Faculty Bibliography

Body mass index is often used to determine kidney transplant (KT) candidacy. However, this measure of body composition (BC) has several limitations, including the inability to accurately capture dry weight. Objective computed tomography (CT)-based measures may improve pre-KT risk stratification and capture physiological aging more accurately. We quantified the association between CT-based BC measurements and waitlist mortality in a retrospective study of 828 KT candidates (2010-2022) with clinically obtained CT scans using adjusted competing risk regression. In total, 42.5% of candidates had myopenia, 11.4% had myopenic obesity (MO), 68.8% had myosteatosis, 24.8% had sarcopenia (probable = 11.2%, confirmed = 10.5%, and severe = 3.1%), and 8.6% had sarcopenic obesity. Myopenia, MO, and sarcopenic obesity were not associated with mortality. Patients with myosteatosis (adjusted subhazard ratio [aSHR] = 1.62, 95% confidence interval [CI]: 1.07-2.45; after confounder adjustment) or sarcopenia (probable: aSHR = 1.78, 95% CI: 1.10-2.88; confirmed: aSHR = 1.68, 95% CI: 1.01-2.82; and severe: aSHR = 2.51, 95% CI: 1.12-5.66; after full adjustment) were at increased risk of mortality. When stratified by age, MO (aSHR = 2.21, 95% CI: 1.28-3.83; P interaction = .005) and myosteatosis (aSHR = 1.95, 95% CI: 1.18-3.21; P interaction = .038) were associated with elevated risk only among candidates <65 years. MO was only associated with waitlist mortality among frail candidates (adjusted hazard ratio = 2.54, 95% CI: 1.28-5.05; P interaction = .021). Transplant centers should consider using BC metrics in addition to body mass index when a CT scan is available to improve pre-KT risk stratification at KT evaluation.

BACKGROUND:Recent clinical trials demonstrate benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with chronic kidney disease, but data on use in kidney transplant (KTx) recipients are limited. METHODS:). RESULTS:vs. prior years). CONCLUSION:SGLT2i use is increasing in KTx recipients but varies with factors including race, education, and insurance. While ongoing study is needed to define risks and benefits of SGLT2i use in KTx patients, attention should also focus on reducing treatment disparities related to sociodemographic traits.

The first 2 living recipients of pig hearts died unexpectedly within 2 months, despite both recipients receiving what over 30 years of nonhuman primate (NHP) research would suggest were the optimal gene edits and immunosuppression to ensure success. These results prompt us to question how faithfully data from the NHP model translate into human outcomes. Before attempting any further heart xenotransplants in living humans, it is highly advisable to gain a more comprehensive understanding of why the promising preclinical NHP data did not accurately predict outcomes in humans. It is also unlikely that additional NHP data will provide more information that would de-risk a xenoheart clinical trial because these cases were based on the best practices from the most successful NHP results to date. Although imperfect, the decedent model offers a complementary avenue to determine appropriate treatment regimens to control the human immune response to xenografts and better understand the biologic differences between humans and NHP that could lead to such starkly contrasting outcomes. Herein, we explore the potential benefits and drawbacks of the decedent model and contrast it to the advantages and disadvantages of the extensive body of data generated in the NHP xenoheart transplantation model.

BACKGROUND:Cytomegalovirus (CMV)-seronegative lung transplant recipients (LTRs) with seropositive donors (CMV D+/R-) have the highest mortality of all CMV serostatuses. Due to immunosenescence and other factors, we hypothesized CMV D+/R- status might disproportionately impact older LTRs. Thus, we investigated whether recipient age modified the relationship between donor CMV status and mortality among CMV-seronegative LTRs. METHODS:Adult, CMV-seronegative first-time lung-only recipients were identified through the Scientific Registry of Transplant Recipients between May 2005 and December 2019. We used adjusted multivariable Cox regression to assess the relationship of donor CMV status and death. Interaction between recipient age and donor CMV was assessed via likelihood ratio testing of nested Cox models and by the relative excess risk due to interaction (RERI) and attributable proportion (AP) of joint effects. RESULTS:We identified 11,136 CMV-seronegative LTRs. The median age was 59 years; 65.2% were male, with leading transplant indication of idiopathic pulmonary fibrosis (35.6%); and 60.8% were CMV D+/R-. In multivariable modeling, CMV D+/R- status was associated with 27% increased hazard of death (adjusted hazard ratio: 1.27, 95% confidence interval: 1.21-1.34) compared to CMV D-/R-. Recipient age ≥60 years significantly modified the relationship between donor CMV-seropositive status and mortality on the additive scale, including RERI 0.24 and AP 11.4% (p = 0.001), that is, the interaction increased hazard of death by 0.24 and explained 11.4% of mortality in older CMV D+ recipients. CONCLUSIONS:Among CMV-seronegative LTRs, donor CMV-seropositive status confers higher risk of posttransplant mortality, which is amplified in older recipients. Future studies should define optimal strategies for CMV prevention and management in older D+/R- LTRs.

