Transplant Registry Research Articles

Type of calcineurin inhibitor and long-term outcomes following liver transplantation in patients with primary biliary cholangitis – an ELTR study

BackgroundTacrolimus has been associated with recurrence of primary biliary cholangitis (PBC) after liver transplantation (LT), which in turn may reduce survival. This study aimed to assess the relation between the type of calcineurin inhibitor (CNI) and long-term outcomes following LT in patients with PBC. MethodsSurvival analyses were used to assess the association between immunosuppressive drugs and graft or patient survival among adult patients with PBC in the dataset of the European Liver Transplant Registry. Patients who received a donation after brain death (DBD) graft between 1990 and 2021 with at least one year of event-free follow-up were included. ResultsIn total, 3175 PBC patients were followed for a median duration of 11.4 years (IQR 5.9 – 17.9) after LT. Tacrolimus (Tac) was registered in 2056 (64.8%) patients and cyclosporin (CsA) in 819 (25.8%). Adjusted for recipient age, recipient sex, donor age, and year of LT, Tac was not associated with higher risk of graft loss (aHR 1.07, 95%CI 0.92-1.25, p=0.402) or death (aHR 1.06, 95%CI 0.90-1.24, p=0.473) over CsA. In this model maintenance mycophenolate was associated with a lower risk of graft loss (aHR 0.72, 95%CI 0.60-0.87, p<0.001) or death (aHR 0.72, 95%CI 0.59-0.87, p<0.001), while these risks were higher with use of steroids (aHR 1.31, 95%CI 1.13-1.52, p<0.001, and aHR 1.34, 95%CI 1.15-1.56, p<0.001, respectively). ConclusionsIn this large LT registry, type of CNI was not associated with long-term graft or recipient survival, reassuring us to continue the use of Tac post LT in the population with PBC. Patients using MMF had a lower risk of graft loss and death, indicating that threshold for combination treatment with Tac and MMF should be low. Impact And ImplicationsThis study investigated the association between immunosuppressive drugs and the long-term survival of patients with primary biliary cholangitis (PBC) following DBD liver transplantation (LT). While tacrolimus has been previously related to a higher risk of PBC recurrence, the type of calcineurin inhibitor was not related to graft or patient survival among patient transplanted for PBC in the European Liver Transplant Registry. Additionally, maintenance use of mycophenolate was linked to lower risks of graft loss and death, while these risks were higher with maintenance use of steroids. Our findings reassure physicians on the continued use of Tac after LT in the population with PBC, and suggest potential benefit from combination therapy with mycophenolate.

Impact of Asian and Black Donor and Recipient Ethnicity on the Outcomes After Deceased Donor Kidney Transplantation in the United Kingdom.

Patients of Asian and black ethnicity face disadvantage on the renal transplant waiting list in the UK, because of lack of human leucocyte antigen and blood group matched donors from an overwhelmingly white deceased donor pool. This study evaluates outcomes of renal allografts from Asian and black donors. The UK Transplant Registry was analysed for adult deceased donor kidney only transplants performed between 2001 and 2015. Asian and black ethnicity patients constituted 12.4% and 6.7% of all deceased donor recipients but only 1.6% and 1.2% of all deceased donors, respectively. Unadjusted survival analysis demonstrated significantly inferior long-term allograft outcomes associated with Asian and black donors, compared to white donors. On Cox-regression analysis, Asian donor and black recipient ethnicities were associated with poorer outcomes than white counterparts, and on ethnicity matching, compared with the white donor-white recipient baseline group and adjusting for other donor and recipient factors, 5-year graft outcomes were significantly poorer for black donor-black recipient, Asian donor-white recipient, and white donor-black recipient combinations in decreasing order of worse unadjusted 5-year graft survival. Increased deceased donation among ethnic minorities could benefit the recipient pool by increasing available organs. However, it may require a refined approach to enhance outcomes.

A prospective observational cohort study of covid-19 epidemiology and vaccine seroconversion in South Western Sydney, Australia, during the 2021–2022 pandemic period.

