714 URINE KIDNEY INJURY MOLECULE-1 A NON-INVASIVE SCREENING TOOL FOR PATIENTS WITH RENAL CELL CARCINOMA

Abstract

INTRODUCTION AND OBJECTIVES: Kidney injury molecule-1 (KIM-1) is a type I transmembranous protein and specific injury marker of renal proximal tubules. Our previous study demonstrates that KIM-1 is prominently up regulated in proximal tubule-derived renal cell carcinoma (RCC), including clear cell and papillary RCC, but not in chromophobe RCC (a distal tubule tumor). Additionally, pre-operative KIM-1 levels in urine samples were significantly elevated in patients with RCC. This study was designed to examine urine KIM-1 level before and 1 month after surgical removal of renal tumors. METHODS: 19 patients with localized radiographic renal lesions were prospectively enrolled into the study. Pre-operative and post-operative urine KIM-1 levels were measured using a human KIM-1 ELISA. The urine KIM-1 levels were normalized by urine creatinine levels as a urine KIM-1/creatinine ratio (UKCR). Renal tumors were also stained for KIM-1, using an immuno-histochemical AKG7 antiKIM-1 antibody, which divided patients into a KIM-1 positive or negative group. RESULTS: The KIM-1 negative group included 7 cases (2 chromophobe RCC, 4 benign cystic lesions and one hematoma), and the KIM-1 positive group was composed of 12 cases (6 C-RCC, 5 P-RCC and 1 XP11.2 translocation RCC). In both groups, serum creatinine (sCR) levels were significantly elevated after nephrectomy. In the KIM-1 negative group, sCr levels increased from pre-operative level of 1.011 0.053 mg/dl to post-operative level of 1.366 0.150 mg/dL, and in the KIM-1 positive group the pre-sCr level of 1.012 0.094 mg/dl significantly increased to 1.447 0.129 mg/dl. In the KIM-1 negative group, UKCR remained at a similar level before (0.367 0.095 ng/mg Cr) and after nephrectomy (0.323 0.014 ng/mg Cr). However, in the KIM-1 positive group, the elevated UKCR at 1.200 0.310 ng/mg Cr, was significantly reduced to 0.362 0.099 ng/mg Cr, after nephrectomy. CONCLUSIONS: Our small but prospective study showed significant reduction in UKCR after nephrectomy, suggesting that urine KIM-1 appears to be a non-invasive pre-operative measure to evaluate the malignant potential of renal masses and may also represent a surrogate biomarker for KIM-1 positive RCC.