Multiorgan Transplant Recipients Research Articles

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.

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.

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.

#4743 OMNIGRAF (COMBINED GENE EXPRESSION AND DD-CF DNA) USE IN MONITORING RENAL ALLOGRAFT REJECTION IN MULTIORGAN TRANSPLANT RECIPIENTS

Abstract Background and Aims To date there is no clinically available non-invasive biomarker to monitor for renal allograft rejection in multiorgan transplant recipients. TruGraf (Gene expression profile) and TRAC (dd-cf DNA), as part of the biomarker panel OmniGraf, have shown to be reliable “rule out” tests for subclinical rejection in stable kidney transplant recipients. However, the validity and utility of these tests in monitoring for renal allograft rejections in the setting of multiorgan transplants has yet to be assessed. The aim of this study is to assess the feasibility of using the biomarkers individually, as well as together in the OmniGraf biomarker panel, to assist in making the decision to perform a renal allograft biopsy in multiorgan transplant recipients. Method This is an ongoing prospective, observational sample collection study in any multiorgan (kidney + non-renal organ) undergoing a renal allograft biopsy. Biopsies were considered positive if they showed rejection in the kidney based on Banff 2019 and included borderline changes as positive results. Copper-Pearson 95% CI were used for sensitivity, specificity, and accuracy; standard logit CIs were used for NPV and PPV. For TruGraf, (TX = negative result) and (not-TX = positive test). For TRAC, 0.7% was used as the threshold for all organs except for those that had a liver transplant, where a threshold of 15% was used to determine positive vs. negative. Results Paired renal allograft surveillance biopsies and biomarker samples were available for 20 patients. Of the 20, 9 (45%) were liver-kidney transplants, 6 (30%) were heart-kidney transplants, and 5 (25%) were kidney-pancreas transplants. Nine (45%) of the patients were male, 14 (70%) were White, 5 (25%) were Black, and 1 patient was Hispanic. The mean age was 50 ± 13 years. Average SrCr was 1.3 ± 0.5 mg/dL. Of the 20 paired biopsies and samples, 2 (10%) had only TruGraf results, while the other 18 (90%) had OmniGraf (TruGraf and TRAC). There were 2 rejections (borderline changes). Diagnostic performance is presented in tables 1–4. Both TruGraf and TRAC individually had NPV of 89% and 85%, respectively, and PPV of 65% and 73%, respectively. When analyzing the performance of the OmniGraf biomarker panel, OmniGraf +/+ showed a 100% PPV and OmniGraf -/- showed a 100% NPV. Conclusion In this analysis of renal allograft biopsies in a multiorgan transplant cohort, TruGraf, TRAC (when using organ-dependent thresholds) had reasonable diagnostic performance as a “rule out” test. When the tests are combined into OmniGraf, the PPV and NPV were 100% when both tests agreed with each other. These outcomes justify potential use and the need for continued analysis of the utility of the OmniGraf biomarker panel in monitoring renal allograft in multiorgan transplant recipients.

Normal Saline vs Plasma-Lyte A Use Intra- and Post-Operatively in Adult Kidney Transplant Recipients

Fluid management intra- and post-operatively for kidney transplant recipients (KTR) is essential to maintain adequate perfusion to the kidney. 0.9% normal saline (NS) is commonly used, but it can cause hyperchloremic metabolic acidosis, which may result in hyperkalemia and lead to delayed graft function (DGF). Plasma-Lyte A (PA) is an alternative option that has a lower amount of chloride and a neutral pH, which may offset the risk of hyperkalemia. The aim of this study is to determine the incidence of DGF in KTRs comparing NS vs PA use intra- and initially post-operatively. This single-center, retrospective cohort study in adult KTRs from January 1, 2016 to February 1, 2021 consisted of two cohorts, those receiving NS vs PA. Multi-organ transplant recipients were excluded. The primary outcome was the incidence of DGF. A total of 244 KTRs in the NS group and 263 KTRs in the PA group were included. There was no significant difference in incidence of DGF between the groups, (NS 23.4% vs PA 25.9%, p = 0.537). The logistic regression for only deceased donors were not significantly different (OR 1.369 (0.819-2.288). There was no difference in the incidence of DGF when comparing NS vs PA.