BackgroundIt is known that COVID-19 disproportionally adversely affects the immunocompromised, including kidney transplant recipients (KTR), as compared to the general population. Risk factors for adverse outcomes and vaccine seroconversion patterns are not fully understood. Australia was uniquely positioned to reduce initial case numbers during the 2021–2022 pandemic period due to its relative isolation and several significant public health interventions. South-Western Sydney Local Heath District was one of the predominant regions affected.MethodsA single centre, prospective cohort study of prevalent renal transplant recipients was conducted between 25th July 2021 and 1st May 2022. Baseline characteristics, COVID-19 vaccination status, COVID-19 diagnosis and outcomes were determined from the electronic medical record, Australian vaccination register and Australian and New Zealand Dialysis and Transplant Registry. Assessment of vaccine-induced seroconversion was assessed with ELISA in a subpopulation. Analysis was performed using SPSS v.28.ResultsWe identified 444 prevalent transplant recipients (60% male, 50% diabetic, median age 58 years (Interquartile range (IQR)21.0) and eGFR 56 ml/min/1.73m2 (IQR 21.9). COVID-19 was identified in 32% (n = 142) of patients, of which 38% (n = 54) required hospitalisation and 7% (n = 10) died. At least one COVID-19 vaccination was received by 95% (n = 423) with 17 (4%) patients remaining unvaccinated throughout the study period. Seroconversion after 2 and 3 doses of vaccine was 22% and 48% respectively. Increased COVID-19 related deaths were associated with older age (aOR 1.1, 95% CI 1.004–1.192, p = 0.040), smoking exposure (aOR 8.2, 05% CI 1.020-65.649, p = 0.048) and respiratory disease (aOR 14.2, 95%CI:1.825–110.930, p = 0.011) on multi-variable regression analysis. Receipt of three doses of vaccination was protective against acquiring COVID-19 (aOR 0.48, 95% CI 0.287–0.796, p = 0.005) and death (aOR 0.6, 95% CI: 0.007–0.523, p = 0.011), but not against hospitalisation (p = 0.32). Seroconversion was protective for acquiring COVID-19 on multi-variable regression independent of vaccination dose (aOR 0.1, 95%CI: 0.0025–0.523, p = 0.011).ConclusionsCOVID-19 was associated with a high mortality rate. Older age, respiratory disease and prior smoking exposure may be risk factors for increased mortality. Vaccination of 3 doses is protective against acquiring COVID-19 and death, however not hospitalisation. Antibody response is protective for acquiring COVID-19, however seroconversion rates are low.

Demand for Continuous and Long-Term Care in Transplant Recipients: Data From the Organ Transplantation Registry—Poltransplant Activity

This study aimed to determine the number of recipients with active transplants under the care of transplant centers in 2022 and the current volume and needs for continuous and long-term care in this group of transplant recipients. Data came from the organ transplant registry, one of the registries maintained by the Polish Transplant Coordinating Center Poltransplant. We included recipients of individual organs who, on January 1, 2022, were living with an active transplant performed in previous years and recipients who received a transplant in 2022. The number of recipients under the care of transplant centers in 2022 was 20,994 (55% of all transplants performed in Poland since the beginning of activity in 1966).

Greater haemodialysis exposure (‘quotidian haemodialysis’) has different mortality associations by patient age group

ABSTRACT Background Worldwide, most people requiring kidney replacement therapy receive haemodialysis (HD) three times per week. Greater HD time and/or frequency may improve survival, but implementation requires understanding potential benefits across the range of patients. Methods Using data from the Australia and New Zealand Dialysis and Transplant Registry, we assessed whether quotidian HD (defined as &amp;gt;3 sessions/week and/or &amp;gt;5 h/session) was associated with reduced mortality in adult patients. The primary outcome of all-cause mortality was analysed by a time-varying Cox proportional hazards model with quotidian HD as the exposure of interest. Results Of 24 138 people who received HD between 2011 and 2019, 2632 (10.9%) received quotidian HD at some stage. These patients were younger, more likely male and more likely to receive HD at home. Overall, quotidian versus standard HD was associated with a decreased risk for all-cause mortality {crude hazard ratio [HR] 0.50 [95% confidence interval (CI) 0.45–0.56]}, but an interaction between quotidian HD and age was identified (P = .005). Stratified by age groups and splitting follow-up time where proportional hazards were violated, the corresponding HR compared with standard HD was 2.43 (95% CI 1.56–3.79) for people &amp;gt;75 years of age in the first year of quotidian HD, 1.52 (95% CI 0.89–2.58) for 1–3 years and 0.95 (95% CI 0.51–1.78) for ≥3 years. There was no significant survival advantage in younger people. Conclusions Although quotidian HD conferred survival benefit in crude analyses, people ≥75 years of age had greater mortality with quotidian HD than standard HD. The mortality benefit in younger people was attenuated when adjusted for known confounders.

