With 30 million people in the U.S. stricken with potentially life-threatening kidney problems, the UW is going the extra mile to find solutions to this near epidemic. This journey into space will allow researchers to measure the effect of weightlessness on both healthy and diseased kidney cells. A group effort among the UW School of Pharmacy, UW Medicine, the Kidney Research Institute and BioServe Space Technologies at the University of Colorado, the Kidney-on-a-Chip Space Project is one of several UW advances that might transform care of kidney patients.
Jonathan Himmelfarb is the director of the Kidney Research Institute, a collaborative effort between UW Medicine and Northwest Kidney Centers. As one of the inventors of the kidney-on-a-chip, he understands the legacy he and his colleagues inherited when it comes to kidney research and treatment.
“We are standing on the shoulders of giants,” he says, referring to professors Belding Scribner and Albert Babb and UW staff bioengineer Wayne Quinton, ’58, who, in 1960, invented the shunt that made long-term dialysis possible, an innovation that has saved millions of lives worldwide. The kidney-on-a-chip allows resdearchers to see how, outside a human body, the kidney metabolizes a medication.
“Chip technology represents a fundamental shift in how we conduct drug safety testing,” says Ed Kelly, associate professor in the UW School of Pharmacy and co-principal investigator on the kidney-on-a-chip space project. “The typical pathway is from in vitro to animals to human clinical trials. The kidney-on-a-chip potentially leapfrogs animal trials by testing the effects of new drug candidates directly in human organs ex vivo using chip technology, in our case the kidney.”
One reason so few drugs have been developed for kidney problems is the expense of running clinical trials and the potential risk to patients. “It’s great if a medication turns out to be safe and effective but it would be good to find out before exposing patients,” says Himmelfarb.
The UW is going to such great lengths with the kidney-on-a-chip because the need for solutions to kidney disease is urgent. In 2015, the last year statistics are available, more than 1.2 million people worldwide died from chronic kidney disease. Few drugs have been developed to prevent the progression to end-stage renal disease since 1995, when Losartan, a blood-pressure control medication, came on the market.
Benjamin Freedman, assistant professor of medicine, has invented “mini-kidney organoids” in cell-culture dishes. Imagine a tiny organ, growing in a Petri dish, about the size of a quarter. Just like real kidneys, these “minis” contain cells that control filtration from the blood and blood-vessel cells. Freedman has tested drugs that are known to cause kidney problems in patients: cisplatin, a chemotherapy drug prescribed for a variety of cancers; and gentamicin, an antibiotic. When Freedman’s lab put these drugs to the test, the mini-kidneys began to fail.
Freedman anticipates conducting clinical trials in a dish test on mini kidneys developed from, say, 10,000 kidney cells representing diverse populations of the world. His lab also uses a genetic tool called CRISPR to develop mini-kidneys with characteristics of two kidney diseases: polycystic kidney disease and glomerulonephritis. The hope is to use genetic tools in the future to correct these conditions. By sequencing the genome of individual patients, it will be possible to identify the specific DNA mutations that cause disease, and correct them using gene therapy.
Kidney disease isn’t the only problem UW Medicine is working on. Adam Maxwell, a UW Medicine urology researcher, is tackling the problem of kidney stones. He developed an ultrasound technique to nudge the stones to the urethra, so they can be passed from the body. Maxwell and Michael Bailey, an Applied Physics Lab engineer, found that short ultrasound pulses broke up stones faster than lithotripsy, which has been used for 20 years to blast apart kidney stones.
Another potential blockbuster is the work being done at the UW’s Center for Dialysis Innovation on a mobile artificial kidney, which had its first clinical trial in 2014. Columns magazine covered the clinical trial of the Wearable Artificial Kidney in the December 2014 issue. Since then 19 people have posted online. A man identifying himself as Prabal said, “I am in India. My mother has to have dialysis twice a week. When will this device be available? Will it be too late for many patients in developing countries? … Please develop it fast. It’s the need of the hour for all kidney patients, all over the world.”