Faculty Bibliography

Liver transplant (LT) recipients experience a wide range of comorbidities, leading to frequent healthcare encounters. Until now, national registries, which have limited exposures and outcomes, and laborious small cohort studies have been the main data sources for LT research. Cosmos database offers electronic health record (EHR)-based insights into LT recipients at the national level with granular data. We evaluated if Cosmos data is representative of the entire US LT recipient population. Using Cosmos (N=20,235) and the national Scientific Registry of Transplant Recipients (SRTR) (N=51,281), we identified adult, first-time LT recipients between 7/2016-12/2022. We compared demographics, clinical data, and mortality across datasets, calculating Kaplan-Meier survival estimates and multi-variable Cox regressions. Recipient characteristics were highly comparable (e.g., female: Cosmos=36.5% vs. SRTR=36.4%, Black: 6.8% vs. 7.2%; BMI: 28.5 kg/m2 [24.8-32.9] vs. 28.2 [24.6-32.4]). Lab values were similar across cohorts, including MELD (24 [17-30] vs. 23 [16-30]). Transplant indications, donor characteristics, and 5-year survival (Cosmos 83.1% [82.3-83.8) vs. SRTR 80.9% [80.4-81.3]) were similar. The associations of clinical factors with survival were similar across both groups. Cosmos database demonstrated acceptable generalizability to the general US LT recipient population, which may advance LT research through a better understanding about LT recipients' experiences and outcomes.

BACKGROUND:Access to liver transplantation (LT) for pediatric registrants is complex and impacted by many factors. Assessing the state of pediatric LT requires understanding the balance between policy, the availability of livers, and the quantity of pediatric patients requiring LT. METHODS:Using Scientific Registry of Transplant Recipients data with Cox regression (to compare rates) and competing risk regression (to compare cumulative incidence), we evaluated pediatric patient characteristics, number of registrants transplanted, and waitlist mortality from (January 1, 2017-February 4, 2020) to (May 1, 2020-June 4, 2023) using the implementation of acuity circles to divide the eras. RESULTS:In 4314 pediatric LT registrants, transplantation rate increased in the post-policy era, compared with the pre-policy era (adjusted hazard ratio [HR], 1.05 1.12 1.20 ; P  < 0.001). When accounting for competing risks, the increase was attenuated and not statistically significant (adjusted subdistribution HR, 0.99 1.06 1.14 ; P  = 0.08); recipients were no more likely to die on the waitlist (adjusted subdistribution HR, 0.78 1.01 1.30 ; P  = 0.99). Importantly, the prevalent pediatric waitlist dropped from 396 (2017) to 225 (2023), the rate of deceased donor LT from pediatric donors increased (weighted HR, 1.20 1.31 1.42 ; P  < 0.001), and access to living donor LT increased, compared with the pre-policy era (weighted HR, 1.11 1.33 1.59 ; P  = 0.002). The transplant rate for pediatric patients did not decrease during the study period despite the introduction of acuity circles. During the study period, the prevalent waitlist shrank, access to LT from pediatric donors increased, and access to living donor LT increased. CONCLUSIONS:Comprehensive assessment following the policy change is necessary to ensure that pediatric candidates maintain priority. Changes in pediatric transplantation are modest and likely related to changes in the pool, rather than to the policy of acuity circles.

Since their early development in the 1980s, Simulated Allocation Models (SAMs) have helped policymakers forecast the impact of proposed allocation policy changes on patient outcomes before implementation. In the United States, models like the Kidney-Pancreas Simulated Allocation Model, Liver Simulated Allocation Model, and Thoracic Simulated Allocation Model have been instrumental in shaping organ allocation policies. Analogous models have emerged globally, including the ETKidney and Eurotransplant Liver Allocation System simulators for the Eurotransplant region, to address country and region-specific allocation challenges. This review categorizes and compares SAMs based on their core assumptions, data, and modeling approaches. We highlight challenges in model validation, the use of synthetic data, and model transparency. While simplifying assumptions are often necessary because of limited data, their influence on results should be clearly communicated to ensure policymakers can interpret model predictions accurately. Furthermore, model validation using both retrospective and prospective data is essential to assess performance under evolving policies. Greater transparency through open-source models, detailed reporting of assumptions, and validation efforts can enhance collaboration, reproducibility, and confidence in transplant research. By providing a global perspective on SAMs, this review aims to inform future research and policy development, promoting evidence-based policy development in organ transplantation.

