Faculty Bibliography

OBJECTIVE:Directly compare the real-world effectiveness of semaglutide and tirzepatide to bariatric operations: sleeve gastrectomy and gastric bypass. METHODS:This study included adults with BMI ≥ 35 who received injectable semaglutide or tirzepatide (GLP-1RAs) or sleeve gastrectomy or gastric bypass (bariatric surgery) at two urban health systems from 2018 to 2024. Total weight loss (TWL) was compared up to 3 years post treatment with inverse probability weighting and mixed linear models. Intention-to-treat (any GLP-1RA) and per-protocol (1 year of continuous GLP-1RA orders) analyses were performed. RESULTS:Of 44,025 patients studied, bariatric surgery was associated with greater weight loss at 1, 2, and 3 years post treatment: semaglutide (n = 25,804) TWL (95% CI): 5.4% (5.3%-5.6%), 6.5% (6.4%-6.7%), and 7.4% (7.3%-7.6%); tirzepatide (n = 7308): 9.1% (8.9%-9.4%) and 10.8% (10.2%-11.3%); sleeve gastrectomy (n = 8728): 24.4% (24.3%-24.6%), 22.4% (22.3%-22.5%), and 22.0% (21.8%-22.1%); gastric bypass (n = 2185): 29.8% (29.7%-29.9%), 28.1% (28.0%-28.2%), and 28.4% (28.3%-28.5%). With 1 year of continuous GLP-1RA, findings were: semaglutide TWL: 7.2% (7.0%-7.4%), 8.0% (7.8%-8.2%), and 8.8% (8.6%-9.0%); tirzepatide TWL: 11.7% (11.4%-11.9%) and 11.9% (11.5%-12.3%). CONCLUSIONS:In this retrospective two-center study, bariatric surgery was associated with greater weight loss than GLP-1RAs among patients eligible for both options.

Pediatric deceased donor kidneys with acute kidney injury (ped-AKI) are at increased risk for non-utilization. To evaluate the post-transplant outcomes of ped-AKI recipients, we conducted a retrospective cohort study, comparing 17,731 adult recipients of kidneys from pediatric donors without AKI (ped-non-AKI, terminal serum creatinine (SCr)<1 mg/dL) to 1,589 ped-AKI recipients (SCr≥2 mg/dL). We used weighted logistic regression to estimate the association between ped-AKI and delayed graft function (DGF), and weighted Cox regression to estimate the association between ped-AKI and primary non-function (PNF) and all-cause graft failure (ACGF). Ped-AKI kidney recipients were at 6.0-fold (aOR=_5.325.98_6.72), 1.9-fold (aHR=_1.361.87_2.58), and 1.4-fold (aHR=_1.161.43_1.76) higher risk of DGF, PNF, and 1-year ACGF compared to ped-non-AKI recipients. En bloc ped-AKI recipients were at 5.6-fold (aOR=_3.295.57_9.43), 3.3-fold (aHR=_1.723.25_6.15), and 2.9-fold (aHR=_1.702.92_5.01) higher risk of DGF, PNF, 1-year ACGF compared to en bloc ped-non-AKI recipients. Among recipients of single kidneys from donors<20kg, ped-AKI recipients were at 8.9-fold (aOR=_4.348.87_18.12), 5-fold (aHR=_1.694.99_14.75), and 3.4-fold (aHR=_1.473.44_8.05) higher risk of DGF, PNF, 1-year ACGF compared to ped-non-AKI recipients. Ped-AKI kidney recipients have higher risks of early graft complications and failure. Risks are greatest for recipients of single kidneys from donors<20kg. Careful recipient selection and counseling are prudent when considering ped-AKI kidney offers.

