Multiorgan Transplantation Research Articles

Cardiovascular risk factors and kidney transplantation: a retrospective analysis

Abstract Introduction Cardiovascular disease (CVD) poses a significant risk to end-stage kidney disease (ESKD) patients and remains the leading cause of morbidity and mortality among kidney transplant (KT) recipients. With a global rise in ESKD patients dependent on dialysis, transplant programs face growing pressure to consider candidates with a greater burden of CVD for KT despite potential long-term risks. Enhancing pre-KT cardiac risk assessment is crucial to prevent cardiovascular complications post-transplant and meet the demand for KT globally. Purpose High-quality studies evaluating pre-KT cardiovascular risk factors in patients with ESKD are lacking. Our study aims to evaluate the association between pre-KT cardiovascular risk factors and the development of major adverse cardiac events (MACE) post-KT. Methods This retrospective cohort study of ESKD patients at a tertiary center consisted of consecutive patients referred for cardiovascular assessment prior to KT between January 2013 and January 2023. Clinical and demographic data prior to KT and outcomes 1-year post-KT were extracted. Patients who underwent multi-organ transplantation were excluded. The primary endpoint was MACE, defined as all-cause death, myocardial infarction (MI), ischemic stroke, coronary revascularization, heart failure requiring hospitalization, and cardiac resuscitation. Results A total of n=233 patients were referred for cardiac evaluation prior to KT. Of these, n=145 (62%) patients had a KT, n=69 (30%) patients died pre-KT, and n=19 (8%) patients were removed from the transplant program. Of the n=143 KT recipients that met our inclusion criteria, 122 (85%) were free of MACE, while 21 (15%) met the primary endpoint in the year following KT. Patients with MACE were significantly older (mean age = 65 vs. mean age = 59, p < 0.001), and more likely to have coronary artery disease (85.7% vs. 50.8%, p = 0.01), cardiomyopathy (42.9% vs. 17.2%, p = 0.04), smoking history (71.4% vs. 46.7%, p = 0.04), and diabetes (85.7% vs. 49.2%, p = 0.02). Furthermore, deceased donor KT was associated with a greater likelihood of MACE (85.0% vs. 57.5%, p = 0.02) compared to living donor recipients. There were no significant differences with respect to left ventricular ejection fraction, diagnosis of heart failure, or prior MI between MACE and non-MACE groups (p > 0.17 for all). Conclusion Among pre-KT patients with CVD, there is a high mortality rate (30%) prior to KT. Following a successful KT, 15% of patients experienced MACE within 1-year. Our findings underscore the urgency of developing strategies to facilitate timely kidney transplantation, particularly in light of the anticipated rise in demand for kidney transplants. The elevated incidence of major adverse events in the year following a successful KT emphasizes the necessity of collaborative care by cardiologists and nephrologists for these patients, and the need for further studies to improve long-term outcomes.

Outcomes of Multiorgan Heart Transplant Between Donation After Circulatory Death and Brain Death.

There is insufficient data on the outcomes of donation after circulatory death (DCD) multiorgan transplant that includes heart. The primary objective of this study is to compare the overall survival outcomes of DCD and donation after brain death (DBD) multiorgan transplants. We identified all heart transplant patients from 2019 to June of 2023 using the United Network for Organ Sharing (UNOS) Database who also received an additional organ (kidney, liver, and lungs). A total of 1,844 DBD and 91 DCD multiorgan transplants occurred within the study period, the majority being combined heart-kidney transplantation. More patients were listed at a higher status in the DBD group (p < 0.05) and were in the intensive care unit (ICU) before transplant (p < 0.05). Despite the higher ischemia time in the DCD group (p < 0.05), the overall unmatched survival did not differ between the two groups (p < 0.05). Within the heart-kidney transplants, the overall survival between DBD and DCD heart-kidney transplants did not differ in either unmatched or matched groups (unmatched p = 0.5, matched p = 0.5). In conclusion, the data on the outcomes of DCD multiorgan transplants are limited. Still, our analysis of the currently available data suggests that the overall survival is comparable in the DCD multiorgan transplants.

High Intrapatient Tacrolimus Variability and Increased Cell-Free DNA in Kidney Transplant Recipients.

