Faculty Bibliography

INTRODUCTION/BACKGROUND:Obesity prevalence has dramatically increased; candidates with obesity have higher waitlist mortality and are less likely to undergo liver transplantation. The association of obesity with post-transplant mortality is inconsistent. MATERIALS AND METHODS/METHODS:. Risks of waitlist and post-transplant mortality were quantified using adjusted competing risks and Cox proportional hazards. RESULTS:Of 103,640 candidates and 58,692 recipients, candidates with higher obesity classes had higher listing MELD that increased over time. Candidates with class III obesity were listed and transplanted at higher MELD compared to candidates without obesity, class I and II obesity; nearly 40% of candidates with class III obesity had listing MELD≥30. From 2013-2017 to 2018-2023, waitlist mortality decreased 35% in candidates with class III obesity (SHR:0.65(0.58-0.73),p<0.001) and post-transplant mortality decreased 20% for recipients with class III obesity (HR:0.80(0.66-0.96),p=0.02). However, over time, post-transplant mortality differed by obesity class with no reduction in post-transplant mortality for recipients with class I or II obesity. CONCLUSION/CONCLUSIONS:Candidates and recipients with class III obesity are being listed and transplanted at higher MELD scores with improvement in outcomes over time. Although higher risk, temporal trends for LT in this population are favorable. Given the higher disease severity at listing for candidates with class III obesity, referral patterns for LT evaluation in these patients should be evaluated.

BACKGROUND:To encourage high-quality, reduced-cost care for total joint arthroplasty (TJA), the Centers of Medicare & Medicaid Services mandated a pay-for-performance model, the Comprehensive Care for Joint Replacement (CJR), as part of the Patient Protection and Affordable Care Act (PPACA). The CJR incentivizes cost containment, and it was anticipated that its implementation would reduce access to TJA for high-cost populations. Patients with end-stage kidney disease (ESKD) undergoing kidney replacement therapy (dialysis and kidney transplant) are costly compared with healthier patients, but it was unknown whether this population lost access to hip and knee replacement because of CJR implementation. This population allows study of whether TJA is accessible for medically complex patients whose risk of surgical complications has been mitigated, as kidney transplantation improves outcomes compared with dialysis, allowing evaluation as to whether access improved when patients crossed over from dialysis to transplantation. Because all patients with ESKD are included in a mandated national registry, we can quantify whether access changed for patients who underwent dialysis and transplantation. QUESTIONS/PURPOSES/OBJECTIVE:(1) How did the rate of TJA change amid the shift to bundled payments for patients with ESKD receiving dialysis? (2) How did the rate of TJA change amid the shift to bundled payments for patients with ESKD after kidney transplant? METHODS:This was an observational cohort study from 2008 to 2018 using the United States Renal Data System, a mandatory national registry that allows for the opportunity to study all individuals with ESKD. During the study period, we identified 1,324,614 adults undergoing routine dialysis and 187,212 adult kidney transplant recipients; after exclusion for non-Medicare primary insurance (n = 785,224 for dialysis and 78,011 for transplant), patients who were 100 years or older (n = 79 and 0, respectively), those who resided outside of 50 US states and Puerto Rico (n = 781 and 87, respectively), missing dialysis status for the dialysis cohort (n = 8658), and multiorgan transplant recipients for the transplant cohort (n = 2442), our study population was 40% (529,872) of patients who underwent routine dialysis and 57% (106,672) of adult kidney transplant recipients, respectively. TJA was ascertained using Medicare Severity Diagnosis Related Groups and ICD-9 and ICD-10 codes. We divided the study period by PPACA (January 1, 2014, to March 31, 2016) and CJR (April 1, 2016, to December 31, 2018) implementation and compared the incidence of TJA by era using mixed-effects Poisson regression adjusting for calendar time and clinical and demographic variables. RESULTS:After adjustment for linear temporal trend and patient case mix, there was no evidence of association between policy implementation and the incidence of TJA. In the dialysis cohort, the adjusted incidence rate ratio (IRR) for TJA was 1.06 (95% confidence interval [CI] 0.98 to 1.14; p = 0.2) comparing PPACA with the previous period and 1.02 (95% CI 0.96 to 1.08; p = 0.6) comparing CJR with the previous periods. Similarly, in the transplant cohort, the adjusted IRR for TJA was 0.82 (95% CI 0.67 to 1.02; p = 0.07) comparing PPACA with the previous period and 1.10 (95% CI 0.94 to 1.28; p = 0.9) comparing CJR with the previous periods. CONCLUSION/CONCLUSIONS:There was no loss in access to TJA for medically complex patients receiving kidney replacement therapy. The increase in TJA incidence for patients after kidney transplant and decrease for patients receiving dialysis suggest that surgeons continued to provide care for higher risk patients whose risk of morbidity or mortality with total joint replacement has been maximally improved after transplantation. LEVEL OF EVIDENCE/METHODS:Level III, prognostic study.