(195) Comparison of CAV Development in Simultaneous Multi-Organ and Isolated Heart Transplant Recipients in the United States

(195) Comparison of CAV Development in Simultaneous Multi-Organ and Isolated Heart Transplant Recipients in the United States

Donation after circulatory death heart procurement strategy impacts utilization and outcomes of concurrently procured abdominal organs

The impact of donation after circulatory death (DCD) heart procurement techniques on the utilization and outcomes of concurrently procured DCD livers and kidneys remains unclear. Using the United Network for Organ Sharing database, we identified 246 DCD donors whose heart was procured using direct procurement and ex-situ machine perfusion and 128 DCD donors whose heart was procured using in-situ thoracoabdominal normothermic regional perfusion (12/2019-03/2022). We evaluated the transplantation rate of concurrently procured DCD livers and kidneys (defined as the number of organs transplanted/total number of organs available for procurement) and their post-transplant outcomes. The transplantation rate of concurrently procured DCD livers was higher with in-situ perfusion compared to direct procurement (67.1% vs 56.5%, p=0.045). After excluding pediatric, multiorgan, and repeat transplant recipients, there was no difference in 6-month liver graft failure rate (direct procurement 0.9% vs in-situ perfusion 0%, p > 0.99). Recipients of kidneys procured with in-situ perfusion had less delayed graft function (11.3% vs 41.5%, p < 0.0001) shorter length of stay, and lower serum creatinine at discharge (both p < 0.05). Six-month recipient survival in the direct procurement and in-situ perfusion group were similar after DCD liver and kidney transplantation (p=0.24 and 0.79 respectively). Compared to direct procurement, DCD heart procurement with in-situ thoracoabdominal normothermic regional perfusion was associated with increased utilization of DCD livers and a lower incidence of delayed graft function in concurrently procured DCD kidneys. Broader implementation of DCD heart transplantation must maximize the transplant potential of concurrently procured abdominal organs and ensure their successful outcomes.

The teammate trial: Study design and rationale tacrolimus and everolimus against tacrolimus and MMF in pediatric heart transplantation using the major adverse transplant event (MATE) score

Currently there are no immunosuppression regimens FDA-approved to prevent rejection in pediatric heart transplantation (HT). In recent years, everolimus (EVL) has emerged as a potential alternative to standard tacrolimus (TAC) as the primary immunosuppressant to prevent rejection that may also reduce the risk of cardiac allograft vasculopathy (CAV), chronic kidney disease (CKD) and cytomegalovirus (CMV) infection. However, the two regimens have never been compared head-to-head in a randomized trial. The study design and rationale are reviewed in light of the challenges inherent in rare disease research. The TEAMMATE trial (NCT03386539, IND 127980) is the first multicenter randomized clinical trial (RCT) in pediatric HT. The primary purpose is to evaluate the safety and efficacy of EVL and low-dose TAC (LD-TAC) compared to standard-dose TAC and mycophenolate mofetil (MMF). Children aged <21 years at HT were randomized (1:1 ratio) at six months post-HT to either regimen, and followed for 30 months. Children with recurrent rejection, multi-organ transplant recipients, and those with an estimated glomerular filtration rate (eGFR) <30 ml/min/1.73m2 were excluded. The primary efficacy hypothesis is that, compared to TAC/MMF, EVL/LD-TAC is more effective in preventing 3 MATEs: acute cellular rejection (ACR), CKD and CAV. The primary safety hypothesis is that EVL/LD-TAC does not have a higher cumulative burden of 6 MATEs (antibody mediated rejection [AMR], infection, and post-transplant lymphoproliferative disorder [PTLD] in addition to the 3 above). The primary endpoint is the MATE score, a composite, ordinal surrogate endpoint reflecting the frequency and severity of MATEs that is validated against graft loss. The study had a target sample size of 210 patients across 25 sites and is powered to demonstrate superior efficacy of EVL/LD-TAC. Trial enrollment is complete and participant follow-up will be completed in 2023. The TEAMMATE trial is the first multicenter RCT in pediatric HT. It is anticipated that the study will provide important information about the safety and efficacy of everolimus- vs tacrolimus-based regimens and will provide valuable lessons into the design and conduct of future trials in pediatric HT.

