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Urine Biomarkers for Kidney Cancer

The American Cancer Society estimates that in 2010 over 58,000 people will be diagnosed with kidney cancer and more than 13,000 of those will die. Kidney cancer does not always cause obvious symptoms. It is frequently discovered while investigating other medical issues, oftentimes when in advanced stages when prognosis is poor. Patients who are diagnosed early have an excellent survival rate. Unfortunately, no early diagnosis for kidney cancer exists. Biomarkers are molecules or other substances in the blood, body fluid or tissue that can be used to diagnose or monitor a particular disorder. In recent years, enormous research has been directed into the use of biomarkers for the detection and monitoring of cancer. Science suggests panels rather than individual biomarkers offer the most clinical utility.
Research has produced a great amount of information regarding kidney cancer biomarkers. Overexpression of certain proteins in kidney mass tissue has been noted. Additionally, researchers know that the metabolic analysis of urine can be used to separate kidney cancer patients from healthy patients.

A significant contribution to kidney cancer biomarker research was recently made when investigators at Washington University in St. Louis identified urine biomarkers sensitive and specific to kidney cancer. Previous investigations identified proteins that were elevated in kidney tumor tissue, aquaporin-1 (AQP1) and adipophilin (ADFP). Washington University researchers tested the urine of patients for the presence of the aforementioned proteins. The study included prenephrectomy and postnephrectomy urine of 42 patients with kidney cancer, preoperative and postoperative urine of 15 control patients who underwent non-kidney surgery, and random urine of 19 healthy volunteers.

Both AQP1 and ADFP were found in significant concentrations in the prenephrectomy urine of patients with kidney cancer. Urinary AQP1 and ADFP were significantly decreased in the postnephrectomy urine samples. The urine samples of the non-kidney surgery patients and the healthy volunteers did not have significant levels of either protein. These findings suggest AQP1 and ADFP could be used as sensitive and specific urine biomarkers for the early detection of kidney cancer.

Human kidney injury molecule-1 (hKIM-1) has also been identified as a urine biomarker for kidney cancer. hKIM-1 is not detectable in normal kidneys, but high levels are found in kidney tumors. Studies identified high levels of hKIM-1 in the prenephrectomy urine of kidney tumor patients. The levels were dramatically reduced postnephrectomy. hKIM-1 however, is not specific to kidney cancer, it is also found in acute kidney injury. It still may prove useful on a panel of urine biomarkers for kidney cancer.

More research is on the use of urine biomarkers for kidney cancer screening is needed. The clinical utility of screening and early diagnosis must be determined. If determined to be useful, larger studies confirming these findings must be conducted. Cost effective methods of detection must be devised.

References:
(1) AmericanCancerSociety.Cancer Facts & Figures 2010.Atlanta:AmericanCancerSociety;2010.
(2) Han, W.K., Alinani, A., Wu, C.L., Michaelson, D., Loda, M., McGovern, F.J., Thadhani, R., and Bonventre, J.V. Human kidney injury molecule-1 is a tissue and urinary tumor marker of renal cell carcinoma. J Am Soc Nephrol. Apr;16(4):1126-34, 2005.
(3) Kim, K.M., Aronov, P.A, Zakharkin, S.O., Anderson, D., Perroud, B., and Weiss, RH. Urine metabolomic analysis for kidney cancer detection and biomarker discovery, Molecular and Cellular Proteomics, Mar; 8(3):558-70, 2009.
(4) Morrissey, J.J., London, A.N., Luo, J., and Kharasch, E.D. Urinary biomarkers for the early diagnosis of kidney cancer. Mayo Clin Proc. May;85(5):413-21, 2010.
(5) Srivastava, S., and Gopal-Srivastava, R. Biomarkers in cancer screening: a public health perspective. J Nutr. 132(8 Suppl):2471S-2475S, 2002.