Kidney Injury Molecule-1 (KIM-1) in Renal Cell Carcinoma: Bridging Tumor Biology and Clinical Decision-Making

Renal cell carcinoma (RCC) remains a biologically heterogeneous disease with variable clinical outcomes, underscoring the need for robust biomarkers to guide risk stratification and therapeutic decision-making. Despite advances in immune checkpoint inhibitors and targeted therapies, clinically validated biomarkers are lacking, particularly in the perioperative setting. Kidney injury molecule-1 (KIM-1; also known as HAVCR1 or TIM-1) has emerged as a promising candidate with strong biological and clinical rationale. KIM-1 is a transmembrane glycoprotein minimally expressed in normal kidney tissue but markedly upregulated in injured and dedifferentiated proximal tubular epithelial cells, the cell of origin for clear cell RCC. Its extracellular domain is shed into circulation and urine, enabling non-invasive quantification. Beyond its role as a marker of renal injury, KIM-1 is implicated in immune modulation, chronic inflammation, and tumor biology, supporting its role as a dynamic indicator of tumor burden and disease aggressiveness. This review presents the current evidence supporting KIM-1 as a circulating biomarker and therapeutic target in RCC and discusses emerging strategies to address disease heterogeneity through biomarker-driven approaches. We examine its biological role, clinical utility in early detection and postoperative risk stratification, integration with other emerging biomarkers, and its development as a target for antibody–drug conjugates. The review concludes with a summary of the evolving landscape of KIM-1–directed biomarker strategies in RCC, which hold promise to refine patient selection, improve risk-adapted management, and advance precision oncology in this complex disease.