Transplantation proceedings最新文献

Transient or permanent mixed hematopoietic chimerism (MC) is associated with immunologic tolerance in combined solid organ and hematopoietic stem cell transplantation. This tolerance allows for the reduction or sometimes even suspension of systemic immunosuppression without graft rejection, with clear benefits regarding the side effects associated with lifelong immunosuppression. However, studies to date have included only living, HLA-matched donors to reduce the risk of graft-versus-host disease (GvHD), whereas the degree of HLA incompatibility between deceased donors and recipients is typically higher. Here we present a narrative review aimed at identifying the conditioning regimens predictive of MC in hematologic patients who have received an HLA-mismatched transplant, to provide some information on immunotolerance for future combined solid organ and stem cell transplantation in an HLA-mismatched setting. Among a total of 90 identified studies, 20 contained some information on MC, with a reported percentage of 2% to 100% of patients; 1186 patients were described in these 20 articles, with a median of 40 (range, 12 to 265) per study. When examining the conditioning regimens associated with MC ≥20% and GvHD <25% (n = 5), it was observed that 4 out of 5 studies contained antithymocyte globulin. The data suggest the importance of T lymphocyte depletion for achieving MC, associated with a low incidence of acute GvHD in hematopoietic stem cell transplantation from HLA-mismatched donors. Although additional work is needed, particularly on the ideal stem cell dose (ie, CD34⁺ and CD3⁺ cells), this information could be translated into the field of solid organ transplantation (SOT) to design a potential combined solid organ-stem cell transplantation protocol aimed at achieving MC for immune tolerance. The present work supports a translational perspective in the setting of SOT, where long-term immune tolerance is a major goal.

Introduction: Standard renal transplantation uses external iliac vessels. Iliac or IVC occlusion often excludes candidates, but a patent proximal IVC offers an alternative outflow.

Methods: We retrospectively reviewed kidney transplants with IVC anastomosis at a tertiary hospital (Jan 2000-Aug 2024). Outcomes were 30-day mortality and long-term graft survival.

Results: Among 1235 transplants, 14 required IVC anastomosis. Median follow-up was 110 months; median age 34 years; 8/14 were men. Indications included ilio-cava thrombosis, multiple transplants, or adult grafts in low-weight children. Thirteen grafts were placed in the right iliac fossa, one intraperitoneally; 10 were right kidneys, 12 from deceased donors. Seven cases used donor vena cava for vein extension. Two grafts failed (humoral rejection at 5 years; acute ischemia at 3 months). Remaining grafts functioned with mean creatinine 1.55 mg/dL at 5 years. No patient died within 30 days.

Conclusion: With longer End Stage Renal Disease survival, cases with limited vascular access or multiple transplants will rise. Proximal IVC anastomosis, though complex, is feasible and provides durable venous drainage.

Introduction: Disparities in heart and lung transplantation persist in the United States, yet most studies focus only on patients already referred or listed. We aimed to evaluate racial and socioeconomic disparities in access and receipt of transplantation among patients with chronic heart or lung disease.

Methods: We conducted a retrospective analysis using the National Inpatient Sample (2016-2022) to identify adults hospitalized with chronic heart or lung disease. Patients undergoing heart or lung transplantation and combine heart and lung transplantation were identified via ICD-10 codes. Multivariable logistic regression assessed associations between transplant receipt and race/ethnicity and ZIP-code-level income, after adjustment for age, sex, insurance status, comorbidities, and diagnosis.

Results: Among 5.1 million chronic lung and 2.1 million chronic heart disease hospitalizations, 4776 lung, 1537 heart transplants and 76 combined heart and lung transplants were identified. White patients had significantly higher odds of receiving lung transplantation (aOR: 3.97; 95% CI, 1.72-9.13, p < .01) than Black, Hispanic and Native American patients while in heart transplantation, Black patients had higher odds of getting transplanted (aOR: 3.09; 95% CI, 1.17-8.17, p = .02) than White, Hispanic and Native American patients. Patients from the highest-income ZIP codes were more likely to undergo lung (aOR: 3.63; 95% CI, 3.24-4.05, p < .01) or heart (aOR: 1.33; 95% CI, 1.13-1.55, p < .01) transplantation. No significant disparities were observed in combine heart and lung transplant patients.

