Fewer tests, lower costs …through urine?

(Harald/Flickr)
Lee’s team is using proteomics and glycomics to establish normal urine profiles, as well as biomarkers of kidney damage. (Harald/Flickr)

Part 1 of a two-part series on kidney disease. Part 2 is here.

In up to 5 percent of all pregnancies, children are born with some degree of kidney dilation or swelling, known as hydronephrosis. Unfortunately, says urologist Richard Lee, MD, of Boston Children’s Hospital, “many of these kids go through a lot of testing after birth and are followed for a long period of time—sometimes unnecessarily.”

Hoping to reduce such testing, Lee and his colleagues are turning to urine. They’ve been collecting comprehensive data on the urinary proteome—all the proteins urine normally contains. With this baseline information, they hope to establish biomarkers that identify kidney damage.

In a recently published study, Lee and his coauthors compared the urinary proteomes of healthy infant boys versus men to find out what happens naturally with age. Through their work, they identified nearly 1,600 protein groups and determined that the healthy male urinary proteome changes over time. These changes include differences in proteins involved in metabolism, cellular growth, immune response and cell adhesion.

Proteomics can provide a better understanding of a physiologic problem than genomics, Lee explains. “Each protein can have various isoforms or slight, minor modifications that might change its function, but that’s not always reflected in the transcribed genome,” he says.

Lee suggests the research could pave the way for clinical applications of urinary proteomics. As a start, he believes proteomics will be the key to determining which kids with hydronephrosis need to be treated and tested. Going forward, he says, “We’re developing a panel of urine markers for clinical use to determine which kids need operative intervention and which kids don’t.”

Setting the baseline was crucial because “you can’t figure out what’s abnormal until you know what’s normal,” says Lee.

This search for “normal” and “abnormal” has led Lee and his team to begin a parallel investigation into sugars in urine, looking for specific patterns that indicate a likelihood of urinary tract infection. “Urinary tract infections are mediated by bacteria binding to sugar molecules in our bladder,” he explains.

To study these sugar patterns, researchers are creating a “library” of sugar biomarkers in urine. “With the new techniques that we have pioneered, our data banks and our experience at looking the urinary proteome, we will be able to look at this population very closely to find out who is at risk,” Lee says.

Advancements in non-invasive diagnostics will improve the care of children by helping make the right treatment choice, reducing exposure to x-ray radiation and decreasing the invasiveness of testing. “It also will significantly economize care,” Lee says. “Finding ways to decrease the amount of testing is critical to reducing costs in health care.

“In the current health care environment, we need new diagnostics,” he adds. “We need to know who needs to be treated and who doesn’t need to be treated. If we’re talking about affordable care—saving money—that’s where the big bang is.”

For more about Lee’s proteomics and glycomics technologies, or to inquire about collaboration opportunities, email Rajinder.Khunkhun@childrens.harvard.edu, Licensing Manager at the Boston Children’s Technology and Innovation Development Office (TIDO).