Circulating kidney injury molecule-1 (KIM-1) in association with kidney injury biomarkers and outcomes in metastatic renal cell carcinoma.
Authors: Clara Steiner, Eddy Saad, Renee Maria Saliby, Marc Eid, Karl Semaan, Marc Machaalani, Emre Yekeduz, Jack T. Horst, Jasmine Lee, Noa Phillips, Rachel Trowbridge, Marta Pirovano, Carolina Saldanha Neves Horta Lima, Shruti Gupta, Gwo-Shu Mary Lee, Yehonatan Elon, Adam P. Dicker, Joseph Bonventre, Toni K. Choueiri, Wenxin Xu
Journal: Journal of Clinical Oncology (2025)

582 Background: Kidney injury molecule-1 (KIM-1) is overexpressed in clear cell and papillary renal cell carcinoma (RCC) and in proximal tubular kidney injury. While circulating KIM-1 is a minimally invasive biomarker for RCC, it is unknown whether kidney disease, a common comorbidity among RCC patients, impacts the association of KIM-1 with RCC outcomes. We evaluated the association between KIM-1 and outcomes in metastatic RCC after adjustment for multiple kidney injury biomarkers using plasma proteomics. Methods: Plasma samples from patients with metastatic clear cell and papillary RCC were obtained prior to 1 st line systemic therapy. Samples were analyzed using a high-throughput aptamer-based proteomics assay (SomaLogic), and results were log-transformed for analysis. Clinical and laboratory data, as well as cancer outcomes, were retrospectively curated. Spearman’s ρ was used to evaluate correlations between circulating KIM-1 and kidney injury biomarkers (cystatin C, TNFR1, TNFR2, eGFR). Cox regression analyses were used to evaluate the association between KIM-1 as a continuous variable and overall survival (OS) and progression-free survival (PFS), after adjusting for kidney injury biomarkers. Performance of KIM-1 tertiles versus IMDC risk groups for prognosticating OS was evaluated using the C-index. Results: Among 210 patients, higher baseline KIM-1 was associated with worse PFS (p = 0.004) and OS (p &lt; 0.001) in univariate Cox regression analysis (Table). The prognostic value of KIM-1 was consistent across clear cell and papillary RCC (p-value for interaction = 0.98). KIM-1 remained prognostic for PFS (p = 0.01) and OS (p &lt; 0.001) after multivariable adjustment for kidney injury biomarkers and eGFR (Table). Median follow-up was 22.1 months. Kidney injury biomarkers (cystatin C, TNFR1, TNFR2, eGFR) were correlated with each other but not with plasma KIM-1. KIM-1 tertiles (high/medium/low) were more prognostic for OS than the IMDC risk groups (C-index, KIM-1 0.63 vs. IMDC groups 0.58) and the addition of KIM-1 to the IMDC model improved its performance (C-index, KIM-1 + IMDC groups 0.64). Conclusions: Plasma KIM-1 was associated with PFS and OS in metastatic clear cell and papillary RCC. Plasma KIM-1 was not correlated with kidney injury biomarkers, suggesting that at least in metastatic RCC, circulating KIM-1 derives predominantly from tumor rather than benign kidney. The addition of KIM-1 improves IMDC model performance and may be useful for risk prognostication in RCC. Association of KIM-1 with PFS and OS in metastatic RCC. Multivariable models are adjusted for kidney injury markers (cystatin C, TNFR1, TNFR2) and eGFR. log KIM-1 HR (95% CI) p-value OS (univariate) 1.4 (1.2 – 1.7) &lt;0.001*** PFS (univariate) 1.2 (1.1 – 1.4) 0.004** OS (multivariate) 1.4 (1.2 – 1.6) &lt;0.001*** PFS (multivariate) 1.2 (1.1 – 1.3) 0.01**