Current Opinion in Organ Transplantation最新文献

Purpose of review: Normothermic machine perfusion (NMP) has emerged as technology for organ preservation and assessment. While NMP has been widely adopted for liver, lung, and heart transplantation, kidney NMP has faced slower clinical integration. Normothermic perfusion may potentially improve kidney transplant through improved preservation, graft viability assessment, mitigation of ischemia reperfusion injury, and treatment prior to transplant. The purpose of this review is to highlight the applications of NMP in kidney transplantation.

Recent findings: Kidney NMP has been proven well tolerated and feasible in multiple studies. Two recent randomized controlled trials did not demonstrate a benefit of NMP compared to cold storage. The use of NMP may increase utilization through improved logistics. Graft assessment during perfusion may allow for well tolerated transplantation of marginal kidneys. Successful long-term perfusion up to 4 days of discarded kidneys has been performed. Gene therapies and treatments, including immune modification, have been carried out during kidney NMP.

Summary: Normothermic perfusion has several applications to kidney transplantation including preservation, assessment, and treatment. Perfusion protocols viability criteria need to be defined. A portable, commercially available device is needed to increase clinical use. Further studies are needed to compare NMP to current preservation methods.

Purpose of review: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading reason for liver transplantation (LT) worldwide. With limited donor availability and rising posttransplant morbidity due to chronic noncommunicable disease, preventive strategies are urgently needed. This review highlights the role of physical activity in MASLD before and after LT.

Recent findings: Epidemiologic and interventional studies show that regular physical activity reduces liver fat, improves insulin sensitivity, and lowers aminotransferases, even without significant weight loss, in individuals with noncirrhotic MASLD. Physical activity also enhances muscle strength, physical performance, and quality of life. Although most research has focused on earlier disease stages, physical activity remains feasible and beneficial for patients with advanced chronic liver disease (advCLD) due to MASLD, improving performance, reducing frailty, and maintaining transplant candidacy. Following LT, preliminary studies suggest that regular physical activity may reduce cardiometabolic complications and improve functional recovery, though data on preventing recurrent MASLD or improving long-term outcomes is inconclusive.

Summary: Physical activity should be integrated into clinical pathways before and after LT for individuals living with MASLD. Future studies should address the unmet needs in both the advCLD and post-LT populations where maintaining LT candidacy and optimizing survival, quality of life, and long-term outcomes remains of high public health significance.

Purpose of review: The current global shortage of organs from human donors has resulted in long wait lists and increasing mortality among patients with end-stage organ failure. Pig-to-human xenotransplantation has been touted as a solution to this problem. However, significant infectious diseases and public health considerations exist with such a technological advancement.

Recent findings: Infectious diseases hazards with public health implications of pig-to-human xenotransplantation may be categorized taxonomically, according to temporality of potential exposure and/or reactivation, or according to anthroponotic versus zoonotic transmission. Additionally, the potential for escalating proportions of immunosuppression-at-scale in the context of the theoretically less-constrained resource of xenografts warrants particular consideration given that impacts will be differentially borne by those most affected by reactivating infections including but not limited to tuberculosis (TB), hepatitis B (HBV), and strongyloidiasis. TB, HBV, and strongyloidiasis all represent chronic infections with potential for reactivation under circumstances of immunosuppression - owing to either allograft or xenograft transplantation - that differentially impact those living in rural poverty globally, and those with risk factors for acquisition related to crowding, poor sanitation, undernutrition, and economic disenfranchisement. Chagas disease and leishmaniasis portend similar possibility of reactivation and differentially affect those residing in the global South.

Summary: We herein situate the public health implications of xenotransplantation at scale within the broader landscape of infectious diseases hazards related to the technology, and propose a health equity and human rights based framework for global risk assessment.

Purpose of review: The integration of artificial intelligence into allocation, organ retrieval and transplantation processes represents an innovative approach to address these challenges and enhance the efficiency and effectiveness of healthcare delivery systems. The rationale for applying artificial intelligence in organ transplantation in the elderly is two folds: the increasing number of older deceased donors the increasing number of older recipients in the waiting lists.

Recent findings: To date, older donor and/or older recipients have not specifically focused in artificial intelligence investigations. Age has been considered as a continuous variable in most machine learning prediction models.

Summary: Considering elderly donors, it may be speculated that dedicated datasets should be built, due to the epidemiological changes in donor panorama and the increasing number of older recipients in the waiting lists. So far, only some transplant centers have gained experiences in managing elderly donors, so there is the need of generalized standard protocols for data exchange. To assess organ suitability for transplant, elaborating data from ex vivo machine perfusion would be of utmost importance. Regarding elderly recipients, post-transplant complications (in primis cardiovascular ones) should be considered to elaborate machine learning prediction models for patient outcome.

Purpose of review: The science and practice of xenotransplantation is advancing more rapidly than the regulatory infrastructure that will be necessary to ensure the promise of alleviating the organ shortage can be safely and equitably met.