Introduction: An inverse relationship has been identified between tacrolimus serum concentrations and donor-derived cell-free DNA (dd-cfDNA) levels after lung transplant, but limited data exists on this relationship in the kidney transplant population. Project Aim: The purpose of this evaluation was to examine the relationship between high tacrolimus variability and elevated dd-cfDNA levels in kidney and simultaneous pancreas-kidney transplant recipients at a single center. Design: Single-center, retrospective, descriptive comparative evaluation of kidney and pancreas-kidney transplant recipients who received longitudinal ddcfDNA surveillance. Intrapatient tacrolimus variability was assessed using the coefficient of variation (%CV) measured between 1 and 12 months posttransplant. Pediatrics, retransplant or multiorgan transplant recipients, and pregnant recipients were excluded. Results: One hundred fifteen recipients with 518 dd-cfDNA levels and 3028 tacrolimus troughs were assessed. Pancreas-kidney recipients had significantly higher median dd-cfDNA (0.29% vs. 0.18%, P = .034) and were excluded from analysis. Ninety-nine kidney transplant recipients were included for analysis. Recipients with tacrolimus %CV ≥30 (N = 66) had significantly higher median dd-cfDNA than %CV <30 (0.22% vs. 0.17%, P = .031). Tacrolimus %CV ≥30 demonstrated higher median peak dd-cfDNA than %CV <30, though this was not statistically significant (0.36% vs. 0.28%, P = .058). Conclusion: These data demonstrated that high intrapatient tacrolimus variability may be associated with elevated dd-cfDNA in the first year after kidney transplant.

Clinical Utility of Donor-Derived Cell-Free DNA in Heart Transplant Recipients With Multi-Organ Transplants.

Donor-derived cell-free DNA (dd-cfDNA) has emerged as a reliable, noninvasive method for the surveillance of allograft rejection in heart transplantation (HT) patients, but its utility in multi-organ transplants (MOT) is unknown. We describe our experience using dd-cfDNA in simultaneous MOT recipients. A single-center retrospective review of all HT recipients between 2018 and 2022 that had at least one measurement of dd-cfDNA collected.Patients who had simultaneous MOT were identified and included in this study.Levels of dd-cfDNA were paired with endomyocardial biopsies (EMB) performed within 1 month of blood testing if available. Acute cellular rejection (ACR) was defined as ISHLT (International Society for Heart and Lung Transplantation) grade≥2R. and antibody-mediated rejection (AMR) was defined as pAMR grade > 0.The within-patient variability score of the dd-cfDNA was calculated by the variance/average. The study included 25 multiorgan transplant recipients: 13 heart-kidney (H-K), 8 heart-liver (H-Li), and 4 heart-lung (H-Lu). The median age was 55 years, 44% were female; the median time from HT until the first dd-cfDNA measurement was 4.5 months (IQR 2, 10.5).The median dd-cfDNA level was 0.18% (IQR 0.15%, 0.27%) for H-K, 1.15% (IQR 0.77%, 2.33%) for H-Li, and 0.69% (IQR 0.62%, 1.07%) for H-Lu patients (p < 0.001).Prevalence of positive dd-cfDNA tests (threshold of 0.20%) were 42.2%, 97.3%, and 92.3% in the H-K, H-Li, and H-Lu groups, respectively. The within-patient variability score was highest in the H-Li group (median of 0.45 [IQR 0.29, 0.94]) and lowest in the H-K group (median of 0.09 [IQR 0.06, 0.12]); p = 0.002. No evidence of cardiac ACR or AMR was found. Three patients experienced renal allograft ACR and/or AMR, two patients experienced rejection of the liver allograft, and one patient experienced an episode of AMR-mediated lung rejection. One person in the H-K group experienced an episode of cardiac allograft dysfunction that was not associated with biopsy-confirmed rejection. Dd-cfDNA is chronically elevated in most MOT recipients.There is a high degree of within-patient variability in levels (particularly for H-Li and H-Lu recipients), which may limit the utility of this assay in monitoring MOT recipients.

Navigating the changing landscape of transplant research: Trends, topics, and gender disparities

BackgroundTransplantation is a rapidly evolving field, reflecting advances in medical science and changing healthcare needs. This study aims to elucidate shifts in research focus over a decade, providing insights into emerging trends in transplant research. MethodsWe conducted a comprehensive analysis of 9,250 articles published in five high-impact transplant journals from 2012 to 2021. Article titles were processed to extract keywords using R Studio (v. 4.3.0). STATA 18 was used for t-tests and logistic regressions, with significance set at p ​< ​0.05. ResultsEmerging topics over the decade included outcomes and survival, surgical innovations, and lung transplantation. There was a downward trend in research on immunosuppression, genetics, and immunology. Over the decade, the odds of women's first authorship were higher for subjects such as public health, pediatric transplantation, infectious diseases, renal transplantation, and psychological aspects. Similarly, there were lower odds for women as first authors on surgical innovations, organ preservation, living donor transplantation, liver and lung transplantation, and multiorgan transplantation. Senior women authors had higher odds of publishing on the same topics as first author, plus immunology, kidney and heart transplantation. There were lower odds that a woman would be last author of regenerative medicine and xenotransplantation. Over the decade, there were higher odds of funding for research published on xenotransplantation, regenerative medicine, and immunology. Living donor, infectious diseases, and liver transplantation had lower odds of being funded over time. ConclusionThis cross-sectional study highlights the dynamic nature of transplant research, underscoring the importance of continuous observation of trends to anticipate future directions and needs in the field. The emergence of new focal areas, especially those related to technological advancements and social issues, reflects a broader trend in medical research responding to evolving challenges and opportunities. Notably, women's authorship was more prevalent in public health but less in surgical innovation. These insights can guide future research priorities, funding allocation, and clinical practices in transplantation.

