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 that predict 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 aimed to investigate the association between baseline and on-treatment serum KIM-1 levels and clinical outcomes in mRCC patients receiving IO-based therapy.
We retrospectively analyzed 73 patients with mRCC who received first-line IO+IO (n = 36) or IO+TKI (n = 37) therapy 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 levels. 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.
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=0.016). In multivariable Cox regression adjusted for IMDC risk, age, and sex, high baseline 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 revealed that among 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 a higher ORR, although PFS did not differ significantly between the increase and decrease groups.
These findings support serum KIM-1 as a promising biomarker for predicting therapeutic efficacy in mRCC.
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