Nephrologist William Fissell IV, M.D., associate professor of Medicine and Biomedical Engineering, is intent on creating and mass-producing an implantable bioartificial kidney that can transform quality of life and prospects for survival for people with chronic kidney disease who would otherwise be forced onto dialysis.
Donor kidneys are in very short supply for the approximately 600,000 Americans who have end-stage renal disease. Only 50 percent of dialysis patients are still alive three years after the start of therapy for kidney disease, compared with 91 percent survival at three years for those who instead receive a preemptive kidney transplant.
Dialysis costs $80,000 per patient per year, and the total U.S. cost for treatment of end-stage renal disease is upward of $40 billion.
Vanderbilt and the University of California at San Francisco are the lead institutions for development of the bioartificial kidney. Fissell, who relocated from the Cleveland Clinic to Vanderbilt last August, has invested years of groundwork in the device, in collaboration with bioengineer Shuvo Roy, Ph.D., of UCSF, and other far-flung researchers.
Fissell estimates the project has garnered $7 million in funding to date from the National Institutes of Health (NIH) and private benefactors. Last year the project received a significant boost when the Food and Drug Administration selected it for a new fast-track approval program.
Fissell had kidney troubles as a child, from which he has recovered. When he worked as an emergency medical technician (during an extended break from college) he got to know many patients on dialysis.
As he was studying for his medical boards, Fissell found himself contemplating the miniscule structure of the glomerular slit diaphragm, the filter that is broken in chronic kidney disease. His mind suddenly cast back to work he had done as an MIT undergrad in physics and electrical engineering.
“I had this epiphany, as it were. I said to myself, ‘I’ve seen something like that before; in fact I’ve made something like that before.’”
At MIT Fissell had worked in a lab that was developing a piece of technology called an X-ray diffraction grating, used by astronomers to analyze the atomic constituency of stars.
“I saw that the very structures destroyed in most chronic kidney disease had the same approximate size and shape as these devices I had been involved in making and testing as an undergraduate. That’s what started the journey: could we bring these tools from electrical engineering to bear to assist a population of patients that had immense unmet need?”
Fissell is still struck by the next coincidence in this story. Even before completing his residency at Case Western, he met Shuvo Roy, who was already making similar nanostructures for a drug delivery application. They’ve been pursuing the bioartificial kidney ever since.
Using silicon nanotechnology similar to computer microprocessor technology, the bioartificial kidney marries nano filters made of silicon with living human kidney cells cultured in the lab from samples harvested from deceased donors. The donated cells form a membrane positioned downstream from the device’s intake filter, out of reach of the body’s immune response, so rejection is not an issue. The device will run on the body’s normal blood pressure, with no other power source required.
Beyond filtering waste from the blood, the bioartificial kidney will also perform other vital functions of the kidney, including maintenance of blood pressure and pH levels and vitamin synthesis.
In clinical research conducted at the University of Michigan, intensive care patients with kidney failure were greatly helped by an externally deployed, large-scale version of the device, developed by H. David Humes, M.D., with whom Fissell trained. The challenge now is to stuff this successful new technology into a mass-producible package the size of a bar of soap.
“Phase one, the proof of concept stuff, all of that is done. Phase two is the difficult task of scaling up the prototype devices to clinical function. We can make one or two at a time, but can we make four million that all work exactly the same? And how long can we make the cells last? How often will you have to come back to the clinic for a replace/renew/refresh cycle?”
Preclinical testing is ongoing and Fissell hopes to begin testing an implantable device in humans in 2017.
“My professional identity is that I’m the nephrologist who’s trying to make an implantable artificial kidney. I’m pursuing this approach because I think it’s not susceptible to some of the vulnerabilities of other approaches. If someone else succeeds meanwhile with another strategy, God bless.
“I’d love it if someone put us out of business. I’ll be the first person to cheer.”
