Clinical Transplantation最新文献

Solid organ transplantation is a life-saving procedure, yet its long-term success is limited by rejection and other pathological processes. Traditional histopathology and bulk molecular analysis lack the necessary spatial resolution to resolve the complex cellular interactions within the allograft microenvironment. The emergence of spatial-omics technologies offers new capabilities for molecular analysis within intact tissue architecture. This review provides an overview of major spatial transcriptomic and proteomic platforms, including sequencing-based technologies, imaging-based technologies, and high-plex protein imaging technologies. We synthesize and provide mechanistic insights into the key findings from the application of these tools in kidney, lung, liver, and heart transplantation. Key applications discussed include as follows: resolving the heterogeneity of rejection (T-cell mediated and antibody-mediated rejection (ABMR)), elucidating the driving mechanisms of chronic allograft dysfunction and ischemia-reperfusion injury (IRI), and delineating the immune microenvironments associated with operational tolerance (OT) and tertiary lymphoid structures (TLS). We further explore how these technologies are beginning to refine our understanding of transplant pathology from a diffuse inflammatory process to the identification of specific pathogenic microenvironments. Finally, we discuss the challenges and prospects of translating these powerful research tools toward the long-term goal of precision immunosuppression, for instance, through the potential future development of digital biopsies to help guide individualized therapies.

Since FDA approval in 2021, normothermic machine perfusion (NMP) has emerged as a transformative tool to expand transplantation access for patients with end-stage liver disease. This study details the design, implementation, and outcomes of our liver NMP program, highlighting implementation of a stratification algorithm for grafts into low-, medium-, and high-risk categories and evaluation of high-risk grafts from the first 100 cases. A secondary analysis compares NMP outcomes with historical cohorts.

The final analysis included 53 grafts from donation after brain death (DBD) and 39 from donation after circulatory death (DCD) donors, excluding eight NMP grafts that were not transplanted. No significant differences were observed in allograft dysfunction, primary non-function, biliary or arterial complications, or patient survival, even among high-risk graft recipients. NMP significantly reduced intraoperative cryoprecipitate (0.41 vs. 1.44 units, p = 0.003) and platelet (0.59 vs. 1.56 units, p = 0.001) use in DCD recipients. While recipients of DBD-NMP grafts experienced longer ICU stays (17.17 vs. 8.96 days, p = 0.03) and higher rates of renal replacement therapy (41.14% vs. 20.75%, p = 0.04) than the historic cohort, inpatient length of stay and long-term dialysis requirements were unaffected. Higherrisk graft use facilitated transplant access for patients with lower MELD scores at our center.

These findings highlight NMP's potential to safely expand the donor pool, facilitating transplantation of previously non-utilized livers while maintaining comparable outcomes. The risk stratification developed alongside our program provides a practical algorithm to advance equity in organ allocation through NMP by enabling safe access to high-risk grafts and demonstrates its value in optimizing liver transplantation practices.

Despite substantial advances in surgical technique and immunosuppressive therapy, kidney transplantation continues to face limitations in long-term graft and patient survival. Increasingly, attention is shifting toward the exposome, the comprehensive profile of environmental, social, and biological exposures accumulated across the lifespan, as a critical yet under-investigated determinant of transplant outcomes. Evidence from diverse domains, including air pollution, heavy metal burden, dietary composition, infections, microbiome dynamics, psychosocial context, and digital health engagement, suggests that these factors exert profound effects on immune regulation, metabolic health, and graft integrity. By applying innovative approaches such as exposome-wide association studies, high-resolution biomonitoring, and multi-omics integration, researchers can begin to unravel complex exposure–disease relationships and identify previously unrecognized modifiable risks. Positioning the exposome within the kidney transplantation paradigm offers a pathway toward precision environmental medicine, enabling refined risk stratification, novel preventive strategies, and ultimately improved durability of both graft function and patient survival. However, exposome influences are highly individualized and interact in complex, non-additive ways; current evidence remains largely associative and hypothesis-generating rather than causal.