Home versus in-centre haemodialysis for people with kidney failure.

Home versus in-centre haemodialysis for people with kidney failure.

The Potential for Information Sharing Between an Electronic Medical Record System and the Moroccan Transplantation and Dialysis Registry: Examining Semantic Interoperability.

Background and aim In 2005, the Moroccan Ministry of Health established Magredial, a registry to track and monitor patients with end-stage renal disease (ESRD), with the aim of improving healthcare outcomes. After achieving initial success, Magredial's activity decreased, leading to its inactivity by 2015. Currently, efforts are underway to revive Magredial's use. The main goal of this study is to investigate the feasibility of data transfer between the electronic medical records (EMRs) of Hassan II Hospital of Fes, Morocco, and the registry by achieving semantic interoperability between the two systems Materials and methods The initial phase of this study involved a detailed review of existing literature, highlighting the importance of registries, especially in nephrology. This part of the study also aims to emphasize the role of semantic interoperability in facilitating the sharing of data between EMRs and registries. Following that, the study's second phase, which centered on the case study, conducted a detailed analysis of the data architectures in both Magredial and the EMR of the nephrology department to pinpoint areas of alignment and discrepancy. This step required cooperative efforts between the nephrology and IT departments of Hassan II Hospital. Results Our findings indicate a significant interoperability gap between the two systems, stemming from differences in their data architectures and semantic frameworks. Such discrepancies severely impede the effective exchange of information between the systems. To address this challenge, a comprehensive restructuring of the EMR is proposed. This strategy is designed to align disparate systems and ensure compliance with the interoperability standards the Health Level 7 Clinical Document Architecture (HL7-CDA) set forth. Implementing the proposed medical record approach is complex and time-consuming, necessitatinghealthcare professional commitment, and adherence to ethical standards for patient consent and data privacy. Conclusions Implementing this strategy is expected to facilitate the seamless automation of data transfer between the EMR and Magredial. It introduces a framework that could be a foundational model for establishing a robust interoperability framework within nephrology information systems in line with international standards. Ultimately, this initiative could lead to creating a nephrologist-shared health record across the country, enhancing patient care and data management within the specialty.

Abstract CT278: [DREAM] Double lung transplant registry aimed for lung-limited malignancies - a prospective registry study for medically refractory cancers

