Transplantation最新文献

Background: Since Share-35 and continuing under the Acuity Circle (AC) policy, US liver transplant (LT) allocation has relied on Model for End-Stage Liver Disease (MELD) thresholds that may distort fair and seamless access.

Methods: We analyzed adult LT candidates listed from January 2016 to June 2024. Regression discontinuity analysis using Poisson regression for top-5 offer rates and discrete-time hazard regression for transplant rates and waitlist mortality estimated policy effects at a MELD score of 35 (MELD-35; Share-35) and MELD scores of 33 and 37 (MELD 33/37; AC). Secondary analyses were used to analyze the offer decline rates and donor characteristics at each MELD threshold.

Results: In total, 98 896 candidates were analyzed. During Share-35, crossing the MELD-35 threshold was associated with significant increases in offers (rate ratio [RR], 3.39; 95% confidence interval [CI], 3.22-3.57) and transplants (odds ratio [OR], 2.13; 95% CI, 1.89-2.41). Under AC, smaller but significant effects were observed at MELD-37 (RR, 1.37; 95% CI, 1.31-1.44; OR, 1.15; 95% CI, 1.01-1.30) and at MELD-33 (RR, 1.48; 95% CI, 1.21-1.38 and OR, 1.16; 95% CI, 1.03-1.30). Candidates with an MELD score <37 experienced significantly higher waitlist mortality (OR, 0.40; 95% CI, 0.24-0.67). Secondary analyses showed higher decline rates at MELD-35 under Share-35, but lower rates at MELD 33/37 under AC with reduced marginal donor use.

Conclusions: MELD thresholds continue to influence LT access and donor quality/selection, creating artificial discontinuities and unintended disparity that misalign allocation with true disease severity. These findings support avoiding rigid score-based cutoffs not only in future US allocation models (eg, continuous distribution), but also in broader international allocation frameworks moving forward.

Although maintenance immunosuppression with calcineurin inhibitors (CNIs) has greatly reduced rejection rates in renal transplant recipients, long-term use can contribute to eventual nephrotoxicity, potentially leading to allograft injury and loss. Several clinical trials have shown that, compared with CNIs, belatacept-based maintenance immunosuppression can improve renal function, reduce the incidence of de novo donor-specific antibodies, and improve long-term patient/graft survival. However, the US Food and Drug Administration-approved belatacept-based regimen is also associated with higher acute rejection (AR) rates than CNI-based immunosuppression. Recent data from clinical trials and real-world studies suggest that initial posttransplant treatment with CNI-based immunosuppression followed by conversion to a belatacept-based regimen can lower the AR risk while preserving patient and renal health. This review article summarizes the available data pertaining to belatacept treatment protocols, with a focus on conversion to belatacept. Also discussed are studies of protocol modifications intended to further mitigate AR risks and belatacept-related outcomes in special populations, such as patients receiving marginal kidneys and those at risk of new-onset diabetes. Overall, the available data suggest that conversion from CNI- to belatacept-based immunosuppression ≥6 mo posttransplant appears to be effective in lowering the AR risk compared with belatacept use in the de novo setting or conversion <6 mo posttransplant. The addition of an extended transient or low-dose CNI treatment to de novo belatacept or a prolonged CNI taper in the conversion setting may also help lower the AR risk. However, additional studies will be needed to optimize the many variables applicable to belatacept treatment, particularly for different patient subgroups.

Background: Peritubular capillary multilayering (PTCML) of basement membranes is an ultrastructural feature of chronic antibody-mediated rejection (AMR) with uncertain diagnostic thresholds.

Methods: This single-center, prospective cohort study evaluated the relationships of PTCML with chronic AMR in 2541 kidney samples from 1195 recipients.

Results: Epidemiological modeling found that younger recipients, living donation, early AMR, pulse corticosteroid rejection treatment, later presentation, and higher donor-specific antibody strength were clinical risk factors for an abnormal PTCML score of ≥3. The total number of PTC layers was correlated with posttransplant time, AMR histology, donor-specific antibody positivity, renal dysfunction, proteinuria, and graft failure. Histological Banff cg, ptc, C4d ptc , and C4d glom independently predicted PTCML ≥3. Mild PTCML of 3-4 layers with circumferential remodeling in multiple PTC showed 82.9% sensitivity and 72.7% specificity against the Banff cg≥1a reference test, verified using Banff 2022 AMR criteria, and considered "suspicious" for chronic AMR. PTCML ≥5 correlated with late graft failure. Normal PTC (n = 322) in early protocol samples showed 1 basement membrane layer, except for 12.5% with mild segmental reduplication involving 13.7 ± 10.2% capillary circumference. Circumferential scoring efficiently separated mild segmental PTCML from normal variability against pathological AMR multilayering. The poor 30.0% sensitivity and 91.1% specificity (n = 374 late indication biopsies, 2029 PTCs) of the Banff 2013 AMR criteria improved to 55.0% and 89.7% using modified PTCML ≥7 or 2×PTCML ≥5 criteria, which allowed for a diagnostic disease "rule-in."

Conclusions: Circumferential multilayering from PTCML ≥3 replicated across multiple capillaries optimally recognized mild chronic AMR as a superior histological marker of chronic tissue injury with high sensitivity. These ultrastructural diagnostic criteria for the detection of early chronic AMR phenotypes require multicenter validation.

The Immunobiology of Transplantation and Alloimmunity study section and federal funding, more broadly, is integral to the health and future of transplantation. Here, we articulate the progress we have made in the field of transplantation with the help of federal funding and the work that remains as an unmet need. We described the foundation that the National Institutes of Health has built and what the support from federal dollars can do to transform ideas into clinical realities.