Intercostal Nerve Cryoablation in Lung Transplantation: A Single-Center, Propensity-Matched Analysis

ObjectiveAchieving adequate pain control after lung transplantation is an essential milestone in a patient’s recovery. We compared postoperative opioid use, clinical outcomes, and respiratory function in lung transplant recipients treated with intercostal nerve cryoablation (INC) vs standard pain management. MethodsWe reviewed all adult lung transplants performed at our center between January 2016 and December 2022. We excluded cases performed through median sternotomy , patients with prior thoracotomies, multiorgan transplants, and redo transplants. We performed a propensity matched analysis, comparing patients who received INC versus standard pain management The primary outcome was cumulative postoperative opioid use in morphine milligram equivalents (MME) by POD 14. Secondary outcomes included opioid use on POD5 and POD10, perioperative outcomes, 1-year survival and longitudinal measurement of respiratory function. ResultsPropensity matching resulted in 85 patients in each group. Compared to standard pain management, the INC group had a lower cumulative opioid use by POD 14 (509 vs 864 MME, p=0.032). In addition, the INC group had a lower opioid use at POD5, POD10, POD14, no difference in perioperative outcomes, and similar 1-year survival. The INC group had better respiratory function at 6 and 12-months posttransplant compared to the standard pain management group. ConclusionsIn our single center analysis, INC was associated with lower opioid use and improved respiratory function after lung transplant. This report adds to the growing literature supporting the use of INC in multimodal pain management strategies and enhanced recovery protocols in lung transplant.

The association between pretransplant malignancy and post-transplant survival and cancer recurrence in bilateral lung transplantation: An analysis of 23,291 recipients

BackgroundGiven the increasing need for lung transplants among older patients with a history of cancer, this study analyzed database registry to assess outcomes for BLT recipients with Pre-TM. MethodsThis study evaluated the United Network for Organ Sharing (UNOS) registry for adult BLT performed between 2005 and 2023. Patients with a history of previous or multi-organ transplants, and those with donors who had cancer history, were excluded. Propensity-score matching was used to compare patients with or without Pre-TM. Overall and Post-TM-free survival were analyzed. ResultsAmong the 23,291 recipients of BLT, 8.0%(1,870) had Pre-TM. Compared to those without Pre-TM, patients with Pre-TM had worse overall (hazard ratio[HR] 1.20, 95% confidence interval[CI] 1.12-1.29, p<0.001) and Post-TM-free survival (HR 1.32, 95% CI 1.24-1.41, p<0.001). However, after adjusting for age, sex, and race through propensity-score matching, the survival difference between the groups became non-significant (HR 1.05, 95% CI 0.97-1.13, p=0.229). While the Pre-TM group still had worse Post-TM-free survival, this difference diminished after excluding cutaneous Post-TM (HR 1.06, 95% CI 0.99-1.15, p=0.116). Additionally, the recurrence rate of Pre-TM after transplant wasn't higher than de novo cancers in patients without Pre-TM. ConclusionPatients with Pre-TM had similar overall survival rates after BLT as those without Pre-TM. Importantly, there was no increased risk of the primary Pre-TM type recurring post-transplant compared to patients without Pre-TM. If patients with PreTM are free from recurrence or metastasis for a significant amount of time, there could be some who can benefit from BLT. Further data regarding timeline between PreTM and BLT would be necessary to draw conclusion in this issue.