Abstract BackgroundAdenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) are listed as ‘special circumstances’ for lung transplantation according to a consensus document from the International Society for Heart and Lung Transplantation (ISHLT) (Weill D et al., 2015). Five studies have reported on lung transplantation in carefully selected subsets of patients with multifocal lung adenocarcinoma (Raemdonck DV et al., 2016; Glanville AR et al., 2018). The 5-year survival rate of bilateral sequential lung transplantation was estimated at over 50% in patients with multifocal BAC, invasive adenocarcinoma, and NSCLC (Ahmad U et al., 2012; Paloyan EB et al., 2000; Zorn GL et al., 2003; de Perrot M et al., 2004). Another a case series reported a post-transplant recurrence-free survival of 23 to 56 months in three patients (Garver RI et al., 1999). Moreover, there is an unmet need for patients who have lung-limited metastasis after successful treatment for primary tumors such as sarcomas or colorectal cancer (CRC). As with liver transplantation for CRC patients who have liver-confined metastases (Dueland S et at., 2020; Hernandez-Alejandro R et al., 2022), the applicability of lung transplantation in lung-limited metastatic patients should be explored. There is also an unmet need for patients with respiratory failure with a history of cancer in the last 5 years. MethodsThis is a prospective registration trial to evaluate outcomes of patients who undergo double lung transplantation for the treatment of the select groups of medically refractory cancers (primary lung cancers or metastatic cancers in lungs). Overall survival (OS), disease-free survival (DFS), allograft rejection (AR) and allograft survival (AS) as well as molecular and genetic biomarkers will be monitored to investigate the correlation with prognosis.The study duration will be 10 years including surveillance. Recruitment is to occur during the first 5 years of the study. The goal is to enroll 125 participants through the Northwestern Medicine Clinical Programs.Essential Criteria:1.The tumor should be without any extrapulmonary metastasis as determined by standard of care diagnostic and staging workup.2.All standard of care or experimental oncological treatments known to improve survival should have failed or deemed infeasible 3.Patients should meet the general criteria for lung transplant evaluation and listing Study cohorts:•Cohort A: Primary lung cancers - Examples include, but not limited to, invasive mucinous/non-mucinous non-small cell lung cancers and multifocal carcinomas.•Cohort B: Metastatic cancers to the lung only - Examples include, but not limited to, germ cell tumors, head &amp; neck tumors, colorectal tumors, renal cell tumors, testicular cancers.•Cohort C: Respiratory failure with a history of cancer in the last 5 years- Examples include, but not limited to interstitial lung disease (ILD), pulmonary fibrosis (idiopathic or secondary), advanced chronic obstructive pulmonary disease (COPD), bronchiectasis, emphysema, cystic fibrosis (CF), emphysema due to alpha-1 antitrypsin deficiency, and pulmonary arterial hypertension (PAH) Clinical trial registry number : NCT05671887.Enrollment began November 16, 2022. Trial is open and continues to enroll participants as of Jan 8, 2024. Citation Format: Young Kwang Chae, Liam Il-Young Chung, Rade Tomic, Ankit Bharat. [DREAM] Double lung transplant registry aimed for lung-limited malignancies - a prospective registry study for medically refractory cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT278.

Impact of Everolimus Initiation and Corticosteroid Weaning During Acute Phase After Heart Transplantation on Clinical Outcome: Data from the Korean Organ Transplant Registry (KOTRY).

The effect of changes in immunosuppressive therapy during the acute phase post-heart transplantation (HTx) on clinical outcomes remains unclear. This study aimed to investigate the effects of changes in immunosuppressive therapy by corticosteroid (CS) weaning and everolimus (EVR) initiation during the first year post-HTx on clinical outcomes. We analyzed 622 recipients registered in the Korean Organ Transplant Registry (KOTRY) between January 2014 and December 2021. The median age at HTx was 56years (interquartile range [IQR], 45-62), and the median follow-up time was 3.9years (IQR 2.0-5.1). The early EVR initiation within the first year post-HTx and maintenance during the follow-up is associated with reduced the risk of primary composite outcome (all-cause mortality or re-transplantation) (HR, 0.24; 95% CI 0.09-0.68; p < 0.001) and cardiac allograft vasculopathy (CAV) (HR, 0.39; 95% CI 0.19-0.79; p = 0.009) compared with EVR-free or EVR intermittent treatment regimen, regardless of CS weaning. However, the early EVR initiation tends to increase the risk of acute allograft rejection compared with EVR-free or EVR intermittent treatment.

Impact of preoperative infection on the outcomes of liver transplant recipients: a national propensity score-matched retrospective cohort study in China.

Impact of preoperative infection on liver transplantation (LT) needs further investigation. From January 1, 2015 to December 31, 2022, 24,122 eligible patients receiving LT were enrolled from the China Liver Transplant Registry database. The outcomes of LT were compared after using the propensity score-matched analysis. Compared to the non-infection group, patients in the infection group were more likely to have postoperative effusion, infection, abdominal bleeding and biliary complications (all P<0.01), and they had shorter 30-day, 90-day survival and overall survival (OS) (all P<0.01). Cox proportional hazards regression analysis revealed that MELD score and cold ischemia time were risk factors for the OS in the infection group (both P<0.05). Besides, compared to the non-pulmonary group, patients in the pulmonary group were more likely to have postoperative effusion and infection (both P<0.0001), and less likely to have postoperative abscess and early allograft dysfunction (both P<0.05). Patients in the non-abdominal group also had a higher proportion of postoperative infection than those in the abdominal group (P<0.05). Furthermore, compared to the number=1 group, patients in the number≥2 group were more prone to postoperative effusion and infection (both P<0.01), and they also had shorter 30-day and 90-day survival (both P<0.05). Preoperative infection can result in a higher incidence of early postoperative complications and shorter survival in liver transplant recipients. The types and number of infection sites will also influence the prognosis of liver transplant recipients.

