Transplantation最新文献

Background: Bone health is frequently compromised in patients with type 1 diabetes and advanced diabetic kidney disease. While simultaneous pancreas-kidney transplantation (SPKT) is the treatment of choice for selected patients, concerns remain about its skeletal impact, particularly because of immunosuppressive regimens.

Methods: We conducted a retrospective intraindividual comparison of bone mineral density (BMD) and trabecular bone score (TBS) before and after SPKT in 48 patients (mean age 41.5 ± 10.1 y) managed under a corticosteroid-sparing immunosuppressive protocol (tacrolimus + mycophenolate mofetil/sirolimus + prednisone only 4 wk after SPKT). Dual-energy X-ray absorptiometry scans were assessed at 3 time points: before listing, peritransplant (within 28 d from the date of SPKT, both before and after), and 2 y posttransplant. Annualized changes in BMD and TBS were analyzed along with predictors of bone outcomes.

Results: During the pretransplant period, BMD declined significantly at the femoral neck (-0.011 g/cm2/year; 95% confidence interval [CI],-0.019 to -0.003) and TBS decreased by -0.032/year (95% CI, -0.049 to -0.014). After SPKT, lumbar spine BMD increased (+0.039 g/cm2/year; 95% CI, 0.028-0.050), TBS improved (+0.019/year; 95% CI, -0.000 to 0.039), and femoral neck BMD stabilized. Distal radius BMD declined posttransplant (-0.011 g/cm2/year; 95% CI, -0.018 to -0.004). Trend differences between pretransplant and posttransplant periods were significant for lumbar spine BMD (P < 0.001), femoral neck BMD (P = 0.01), and TBS (P = 0.003).

Conclusions: SPKT under a corticosteroid-sparing regimen not only halts but may reverse bone loss at trabecular rich sites in type 1 diabetes with advanced diabetic kidney disease. In particular, the increase in BMD in the lumbar spine can be considered clinically significant. Our data support the strategy of early referral for SPKT in eligible patients.

Background: Extracorporeal membrane oxygenation (ECMO) systems for permanent respiratory support are currently under development as an alternative to lung transplantation. Direct oral anticoagulants are a promising alternative to heparin due to their oral administration and predictable pharmacology.

Methods: The efficacy of rivaroxaban for artificial surface anticoagulation was evaluated using 3 studies that determined (1) the pharmacological behavior of 0.25, 0.5, and 1 mg/kg doses of rivaroxaban in sheep; (2) the artificial surface anticoagulation efficacy of these 3 doses compared with heparin in a short-term mini-ECMO model; and (3) the efficacy of the optimal dose from study 2 with simulated oral pharmacokinetics in an extended-duration mini-ECMO model.

Results: Study 1 found that sheep have a higher volume of distribution (2.2 ± 0.4 L/kg) and a shorter half-life (1.4 ± 0.1 h) for rivaroxaban than humans but a similar linear relationship between prothrombin time and rivaroxaban plasma concentration. In study 2, device survival time in the heparin group (57.5 ± 13.0 min) was most similar to the 0.5 mg/kg rivaroxaban group (51.3 ± 8.8 min; P = 0.287). This dose was selected for study 3, and no difference was found in device survival time between heparin (6.3 ± 1.3 h) and the 0.5 mg/kg rivaroxaban infusion (6.3 ± 1.6 h; P = 0.837). Furthermore, the calculated rivaroxaban exposure was similar to the clinically approved oral rivaroxaban doses (24-h area under the plasma concentration curve = 2074 µg h/L).

Conclusions: These results demonstrate that rivaroxaban has artificial surface anticoagulation efficacy similar to that of heparin at dosages that are feasible for oral administration in humans. Future studies will evaluate rivaroxaban anticoagulation using a 10-d full-scale ovine ECMO model.

The World Transplant Congress 2025 showcased pivotal advances shaping the future of transplantation. Global efforts to expand access to transplantation accelerated on multiple fronts. Machine perfusion has progressed from an experimental approach to an emerging clinical standard: the Central Preservation and Assessment Service to Optimize Donor Kidney Allocation trial confirmed its value in rescuing discarded kidneys and explored its potential for ex vivo organ repair. For highly sensitized patients, novel desensitization regimens incorporating new proteasome inhibitors and anti-CD38 antibodies (daratumumab, felzartamab) effectively reduced donor-specific antibodies, enabling transplantation in previously ineligible candidates. Improving long-term graft survival remains a central goal, with new immunosuppressive strategies beginning to redefine the therapeutic landscape. Anti-CD38 antibodies also show promise in treating antibody-mediated rejection, while early trials of costimulatory blockade, including anti-CD28, suggest a pathway toward safe tacrolimus minimization or withdrawal. Finally, growing emphasis on novel endpoints and biomarkers reflects a shift toward precision medicine. Artificial intelligence tools that integrate multiomics data are emerging as powerful predictors of graft outcomes. Collectively, these innovations address critical challenges of organ shortage, rejection, and individualized care, charting the next era in transplantation.

Summary: Since their early development in the 1980s, Simulated Allocation Models (SAMs) have helped policymakers forecast the impact of proposed allocation policy changes on patient outcomes before implementation. In the United States, models like the Kidney-Pancreas Simulated Allocation Model, Liver Simulated Allocation Model, and Thoracic Simulated Allocation Model have been instrumental in shaping organ allocation policies. Analogous models have emerged globally, including the ETKidney and Eurotransplant Liver Allocation System simulators for the Eurotransplant region, to address country and region-specific allocation challenges. This review categorizes and compares SAMs based on their core assumptions, data, and modeling approaches. We highlight challenges in model validation, the use of synthetic data, and model transparency. While simplifying assumptions are often necessary because of limited data, their influence on results should be clearly communicated to ensure policymakers can interpret model predictions accurately. Furthermore, model validation using both retrospective and prospective data is essential to assess performance under evolving policies. Greater transparency through open-source models, detailed reporting of assumptions, and validation efforts can enhance collaboration, reproducibility, and confidence in transplant research. By providing a global perspective on SAMs, this review aims to inform future research and policy development, promoting evidence-based policy development in organ transplantation.