Faculty Bibliography

BACKGROUND:Given the cardiovascular, renal, and survival benefits of GLP-1 receptor agonists for diabetes, these agents could be effective among kidney transplant recipients. However, kidney transplant recipients are distinct from GLP-1 receptor agonist trial participants, with longer diabetes duration and severity, greater end-organ damage, increased cardiovascular risk, and multimorbidity. We examined GLP-1 receptor agonist real-world effectiveness and safety in kidney transplant recipients with diabetes. METHODS:This USA-based retrospective cohort study included kidney transplant recipients with type 2 diabetes at transplantation and Medicare as their primary insurance from a national registry linked with Medicare claims. Post-transplantation GLP-1 receptor agonist use was identified through Medicare claims. Death-censored graft loss was estimated using the Fine-Gray sub-distribution hazard model and extended Cox models were used for mortality and safety endpoints. Models incorporated inverse probability of treatment weights. To further test whether bias could affect the main results, a cohort was created in which each GLP-1 receptor agonist user was matched with a kidney transplant recipient who had not started a GLP-1 receptor agonist, was alive with a functioning graft, and had accrued the same amount of post-transplant survival time. FINDINGS/RESULTS:Between Jan 1, 2013 and Dec 31, 2020, we identified 44 536 first time kidney transplant recipients with Medicare as primary payer in the 6 months before and at transplantation. 24 192 patients were excluded as they did not have type 2 diabetes. 2328 patients were ineligible (1916 had missing values and 412 used GLP-1 receptor agonists before transplantation). The primary cohort thus consisted of 18 016 kidney transplant recipients with diabetes. Of these patients, 1969 (10·9%) had at least one GLP-1 receptor agonist prescription filled post-transplant. Compared with patients who had not received a GLP-1 receptor agonist, GLP-1 receptor agonist users were younger (median age at transplant 57 years [IQR 49-64] vs 60 years [51-66], p<0·0001) and more likely to be female (786 [39·9%] vs 5645 [35·2%], p<0·0001). Among GLP-1 receptor agonist users, 552 [28·0%] were non-Hispanic White, 703 [35·7%] were non-Hispanic Black, and 568 [28·8%] were Hispanic. The 5-year unadjusted cumulative incidence of death-censored graft loss from a cohort matched on survival time before GLP-1 receptor agonist initiation was 6·0% for GLP-1 receptor agonist users and 10·7% for non-users (Gray's test p=0·004). The 5-year unadjusted cumulative incidence for mortality from a cohort matched on survival time before GLP-1 receptor agonist initiation was 17·0% for GLP-1 receptor agonist users and 25·8% for non-users (log-rank p=0·0006). The 5-year unadjusted cumulative incidence for mortality was 13·5% for GLP-1 receptor agonist users and 19·9% for non-users (log-rank p<0·0001). GLP-1 receptor agonist use was associated with a 49% lower incidence of death-censored graft loss (adjusted subhazard ratio [aSHR] 0·51, 95% CI 0·36-0·71; p=0·0001) and 31% lower mortality (adjusted hazard ratio [aHR] 0·69, 95% CI 0·55-0·86; p=0·001). Inferences were robust when matched on survival time (death-censored graft loss aSHR 0·53, 95% CI 0·37-0·75; p=0·0005; mortality aHR 0·70, 95% CI 0·55-0·88; p=0·003). Safety endpoints were rare and not associated with GLP-1 receptor agonists, with the exception of diabetic retinopathy (aHR 1·49, 1·11-2·00; p=0·008). INTERPRETATION/CONCLUSIONS:GLP-1 receptor agonists were associated with better graft and patient survival. Clinical trials are needed to confirm these findings. FUNDING/BACKGROUND:National Institutes of Health.

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.

