Most drugs a person takes will ultimately be cleared from their body into urine by their kidneys. The role of these hard-working organs in drug clearance makes them particularly susceptible to the toxic effects of certain medications. Unfortunately, unlike livers, kidneys can’t regenerate. That’s bad in part because, once they start to fail, they limit the ability of a patient to process drugs—complicating treatment for a range of diseases, including kidney disease.
In the past, a medical researcher who wanted to test the effects of a new drug on the kidneys might have applied the drug to cultured kidney cells on a plate. Regrettably, that test wouldn’t model what happens in the body very well because it wouldn’t replicate blood flow. A more expensive and ethically complicated option would be to conduct tests on animals. However, animals are not always predictive of human responses.
Fortunately, a recent breakthrough by a team co-led by members, , and , with colleague , gives researchers a new option—kidney-on-a-chip. While it might sound like some kind of British hors-d'oeuvres, kidney-on-a-chip is actually a revolutionary new device that functions as a normal kidney, allowing researchers to test drugs as well as xenobiotics in a much more natural laboratory model.
The genius of kidney-on-a-chip is that it incorporates flow to mimic normal kidney function. A tubule of kidney cells are enclosed inside a plastic case through which drugs can be passed in a system that closely replicates a working kidney. Researchers can apply experimental drugs to kidney-on-a-chip with a syringe, pushing medications through the system—even multiple medications at once—without the need for gravity.
Kelly and Himmelfarb are already using kidney-on-a-chip to compare the toxicity of antibiotics and herbal products on the kidney to compare the effects of different doses. By detecting harmful effects with the chip, they’re able to optimize treatment options for patients while reducing the need for human and animal testing. In the future, they hope to use the chips not only to improve treatment and prevention of disease but also to develop cures.
As exciting as the chip advance has been for kidney research, it’s about to get better. Thanks to recent federal grants from the and NASA’s , kidney-on-a-chip is preparing for its first cosmic voyage—to the .
Why send kidney-on-a-chip to space? Because there’s so much to learn. First of all, microgravity will speed up processes related to the development of kidney disease, so that problems that take decades to develop on Earth could appear within weeks or months in space. This will potentially give researchers rare insights into the long-term effects of drug treatment.
Second, studying kidney-on-a-chip in space can provide important insights into the medical complications associated with weightlessness. Bone loss is one problem that plagues astronauts. Kidneys make the active form of vitamin D that keeps bones healthy, so it’s important to understand how that function occurs in a weightless environment.
Cells have never been sent to space like this. This experiment will allow scientists to probe the long-term effects of a lower-gravity environment on a human organ. What the team learns will dramatically improve our understanding of issues like potential medical challenges for Mar’s first colonists. As Yeung explains it, “This is experimental in the truest sense of the word, which is incredibly exciting.”
Kidney-on-a-chip project co-lead, Edward Kelly, is an Associate Professor in the University of Washington (UW)’s School of Pharmacy and directs the EDGE microphysiological systems unit. Co-lead, Jonathan Himmelfarb, holds an Endowed Chair in Kidney Research at the UW School of Medicine, directs the , and co-leads the EDGE Collaborative Research Team (CRT) on Hepatic, Renal and GI Diseases. Terrance Kavanagh, EDGE Science Director, and , co-lead of the EDGE Developmental and Reproductive Disorders CRT, co-direct a predictive toxicology group that supported the development of kidney-on-a-chip and continues to support the use of this technology for environmental health research.