Association of serum kidney injury molecule-1 with treatment response and survival in metastatic renal cell carcinoma.

534 Background: First-line immune checkpoint inhibitor (IO)-based therapies have improved the prognosis of patients with metastatic renal cell carcinoma (mRCC). However, reliable blood-based biomarkers predicting treatment response and survival are lacking. Kidney Injury Molecule-1 (KIM-1) is a tubular injury marker overexpressed in RCC and detectable in serum. We investigated the association between baseline and on-treatment serum KIM-1 levels and clinical outcomes in mRCC patients receiving IO-based therapy. Methods: We retrospectively analyzed 73 patients with mRCC who received first-line IO+IO (n=36) or IO+TKI (n=37) between 2018 and 2024. Serum KIM-1 was measured at baseline in all patients and at 3 weeks in 63 patients. Patients were stratified into tertiles according to baseline KIM-1 values. Clinical characteristics, objective response rate (ORR), and progression-free survival (PFS) were compared among groups. Kaplan–Meier curves and Cox regression models were used for survival analysis. Subgroup analyses were performed according to primary tumor status. Results: Higher baseline KIM-1 was associated with adverse outcomes. Kaplan–Meier analysis showed significantly shorter PFS in the high KIM-1 group compared with the low/intermediate groups (HR 2.18, 95% CI 1.15–4.16, p=0.017). In multivariable Cox regression adjusted for IMDC risk, baseline high KIM-1 was not an independent predictor but showed a trend toward worse PFS (HR 2.01, 95% CI 0.98–4.12, p=0.056). Subgroup analysis by primary tumor status showed that in patients without primary tumors, high baseline KIM-1 was significantly associated with shorter PFS (HR 2.80, 95% CI 1.15–6.81, p=0.023), whereas in those with primary tumors, baseline KIM-1 levels did not significantly affect PFS. Among 63 patients with paired samples, responders showed a greater KIM-1 decrease than non-responders (median decrease 754 vs 258 pg/mL, p=0.018). Patients with a KIM-1 decrease had higher ORR, although PFS did not differ significantly between the increase and decrease groups. Conclusions: These findings support serum KIM-1 as a promising biomarker for predicting therapeutic efficacy in mRCC. Results of multivariate analysis for progression-free survival. Varieble Univariate analysis Multivariate analysis HR(95%CI) p HR(95%CI) p Age 0.94(0.20-4.64) 0.9346 1.01(0.40-2.53) 0.9038 Sex(male) 1.27(0.53-3.07) 0.5824 1.14(0.59-2.20) 0.7371 IMDC risk 1.47(0.78-2.79) 0.1231 1.33(0.68-2.61) 0.4307 pKIM1 5.22(1.25-16.97) 0.0115 2.01(0.98-4.12) 0.056