KEY POINTS:In frail kidney transplant (KT) candidates with obesity, unintentional weight loss preceding KT evaluation is associated with lower chance of listing. In frail candidates with obesity, both unintentional and intentional weight loss is associated with higher waitlist mortality. Results suggest that in frail candidates with obesity, careful supervision of weight loss prior to KT should be considered, emphasizing strategies to preserve muscle mass and function. BACKGROUND:Unintentional weight loss, a hallmark of frailty, predicts worse post–kidney transplantation (KT) outcomes. However, weight loss in candidates with obesity is often recommended to enhance transplant eligibility. We tested whether pre-evaluation weight change is associated with listing/waitlist mortality, considering intentionality and frailty. METHODS:) enrolled in a prospective multicenter cohort study. We estimated the association between pre-evaluation weight change (stable, gain, unintentional/intentional loss) with chance of listing/waitlist mortality using Cox proportional hazards/competing-risks models. RESULTS:Among candidates with obesity, 48% had stable weight, 17% had weight gain, 16% had unintentional weight loss, and 20% had intentional weight loss over the year before evaluation. Among frail candidates with obesity, stable weight was associated with a 27% lower chance of listing (adjusted hazard ratio [aHR], 0.73; 95% confidence intervals [CI], 0.55 to 0.96), weight gain with a 47% lower chance of listing (aHR, 0.53; 95% CI, 0.34 to 0.80), and unintentional weight loss with a 48% lower chance of listing (aHR, 0.52; 95% CI, 0.32 to 0.84) compared with nonfrail candidates with stable weight. However, in frail candidates with obesity, intentional weight loss was not associated with a significantly lower chance of listing compared with nonfrail candidates with stable weight. In addition, among frail candidates with obesity, stable weight (adjusted subhazard ratio [aSHR], 1.72; 95% CI, 1.01 to 2.90), unintentional weight loss (aSHR, 2.78; 95% CI, 1.23 to 6.27), and intentional weight loss (aSHR, 2.26; 95% CI, 1.05 to 4.85) were associated with higher waitlist mortality compared with nonfrail candidates with stable weight. Among nonfrail candidates, no associations were observed for weight change and frailty status with either chance of listing or waitlist mortality. CONCLUSIONS:Among frail candidates with obesity, unintentional pre-KT weight loss is associated with a lower chance of listing; however, any weight loss is associated with higher waitlist mortality. Our findings suggest that frail candidates with obesity may benefit from clinician supervision of pre-KT weight loss.

IMPORTANCE/UNASSIGNED:Identifying the mechanisms of structural racism, such as racial and ethnic segregation, is a crucial first step in addressing the persistent disparities in access to live donor kidney transplantation (LDKT). OBJECTIVE/UNASSIGNED:To assess whether segregation at the candidate's residential neighborhood and transplant center neighborhood is associated with access to LDKT. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:In this cohort study spanning January 1995 to December 2021, participants included non-Hispanic Black or White adult candidates for first-time LDKT reported in the US national transplant registry. The median (IQR) follow-up time for each participant was 1.9 (0.6-3.0) years. MAIN OUTCOME AND MEASURES/UNASSIGNED:Segregation, measured using the Theil H method to calculate segregation tertiles in zip code tabulation areas based on the American Community Survey 5-year estimates, reflects the heterogeneity in neighborhood racial and ethnic composition. To quantify the likelihood of LDKT by neighborhood segregation, cause-specific hazard models were adjusted for individual-level and neighborhood-level factors and included an interaction between segregation tertiles and race. RESULTS/UNASSIGNED:Among 162 587 candidates for kidney transplant, the mean (SD) age was 51.6 (13.2) years, 65 141 (40.1%) were female, 80 023 (49.2%) were Black, and 82 564 (50.8%) were White. Among Black candidates, living in a high-segregation neighborhood was associated with 10% (adjusted hazard ratio [AHR], 0.90 [95% CI, 0.84-0.97]) lower access to LDKT relative to residence in low-segregation neighborhoods; no such association was observed among White candidates (P for interaction = .01). Both Black candidates (AHR, 0.94 [95% CI, 0.89-1.00]) and White candidates (AHR, 0.92 [95% CI, 0.88-0.97]) listed at transplant centers in high-segregation neighborhoods had lower access to LDKT relative to their counterparts listed at centers in low-segregation neighborhoods (P for interaction = .64). Within high-segregation transplant center neighborhoods, candidates listed at predominantly minority neighborhoods had 17% lower access to LDKT relative to candidates listed at predominantly White neighborhoods (AHR, 0.83 [95% CI, 0.75-0.92]). Black candidates residing in or listed at transplant centers in predominantly minority neighborhoods had significantly lower likelihood of LDKT relative to White candidates residing in or listed at transplant centers located in predominantly White neighborhoods (65% and 64%, respectively). CONCLUSIONS/UNASSIGNED:Segregated residential and transplant center neighborhoods likely serve as a mechanism of structural racism, contributing to persistent racial disparities in access to LDKT. To promote equitable access, studies should assess targeted interventions (eg, community outreach clinics) to improve support for potential candidates and donors and ultimately mitigate the effects of segregation.