BACKGROUND:Donor pool expansion is critical as lung candidates suffer high mortality, yet older donor lungs remain underutilized. We evaluated whether accepting an older donor (defined 4 ways: donor age 30-39, 40-49, 50-59, or 60-69 y) lung transplant was associated with a survival benefit over waiting for a younger donor offer. METHODS:Adult candidates who received a lung offer were identified using Scientific Registry of Transplant Recipients data, 2015-2022. Offers were categorized by donor age and candidate lung allocation score (LAS; <40, 40-55, >55). Postoffer mortality was compared between candidates for whom the offer was accepted ("acceptors") versus declined ("decliners") within each age-LAS category using weighted Cox regression. RESULTS:A total of 21 426 candidates received an offer from a donor age ≥30 y; 11 679 accepted. For LAS >55 candidates, a survival benefit was observed for acceptors of donors ages 30-39 y (weighted hazard ratio [wHR] of mortality: 0.450.520.59), 40-49 y (wHR: 0.610.700.79), and 50-59 y (wHR: 0.670.770.88); P < 0.001. For candidates with LAS 40-55, results suggest a survival benefit of accepting lung offers from donors age 30-39 y (wHR: 0.770.870.99) and 40-49 y (wHR: 0.760.870.99); P = 0.03. However, for candidates with LAS <40, a survival benefit was not observed for accepting any older donor transplant, with possible harm in accepting an age 50+ donor offer. CONCLUSIONS:Compared with declining and waiting for a younger donor offer, accepting an older donor lung transplant was associated with a survival advantage in candidates with high LAS in the precontinuous distribution era. Decision makers should consider these findings while recognizing potential changes in waiting time dynamics in the current era.

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.

BACKGROUND:Parents of pediatric heart transplant (HTx) recipients have a unique perspective on the challenges associated with the transition into adult care networks. We sought to assess parental perceptions of the challenges pediatric HTx recipients face daily and parental concerns around the transition from pediatric care networks. METHODS:A 15-item online survey was developed in partnership with parent-stakeholders and administered to parents of pediatric HTx recipients in September 2023. Closed and open-ended questions assessed (1) the patients' diagnosis, age at diagnosis, and age at transplant, (2) parents' daily concerns about their child's well-being, (3) parents' overall concerns about their child's well-being as they transition into adulthood, (4) parents' perceptions of their child's quality-of-life (QoL) and health, and (5) parents' demographic characteristics. RESULTS:Eighty-six parents completed the survey. On a scale of 1 (worst) to 10 (best), 75% of parents rated their child's overall QoL at 8 or higher and 76% rated their child's health-related QoL at 8 or higher. Parents' daily concerns about their child's well-being included infectious diseases, health behaviors and care management, transplant-related concerns, socialization and education, mental health, and care coordination. Concerns related to the transition into adulthood included health behaviors and self-management, life satisfaction, finances, family, transplant-related concerns, and care coordination. CONCLUSIONS:Although parents of pediatric HTx recipients reported mostly positive QoL outcomes, they have concerns related to care management, life satisfaction, and healthcare access as their children transition into adulthood. Comprehensive transition-specific interventions and guidelines are needed to support families during this high-risk period.

