KIM-1 Emerges as Potential Biomarker in Renal Cell Carcinoma

Kidney injury molecule–1 (KIM-1) has emerged as a potential prognostic biomarker for response to therapy and could be used to inform clinical decision-making for the treatment of patients with renal cell carcinoma (RCC), according to a presentation by Wenxin (Vincent) Xu, MD, given during the 2025 Kidney Cancer Research Summit.¹

“We know that KIM-1 is overexpressed in kidney tumors, especially those coming from the proximal tubular epithelium and [that] it is shed into circulation,” Xu, a medical oncologist at Dana-Farber Cancer Institute and an assistant professor of medicine at Harvard Medical School, both in Boston, Massachusetts, said during the presentation. “It has [also] been shown that KIM-1 is not just elevated in the blood, but it’s elevated in the blood per bank sample up to 5 years before kidney cancer diagnosis. This [has] led to the question of whether we can validate KIM-1 as a potential circulating biomarker to detect kidney cancer, to risk stratify, and to indicate the likelihood of response.”

Xu began his presentation by noting that KIM-1 has been examined as a potential biomarker across the disease spectrum of RCC, including in clear cell and papillary disease. Findings published in the Journal of Clinical Oncology indicated that prenephrectomy plasma KIM-1 levels displayed a 92.5% sensitivity and 60% specificity in terms of identifying clear cell RCC vs benign renal masses.² Additional data showed that high KIM-1 levels were associated with worse metastasis-free survival in multiple cohorts of patients.

“[Patients] with higher KIM-1 [with] a renal tumor are more likely to have aggressive malignancies of the tumor after nephrectomy, and, ultimately, a higher chance of dying from kidney cancer,” Xu noted.

Moreover, the presence of persistent KIM-1 following nephrectomy has been associated with disease recurrence, Xu said. Findings from the phase 3 ECOG-ACRIN E2805 (ASSURE; NCT00326898), CheckMate 914 (NCT03138512), and IMmotion010 (NCT03024996) studies showed that KIM-1 was a strong prognostic biomarker for progression-free survival, disease-free survival (DFS), and DFS, respectively.¹

KIM-1 Shows Response Prognostication

For patients with metastatic disease, data from a post hoc analysis of the phase JAVELIN Renal 101 (NCT02684006) trial demonstrated that patients with high KIM-1 levels (n = 306) experienced a PFS (log-rank P = .0011) and overall survival (OS; log-rank P <.0001) benefit compared with those with low KIM-1 levels (n = 306).³

In IMmotion010, patients with high KIM-1 experienced a significant DFS benefit with adjuvant atezolizumab compared with those who received placebo (HR, 0.72; 0.530.99). The respective median DFS values in the atezolizumab (n = 151) and placebo (n = 149) groups were not evaluable (NE) and 21.16 months.⁴

Xu also noted that the KIM-1 ratio at 3 weeks has been shown to be predictive of response to immunotherapy in the metastatic setting. Specifically, in the phase 3 CheckMate 214 trial (NCT02231749), patients who received nivolumab plus ipilimumab who experienced greater than a 30% increase in KIM-1 ratio at 3 weeks had a significant worsening of OS compared with those who did not (HR, 2.40; 95% CI, 1.70-3.40).⁵

Regarding overall response rate (ORR), the ORR among patients with a 30% decrease in KIM-1 rate (n = 140) was 69.3% (95% CI, 60.9%-76.8%).

“The KIM-1 ratio, which is defined as the percentage change in KIM-1 from baseline to 3 weeks, was a strong predictor of response to immunotherapy regimens,” Xu explained. “This was particularly striking in CheckMate 214. Patients with a KIM-1 decrease at 3 weeks were the exceptional responders and [those] who failed to have a favorable KIM-1 ratio by the 3-week mark after one dose of nivolumab/ipilimumab were generally not exceptional responders to nivolumab/ipilimumab and had quite poor outcomes.”

Xu concluded his presentation by noting that, “We give [patients] nivolumab/ipilimumab because we hope for a slam dunk. [However], one of the main reasons we are held back is a fear of rapid [disease] progression within the first 12 weeks. Many patients who receive nivolumab/ipilimumab and don’t respond fail to make it to second-line therapy. Perhaps by assessing the KIM-1 ratio, we can single out the exceptional responders, and for those who will not have a good response, we can divert them to a more effective regimen ahead of time.”

REFERENCES:

1. Xu W. From bench to bedside: advancing KIM-1 as a tool for clinical decision-making. Presented at: 2025 Kidney Cancer Research Summit; July 17-18, 2025; Boston, MA.

2. Xu W, Gaborieau V, Niman SM, et al. Plasma kidney injury molecule-1 for preoperative prediction of renal cell carcinoma versus benign renal masses, and association with clinical outcomes. J Clin Oncol. 2024;42(22):2691-2701. doi:10.1200/JCO.23.00699

3. Machaalani M, Saliby RM, Zhong C, et al. KIM-1 as a circulating biomarker in metastatic RCC: post-hoc analysis of JAVELIN Renal 101. J Clin Oncol. 2025;43(suppl 5):594. doi:10.1200/JCO.2025.43.5_suppl.594

4. Albiges L, Bex A, Suárez C, et al. Circulating kidney injury molecule-1 (KIM-1) biomarker analysis in IMmotion010: a randomized phase 3 study of adjuvant (adj) atezolizumab (atezo) vs placebo (pbo) in patients (pts) with renal cell carcinoma (RCC) at increased risk of recurrence after resection. J Clin Oncol. 2025;42(suppl 16):4506. doi:10.1200/JCO.2024.42.16_suppl.4506

5. Xu W, Vemula SV, Motzer RJ, et al. Evaluation of circulating kidney injury marker-1 (KIM-1) as a prognostic and predictive biomarker in advanced renal cell carcinoma (aRCC): post-hoc analysis of CheckMate 214. J Clin Oncol. 2025;43(suppl 5):437. doi:10.1200/JCO.2025.43.5_suppl.437