Faculty Bibliography

OBJECTIVE:Liver transplant (LT) evaluation is a complex process for patients involving multi-step and parallel medical, surgical, and psychosocial assessments of a patient's appropriateness for transplant. Patients may experience difficulties in navigating the evaluation process, potentially leading to disengagement and resulting in further health decline or death prior to completing evaluation. We aimed to identify and characterize patients' perceptions of undergoing LT evaluation. METHODS:We performed fourteen 30-45 min, semi-structured interviews between 3/2021-5/2021 with patients at a large LT center. Using the constant comparison method, we individually noted themes within and across interviews and codes. RESULTS:Our analysis generated 5 thematic dimensions related to patient engagement (i.e., patient involvement/activation): (1) psychological impact of evaluation on patients' lives; (2) information received during evaluation; (3) prior medical experience of the patient; 4) communication between patients and transplant providers; and (5) support system of the patients. Among these dimensions, we identified 8 themes. CONCLUSION/CONCLUSIONS:LT patient engagement is a multi-dimensional component of LT evaluation that incorporates the psychological impact, information received, prior medical experience, communication, and support systems of patients. PRACTICAL IMPLICATIONS/CONCLUSIONS:This work can inform targeted interventions for increasing patient engagement during the LT evaluation process.

BACKGROUND/UNASSIGNED:Fewer minoritized patients with end-stage kidney disease (ESKD) receive kidney transplantation (KT); efforts to mitigate disparities have thus far failed. Pinpointing the specific stage(s) within the transplant care continuum (being informed of KT options, joining the waiting list, to receiving KT) where disparities emerge among each minoritized population is pivotal for achieving equity. We therefore quantified racial and ethnic disparities across the KT care continuum. METHODS/UNASSIGNED:We conducted a retrospective cohort study (2015-2020), with follow-up through 12/10/2021. Patients with incident dialysis were identified using the US national registry data. The exposure was race and ethnicity (Asian, Black, Hispanic, and White). We used adjusted modified Poisson regression to quantify the adjusted prevalence ratio (aPR) of being informed of KT, and cause-specific hazards models to calculate adjusted hazard ratios (aHR) of listing, and transplantation after listing. FINDINGS/UNASSIGNED:Among 637,951 adults initiating dialysis, the mean age (SD) was 63.8 (14.6), 41.8% were female, 5.4% were Asian, 26.3% were Black, 16.6% were Hispanic, and 51.7% were White (median follow-up in years [IQR]:1.92 [0.97-3.39]). Black and Hispanic patients were modestly more likely to be informed of KT (Black: aPR = 1.02, 95% confidence interval [CI]:1.01-1.02; Hispanic: aPR = 1.03, 95% CI: 1.02-1.03) relative to White patients. Asian patients were more likely to be listed (aHR = 1.18, 95% CI: 1.15-1.21) but less likely to receive KT (aHR = 0.56, 95% CI: 0.54-0.58). Both Black and Hispanic patients were less likely to be listed (Black: aHR = 0.87, 95% CI: 0.85-0.88; Hispanic: aHR = 0.85, 95% CI: 0.85-0.88) and receive KT (Black: aHR = 0.61, 95% CI: 0.60-0.63; Hispanic: aHR = 0.64, 95% CI: 0.63-0.66). INTERPRETATION/UNASSIGNED:Improved characterization of the barriers in KT access specific to each racial and ethnic group, and the interventions to address these distinct challenges throughout the KT care continuum are needed; our findings identify specific stages most in need of mitigation. FUNDING/UNASSIGNED:National Institutes of Health.

INTRODUCTION/BACKGROUND:ChatGPT has shown the ability to answer clinical questions in general medicine but may be constrained by the specialized nature of kidney transplantation. Thus, it is important to explore how ChatGPT can be used in kidney transplantation and how its knowledge compares to human respondents. METHODS:We prompted ChatGPT versions 3.5, 4, and 4 Visual (4 V) with 12 multiple-choice questions related to six kidney transplant cases from 2013 to 2015 American Society of Nephrology (ASN) fellowship program quizzes. We compared the performance of ChatGPT with US nephrology fellowship program directors, nephrology fellows, and the audience of the ASN's annual Kidney Week meeting. RESULTS:Overall, ChatGPT 4 V correctly answered 10 out of 12 questions, showing a performance level comparable to nephrology fellows (group majority correctly answered 9 of 12 questions) and training program directors (11 of 12). This surpassed ChatGPT 4 (7 of 12 correct) and 3.5 (5 of 12). All three ChatGPT versions failed to correctly answer questions where the consensus among human respondents was low. CONCLUSION/CONCLUSIONS:Each iterative version of ChatGPT performed better than the prior version, with version 4 V achieving performance on par with nephrology fellows and training program directors. While it shows promise in understanding and answering kidney transplantation questions, ChatGPT should be seen as a complementary tool to human expertise rather than a replacement.