BACKGROUND/UNASSIGNED:With the introduction of sirolimus as medical therapy for lymphangioleiomyomatosis (LAM), an updated evaluation of LAM lung transplant (LT) outcomes and characterization of peritransplant sirolimus use is needed. METHODS/UNASSIGNED:We identified adult LT recipients from 2005-2021 using the Scientific Registry of Transplant Recipients database and stratified by diagnosis (LAM vs other). Multivariable Cox regression was performed to calculate the adjusted hazard ratio for LAM vs other diagnoses. A pharmacy claims database was linked to provide sirolimus prescription information, and a subgroup analysis comparing outcomes with pre- vs posttransplant sirolimus use was performed. RESULTS/UNASSIGNED: = .003). CONCLUSIONS/UNASSIGNED:This study supports lung transplant as a treatment for severe pulmonary LAM and identifies increased mortality associated with pre-LT sirolimus, though this may be due to uncharacterized baseline differences.

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:Given the cardiovascular, renal, and survival benefits of GLP-1 receptor agonists for diabetes, these agents could be effective among kidney transplant recipients. However, kidney transplant recipients are distinct from GLP-1 receptor agonist trial participants, with longer diabetes duration and severity, greater end-organ damage, increased cardiovascular risk, and multimorbidity. We examined GLP-1 receptor agonist real-world effectiveness and safety in kidney transplant recipients with diabetes. METHODS:This USA-based retrospective cohort study included kidney transplant recipients with type 2 diabetes at transplantation and Medicare as their primary insurance from a national registry linked with Medicare claims. Post-transplantation GLP-1 receptor agonist use was identified through Medicare claims. Death-censored graft loss was estimated using the Fine-Gray sub-distribution hazard model and extended Cox models were used for mortality and safety endpoints. Models incorporated inverse probability of treatment weights. To further test whether bias could affect the main results, a cohort was created in which each GLP-1 receptor agonist user was matched with a kidney transplant recipient who had not started a GLP-1 receptor agonist, was alive with a functioning graft, and had accrued the same amount of post-transplant survival time. FINDINGS/RESULTS:Between Jan 1, 2013 and Dec 31, 2020, we identified 44 536 first time kidney transplant recipients with Medicare as primary payer in the 6 months before and at transplantation. 24 192 patients were excluded as they did not have type 2 diabetes. 2328 patients were ineligible (1916 had missing values and 412 used GLP-1 receptor agonists before transplantation). The primary cohort thus consisted of 18 016 kidney transplant recipients with diabetes. Of these patients, 1969 (10·9%) had at least one GLP-1 receptor agonist prescription filled post-transplant. Compared with patients who had not received a GLP-1 receptor agonist, GLP-1 receptor agonist users were younger (median age at transplant 57 years [IQR 49-64] vs 60 years [51-66], p<0·0001) and more likely to be female (786 [39·9%] vs 5645 [35·2%], p<0·0001). Among GLP-1 receptor agonist users, 552 [28·0%] were non-Hispanic White, 703 [35·7%] were non-Hispanic Black, and 568 [28·8%] were Hispanic. The 5-year unadjusted cumulative incidence of death-censored graft loss from a cohort matched on survival time before GLP-1 receptor agonist initiation was 6·0% for GLP-1 receptor agonist users and 10·7% for non-users (Gray's test p=0·004). The 5-year unadjusted cumulative incidence for mortality from a cohort matched on survival time before GLP-1 receptor agonist initiation was 17·0% for GLP-1 receptor agonist users and 25·8% for non-users (log-rank p=0·0006). The 5-year unadjusted cumulative incidence for mortality was 13·5% for GLP-1 receptor agonist users and 19·9% for non-users (log-rank p<0·0001). GLP-1 receptor agonist use was associated with a 49% lower incidence of death-censored graft loss (adjusted subhazard ratio [aSHR] 0·51, 95% CI 0·36-0·71; p=0·0001) and 31% lower mortality (adjusted hazard ratio [aHR] 0·69, 95% CI 0·55-0·86; p=0·001). Inferences were robust when matched on survival time (death-censored graft loss aSHR 0·53, 95% CI 0·37-0·75; p=0·0005; mortality aHR 0·70, 95% CI 0·55-0·88; p=0·003). Safety endpoints were rare and not associated with GLP-1 receptor agonists, with the exception of diabetic retinopathy (aHR 1·49, 1·11-2·00; p=0·008). INTERPRETATION/CONCLUSIONS:GLP-1 receptor agonists were associated with better graft and patient survival. Clinical trials are needed to confirm these findings. FUNDING/BACKGROUND:National Institutes of Health.

