Glucagon like peptide-1 receptor agonist therapy and long-term renal outcomes after radical nephrectomy: a propensity-matched cohort analysis

OBJECTIVE: To evaluate the association between glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy and long-term renal function outcomes following radical nephrectomy (RN). METHODS: Using the TriNetX Research Network, we identified adults who underwent RN between 2005 and 2025. Patients were stratified based on GLP-1 RA use in the peri-operative period. Propensity score matching (1:1) was performed to control for demographic factors, baseline laboratory parameters, and relevant comorbidities. Baseline renal function, including serum creatinine and estimated glomerular filtration rate (eGFR), was included in the matching process. Renal outcomes included acute kidney injury (AKI), chronic kidney disease (CKD) stage 3, CKD stage 4, CKD stage 5, dialysis dependence, and eGFR, assessed at 1-, 2-, and 5-year follow-up intervals. Time-to-event analyses were conducted using Kaplan-Meier methods and Cox proportional hazards models. RESULTS: After matching, 3316 patients (1658) per group) were included in the final analysis. GLP-1 RA users demonstrated significantly lower AKI incidence at 1 year (6.3% vs 12.4%), 2 years (9.5% vs 16.8%), and 5 years (13.4% vs 22.1%) (all p < 0.001). GLP-1 RA use was associated with significantly lower incidence of CKD Stage 3 (at 1 year (12.3% vs 17.2%), 2 years (15.% vs 21.7%, and 5 years (19.7%, vs 25.4%), CKD stage 4 at 1 year (3.1% vs 6.9%), 2 years (4.7% vs 9.0%), and 5 years (6.2% vs 10.9%), and CKD stage 5 at 2 years (1.2% vs 3.9%) and 5 years (1.7% vs 4.7%) (all p < 0.001). Dialysis dependence was also markedly reduced in the GLP-1 RA cohort (2 years: 1.0% vs 5.6%; 5 years: 1.7% vs 7.3%; all p < 0.001). Kaplan-Meier analyses demonstrated improved AKI-free, advanced CKD-free, and dialysis-free survival among GLP-1 RA users, with Cox proportional hazards models confirming significantly lower hazards of AKI, advanced CKD (stage 3-5), and dialysis dependence. CONCLUSION: GLP-1 RA therapy is associated with improved renal function outcomes following radical nephrectomy, with the most consistent benefit observed in reducing progression to advanced CKD (stage 3-5) and dialysis dependence. These findings support further investigation of GLP-1 RAs as a potential renal protective strategy in patients after nephrectomy.