Jain, Nishank

e16564 Background: Urothelial carcinoma (UC) predominantly affects older adults with a high burden of comorbidities, particularly chronic kidney disease (CKD), which affects 30–40% of patients at diagnosis and is more prevalent in advanced disease. Enfortumab vedotin plus pembrolizumab (EV+P) has become a frontline standard for advanced UC; however, patients with moderate-to-severe CKD were underrepresented in pivotal trials. Enfortumab vedotin targets Nectin-4 expressed in renal tubular epithelium, and immune checkpoint inhibitors are associated with immune-mediated nephrotoxicity, raising concern for renal vulnerability in patients with reduced renal reserve. Real-world data evaluating renal and clinical outcomes of EV+P in patients with baseline CKD are limited. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network, identifying adult patients with UC treated with EV+P between January 2020 and December 2025. Baseline CKD status (stages 3–5; eGFR < 60 mL/min/1.73 m²) was determined by diagnostic codes and laboratory data obtained prior to EV+P initiation.Patients were stratified into CKD and non-CKD cohorts. Propensity score matching (1:1) was performed for demographics, comorbidities, laboratory values, and prior therapies. Outcomes assessed within 180 days of treatment initiation included overall survival (OS), major adverse kidney events (MAKE; composite of acute kidney injury, dialysis initiation or dependence, or death), and selected treatment-related toxicities. Kaplan–Meier and Cox proportional hazards models were used. Results: After matching, 386 patients were included in each cohort (median age 75 years), with well-balanced baseline characteristics (all post-matching standardized mean differences < 0.1). Prior to matching, patients with CKD had a higher burden of cardiovascular comorbidities. Baseline renal function differed by design, with lower mean eGFR and higher serum creatinine in the CKD cohort. Overall survival was similar between CKD and non-CKD cohorts (HR 0.96; 95% CI, 0.69–1.35; p = 0.83), with 180-day survival rates of 79.9% and 79.3%, respectively. Patients with CKD had a higher incidence of MAKE, reflected by lower 180-day event-free survival (49.4% vs 59.1%; HR 1.41; 95% CI, 1.13–1.76; p = 0.002). Treatment-related toxicities were also more frequent in the CKD cohort (HR 1.35; 95% CI, 1.05–1.74; p = 0.020), with a higher mean number of toxicity events (4.3 vs 3.4). Conclusions: In this large real-world analysis, EV+P use was associated with comparable short-term overall survival in UC patients with and without CKD but with higher rates of renal events and treatment-related toxicities among patients with baseline CKD. These findings support the use of EV+P in select UC patients with CKD, with close monitoring of renal function and treatment-related toxicity.

ImportancePatients with kidney failure (KF) receiving long-term dialysis have increased incidence of atrial fibrillation (AF). Patients with KF and AF have increased risk of stroke, death, and bleeding compared with age-matched cohorts. In KF, the use of oral anticoagulants (OACs) increases hemorrhage risk, offsetting potential benefits and making left atrial appendage occlusion (LAAO) a potentially promising solution for risk reduction in AF.ObjectivesTo compare the outcomes and safety of OACs and LAAO for risk reduction of AF in patients with KF.Design, Setting, and ParticipantsThis retrospective cohort study assessed patients with KF enrolled in the US Renal Data System registry between January 1, 2015, and December 31, 2018, who were diagnosed with AF after initiation of long-term dialysis. On average, patients met inclusion criteria for 22 months. Data analysis was completed in May 2024.ExposureMedicare claims were used to identify patients who received OACs and LAAO after AF diagnosis. A propensity-matched cohort was created based on the CHA2DS2-VASc score and year of treatment.Main Outcomes and MeasuresDeath, nonfatal bleeds, and nonfatal strokes.ResultsThe final cohort included 2344 patients with KF and a new AF diagnosis (median [IQR] age, 66.0 [57.0-73.0] years; 1341 [57.2%] male). Of these patients, 293 received LAAO and 2051 received OACs. A total of 2194 patients (93.6%) were receiving hemodialysis, with the remaining 150 (6.4%) receiving peritoneal dialysis. In the LAAO group, 79 deaths (27.0%) and 21 nonfatal strokes (7.2%) occurred, and 117 patients (39.9%) experienced 234 bleeding events. In the OAC group, 729 deaths (35.5%) and 163 strokes (8.0%) occurred, and 687 patients (33.5%) experienced 1114 bleeding events. After accounting for correlation between bleeds and death, the joint frailty model showed evidence of a treatment association of LAAO compared with OACs on recurrent bleeding events (hazard ratio [HR], 0.74; 95% CI, 0.56-0.98) and death (HR, 0.47; 95% CI, 0.30-0.72). There was a reduced risk of nonfatal stroke in the LAAO group (HR, 0.55; 95% CI, 0.32-0.94), but this finding was not significant after adjustment (HR, 1.18; 95% CI, 0.76-1.81).Conclusions and RelevanceIn this cohort study, LAAO compared with OACs was associated with improved survival and reduced bleeding risk in patients with KF and AF. These findings suggest that these data should be considered in shared decision-making in consideration of LAAO for patients with KF and AF.