Current Opinion in Organ Transplantation最新文献

Purpose of review: Donation after circulatory death (DCD) is one of the most promising methods for expanding the organ pool for transplantation. Yet realizing the promise of DCD depends on careful coordination of end of life treatment with organ donation authorization, organ preservation, and recovery.

Recent findings: As organ procurement organizations (OPO) increase their DCD efforts, challenges regarding timely referral, delays in organ recovery coordination, and the requisite separation of clinical decisions from organ donation decisions are potentially preventing successful organ recovery, and having negative consequences for trust between OPOs, hospital staff, and donor families.

Summary: Recent DCD cases should be scientifically studied to understand the variables that lead to successful versus unsuccessful DCD. These variables need to be understood in order to adjust legal, logistical, and ethical approaches to DCD and thus ensure the expansion of the organ pool while preserving trust in organ transplantation.

Purpose of review: This review aims to address the critical issue of expanding deceased donor kidney pool and reducing the discard rates of viable kidneys in the United States. It highlights advances in organ preservation techniques and explores strategies for expanding the donor pool by leveraging suboptimal and high-risk nonuse kidneys, including those affected by acute kidney injury (AKI), hepatitis C virus (HCV), and hepatitis B virus (HBV).

Recent findings: Innovations in organ preservation, including hypothermic and normothermic machine perfusion, have demonstrated efficacy in improving outcomes for marginal and extended-criteria kidneys. The integration of normothermic regional perfusion (NRP) for donation after cardiac death (DCD) donors has enhanced organ utilization and graft viability. Additionally, research confirms that kidneys from AKI and HCV-positive donors, when managed with appropriate protocols, yield comparable long-term outcomes to standard transplants. Emerging data on HBV-positive donor kidneys further underscore their potential to safely expand transplant access with targeted antiviral prophylaxis.

Summary: Optimizing deceased donor kidney utilization requires a multi-faceted approach, including advancements in preservation technologies, evidence-based decision-making for high-risk organs, and policy innovations. Leveraging these strategies can help address the growing organ shortage, enhance transplant outcomes, and ensure broader access to life-saving kidney transplants.

Purpose of review: Despite the introduction of many new immunosuppressive medications, allograft rejection remains a significant complication in transplantation. The use of "liquid biopsy" to evaluate allograft function and detect early rejection has recently become a prominent focus of investigation as it holds promise in providing noninvasive and immediate insights into the cellular and molecular makeup of the graft.

Recent findings: In recent years, the introduction of molecular medicine along with the use of new technologies, including high-throughput techniques, has not only accelerated biomarker discovery but has also contributed to improving our understanding of the mechanisms underlying immune rejection. Genomics, transcriptomics, and metabolomics approaches, along with the increasing use of machine learning techniques, have paved the way for the discovery and development of novel biomarkers.

Summary: Each year, there are hundreds of new biomarker discoveries in the publications. However, only a small fraction can be practically used as clinical tests or surrogate endpoints, receive FDA approval, and reach clinical application. Well designed and reproducible discovery and validation studies are rare and crucial. A contributing factor could be poor study design or quality of biospecimen repositories. In this review, we discuss urinary biomarkers of kidney allograft rejection that have shown promising findings but have yet to be successfully transitioned from bench to bedside.

Purpose of review: This review highlights recent advancements in liver organ allocation, specifically the transition to MELD 3.0 and the potential introduction of continuous distribution. These developments are timely, as they address the increasing need for a more efficient, equitable, and personalized system for prioritizing liver transplant candidates.

Recent findings: The review covers two key innovations: MELD 3.0: A refined version of the original MELD score, designed to improve the prioritization process by incorporating additional factors that offer a more accurate and urgent measure of transplant need. This approach aims to better assess the severity of liver disease and the need for transplantation. Continuous distribution: A dynamic approach that shifts away from the static allocation model. It integrates multiple donor and recipient variables - such as geographic location, organ quality, and recipient condition - into a continuous, flexible allocation process. This framework seeks to make more nuanced decisions based on a broader set of factors that reflect transplant suitability.