Isolated Hepatic Chronic Ductopenic Rejection Requiring Liver Retransplant in the Absence of Kidney Graft Rejection After Combined Liver-Kidney Transplant: A Case Report

The liver is considered the most immunotolerant organ among all solid-organ transplants. Liver transplant recipients have a lower incidence of rejection and better outcomes after episodes of rejection, with spontaneous operational tolerance developing in up to 20%. In multiorgan transplants, a protective effect of the liver allograft on simultaneously transplanted organs from the same donor has been demonstrated. We describe an unusual case of isolated liver allograft rejection in a patient with polycystic liver and kidney disease who received a combined liver-kidney transplant from the same donor. After initial discharge from the hospital, our patient had 2 episodes of biopsy-proven late acute cellular rejections, despite higher levels of immunosuppression required for her kidney allograft, which were addressed with pulsed steroid therapy. She had no evidence of ischemic cholangiopathy on imaging. Later, a subsequent liver biopsy demonstrated features consistent with chronic ductopenic rejection. She was eventually listed for liver retransplant and has recently received a second liver transplant while continuing to have no concerns with her kidney allograft function. Examination of the explanted liver confirmed graft loss from chronic ductopenic rejection. The exact reasons why our patient developed acute graft rejection progressing to chronic end-stage rejection of the liver allograft despite not developing graft rejection in the kidney allograft from the same donor remains elusive. Our experience demonstrates that graft tolerance in multiorgan transplant recipients can be organ specific and despite the belief of "immunologic privilege," isolated liver allograft rejection can occur in multiorgan transplant, resulting in graft loss.

Single Center Experience with Incidence, Impact and Predictors of Biliary Complications in Donation After Circulatory Death Liver Transplantation.

Introduction: Utilizing allografts from donors after cardiac death (DCD) has improved organ availability, and DCD livers comprise a growing proportion of transplantations. However, it has been suggested that DCD transplantations have worse outcomes. Research Questions: We aimed to characterize outcomes in a large cohort of DCD transplantations, identify trends in outcomes over time, and identify factors associated with the development of biliary complications. Design: We conducted an observational retrospective cohort study of patients receiving DCD liver allografts within a large academic teaching hospital with a high transplantation volume. Consecutive patients who underwent Type III DCD liver transplantation from 2006-2016 were included in our cohort. Re-transplantations and multi-organ transplant recipients were excluded. Results: Ninety-six type III DCD transplantations occurred between 2006-2016. We report a 1one-year patient survival of 90.6% (87) and a 5five-year patient survival of 69.8% (67). Twenty-nine (30.2%) patients experienced any biliary complication in the first year following discharge, with 17 (17.7%) experiencing ischemic cholangiopathy. Five-year patient (P = 0.04) and graft (P = 0.005) survival improved over time. Post-operative biliary complications experienced during index admission and prior to discharge were found to be associated with the development of biliary complications (P = 0.005) and ischemic cholangiopathy (P = 0.01) following discharge. Conclusion: Our data suggested that outcomes using DCD allografts have improved, however biliary complications remain a significant issue in DCD transplantation. Patients who experienced post-operative biliary complications during index admission may require more frequent screening to allow the initiation of earlier treatment for biliary complications.

