Faculty Bibliography

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are incretin-based therapies with demonstrated efficacy in glycaemic control, weight reduction and cardiovascular and renal protection. Although data in kidney transplant recipients (KTRs) remain limited, the high prevalences of overweight and obesity, post-transplant diabetes mellitus and cardiovascular disease in this population make GLP-1RAs a promising therapeutic strategy. This narrative review outlines the rationale for their use in KTRs, drawing from recent trials in non-transplant populations and emerging real-world evidence in KTRs. We summarize key clinical considerations, including patient selection, dose escalation and monitoring strategies, as well as existing retrospective and prospective studies examining safety and efficacy in the post-transplant setting. Available data suggest that GLP-1RAs are generally well tolerated, without clear evidence of increased risk for graft rejection, acute pancreatitis or interaction with immunosuppressive agents. However, gastrointestinal side effects and early discontinuation remain common, emphasizing the need for tailored counselling and dose titration. Importantly, the current evidence is constrained by small sample sizes, short follow-up and potential selection bias; these limitations lessen the certainty of safety and effectiveness estimates. Translational inferences from non-transplant trials (e.g. SELECT, FLOW, SMART) should also be made cautiously. Future studies should investigate long-term graft outcomes, changes in body composition and optimal integration with immunosuppressive regimens. A clear research agenda prioritizing graft survival, cardiovascular and kidney outcomes, quality of life, cost-effectiveness and patient-reported outcomes-ideally via randomized, multicentre or registry-based pragmatic designs-will be critical. As GLP-1RAs become increasingly accessible and clinically relevant, a multidisciplinary and patient-centred approach is essential to guide their safe and effective use in KTRs. This narrative review provides a framework for thoughtful clinical application and highlights areas for future investigation.

Obesity is highly prevalent among patients with end-stage kidney disease (ESKD) and remains a major barrier to kidney transplantation, the optimal kidney replacement therapy for improving survival and quality of life. Weight loss strategies tailored to the ESKD population are urgently needed to expand access. This review examines the role of lifestyle interventions, pharmacotherapy, and bariatric surgery in supporting transplant candidacy. While lifestyle modification is foundational, its effectiveness in ESKD is limited by metabolic, physical, and psychosocial barriers. Pharmacologic agents, particularly glucagon-like peptide-1 receptor agonists, offer promising weight loss and metabolic benefits, though access and safety data in ESKD remain limited. Bariatric surgery, increasingly performed in this population, provides durable weight loss, especially for patients requiring ≥20% reduction in weight to meet transplant body mass index criterion. We also highlight systemic barriers, including payer policies, program-level variability, and disparities in access, that shape patient outcomes. An integrated approach combining clinical strategies with supportive policies is essential to reduce inequities and expand timely access to kidney transplantation for patients with ESKD and obesity.

Liver transplant (LT) recipients experience a wide range of comorbidities, leading to frequent healthcare encounters. Until now, national registries, which have limited exposures and outcomes, and laborious small cohort studies have been the main data sources for LT research. Cosmos database offers electronic health record (EHR)-based insights into LT recipients at the national level with granular data. We evaluated if Cosmos data is representative of the entire US LT recipient population. Using Cosmos (N=20,235) and the national Scientific Registry of Transplant Recipients (SRTR) (N=51,281), we identified adult, first-time LT recipients between 7/2016-12/2022. We compared demographics, clinical data, and mortality across datasets, calculating Kaplan-Meier survival estimates and multi-variable Cox regressions. Recipient characteristics were highly comparable (e.g., female: Cosmos=36.5% vs. SRTR=36.4%, Black: 6.8% vs. 7.2%; BMI: 28.5 kg/m2 [24.8-32.9] vs. 28.2 [24.6-32.4]). Lab values were similar across cohorts, including MELD (24 [17-30] vs. 23 [16-30]). Transplant indications, donor characteristics, and 5-year survival (Cosmos 83.1% [82.3-83.8) vs. SRTR 80.9% [80.4-81.3]) were similar. The associations of clinical factors with survival were similar across both groups. Cosmos database demonstrated acceptable generalizability to the general US LT recipient population, which may advance LT research through a better understanding about LT recipients' experiences and outcomes.

BACKGROUND:Extended-course enoxaparin is increasingly used after bariatric surgery to prevent venous thromboembolism (VTE), the leading cause of death after bariatric surgery. Direct oral anticoagulants are widely used for extended thromboprophylaxis outside of bariatric surgery and offered to patients in our program who cannot tolerate or obtain enoxaparin. We evaluated the safety and efficacy of apixaban 2.5 mg twice daily relative to a weight-based dose of enoxaparin 40 mg or 60 mg twice daily for 30 days after discharge following sleeve gastrectomy. METHODS:Patients aged ≥18 years who underwent laparoscopic sleeve gastrectomy from 2019 to 2024 at a single high-volume urban academic center were included. Bleeding and thrombosis outcomes within 30 days were compared between patients receiving enoxaparin 40 mg twice daily or apixaban 2.5 mg twice daily. Weighted modified Poisson analyses were used to obtain covariate balance and assess differences in bleeding and thrombosis events. RESULTS:A total of 5921 patients were included for analysis (5274 enoxaparin 40 mg twice daily, 486 enoxaparin 60 mg twice daily, and 161 apixaban 2.5 mg twice daily). The 30-day thrombosis rate was significantly lower with enoxaparin versus apixaban (.1% versus 1.9%, P < .001). The composite outcome (VTE, portomesenteric venous thrombosis, and major/minor bleeding) was also significantly lower with enoxaparin versus apixaban (1.7% versus 5.6%, P < .01). In adjusted analyses, apixaban was associated with a relative risk of 12.09 for thrombosis (95% confidence interval [CI], 5.71-31.18), 1.93 for bleeding (95% CI, 1.27-3.00), and 2.59 (95% CI, 2.06-3.27) for any adverse outcome relative to enoxaparin. CONCLUSION/CONCLUSIONS:Enoxaparin is associated with both lower thrombosis and bleeding rates compared with apixaban for extended thromboprophylaxis after sleeve gastrectomy.