(1064) - Predicting Survival After Heart Transplantation: Validation of DRI, RSS and OPTN Risk Scores in the UK Transplant Registry

(1064) - Predicting Survival After Heart Transplantation: Validation of DRI, RSS and OPTN Risk Scores in the UK Transplant Registry

Incomplete reporting of clinically significant acute rejection episodes in the national kidney transplant registry

Administrative claims data could provide a unique opportunity to identify acute rejection (AR) events using specific antirejection medications and to validate rejected data reported to the Organ Procurement and Transplantation Network. This retrospective cohort study examined differences in registry-reported events and those identified using claims data among adult kidney transplant recipients from 2012 to 2017 using Standard Analysis Files from the US Renal Data System. Rejection rates, survival estimates, and center-level differences were assessed using each approach. Among 45 880 first-time kidney transplant recipients, we identified 3841 AR events within 12 months of transplant reported by centers in the registry; claims data yielded 2945 events. Of all events occurring within 12 months of transplant, 48.5% were reported using registry only, 32.9% were identified using claims only, and 18.6% were identified using both approaches. A 3-year death-censored graft survival probability was 90.0%, 88.4%, and 81.2% (P < .001) for ARs identified using registry only, claims data only, and both approaches, respectively. The large discordance between registry-reported and claims-based events suggests incomplete and potentially inaccurate reporting of events in the Organ Procurement Transplant Network registry. These findings have important implications for analyses that use AR data and underscore the need for improved capture of clinically meaningful events.

Abstract 6495: Lenvatinib as a potential treatment option for invasive mucinous lung adenocarcinoma

Abstract Introduction: Invasive mucinous adenocarcinoma (IMA) accounts for approximately 4-20% of non-small-cell lung carcinoma (NSCLC). Genetic alterations and RNA sequencing analysis of IMAs reveal a unique mucinous signature similar to gastrointestinal mucinous tumors. Due to its rarity, focused clinical trials for IMA patients are often not feasible. These patients respond poorly to platinum-based conventional chemotherapy, or immunotherapy. Lenvatinib is a multitargeted-TKI with demonstrated activity in patients with RET fusion-positive lung adenocarcinoma, thyroid, hepatocellular and gastric carcinoma. Methods: Here, we present two RET fusion-negative mucinous lung adenocarcinoma cases that received a multitargeted TKI lenvatinib with a clinical and survival benefit. Results: Case #1: An 81-year-old female initially diagnosed with cT4N0M0 IMA (TTF1 and CDX2 focally positive) was started on neoadjuvant treatment for a 12cm tumor. She underwent right thoracotomy/right lower lobectomy/mediastinal lymph node dissection, and pathology confirmed ypT4N1M0 mucinous adenocarcinoma. Three months post-operatively, the patient had disease progression in the lungs. She had no targetable mutations. She had four subsequent lines of treatment including nivolumab/nab-paclitaxel as the fourth-line treatment. After six months of nivolumab/nab-paclitaxel, lenvatinib was added to the combination due to clear disease progression evident on imaging. After twelve cycles of nivolumab/nab-paclitaxel/lenvatinib combination treatment, patient achieved a partial response per RECIST 1.1 (-35.7% change from baseline to current). The patient reported less dyspnea and increased activity tolerance. Approximately nine months after the start of the treatment, patient showed progressive lung disease. The patient died after one more line treatment with 41 months of total overall survival. Case#2: A 56-year-old male initially diagnosed with stage IVA IMA (TTF1 negative). After four lines of treatments, patient was started on lenvatinib alone. The patient reported marked improvement in dyspnea and pain and increased activity tolerance with lenvatinib. Imaging confirmed treatment response after three months of treatment. The patient was subsequently enrolled in the double lung transplant (DLT) registry aimed for lung-limited malignancies (D.R.E.A.M.) registry study (NCT05671887), and he is alive with 25 months follow-up since DLT. Conclusion: We report two cases of metastatic RET fusion-negative mucinous lung adenocarcinoma, in which treatment with the multitargeted TKI Lenvatinib led to significant clinical improvement. Biological rationale to explain the effect of lenvatinib in invasive mucinous lung adenocarcinoma needs to be explored. Citation Format: Tarik Demir, Carolyn Moloney, Liam Il-Young Chung, Young Kwang Chae. Lenvatinib as a potential treatment option for invasive mucinous lung adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6495.