Outcomes of Donation After Circulatory Death (DCD) and Ex-Vivo Lung Perfusion (EVLP) Lung Transplantation

BackgroundDonation after circulatory death (DCD) and ex-vivo lung perfusion (EVLP) have been adopted to expand the donor pool in lung transplantation, but outcomes data have been conflicting. This study explores mid-term outcomes of DCD lung transplantation in the modern era, with a focus on EVLP and risk factors for graft failure. MethodsThe United Network for Organ Sharing (UNOS) database was queried for adult lung transplants from 1/1/2015 to 3/1/2023. Loss to follow-up, multiorgan and prior lung transplants were excluded. DCD vs DBD (donation after brain death) lung transplants were compared, with subgroup analysis +/- EVLP. Outcomes were survival and postoperative complications. Overall survival was analyzed separately for an early era (2015-2018) and modern era (2019-2023). ResultsThe study included 1103 DCD (221 with EVLP, and 882 without) and 17973 donation after brain death (DBD) lung transplants (524 with EVLP, and 17449 without). Median follow-up was 3 years. DCD donors were less likely to be CDC high risk (19.3% vs 24.1%, p<0.001), have purulence on bronchoscopy (13.3% vs 18.3%, p<0.001) or infiltrates on chest x-ray (66.7% vs 67.8%, p=0.013). EVLP was more likely to be used for DCD transplants (20.0% vs 2.9%, p<0.001).After transplant, DCD recipients were more likely to be reintubated (24.3% vs 18.5%, p<0.001) and require ECMO within 72 hours (14.9% vs 7.8%, p<0.001), and DCD donation was an independent risk factor for these complications on multivariable logistic regression. Overall survival did not differ significantly between DCD and DBD transplants on adjusted survival analysis in the early or modern era (p=0.774 and p=0.468 respectively). On multivariable Cox regression, DCD and EVLP were not independent risk factors for mortality.On subgroup analysis, the DCD+EVLP cohort had significantly worse survival in the modern era, which remained significant after adjusting for donor and recipient factors (p=0.005). EVLP was an independent risk factor for graft failure in the DCD cohort (HR 1.33, 95% CI 1.00-1.77, p=0.047), but did not significantly affect DBD graft survival (p=0.870). Risk factors for graft failure and mortality in the DCD+EVLP cohort included pulmonary hypertension (HR 77.5, 95% CI 6.15-979, p<0.001), transfusion prior to transplant (HR 2.60, 95% CI 1.07-6.31, p=0.035), elevated creatinine (HR 2.82, 95% CI 1.34-5.90, p=0.006), and higher allocation score (HR 1.02, 95% CI 1.00-1.04, p=0.017) ConclusionStudy findings suggest increased risks of mortality and perioperative complications following transplantation with DCD lungs that have undergone EVLP. DCD lung transplantation without EVLP confers equivalent survival but with some increase in perioperative complications. Further investigation and careful recipient selection is warranted to optimize the use of these extended criteria donors in the modern era.

Extracorporeal membrane oxygenation as a bridge to thoracic multiorgan transplantation

BackgroundExtracorporeal membrane oxygenation (ECMO) has emerged as a crucial tool in the care of patients with multiorgan failure, and is increasingly utilized as a bridge to transplantation. While data on ECMO as a bridge to isolated heart and lung transplantation have been described, our emerging experience with ECMO as a bridge to thoracic multiorgan transplantation is not yet well understood. This study aims to investigate temporal trends, utilization, and outcomes in ECMO as a bridge to thoracic multiorgan transplantation. MethodsThe United Network for Organ Sharing database was used to identify adult patients undergoing thoracic multiorgan transplantation between 1987 and 2022. Exclusion criteria were recipient age <18 and bridging with other mechanical circulatory support including ventricular assist device (VAD) and intra-aortic balloon pump (IABP). Survival analysis was performed to compare outcomes between patients bridged to transplantation with ECMO and those who were not bridged. ResultsOf 3,927 patients undergoing thoracic multiorgan transplantation, a total of 203 (5.2%) patients received ECMO as a bridge to transplantation. Among ECMO recipients, patients were most commonly bridged to heart-lung (45.8%), followed by heart-kidney (34.5%), and lung-kidney transplantation (11.8%). At a median follow-up of 35.5 months, unadjusted survival among patients bridged with ECMO was decreased versus multiorgan transplant recipients who were not bridged (p<0.001). With adjusted multivariable Cox regression, ECMO was independently associated with an elevated risk of mortality following multiorgan transplantation (HR 1.56 [1.21-2.02], p<0.01). Among patients surviving past 30 days following transplantation, conditional long-term survival was similar between those bridged with ECMO and those not bridged (p = 0.82). ConclusionECMO is increasingly utilized as a bridge to thoracic multiorgan transplantation, and is associated with increased 30 day mortality and decreased long-term survival. In select patients surviving to 30 days following transplantation, similar long-term survival is seen between patients bridged with ECMO and those not bridged.

Providing red blood cells to facilitate organ transplant via normothermic perfusion techniques: A single-center experience.

