Faculty Bibliography

Solid organ transplant recipients (SOTRs) have heightened risk of adverse COVID-19 outcomes due to immunosuppression and medical comorbidity. We quantified the burden of COVID-19 mortality in US SOTRs. A sample of deaths documented in the US solid organ transplant registry from June 2020 through December 2022 were linked to the National Death Index to identify COVID-19 deaths and weighted to represent all SOTR deaths during the study period. Among 505,757 SOTRs, 57,575 deaths occurred and based on the linkage, 12,396 (21.5%) were due to COVID-19. COVID-19 mortality was higher in males (mortality rate ratio [MRR]: 1.13), SOTRs aged 65 and older (MRR: 1.50 in ages 65-74 vs. ages 55-64), and non-Hispanic Black and Hispanic SOTRs (MRRs: 1.55 and 1.79 vs. non-Hispanic White SOTRs). Kidney and lung recipients had the highest COVID-19 mortality, followed by heart, then liver recipients. COVID-19 mortality also varied over time and across US states. Overall, SOTRs had 7-fold increased risk of COVID-19 death compared to the US general population. SOTRs comprised 0.13% of the US population but accounted for 1.46% of all US COVID-19 deaths. SOTRs experience greatly elevated COVID-19 mortality. Clinicians should continue to prioritize COVID-19 prevention and treatment in this high-risk population.

BACKGROUND/UNASSIGNED:Preoperative opioid use (OU) is a strong risk factor for poor postoperative outcomes in other surgical populations but has not been explored in lung transplant (LT) recipients nationally. METHODS/UNASSIGNED:The study identified adult (aged ≥18 years) US lung transplant (LT) recipients from 2011 to 2021 in the Scientific Registry of Transplant Recipients with prescription data through a pharmacy data set. Posttransplantation ventilatory support, infection, and mortality by pretransplantation OU (prescription fill ≤6 months before transplantation) were compared using multivariable regression. RESULTS/UNASSIGNED: = .006). CONCLUSIONS/UNASSIGNED:Pretransplantation OU was the strongest independent risk factor for posttransplantation OU and was associated with greater morbidity and mortality. Reducing pretransplantation and posttransplantation OU could benefit LT recipients and should be explored.

BACKGROUND:Despite excellent outcomes of heart transplants from hepatitis C virus (HCV)-positive donors (D+), many candidates are not listed to even consider HCV D+ offers. METHODS:Using the Scientific Registry of Transplant Recipients, we identified adult (age ≥18 years) heart transplant candidates prevalent on the waitlist between 2018 and March 2023. We compared the likelihood of waitlist mortality or heart transplant by candidate willingness to consider HCV D+ offers using competing risk regression. RESULTS:We identified 19,415 heart transplant candidates, 68.9% of whom were willing to consider HCV D+ offers. Candidates willing to consider HCV D+ offers had a 37% lower risk of waitlist mortality (subhazard ratio [SHR], 0.63; 95% confidence interval [CI], 0.56-0.70; P < .001) than candidates not willing to consider HCV D+ offers, after adjustment for covariates and center-level clustering. Over the same period, heart transplant candidates willing to consider HCV D+ offers had a 21% higher likelihood of receiving a transplant (SHR, 1.21; 95% CI, 1.7-1.26; P < .001). As a result, among candidates willing to consider HCV D+ offers, 74.9% received a transplant and 6.1% died/deteriorated after 3 years, compared to 68.3% and 9.1%, respectively, of candidates not willing to consider HCV D+ offers. Lower waitlist mortality also was observed on subgroup analyses of candidates on temporary and durable mechanical circulatory support. CONCLUSIONS:Willingness to consider HCV D+ heart offers was associated with a 37% lower risk of waitlist mortality and a 21% higher likelihood of receiving a transplant. We urge providers to encourage candidates to list as being willing to consider offers from donors with hepatitis C to optimize their waitlist outcomes and access to transplantation.

