UW School of Pharmacy team's work could change the future of precision medicine and kidney research — with a device the size of a credit card.
The Centers for Disease Control and Prevention estimates that while 15 percent of American adults have chronic kidney disease, most of them don’t even know it.
Only when the disease is in its later stages — when it’s often too late for reversal — do more severe symptoms cause people to seek help, says Catherine Yeung, research assistant professor at the University of Washington School of Pharmacy.
An inability to track the early stages of chronic kidney disease leaves researchers like Yeung at a loss for what early biological markers might look like. There’s also much to learn about how kidney problems affect the body’s ability to eliminate medications.
At the School of Pharmacy, an interdisciplinary team is undertaking revolutionary work that could change the future of precision medicine and kidney research — all with a device the size of a credit card.
It’s called kidney-on-a-chip. Inside its small frame are thousands of live kidney cells that can model the functions of a human kidney.
A breakthrough in kidney research
“Kidneys are part of the ‘holy trinity’ of drug clearance,” says Edward Kelly, associate professor at the School of Pharmacy and the lead investigator on the project. “The intestine is involved in absorption, the liver is involved in metabolism and the kidneys are involved in excretion,” meaning they help the body clear medication via urine.
People with failing kidneys might not be able to process medications as efficiently as those with healthy kidneys. On top of that, there’s the possibility that certain medications could further compromise their kidneys. This is critical because — unlike the liver and other organs — the kidney lacks the ability to regenerate.
That’s where the UW is focusing with kidney-on-a-chip.
Working alongside Kelly and Yeung is Jonathan Himmelfarb, M.D., the Joseph W. Eschbach, M.D., Endowed Chair in Kidney Research at the UW School of Medicine and the internationally renowned director of the Kidney Research Institute, a collaborative effort between UW Medicine and Northwest Kidney Centers.
With support from both the UW and Northwest Kidney Centers, team members brought their expertise together for the kidney-on-a-chip project. They have already begun testing various drugs, including antibiotics that are less harmful to kidneys. Instead of giving patients experimental treatments that may or may not work, “We could see the effects in kidney-on-a-chip before we test them in humans,” says Kelly.
Kidney-on-a-chip heads to outer space
But what if you could speed up the development of kidney disease? In 2018, the UW team is sending kidney-on-a-chip to the one place where time does speed up: outer space.
Microgravity acts as an accelerant, so kidney problems that take decades to develop on Earth need only weeks or months on the International Space Station, where astronauts will study the chips over the course of a few weeks.
Team member Kenneth Thummel, the Milo Gibaldi Endowed Chair in Pharmaceutics at the School of Pharmacy, has previous experience keeping astronauts healthy. With long-standing research interests in vitamin D metabolism and the regulation of mineral homeostasis, a key component of kidney function, Thummel was part of a special National Research Council committee that established guidelines for chemical exposure in spacecraft air and water.
Bone loss is a major concern for astronauts, Kelly says. “That’s why astronauts exercise and employ other means to counter this issue when they’re in space. Kidneys synthesize the active form of vitamin D, which is necessary to maintain healthy bones, so we’ll be asking if kidney cells still perform that function in microgravity.”
Sending the chips to the Space Station also stands to benefit another group of space travelers: the first Mars colonists.
The current record for the most consecutive days in space is 438 — but in theory, Mars colonists would remain for decades. After studying chips on the Space Station, researchers might have a better idea of how to help the human body withstand the effects of spending so much time in a lower-gravity environment.
For the researchers involved, kidney-on-a-chip might very well bring about changes in their lifetime, a rarity for big medical breakthroughs. This trailblazing science is made possible in large part by donors who support the Pharmaceutics Fund for Excellence, which invests in startup research projects like kidney-on-a-chip.
“As a pharmacist, I’m very satisfied to be able to show people what we’re doing and where their research dollars are going,” says Yeung. “With kidney-on-a-chip, we have an actual chance to impact the lives of patients.”
This project is supported by a four-year, $3 million grant (1 UG3 TR002178-01) awarded by National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH). The Center for the Advancement of Science in Space (CASIS), the organization tasked by NASA to manage the International Space Station U.S. National Laboratory, will contribute the space flight, time in station, and Space Station crew costs, for an in-kind total of $8 million. The content of this story is solely the responsibility of the authors and does not necessarily represent the official views of these agencies.