Normothermic regional perfusion (NRP) and normothermic machine perfusion (NMP) are organ procurement and transport techniques that can improve organ quality, facilitate longer transport, and reduce postoperative complications, increasing organ availability and improving outcomes. NRP and NMP often require allogeneic red blood cells (RBCs). Our academic transfusion service began providing RBCs to support NRP and NMP for adult heart transplant (HT), orthotopic liver transplant (OLT), and multiorgan transplant (MOT) in August 2020. This single-center, retrospective study describes the implementation process and analyzes the characteristics of RBC support during the first 3 years of the perfusion programs. Timing and quantity of units issued and used, organ recipient demographics, and transplant outcomes were obtained from transfusion service and electronic medical records. From 2020 to 2023, the transfusion service received 233 requests to support NRP and NMP perfusion cases. Of these, 105 cases resulted in RBC use, and units were returned or discarded in 112 cases. A total of 131 patients received perfusion-facilitated transplants (92 HT, 27 OLT, and 12 MOT). The majority of perfusion-facilitated HTs utilized NRP (81/92, 88%), whereas most perfusion-facilitated OLTs utilized NMP (21/27, 78%). Across all 233 requests, a total of 381 RBC units were used to facilitate 131 transplants, averaging 2.91 units/transplant. Provision of RBCs for NRP and NMP techniques represents a novel method for transfusion services to support and facilitate life-saving organ transplants with only modest product use, about three RBC units per organ transplant in this single-center study.

Impact of Religious Affiliation on Clinical Outcomes in Liver Transplant Patients.

While the impact of spirituality as it relates to quality of life post-liver transplant (LT) has been studied, there are limited data showing how religious affiliation impacts objective measures such as survival. The aim of the study is to investigate whether LT recipientswho identified as having a religious affiliation had better clinical outcomes when compared to LT recipientswho did not. Religious affiliation is obtained as part of general demographic information for patients within our institution (options of "choose not to disclose" and "no religious affiliation" are available). Subjects in this retrospective cohort study which conformed with the Declarations of Helsinki and Istanbul were separated into cohorts: LT recipientswho self-reported religious affiliation and LT recipients who did not. All LT recipients between March 2007 and September 2018 who had available information regarding their reported religion were included. Excluded patients included those who received a multi-organ transplant, underwent re-transplantation, received a partial liver graft, and identified as agnostic. Outcomes included 30-day readmission, death, and the composite outcome of re-transplantation/death. In an unadjusted analysis of 378 patients, there were no statistically significant differences between the two groups for 30-day readmission (OR=1.15, P=0.71), death (HR=0.63, P=0.19), or re-transplantation/death (HR=0.90, P=0.75). In multivariable analysis, adjusting for age at transplant and hospital admittance status when called for transplant, results were similar. We found no statistically significant difference in the outcomes measured between patients with and without self-reported religious affiliation. Further studies into the role of participation in religious activity and the impact of engagement with a religious community should be conducted in the future.

Trends in heart transplant outcomes for patients over the age of 70 years in the United States: An analysis of the scientific registry of transplant recipients database

BackgroundPatients of advanced age are often considered to be poor candidates for heart transplant (HT). As the U.S. population continues to age, it is important for clinicians to understand how best to select patients for advanced therapies. MethodsThis was a retrospective analysis of the U.S. Scientific Registry of Transplant Recipients data from 2006 to August 2022 in adult recipients. Patients were excluded if they were multiorgan transplant, re-do transplants, or less than 1 year post transplant. ResultsRecipients ≥70 had a one-year survival of 87.5%, compared to 91.1% for <60, and 88.4% for 60-69 years (p<0.001). Survival improved numerically, but not significantly, as transplant eras progressed for those ≥70 years. Survival by Kaplan-Meier analysis was greatest at five years for <60 years (80.6%), compared to 60-69 years (78.2%) and ≥70 years (77.1%). When comparing 60-69 years to ≥70 years by this same metric, there was significant difference (p=0.12). One year survival for those ≥70 years has improved from 2000-2009 (80.7%) to 88.5% since October 2018 (p<0.001). As recipients increased in age, they were more likely to be male, and less likely to be Black or Hispanic/Latino (p<0.001). ConclusionOverall, HT outcomes are excellent for carefully selected patients ≥70 years, and transplanting patients in this age cohort can be considered.