BACKGROUND:In the 2018 Organ Procurement and Transplantation Network donor heart allocation system, patients listed for re-transplantation due to cardiac allograft vasculopathy (CAV) are assigned to Status 4 unless hemodynamic criteria are met. We aim to examine waitlist outcomes of CAV patients among adult heart transplant candidates. METHODS:We examined waitlist mortality stratified by CAV and waitlist status among adult heart transplant candidates using Scientific Registry of Transplant Recipients data from 10/1/2018-11/1/2023. We analyzed waitlist mortality using Kaplan-Meier curves and doubly-robust Cox regressions adjusted for age, gender, sex, race, and dialysis. We compared CAV to non-CAV patients by initial waitlist status, first status of interest, and time-dependent status. RESULTS:Of 21,586 listed patients, 368 were listed for CAV. CAV patients were most often listed at Status 4 with lower proportions at Status 3/2/1 compared with non-CAV patients. Status 4 and Status 3 CAV candidates demonstrated higher than expected waitlist mortality compared to non-CAV counterparts (Status 4: HR 0.51, 95% CI 0.31-0.84; p < 0.01; Status 3: HR 0.61, 95% CI 0.23-1.64; p = 0.33) with similar mortality to non-CAV patients in Status 3 and 2, respectively (Status 4: HR 0.80, 95% CI 0.48-1.35; p = 0.4; Status 3: HR 1.07, 95% CI 0.40-2.86; p = 0.89). When stratifying by status tier, CAV waitlist patients ever listed at Status 4 and 3 had a higher probability of death compared to their non-CAV counterparts (Status 4: HR 1.99, 95% CI 1.20-3.31, p < 0.01; Status 3: HR 3.06, 95% CI 1.06-8.87, p = 0.04). CONCLUSIONS:After 2018, CAV patients had a higher risk of waitlist mortality at Status 4 and 3 compared to non-CAV patients. These results suggest that CAV patients are underprioritized in the current allocation system.

The proportion of deceased donor kidneys recovered for transplantation that are not transplanted reached 28% in 2023. Past research demonstrated that >90% of the non-use rate increase in the 2000s could be explained by the broadening donor pool. We used OPTN data to study kidneys recovered 2010-2023, applying causal inference methods to assess the degree to which the recent, sharp rise in the non-use rate could be explained by changes in donor clinical characteristics. Unadjusted odds of kidney non-use were 63% higher (95% CI: 56%, 70%) in 2023 vs 2018. After adjusting for donor factors, odds of non-use were only 12% (9%, 15%) higher in 2023. Both regression and propensity weighting demonstrated that 75-80% of the recent non-use rate increase can be explained by a rapidly expanding donor pool. Encouragingly, the non-use rate has not increased and remains low for above-average quality kidneys. However, the unexplained risk of non-use for kidneys in the highest kidney donor risk index quartile increased by ∼30%, potentially due to residual confounding and/or system-level, exogenous factors such as allocation policy changes. To improve placement efficiency, allocation policy should adapt to the increasingly heterogeneous donor pool by allocating kidneys differently along the donor quality spectrum.

Graft failure and recipient death with functioning graft are important competing outcomes after kidney transplantation. Risk prediction models typically censor for the competing outcome thereby overestimating the cumulative incidence. The magnitude of this overestimation is not well described in real-world transplant data. This retrospective cohort study analyzed data from the European Collaborative Transplant Study (n = 125 250) and from the American Scientific Registry of Transplant Recipients (n = 190 258). Separate cause-specific hazard models using donor and recipient age as continuous predictors were developed for graft failure and recipient death. The hazard of graft failure increased quadratically with increasing donor age and decreased decaying with increasing recipient age. The hazard of recipient death increased linearly with increasing donor and recipient age. The cumulative incidence overestimation due to competing risk-censoring was largest in high-risk populations for both outcomes (old donors/recipients), sometimes amounting to 8.4 and 18.8 percentage points for graft failure and recipient death, respectively. In our illustrative model for posttransplant risk prediction, the absolute risk of graft failure and death is overestimated when censoring for the competing event, mainly in older donors and recipients. Prediction models for absolute risks should treat graft failure and death as competing events.

BACKGROUND/UNASSIGNED:For patients with alpha-1 antitrypsin (AAT) deficiency, AAT augmentation therapy can be an important part of care. However, for those who require a lung transplant (LT), there is currently only limited information to guide the use of AAT augmentation therapy post-LT. METHODS/UNASSIGNED:We identified all LT recipients from 2011-2021 in the Scientific Registry of Transplant Recipients with an AAT deficiency diagnosis. We categorized recipients by use of AAT augmentation therapy post-LT and compared their baseline characteristics using Fisher's exact test and Wilcoxon rank-sum tests. We used Kaplan-Meier analyses and estimated the average treatment effect (ATE) of post-LT AAT augmentation therapy on mortality and all-cause graft failure (ACGF). The ATE measures the observed effect we would see if everyone in the population received the intervention as opposed to just a subset. RESULTS/UNASSIGNED: = 0.02, log-rank test). CONCLUSIONS/UNASSIGNED:In our study, the use of augmentation therapy post-LT was associated with improved survival. Confirmatory prospective studies should be considered to inform post-LT AAT therapy guidelines.

