications is a major financial loss. The program was designed to ensure a positive outcome, aligning the incentives of providers, patients, and the program. As a result, the program was solvent, efficient, and ethical.

Summary: In conclusion, moral critiques of managed care plans overlook the benefits for individuals and society. The eventual advantage to healthcare and the individual is assured when principles and incentives are aligned.

Purpose of review: Liver transplantation using pediatric and technical variant grafts presents unique challenges due to graft size, vascular anomalies, and ischemia-reperfusion injury. Static cold storage has been the standard preservation method, but machine perfusion is emerging as a superior technique for improving graft function and posttransplant outcomes. This review addresses the role of machine perfusion in preserving pediatric and technical variant grafts with a focus on feasibility and impact on graft viability and early allograft function.

Recent findings: Clinical and experimental studies of hypothermic and normothermic machine perfusion were reviewed for pediatric and technical variant grafts. Key parameters, perfusion dynamics, biochemical markers, and outcomes were investigated and suggested that machine perfusion enhances graft quality. In addition, the feasibility and potential of liver splitting during machine perfusion along with technical considerations is being addressed.

Summary: Machine perfusion represents a transformative approach for pediatric and technical variant grafts, improving preservation quality and posttransplant outcomes while minimizing adverse events especially primary graft nonfunction. Currently, only normothermic machine perfusion enables viability assessment, offering a potential for expanding the donor pool. Due to the low number of pediatric liver transplantation and utilization of technical variant grafts, multicenter studies are required to define protocols and selection criteria for individual grafts, and establish machine perfusion as a standard practice in pediatric liver transplantation.