Incidence of Post-Transplant Lymphoproliferative Disease: A Systematic Literature Review

Introduction: Post-transplant lymphoproliferative disease (PTLD) is an ultra-rare lymphoma following allogeneic hematopoietic stem cell transplant (HCT) or solid organ transplant (SOT). Incidence of PTLD varies over time after transplant with majority of cases occurring within the first year (yr) after HCT (Garcia-Cadenas, Eur J Haematol. 2019). In the SOT setting, PTLD can occur up to 30 yrs post-transplant and is largely dependent on the transplanted organ, the type and degree of immunosuppression, and transplant recipient characteristics (Dierickx, N Eng J Med. 2018; Trappe, J Clin Oncol. 2017). Published literature reports wide ranges of epidemiological estimates due to variation in the follow-up time, transplant type and sample size. We conducted a systematic literature review (SLR) to summarize the incidence of PTLD to better understand the reasons for such variation.Methods: A SLR on the burden of PTLD was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines with the scope defined in terms of Population, Intervention Comparators, Outcomes and Study design (PICOS) criteria. Pertinent literature on epidemiology of PTLD published between January 2010 to February 2020 and relevant conference abstracts published between January 2018 to February 2020 were identified. Comprehensive literature searches were performed using the Ovid platform to identify articles indexed in PubMed, Embase, PsycINFO, and the National Health Service Economic Evaluation Database. Study designs were limited to population/registry-based studies, observational cohort studies (prospective/retrospective), and cross-sectional studies. Studies reporting incidence of PTLD were limited to those with at least 1000 total transplant recipients. All titles and abstracts were reviewed by two independent researchers with any discrepancies resolved by a third researcher. Incidence estimates were calculated by data extractors when it was not directly reported in the literature.Results: A total of 177 studies reporting epidemiological data on PTLD were identified using pre-specified SLR criteria. Most of the studies (n=150) were retrospective in design. Incidence was reported in 114 studies. Majority of the studies reported cumulative incidence (CI) over specified times such as 5-yr or 10-yr incidence or proportion of patients (pts) with PTLD out of a sample of transplanted pts. In the HCT setting, only CI was reported; twelve studies reported CI ranging from 0.1% among 15094 pts receiving autologous HCT over a 19-yr period to 4% in a cohort of 1021 pts receiving allogeneic HCT over a 16-yr period. A total of 100 studies reported incidence of PTLD in SOT pts which was highly influenced by the study population, EBV status at the time of transplant and follow-up time. Of these, 12 reported incidence rates ranging from 24 EBV negative PTLD cases per 100,000 person-years (PY) within 1-5 yrs post-transplant to 3460 PTLD cases per 100,000 PY at 20 yrs post-transplant. Eighty studies reported CI, 19 of which reported CI for various timepoints. In a group of 23171 heart transplant pts CI was 1% during a median follow-up of 4.3 yrs, while in a subgroup of four pediatric multi-organ transplant recipients followed from 2003 to 2011 CI was 25%. Across studies, CI at 1-yr post-transplant ranged from 0.1% to 4.9% and 5-yr CI ranged from 0.7% to 12.1% in select group of transplant pts. Twenty-four studies reported CI by transplant organ type ranging from 0.2% in kidney transplant pts within the first year to 12.1% in lung transplant pts over 7.5 yrs, with higher estimates reported in studies with smaller sample sizes.Conclusions: Our SLR shows large variation in the reported incidence of PTLD due to heterogeneity in the methodology and the study populations in both HCT and SOT settings. Published literature lacks the granularity to correctly interpret the incidence of PTLD in the general transplant population. Thus, additional methods and data considerations such as population type (HCT/SOT transplants, adult/pediatric pts, etc.), representativeness (single institutional data/multi-center/country level registry), unit of measurement of risk (CI/incidence rate, etc.), type of study (retrospective/prospective), length of follow-up, sample size, trends in transplant and treatment landscape over time are needed to ensure accuracy in the estimation of incidence of PTLD. DisclosuresThirumalai: Atara Biotherapeutics: Current Employment. Watson: Atara Biotherapeutics: Current Employment, Current holder of individual stocks in a privately-held company. Xun: Atara Biotherapeutics: Current Employment. Sadetsky: Atara Biotherapeutics: Current Employment. Schaible: Evidera: Current Employment. Barlev: Atara Biotherapeutics: Current Employment.