Recent findings: While countries leading the way have developed some regulatory guidance to support first in human "compassionate use" xenotransplant interventions and the first clinical trials, existing legislative, regulatory, and operational frameworks for human allotransplantation have not been explicitly extended to nonhuman animal organs.

Summary: To address safety concerns and other ethics challenges unique to xenotransplantation, existing policies must be amended and new policies must be implemented to protect patients and ensure equitable access to xenotransplantation.

Purpose of review: Xenotransplantation is closer to clinical reality than ever, with planned clinical trials in development. Enrolling participants in these trials may be difficult without an understanding of patient and public perceptions, attitudes, and ethical concerns related to xenotransplantation. In this article, we summarize recent literature and discuss areas for continued focus related to the public perception of xenotransplantation.

Recent findings: Following the first living human xenotransplant in January 2022, several surveys have assessed various groups' acceptance of xenotransplantation. Awareness of xenotransplant remains low despite the widely publicized first-in-human experiences. Acceptance rates vary widely and depend on the scenario presented (factors such as success compared to allotransplant) and the level of existing knowledge. However, evidence is highly focused on Western populations and upper middle-income countries. The public's understanding and thoughts related to issues such as informed consent, animal welfare, the influence of religion, and zoonosis have not been adequately addressed.

Summary: Despite decades of attempts to understand public perception and attitudes around xenotransplantation, there remains little information, and essential knowledge gaps exist. More active involvement of diverse populations should be considered to support the future of equitable xenotransplantation.

Purpose of review: Optimizing outcomes for kidney transplant recipients requires both minimizing premature death related to over-immunosuppression and avoiding alloimmune injury associated with under-immunosuppression. Both of these goals require a precise understanding of the alloimmune risk faced by the recipient. Although the assessment of HLA mismatch at the antigen level lacks refinement, molecular mismatch has been shown to increase precision in alloimmune risk assessment. This review discusses the expansion of the role of molecular mismatch in optimizing the clinical management of kidney transplant recipients.

Recent findings: Eplet mismatch has been reported as a reliable predictive biomarker for immunosuppression adequacy and to identify recipients who are less likely to tolerate minimization or nonadherence. Human leukocyte antigen DR and/or DQ (HLA-DR/DQ) single-molecule mismatch has also been validated as a prognostic biomarker in immunosuppression conversion studies, providing a precise, individualized assessment of alloimmune risk to guide decision-making regarding immunosuppression. PIRCHE-II scores have been observed to potentiate the risk of dnDSA development. The use of molecular mismatch can also be expanded to personalized posttransplant alloimmune monitoring and dnDSA surveillance.

Summary: To facilitate precision medicine in transplantation, molecular mismatch has the potential to serve as a prognostic and predictive biomarker for primary alloimmunity.

Purpose of review: Across the world, several solid organ xenotransplants have been reported as being provided to deceased people and to living patients. In the United States, xenotransplants to living patients have been authorized under the Food and Drug Administration's Expanded Access program, and clinical liver and kidney xenotransplants have also been reported in China. During 2025, the first clinical trials of kidney and liver xenotransplants have been approved in the United States. These developments make it necessary to understand the regulatory and governance issues and challenges raised by clinical xenotransplants.

Recent findings: Key regulatory and governance issues remain to be addressed before xenotransplant clinical trials begin, including identifying the responsible regulator, drafting informed consent protocols, and establishing long-term monitoring regimens. International cooperation and collaboration are key to establishing appropriate and effective regulatory regimes and frameworks which enable science to proceed while offering the necessary protections to those involved. Public awareness, education and trust are central to the success of clinical xenotransplantation.

Summary: Starting xenotransplant clinical trials too soon and without appropriate regulation and governance, may affect public trust in this biotechnology specifically and science more generally. The possible risks of xenotransplantation necessitate exploration of global harmonization and regulatory frameworks for clinical xenotransplantation.

Purpose of review: After many decades of experimental studies and the advent of genetic engineering for pig organs, xenotransplantation has finally reached clinical application. Clinical trials are beginning, and a review of the recent preclinical and clinical studies is paramount. More specifically, reviewing the pathologic findings in biopsies and terminal samples of transplanted pig organs are integral to assessing xenograft acceptance and clinical success.

Recent findings: This review aims to summarize the current literature in xenotransplantation and enumerate both typical and novel pathological findings in xenografts. This holds an opportunity to identify both diagnostic clues and gaps that are critical to treatment protocol modifications and to improving xenograft survival. While thrombotic microangiopathy and antibody mediated rejection are known pathologic entities in xenograft pathology, we re-examine their occurrence in the context of other diagnostic parameters, and we revisit the importance of integrating clinical findings and molecular techniques to aid pathological diagnosis. We also describe the novel findings in xenografts from both nonhuman primate and human recipients.

Summary: With the recently observed pathological features, a structured approach to xenograft pathology diagnosis can be proposed for use in clinical practice and is an effort that can impact therapeutic and genetic modification strategies.