Transplantation最新文献

Background: It remains unclear whether physicians should accept transplantation offers for candidates with a positive SARS-CoV-2 reverse transcription polymerase chain reaction test due to the potential risk of severe infection after initiating immunosuppressive therapy.

Methods: A multicenter observational study was conducted in 19 French solid organ transplantation units. Patients on the waiting list for liver or kidney transplants who had a positive SARS-CoV-2 reverse transcription polymerase chain reaction nasopharyngeal swab at the time of transplantation were recorded.

Results: Sixty-five patients were included. The recipients were predominantly men (n = 40; 62%) with a mean age of 55.4 y (SD = 16.5). On the day of transplantation, 2 patients exhibited symptoms compatible with COVID-19. The majority of patients (n = 55; 85%) underwent thoracic imaging, with only 3 patients showing imaging results compatible with COVID-19. Ten patients (28%) had a cycle threshold value <30. Anti-SARS-CoV-2 spike protein serology within 3 mo before transplantation was available for 36 patients; only 2 patients were seronegative. Due to COVID-19, physicians adapted the immunosuppressive therapy for 16 patients (25%). Specific antiviral therapy was used for 15 patients (23%), primarily remdesivir (n = 12). Overall, the majority of patients did not receive any adjustment of immunosuppressive therapy or antiviral treatment (n = 36; 55%). The outcomes were generally favorable even for patients with the lowest cycle threshold values, indicating a high viral load. Four patients died during follow-up, although none of these deaths were attributable to COVID-19.

Conclusions: Transplantation appears to be safe for patients who are asymptomatic or have mild symptoms, reassuring thoracic imaging, and a history of anti-SARS-CoV-2 infection and/or immunization.

Background: Early allograft dysfunction (EAD) affects outcomes in liver transplantation (LT). Existing risk models developed for deceased-donor LT depend on posttransplant factors and fall short in living-donor LT (LDLT), where pretransplant evaluations are crucial for preventing EAD and justifying the donor's risks.

Methods: This retrospective study analyzed data from 2944 adult patients who underwent LDLT at 17 centers between 2016 and 2020. We developed a logistic regression model to predict EAD based on this development cohort. We used data from 1020 patients at the King Faisal Transplant Center for external validation.

Results: In the development cohort, 321 patients (10.9%) experienced EAD. These patients had poorer health status, more liver decompensation, and higher requirements of hospitalization than those without EAD. Multivariable logistic regression identified independent pretransplant predictors of EAD: laboratory Model for End-Stage Liver Disease score (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.06-1.09), the necessity for hospitalization at the time of transplant (OR, 2.58; 95% CI, 2.00-3.30), and graft weight in kilogram (OR, 0.27; 95% CI, 0.17-0.45). Using these predictors, we developed the model for EAD after LDLT, which demonstrated strong discriminative ability in the development cohort with an area under the curve (AUC) of 0.71 (95% CI, 0.68-0.74). The model maintained high discrimination during internal validation (AUC, 0.70; 95% CI, 0.67-0.73) and showed a modest reduction in discriminative power in external validation (AUC, 0.65; 95% CI, 0.61-0.68).

Conclusions: EAD post-LDLT is influenced by the recipient's pretransplant health condition and the graft weight. Integrating the model for EAD after LDLT into the pretransplant process of pairing donors and recipients can enhance the safety and efficacy of LDLT.

Reduced dependence on antirejection agents, improved long-term allograft survival, and induction of operational tolerance remain major unmet needs in organ transplantation due to the limitations of current immunosuppressive therapies. To address this challenge, investigators are exploring the therapeutic potential of adoptively transferred host- or donor-derived regulatory immune cells. Extracellular vesicles of endosomal origin (exosomes) secreted by these cells seem to be important contributors to their immunoregulatory properties. Twenty years ago, it was first reported that donor-derived exosomes could extend the survival of transplanted organs in rodents. Recent studies have revealed that regulatory immune cells, such as regulatory myeloid cells (dendritic cells, macrophages, or myeloid-derived suppressor cells), regulatory T cells, or mesenchymal stem/stromal cells can suppress graft rejection via exosomes that express a cargo of immunosuppressive molecules. These include cell surface molecules that interact with adaptive immune cell receptors, immunoregulatory enzymes, and micro- and long noncoding RNAs that can regulate inflammatory gene expression via posttranscriptional changes and promote tolerance through promotion of regulatory T cells. This overview analyzes the diverse molecules and mechanisms that enable regulatory immune cell-derived exosomes to modulate alloimmunity and promote experimental transplant tolerance. We also discuss the potential benefits and limitations of their application as therapeutic entities in organ transplantation.

Background: Simultaneous pancreas-kidney (SPK) transplantation is an effective treatment option for type 1 diabetes mellitus and concurrent end-stage kidney disease. However, the diabetogenic effects of immunosuppression can counteract the beneficial effects of sustained normoglycemia. Long-term metabolic trends that reflect cardiovascular risk are reported poorly in the literature.

Methods: A total of 500 patients with type 1 diabetes mellitus receiving SPK transplants at a single center with at least 2-y follow-up were evaluated retrospectively. Metabolic parameters and allograft function were followed longitudinally, including patient and allograft survival, body mass index (BMI), lipid profile, quantitative insulin sensitivity check index, estimated glomerular filtration rate, and urinary albumin-creatinine ratio up to 10 y posttransplant.

Results: Patient survival at 1, 5, and 10 y was 97%, 92%, and 87%, and overall death-censored graft survival was 87%, 84%, and 80%, respectively. Survival remained unchanged when stratified by BMI. Compared with pretransplant measurements, BMI significantly increased at 1, 3, and 5 y posttransplant. Total cholesterol, triglycerides, and low-density lipoprotein cholesterol decreased at 10 y posttransplant, with significantly increased high-density lipoprotein cholesterol at 5 y posttransplant. Insulin sensitivity improved significantly at 10 y posttransplant but did not normalize. Urinary albumin-creatinine ratio decreased by 3 y posttransplant but increased significantly between 3 and 10 y posttransplant, although the estimated glomerular filtration rate was unchanged during this time.

Conclusions: SPK transplantation is associated with excellent patient and graft survival. Significant long-term weight gain occurs despite improving lipid profiles and insulin sensitivity posttransplant. These data potentially reflect an overall cardiovascular burden that should be addressed in this population.