BACKGROUND:Semaglutide and tirzepatide have transformed obesity treatment, but recent changes to bariatric surgery utilization are not well understood. METHODS:Epic's nationwide Cosmos database was queried for patients who underwent primary sleeve gastrectomy or gastric bypass between 2018 and 2025. Patient characteristics including preoperative semaglutide or tirzepatide dispense history were compared using chi-squared and Wilcoxon rank sum tests. Modified Poisson regression was used to identify factors independently associated with pre-surgery GLP-1RA use. Multilevel models were used to examine hospital- and state-level variation in pre-surgery GLP-1RA use. RESULTS:Bariatric surgery utilization increased after Q3 2018, peaked in Q4 2022, and subsequently decreased 39% through Q4 2025. Between Q4 2018 and Q4 2025, the proportion of Hispanic bariatric surgery patients increased (8.1% vs. 16.8%, p < 0.001), and the proportion of patients who received pre-surgery GLP-1RA increased (0.2% vs. 35.3%, p < 0.001). Factors associated with receiving pre-surgery GLP-1RA were year, private insurance, White race, type 2 diabetes (RR 2.94 [2.88-3.00]), older age, sleep apnea, and metabolic dysfunction-associated steatotic liver disease. Factors associated with receiving surgery upfront were Hispanic ethnicity, Black race, and public or no insurance. After adjusting for patient characteristics and year, there was a 15-fold difference in pre-surgery GLP-1RA use between the highest and lowest hospitals (RR 0.19-2.88). CONCLUSIONS:In the Epic Cosmos database, bariatric surgery utilization decreased from 2022 to 2025, and those who underwent bariatric surgery increasingly received GLP-1RA before surgery. Patients who received pre-surgery GLP-1RA were older, White, privately insured, with diabetes and other weight-related comorbidities, while patients who received surgery upfront were Hispanic, Black, and publicly insured. Pre-surgery GLP-1RA use was also driven by center-specific non-clinical factors.

Hypothermic machine perfusion (HMP) has surged in popularity for donor kidney preservation. Continuous-HMP (cHMP) has shown clear benefits over static cold storage (SCS), whereas randomized trials on short-duration end-ischemic-HMP (eiHMP) have not. We assessed whether HMP modulates injury from increasing cold-preservation-time and analyzed the impact of HMP on short- and long-term outcomes, using OPTN data (2010-2024) on single-kidney-transplant recipients (n=137,835). Multivariable non-linear (restricted cubic spline) regression with interaction terms were used. Median cold-preservation-time was long (17.3hrs,IQR:12.0-22.9), especially in the eiHMP cohort (median=23.0hrs,IQR:17.3-30.5). HMP was associated with significant reductions in DGF (cHMP:aOR=0.484,95%CI=0.467-0.501; eiHMP:aOR=0.459,95%CI=0.435-0.485; transport-only-HMP:aOR=0.535,95%CI=0.512-0.558) and LOS. Interaction analyses revealed HMP mitigated the negative effect of increasing cold-preservation-time compared with SCS. cHMP showed benefit across all cold-preservation-times, whereas eiHMP was beneficial only at longer cold-preservation-times. HMP was also associated with improved 5-year graft and patient survival. In conclusion, HMP reduces the negative impact of each additional hour of cold-preservation-time. Therefore, the treatment effect is not fixed and increases as cold-preservation-time increases, likely explaining the lack of benefit in trials of short-duration eiHMP. The association with improved 5-year graft survival and mortality provides IDEAL stage 4 evidence. This study addresses questions beyond the reach of randomized trials but of clear clinical relevance.

INTRODUCTION/BACKGROUND:Technological advances in organ preservation and reconditioning have enabled increased use of donation after circulatory death (DCD) organs. We aimed to characterize temporal trends in pediatric DCD (pDCD) in the United States. METHODS:We used Organ Procurement and Transplantation Network data to identify all pediatric (age < 18 years) deceased organ donors in the US, 2000-2025. We calculated the number and proportion of pediatric donation after brain death (pDBD) and pDCD donors by year. We calculated the number and type of recovered and transplanted pDBD and pDCD organs by year. RESULTS:The annual number of pDBD donors fell from 985 in 2000 to 530 in 2025, whereas pDCD donors increased from 21 to 244. The rise in pDCD recovery was observed for all organs: 32%, 19%, 16%, 14%, and 12% of recovered pediatric kidneys, livers, lungs, hearts, and pancreata by 2025. Among transplants with pediatric recipients in 2000, there was 1 pDCD liver transplant and no pDBD kidney, heart, lung, or pancreas transplants. By 2025, pDCD transplants accounted for 3%, 2%, and 8% of kidney, liver, and heart transplants with pediatric recipients. CONCLUSION/CONCLUSIONS:pDBD donors have fallen over the last 25 years, whereas pDCD donors have increased over 10-fold over the same period. Given the ongoing need for pediatric organ transplantation and the ethical importance of preserving opportunities for donation, there is an urgent need to develop a parallel communication and ethical framework to support families, clinicians, and transplant teams in navigating these donation opportunities.