Effect of Lymphocyte Depletion in Post Heart Transplant Outcomes of Children with Protein Losing Enteropathy

<h3>Purpose</h3> Children with Fontan-related protein-losing enteropathy (PLE) demonstrate immunodeficiency due to lymphatic-intestinal losses of immunoglobulins and lymphocytes. Use of lymphocyte depleting agents such as rabbit antithymocyte globulin (RATG) at time of orthotopic heart transplant (OHT) may result in excessive immunosuppression and post-transplant complications. Our aim was to compare post-transplant outcomes such as rejection, infections, and malignancies between PLE patients who received RATG for induction opposed to a RATG-sparing protocol. <h3>Methods</h3> Retrospective, single center study of pediatric OHT recipients with PLE transplanted from 1/2014 to 12/2019. Multi-organ transplant and heart re-transplant recipients were excluded. Data collected included: demographic variables, immunosuppression type and levels, immune cell function assays, CD3 levels, CMV and EBV viremia, clinical rejection/biopsy results, and diagnoses of malignancy. Minimum follow-up time included 6 months from time of OHT. <h3>Results</h3> Twelve patients were identified of whom 6 received RATG with a median dose of 7.4 (4.4-7.6) mg/kg total. Median age at the time of OHT was 12.5 (11.5-16.5) years. One RATG patient had clinical rejection requiring ECMO support. Otherwise, all biopsies were grade 0 except for one 2R/3A and one 1R/1A in the RATG group and two 1R/1A in the non-RATG group. One patient in each group experienced AMR warranting intervention. Infections were more frequent in the RATG group with 2 patients with low-grade CMV viremia despite adequate prophylaxis and 3 RATG patients with EBV viremia compared to 1 EBV viremia in non-RATG group. Two diagnoses of PTLD occurred during the follow-up period, both of whom were in the RATG group. Trends of immune cell function assays and CD3 counts for the two groups are shown in Fig. 1. <h3>Conclusion</h3> Based on this pilot study, induction with RATG in PLE pediatric OHT patients may predispose them to higher frequency of post-transplant complications.

Dual Procurement of Lung and Heart Allografts Does Not Negatively Affect Lung Transplant Outcomes

BackgroundThe data that exists regarding multiorgan procurement outcomes is conflicted. Given the increasing demand for pulmonary allografts, it is critical to assess the impact of dual procurement on lung transplant recipient outcomes. MethodsThe United Network for Organ Sharing transplant registry was queried for all first-time adult (age ≥18) lung transplant recipients between 2006 and 2018 and stratified by concurrent heart donor status. Multiorgan transplant recipients and recipients with missing survival time were excluded. Donors were excluded if they were donating after circulatory death, did not consent or were not approached for heart donation, the heart was recovered for nontransplant purposes, or the heart was recovered for transplant but not transplanted. Post-transplant survival was analyzed using the Kaplan–Meier method and multivariable Cox proportional hazards regression. ResultsA total of 18,641 recipients met inclusion criteria, including 6230 (33.4%) in the nonheart donor group (NHD) and 12,409 (66.6%) in the heart donor group (HD). HD recipients demonstrated longer survival at 10 years posttransplant, with a median survival of 6.5 years as compared with 5.9 years in NHD recipients. On adjusted analysis, HD and NHD recipients demonstrated comparable survival (AHR 0.95, 95% CI 0.90-1.01). ConclusionsConcomitant heart and lung procurement was not associated with worse survival. This finding encourages maximizing the number of organs procured from each donor, particularly in the setting of urgency-driven thoracic transplantation.

The impact of multi-organ transplant allocation priority on waitlisted kidney transplant candidates.

