Faculty Bibliography

BACKGROUND:Recent data suggest patients with graft failure had better access to repeat kidney transplantation (re-KT) than transplant-naive dialysis accessing first KT. This was postulated to be because of better familiarity with the transplant process and healthcare system; whether this advantage is equitably distributed is not known. We compared the magnitude of racial/ethnic disparities in access to re-KT versus first KT. METHODS:Using United States Renal Data System, we identified 104 454 White, Black, and Hispanic patients with a history of graft failure from 1995 to 2018, and 2 357 753 transplant-naive dialysis patients. We used adjusted Cox regression to estimate disparities in access to first and re-KT and whether the magnitude of these disparities differed between first and re-KT using a Wald test. RESULTS:Black patients had inferior access to both waitlisting and receiving first KT and re-KT. However, the racial/ethnic disparities in waitlisting for (adjusted hazard ratio [aHR] = 0.77; 95% confidence interval [CI], 0.74-0.80) and receiving re-KT (aHR = 0.61; 95% CI, 0.58-0.64) was greater than the racial/ethnic disparities in first KT (waitlisting: aHR = 0.91; 95% CI, 0.90-0.93; Pinteraction = 0.001; KT: aHR = 0.68; 95% CI, 0.64-0.72; Pinteraction < 0.001). For Hispanic patients, ethnic disparities in waitlisting for re-KT (aHR = 0.83; 95% CI, 0.79-0.88) were greater than for first KT (aHR = 1.14; 95% CI, 1.11-1.16; Pinteraction < 0.001). However, the disparity in receiving re-KT (aHR = 0.76; 95% CI, 0.72-0.80) was similar to that for first KT (aHR = 0.73; 95% CI, 0.68-0.79; Pinteraction = 0.55). Inferences were similar when restricting the cohorts to the Kidney Allocation System era. CONCLUSIONS:Unlike White patients, Black and Hispanic patients with graft failure do not experience improved access to re-KT. This suggests that structural and systemic barriers likely persist for racialized patients accessing re-KT, and systemic changes are needed to achieve transplant equity.

IMPORTANCE/UNASSIGNED:Cytomegalovirus (CMV) is associated with significant morbidity and mortality in solid organ transplant (SOT) recipients. The risk factors for CMV seropositivity in SOT recipients, including area-level social deprivation in the US, have not been fully characterized. OBJECTIVE/UNASSIGNED:To (1) evaluate CMV seroprevalence, (2) assess the recipient characteristics associated with CMV seropositivity, and (3) assess the association of area-level social deprivation index (SDI) scores with pretransplant CMV serostatus. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This retrospective cross-sectional analysis of the Scientific Registry of Transplant Recipients database included all adult (aged ≥18 years) SOT recipients from January 1, 2008, to May 31, 2022. Data were analyzed from April 10 to October 25, 2023. EXPOSURE/UNASSIGNED:Recipient characteristics and area-level SDI. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Multivariable generalized linear models were used to evaluate the association between (1) patient characteristics and CMV and (2) social deprivation (measured by SDI scores, which were assessed in quintiles, from lowest to highest) and CMV seropositivity. In addition, differences based on patient demographics and the transplanted organ(s) were evaluated. RESULTS/UNASSIGNED:Among the 389 288 SOT recipients included in the analysis, mean (SD) age was 53.3 (13.0) years; 63.0% were male, 21.4% were Black, 15.2% were Hispanic White, 56.2% were non-Hispanic White, and 62.7% were CMV seropositive. The mean (SD) age was higher among CMV seropositive (54.0 [12.7] years) compared with CMV seronegative (52.0 [13.5] years) patients. Seropositivity for CMV was higher among women (69.9%) than men (58.5%) and among Black (74.8%) and Hispanic White (80.2%) patients compared with non-Hispanic White patients (50.4%). Seropositivity for CMV was highest among kidney (64.5%), liver (63.6%), and kidney and liver (66.2%) recipients. Greater SDI scores were associated with greater CMV seropositivity, ranging from 51.7% for the least deprived to 75.5% for the most deprived quintiles (P < .001), independent of age, sex, or race. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this cross-sectional study, an association between SDI and CMV seropositivity was observed among SOT recipients, independent of age, sex, or race and ethnicity. To optimize posttransplant outcomes in CMV seropositive recipients, efforts targeting prevention of CMV reactivation need to be prioritized in these higher-risk populations.

