Faculty Bibliography

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/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: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.

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.

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.

RATIONALE & OBJECTIVE/OBJECTIVE:Despite substantial growth in the population of older adults with kidney disease, there remains a lack of evidence to guide clinical care for this group. The Kidney Disease and Aging Research Collaborative (KDARC) conducted a Delphi study to build consensus on research priorities for clinical geriatric nephrology. STUDY DESIGN/METHODS:Asynchronous modified Delphi study. SETTING & PARTICIPANTS/METHODS:Clinicians and researchers in the US and Canada with clinical experience and/or research expertise in geriatric nephrology. OUTCOME/RESULTS:Research priorities in geriatric nephrology. ANALYTICAL APPROACH/METHODS:In the first Delphi round, participants submitted free-text descriptions of research priorities considered important for improving the clinical care of older adults with kidney disease. Delphi moderators used inductive content analysis to group concepts into categories. In the second and third rounds, participants iteratively reviewed topics, selected their top 5 priorities, and offered comments used to revise categories. RESULTS:Among 121 who were invited, 57 participants (47%) completed the first Delphi round and 48 (84% of enrolled participants) completed all rounds. After 3 rounds, the 5 priorities with the highest proportion of agreement were: 1) Communication and Decision-Making about Treatment Options for Older Adults with Kidney Failure (69% agreement), 2) Quality of Life, Symptom Management, and Palliative Care (67%), 3) Frailty and Physical Function (54%), 4) Tailoring Therapies for Kidney Disease to Specific Needs of Older Adults (42%), and 5) Caregiver and Social Support (35%). Health equity and person-centricity were identified as cross-cutting features that informed all topics. LIMITATIONS/CONCLUSIONS:Relatively low response rate and limited participation by private practitioners and older clinicians and researchers. CONCLUSIONS:Experts in geriatric nephrology identified clinical research priorities with the greatest potential to improve care for older adults with kidney disease. These findings provide a roadmap for the geriatric nephrology community to harmonize and maximize the impact of research efforts.