Prognostic Impact of Glomerular Filtration Rate Decline on Survival Outcomes in Metastatic Renal Cell Carcinoma Treated with Targeted Therapy

<i>Background and Objectives:</i> The prognostic significance of dynamic changes in glomerular filtration rate (GFR) during targeted therapies in metastatic renal cell carcinoma (mRCC) is not well understood. Thus, we aimed to investigate the prognostic significance of GFR value at 6 months in patients with mRCC receiving first-line targeted therapy. <i>Materials and Methods:</i> This retrospective cohort study included 260 mRCC patients at two tertiary centers in Turkey between 2015 and 2025. Patients were stratified into three groups according to GFR at 6 months: ≥60, 30-60, and <30 mL/min/1.73 m². Kaplan-Meier curves were used to estimate progression-free survival (PFS) and overall survival (OS) in prognostic subgroups. Cox proportional hazard models assessed associations between clinicopathologic variables, including GFR categories, and PFS and OS. <i>Results:</i> The median PFS for the cohort was 11.1 months (95% confidence interval [CI]: 9.3-12.9), and the median OS was 40.0 months (95% CI: 30.3-49.7). In multivariate analysis, GFR < 30 mL/min/1.73 m² was independently associated with shorter PFS (hazard ratio [HR]: 1.54, 95% CI: 1.01-2.33, <i>p</i> = 0.040) and OS (HR: 3.80, 95% CI: 2.06-7.01, <i>p</i> < 0.001), while GFR 30-60 mL/min/1.73 m² was linked to reduced OS (HR: 2.07, 95% CI: 1.08-3.98, <i>p</i> = 0.028). Additional independent predictors of worsened PFS were intermediate (<i>p</i> = 0.028) and poor IMDC risk (<i>p</i> < 0.001. For OS, liver metastases (<i>p</i> = 0.017), bone metastases (<i>p</i> = 0.014), brain metastases (<i>p</i> = 0.002), and intermediate (<i>p</i> = 0.014) or poor IMDC risk (<i>p</i> < 0.001) were also significant. <i>Conclusions:</i> In patients with mRCC treated with targeted therapy, the GFR at 6 months is an independent factor in predicting survival outcomes, indicating the clinical significance of serial kidney function monitoring.