Kidney-alone transplant (KAT) candidates may be disadvantaged by the allocation priority given to multi-organ transplant (MOT) candidates. This study identified potential KAT candidates not receiving a given kidney offer due to its allocation for MOT. Using the Organ Procurement and Transplant Network (OPTN) database, we identified deceased donors from 2002 to 2017 who had one kidney allocated for MOT and the other kidney allocated for KAT or simultaneous pancreas-kidney transplant (SPK) (n=7,378). Potential transplant recipient data were used to identify the "next-sequential KAT candidate" who would have received a given kidney offer had it not been allocated to a higher prioritized MOT candidate. In this analysis, next-sequential KAT candidates were younger (p<.001), more likely to be racial/ethnic minorities (p<.001), and more highly sensitized than MOT recipients (p<.001). A total of 2,113 (28.6%) next-sequential KAT candidates subsequently either died or were removed from the waiting list without receiving a transplant. In a multivariable model, despite adjacent position on the kidney match-run, mortality risk was significantly higher for next-sequential KAT candidates compared to KAT/SPK recipients (hazard ratio 1.55, 95% confidence interval 1.44, 1.66). These results highlight implications of MOT allocation prioritization, and potential consequences to KAT candidates prioritized below MOT candidates.

PULSATILE PERFUSION IN PEDIATRIC KIDNEY TRANSPLANTATION

Introduction: Pulsatile perfusion of deceased donor kidneys is commonly practiced in adult kidney transplantation. We examined the practice of pulsatile perfusion in pediatric patients undergoing kidney transplantation and compared outcomes from preservation using pulsatile perfusion (PUMP) and static cold storage (COLD) in pediatric recipients. Methods: The UNOS database was used to determine outcomes in all pediatric kidney recipients (<18 years) who were transplanted between 1994—2018. Living donor and multi-organ transplant recipients were excluded. Patients were divided according to preservation method into PUMP or COLD groups. Donor and recipient demographic data were examined, as were survival and outcomes. A p-value of <0.05 was considered to be significant. Results: There were 10,045 pediatric kidney transplants performed during the study period, of which 1,619 were PUMP (16.1%) and 8,426 were COLD (83.9%). PUMP donors were significantly younger (22.7 vs. 23.8 years), had a higher KDPI (22.4% vs. 19.7%), longer cold storage time (18.8 vs. 14.1 hours), more frequent donation after cardiac death (DCD) donor status (12.9% vs. 1.3%), and more likely to be an increased risk of disease (IRD) transmission donor (9.1% vs. 4.8%). PUMP kidneys were also more likely to have been biopsied (18.1% vs. 3.3%). There were no differences in donor creatinine (0.99 vs. 0.96 mg/dL). Recipients of PUMP kidneys were significantly older (12.0 vs. 11.6 years), had a shorter wait time (287.7 vs. 320.2 days), and greater HLA mismatch (4.5 vs. 4.3). There were no differences in BMI, initial or final cPRA, length of stay, or serum creatinine at the time of discharge (1.42 vs. 1.42 mg/dL). No differences in allograft survival at 10 years were noted between PUMP and COLD groups (Figure 1). Additionally, delayed graft function (DGF) occurrence (8.5% vs. 12.5%, p<0.05) and rejection rate in the initial 12 months post transplant (11.5% vs. 13.8%) were significantly lower in the PUMP group compared with the COLD group.Conclusions: Despite multiple unfavorable characteristics noted in PUMP donors, recipients of these kidneys have no difference in allograft survival and have a lower DGF rate. These data support the utilization of pulsatile perfusion during the evaluation of higher risk pediatric kidney donors and a possible role in improving outcomes for pediatric kidney transplantation.