BACKGROUND:Kidney transplant (KT) candidates with HIV face higher mortality on the waitlist compared with candidates without HIV. Because the HIV Organ Policy Equity (HOPE) Act has expanded the donor pool to allow donors with HIV (D+), it is crucial to understand whether this has impacted transplant rates for this population. METHODS:Using a linkage between the HOPE in Action trial (NCT03500315) and Scientific Registry of Transplant Recipients, we identified 324 candidates listed for D+ kidneys (HOPE) compared with 46 025 candidates not listed for D+ kidneys (non-HOPE) at the same centers between April 26, 2018, and May 24, 2022. We characterized KT rate, KT type (D+, false-positive [FP; donor with false-positive HIV testing], D- [donor without HIV], living donor [LD]) and quantified the association between HOPE enrollment and KT rate using multivariable Cox regression with center-level clustering; HOPE was a time-varying exposure. RESULTS:HOPE candidates were more likely male individuals (79% versus 62%), Black (73% versus 35%), and publicly insured (71% versus 52%; P < 0.001). Within 4.5 y, 70% of HOPE candidates received a KT (41% D+, 34% D-, 20% FP, 4% LD) versus 43% of non-HOPE candidates (74% D-, 26% LD). Conversely, 22% of HOPE candidates versus 39% of non-HOPE candidates died or were removed from the waitlist. Median KT wait time was 10.3 mo for HOPE versus 60.8 mo for non-HOPE candidates (P < 0.001). After adjustment, HOPE candidates had a 3.30-fold higher KT rate (adjusted hazard ratio = 3.30, 95% confidence interval, 2.14-5.10; P < 0.001). CONCLUSIONS:Listing for D+ kidneys within HOPE trials was associated with a higher KT rate and shorter wait time, supporting the expansion of this practice for candidates with HIV.

Obesity is a chronic, relapsing disease that increases the risks of living kidney donation; at the same time, transplant centers have liberalized body mass index constraints for donors. With the increasing number of anti-obesity medications available, the treatment of obesity with anti-obesity medications may increase the pool of potential donors and enhance donor safety. Anti-obesity medications are intended for long-term use given the chronic nature of obesity. Cessation of treatment can be expected to lead to weight regain and increases the risk of comorbidity rebound/development. In addition, anti-obesity medications are meant to be used in conjunction with-rather than in replacement of-diet and physical activity optimization. Anti-obesity medication management includes selecting medications that may ameliorate any co-existing medical conditions, avoiding those that are contraindicated in such conditions, and being sensitive to any out-of-pocket expenses that may be incurred by the potential donor. A number of questions remain regarding who will and should shoulder the costs of long-term obesity treatment for donors. In addition, future studies are needed to quantify the degree of weight loss and duration of weight loss maintenance needed to normalize the risk of adverse kidney outcomes relative to comparable non-donors and lower weight donors.

BACKGROUND:The Lung Allocation Score, implemented in 2005, prioritized lung transplant candidates by medical urgency rather than waiting list time and was expected to improve racial disparities in transplant allocation. We evaluated whether racial disparities in lung transplant persisted after 2005. METHODS:We identified all wait-listed adult lung transplant candidates in the United States from 2005 through 2021 using the Scientific Registry of Transplant Recipients. We evaluated the association between race and receipt of a transplant by using a multivariable competing risk regression model adjusted for demographics, socioeconomic status, Lung Allocation Score, clinical measures, and time. We evaluated interactions between race and age, sex, socioeconomic status, and Lung Allocation Score. RESULTS:We identified 33,158 candidates on the lung transplant waiting list between 2005 and 2021: 27,074 White (82%), 3350 African American (10%), and 2734 Hispanic (8%). White candidates were older, had higher education levels, and had lower Lung Allocation Scores (P < .001). After multivariable adjustment, African American and Hispanic candidates were less likely to receive lung transplants than White candidates (African American: adjusted subhazard ratio, 0.86; 95% CI, 0.82-0.91; Hispanic: adjusted subhazard ratio, 0.82; 95% CI, 0.78-0.87). Lung transplant was significantly less common among Hispanic candidates aged >65 years (P = .003) and non-White candidates from higher-poverty communities (African-American: P = .013; Hispanic: P =.0036). CONCLUSIONS:Despite implementation of the Lung Allocation Score, racial disparities persisted for wait-listed African American and Hispanic lung transplant candidates and differed by age and poverty status. Targeted interventions are needed to ensure equitable access to this life-saving intervention.

