Faculty Bibliography

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.

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.

The prevalence of comorbid metabolic dysfunction-associated steatotic liver disease (MASLD) and obesity has increased exponentially over the last several years, with current estimates demonstrating that up to 40% of adults in the United States have MASLD. Metabolic associated steatohepatitis (MASH) is now a leading indication for liver transplantation and rates of obesity and MASLD pre- and post-transplant are on the rise. Our understanding of the physiology of obesity and metabolic disease and the availability of effective obesity treatments has evolved over the same time frame. With the availability of new anti-obesity medications (AOM), there has been a debate over the role of pharmacotherapy versus interventional approaches in the treatment of obesity and MASLD in the liver transplantation population. In October 2024, the American Society of Transplantation (AST) Liver and Intestinal Community of Practice held a virtual Controversies Conference on obesity and liver transplantation. Experts in the field presented the available data and smaller working groups had interactive breakout sessions that identified knowledge gaps and developed recommendations. This perspective prepared on behalf the participants of the AST Controversies Conference on obesity and liver transplant aims to summarize the available evidence for surgical and pharmaceutical treatment in the liver transplantation population.

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.

There is growing kidney transplant program-level interest in addressing obesity. The American Society of Transplantation Kidney Pancreas Community of Practice Obesity Work Group surveyed U.S. programs to characterize evaluation, listing, and weight management practices. A web-based survey was administered to professionals involved in kidney transplant care (transplant nephrologists/surgeons/coordinators/dietitians, endocrinologists, bariatric surgeons, obesity medicine specialists) from 5-9/2024. The 275 respondents from 113 programs represented 70.7% of U.S. transplant volume. A body mass index (BMI) cutoff-commonly 40 kg/m²-is used for evaluation/listing at 72.5%/74.3% of programs. For recipients, BMI 40 kg/m² was the most common threshold for referral for medical and surgical weight loss. Most (73.4%) programs have a weight management programs within their institution; 19.4% have a program integrated into their transplant program. One of the most common reasons for not referring for weight management was a preference that primary care providers/general nephrologists manage this, particularly pre-transplant. 27.6% of programs offer robotic kidney transplantation; 38.5% offer it only to patients above a BMI threshold (32-40 kg/m²). Obesity management is heterogeneous. Most use a BMI cutoff-typically 40 kg/m²-for evaluation and listing. These data provide the most comprehensive and contemporary overview of practices at U.S. programs.

INTRODUCTION/BACKGROUND:GLP-1 receptor agonists (GLP1-RAs) are increasingly prescribed as an alternative to bariatric surgery for weight loss, and may pose as an alternative to conversion Roux-En-Y Gastric Bypass (cRYGB) in patients with insufficient weight loss or weight recurrence after sleeve gastrectomy [A C, N C, A I. Postoperative morbidity and weight loss after revisional bariatric surgery for primary failed restrictive procedure: a systematic review and network meta-analysis. International Journal of Surgery; 2022;Jensen et al. in Obes Surg 33:1017-1025, 2023; Jamal et al. in Obes Surg 34:1324-1332, 2024; Lautenbach A, Wernecke M, Stoll FD, Meyhöfer SM, Meyhöfer S, Aberel J. 1422-P: The potential of semaglutide once-weekly in patients without Type 2 Diabetes with weight regain or insufficient weight loss after bariatric surgery. Diabetes 2022; 71(Supplement_1);]. METHODS AND PROCEDURES/METHODS:Adult patients ≥ 18 years old, who previously underwent a sleeve gastrectomy and were subsequently treated with weekly injectable Semaglutide or Tirzepatide, or treated with conversion from sleeve gastrectomy were included for analysis. Patients converted for GERD, GLP1-RA use with BMI ≤ 35, or pre operative GLP1-RA use were excluded. Post operative weights and Hgb A1C were assessed from 3 months to 3 years post intervention (start of GLP1-RA or surgery). T-test, ANOVA, and chi-squared analysis were used to compare groups, while multivariable linear regression analysis was used to evaluate the effect of bariatric surgery on %TBWL at 3 years post intervention when adjusting for baseline characteristics. RESULTS:4901 patients were included for analysis (3004 cRYGB, 1897 GLP1-RA). There was no difference in pre-intervention weight (242.8 ± 44.4 GLP1-RA vs 242.3 ± 57.8 cRYGB, p = .993). cRYGB patients had a higher baseline Hgba1c (6.19 ± 1.4 vs 5.85 ± 1.2, p < 0.001). cRYGB was associated with significantly greater weight loss at all post operative time points up to 3 years post intervention, (26.1 vs 13.7%, p < 0.001). There was no significant difference in Hgba1c control between treatments at all post intervention time points (all p > 0.05). In the multivariate linear regression analysis, when adjusting for sex, baseline BMI, baseline age, and non-white race, cRYGB was associated with an 11% greater %TBWL compared to those who were treated with a GLP1-RA. CONCLUSIONS:For patients who have had insufficient weight loss or weight recurrence following sleeve gastrectomy, conversion to RYGB offers greater, long-term weight loss compared to GLP1-RAs.

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.

PURPOSE OF REVIEW/OBJECTIVE:We provide a review on the incidence, consequences, and management of obesity in patients before and after pancreas transplant. RECENT FINDINGS/RESULTS:Obesity is common in patients with both type 1 and type 2 diabetes. Obesity at the time of pancreas transplant is associated with worse graft and patient survival, while weight gain after transplant is associated with insulin resistance and posttransplant diabetes. Currently, lifestyle interventions are the backbone of obesity management and can improve insulin sensitivity, but result in only modest weight loss. Metabolic and bariatric surgery (MBS) offers the potential for substantial and durable weight loss. Laparoscopic sleeve gastrectomy is the procedure of choice and can be performed safely both before and after pancreas transplant. Antiobesity medications (AOMs) may also be effective, but concerns remain regarding determine the safety and efficacy when used in pancreas transplant recipients. More evidence is needed to guide the use of AOMs and MBS in pancreas transplant recipients. SUMMARY/CONCLUSIONS:Lifestyle interventions, MBS, and AOMs each have a role in managing obesity after pancreas transplantation. In light of limited evidence and unique challenges in pancreas transplant patients, obesity management in pancreas transplant patients requires an individualized approach that leverages multidisciplinary expertise.