Faculty Bibliography

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.

[This corrects the article DOI: 10.1016/j.lana.2024.100895.].

Unauthorized immigrants and permanent residents may experience challenges in accessing kidney transplantation due to limited healthcare access, socioeconomic and cultural barriers. Understanding the United States (US) national landscape of kidney transplantation for non-citizens may inform policy changes. To evaluate this, we utilized two cohorts from the US national registry (2013-2023): 287,481 adult candidates for first transplant listing and 190,176 adult first transplant recipients. Citizenship was categorized as US citizen (reference), permanent resident, and presumed unauthorized immigrant. Negative binomial regression was used to quantify the incidence rate ratio over time by citizenship status. Cause-specific hazards models, with clustering at the state of listing/transplant, were used to calculate the adjusted hazard ratio of waitlist mortality, kidney transplant, and post-transplant outcomes (mortality/death-censored graft failure) by citizenship category. The crude proportion of presumed unauthorized immigrants listed increased over time (2013: 0.9%, 2023:1.9%). However, after accounting for case mix and waitlist size, there was no change in listing over time. Presumed unauthorized immigrants were less likely to experience waitlist mortality (adjusted Hazard Ratio 0.54, 95% Confidence Interval: 0.46-0.62), were more likely to obtain deceased donor kidney transplant (1.11: 1.05-1.18), but less likely to receive live donor (0.80: 0.71-0.90) or preemptive kidney transplant (0.52: 0.43- 0.62). When stratified by insurance status, presumed unauthorized immigrants on Medicaid were less likely to receive deceased donor kidney transplants compared to their citizen counterparts; however, presumed unauthorized immigrants with Private insurance or Medicare were more likely to receive deceased donor kidney transplants. Presumed unauthorized immigrants were less likely to experience post-transplant death (0.56: 0.43-0.69) and graft failure (0.69: 0.57-0.84). Residents had similar pre- and post-transplant outcomes. Despite the barriers to kidney transplantation faced by presumed unauthorized immigrants and residents in the US, better post-transplant outcomes for presumed unauthorized immigrants compared to citizens persisted, even after accounting for differences in patient characteristics.

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.

INTRODUCTION/BACKGROUND:Obesity prevalence has dramatically increased; candidates with obesity have higher waitlist mortality and are less likely to undergo liver transplantation. The association of obesity with post-transplant mortality is inconsistent. MATERIALS AND METHODS/METHODS:. Risks of waitlist and post-transplant mortality were quantified using adjusted competing risks and Cox proportional hazards. RESULTS:Of 103,640 candidates and 58,692 recipients, candidates with higher obesity classes had higher listing MELD that increased over time. Candidates with class III obesity were listed and transplanted at higher MELD compared to candidates without obesity, class I and II obesity; nearly 40% of candidates with class III obesity had listing MELD≥30. From 2013-2017 to 2018-2023, waitlist mortality decreased 35% in candidates with class III obesity (SHR:0.65(0.58-0.73),p<0.001) and post-transplant mortality decreased 20% for recipients with class III obesity (HR:0.80(0.66-0.96),p=0.02). However, over time, post-transplant mortality differed by obesity class with no reduction in post-transplant mortality for recipients with class I or II obesity. CONCLUSION/CONCLUSIONS:Candidates and recipients with class III obesity are being listed and transplanted at higher MELD scores with improvement in outcomes over time. Although higher risk, temporal trends for LT in this population are favorable. Given the higher disease severity at listing for candidates with class III obesity, referral patterns for LT evaluation in these patients should be evaluated.

Developing real-world evidence from electronic health records (EHR) is vital to advance kidney transplantation (KT). We assessed the feasibility of studying KT using the Epic Cosmos aggregated EHR dataset, which includes 274 million unique individuals cared for in 238 U.S. health systems, by comparing it with the Scientific Registry of Transplant Recipients (SRTR). We identified 69,418 KT recipients transplanted between January 2014 and December 2022 in Cosmos (39.4% of all US KT transplants during this period). Demographics and clinical characteristics of recipients captured in Cosmos were consistent with the overall SRTR cohort. Survival estimates were generally comparable, although there were some differences in long-term survival. At 7 years post-transplant, patient survival was 80.4% in Cosmos and 77.8% in SRTR. Multivariable Cox regression showed consistent associations between clinical factors and mortality in both cohorts, with minor discrepancies in the associations between death and both age and race. In summary, Cosmos provides a reliable platform for KT research, allowing EHR-level clinical granularity not available with either the transplant registry or healthcare claims. Consequently, Cosmos will enable novel analyses to improve our understanding of KT management on a national scale.

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.