Kidney transplantation (KT) experts did not support the use of subjective unintentional weight loss to measure shrinking in the physical frailty phenotype (PFP); a clinically feasible and predictive measure of shrinking is needed. To test whether unintentional weight loss could be replaced by an assessment of sarcopenia using existing CT scans, we performed a prospective cohort study of adult KT recipients with original PFP (oPFP) measured at admission (December 2008-February 2020). We ascertained sarcopenia by calculating skeletal muscle index from available, clinically obtained CTs within 1-year pre-KT (male < 50 cm² /m² ; female < 39 cm² /m² ) and combined it with the original four components to determine new PFP (nPFP) scores. Frailty was classified by frailty score: 0: non-frail; 1-2: pre-frail; ≥3: frail. Mortality and graft loss hazard ratios (HRs) were estimated using adjusted Cox proportional hazard models. Model discrimination was quantified using Harrell's C-statistic. Among 1113 recipients, 18.6% and 17.1% were frail by oPFP and nPFP, respectively. Compared to non-frail recipients, frail patients by either PFP had higher risks of mortality (oPFP HR = 1.67, 95% CI: 1.07-2.62, C = 0.710; nPFP HR = 1.68, 95% CI: 1.06-2.66, C = 0.710) and graft loss (oPFP HR = 1.67, 95% CI: 1.17-2.40, C = 0.631; nPFP HR = 1.66, 95% CI: 1.15-2.40, C = 0.634) with similar discriminations. oPFP and nPFP are equally useful in risk prediction for KT recipients; oPFP may aid in screening patients for pre-KT interventions, while nPFP may assist in nuanced clinical decision-making.

IMPORTANCE/UNASSIGNED:Neighborhood segregation, a mechanism of structural racism, is associated with racial and ethnic disparities in health care access and outcomes. Live donor liver transplant (LDLT) is the ideal treatment for cirrhosis, improving survival and quality of life. Understanding the role of segregation in LDLT access is important to address disparities. OBJECTIVE/UNASSIGNED:To assess the associations between residential and transplant center neighborhood segregation and LDLT access. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cohort study used data from a US national transplant registry on adult candidates (age ≥18 years) for first-time liver transplant between February 1, 2016, and June 30, 2025, at centers that performed 1 or more LDLT annually during that time. EXPOSURE/UNASSIGNED:Residential and transplant center neighborhood segregation, measured using the Thiel H method at the zip code tabulation area level and dichotomized at the respective median values. MAIN OUTCOMES AND MEASURES/UNASSIGNED:A Cox proportional hazards regression model quantified the adjusted hazard ratio (AHR) of LDLT and included interactions with race and ethnicity and insurance. LDLT access within high-segregation residential neighborhoods by racial and ethnic composition (predominantly White or predominantly racial and ethnic minoritized population) was also quantified. RESULTS/UNASSIGNED:Among 22 223 adult liver transplant candidates, mean (SD) age was 55.3 (11.2) years, 13 518 (60.8%) were male, 1476 (6.6%) were Black, 5097 (22.9%) were Hispanic or Latino, and 15 650 (70.4%) were White. Most (11 669 [52.5%]) had private insurance. After adjustment, candidates residing in high-segregation neighborhoods had lower likelihood of LDLT access (AHR, 0.81; 95% CI, 0.74-0.88). Hispanic or Latino candidates in high-segregation neighborhoods had lower likelihood of LDLT access than their counterparts in low-segregation neighborhoods (AHR, 0.59; 95% CI, 0.49-0.72; P < .001 for interaction), but associations between neighborhood segregation and LDLT did not vary significantly by insurance type (P = .52 for interaction). Candidates wait-listed at transplant centers in high-segregation neighborhoods had lower likelihood of LDLT access (AHR, 0.64; 95% CI, 0.59-0.70). Candidates with Medicare or Medicaid wait-listed at centers in high-segregation neighborhoods had lower likelihood of LDLT access than their counterparts in low-segregation neighborhoods (AHR, 0.53; 95% CI, 0.45-0.51; P < .001 for interaction). Within high-segregation residential neighborhoods, candidates in neighborhoods with a larger racial and ethnic population had lower likelihood of LDLT access than those living in neighborhoods with a larger White population (AHR, 0.68; 95% CI, 0.59-0.78). CONCLUSION AND RELEVANCE/UNASSIGNED:In this national cohort study, living in or being wait-listed at centers in high-segregation neighborhoods was associated with lower likelihood of LDLT access and candidates living in high-segregation neighborhoods with a larger racial and ethnic minority population compared with a larger White population had lower likelihood of LDLT. Investing in high-segregation neighborhoods to address these structural disadvantages may help improve equity in LDLT access.