Unauthorized immigrants and permanent residents may experience challenges in accessing kidney transplantation due to limited healthcare access, socioeconomic and cultural barriers. Understanding the United States (US) national landscape of kidney transplantation for non-citizens may inform policy changes. To evaluate this, we utilized two cohorts from the US national registry (2013-2023): 287,481 adult candidates for first transplant listing and 190,176 adult first transplant recipients. Citizenship was categorized as US citizen (reference), permanent resident, and presumed unauthorized immigrant. Negative binomial regression was used to quantify the incidence rate ratio over time by citizenship status. Cause-specific hazards models, with clustering at the state of listing/transplant, were used to calculate the adjusted hazard ratio of waitlist mortality, kidney transplant, and post-transplant outcomes (mortality/death-censored graft failure) by citizenship category. The crude proportion of presumed unauthorized immigrants listed increased over time (2013: 0.9%, 2023:1.9%). However, after accounting for case mix and waitlist size, there was no change in listing over time. Presumed unauthorized immigrants were less likely to experience waitlist mortality (adjusted Hazard Ratio 0.54, 95% Confidence Interval: 0.46-0.62), were more likely to obtain deceased donor kidney transplant (1.11: 1.05-1.18), but less likely to receive live donor (0.80: 0.71-0.90) or preemptive kidney transplant (0.52: 0.43- 0.62). When stratified by insurance status, presumed unauthorized immigrants on Medicaid were less likely to receive deceased donor kidney transplants compared to their citizen counterparts; however, presumed unauthorized immigrants with Private insurance or Medicare were more likely to receive deceased donor kidney transplants. Presumed unauthorized immigrants were less likely to experience post-transplant death (0.56: 0.43-0.69) and graft failure (0.69: 0.57-0.84). Residents had similar pre- and post-transplant outcomes. Despite the barriers to kidney transplantation faced by presumed unauthorized immigrants and residents in the US, better post-transplant outcomes for presumed unauthorized immigrants compared to citizens persisted, even after accounting for differences in patient characteristics.

INTRODUCTION/BACKGROUND:Some living organ donors will decide to donate again at a later date. Evidence has indicated that this practice may have increased in recent years. We evaluated the incidence and outcomes of this practice to inform counseling of potential repeat donors. METHODS:Using SRTR data from 1994 to 2023, we identified 220 repeat living donors and their 415 recipients. We constructed donor comparison groups using weighting by the odds. We described clinical and lab results at 6 months, 1 year, and 2 years post-donation separately for kidney-second donors and liver-second donors. We compared all-cause graft failure for their recipients with those of comparison donors. RESULTS:The annual count of repeat living donors increased from 5 in 2018 to 25 in 2019 (p < 0.001). Of 220 donors, 159 were liver-second donors (72.3%) and 55 were kidney-second donors (25.0). The percentage of nondirected donations increased from 30.5% at first donation to 53.2% at second donation (p < 0.001). Liver-second donors had one death approximately 2.5 years post-donation. Seventeen were re-admitted and 20 experienced complications requiring an interventional procedure or re-operation. Among kidney-second donors, no deaths, re-admissions, or post-donation complications were reported. Post-donation outcomes in both groups were comparable when evaluated against organ-specific comparison donors. Recipients of repeat living donors experienced graft survival similar to recipients of comparison donors. CONCLUSIONS:Repeat living donation may be a safe practice for carefully selected living donors in the short term; however, long term safety is unknown. Outcomes for recipients are similar to recipients of comparison donors.