Summary: These innovations aim to enhance fairness and patient outcomes by refining candidate prioritization and reducing disparities in access to transplants. However, implementing these systems presents challenges, such as technical complexities and regional differences in access. Ongoing evaluation is necessary to ensure their effectiveness and equitable implementation across diverse patient populations.

Purpose of review: Liver transplantation for metastatic colorectal cancer has been shown to be efficacious in the well selected patient. In the United States, there remains controversy on the appropriate selection criteria and optimal graft type to be utilized in these patients. Our group advocates for strict recipient selection and early access to quality grafts for these recipients.

Recent findings: In the past two years, there has been an explosion of centers reporting outcomes after liver transplantation for colorectal liver metastases. In North America, the publications have focused on single center experiences. The group in Oslo has reported their long-term outcomes of all transplanted patients. The TransMet randomized controlled trial has demonstrated efficacy of liver transplantation with chemotherapy over chemotherapy alone.

Summary: Liver transplantation for metastatic colorectal cancer is an efficacious procedure for the well selected patient. Regardless of graft type, potential liver transplant recipients with liver limited unresectable colorectal liver metastases should be evaluated with a strict criterion to determine eligibility. Once eligible, patients should receive early access to high quality grafts.

Purpose of review: The objective of this review is to provide an update on the application of artificial intelligence (AI) for the histological interpretation of kidney transplant biopsies.

Recent findings: AI, particularly convolutional neural networks (CNNs), has demonstrated great potential in accurately identifying kidney structures, detecting abnormalities, and diagnosing rejection with improved objectivity and reproducibility. Key advancements include the segmentation of kidney compartments for accurate assessment and the detection of inflammatory cells to aid in rejection classification. Development of decision support tools like the Banff Automation System and iBox for predicting long-term allograft failure have also been made possible through AI techniques. Challenges in AI implementation include the need for rigorous evaluation and validation studies, computational resource requirements and energy consumption concerns, and regulatory hurdles. Data protection regulations and Food and Drug Administration (FDA) approval represent such entry barriers. Future directions involve the integration of AI of histopathology with other modalities, such as clinical laboratory and molecular data. Development of more efficient CNN architectures could be possible through the exploration of self-supervised and graph neural network approaches.

Summary: The field is progressing towards an automated Banff Classification system, with potential for significant improvements in diagnostic processes and patient care.

Purpose of review: Estimation of genetic risk is crucial for understanding heritable diseases but also transplant outcomes. Polygenic risk scores (PRSs) are constructed from genome-wide association studies (GWAS) summing an individual's risk alleles weighted by their effect size. Introducing PRSs into transplant medicine may improve predictions of outcomes such as rejection, graft loss or death. This review of recent publications highlights the additional variability in outcomes explained by PRSs beyond established clinical models.

Recent findings: Four studies on PRSs in transplantation have examined outcomes such as acute rejection, changes in posttransplant estimated glomerular filtration rate (eGFR) and posttransplant diabetes mellitus (PTDM) and explored the role of donor polygenic burden for cerebrovascular traits. PRSs have been showing utility in predicting PTDM [adjusted odds ratio (OR):1.48 (95% confidence interval (CI): 1.06, 2.08]. A PRS based on a non-HLA alloimmunity GWAS explained additional variability for acute rejection [adjusted hazard ratio (HR): 1.54, 95% CI: 1.07, 2.22]. Donor PRSs for hypertension and cerebrovascular traits correlated with lower recipient eGFR (HR: 1.44, 95% CI: 1.07, 1.93). Genetic variation was also linked to long-term kidney function, though clinical variables explained a greater proportion of the variability (0.3% vs. 32%).

Summary: Currently, PRSs modestly enhance outcome prediction in transplantation when added to clinical models. With a more biologically based selection of variants, PRSs may gain greater value in transplant risk assessment.