Faculty Bibliography

BACKGROUND:Organ Procurement and Transplantation Network (OPTN) policy requires 2 years of follow-up for living kidney donors (LKDs); however, many transplant hospitals struggle to meet this requirement. We developed and tested a mobile health (mHealth) system for LKD follow-up in a pilot randomized-controlled trial (RCT). METHODS:LKDs were randomly assigned to either the intervention (mHealth + standard of care) or control arm (standard of care). We assessed OPTN policy-defined completeness and timeliness of 6-month, 1-year, and 2-year follow-ups. Four hundred LKDs were enrolled in the study (June 2018 to February 2021). RESULTS:At 6-month follow-up, a higher proportion of the intervention arm participants completed composite visits (97.5% vs. 91.5%, p = 0.01). Both arms had similar compliance rates at 1- and 2-year follow-up (92.0% vs. 89.5%, p = 0.49, and 66.5% vs. 65.0%, p = 0.83). Intervention arm participants completed 6-month follow-up 11 days earlier than their counterparts (p = 0.009). CONCLUSION/CONCLUSIONS:mHealth technologies improved 6-month follow-up, but did not impact 1- and 2-year LKD follow-up in this single-center RCT. Other strategies, such as providing services beyond data collection, may be necessary to improve donor engagement and support LDK's long-term follow-up.

INTRODUCTION/BACKGROUND:Predicting graft failure risk in pediatric liver transplantation (LT) recipients could identify areas for improving management. Persistent cognitive, motor, academic, and functional deficits are common in recipients and their impact on graft survival following LT helps inform risk prediction. METHODS:Using SRTR data 2008-2023, we evaluated the cognitive, motor, academic, and functional deficits of LT recipients at time of transplant to 14 years post-LT. We compared all cause graft failure (ACGF) among patients with versus without pre-LT and 1-year post-LT deficits using Cox regression, adjusting for recipient characteristics. We calculated an individual risk score for ACGF. RESULTS:In 8062 pediatric LT recipients median age 3 (IQR: 1, 10), 28.0%, 29.5%, 35.0%, and 79.8% of recipients had pre-LT deficits in cognition, motor, academic activity, and functional status respectively. This decreased to 23.0%, 18.1%, 14.2%, and 38.7% 1-year post-LT. Increased hazard of ACGF was noted in recipients with pre-LT decreased functional status (aHR = 1.13 (per 10% decrease), 95% CI: 1.10-1.15, p < 0.001), definite motor delay (aHR = 1.60, 95% CI: 1.21-2.10, p < 0.001), and inability to participate in academics (aHR = 1.49, 95% CI: 1.08-1.89, p = 0.01), but not delays in cognition (aHR = 0.91, 95% CI: 0.69-1.21, p = 0.19). Our risk score predicting ACGF demonstrated improved predictive performance compared to clinical parameters alone (C-statistic = 0.70 (0.67, 0.72) vs. 0.66 (0.64, 0.69), p < 0.001). CONCLUSIONS:Pediatric LT recipients with pre- or post-LT motor, academic, and functional deficits are at higher risk for ACGF. Care should be taken to assess deficits to identify patients who may benefit from functional intervention to potentially reduce ACGF risk.

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.

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: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.

Racial/ethnic disparities in the deceased organ donor referral process may contribute to the organ shortage and place minority communities at a greater disadvantage. Prior literature cites substantial inequalities, though methodological concerns may bias estimates. Using Organ Retrieval and Collection of Health Information for Donation data, we conducted a simulation study and re-analysis of 132,968 referrals 2015-2021 across six organ procurement organizations (OPOs). We excluded brain death declaration and cause/mechanism/circumstances of death from the approach model and conducted Poisson regression with robust standard errors. We found Black patients were approached at a more similar rate relative to White patients, although disparities remained (incidence rate ratio (IRR): _0.910.94_0.97). Black patients provided authorization at a 31% lower rate than White patients (IRR: _0.670.69_0.71). Slight disparities were observed at procurement (IRR: _0.940.96_0.99). Our findings are directionally similar to prior literature but suggest substantially less inequality (vs 23% and 65% higher risk of approach and authorization, for non-Black vs Black referrals). Accurate quantification of racial/ethnic disparities in transplantation impacts public perception of those involved, particularly OPOs, and is paramount to any study. Importantly, continued measures are needed to promote equality among Black and minority patients in our national organ donation and transplant system.

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: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.

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.