Current Opinion in Organ Transplantation最新文献

Purpose of review: Recent advancements in genetic engineering have propelled the field of xenotransplantation from preclinical models to early compassionate use cases. As first-in-human clinical trials (FIHCTs) approach, we examine recent developments, ethical and regulatory challenges, immunological considerations, and the clinical infrastructure necessary for successful xenotransplantation trials.

Recent findings: Expanded access transplants of pig hearts, kidneys, and livers have identified key challenges. Heart xenotransplants revealed risks of antibody-mediated rejection and zoonotic infections, while kidney xenotransplants suggest that patient selection, rather than immune rejection, may have caused failures. While there has been a report of auxiliary liver transplantation conducted abroad, profound thrombocytopenia poses an obstacle. As FIHCTs draw near, critical clinical challenges include determining the optimal donor genetic constructs and immunosuppressive regimens. Enrollment criteria and patient selection pose additional complexity, alongside ethical concerns such as lifelong zoonosis monitoring. Only a limited number of centers have the expertise needed to conduct these complex trials.

Summary: Xenotransplantation holds great promise as a solution to organ shortages, but success in FIHCTs will require careful design, multidisciplinary collaboration, and strong infrastructure. Addressing immunologic, ethical, and patient selection challenges will be critical. With proper preparation, xenotransplantation could transform organ transplantation.

Purpose of review: Demonstrate the impact of allocation system design on access to the waitlist and transplantation for patients with end-stage kidney disease (ESKD).

Recent findings: Minoritized groups are more likely to be declined from transplant listing owing to psychosocial criteria. Lack of consistent definitions, screening tools with differential subgroup validity, and insufficient evidence-base contribute to concerns about reliance on psychosocial factors in transplant listing decisions.

Summary: Although kidney transplantation is the preferred treatment choice, a shrinking proportion of prevalent patients are waitlisted for this option in the United States, even among our youngest ESKD patients. Recent HRSA proposals to expand data collection to encompass the prewaitlisting process suggest a timely need to capture additional data on transplant referrals to improve access to transplantation. In 2021, KAS250 was implemented in response to concerns of geographic inequities in transplant rates. However, updates to this system have also resulted in a dramatic rise in organ offers, the number of offers needed to successfully place an organ and lowered utilization rates. Since KAS250, the use of alternative pathways to improve organ utilization rates, such as out-of-sequence placements has increased dramatically across the organ quality spectrum and risk exacerbating disparities in access to transplant. Additionally, the current absence of meaningful oversight risks undermining the perception of the transplant system as an objective process.

Summary: There is a need for a more robust evaluation of recent iterative changes in waitlist and organ allocation practices to ensure equity in access for our most vulnerable patients.

Purpose of review: Disparities in access to transplantation are persistent and pervasive among minoritized populations, and remain incompletely explained by socioeconomic status, insurance, geography, or medical factors. Although much attention has been paid to factors contributing to disparities in organ allocation, fewer studies have focused on barriers to the transplant waitlist. Given increasing calls for equity in organ transplantation, we examine the role of nonmedical factors used in transplant listing decisions, including psychosocial factors like social support, motivation, and knowledge in improving utility in transplant listing decisions, as well as their potential for reinforcing bias.

Recent findings: Minoritized groups are more likely to be declined from transplant listing owing to psychosocial criteria. Lack of consistent definitions, screening tools with differential subgroup validity, and insufficient evidence-base contribute to concerns about reliance on psychosocial factors in transplant listing decisions.

Summary: Improving consistency and evidence-based approaches in patient evaluation and listing decisions will require greater efforts to identify which psychosocial risk factors are predictive of posttransplant outcomes. Social needs screening presents a strengths-based framework for incorporating psychosocial factors in transplant listing decisions.

Purpose of review: Increasing transplant access overall and particularly among historically underserved and marginalized patient groups is a shared goal nationwide. Patient challenges with psychosocial factors, such as social support and health literacy, are recognized as among the top reasons patients may not be referred, evaluated, or waitlisted, key steps along the pathway to transplantation. Yet referring providers' (e.g., dialysis clinics') and transplant centers' processes for measuring, communicating about, and addressing patients' psychosocial challenges are inconsistent, can emphasize measures more relevant to dialysis care than transplant care, and are highly susceptible to implicit bias.

Recent findings: In this article, we illuminate the opportunity to standardize the patient psychosocial information that dialysis clinics and other nephrology care providers share with the transplant center when referring a patient for transplant evaluation. We highlight potential benefits and trade-offs to this approach and describe how regional coalitions comprising patients, caregivers, and community members can support developing and implementing a standardized template for this purpose, as well as the objectives that the coalition's efforts should pursue to this end.

Summary: Standardized templates for psychosocial information sharing at referral represent a key opportunity to improve quality, efficiency, and equity in pretransplant care as well as transplant access outcomes broadly.