INTRODUCTION/BACKGROUND:Following implementation of the U.S. Kidney Allocation System (KAS) in 2014, deceased donor kidneys with a kidney donor profile index (KDPI) < 35% are prioritized for allocation to pediatric candidates. Early post-KAS data suggested this prioritization may have led to more frequent delayed graft function compared to pre-KAS, when pediatric allocation priority was based on donor age < 35 years. We sought to understand the impact of this allocation change on longer-term pediatric kidney transplant outcomes. METHODS:We used SRTR data to identify all deceased donor kidney transplants with pediatric recipients during two eras: "Pre-KAS" (12/1/2009-11/30/2014) and "KAS" (12/1/2015-11/30/2020). We used Cox proportional hazards models to calculate the association between study era and all-cause graft failure (graft failure or death) after adjusting for recipient characteristics. RESULTS:, p = 0.001). Results were similar in sensitivity analyses limited to recipients < 10 years old and recipients alive with a functioning graft 90 days post-transplant. CONCLUSIONS:KDPI-based prioritization of kidneys for pediatric allocation was associated with a lower risk of graft failure compared to donor age-based prioritization. Further refining donor risk scores may enable additional improvements in graft survival.

The lung continuous distribution system was modified on September 27, 2023, with the goal of increasing transplant access for blood-type-O candidates after an error was discovered in the simulation used to support the development of the initial allocation policy. This retrospective observational study compares national waitlist outcomes (transplant rate, waitlist mortality) under continuous distribution before (3/10/23-9/26/23; premodification) and after (9/27/23-4/14/24; postmodification) the blood-type score modification. We fit adjusted Poisson regression models of the transplant rate and mortality rate. The transplant rate was lowest for type-O candidates in both eras, but significantly increased after the score modification, from a premodification adjusted rate ratio (95% CI) of 0.40 (0.36, 0.45) to postmodification 0.52 (0.45, 0.59), relative to premodification type-A candidates. The adjusted mortality incidence (95% CI) decreased in type-O candidates from 3.6% (3.0%, 4.3%) premodification to 3.2% (2.6%, 3.8%) postmodification. In an exploratory analysis, we estimated there would have been the same number of waitlist deaths (approximately 105) if the modified score had been adopted at the start of continuous distribution; however, transplants would have shifted towards type-O candidates (57.8 [95% CI: 35.1, 80.9] additional transplants) and deaths would have shifted away from type-O candidates (4.6 [95% CI: 2.7, 6.8] fewer deaths).

Human leukocyte antigen-level matching in US kidney allocation has been deemphasized due to its role in elevating racial disparities. Molecular matching based on eplets might improve risk stratification compared to antigen matching, but the magnitude of racial disparities in molecular matching is not known. To assign eplets unambiguously, we utilized a cohort of 5193 individuals with high-resolution allele-level human leukocyte antigen genotypes from the National Kidney Registry. Using repeated random sampling to simulate donor-recipient genotype pairings based on the ethnic composition of the historical US deceased-donor pool, we profiled the percentage of well-matched donors available for candidates by ethnicity. The prevalence of well-matched donors with 0-DR/DQ eplet mismatch was 3-fold less racially disparate for Black and Asian candidates and 2-fold less for Latino candidates compared to 0-ABDR antigen mismatches. Compared to 0-DR antigen mismatch, 0-DR eplet mismatch was 1.33-fold more racially disparate for Asian and 1.28-fold more for Latino, with similar disparity for Black candidates, whereas 0-DQ eplet mismatch reduced disparities, showing 1.26-fold less disparity for Black, 1.14-fold less for Latino, but 1.26-fold higher for Asian candidates. The prevalence of well-matched donors for candidates of different ethnicities varied according to which molecules were chosen to define a low-risk match.

Developing real-world evidence from electronic health records (EHR) is vital to advance kidney transplantation (KT). We assessed the feasibility of studying KT using the Epic Cosmos aggregated EHR dataset, which includes 274 million unique individuals cared for in 238 U.S. health systems, by comparing it with the Scientific Registry of Transplant Recipients (SRTR). We identified 69,418 KT recipients transplanted between January 2014 and December 2022 in Cosmos (39.4% of all US KT transplants during this period). Demographics and clinical characteristics of recipients captured in Cosmos were consistent with the overall SRTR cohort. Survival estimates were generally comparable, although there were some differences in long-term survival. At 7 years post-transplant, patient survival was 80.4% in Cosmos and 77.8% in SRTR. Multivariable Cox regression showed consistent associations between clinical factors and mortality in both cohorts, with minor discrepancies in the associations between death and both age and race. In summary, Cosmos provides a reliable platform for KT research, allowing EHR-level clinical granularity not available with either the transplant registry or healthcare claims. Consequently, Cosmos will enable novel analyses to improve our understanding of KT management on a national scale.