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.

BACKGROUND/UNASSIGNED:Kidney transplant recipients are at risk for adverse health outcomes. Digital health tools such as wearable accelerometers and continuous glucose monitors (CGMs) can provide detailed, noninvasive tracking of health behaviors and measures, such as physical activity, sleep, and glucose levels, that may offer insights into future health concerns, such as posttransplant diabetes mellitus, cognitive health, and transplant rejection. However, there is limited evidence on the feasibility and acceptability of these devices in kidney transplant candidates older than 50 y. METHODS/UNASSIGNED:This observational cross-sectional pilot study aimed to examine the feasibility of 2 digital health tools: an accelerometer and a continuous glucose monitor. Participants were eligible for the study if they were living donor kidney transplant candidates, aged 50 y or older, had no known cognitive impairments, and could provide informed consent. Participants were asked to wear a CGM and an accelerometer for up to 14 d before their kidney transplant surgery. Device feasibility was quantified by (1) the total time the devices were worn, and (2) the validated System Usability Scale survey administered after the devices were returned. RESULTS/UNASSIGNED:20 participants enrolled in the study (mean age 64 ± 9 y, 25% women, 40% with type 2 diabetes). The median number of days of accelerometer and CGM wear were 7 (interquartile range, 6-10) d and 7 (interquartile range, 7-10) d, respectively. Ninety percent of participants reported a favorable opinion of both devices. Participants wore the CGM 100% of the time and the accelerometer 90% of the time, indicating high adherence. CONCLUSIONS/UNASSIGNED:The use of digital devices was acceptable among kidney transplant candidates aged older than 50 y, paving the way for larger studies to identify early digital biomarkers of health outcomes in this high-risk population.

BACKGROUND:Frailty is a multi-system syndrome of decreased physiologic reserve with high prevalence, early incidence, and prognostic significance in kidney disease. Apart from the Physical Frailty Phenotype (PFP), less is known regarding psychometric properties of other instruments. We critically appraise the validity and reliability of frailty instruments across the kidney disease continuum, acknowledge limitations, and highlight knowledge gaps. METHODS:Following PRISMA-ScR guidelines, we searched PubMed, EMBASE, Cochrane, CINAHL, Web of Science, ClinicalTrials.gov, and PsycInfo from website inception through 9/2024. Eligible studies applied a validated frailty instrument apart from the PFP to a kidney disease population. RESULTS:We identified 136 articles after screening 4,048 initial results. The most commonly cited instruments were the Clinical Frailty Scale (CFS; N=56), FRAIL Scale (N=30), and Edmonton Frail Scale (N=16). Most studies included adults receiving hemodialysis (N=85) and with chronic kidney disease (N=39). Median age ranges were 53-83 years. Most frailty instruments demonstrated predictive validity for mortality and hospitalizations. Concurrent validity was most frequently demonstrated between frailty and older age, female sex, greater comorbidities, and lower albumin. Seven studies reported reliability. While some instruments were feasible (CFS, FRAIL scale), their measurement could result in higher frailty prevalence compared to the PFP. Existing instruments do not capture the full spectrum of psychosocial and physiologic domains of frailty. CONCLUSIONS:The CFS demonstrates the strongest validity, apart from the PFP, although its use may result in higher measured frailty prevalence. Further research should test the feasibility of screening for frailty in clinical practice; the psychometric properties (i.e., responsiveness) of frailty instruments in younger adults, those with acute kidney injury, kidney transplant recipients, and those receiving conservative kidney management; and whether adding psychosocial and/or physiological markers improves frailty measurement validity. Addressing these gaps will facilitate wider frailty measurement in kidney disease research and aid adoption into practice.

INTRODUCTION/BACKGROUND:Elevated concentrations of air pollutants in residential neighborhoods are associated with poorer survival, cognitive, and cardiovascular health among older adults. Older kidney transplant (KT) recipients may be more vulnerable due to chronic immunosuppression and age-related co-morbidities. Therefore, we quantified the associations between pollutant concentrations and post-KT outcomes among older recipients. METHODS:]) were obtained from the Center for Air, Climate and Energy Solutions, and matched by ZIP code and year of KT. We used shared frailty models (cluster = state) to estimate the adjusted hazard ratios (aHR) of mortality and death-censored graft failure (DCGF) and competing risk models with cluster-robust standard errors to estimate the adjusted subhazard ratios (aSHR) of dementia and stroke by pollutant concentrations. RESULTS:concentrations were associated with a 3% (aSHR = 1.03, 95% CI: 1.00-1.07) and 4% higher risk of stroke (aSHR = 1.04, 95% CI: 1.02-1.07), respectively. CONCLUSION/CONCLUSIONS:Residence in neighborhoods with high concentrations of ambient air pollutants can worsen patient and graft survival, as well as increase the risk of stroke among older KT recipients. Early screening and interventions targeting older recipients living in such neighborhoods may be crucial for preserving cognitive and cerebrovascular health, as well as improving longitudinal quality of life.