BERKELEY, CA (UroToday.com) - KIM-1 was cloned in 1998 in the laboratory of Dr. Joseph V. Bonventre, Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA. Based on human renal biopsy studies and animal models, KIM-1 was found to be a specific biomarker to indicate proximal tubular injury in the kidneys. Retrospectively, Bonventre’s group found that baseline levels of KIM-1 were significantly elevated in urine from patients with renal cell carcinoma (RCC) derived from the proximal tubules. Ninety percent of all RCC tumors with either clear type or papillary variant originate in the proximal tubules. Using the same monoclonal antibody for human urine KIM-1, our prospective study (in collaboration with the Bonventre group) found that 50% of the RCC patients had significantly higher baseline levels of urine KIM-1, which were reduced to the control levels one month after nephrectomy (Zhang et al., Int Urol Nephrol DOI 10.1007/s11255-013-0522-z). None of the control cases with benign renal lesions had elevated baseline level of urine KIM-1. Additionally, all of the RCC tumors that stained for KIM-1 showed a significant reduction in the serum KIM-1 levels following surgical resection. This non-invasive method to detect RCC appears plausible for further confirmation of RCC in a patient with a suspicious renal mass and may potentially serve as a surrogate marker of RCC in a follow-up setting.
To further investigate the role of KIM-1 in RCC, we sequenced the DNA of KIM-1 in RCC and DNA sequence of KIM-1 in a non-tumor kidney. We found the KIM-1 DNA was not changed in the RCC, implying an intact function of KIM-1 in the renal tumors. As KIM-1 is involved in phagocytosis of injured proximal tubules, we stained KIM-1 and another phagocytotic factor, CD68, in the current renal tumors and archival renal tumors. In these studies, there appeared to be parallel stain intensity between the KIM-1 and CD68. This data suggests that KIM-1 may participate in cellular clearing in RCC. This also raises the question as to whether KIM-1 plays a role in drug resistance. More recently, Bonventre’s group reported that their serum KIM-1 test became available for detecting acute kidney injury, implying that KIM-1 generated from kidney can flow back from injured proximal tubules into the blood stream (Annual Meeting of American Society of Nephrology, November 2013, Philadelphia, PA).
Our recent pilot study revealed that RCC tumors that stained for KIM-1 had high levels of serum KIM-1, preoperatively, which were significantly reduced following surgical resection. We speculate that serum KIM-1 test may be used to detect and monitor RCC similar to how PSA is routinely used for screening and monitoring prostate carcinoma. Clearly, further studies are required.
Ping L. Zhang, MD, PhD, FCAP, FASNa and Jason M. Hafron, MDb as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
a Department of Anatomic Pathology, and
b Department of Urology, William Beaumont Hospital, Royal Oak, Michigan USA