Current Opinion in Organ Transplantation最新文献

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: Calcineurin inhibitors (CNIs) are central to immunosuppression in kidney transplantation (KT), improving short-term outcomes but falling short in enhancing long-term outcomes due to cardiovascular, metabolic, and renal complications. Belatacept, an FDA-approved costimulation blocker, offers a less toxic alternative to CNIs but is limited by its intravenous administration and reduced efficacy in high-immunological-risk patients.

Recent findings: Emerging therapies target more specific pathways to improve efficacy and accessibility. Abatacept, a first-generation cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) immunoglobulin, has shown favorable outcomes in small studies. VEL-101 and Lulizumab selectively block CD28 while preserving CTLA-4 signaling, showing promise in early trials. In the CD40/CD40L pathway, results have been mixed. Iscalimab (CD40 antibody) was inferior to tacrolimus in Phase 2 trials, and Bleselumab (CD40 antibody) showed variable rejection rates despite being noninferior to tacrolimus. CD40L-targeting agents such as TNX-1500, Tegoprubart, and Dazodalibep have demonstrated promising efficacy and safety in rejection prophylaxis.

Summary: The focus in transplantation is shifting toward safer, long-term therapies with greater accessibility. Investigational agents with subcutaneous delivery methods could overcome logistical challenges, improve adherence, and redefine posttransplant care. These advancements in costimulation blockade may enhance long-term graft survival and transform the management of KT recipients.

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: Despite technical and therapeutic advances, only 20-40% of patients with colorectal liver metastases (CRLM) have resectable disease. Historically, the remaining patients with unresectable, liver-only CRLM would receive palliative chemotherapy, with a median survival of 8 months.

Recent findings: Liver transplantation has emerged as a viable option for selected patients with CRLM. This advancement stems from improved understanding of tumour genomics and biology and better patient selection criteria. The results of recent prospective clinical trials have further ignited enthusiasm for liver transplantation as a viable therapeutic option. Living donor liver transplantation (LDLT) offers several advantages over deceased donor liver transplantation (DDLT) for this disease, including reduced wait-time and optimized timing and coordination of oncologic therapy. On-going LDLT clinical trials have demonstrated favourable outcomes as compared with other liver transplantation indications. However, there is no established consensus or standardization in the implementation of LDLT for CRLM, beyond trials and centre-specific protocols.

Summary: LDLT is an excellent therapeutic option in highly selected patients with CRLM. Refining prognostic factors and selection criteria will help to further optimize the utility and broaden the acceptance and implementation of LDLT for patients with CRLM.

Purpose of review: Transplant oncology encompasses and utilizes liver transplantation (LT) in combination with other aspects of cancer care to offer improved long-term outcomes for patients with liver cancer, but not all patients have equal access and ability to undergo LT. Social determinants of health may negatively impact a patient's ability to receive liver-related oncologic care, including LT. This review highlights recent work exposing gaps in access to LT, including transplant oncology, and interventions to ameliorate these disparities.

Recent findings: Members of racial and ethnic minorities and indigenous groups, females, socioeconomically disadvantaged persons, and patients from rural areas are less likely to undergo LT. Recent studies have also described programs that have successfully mitigated some of the barriers in access to transplant oncology that these patients experience, including targeted outreach programs and access to virtual healthcare.

Summary: Disparities in access to LT for liver cancer are increasingly well described, but additional research is needed to find effective ways to ameliorate these differences.

Purpose of review: Molecular matching continues to be an important topic in organ transplantation. Over the years, several studies - larger and smaller - supported correlations of molecular incompatibility loads and clinical outcomes. However, their practical utility for clinical decision making remains controversial and there is no consensus on the context in which they should be used.

Recent findings: The recent literature on molecular matching can be divided into four main areas of research: several groups present improvements of the algorithmic pipelines (1), increasing the robustness of previous findings. Further clinical evidence is reported (2) in various cohorts and other organ transplant domains, such as liver and lung transplantation. Consideration is given to the application of molecular matching in the allocation of deceased organs (3), suggesting options to improve allocation equity and utility. Furthermore, evidence is provided for personalized immunosuppression based on immunological risk (4), including infection and post graft failure management.

Summary: There is ample evidence that current molecular matching algorithms add value to immunologic risk stratification for organ transplant recipients. First studies on how to translate these insights into patient management with respect to organ allocation and personalized medicine are underway and require further support.

Purpose of review: This review summarizes the different instruments for evaluating the psychosocial health of transplant candidates, the evidence demonstrating how these instruments relate to probability of transplant waitlisting and transplant outcomes, and the critical knowledge gaps that exist in the causal pathway between psychosocial health and clinical transplant trajectory.

Recent findings: The current literature reveals that psychosocial assessments are a common reason for racial and ethnic minorities to be denied access to the transplant list. Given evidence that a lack of clinician consensus exists regarding the definition of, importance of, and reproducibility of psychosocial support evaluations, this facet of the holistic evaluation process may create a unique challenge for already vulnerable patient populations. Though recent evidence shows that psychosocial evaluation scores predict select transplant outcomes, these findings remain inconsistent.

Summary: Multiple instruments for psychosocial transplant evaluation exist, though the utility of these instruments remains uncertain. As equity becomes an increasingly urgent priority for the transplant system, rigorous interrogation of the causal pathway between psychosocial health and transplant longevity is still needed.

Purpose of review: Hispanics with limited English proficiency (LEP) face unique challenges in accessing organ transplantation due to limited culturally concordant care and linguistically appropriate resources, leading to disparities in healthcare delivery and transplantation outcomes. This review examines how language barriers affect access to kidney and liver transplant, and highlights the importance of institutional support for quality interpretation services in promoting healthcare equity in transplantation.

Recent findings: Hispanics experience greater disease burden, but are less likely to receive a transplant compared to non-Hispanic Whites. LEP is a significant barrier to transplantation. Culturally and linguistically concordant interventions, such as the "Hispanic Kidney Transplant Program," have demonstrated success in improving transplant-related outcomes among Hispanics. However, limited resources affect widespread implementation, and the broad lack of interpretation services in healthcare settings delay timely care in transplantation.

Summary: Despite some progress demonstrated by culturally and linguistically concordant clinical intervention trials, disparities in transplantation for Hispanics with LEP remain. Enhancing the availability of interpretation services, recruiting and hiring bilingual healthcare professionals, and training healthcare staff to effectively engage with language and interpretation resources are critical to improving health equity. Efforts must prioritize language access and cultural concordance to address the unique challenges faced by Hispanics with LEP.