Conclusion: Significant disparities by race and socioeconomic status persist in transplant access both in lung and heart transplantation. These findings highlight upstream structural barriers and offer a pre-Composite Allocation Score (CAS) baseline for future policy evaluation.

Introduction: Kidney transplant recipients remain susceptible to severe infectious disease such as the coronavirus associated infectious disease 2019 (COVID-19). Vaccination remains an important step in prevention, but data is needed to support the efficacy in this high-risk population. We sought to evaluate risk factors for breakthrough COVID-19 infection following vaccination among a single US state's resident with kidney transplant (KT).

Methods: Patients with a KT diagnosis prior to the COVID-19 pandemic period from 2019 to 2022 were compared to individuals without KT from a US statewide health registry for South Carolina. Propensity score matching used to match KT and non-KT recipients. Risk of breakthrough infections compared using Cox proportional hazards models. Outcomes (hospitalization and death) associated with breakthrough infection were similarly evaluated.

Results: After propensity score matching, 1270 KT and 2540 non-KT remained for analysis. Baseline covariates were well matched. Hazard ratio (HR) and 95% confidence interval (95%CI) for breakthrough COVID-19 infection for KT was 2.61 (1.94, 3.53; p < .001) versus non-KT. Booster vaccination was associated with lower risk for breakthrough vaccination (OR: 0.19, 95% CI: 0.11, 0.27, p < .001). KT patients with breakthrough COVID-19 infection had an odds ratio (OR) of 18 (95% CI 6.5, 61.1; p < .001) for hospitalization and OR 10.2 (95% CI: 2.65, 53.4; p = .002) for death versus non-KT.

Conclusion: Kidney transplant recipients remain at high risk for breakthrough COVID-19 infection as compared to non-kidney transplant recipients. Vaccination with mRNA-based vaccines and receipt of booster doses appear protective against infection and adverse outcomes.

Background: Mycophenolate mofetil (MMF) is widely recognized for its immunosuppressive effects through its active metabolite mycophenolic acid (MPA). This study utilizes computational approaches-molecular docking and molecular dynamics (MD) simulations-to explore MMF' s direct regulatory role in allograft rejection (AR), particularly in liver transplantation.

Methods: Potential targets of MMF were retrieved from Super-PRED, while AR-related genes were identified via Gene Set Enrichment Analysis (GSEA). Overlapping genes were analyzed using DAVID for functional enrichment (GO and REACTOME). A PPI network was constructed with STRING and visualized in Cytoscape. Core targets were subjected to molecular docking and MD simulations. Protein expression in liver tissues was validated using the Human Protein Atlas.

Results: GSEA identified 257 AR-associated targets. Intersection with MMF targets revealed 7 core genes. Functional analysis indicated their involvement in key biological processes and pathways. Molecular docking showed strong binding of MMF to core targets, especially HIF1A and PDGFRA, which was further confirmed by stable binding in MD simulations. Human Protein Atlas data indicated specific expression of HIF1A and PDGFRA within mobile immune cells in hepatic vasculature.

Conclusion: This study suggests a novel mechanism by which MMF may directly modulate specific targets, providing a theoretical basis for new MMF-based therapies and supporting further clinical exploration in transplantation immunology.

Background: End Stage Renal Disease (ESRD) occurs more frequently in people with cystic fibrosis (PwCF) than in the general population. We describe the characteristics and outcomes of kidney transplantation in PwCF.

Methods: We used data from the US Renal Data System, a virtually compete registry of US persons with ESRD. We compared patient characteristics and patient and graft survival of PwCF with kidney transplant with those without cystic fibrosis (CF), and PwCF with and without kidney transplant. We used linear and logistic regression, multivariable models, and Kaplan-Meier and log-rank tests with stratification/binning by propensity scores.