Purpose of review: Our goal was to review and summarize the current state of global disease burden from organ failure and the efforts to improve outcomes with organ transplantation. We also reviewed intra- and inter-country disparities in organ failure and organ transplantation along with potential mechanisms to improve access to organ transplantation globally.

Recent findings: Many disparities and inequities observed globally can be characterized by the country's income category. Low- and lower-middle income countries (LLMICs) have higher rates of communicable disease-attributed organ failure, while upper-income countries (UICs) have high overall prevalence due to global growth in noncommunicable etiologies of organ failure. Many downstream disparities in access to organ transplantation and outcomes are associated with country income designation. Improvements in data collection and surveillance of populations with organ failure and organ transplantation are urgently needed.

Summary: Improving outcomes for patients with end-organ disease globally will require countries to improve organ transplantation access and care. For LLMICs, collaboration with international transplant systems and engagement with neighboring countries may establish important foundations for organ transplant systems. For UICs, increasing organ donor availability through technological advances and increasing public engagement will help meet the growing needs for organ transplantation as an important treatment modality.

Purpose of review: Highlight the importance of acute kidney injury (AKI) among liver transplant candidates, its importance of survival and the vital role of continuous renal replacement therapy (CRRT) as a supportive therapy.

Recent findings: Kidney dysfunction is common in the preliver transplant patient. Early recognition, broad diagnostic work up, and therapeutic interventions are vital in minimizing morbidity and mortality in this critically ill group of patients. Liver dysfunction can impact kidney function in multiple ways, leading to worsening of clinical illness. High mortality and poor prognosis in those with AKI without CRRT and Liver Transplant are highlighted.

Summary: Etiology of AKI may not be as important as is the potential for liver transplant (LT) listing in offering CRRT. Non eligibility for a LT does not by default imply non eligibility for CRRT. Multidisciplinary approach should be adopted among those with a need for CRRT in the setting of end-stage liver disease. Goals of care conversations are key, in evaluating the role of CRRT in this group of individuals as they have a very high risk of mortality.

Purpose of review: Patients undergoing re-transplantation constitute a growing proportion of annual lung transplants. It is necessary to consider ethical considerations of re-transplantation in parallel with clinical progress.

Recent findings: Most clinical data demonstrate patients undergoing re-transplantation have worse survival outcomes; however, there is limited discussion of the ethical principles surrounding re-transplantation. Ethical guidance in re-transplantation trails clinical advancement.

Summary: The four-box model offers a valuable framework for assessing the ethical considerations in re-transplantation. This includes an analysis of medical indications, patient preferences, quality-of-life and contextual factors to support the ethical use of scarce donor lungs.

Purpose of review: The controversial medical procedure of abortion is the subject of this article. It argues that for transplant patients, including recipients, abortion is ethical.

Recent findings: In June 2022, the United States Supreme Court overturned the long-standing decision of Roe v. Wade. This decision has led to a socio-legal environment where obtaining an abortion is impossible for some patients. However, the moral position relating to patients who have undergone transplants or are on a waiting list has been largely overlooked. End-stage renal, liver, and heart disease presents a hazardous situation for pregnancy, posing risks to both the fetus and the pregnant person. The abortion procedure is medically safer and allows a patient to proceed with a transplant. Limiting access to abortion or preventing it altogether will have a significant negative impact on transplant patients. The ethical analysis of abortion can be likened to compelling a relative or loved one of a transplant recipient to donate an organ to their family member or loved one.

Summary: This article emphasizes the importance of maintaining the legal availability of abortion for transplant patients. Allowing abortions in transplant patients upholds ethical parity, as seen in the analogous situation of live organ donation.

Purpose of review: Primary graft dysfunction (PGD) and chronic lung allograft dysfunction (CLAD) are the leading causes of graft loss in lung transplant recipients. The development of mouse lung transplant models has allowed for the genetic dissection of cellular and molecular pathways that prevent graft survival. This review provides an overview into recent mechanistic insights into PGD and CLAD.

Recent findings: Mouse orthotopic lung transplant models and investigations of human lung transplant recipeints have revealed new molecular and cellular targets that promote PGD and CLAD. Donor and recipient-derived innate immune cells promote PGD and CLAD. PGD is driven by communication between classical monocytes and tissue-resident nonclassical monocytes activating alveolar macrophages to release chemokines that recruit neutrophils. Products of cell damage trigger neutrophil NET release, which together with NK cells, antibodies and complement, that further promote PGD. The development of CLAD involves circuits that activate B cells, CD8 + T cells, classical monocytes, and eosinophils.

Summary: Effective targeted management of PGD and CLAD in lung transplant recipient to improve their long-term outcome remains a critical unmet need. Current mechanistic studies and therapeutic studies in mouse models and humans identify new possibilities for prevention and treatment.