BACKGROUND/UNASSIGNED:Although technology usage is steadily increasing among older adults, adoption and confidence greatly lag behind their younger counterparts. Sociocultural and health disparities intersect with aging to present distinct structural and psychosocial barriers to the adoption of newer technologies. Digital health literacy interventions can improve task-specific skills, technological self-efficacy, and use frequency, but most do not systematically incorporate older adults' values and goals, which are key drivers of sustained behavior change. OBJECTIVE/UNASSIGNED:The proposed study aims to develop and evaluate the acceptability and feasibility of a person-directed, values-based, in-home digital literacy intervention for older adults, entitled values-informed solutions for technology adoption (VISTA). METHODS/UNASSIGNED:VISTA begins with a values and goals discussion rather than a skills test, mapping "What Matters Most" to individualized, SMART (specific, measurable, achievable, relevant, and time-bound) technology goals. Over 8 to 12 weeks, interventionists co-developed personalized learning plans with participants, delivering up to 6 in-home biweekly visits and interim phone calls. The study provided a tablet and assistance with obtaining home internet when needed. Outcomes included digital literacy (Mobile Device Proficiency Questionnaire), technology and chronic disease self-efficacy, social networks, multimorbidity, and frailty (Fried Frailty Phenotype). Feasibility was assessed via recruitment, retention or completion, data collection rates, survey administration time, withdrawal, intervention fidelity, and per-person cost; acceptability was assessed via a postintervention satisfaction survey (Likert and open-ended items) and willingness to recommend. RESULTS/UNASSIGNED:Funding was secured in November 2023. Institutional review board approval, intervention development, and focus groups were completed throughout 2024. Recruitment and baseline assessments occurred from January 2025 to July 2025, enrolling 21 participants and randomizing 11 to immediate intervention and 10 to waitlist control (waitlist participants received the intervention after a 3-month control period). One consented participant was unable to participate early in the intervention and is not included in analyses. Inclusion criteria included being aged 65 years and older, having English proficiency, and demonstrating a willingness to improve digital literacy. Exclusion criteria involved severe cognitive impairment. At baseline, participants had a mean age of 75.7 (SD 7.74) years and were predominantly female (n=13, 65%) and Black (n=19, 95%); most reported having a low income (10/12, 83%), living alone (12/14, 85.7%), and multimorbidity (mean disease count 3.95, SD 2.46). Follow-up assessments concluded in March 2026; data cleaning and analysis are ongoing, with primary feasibility and acceptability findings anticipated for fall 2026. CONCLUSIONS/UNASSIGNED:This protocol offers a unique model centering on the values and goals of older adults to improve access, use, and understanding of technology. Tapping into the motivators of older adults may provide a more beneficial way to encourage older adult technology use. VISTA could be useful in many general contexts, more specifically for older adults who are homebound or have serious illnesses, or as a preintervention for interventions involving advanced technology understanding.

INTRODUCTION/BACKGROUND:Hyperparathyroidism (HPT) commonly persists following kidney transplant (KT) and can result in bone alterations. However, the association between persistent HPT post-KT and fracture risk is not well-understood. We sought to quantify the association between persistent HPT at 1-year post-KT and fracture risk among KT recipients. METHODS:We leveraged a longitudinal prospective cohort of 344 adult KT recipients who underwent KT at a single institution (12/2008-07/2019). PTH levels were retroactively abstracted, and fractures after 1-year-post-KT were ascertained using ICD-9/ICD-10 codes. Competing risk models were used to estimate the association between persistent HPT (PTH ≥ 70 pg/mL) at 1-year post-KT and the risk of fracture, with death treated as a competing event. RESULTS:Among 344 KT recipients, 227 (66.0%) had persistent HPT at 1-year post-KT. After adjusting for confounders, HPT 1-year after KT was associated with a 3.11-fold increased risk of fractures (95% CI: 1.08-8.91). There were no differences in this association by age, sex, race, eGFR at 1-year-post-KT, osteoporosis at KT, or dialysis vintage. CONCLUSION/CONCLUSIONS:Recipients with HPT 1-year after KT had a significantly higher risk of fractures than those without persistent HPT. Future studies should establish standardized practice guidelines for the treatment of persistent HPT to mitigate fracture-related morbidity and mortality.