Creating synthetic populations in transplantation: A Bayesian approach enabling simulation without registry re-sampling.

Computer simulation has played a pivotal role in analyzing alternative organ allocation strategies in transplantation. The current approach to producing cohorts of organ donors and candidates for individual-level simulation requires directly re-sampling retrospective data from a transplant registry. This historical data may reflect outmoded policies and practices as well as systemic inequities in candidate listing, limiting contemporary applicability of simulation results. We describe the development of an alternative approach for generating synthetic donors and candidates using hierarchical Bayesian network probability models. We developed two Bayesian networks to model dependencies among 10 donor and 36 candidate characteristics relevant to waitlist survival, donor-candidate matching, and post-transplant survival. We estimated parameters for each model using Scientific Registry of Transplant Recipients (SRTR) data. For 100 donor and 100 candidate synthetic populations generated, proportions for each categorical donor or candidate attribute, respectively, fell within one percentage point of observed values; the interquartile ranges (IQRs) of each continuous variable contained the corresponding SRTR observed median. Comparisons of synthetic to observed stratified distributions demonstrated the ability of the method to capture complex joint variability among multiple characteristics. We also demonstrated how changing two upstream population parameters can exert cascading effects on multiple relevant clinical variables in a synthetic population. Generating synthetic donor and candidate populations in transplant simulation may help overcome critical limitations related to the re-sampling of historical data, allowing developers and decision makers to customize the parameters of these populations to reflect realistic or hypothetical future states.

People with genetic kidney diseases on kidney replacement therapy have different clinical outcomes compared to people with other kidney diseases

Despite increasing awareness of genetic kidney disease prevalence, there is limited population-level information about long term outcomes of people with genetic kidney disease receiving kidney replacement therapy. This analysis included people who commenced kidney replacement therapy between 1989 and 2020 as recorded in the Australian and New Zealand Dialysis and Transplant registry. Genetic kidney diseases were subclassified as majority and minority monogenic. Non-genetic kidney diseases were included as the comparator group. Primary outcome measures were 10-year mortality and 10-year graft failure. Cox proportional hazard regression were used to calculate unadjusted and adjusted hazard ratios (AHRs) for primary outcomes. There were 59,231 people in the dialysis subgroup and 21,860 people in the transplant subgroup. People on dialysis with genetic kidney diseases had reduced 10-year mortality risk (majority monogenic AHR: 0.70, 95% CI 0.66–0.76; minority monogenic AHR 0.86, 95% CI 0.80–0.92). This reduced 10-year mortality risk continued after kidney transplantation (majority monogenic AHR: 0.82, 95% CI 0.71–0.93; minority monogenic AHR 0.80, 95% CI 0.68–0.95). Majority monogenic genetic kidney diseases were associated with reduced 10-year graft failure compared to minority monogenic genetic kidney diseases and other kidney diseases (majority monogenic AHR 0.69, 95% CI 0.59–0.79). This binational registry analysis identified that people with genetic kidney disease have different mortality and graft failure risks compared to people with other kidney diseases.

