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

  • Urology - Original Paper
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Abstract

Background

KIM-1 staining is upregulated in proximal tubule-derived renal cell carcinoma (RCC) including clear renal cell carcinoma and papillary renal cell carcinoma, but not in chromophobe RCC (distal tubular tumor). This study was designed to prospectively examine urine KIM-1 level before and 1 month after removal of renal tumors.

Patients and design

A total of 19 patients were eventually enrolled in the study based on pre-operative imaging studies. Pre-operative and follow-up (1 month) urine KIM-1 levels were measured. The urine KIM-1 levels (uKIM-1) were then normalized to urine creatinine levels (uCr). Renal tumors were also stained for KIM-1 using immunohistochemical techniques.

Results

The KIM-1-negative staining group included 7 cases, and the KIM-1-positive group consisted of 12 cases. The percentage of KIM-1-positive staining RCC cells ranged from 10 to 100 %, and the staining intensity ranged from 1+ to 3+. In both groups, serum creatinine levels were both significantly elevated after nephrectomy. 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 small but prospective study showed significant reduction in uKIM-1/uCr after nephrectomy in the KIM-1 positive group, 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.

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Acknowledgments

Authors thank Beaumont Health System and Geisinger Health System for funding the internal grants and National Institutes of Health awards DK 39773, DK 72381 and DK 38452 (to J.V.B.). Authors appreciate excellent assistance from Ms. Sharon K. Hick.

Conflict of interest

J.V.B is a co-inventor of KIM-1 patents that are assigned to Partners HealthCare and licensed by Partners to Johnson & Johnson, Sekisui Medical, Biogen Idec and a number of research reagent companies. J.V.B. is a consultant for Sekisui Medical.

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Authors and Affiliations

  1. Department of Anatomic Pathology, William Beaumont Hospital, 3601 W. 13 Mile Rd, Royal Oak, MI, USA

    Ping L. Zhang, Stacy C. Wolforth & Mitual B. Amin

  2. Department of Urology, William Beaumont Hospital, 3601 W. 13 Mile Rd, Royal Oak, MI, USA

    Joseph W. Mashni, Kenneth M. Kernen, Brian D. Seifman & Jason M. Hafron

  3. Renal Division, Brigham and Women’s Hospital, Boston, MA, USA

    Venkata S. Sabbisetti & Joseph V. Bonventre

  4. Weis Research Center and Lab Medicine, Geisinger Medical Center, Danville, PA, USA

    Charles M. Schworer & Fan Lin

  5. Beaumont Research Institute, William Beaumont Hospital, 3601 W. 13 Mile Rd, Royal Oak, MI, USA

    George D. Wilson & Timothy J. Geddes

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  1. Ping L. Zhang
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  2. Joseph W. Mashni
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  3. Venkata S. Sabbisetti
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Corresponding author

Correspondence to Jason M. Hafron.

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Zhang, P.L., Mashni, J.W., Sabbisetti, V.S. et al. Urine kidney injury molecule-1: a potential non-invasive biomarker for patients with renal cell carcinoma. Int Urol Nephrol 46, 379–388 (2014). https://doi.org/10.1007/s11255-013-0522-z

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  • DOI: https://doi.org/10.1007/s11255-013-0522-z

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