Results: Of PwCF and ESRD, 50.6% received their first kidney transplant. PwCF with transplant were younger and more likely to be female than those without. and had lower odds of diabetes and higher odds of complications of lung transplantation being the cause of ESRD. CF was associated with greater odds of a living donor graft. Median survival with a kidney transplant was 21.1 years for PwCF and 38.1 years for those without. Death-censored graft survival was 20.5 years for PwCF and 13.3 years for those without.

Conclusions: The demographic and disease profiles of PwCF and kidney transplant differed transplant recipients without CF. Diabetes was found less frequently, and complications of lung and other organ transplants found more frequently, to be the cause of ESRD in PwCF. Survival with a kidney transplant was shorter for PwCF but was substantial. Graft survival was longer for PwCF than those without. The diagnosis of CF should not exclude appropriate PwCF from consideration for kidney transplantation.

Background: Kidney transplantation is the optimal treatment for end-stage renal disease, yet post-transplant complications remain a major threat to graft survival. Interventional radiology (IR) has emerged as a minimally invasive alternative to surgery, but the comparative evidence base is fragmented and limited.

Methods: This systematic review synthesized evidence from 12 studies, conducted in accordance with PRISMA guidelines, to evaluate the effectiveness of IR versus surgical management of vascular, urological, and lymphatic complications after kidney transplantation.

Results: All included studies were retrospective and single-center, with a moderate to high risk of bias. Despite this, IR consistently demonstrated high technical (94%-100%) and clinical success rates, particularly for transplant renal artery stenosis (TRAS), where endovascular interventions improved renal function and blood pressure control, achieving superior graft survival compared to conservative management. For ureteric complications, IR provided immediate functional recovery, but 38% required surgical conversion, with surgery delivering superior durability in long or fibrotic strictures. In cases of lymphatic complications, percutaneous drainage was effective as a first-line measure; however, surgical fenestration achieved lower recurrence rates (<15%).

Conclusion: The current evidence suggests that IR should be considered the first-line treatment for many vascular and urological complications, while surgery remains indispensable for complex or recurrent cases. The proposed algorithm is applicable to both adult and pediatric recipients, though pediatric cases require tailored approaches due to anatomical and physiological differences. This review is the first to consolidate existing evidence into a complication-specific, stepwise management algorithm, providing a structured clinical framework for decision-making. Prospective, multicenter validation is urgently needed; however, adoption of this algorithm could reduce graft loss, optimize healthcare resources, and redefine standard practice in managing renal allograft dysfunction.

Background: Acute antibody-mediated rejection (AMR) is a rare but serious complication following liver transplantation that can lead to graft loss. AMR is caused by preformed anti-donor antibodies, ABO incompatibility, or de novo antibodies that develop post-transplantation. In this study, we aimed to evaluate the diagnosis of AMR by comparing the preoperative and postoperative Panel Reactive Antibody (PRA) Class I and Class II results of patients who underwent liver transplantation at our clinic.

Materials and methods: Seventy consecutive patients and their donors who underwent living donor liver transplantation at our institution between November 2017 and March 2018 were included in this study. Patients were divided into 2 groups: those who developed a more than 3-fold increase in liver function tests (LFTs) in the early postoperative period and those with a normal clinical course. The Mann-Whitney U test was used to compare quantitative data between the groups. The Chi-square test was used for the comparison of qualitative data, and a p-value of less than .05 was considered statistically significant. The nonparametric Wilcoxon Signed Rank test was used to evaluate the difference between preoperative and postoperative PRA I and PRA II levels in patients with elevated enzymes.

Results: Postoperative PRA I levels were found to be increased in 9 patients and decreased in 6 patients compared to preoperative levels. No change was observed in the remaining 3 patients. Although this may appear clinically significant, no statistically significant difference was found between postoperative and preoperative PRA I levels (p = .363). Similarly, postoperative PRA II levels were decreased in 9 patients, increased in 5, and unchanged in 4 when compared to preoperative PRA II levels. This result was also not statistically significant (p = .721).