Transplant benefit-based offering of deceased donor livers in the United Kingdom

The National Liver Offering Scheme (NLOS) was introduced in the UK in 2018 to offer livers from deceased donors to patients on the national waiting list based, for most patients, on calculated transplant benefit. Before NLOS, livers were offered to transplant centres by geographic donor zones and, within centres, by estimated recipient need for a transplant. UK Transplant Registry data on patient registrations and transplants were analysed to build statistical models for survival on the list (M1) and survival post-transplantation (M2). A separate cohort of registrations - not seen by the models before - was analysed to simulate what liver allocation would have been under M1, M2 and a transplant benefit score (TBS) model (combining both M1 and M2), and to compare these allocations to what had been recorded in the UK Transplant Registry. The number of deaths on the waiting list and patient life years were used to compare the different simulation scenarios and to select the optimal allocation model. Registry data were monitored, pre- and post-NLOS, to understand the performance of the scheme. The TBS was identified as the optimal model to offer donation after brain death (DBD) livers to adult and large paediatric elective recipients. In the first 2 years of NLOS, 68% of DBD livers were offered using the TBS to this type of recipient. Monitoring data indicate that mortality on the waiting list post-NLOS significantly decreased compared with pre-NLOS (p <0.0001), and that patient survival post-listing was significantly greater post- compared to pre-NLOS (p= 0.005). In the first two years of NLOS offering, waiting list mortality fell while post-transplant survival was not negatively impacted, delivering on the scheme's objectives. The National Liver Offering Scheme (NLOS) was introduced in the UK in 2018 to increase transparency of the deceased donor liver offering process, maximise the overall survival of the waiting list population, and improve equity of access to liver transplantation. To our knowledge, it is the first scheme that offers organs based on statistical prediction of transplant benefit: the transplant benefit score. The results are important to the transplant community - from healthcare practitioners to patients - and demonstrate that, in the first two years of NLOS offering, waiting list mortality fell while post-transplant survival was not negatively impacted, thus delivering on the scheme's objectives. The scheme continues to be monitored to ensure that the transplant benefit score remains up-to-date and that signals that suggest the possible disadvantage of some patients are investigated.

Cost-effectiveness of Accepting Kidneys From Deceased Donors With Common Cancers-A Modeling Study.

The disparity between the demand for and supply of kidney transplants has resulted in prolonged waiting times for patients with kidney failure. A potential approach to address this shortage is to consider kidneys from donors with a history of common cancers, such as breast, prostate, and colorectal cancers. We used a patient-level Markov model to evaluate the outcomes of accepting kidneys from deceased donors with a perceived history of breast, prostate, or colorectal cancer characterized by minimal to intermediate transmission risk. Data from the Australian transplant registry were used in this analysis. The study compared the costs and quality-adjusted life years (QALYs) from the perspective of the Australian healthcare system between the proposed practice of accepting these donors and the conservative practice of declining them. The model simulated outcomes for 1500 individuals waitlisted for a deceased donor kidney transplant for a 25-y horizon. Under the proposed practice, when an additional 15 donors with minimal to intermediate cancer transmission risk were accepted, QALY gains ranged from 7.32 to 20.12. This translates to an approximate increase of 7 to 20 additional years of perfect health. The shift in practice also led to substantial cost savings, ranging between $1.06 and $2.3 million. The proposed practice of accepting kidneys from deceased donors with a history of common cancers with minimal to intermediate transmission risk offers a promising solution to bridge the gap between demand and supply. This approach likely results in QALY gains for recipients and significant cost savings for the health system.

O169: The impact of time to death in donors after circulatory death on recipient outcome in simultaneous pancreas-kidney transplantation

Abstract Background Agonal times can vary between organ donors after circulatory death (DCD) following withdrawal of treatment, which leads to variable warm ischaemic damage to pancreas grafts. Currently there is little evidence supporting procurement team standdown times based on donor time to death (TTD). We examined what impact TTD had on pancreas graft outcomes following DCD transplantation. Methods Data were extracted from the UK transplant registry from 2014 to 2022. TTD was defined as withdrawal of life-sustaining treatment to donor asystole; asystolic time was the time from asystole to aortic perfusion. Predictors of graft loss were fitted into a Cox proportional hazards model. Adjusted restricted cubic spline (RCS) models were generated to further delineate the relationship between TTD and outcome. Statistical significance was set at P&amp;lt;0.05. Results 375 DCD simultaneous kidney-pancreas transplant recipients were included. Median TTD was 13-minutes (IQR 10 to 16-minutes), median asystolic time was 13-minutes (IQR 11 to 15-minutes). Increasing TTD was not associated with poorer graft survival (aHR 0.98, 95% CI 0.68-1.41, P=0.901). Increasing asystolic time was significantly associated with worse graft survival in the TTD model (aHR 2.51, 95%CI 1.16-5.43, P=0.020). RCS modelling confirmed there was no relationship between TTD and graft survival, however a non-linear relationship was demonstrated between asystolic time and graft survival. Conclusion We found no evidence that TTD impacts pancreas graft survival in DCD SPK transplantation, however increasing asystolic time was significant predictors of graft loss. Procurement teams should attempt to minimise asystolic time to reduce ischaemic injury to the pancreas graft.

