Faculty Bibliography

BACKGROUND:Kidney transplantation (KT) from donors with human immunodeficiency virus (HIV-1) to recipients with HIV (HIV D+/R+) is noninferior to KT from donors without HIV (HIV D-/R+) with regard to safety. However, there may be differences in posttransplant infections. METHODS:We performed a secondary analysis of the HOPE in Action KT Study (NCT02602262) comparing the time to first clinically relevant infection within 24 months posttransplantation in 99 HIV D+/R+ versus 99 HIV D-/R+. Secondary outcomes included incidence rates, infection-related death, and timing of clinically relevant infection, each stratified by donor HIV status. RESULTS:The cumulative incidence of a clinically relevant infection at 24 months posttransplantation was 73.8% (95% confidence interval [CI]: 63.1%-81.2%) for HIV D+/R+ versus 64.7% (95% CI: 53.0%-73.4%) for HIV D-/R+. Comparing time to first clinically relevant infection in HIV D+/R+ versus HIV D-/R+, the adjusted hazard ratio (aHR) was 1.44 (95% CI: 1.01-2.04) at 24 months posttransplantation; for infections associated with hospitalization, the aHR was not significantly higher (1.21 [95% CI: .78-1.86). There were no significant differences in the number of infections, death from infection, duration, or site of infection between HIV D+/R+ versus HIV D-/R+, though viral infections were numerically more common in HIV D+/R+ (40% vs 35%). CONCLUSIONS:Although there was a statistically significant association between receipt of a kidney from a donor with HIV and time to first clinically relevant infection in the 24 months posttransplantation, there were no differences in infections associated with hospitalization. These data are overall reassuring as this emerging practice expands into clinical care. Clinical Trials Registration. NCT02602262.

People with HIV have higher risk for rejection after kidney transplantation but the mechanism is poorly understood. As HIV latency promotes immune dysregulation and chronic inflammation, we evaluated whether the size of the HIV latent viral reservoir (LVR) at baseline and through 52-weeks is associated with rejection in kidney transplant recipients with HIV from donors with and without HIV. Using the intact proviral DNA assay, we found no differences in the LVR between those who experienced rejection (n=14) versus those who did not (N=55) regardless of donor HIV status. These data support the feasibility of HIV+ to HIV+ organ transplantation. Clinical Trials Registration. NCT03500315.

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.

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.

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.

BACKGROUND:Under the HOPE Act, transplants from donors with HIV to recipients with HIV (HIV D+/R+) have been largely limited to kidney and liver. However, recent modifications to HOPE research guidelines allow broader participation of cardiothoracic programs. METHODS:To quantify potential cardiothoracic HOPE donors, we used SRTR data (3/2016-12/2024) to identify 101,200 donors without HIV and 273 HOPE donors (with true and false positive HIV tests). Using logistic regression, we predicted the probability of having a heart or lung(s) used for transplant among donors without HIV that had a kidney or liver used. We then applied model parameters to HOPE donors that had a kidney or liver used to estimate the number of HOPE donors that might have been cardiothoracic donors if the practice were expanded. RESULTS:Among donors without HIV, cardiothoracic donation was associated with age, cause of death, hepatitis C, hypertension, diabetes, smoking, cardiovascular disease, blood gas, and circulatory death. Applying our model, an estimated 41.0% (N=111), 18.7% (N=51), and 15.2% (N=41) of HOPE donors were potential heart, any lung (single or double), or double-lung donors, as compared to 32.3%, 21.8%, and 18.2% of abdominal organ donors without HIV, respectively. This translated to an annual 13-18 potential heart and 5-8 potential lung transplants (of which 4-6 would be double-lung transplants) from HOPE donors. CONCLUSIONS:If HIV D+/R+ is more widely expanded to cardiothoracic transplantation, 41% of HOPE kidney and liver donors have potential to donate a heart and almost 20% to donate a lung to candidates with HIV.

Hypothermic machine perfusion (HMP) has surged in popularity for donor kidney preservation. Continuous-HMP (cHMP) has shown clear benefits over static cold storage (SCS), whereas randomized trials on short-duration end-ischemic-HMP (eiHMP) have not. We assessed whether HMP modulates injury from increasing cold-preservation-time and analyzed the impact of HMP on short- and long-term outcomes, using OPTN data (2010-2024) on single-kidney-transplant recipients (n=137,835). Multivariable non-linear (restricted cubic spline) regression with interaction terms were used. Median cold-preservation-time was long (17.3hrs,IQR:12.0-22.9), especially in the eiHMP cohort (median=23.0hrs,IQR:17.3-30.5). HMP was associated with significant reductions in DGF (cHMP:aOR=0.484,95%CI=0.467-0.501; eiHMP:aOR=0.459,95%CI=0.435-0.485; transport-only-HMP:aOR=0.535,95%CI=0.512-0.558) and LOS. Interaction analyses revealed HMP mitigated the negative effect of increasing cold-preservation-time compared with SCS. cHMP showed benefit across all cold-preservation-times, whereas eiHMP was beneficial only at longer cold-preservation-times. HMP was also associated with improved 5-year graft and patient survival. In conclusion, HMP reduces the negative impact of each additional hour of cold-preservation-time. Therefore, the treatment effect is not fixed and increases as cold-preservation-time increases, likely explaining the lack of benefit in trials of short-duration eiHMP. The association with improved 5-year graft survival and mortality provides IDEAL stage 4 evidence. This study addresses questions beyond the reach of randomized trials but of clear clinical relevance.