Faculty Bibliography

BACKGROUND:on dementia may be more severe in this population. METHODS:and dementia risk factors using a Wald test. Models were adjusted for confounders, including social determinants of health. RESULTS:was associated with 1.90-fold higher odds of global cognitive impairment (95% CI: 1.48-2.46), and 3.29-fold higher risk of dementia (95% CI: 1.14-9.55). CONCLUSION/CONCLUSIONS:neighborhoods should discuss cognitive assessments and ways to increase physical activity with providers.

BACKGROUND:Frail kidney transplant (KT) candidates, characterized by low physical activity/function, have decreased chances of listing and increased risk of waitlist mortality. Impairments in these physical domains contribute to perceived physical burden and may exacerbate one another. Further, understanding the association of each domain individually with adverse outcomes may improve pre-KT risk stratification. METHODS:We leveraged 2708 KT candidates (age ≥ 18) from a two-center prospective cohort study (2014-2024). We assessed physical activity (Minnesota Leisure Time Physical Activity Questionnaire), physical function (gait speed), and physical burden (10 questions from the Kidney Disease Quality of Life Short Form) at evaluation. We quantified the association of these three physical domains with listing (Cox proportional hazards) and waitlist mortality (competing risks, Harrell's C-statistic). RESULTS:Among 2708 candidates, 40% had low physical activity, 16% had low physical function, and 54% had high physical burden. Candidates with impairment in these three physical domains were less likely to be listed (activity: adjusted hazard ratio [aHR] = 0.86, 95% confidence interval [CI]: 0.75-0.99; function: aHR = 0.54, 95%CI: 0.45-0.64; burden: aHR = 0.75, 95%CI: 0.67-0.83) and had a higher risk of waitlist mortality (activity: adjusted sub-hazard ratio [aSHR] = 1.51, 95%CI: 1.11-2.04; function: aSHR = 1.83, 95%CI: 1.30-2.58; burden: aSHR = 1.40, 95%CI: 1.09-1.82). Physical burden showed the best discrimination in predicting mortality after adjustment (Harrell's C-statistic = 0.6899). CONCLUSION/CONCLUSIONS:Although impairment in physical activity, function, and burden was all associated with KT listing and waitlist mortality, physical burden was the strongest predictor of waitlist mortality. KT centers should consider measuring physical burden - a simple, low-cost tool to help identify high-risk candidates for prehabilitation.

BACKGROUND/UNASSIGNED:; environmental injustice) by racial/ethnic segregation (social injustice) on dementia diagnosis in ESKD. METHODS/UNASSIGNED:concentrations (annualized and matched to older adults' residential ZIP code at dialysis initiation) and by segregation scores (Theil's H method). FINDINGS/UNASSIGNED:and segregation. INTERPRETATION/UNASSIGNED:experienced an increased risk of dementia; this risk was particularly pronounced among individuals in high segregation and predominantly minority neighborhoods. Environmental and social injustices likely drive racial and ethnic disparities in dementia for older adults with ESKD, underscoring the need for interventions and policies to mitigate these injustices. FUNDING/UNASSIGNED:National Institutes of Health.

BACKGROUND:Glucagon-like peptide-1 receptor agonists (GLP1RA) provide survival benefits in people with diabetes, including kidney transplant (KT) recipients with pre-existing diabetes. Post-transplant diabetes mellitus (PTDM) is common, but the benefits of GLP1RAs remain undefined in this population. We aim to describe current usage practices and outcomes in PTDM. METHODS:We used USRDS and Medicare claims data (2013-2022) to conduct a drug utilization profile of GLP1RA among 7681 first-time adult KT recipients with PTDM. We used survival analysis to estimate GLP1RA initiation incidence and associated patient, graft, and safety outcomes. RESULTS:A total of 430 adult KT recipients with PTDM were prescribed GLP1RA. Dulaglutide was the most commonly prescribed medication (46.1%). The 5-year cumulative incidence of GLP-1 receptor agonists prescription was 9.8%. Median (interquartile range) time from PTDM diagnosis to first prescription was 1.7 (0.6, 3.4) years. GLP1RA use was not associated with a difference in the risk of mortality or graft failure but was associated with a 1.80-fold (95% confidence interval [CI]: 1.11-2.91) increased risk of diabetic retinopathy. No increased risk of pancreatitis, biliary complications, or medullary thyroid cancer were identified. CONCLUSIONS:GLP1RA use in KT recipients with PTDM was not associated with graft or patient survival, though longer follow-up is necessary. GLP1RA use was associated with an increased risk of diabetic retinopathy, and care should be taken when initiating these agents.