O72: Machine perfusion in deceased-donor kidney transplantation: Cochrane review and meta-analysis

Abstract Background Several novel machine perfusion technologies have been developed which aim to improve kidney transplant outcomes compared with ice-box static cold storage (SCS). These machine perfusion technologies can be applied “continuous” from donor centre, or only at the recipient centre (“end-ischaemic”). We aimed to compare machine perfusion technologies with each other and with SCS. Methods We searched the Cochrane Kidney and Transplant Register of Studies to 20 June 2023. Two independent authors screened articles and extracted data. Pairwise random-effects meta-analysis was performed, with additional indirect comparisons performed. Main results 22 studies (4007 participants) were included. “Continuous” non-oxygenated hypothermic machine perfusion (HMP) versus SCS improves graft-survival (follow-up=1-10 years, HR=0.55, 95% confidence interval=0.40-0.77, P=0.0005, GRADE: high-certainty evidence), reduces delayed graft function (RR 0.78, 0.64-0.96, P=0.02; high-certainty evidence) and is cost-saving. Beneficial effects persist when cold ischaemic times were short, but were only seen when HMP was “continuous”; End-ischaemic oxygenated HMP (median 4.6hours) does not improve outcomes. Addition of oxygen to continuous HMP further improves graft-survival in DCD donors. End-ischaemic normothermic machine perfusion (NMP) does not improve outcomes versus SCS; indirect comparison revealed that continuous non-oxygenated HMP was associated with improved graft survival compared with end-ischaemic NMP (HR=0.31, 0.11-0.92, P=0.03). Conclusions Continuous HMP (initiated in donor hospital) is superior to SCS in deceased-donor kidney transplantation. Timing of HMP is important, and benefits have not been demonstrated with end-ischaemic HMP. Whilst end-ischaemic NMP is inferior to continuous HMP on indirect comparisons, further studies assessing NMP for viability assessment and therapeutic delivery are in progress.

Drug utilization in patients starting haemodialysis with a focus on cardiovascular and antidiabetic medications: an epidemiological study in the Lazio region (Italy), 2016–2020

BackgroundEntering dialysis is a critical moment in patients’ healthcare journey, and little is known about drug therapy around it. A study funded by the Italian Medicines Agency offered the opportunity to leverage data from the Lazio Regional Dialysis and Transplant Registry (RRDTL) and perform an observational study on drug use patterns before and after initiating chronic dialysis.MethodsIndividuals initiating dialysis in 2016–2020 were identified from RRDTL, excluding patients with prior renal transplantation, stopping dialysis early, or dying within 12 months. Use of study drugs, predefined by clinicians, in the two years around the index date was retrieved from the drug claims register and described by semester. For each drug group, proportions of users (min 2 claims in 6 months) by semester, and intensity of treatment in terms of Defined Daily Doses (DDDs) for cardiovascular and antidiabetic agents were compared across semesters, stratifying by sex and age.ResultsIn our cohort of 3,882 patients we observed a general increase in drug use after initiating dialysis, with the mean number rising from 5.5 to 6.2. Cardiovascular agents accounted for the highest proportions, along with proton pump inhibitors and antithrombotics over all semesters. Dialysis-specific therapies showed the most evident increase, in particular anti-anaemics (iron 4-fold, erythropoietins almost 2-fold), anti-parathyroids (6-fold), and chelating agents (4-fold). Use of cardiovascular and antidiabetic drugs was characterised by significant variations in terms of patterns and intensity, with some differences between sexes and age groups.ConclusionsEntering dialysis is associated with increased use of specific drugs and goes along with adaptations of chronic therapies.