Plasma Kidney Injury Molecule-1 for Preoperative Prediction of Renal Cell Carcinoma Versus Benign Renal Masses, and Association With Clinical Outcomes

Abstract

Purpose: Both clear cell and papillary renal cell carcinomas (RCCs) overexpress kidney injury molecule-1 (KIM-1). We investigated whether plasma KIM-1 (pKIM-1) may be a useful risk stratification tool among patients with suspicious renal masses.

Methods: Prenephrectomy pKIM-1 was measured in two independent cohorts of patients with renal masses. Cohort 1, from the prospective K2 trial, included 162 patients found to have clear cell RCC (cases) and 162 patients with benign renal masses (controls). Cohort 2 included 247 patients with small (cT1a) renal masses from an academic biorepository, of whom 184 had RCC. We assessed the relationship between pKIM-1, surgical pathology, and clinical outcomes.

Results: In Cohort 1, pKIM-1 distinguished RCC versus benign masses with area under the receiver operating curve (AUC-ROC, 0.81 [95% CI, 0.76 to 0.86]). In Cohort 2 (cT1a only), pKIM-1 distinguished RCC versus benign masses (AUC-ROC, 0.74 [95% CI, 0.67 to 0.80]) and the addition of pKIM-1 to an established nomogram for predicting malignancy improved the model AUC-ROC (0.65 [95% CI, 0.57 to 0.74] v 0.78 [95% CI, 0.72 to 0.85]). A pKIM-1 cutpoint identified using Cohort 2 demonstrated sensitivity of 92.5% and specificity of 60% for identifying RCC in Cohort 1. In long-term follow-up of RCC cases (Cohort 1), higher prenephrectomy pKIM-1 was associated with worse metastasis-free survival (multivariable MFS hazard ratio [HR] 1.29 per unit increase in log pKIM-1, 95% CI, 1.10 to 1.53) and overall survival (multivariable OS HR 1.31 per unit increase in log pKIM-1, 95% CI, 1.10 to 1.54). In long-term follow-up of Cohort 2, no metastatic events occurred, consistent with the favorable prognosis of resected cT1a RCC.

Conclusion: Among patients with renal masses, pKIM-1 is associated with malignant pathology, worse MFS, and risk of death. pKIM-1 may be useful for selecting patients with renal masses for intervention versus surveillance.

Figure 1:

Plasma KIM-1 in patients with clear cell renal cell carcinoma versus benign renal masses. Figure 1A: Plasma KIM-1 values among patients with renal masses (Cohort 1 and Cohort 2) and healthy volunteers. Healthy volunteer plasma samples were taken from the Brigham and Women’s Hospital biorepository. The lower limit of detection is 1.0 pg/mL for the microbead based assay (Cohort 1 and healthy volunteers) and 11.7 pg/mL for the MSD assay (Cohort 2).

Figure 1B:

Receiver operating curve analysis of plasma KIM-1 to distinguish clear cell renal cell carcinoma versus benign renal masses. Cohort 1, all patients

Figure 1C:

Receiver operating curve analysis, Cohort 1, patients stratified by tumor size

Figure 1D:

Receiver operating curve analysis, Cohort 2 (cT1a renal masses)

Figure 1E:

Scatter plot of Lane nomogram score versus plasma KIM-1. The dashed lines represent median values of the Lane score and plasma KIM-1 value, 0.79 and 4.81 pg/mL respectively.

Figure 2a:

Kaplan-Meier curves for metastasis free survival (MFS) by pre-nephrectomy plasma KIM-1 quartile, Cohort 1.

Figure 2b:

Kaplan-Meier curves for overall survival (OS) by pre-nephrectomy plasma KIM-1 quartile, Cohort 1.