Faculty Bibliography

BACKGROUND:Due to high prevalence of Kaposi Sarcoma (KS)-Associated Herpesvirus (KSHV) among people with HIV, KSHV-associated disease (KAD) may be increased after kidney transplantation from donors with HIV (HIV D+) to recipients with HIV (HIV R+). METHODS:Anti-KSHV antibodies were measured in HIV R+ and donors with and without HIV (HIV D-) using a 30-antigen multiplex assay within three multicenter kidney transplantation studies. KSHV seropositivity was defined as reactivity to conventional KSHV antigens (≥1 ORF73 or K8.1); reactivity to expanded 5-antigen and 30-antigen panels were also reported. Risk factors were identified using modified Poisson regression. Recipients were monitored for post-transplant anti-KSHV antibody changes and KAD. RESULTS:KSHV seroprevalence was 40.6% (143/352) among HIV R+, 25.2% (33/131) among HIV D+, and 7.5% (4/53) among HIV D-. In the multivariable model, only men who have sex with men (MSM) was associated with KSHV seropositivity: relative risk 1.51 (95% confidence interval [CI] 1.07-2.14) in recipients and 2.39 (95%CI 1.03-5.53) in donors. Among 418 HIV R+ (215 HIV D+/R+, 203 HIV D-/R+), there were 5 KAD cases (incidence 0.63 cases/100 person-years, 95%CI 0.26-1.52): 3 skin-only KS, 1 multicentric Castleman disease, 1 allograft KS. The allograft KS occurred in a female HIV D+/R+ and was likely donor-derived. Remaining KAD cases occurred in male HIV D-/R+ and were likely recipient KSHV reactivation or acquisition. CONCLUSIONS:In the United States, KSHV seroprevalence in donors and recipients with HIV was high, particularly among MSM. Reassuringly, KSHV-associated disease was rare, and primarily attributed to recipient rather than donor-derived KSHV.

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:Renal dysfunction is common among liver transplant candidates and can resolve, persist, or develop de novo following liver transplantation (LT). In light of the 2017 policy changes to simultaneous liver-kidney transplant and the post-LT kidney transplant safety net eligibility, we evaluated risk factors for and change in the incidence of post-LT renal dysfunction. METHODS:Using SRTR data for adult deceased-donor liver-only transplant recipients 2010-2022, we evaluated secular trends in and risk factors for the development of post-LT ESRD at 1 year and overall using multivariable logistic and Cox regression. We compared observed versus expected incidence of ESRD at 1-year post-LT using weighting by odds. RESULTS:Among 77 565 LT recipients, 6032 (7.8%) developed ESRD during the study period, of whom 2354 (39.0%) developed ESRD within the first year after LT. In a multivariable model, diabetes (aOR 1.63, 95% CI 1.48-1.79, p < 0.001), pre-LT eGFR (aOR 0.97 per unit, 95% CI 0.97-0.97, p < 0.001), and MELD category remained independently associated with ESRD within 1-year post-LT. Odds of ESRD by 1 year post-LT were 47% higher than expected post-2017 after accounting for changes in donor and recipient characteristics. CONCLUSIONS:The rising 1-year post-LT ESRD risk highlights the need to reassess safety net eligibility beyond 1 year and prioritize counseling on risk minimization, including post-transplant diabetes management and potential adjustments to immunosuppression protocols to improve outcomes.

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:HLA-DQ mismatch has been identified as a predictor of de novo donor-specific HLA antibody formation and antibody-mediated rejection. There are insufficient data to guide the incorporation of DQ mismatch into organ allocation decisions. METHODS:We used a retrospective longitudinal cohort of adult living donor kidney transplant recipients from 11 centers across the United States for whom high-resolution class II typing was available. HLA-DQαβ heterodimer allele mismatch was quantified for all donor-recipient pairs, and outcome data were obtained through linkage with the Scientific Registry of Transplant Recipients. RESULTS:We studied 3916 donor-recipient pairs. Recipient characteristics were notable for a median age of 51 (38-61) y, primarily unsensitized, with 74.5% of the cohort having 0% calculated panel-reactive antibody, and 60.4% with private insurance, for a median follow-up time of 5.86 y. We found that the HLA-DQαβ allele and HLA-DR antigen mismatch were each individually associated with an increased hazard of all-cause graft failure (adjusted hazard ratio [aHR] DQ = 1.03 1.14 1.28; aHR DR = 1.03 1.15 1.328), death-censored graft failure (aHR DQ =1.01 1.19 1.40; aHR DR = 0.099 1.18 1.39), and rejection. Having 2 HLA-DQαβ allele mismatches further increased the hazard of rejection even when controlling for HLA-DR mismatch (aHR 1.03 1.68 2.74). CONCLUSIONS:HLA-DQαβ allele mismatch predicted allograft rejection even when controlling for HLA-DR antigen mismatch and were both independently associated with increased risk of graft failure or rejection in adult living kidney transplant recipients. Given the strong burden of disease arising from the HLA-DQ antibody formation, we suggest that HLA-DQαβ should be prioritized over HLA-DR in donor selection.

Developing real-world evidence from electronic health records (EHR) is vital to advance kidney transplantation (KT). We assessed the feasibility of studying KT using the Epic Cosmos aggregated EHR dataset, which includes 274 million unique individuals cared for in 238 U.S. health systems, by comparing it with the Scientific Registry of Transplant Recipients (SRTR). We identified 69,418 KT recipients transplanted between January 2014 and December 2022 in Cosmos (39.4% of all US KT transplants during this period). Demographics and clinical characteristics of recipients captured in Cosmos were consistent with the overall SRTR cohort. Survival estimates were generally comparable, although there were some differences in long-term survival. At 7 years post-transplant, patient survival was 80.4% in Cosmos and 77.8% in SRTR. Multivariable Cox regression showed consistent associations between clinical factors and mortality in both cohorts, with minor discrepancies in the associations between death and both age and race. In summary, Cosmos provides a reliable platform for KT research, allowing EHR-level clinical granularity not available with either the transplant registry or healthcare claims. Consequently, Cosmos will enable novel analyses to improve our understanding of KT management on a national scale.

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.

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.