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/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:Dietary restrictions for patients with end-stage kidney disease (ESKD) are burdensome. Kidney transplantation (KT) candidates who lack neighborhood resources and are burdened by dietary restrictions may have decreased access to KT. METHODS:In our two-center prospective cohort study (2014-2023), 2471 ESKD patients who were evaluated for KT (candidates) reported their perceived burden of dietary restrictions (not at all, somewhat/moderately, or extremely bothered). Neighborhood-level socioeconomic factors were derived from residential ZIP codes. We quantified the association of perceived burden of the dietary restrictions with a chance of listing using Cox models and risk of waitlist mortality using competing risks models. Then we tested whether these associations differed by neighborhood-level socioeconomic factors. RESULTS: = 0.02). The association between dietary burden and waitlist mortality did not differ by neighborhood-level healthy food access. CONCLUSION/CONCLUSIONS:The perceived burden of dietary restrictions is associated with a lower chance of listing for KT, and higher waitlist mortality only among candidates residing in neighborhoods with high food insecurity. Transplant centers should identify vulnerable patients and support them with nutrition education and access to food assistance programs.

Among patients awaiting kidney transplantation (KT), sexual dysfunction is common owing to end-stage kidney disease, but may improve post-KT. Leveraging a 2-center prospective study, 2422 adult KT candidates and 490 adult KT recipients (May 2014 to December 2023) were identified. Using the Kidney Disease Quality of Life Short Form, participants reported on the negative impact of sexual dysfunction due to end-stage kidney disease (ie, sexual bother) at KT evaluation, admission, and post-KT follow-ups. Using mixed-effect logistic regression models, we estimated odds and trajectories for odds of sexual bother. At evaluation, 46.1% of male and 29.6% of female candidates reported sexual bother; 39.0% and 34.5%, respectively, had been sexually active in the past 4 weeks. At admission, 53.8% male and 27.0% female recipients reported sexual bother; 41.6% and 41.8%, respectively, had been sexually active in the past 4 weeks. The estimated prevalence of sexual bother decreased during the first 3 years post-KT (odds ratio per year: 0.39; 95% CI: 0.25-0.60). Sexual activity increased and peaked 1-year post-KT. At 3 years post-KT, 48.9% of male and 50.0% of female recipients were sexually active. Sexual bother is common pre-KT and improves post-KT, and sexual activity increases post-KT. Sexual health is important and should be considered during KT management.

INTRODUCTION/BACKGROUND:Frailty and cognitive function are often measured during kidney transplant evaluation. However, patient perspectives on the ethical considerations of this practice are unclear. RESEARCH QUESTION/OBJECTIVE:What are patient perspectives on the use of aging metrics in kidney transplant decision-making? DESIGN/METHODS:One hundred participants who were evaluated for kidney transplantation and were enrolled in an ongoing prospective cohort study (response rate = 61.3%) were surveyed. Participants were informed of the definitions of frailty and cognitive impairment and then asked survey questions regarding the use of these measures of aging to determine kidney transplant candidacy. RESULTS:Participants (75.6%) thought it was unfair to prevent older adults from receiving a kidney transplant based on age, but there was less agreement on whether it was fair to deny frail (46.5%) and cognitively impaired (45.9%) patients from accessing kidney transplantation. Compared to older participants, younger participants had 5.36-times (95%CI:1.94-14.81) the odds of choosing a hypothetical younger, frail patient to list for kidney transplantation than an older, non-frail patient; they also had 3.56-times (95%CI:1.33-9.56) the odds of choosing the hypothetical frail patient with social support rather than a non-frail patient without social support. Participants disagreed on the use of patient age as a listing criterion; 19.5% ranked it as the fairest and 28.7% as the least fair. CONCLUSION/CONCLUSIONS:The patient views highlighted in this study are an important step toward developing ethical guidelines to ensure fair use of frailty, cognitive function, and chronological age for kidney transplant decision-making.

INTRODUCTION/UNASSIGNED:Uremic toxins contributing to increased risk of death remain largely unknown. We used untargeted metabolomics to identify plasma metabolites associated with mortality in patients receiving maintenance hemodialysis. METHODS/UNASSIGNED:We measured metabolites in serum samples from 522 Longitudinal US/Canada Incident Dialysis (LUCID) study participants. We assessed the association between metabolites and 1-year mortality, adjusting for age, sex, race, cardiovascular disease, diabetes, body mass index, serum albumin, Kt/Vurea, dialysis duration, and country. We modeled these associations using limma, a metabolite-wise linear model with empirical Bayesian inference, and 2 machine learning (ML) models: Least absolute shrinkage and selection operator (LASSO) and random forest (RF). We accounted for multiple testing using a false discovery rate (pFDR) adjustment. We defined significant mortality-metabolite associations as pFDR < 0.1 in the limma model and metabolites of at least medium importance in both ML models. RESULTS/UNASSIGNED:limma. CONCLUSION/UNASSIGNED:Quinolinate and mesaconate were significantly associated with a 1-year risk of death in incident patients receiving maintenance hemodialysis. External validation of our findings is needed.