PURPOSE/OBJECTIVE:In October 2018, the OPTN changed adult heart transplant (HT) allocation policy, increasing the number of adult candidates that had higher priority than pediatric candidates, potentially disadvantaging pediatric waitlist registrants. METHODS:To understand the impact of this policy change, we used SRTR data to identify 1469 pre-policy (7/2016-9/2018) and 2901 (10/2018-12/2022) post-policy pediatric (< 18 years) HT registrants. We quantified mortality and transplant risks using weighted cause-specific hazard models, and then using weighted competing risks regression. We further stratified these analyses by age to understand risks for those in direct competition with adults for organs (≥ 12 years). RESULTS:, p = 0.02). Post policy, 1-year transplant rate did not change in those < 12years (68.2%-71.0%, p = 0.77), but in those ≥ 12years, transplant rate increased (77.3%-81.0%, p = 0.003). CONCLUSIONS:Mortality on the waitlist decreased and access to HT for pediatric registrants did not decline following the 2018 policy change. The decreased mortality rate may reflect changes in patient casemix and/or improved patient care. Continued surveillance is important in ensuring equity in pediatric, and adult, HT.

Since 2021, the Organ Procurement and Transplantation Network has reported a nearly 10-fold rise in out-of-sequence (OOS) kidney allocation, generating concern and halting development of continuous distribution policies. We report contemporary (2022-2023) practice patterns in OOS allocation using Organ Procurement and Transplantation Network data. We examined in sequence vs OOS donors with multivariable logistic regression and skipped vs OOS-accepting recipients with conditional logistic regression. Nearly 20% of kidney placements were OOS, varying from 0% to 43% acsoss organ procurement organizations; the 5 highest OOS-organ procurement organizations accounted for 29% of all OOS. Of OOS kidneys, 33% were declined ≥100 times in the standard allocation sequence and 51% were declined by ≥10 centers before OOS allocation began; 4.5% were made without any in-sequence declines. Nearly, all OOS offers were open offers. OOS kidneys were more likely to be from female, Black, older, donation after cardiac death, hypertensive, diabetic, and elevated creatinine donors. Candidates receiving OOS kidneys were more likely female, Asian, and older than skipped candidates. Higher-volume centers and centers with more White, fewer Hispanic, and more educated waiting list patients underwent transplantation disproportionately with more OOS kidneys. These findings suggest that the current, highly variable, discretionary use of OOS might exacerbate disparities, yet the impact of OOS on organ utilization cannot be determined with data now collected.

BACKGROUND:Highly effective modulator therapies (HEMT) including ivacaftor (IVA) and elexacaftor/tezacaftor/ivacaftor (ETI) have transformed treatment for people with cystic fibrosis (pwCF). However, non-HEMT-responsive mutations are more common in pwCF of non-White race/ethnicity; introduction of HEMT might have exacerbated racial/ethnic disparities in CF care. METHODS:Using the Scientific Registry of Transplant Recipients, we identified all lung transplant candidates and recipients 05/2005-12/2022 and categorized them by diagnosis (CF/non-CF), race/ethnicity (non-Hispanic White/Black/Hispanic) and era [Pre-HEMT (2005-1/30/2012), IVA (1/31/2012-10/30/2019), ETI (10/31/2019-12/31/2022)]. We compared the percentage of patients listed, delisted/died, or transplanted by race/ethnicity and era. RESULTS:34,659 lung transplants were performed: 10,521 pre-HEMT, 15,944 in IVA era, and 7,888 in ETI era. Over the three eras, the percentage of lung recipients with CF of White race decreased (94.5 % to 92.4 % to 78.4 %) and of Black race (1.7 % to 2.4 % to 5.7 %) or Hispanic ethnicity increased (3.5 % to 4.6 % to 14.2 %; p < 0.001). Similarly, among candidates listed for CF over the three eras, the percentage that were of White race decreased (82.0 % vs. 78.6 % vs. 71.0 %) and of Black race (9.2 % vs. 10.0 % vs. 10.3 %) or Hispanic ethnicity increased (6.4 % vs. 8.6 % vs. 13.6 %; p < 0.001). CONCLUSION/CONCLUSIONS:The introduction of HEMT appears to have benefitted CF lung transplant candidates and recipients of Black race or Hispanic ethnicity less than those of White race. This is likely due to the higher prevalence of HEMT-ineligible CFTR mutations among Black and Hispanic patients and underscores the need for therapies aimed at non-HEMT-responsive mutations prevalent in these racial/ethnic populations.