Simple Urine Biomarker Test Could Identify Early-Stage Renal Cell Carcinoma

Evan D. Kharasch, MD, PhD

Two urine biomarkers, aquaporin 1 (AQP1) and perilipin 2 (PLIN2), could be the key to the development of a simple urine test that leads to the detection of asymptomatic, early-stage kidney cancer, according to a recent study. Typically silent, renal cell carcinoma (RCC) is often detected fortuitously during an abdominal CT or MRI scan, said co-investigator Evan D. Kharasch, MD, PhD, the Russell D. and Mary B. Shelden Professor of Anesthesiology at Washington University School of Medicine in St. Louis, Missouri.

“It is not affordable to use abdominal imaging as a population screening method, so our goal has been to develop a urine test to identify kidney cancer early and noninvasively,” said Kharasch. When kidney cancer is not discovered until after it has spread, more than 80% of patients die within five years.

Currently, there is no biochemical screening test commercially available for RCC, but researchers found that the protein biomarkers were more than 95% accurate in identifying early-stage kidney cancers. In addition, there were no false positives caused by noncancerous kidney disease.

A second potential application of the biomarker test is in identifying which patients who have a mass in their kidney actually have cancer. “Having surgery to remove a kidney after a mass is found is the typical default treatment,” said Kharasch. But in about 10% to 15% of individuals, the mass can be noncancerous, “so testing a patient’s urine after a radiographic scan can further help identify whether a mass is cancer or not, and hopefully prevent the removal of a normal kidney.”

Kharasch and principal investigator Jeremiah J. Morrissey, PhD, professor of anesthesiology, analyzed urine samples from 720 patients at Barnes-Jewish Hospital who were about to undergo abdominal CT scans for reasons unrelated to a suspicion of kidney cancer. The researchers also analyzed samples from 80 healthy people and 19 patients previously diagnosed with kidney cancer.

The researchers measured the levels of AQP1 and PLIN2 in the urine and found that none of the healthy people had elevated levels of either protein. Patients with kidney cancer had elevated levels of both proteins.

In addition, three of the 720 patients who had abdominal CT scans, but were not known to have kidney cancer, also had elevated levels of both proteins. Two of those patients were diagnosed subsequently with kidney cancer, and the third patient died from other causes before a diagnosis could be made.

“Each protein, or biomarker, individually pointed to patients who were likely to have kidney cancer, but the two together were more sensitive and specific than either by itself,” said Morrissey in a statement. “When we put the two biomarkers together, we correctly identified the patients with kidney cancer and did not have any false positives.”

Even when patients had other types of noncancerous kidney disease, levels of the two proteins in the urine were not elevated and did not suggest the presence of cancer.

“Patients with other kinds of cancer or other kidney diseases don’t have elevations in these biomarkers,” said Kharasch. “So in addition to being able to detect kidney cancer early, another advantage these biomarkers may be capable of showing who doesn’t have the disease.”

Kharasch and Morrissey are working to develop an easy-to-use screening test for kidney cancer, much like mammograms, colonoscopies, or other tests designed to identify cancer at early, more treatable stages before patients have symptoms.

Licensing the technology and developing the assay would be the next steps, with eventual approval by the US Food and Drug Administration, said Kharasch.

“We hope that if the test becomes available, it will have a significant impact. Our goal is to improve health, advance public health, and reduce the 14,000 deaths caused by kidney cancer each year,” said Kharasch.

The findings were reported in JAMA Oncology.

Morrissey JJ, Mellnick VM, Luo J, et al. Evaluation of urine aquaporin 1 and perilipin 2 concentrations as biomarkers to screen for renal cell carcinoma. [Published online] JAMA Oncology. http://oncology.jamanetwork.com/article.aspx?articleid=2196180&resultClick=3. Accessed May 27, 2015