BACKGROUND:Sarcopenia has been associated with adverse postoperative outcomes in older age cohorts, but has not been assessed in older adults with inflammatory bowel disease (IBD). Further, current assessments of sarcopenia among all aged individuals with IBD have used various measures of muscle mass as well as cutoffs to define its presence, leading to heterogeneous findings. METHODS:In this single-institution, multihospital retrospective study, we identified all patients aged 60 years and older with IBD who underwent disease-related intestinal resection between 2012 and 2022. Skeletal Muscle Index (SMI) and Total Psoas Index (TPI) were measured at the superior L3 endplate on preoperative computed tomography scans and compared through receiver operating characteristic curve. We then performed multivariable logistic regression to assess risk factors associated with an adverse 30-day postoperative outcome. Our primary outcome included a 30-day composite of postoperative mortality and complications, including infection, bleeding, cardiac event, cerebrovascular accident, acute kidney injury, venous thromboembolism, reoperation, all-cause rehospitalization, and need for intensive care unit-level care. RESULTS:A total of 120 individuals were included. Overall, 52% were female, 40% had ulcerative colitis, 60% had Crohn's disease, and median age at time of surgery was 70 years (interquartile range: 65-75). Forty percent of older adults had an adverse 30-day postoperative outcome, including infection (23%), readmission (17%), acute kidney injury (13%), bleeding (13%), intensive care unit admission (10%), cardiac event (8%), venous thromboembolism (7%), reoperation (6%), mortality (5%), and cerebrovascular accident (2%). When evaluating the predictive performance of SMI vs TPI for an adverse 30-day postoperative event, SMI had a significantly higher area under the curve of 0.66 (95% CI, 0.56-0.76) as compared to 0.58 (95% CI, 0.48-0.69) for TPI (P = .02). On multivariable logistic regression, prior IBD-related surgery (adjusted odds ratio [adjOR] 6.46, 95% CI, 1.85-22.51) and preoperative sepsis (adjOR 5.74, 95% CI, 1.36-24.17) significantly increased the odds of adverse postoperative outcomes, whereas increasing SMI was associated with a decreased risk of an adverse postoperative outcome (adjOR 0.88, 95% CI, 0.82-0.94). CONCLUSIONS:Sarcopenia, as measured by SMI, is associated with an increased risk of postoperative complications among older adults with IBD. Measurement of SMI from preoperative imaging can help risk stratify older adults with IBD undergoing intestinal resection.

BACKGROUND:As the inflammatory bowel disease (IBD) patient population is aging, the prevalence of polypharmacy is rising. However, data exploring the prevalence, risk factors, and clinical outcomes associated with polypharmacy among older adults with IBD are limited. AIMS/OBJECTIVE:To determine (i) prevalence of polypharmacy (≥5 medications) and potentially inappropriate medication (PIM) utilization in older adults with IBD, (ii) changes in medications over time (iii) predictors of polypharmacy, and (iv) the impact of polypharmacy/PIMs on one-year hospitalization rates. METHODS:We conducted a retrospective single-center study of older adults with IBD from September 1st 2011 to December 31st 2022. Wilcoxon-signed rank and McNemar's tests were used to assess changes in polypharmacy between visits, with ordinal logistic regression and Cox proportional hazards models used to determine risk factors for polypharmacy and time to hospitalization, respectively. RESULTS:Among 512 older adults with IBD, 74.0% experienced polypharmacy at initial visit, with 42.6% receiving at least one PIM. Additionally, severe polypharmacy (≥10 medications) was present among 28.6% individuals at index visit and increased to 38.6% by last visit (p<0.01). Multivariable analysis revealed that age ≥70 years, BMI ≥30.0 kg/m2, prior IBD-related surgery, and the presence of comorbidities were associated with polypharmacy. Moreover, severe polypharmacy (adjHR 1.95, 95%CI 1.29-2.92), as well as PIM use (adjHR 2.16, 95%CI 1.37-3.43) among those with polypharmacy, were significantly associated with all-cause hospitalization within a year of index visit. DISCUSSION/CONCLUSIONS:Severe polypharmacy was initially present in more than 25% of older adults with IBD and increased to 34% within 4 years of index visit. Severe polypharmacy, as well as PIM utilization among those with polypharmacy, were also associated with an increased risk of hospitalization at one-year, highlighting the need for deprescribing efforts in this population.