INTRODUCTION/BACKGROUND:Following implementation of the U.S. Kidney Allocation System (KAS) in 2014, deceased donor kidneys with a kidney donor profile index (KDPI) < 35% are prioritized for allocation to pediatric candidates. Early post-KAS data suggested this prioritization may have led to more frequent delayed graft function compared to pre-KAS, when pediatric allocation priority was based on donor age < 35 years. We sought to understand the impact of this allocation change on longer-term pediatric kidney transplant outcomes. METHODS:We used SRTR data to identify all deceased donor kidney transplants with pediatric recipients during two eras: "Pre-KAS" (12/1/2009-11/30/2014) and "KAS" (12/1/2015-11/30/2020). We used Cox proportional hazards models to calculate the association between study era and all-cause graft failure (graft failure or death) after adjusting for recipient characteristics. RESULTS:, p = 0.001). Results were similar in sensitivity analyses limited to recipients < 10 years old and recipients alive with a functioning graft 90 days post-transplant. CONCLUSIONS:KDPI-based prioritization of kidneys for pediatric allocation was associated with a lower risk of graft failure compared to donor age-based prioritization. Further refining donor risk scores may enable additional improvements in graft survival.

PURPOSE OF REVIEW/OBJECTIVE:Nearly half of all patients listed for kidney transplant now have obesity, which is associated with increased rates of perioperative complications and graft loss. Here, we provide an update on the management of obesity in patients with end-stage kidney disease (ESKD). RECENT FINDINGS/RESULTS:Lifestyle interventions are the backbone of obesity therapy but may be challenging to implement in transplant candidates due to dietary and activity limitations associated with ESKD and hemodialysis. Antiobesity medications (AOMs) acting on the glucagon-like peptide-1 receptor can result in weight loss up to 22% of total body weight, but evidence in ESKD is limited and their long-term use is limited by a high burden of gastrointestinal side effects and inconsistent insurance coverage. In terms of metabolic and bariatric surgery (MBS), the procedure of choice in transplant candidates is sleeve gastrectomy, which can result in weight loss up to 23% at 1 year and is associated with a lower risk of malabsorption and late complications, and possibly improved mortality compared to Roux-en-Y gastric bypass. SUMMARY/CONCLUSIONS:Lifestyle interventions, AOMs, and MBS are important options for transplant candidates with obesity, but more evidence is needed to define optimal treatment pathways involving AOMs and MBS in this population.

PURPOSE OF REVIEW/OBJECTIVE:To review anti-obesity pharmacotherapy options and data to guide use in liver and kidney transplant recipients. RECENT FINDINGS/RESULTS:) and concurrent disorders continues to grow. Up to 40% of liver and 33% of kidney recipients have obesity at transplant. Post-transplant weight gain is multi-factorial and common. Additionally, obesity and weight gain lead to lower allograft survival, increased cardiovascular risk, and decreased patient survival. Despite the high-risk population, anti-obesity medication use has not been widely studied or used in transplant recipients. Nutrient-stimulated hormones (NuSH) medications (glucagon-like peptide-1 receptor [GLP-1] agonists and dual agonists (GLP-1 and glucose-dependent insulinotropic polypeptide [GIP] receptor agonists) are highly effective agents for obesity treatment and cardiovascular event risk reduction in the general population and have spurred interest in obesity management in the transplant community. Data from randomized, placebo-controlled trials and integration of obesity medication expertise into routine care for transplant recipients is key to ensure improvement in long-term graft and patient survival.

BACKGROUND:Sarcopenia and myosteatosis are indicators of abnormal body composition (BC). Computed tomography (CT) imaging has proven to be an accurate modality for BC quantification in kidney transplantation (KT). We tested whether pre-KT CT-based BC was associated with both all-cause graft loss (ACGL) and mortality among adult recipients from two centers (Johns Hopkins Hospital [JHH] and University Medical Center Groningen [UMCG]). METHODS:Patients who underwent a KT between 2003 and 2020 were followed for a median (interquartile range) follow-up of 6.4 (4.6-8.5) years at JHH and 6.3 (5.1-7.5) years at UMCG. Cox proportional hazard models were used to estimate the associations of BC with ACGL/ mortality. Fine and Gray regression analysis was performed to assess the association between BC and death-censored graft loss. Prior to KT, 49% of recipients had sarcopenia and 66% had myosteatosis. RESULTS:In total 608 patients were included from JHH (N= 294) and UMCG (N=314). Sarcopenia was not associated with post-KT outcomes. Myosteatosis was associated with a higher risk of ACGL (adjusted hazard ratio 1.78, 95%CI:1.08 - 2.93) and mortality (adjusted hazard ratio 2.35, 95%CI: 1.27 - 4.33) at JHH, but showed no significant association at UMCG after adjusting for confounders. Myosteatosis did not show a significant association with death-censored graft loss at both centers. CONCLUSION/CONCLUSIONS:Myosteatosis ascertained from existing CT scans could help identify recipients at higher risk for ACGL who may benefit most from prehabilitation.