Urine kidney injury molecule-1: a potential non-invasive biomarker for patients with renal cell carcinoma

Abstract

Objective To evaluate the use of urine KIM-1 as a biomarker for supporting a diagnosis of kidney cancers before operation. Methods A total of 19 patients were enrolled in the study based on preoperative imaging studies. Pre-operative and follow-up (1 month) uKIM-1 levels were measured and normalized with uCr levels and renal tumors were stained for KIM-1 using immunohistochemical techniques. Results The percentage of KIM-1 positive staining RCC cells ranged from 10 to 100% and the staining intensity ranged from 1+ to 3+. Based on the KIM-1 staining, 19 cases were divided into the KIM-1-negative staining group (n =7) and the KIM-1-positive group (n = 12). Serum creatinine (sCR) levels were significantly elevated after nephrectomy in both groups. In the KIM-1 negative group, uKIM-1/uCr remained at a similar level before (0.37 ± 0.1 ng/mg Cr) and after nephrectomy (0.32 ± 0.01 ng/mg Cr). However, in the KIM-1 positive group, elevated uKIM-1/uCr at 1.20 ± 0.31 ng/mg Cr was significantly reduced to 0.36± 0.1 ng/mg Cr, which was similar to the pre-operative uKIM-1/uCr (0.37 ± 0.1 ng/mg Cr) in the KIM-1 negative group. Conclusion Our study showed significant reduction in uKIM-1/uCr after nephrectomy, suggesting that urine KIM-1 may serve as a surrogate biomarker for kidney cancer and a non-invasive pre-operative measure to evaluate the malignant potential of renal masses.

Identification of immunohistochemical biomarkers that differentiate chromophobe renal cell carcinoma from renal oncocytoma through molecular profiling of renal tumours

“…The poor expression of KIM-1 in chRCC concurred with other previous IHC results where the majority of chRCC were negative for KIM-1. However, our findings of KIM-1 expression in 80% of RO was certainly different to previous reports where RO were all negative for KIM-1 immunostaining (Han et al 2005;Zhang et al 2014) Urinary KIM-1 levels have also been closely associated with renal cancers, especially ccRCC and papillary RCC. In the first study, Han et al showed that in all 5 RCC patients with detectable prenephrectomy urinary KIM-1, there was either complete disappearance or marked reduction after nephrectomy.…”

“…Previous reports have also showed strong expression of KIM-1 in ccRCC (Han et al 2005;Lin et al 2007;Zhang et al 2014). …”

“…The utility of KIM-1 has not gained widespread clinical usage despite its promising published research results in acute and chronic kidney injury studies (Liangos et al 2007, van Timmeren et al 2007). However, there was increased expression of KIM-1 noted in renal tumours compared with normal kidney, mainly in ccRCC (Lin et al 2007;Zhang et al 2014). We wanted to investigate further if there was any differential expression in various renal tumour subtypes apart from ccRCC and to assess if there was any usefulness in differentiating chRCC from RO.…”

“…In renal cancers, KIM-1 has been shown to be expressed in various RCC, especially ccRCC and papillary RCC, both of proximal tubular origin; and urinary KIM-1 is also a good biomarker for RCC detection (Han et al 2005;Zhang et al 2014). The authors concluded that KIM-1 expression occurs with dedifferentiation of the proximal tubule epithelial cell, which is also a property of RCC cells that are derived from the proximal tubule (Bonventre 2014).…”

“…Following the meta-analysis, CK7, Cav-1 and S100A1 were chosen because of their apparent usefulness in differentiating the two renal tumour entities. As novel biomarkers, Ob, ObR and KIM-1 were selected based on literature that indicates KIM-1 expression is increased in ccRCC but not chRCC and RO (Han et al 2005;Zhang et al 2014); and the significant association of obesity as a relative risk factor for development of RCC (Ljungberg et al 2011). Since leptin is an adipokine that is produced by abundant adipocytes in obese patients, it was important to study the relationship of Ob and ObR in differentiation of chRCC and RO, and in malignancies such as ccRCC.…”