Faster Time-to-Therapeutic Tacrolimus Level is Associated with Lower Risk of Cellular Rejection Early after Heart Transplantation

Faster time-to-therapeutic tacrolimus (TTT) levels is associated with lower rates of acute cellular rejection (ACR) in kidney and liver transplantation. Limited data have evaluated this relationship in heart transplant (HT) recipients. Single-center retrospective chart review of patients who received HT from January 1, 2014 to June 30, 2016. Multi-organ transplant recipients, re-transplants, and those who received induction therapy with either basiliximab or thymoglobulin were excluded. A therapeutic tacrolimus concentration was defined as a trough level between 8-15 ng/mL for two consecutive days. The primary outcome was the rates of 30-day ACR in patients who were < and ≥ the median TTT level. Serum creatinine values were also collected for the first 10 post-op days. From a database of 88 HT patients we evaluated 55 patients who did not receive induction therapy (median age=56 (49-65), 73% white, 71% had a VAD prior to HT). The median TTT level was 9 days; patients < the median (n=25) had similar characteristics as those ≥ the median (n=30). Rates of ACR were significantly lower in the < median group (8 v. 43%, p=0.005) (Figure), while serum creatinine values were similar between groups (p>0.05 for each day). Patients without ACR (n=40) had a median TTT level of 8 (6-9.5) days, compared to 10 (9-12) days in the ACR group (n=15) (p=0.01). A multivariate regression model found TTT ≥9 days to be significantly associated with early ACR after adjusting for age, gender, and VAD pre-HT (OR 9.84, 95% CI [1.86-52.90], p=0.007). Quickly achieving a TTT level reduces the risk of ACR early after HT without adversely affecting renal function.

Induction Therapy after Heart Transplantation

The use of induction therapy for orthotopic heart transplant (OHT) recipients is inconsistent between centers and there are limited data that explore the association with post-transplant outcomes. We used the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Transplant Registry to investigate induction therapy use after OHT and its relationship to 1-year survival. This is a retrospective cohort study from the global ISHLT Registry of adult patients who received a first OHT between 1/2005 and 6/2017. We excluded multi-organ transplant recipients, and those with missing induction data or no post-transplant follow up. We describe recipient and donor characteristics, stratified by induction therapy use. We used Kaplan-Meier methods to estimate 1-year mortality for induction therapy use and non-use, with comparison by the log-rank test. Of 27,400 OHT recipients included in this analysis, 13,711 (50%) received induction therapy at the time of transplant. The use of induction therapy remained stable over the study period. Both groups had median age of 55 years and had nonischemic cardiomyopathy as the most frequent diagnosis. There was a higher rate of females in the induction group (25.5% vs 24.2%). Recipients who received induction therapy had higher rates of pre-transplant dialysis (2.5% vs 2.1%) and ventilator use (2.6% vs 1.1%) but not ventricular assist device use (35.5% vs 39.9%). Atgam/thymoglobulin and basiliximab were the most frequently used therapies (N=5139 [37.5%] and N=7691 [56.1%], respectively). There was no significant difference in 1-year unadjusted survival between those who received induction therapy and those who did not. (Figure) CONCLUSION: In a large international cohort, approximately half of OHT recipients received induction therapy after heart transplantation, with similar one-year survival compared to those who did not receive induction therapy. Further study is warranted to determine which recipients warrant consideration for induction therapy and the optimal agent.

SAT-315 Kidney Transplant Recipient Outcomes Using Older Living Donors With Hypertension