Community input enhances the impact of research. Yet, there are challenges when eliciting community perspectives in nephrology/transplant research: recruitment of patients across a wide spectrum of familiarity with kidney disease; a lack of trust from marginalized patients because of health care barriers, institutionalized structural racism, and historical harm; and retention of members facing high burden of care. To address these challenges, we drafted a mission and formed a community advisory board to provide input on nephrology/transplant research. We worked with kidney disease community organizations that prioritize diversity and equity to recruit members with chronic kidney disease, end-stage kidney disease, or a kidney transplant, as well as nephrology/transplant caregivers and kidney donors. We formed a diverse group of 9 members and received feedback on 5 research proposals over 4 quarterly meetings, bridging a communication gap between community perspectives and researchers. The collaborative environment stimulated feedback that improved our nephrology/transplant research to reflect the perspectives of those most affected by research findings. Eight members have remained active for more than 1 year. In this collaborative paper, we describe our process of forming a nephrology/transplant community advisory board, and participants highlight the benefits of sharing their lived experiences to improve and amplify the impact of nephrology/transplant research.

INTRODUCTION/BACKGROUND:Early post-kidney transplant (KT) changes likely impact body composition, resulting in adverse post-KT outcomes. We estimated post-KT trajectories of computed tomography (CT)-based muscle quantity/quality and tested whether they were associated with mortality and death-censored graft loss (DCGL) among frail and nonfrail recipients. METHODS:We leveraged a cohort of 294 adult KT recipients (December 2008-February 2020) with CT measurements (muscle quantity: skeletal muscle index; muscle quality: skeletal muscle radiation attenuation). We used mixed linear regression models to estimate 3-year post-KT muscle quantity/quality trajectories. Cox proportional hazard models quantified the association between time-varying pre-/post-KT muscle mass measurements and post-KT mortality and DCGL. RESULTS:) was associated with elevated mortality risk (aHR: 2.00, 95% CI: 1.08-3.70), but not among nonfrail recipients. Among older (≥65 years) recipients, lower muscle quantity was associated with increased DCGL risk (aHR: 2.70, 95% CI: 1.04-7.04), but not among younger recipients. Lower muscle quality (per 10 HU) was associated with elevated mortality (aHR: 2.23, 95% CI: 1.61-3.08) and DCGL (aHR: 1.90, 95% CI: 1.16-3.12) risk. CONCLUSION/CONCLUSIONS:Lower pre-/post-KT muscle quantity/quality were associated with higher risks of post-KT adverse outcomes. Pre-/post-KT rehabilitation to improve muscle quantity/quality may be an effective clinical intervention to minimize risks of adverse post-KT outcomes.