BACKGROUND AND HYPOTHESIS/OBJECTIVE:Early steroid withdrawal (ESW) is often preferred over conventional steroid maintenance (CSM) therapy for kidney transplant recipients with low immunological risks because it may minimize immunosuppression-related adverse events while achieving similar transplant outcomes. However, the risk-benefit balance of ESW could be less favorable in retransplant recipients given their unique immunological risk profile. We hypothesized that the association of ESW with transplant outcomes would differ between first-transplant and retransplant recipients. METHODS:To assess whether the impact of ESW differs between first and retransplant recipients, we studied 210 086 adult deceased-donor kidney transplant recipients using the Scientific Registry of Transplant Recipients. Recipients who discontinued maintenance steroids before discharge from transplant admission were classified with ESW; all others were classified with CSM. We quantified the association of ESW (vs. CSM) with acute rejection, death-censored graft failure, and death, addressing retransplant as an effect modifier, using logistic/Cox regression with inverse probability weights to control for confounders. RESULTS:In our cohort, 26 248 (12%) were retransplant recipients. ESW was used in 30% of first-transplant and 20% of retransplant recipients. Among first-transplant recipients, ESW was associated with no significant difference in acute rejection (aOR = 1.04 [95% CI = 1.00-1.09]), slightly higher hazard of graft failure (HR = 1.09 [95% CI = 1.05-1.12]), and slightly lower mortality (HR = 0.93 [95% CI = 0.91-0.95]) compared to CSM. Nonetheless, among retransplant recipients, ESW was associated with notably higher risk of acute rejection (OR = 1.42 [95% CI = 1.29-1.57]; interaction p < 0.001) and graft failure (HR = 1.24 [95% CI = 1.14-1.34]; interaction p = 0.003), and similar mortality (HR = 1.01 [95% CI = 0.94-1.08]; interaction p = 0.04). CONCLUSIONS:In retransplant recipients, the negative impacts of ESW on transplant outcomes appear to be non-negligible. A more conservatively tailored approach to ESW might be necessary for retransplant recipients.

Durability of variant neutralization in solid organ transplant recipients following Omicron-containing boosters is unknown. We report wane in XBB.1.5 neutralization by 3 months following a first bivalent booster, improved by a second booster; hybrid immunity improved peak, and duration of neutralization. Boosting at 3 to 6 months appears necessary to maintain neutralization.

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.

UNLABELLED:Solid organ transplant recipients (SOTRs) suffer more frequent and more severe infections due to their compromised immune responses resulting from immunosuppressive treatments designed to prevent organ rejection. Pharmacological immunosuppression can adversely affect immune responses to vaccination. A cohort of kidney transplant recipients (KTRs) received their third dose of ancestral, monovalent COVID-19 vaccine in the context of a clinical trial and antibody responses to the vaccine strain, as well as to Omicron variants BA.1 and BA.5 were investigated and compared with healthy controls. Total IgG and live virus neutralizing antibody titers were reduced in KTRs compared to controls for all variants. KTRs displayed altered IgG subclass switching, with significantly lower IgG3 antibodies. Responses in KTRs were also very heterogeneous, with some individuals showing strong responses but a significant number showing no Omicron-specific neutralizing antibodies. Taken together, immune responses after COVID-19 vaccination in KTRs were not only lower than healthy controls but highly variable, indicating that simply increasing the number of vaccine doses alone may not be sufficient to provide greater protection in this population. IMPORTANCE/UNASSIGNED:This study addresses the challenges faced by kidney transplant recipients (KTRs) in mounting effective immune responses against COVID-19. By evaluating the antibody responses to a third dose of monovalent mRNA COVID-19 vaccine and its effectiveness against Omicron subvariants (BA.1 and BA.5), this study reveals significant reductions in both binding and neutralizing antibodies in KTRs compared to healthy controls. The research highlights altered IgG subclass switching and heterogeneous responses within the KTR population. Reduced recognition of variants, coupled with differences in IgG subclasses, decreases both the quality and quantity of protective antibodies after vaccination in KTRs. These findings underscore the need for tailored vaccination strategies for immunosuppressed populations such as KTRs. Alternative formulations and doses of COVID-19 vaccines should be considered for people with severely compromised immune systems, as more frequent vaccinations may not significantly improve the response, especially regarding neutralizing antibodies.

OBJECTIVE:Incidence and manifestations of postacute sequelae of coronavirus disease 2019 (PASC) are poorly defined among immunosuppressed populations. We reported, phenotyped, and assessed risk factors for PASC in adults with systemic autoimmune diseases. METHODS:Persons aged ≥ 18 years with systemic autoimmune diseases were recruited into a national, prospective observational cohort of SARS-CoV-2 vaccination and infection between December 2020 and April 2021. Serial surveys assessed vaccination status, SARS-CoV-2 infection incidence, and disease flares. Participants reporting SARS-CoV-2 infection received a questionnaire assessing symptom duration, severity, and quality of life (QOL) effect; PASC was defined as ≥ 1 symptom persisting for > 12 weeks. PASC syndromes were mapped by overlapping symptom domains. Characteristics were compared between participants who did vs did not report PASC. RESULTS:= 0.004). CONCLUSION/CONCLUSIONS:In a large, real-world cohort, 29.8% of persons with systemic autoimmune disease reported PASC, often affecting QOL. Preceding vaccination may reduce PASC, whereas multiple infections may increase risk, supporting ongoing booster vaccine campaigns and efforts to limit breakthrough infections.