Although the data supporting long-term safety of nephrectomy in hypertensive donors has been reported, there is scarcity of long term data on the recipient outcomes of such donors. Furthermore the use of older (>60 year) hypertensive donors is even further rare and minimal data exists on the transplant recipient outcomes for these donors. Hence the purpose of our study was to study the demographics of older living donors and their recipient outcomes in the United States. The United States UNOS database was retrospectively reviewed for the purposes of our study for the period January 2000 through Decemeber 2016. We excluded pediatric and multi-organ transplant recipients and limited the time period to minimum one year follow up. Out of 111,483 Living Donors during the study period, we identified 5,695 (5.1%) Living Donor Transplants with a donor age => 60 years that met our criteria.Tabled 1Living Donor Demographics (age> 60)n=5,695Mean Age (yrs)63.4+/-3.2 (Range 60-84)Age 60-64 / >=65+ (%)30.0 / 70.0Race (C/AA/Others) %86/4.2/9.8Gender (M/F) %36.5 / 63.5Donor Blood Type O / A / B / AB %62.3 / 29.3 / 7.4 / 1.0Nephrectomy (Left vs Right) %85.4 / 14.6Donor with h/o HTN (%)9.3Donor Age 65+ and HTN (%)3.2Mean Donor BMI26.6+/-3.9Mean Donor Pre-Donation Creatinine (mg/dl)0.82+/-0.3 Open table in a new tab Tabled 1Recipient Characteristics and OutcomesOverall (n=5,695)Age 60+ HTN Living Donor (n=531)Age 60+ non-HTN Living Donor (n=5,164)Recipient Mean Age (yrs)56.5+/- 12.956.8+/-13.256.5+/-12.9Recipient Race (C/AA/Other) %81.6 / 6.2 / 12.283.6 / 4.3 / 1281.4 /6.4 / 12.2Recipient Gender (M / F)61.9 / 38.163.7 / 36.361.8 / 38.2Mean BMI27.5+/-5.327.7+/-5.427.5+/-5.3Median Waiting Time (days)213201213On Dialysis (%)62.161.862.1Re-Transplants (%)8.38.98.3Delayed Graft Function (%)4.84.74.8Acute Rejection Within 1 yr (%)9.08.99.0Death with Functioning Kidney Graft (%)16.09.616.6* Open table in a new tab There was no difference in all-cause unadjusted graft survival between recipients with Older HTN vs non-HTN donors (p=0.57), or death censored graft survival (p=0.79) or patient survival (p-0.52). Similarly there was no difference in graft survival between these two groups for race, gender, on dialysis, DGF, acute rejection. In the HTN Living Donor Group, there was no difference in graft survival between recipient races, genders, donor races and acute rejection. Graft Survival was inferior in all donors > 65 (p=0.0005), as well as HTN vs non-HTN donors (p=0.035) as compared to donors age 60-64 years.Tabled 1Age60+ HTN Living Donors (n=531)Age60+ Non-HTN Living Donors (n=5,164)Graft SurvivalAll Cause GS / DCGS (%)All Cause GS / DCGS 9%)1yr95 / 9895 / 983yr86 / 9588 / 955yr79 / 8978 / 9110yr61 / 8653 / 7915yr24 / 4530 / 60 Open table in a new tab Transplant Recipient outcomes from Older hypertensive living donors are favorable and comparable to those donors without HTN. Careful selection of such donors and matching to appropriate recipients should not be discouraged when such donors are available.

Donor-to-recipient weight ratio is a risk factor for hepatic artery thrombosis after whole-liver transplantation in children under 25kg.

Hepatic artery thrombosis (HAT) following pediatric liver transplantation increases morbidity and risk of graft failure. We performed a retrospective chart review of all patients who underwent deceased-donor liver transplantation from August 2002 to July 2016. Multi-organ transplant recipients were excluded. We examined the incidence of HAT at our institution and sought to identify associated donor or recipient risk factors. A total of 127 deceased-donor liver transplant patients with a median age of 1.7years (IQR 0.67-6.7) were identified. Of those, 14 developed HAT, all weighing under 25kg. Among 100 patients under 25kg, whole-liver graft recipients had an odds ratio of 3.98 (95% confidence interval [CI]: 1.03, 15.34; P=.045) for developing HAT compared with split-liver graft recipients. Within the whole-liver recipient group under 25kg, 11 patients developed HAT with a median donor-to-recipient ratio (DRWR) of 0.9 (IQR: 0.7-1.2) compared with a median DRWR of 1.4 (IQR: 1.1-1.9) for those who did not develop HAT. Multivariate analysis showed DRWR to be an independent risk factor for HAT in patients weighing under 25kg who received whole organ grafts, with an odds ratio of 3.89 (95% CI: 1.43, 10.54; P=.008) for each 0.5 unit decrease in DRWR. Our results suggest that in recipients under 25kg 1) split-liver grafts may have a lower rate of HAT and 2) selecting whole organ donors with a higher DRWR may decrease the incidence of HAT.