Heart-liver transplantation using the en bloc technique: A single-center experience over two decades

BackgroundCombined heart-liver transplantation (CHLT) is a definitive therapy reserved for patients with concomitant heart failure and advanced liver disease. A limited number of centers perform CHLT, and even fewer use the en bloc implantation technique. Here we review clinical outcomes and immunoprotective effects following CHLT and describe our institution's more than two decades of experience in performing the en bloc technique. MethodsAll patients who underwent CHLT at our institution between January 2003 and July 2023 were identified. Recipient and donor characteristics, operative details, and clinical outcomes were assessed. Kaplan-Meier analysis was performed to evaluate survival following CHLT. ResultsA total of 20 patients underwent CHLT using the en bloc technique at our institution between January 2003 and July 2023. At a median follow-up of 3.8 years for patients who survived the perioperative period (n = 18), estimated survival was 94% at 1 year and 75% at 5 years. There was 100% freedom from acute moderate rejection, acute severe rejection, and chronic rejection in all patients. No patients required retransplantation due to rejection. ConclusionsCHLT is a definitive therapy reserved for patients with multiorgan dysfunction. At our institution, the en bloc technique is the preferred operative approach, as it minimizes cardiac insult, requires fewer anastomoses, minimizes cold ischemia time, and allows for rapid correction of coagulopathy. Overall survival for this cohort is excellent. Episodes of acute rejection were rare, providing further support for the idea that the liver may serve an immunoprotective role in multiorgan transplantation.

Antifungal prophylaxis against invasive Candida and Aspergillus infection in adult heart transplant recipients: protocol for a systematic review and meta-analysis

IntroductionInvasive fungal infections (IFI) can contribute to increased mortality and morbidity rates after heart transplant in adults. The most common causes are Aspergillus and Candida species. There is uncertainty on...

Comparison of cardiac allograft vasculopathy incidence between simultaneous multiorgan and isolated heart transplant recipients in the United States

BackgroundPrior studies have shown reduced development of cardiac allograft vasculopathy (CAV) in multi-organ transplant recipients. The aim of this study was to compare the incidence of CAV between isolated heart transplants and simultaneous multi-organ heart transplants in the contemporary era. MethodsWe utilized the Scientific Registry of Transplant Recipients to perform a retrospective analysis of first-time adult heart transplant recipients between January 1, 2010 and December 31, 2019 in the United States. The primary endpoint was the development of angiographic CAV within 5 years of follow-up. ResultsAmong 20,591 patients included in the analysis, 1,279 (6%) underwent multi-organ heart transplantation (70% heart-kidney, 16% heart-liver, 13% heart-lung, and 1% triple-organ) and 19,312 (94%) were isolated heart transplant recipients. The average age was 53 years and 74% were male. There were no significant between-group differences in cold ischemic time between the groups. The incidence of acute rejection during the first year after transplant was significantly lower in the multi-organ group (18% vs. 33%, p<0.01). The 5-year incidence of CAV was 33% in the isolated heart group and 27% in the multi-organ group (p<0.0001); differences in CAV incidence were seen as early as 1 year after transplant and persisted over time. In multivariable analysis, multi-organ heart transplant recipients had a significantly lower likelihood of CAV at 5 years (hazard ratio=0.76, 95% confidence interval: 0.66-0.88, p<0.01). ConclusionsSimultaneous multi-organ heart transplantation is associated with significantly lower long-term risk of angiographic CAV compared with isolated heart transplantation in the contemporary era.

Abnormal Liver Biopsies of Donor Grafts in Pediatric Liver Transplantation: How Do They Fare?

BACKGROUND Little is known about outcomes of pediatric patients transplanted using donor liver grafts with abnormal biopsy results. We assessed donor liver biopsy data to report characteristics and outcomes of abnormal livers transplanted in pediatric patients. MATERIAL AND METHODS We identified pediatric patients who received a liver transplant from a biopsied deceased donor between 2015 and 2022 using the national database UNOS Standard Transplant Analysis and Research files. Recipients were excluded if they received multi-organ transplants or were lost to follow-up. Livers with ≤5% macrosteatosis, no fibrosis, and no inflammation were classified as normal livers (NL). Allografts with >5% macrosteatosis, any fibrosis, or any inflammation were considered abnormal livers (AL). Donor and recipient demographic data and outcomes were examined. RESULTS Of the 3808 total pediatric liver transplants in the study period, there were 213 biopsied donor liver allografts transplanted into pediatric recipients. Of those, 114 were NL and 99 were AL. 35.4% (35/99) of the AL had >5% macrosteatosis with a mean of 7.6±11.4%, 64.6% (64/99) had any inflammation, and 18.2% (18/99) had any fibrosis. AL donors were significantly older than NL donors. AL recipients had higher PELD scores. There were no significant differences in length of stay, rejection rates and causes, or allograft survival between AL and NL. Multivariable analysis revealed that inflammation was independently associated with a significantly greater risk for graft failure. CONCLUSIONS Outcomes of abnormal livers are excellent. Inflammation was an independent risk factor for poor graft prognosis. Donor biopsies in pediatric liver transplantation can be a useful adjunct to assess outcomes.