IMPORTANCE/UNASSIGNED:Total particulate matter with a diameter of 2.5 µm or less (PM2.5) has been found to be associated with adverse posttransplant outcomes among kidney transplant (KT) recipients. However, PM2.5 is a complex mixture of multiple constituents, all of which have different toxicity profiles, so it is not clear which constituents are most associated with adverse outcomes among KT recipients. OBJECTIVE/UNASSIGNED:To investigate the associations between PM2.5 constituents and post-KT outcomes among KT recipients. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cohort study was conducted among patients who received a KT between January 2000 and December 2016 and lived in the contiguous United States. Follow-up continued through December 2021, and data were analyzed from August 2023 to May 2025. EXPOSURES/UNASSIGNED:Fifteen PM2.5 constituents (including elemental carbon, ammonium, nitrate, organic carbon [OC], sulfate [SO42-], bromine, calcium, copper, iron, potassium, nickel [Ni], lead [Pb], silicon, vanadium, and zinc) at the zip code of residence prior to KT, estimated from ensembled machine learning models. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Adverse post-KT outcomes included acute rejection, delayed graft function (DGF), death-censored graft failure (DCGF), and mortality. The association of PM2.5 constituents and the outcome were evaluated with weighted quantile sum regressions. RESULTS/UNASSIGNED:In total, 192 587 KT recipients were included in the analysis (mean [SD] age at transplant, 51.56 [13.47] years; 75 021 [39.0%] female; 51 455 [26.7%] Black, 28 586 [14.8%] Hispanic, and 97 927 [50.8%] White). Each decile increase in the PM2.5 constituent mixture was associated with a 6.8% (95% CI, 5.8%-7.8%) and 3.6% (95% CI, 2.1%-5.1%) increase in the odds of DGF and acute rejection, respectively. OC and Ni contributed the largest weights to the observed association between PM2.5 mixture and DGF (OC: relative importance, 35.6%; Ni: relative importance, 34.4%), while Pb had the largest impact on acute rejection (relative importance, 75.0%). Each decile increase in PM2.5 constituent mixture was associated with a 4.7% (95% CI, 3.3%-6.3%) and 3.9% (95% CI, 2.5%-5.2%) increase in the hazard of DCGF and all-cause mortality, respectively. The constituent that contributed the largest weight to the observed association between PM2.5 mixture and long-term post-KT outcomes was SO42- (relative importance, 51.3%). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this cohort study, PM2.5 constituents were associated with an increased risk of adverse posttransplant outcomes among KT recipients. Of the PM2.5 constituents included in this study, SO42- contributed most to long-term outcomes, while Pb, OC, and Ni were more associated with short-term outcomes.

BACKGROUND/UNASSIGNED:) and long-term premature cognitive aging. We tested whether CMV was associated with post-KT cognitive impairment. METHODS/UNASSIGNED:In a 2-center prospective cohort study of 574 KTRs (mean age: 54.7 y), we obtained CMV donor/recipient (D/R) serostatus and measured pre- and post-KT cognitive function using the Modified Mini-Mental State Examination. We estimated post-KT global cognitive function trajectories by CMV serostatus using adjusted mixed effect models with linear spline terms. RESULTS/UNASSIGNED:(slope = 0.01 points/year; 95% CI, -1.87 to 1.89). CONCLUSIONS/UNASSIGNED:KTRs may be at elevated risk for post-KT cognitive impairment; clinicians may prioritize early interventions in this population.

Older (aged ≥55 years) kidney transplant (KT) recipients diagnosed with a sleep disorder after transplantation may be at increased risk for developing dementia. Using the United States Renal Data System/Medicare claims (2010-2020), we identified 16 573 older KT recipients with a functioning graft 1-year post-KT. First-time sleep disorders and newly prescribed sleep medications were ascertained within the first year post-KT. We used cause-specific hazard models to estimate the adjusted hazard ratio of diagnosed dementia with inverse probability of treatment weights. Overall, 3615 (21.8%) KT recipients were newly diagnosed with sleep disorders. Recipients diagnosed with a sleep disorder had a 1.32-fold increased risk for dementia (95% CI:1.15-1.51); those with insomnia had a 1.56-fold increased risk (95% CI:1.20-2.03). Of those diagnosed with insomnia, only 7.5% underwent cognitive behavioral therapy for insomnia. Of the recipients, 12.9% with a sleep disorder were prescribed sleep medications. Recipients prescribed sleep medication had a 1.44-fold increased risk for dementia (95% CI:1.16-1.77). Those prescribed zolpidem, the most commonly prescribed medication (80.1%), had a 1.41-fold increased risk (95% CI:1.12-1.78) for dementia; those prescribed other sleep medications had 3.13-fold (95% CI:1.41-6.98) increased risk for dementia. Post-KT sleep disorders are modifiable dementia risk factors; medication-associated dementia risk should be weighed against other therapies such as cognitive behavioral therapy for insomnia during management.