The first test in humans of a bioartificial kidney offers hope of the device's potential to save the lives of people with acute renal failure, researchers at the University of Michigan Health System report.
While the phase I/II study was designed primarily to look at the safety of using this device on humans, the results also suggest improvement in kidney function. The patients enrolled in the trial faced an average 86 percent likelihood of dying at the hospital. Six of those 10 patients survived more than 30 days after treatment with the bioartificial kidney. The study appears in the October issue of the journal Kidney International.
“These results showed this type of human adult stem progenitor/stem cell is well-tolerated by patients with acute renal failure, and there were some very compelling and resulted in some improvement outcomes of the patients' clinical conditions. It's a small study but it was compelling enough for us and the FDA to agree to go forward with a full phase II study,” says lead study author H. David Humes, M.D., professor of Internal Medicine at the U-M Medical School. Humes developed the renal tubule assist device, or RAD, the cell cartridge that is key to the bioartificial kidney.
The RAD is being developed for future commercial applications under license to Nephros Therapeutics Inc.
The phase I/II study enrolled 10 patients at UMHS and the Cleveland Clinic Foundation. Patients were seriously ill, with acute renal failure and multiple other illnesses, including sepsis, multiple organ failure, acute respiratory distress syndrome and postoperative complications.
Each patient received up to 24 hours of treatment with the renal tubule assist device. Several patients were taken off the treatment earlier because of reactions such as hypoglycemia or low platelet counts, or because of complications related to their other medical conditions.
The bioartificial kidney includes a cartridge that filters the blood as in traditional kidney dialysis. That cartridge is connected to a renal tubule assist device, which is made of hollow fibers lined with a type of kidney cell called renal proximal tubule cells. These cells are intended to reclaim vital electrolytes, salt, glucose and water, as well as control production of immune system molecules called cytokines, which the body needs to fight infection.
Conventional kidney dialysis machines remove these important components of blood plasma, along with toxic waste products, and cannot provide the cytokine regulation function of living cells. Traditional therapy for patients with acute or chronic renal failure involves dialysis or kidney transplant, both of which have limitations.
Humes and his colleagues began developing this technology a decade ago, identifying the adult progenitor/stem cells and testing the device in animals. Initial testing in animals, published in the journal Nature Biotechnology in April 1999, found the cells in the RAD perform the metabolic and hormonal functions lost in acute renal failure.
Eventually, researchers hope the device can become implantable in patients with acute or chronic renal failure as a long-term replacement for kidney function. More testing is needed before that can become a reality, and any standard use of this therapy is still many years off.
“The long-term goal, if this shows effectiveness in patients with end stage renal disease, is to build a fully implantable device. Our lab is working with engineers at U-M and the Cleveland Clinic to make nanofabricated membranes that can miniaturize the device so it can be implanted and fully replace organ function,” Humes says.
For now, a randomized, controlled phase II trial of the RAD in acute renal failure is currently underway at six academic medical centers under investigational new drug, sponsored by Nephros Therapeutics Inc. The study is expected to expand to additional centers later this year. UMHS researchers also have planned, for late 2005, a phase I/II trial to investigate the safety of the RAD for people with end-stage chronic renal failure. Investigators are not looking for volunteers for that trial, and the device is not ready to be implanted in patients.
In addition to Humes, U-M study authors were William Weitzel, M.D., assistant professor of Nephrology; Robert Bartlett, M.D., professor of Surgery; and Fresca Swaniker, M.D., assistant professor of Surgery. Other authors were Emil Paganini, M.D., of the Cleveland Clinic, and Jack Luderer , M.D., and Joseph Sobota , M.D., of Nephros Therapeutics .
Funding for the study was from the National Institutes of Health, the Michigan Life Sciences Corridor Fund and Nephros Therapeutics. The renal assist device technology is owned by the University of Michigan and licensed to Nephros Therapeutics Inc., a biotechnology spin-off company of U-M. Humes, Luderer and Sobota are shareholders in Nephros.