Conclusion: When an elevation in LFTs occurs in liver transplant recipients, rejection should be considered after excluding vascular and other pathologies. AMR should be included among the possible diagnoses, and PRA testing should be part of the diagnostic workup. However, as observed in our study, changes in PRA levels may not always correlate with a diagnosis of AMR. Therefore, in such cases, a more appropriate approach would be to evaluate PRA results in conjunction with other diagnostic criteria.

Key words: Antibody mediated rejection, liver transplantation, panel reactive antibody.

The current recommended duration of 12 weeks of post-transplantation hepatitis C virus (HCV) treatment for HCV-uninfected recipients of HCV-infected kidneys (HCV D+/R-) is based on limited data. In March 2020, the transplant center's HCV-treatment protocol was revised by reducing the duration of treatment for glecaprevir/pibrentasvir from 12 weeks to 8 weeks, thus creating a natural experiment to compare sustained virologic response (SVR) rates between the 2 treatment groups. We analyzed HCV treatment outcomes of HCV D+/R- kidney recipients between October 2018 and July 2022 at a single transplant center in all patients treated with glecaprevir/pibrentasvir after kidney transplantation. Fifty-five patients were treated for 12 weeks, and 24 patients were treated for 8 weeks. In the 12-week group, 2 patients died of non-HCV causes after the end of treatment, before SVR; both were aviremic at the end of treatment. The remaining 53 patients achieved SVR. All 24 patients in the 8-week group achieved SVR. The median time to treatment initiation was 14 days (range, 3-138 days) for the 12-week group and 15 days (range, 5-81 days) for the 8-week group (P = .72). Even though most patients started treatment after the first week post-transplantation, 8 weeks of glecaprevir/pibrentasvir was equally effective as 12 weeks of treatment in achieving SVR for HCV D+/R- kidney recipients.

Background: The incidence of postoperative pulmonary infection following renal transplantation is high; however, there is a paucity of studies focused on developing risk prediction models in this patient population.

Objective: To construct a risk prediction model for postoperative pulmonary infection in renal transplant patients and verify the predictive efficacy of the model.

Methods: This was a retrospective case-control study involving 765 patients who underwent renal transplantation in the Renal Transplantation Department of a tertiary hospital in Shandong Province in China between January 2022 and September 2024. According to a 7:3 ratio, 535 patients who received renal transplants from January 2022 to December 2023 were assigned to the model group, while 230 patients who underwent renal transplantation from January 2024 to September 2024 served as the validation group. Logistic regression analysis was used to explore the influencing factors of postoperative pulmonary infection in renal transplant recipients, and a nomogram-based risk prediction model was constructed and validated.

Results: This study found that the incidence of postoperative pulmonary infection in renal transplant recipients was 24.31%. Logistic regression analysis identified gender (male), history of multiple transplants, comorbid hypertension history, comorbid heart disease history , and postoperative rejection as significant influencing factors. The Hosmer-Lemeshow goodness-of-fit test indicated adequate model calibration (χ²= 9.550, P = 0.145). The receiver operating characteristic (ROC) curve analysis yielded an area under the curve (AUC) of 0.740 [95% confidence interval (CI): 0.692-0.788], with a sensitivity of 88.00%, specificity of 49.20%, accuracy of 78.70%, positive predictive value (PPV) of 84.60%, and negative predictive value (NPV) of 56.20%. The calibration curve demonstrated close alignment between predicted and actual probabilities, with a low mean absolute error (MAE = 0.038), indicating robust calibration performance. In the validation cohort, the AUC was 0.705 [95% CI: 0.631-0.799], with an optimal probability threshold of 0.350, sensitivity of 91.90%, specificity of 36.20%, accuracy of 77.80%, PPV of 81.00%, and NPV of 60.00%.

Conclusion: The incidence of postoperative pulmonary infections in renal transplant patients is relatively high and is influenced by various factors (included male, history of multiple transplants, comorbid hypertension history, comorbid heart disease history, and postoperative rejection). The proposed risk prediction model exhibits favorable predictive performance and clinical utility, aiding clinicians in early identification of high-risk patients and guiding targeted preventive interventions.