Adult Congenital Heart Disease Transplantation: Does Univentricle Physiology Impact Early Mortality?

BackgroundWith patients with congenital heart disease increasingly living into adulthood, there is a growing population of patients with adult congenital heart disease (ACHD) who have heart failure. Limited data exist on evaluating heart transplantation in this population. MethodsA retrospective review was performed of patients with ACHD who underwent heart transplantation from November 1990 to January 2023. Kaplan-Meier, cumulative incidence accounting for competing risk of death, and subgroup analyses comparing those patients with biventricular (BiV) and univentricular (UniV) physiology were performed. Data are presented as median (interquartile range [IQR]) or counts (%). ResultsA total of 77 patients with a median age of 36 years (IQR, 27-45 years) were identified, including 57 (74%) BiV and 20 (26%) UniV patients. Preoperatively, UniV patients were more likely to have cirrhosis (9 of 20 [45.0%] vs 4 of 57 [7.0%]; P < .001) and protein losing enteropathy (4 of 20 [20.0%] vs 1 of 57 [1.8%]; P = .015). Multiorgan transplantation was performed in 23 patients (30%) and more frequently in UniV patients (10 [50%] vs 13 [23%]; P = .04). Operative mortality was 6.5%, 2 of 20 (10%) among UniV patients and 2 of 57 (4%) among BiV patients (P = .276). Median clinical follow-up was 6.0 years (IQR, 1.4-13.1 years). Survival tended to be lower among UniV patients compared with BiV patients, particularly within the first year (P = .09), but it was similar for survivors beyond 1 year. At 5 years, the incidence of rejection was 28% (IQR, 17%-38%) and that of coronary allograft vasculopathy was 16% (IQR, 7%-24%). ConclusionsUnderlying liver disease and the need for heart-liver transplantation were significantly higher among UniV patients. Survival tended to be lower among UniV patients, particularly within the first year, but it was similar for survivors beyond 1 year.

Rethinking the impact of pretransplant malignancy on eligibility for double lung transplantation (DLT): An analysis of 23,291 recipients.

11180 Background: The outcomes for double lung transplant recipients with a history of pretransplant malignancy (PreTM) have not been extensively studied in a large, multicenter database. Given the rising need for transplants among older patients with a history of cancer and the improving outcomes of DLT, this study aimed to analyze recipient outcomes in the modern era. Methods: This study evaluated the United Network for Organ Sharing (UNOS) registry for adult DLT performed between 2005 and 2023. Patients with a history of previous or multi-organ transplants, and those with donors who had a history of malignancy, were excluded. Propensity-score matching was used to compare patients with or without PreTM. Posttransplant malignancies (PostTM) were classified into cutaneous and non-cutaneous types. The primary outcomes were overall and PostTM-free survival. Results: Of the 23,291 DLT recipients, 1,870 recipients (8.0%) had a history of PreTM, which was classified into twelve types. Patients with PreTM experienced worse overall (HR 1.20 [95% CI 1.12-1.29], p&lt;0.001) and PostTM-free survival (HR 1.32 [95% CI 1.24-1.41], p&lt;0.001). After propensity-score matching for age, sex, and race, the differences in overall survival between the two groups were diminished (HR 1.05 [95% CI 0.97-1.13], p=0.229). Although PostTM-free survival was still worse in the PreTM group, this difference was not observed after excluding cutaneous PostTM (HR 1.06 [95% CI 0.99-1.15], p=0.116). The incidence of PostTM of the same PreTM type among patients with PreTM was 13.5% (253/1870), which was not higher than the incidence of de novo PostTM incidence among patients without PreTM (p=0.633). Conclusions: Patients with PreTM show similar overall survival rates after DLT as those without PreTM, despite a higher incidence of PostTM, mainly cutaneous. Importantly, there is no increased risk of the original cancer type recurring in PreTM patients compared to the risk of de novo malignancy. These findings highlight the necessity for a more nuanced evaluation of transplant candidacy to prevent premature exclusion of PreTM patients from potentially life-saving surgeries. [Table: see text]

#3036 The influence of first renal graft on second graft rejection and survival: the importance of revisiting histocompatibility and clinical outcomes