RATIONALE & OBJECTIVE/UNASSIGNED:Understanding national attitudes about living kidney donation will enable us to identify and address existing disincentives to living kidney donation. We performed a national survey to describe living kidney donation perceptions, perceived factors that affect the willingness to donate, and analyzed differences by demographic subgroups. STUDY DESIGN/UNASSIGNED:The survey items captured living kidney donation awareness, living kidney donation knowledge, willingness to donate, and barriers and facilitators to living kidney donation. SETTING & POPULATION/UNASSIGNED:We surveyed 802 US adults (aged 25-65 years) in June 2021, randomly selected from an online platform with diverse representation. ANALYTICAL APPROACH/UNASSIGNED:and Fisher exact tests. We inductively evaluated free-text responses to identify additional barriers and facilitators to living kidney donation. RESULTS/UNASSIGNED:Most (86.6%) of the respondents reported that they might or would definitely consider donating a kidney while they were still living. Barriers to living kidney donation included concerns about the risk of the surgery, paying for medical expenses, and potential health effects. Facilitators to living kidney donation included having information on the donation surgery's safety, knowing that the donor would not have to pay for medical expenses related to the donation, and hearing living kidney donation success stories. Awareness of the ability to participate in kidney-paired donation was associated with a higher willingness to donate. LIMITATIONS/UNASSIGNED:Potential for selection bias resulting from the use of survey panels and varied incentive amounts, and measurement error related to respondents' attention level. CONCLUSIONS/UNASSIGNED:Most people would consider becoming a living kidney donor. Increased rates of living kidney donation may be possible with investment in culturally competent educational interventions that address risks associated with donating, policies that reduce financial disincentives, and communication campaigns that raise awareness of kidney-paired donation and living kidney donation.

The coronavirus disease of 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in increased morbidity and mortality in patients with impaired immunity, hematologic malignancies, and immunosuppressive regimens. COVID-19 can cause a cytokine storm with some patients benefiting from blockade of the pro-inflammatory cytokine, interleukin 6 (IL6). As Castleman disease (CD) is an atypical lymphoproliferative disorder that can involve a cytokine storm and often requires immunosuppressive therapies, including IL6 inhibition, we sought to evaluate outcomes following COVID-19 and SARS-CoV-2 vaccination in CD patients. We administered a survey in April 2021 to characterize experiences with COVID-19 and SARS-CoV-2 vaccination among 300 CD patients enrolled in ACCELERATE, a natural history registry of CD patients. Among 128 respondents, the prevalence of SARS-CoV-2 infection (16/95, 17%), severe disease (1/16, 6%), vaccination rates (112/128, 88%), and vaccine adverse effects after dose one (62/112, 55%) were comparable to the general U.S. population. While there were two cases of CD flares occurring shortly after SARS-CoV-2 infection (N=1) and vaccination (N=1), over 100 patients in this study that were infected and/or vaccinated did not experience CD flares. The median anti-spike titer six months after the second dose among CD patients was comparable to individuals with other immune-related diseases and healthy populations. Data from this small cohort suggest that, despite being on immunosuppressive therapies, CD patients do not appear to be at increased risk of poor COVID-19 outcomes and can mount a humoral response to SARS-CoV-2 vaccination. This study was registered on clinicaltrials.gov (#NCT02817997).

INTRODUCTION:Thoracoabdominal normothermic regional perfusion (TA-NRP) following cardiac death is an emerging multivisceral organ procurement technique. Recent national studies on outcomes of presumptive TA-NRP-procured organs are limited by potential misclassification since TA-NRP is not differentiated from donation after cardiac death (DCD) in registry data. METHODS:We studied 22 donors whose designees consented to TA-NRP and organ procurement performed at our institution between January 20, 2020 and July 3, 2022. We identified these donors in SRTR to describe organ utilization and recipient outcomes and compared them to recipients of traditional DCD (tDCD) and donation after brain death (DBD) organs during the same timeframe. RESULTS:All 22 donors progressed to cardiac arrest and underwent TA-NRP followed by heart, lung, kidney, and/or liver procurement. Median donor age was 41 years, 55% had anoxic brain injury, 45% were hypertensive, 0% were diabetic, and median kidney donor profile index was 40%. TA-NRP utilization was high across all organ types (88%-100%), with a higher percentage of kidneys procured via TA-NRP compared to tDCD (88% vs. 72%, p = .02). Recipient and graft survival ranged from 89% to 100% and were comparable to tDCD and DBD recipients (p ≥ .2). Delayed graft function was lower for kidneys procured from TA-NRP compared to tDCD donors (27% vs. 44%, p = .045). CONCLUSION:Procurement from TA-NRP donors yielded high organ utilization, with outcomes comparable to tDCD and DBD recipients across organ types. Further large-scale study of TA-NRP donors, facilitated by its capture in the national registry, will be critical to fully understand its impact as an organ procurement technique.