BACKGROUND:Depressive symptoms are common in end-stage kidney disease (ESKD) patients, and may persist after stopping dialysis due to challenges post-KT despite clinical benefits. We sought to assess changes in depressive symptoms pre- and post-KT. METHODS:We leveraged a multi-center prospective cohort of 4,661 adult (aged ≥18) potential KT candidates and 1,215 recipients (2008-2025). Participants reported depressive symptoms via the Center for Epidemiologic Studies Depression (CES-D) scale (range 0-60, high depressive symptoms≥16) at evaluation, KT, and post-KT. We used linear mixed-effect models to estimate post-KT trajectories of CES-D scores overall and by characteristics at KT admission. RESULTS:19% of potential candidates at evaluation and 15% of recipients at admission had depressive symptoms; 46% and 38%, respectively, were non-Hispanic Black. Over the first 4 years post-KT, depressive symptoms slightly worsened (slope=0.4 points/year, 95% confidence interval [CI]:0.3, 0.6) but remained below the threshold for clinical depression. Post-KT CES-D score change differed by pre-KT high depressive symptoms score (difference=-1.2 points/year, 95%CI:-1.8, -0.6). Specifically, post-KT depressive symptoms were 0.7 points/year lower (95%CI:-1.2, -0.1) among recipients with pre-KT high depressive symptoms and 0.5 points/year higher (95%CI:0.3, 0.7) among those without. CES-D score change also differed by preemptive KT status (difference=-0.6 points/year, 95%CI:-1.0, -0.1, non-preemptive versus preemptive). CONCLUSIONS:Depressive symptoms worsened slightly over the first 4 years post-KT but remained below the threshold for clinical depression. Notably, post-KT CES-D scores decreased in recipients with high pre-KT depressive symptoms. Clinicians should discuss the mental health impact of KT with patients and tailor care decisions to individual needs.

KEY POINTS/CONCLUSIONS:In this cohort study of 720,348 adults referred for kidney transplantation from 2014 to 2025, only 48% were evaluated and 19% were waitlisted. Progression from referral to evaluation, waitlisting and kidney transplantation was limited by individual, center-level, and geographic factors. Some centers evaluated and waitlisted patients at rates far below the national average, and low-volume centers had lower rates of transplantation. BACKGROUND:Kidney transplantation is a cost-effective, lifesaving treatment of kidney failure, compared with dialysis. Unfortunately, most patients with kidney failure never undergo transplantation. METHODS:Using Epic Cosmos electronic health record data on all patients referred for kidney transplantation from 2014 to 2025, we assessed the stage-specific progression and attrition in the process of evaluation, waitlisting, and kidney transplantation. Center-level and individual (socioeconomic, geographic, and insurance status) factors associated with access to evaluation, waitlisting, and kidney transplantation were characterized using modified Poisson regression. RESULTS:Among 720,348 referred candidates, the median age was 55 years (interquartile range [IQR], 42-64); 47% of patients were White, 52% were male, and 87% were English speaking. Eighty-five percent of patients lived in urban areas. Of the referred candidates, 48% initiated evaluation, 19% were waitlisted, and 10% ultimately underwent transplantation. Among the referred patients who initiated evaluation, the median (IQR) time to evaluation initiation was two (1-4) months after referral; among the patients who were waitlisted, the median (IQR) time to waitlisting was four (2-9) months after evaluation initiation. Patients who were never married (0.94; 95% confidence interval [CI], 0.93 to 0.94), had severe obesity (0.70; 95% CI, 0.69 to 0.72), or were from rural zip codes (relative risk, 0.98; 95% CI, 0.97 to 1.00) were less likely to initiate evaluation. Low-volume centers had lower relative rates of transplantation (0.92; 95% CI, 0.88 to 0.96). In centers with documentation for nonprogression to evaluation, reasons for removal included not meeting criteria/not a candidate (18%), patient decision (13%), unable to contact (12%), death (4%), and financial/insurance complications (7%). CONCLUSIONS:Our study shows substantial attrition before kidney transplant waitlisting.