Abstract Background and Aims Kidney retransplantation confers a robust survival benefit over dialysis and recent data has shown similar outcomes to first kidney transplant. The number of HLA mismatches is an important predictor of graft loss and sensitization and the presence of donor specific antibodies (DSA) -pre and -post transplant is a major risk factor for rejection and worst outcomes. However, the importance of HLA matching of first graft and the relevance of first donor DSAs on second graft outcomes is less known. Our aim was to identify risk factors to second graft acute rejection and graft loss, related to second and first graft features. Method We performed a retrospective, longitudinal study including all patients submitted to a 2nd kidney transplant between January 2008 and December 2021, excluding patients with more than 2 grafts or multi-organ transplant. Clinical and histocompatibility data from the first and second donor and recipient were collected. HLA antibodies were detected by solid phase assays and considered if MFI &amp;gt;2500. For subsequent kidney transplants, repeated mismatches are not allowed and unacceptable antigens are those for which the patient has pre-formed -A, -B and -DR antibodies, with MFI&amp;gt;1000. Biopsy proven acute rejection was defined according to Banff 2017 criteria. Follow-up was 31st December 2023 for functioning grafts or time to graft failure, with a mean time of 92 ± 53 months. Results We included 114 patients, 73 (64%) males, mostly Caucasians (96%), with a mean age of 43.9 ± 13 years at 2nd transplant. First kidney transplant was performed before 2010 for 99 patients (87%), with a median first graft survival of 82.5 [12.5-144] months and 19 patients (16.7%) presented primary disfunction due to surgical/vascular complications. After graft loss, 43 patients (37.7%) had their graft removed. For second transplant, 11 (9.6%) patients had a living donor. Induction therapy with thymoglobulin occurred in 94 patients (83%) and maintenance therapy with mycophenolic acid, calcineurin inhibitors and steroids was prescribed in 83 patients (73%). During follow-up, 20 patients (17.5%) presented biopsy proven acute rejection, 13 (65%) T cell mediated and 7 (35%) antibody-mediated, the majority during the first-year post-transplant (N = 17, 85%). The risk factors for second graft rejection are summarized in Table 1. Patients with a first graft nephrectomy had a higher risk of acute rejection (OR 3.9, 95% CI [1.4-10.9], p &amp;lt; 0.006) and were more susceptible to the development of second donor post-transplant DSA (58% vs 35%, p = 0.02). Death censored second allograft loss occurred in 24 patients (21%) at follow up and acute rejection was an important risk factors (OR 4.3, 95% CI [1.5-12.1], p = 0.004). First-year graft survival was 93% and a survival at follow up was 79%. On survival analysis the presence of second graft DSA was a major risk factor for graft loss, especially class 2 -DQ and -DR. First transplant total mismatch load, especially on class 1 contributed to worst graft survival. Conclusion Worst outcomes in first kidney transplant were related with an increased risk of acute rejection in second graft and 1st graft nephrectomy increases the risk of the development of 2nd graft DSA and acute rejection. First transplant mismatch load decreased second graft survival.

Challenges in perioperative blood transfusions in kidney transplantation and the need for Patient Blood Management.

Anemia is highly prevalent in end-stage chronic kidney disease patients, increasing their risk of receiving blood transfusions during and on the days after a kidney transplant (KTx) surgery. However, there is currently a lack of data that thoroughly describes this phenomenon in this population, the associated risk factors, and how they could benefit from the application of Patient Blood Management (PBM) guidelines. Observational study. All adult patients who received a KTx between January 1st, 2020, and December 31st, 2021, were included and followed up to six months after transplantation. Those who received a multiorgan transplant, whose data was missing in the electronic health records, and who had primary non-function were excluded. We recorded donor and recipient characteristics, cold ischemia time, preoperative hemoglobin concentration, iron status deficiency biomarkers, incidence of delayed graft function and biopsy-proven graft rejections, and graft function at discharge and 6 months after transplantation. We found that a high amount (39%) of KTx recipients required at least one blood transfusion during the perioperative period. And that 1) most of these patients had anemia at the time of transplantation (85.4%), 2) iron status upon admission was associated with the transfusion of more blood units (3.9 vs 2.7, p=0.019), 3) surgical reintervention (OR 7.28, 2.35-22.54) and deceased donor donation (OR 1.99, 1.24-3.21) were associated with an increased risk of transfusion, and finally, 4) there was an association between a higher number of blood units transfused and impaired kidney graft function six months after hospital discharge (1.6 vs 1.9, p=0.02). In conclusion, PBM guidelines should be applied to patients on the KTx deceased donor waiting list and especially those scheduled to receive a transplant from a living donor. This could potentially increase the utilization efficiency of blood products and avoid transfusion-related severe adverse effects.