Bioartificial kidney speeds recovery, reduces mortality

Apr 24 2008

Another promising clinical trial for the bioartificial kidney is offering researchers even more hope that within the next few years the device will be available to save lives of patients with acute renal failure.

The latest University of Michigan Health System-led study reveals that short-term replacement of renal cell function using the renal tubule assist device, or RAD - the living cell cartridge that is key to the function of the bioartificial kidney - significantly reduces mortality risk and speeds recovery of kidney function for patients with acute renal failure resulting from acute kidney injury.

When compared to a more traditional approach - continuous renal replacement therapy - the mortality rate after a 28-day-period for the patients who received continuous venovenous hemofiltration combined with RAD was 33 percent. The mortality rate for those who only had the continuous renal replacement therapy was at 66 percent.

Plus, during the 180 days following treatment, patients who received the combined therapy had a 50 percent reduction in mortality risk. Results from the trial are now online in the Journal of the American Society of Nephrology.

"Our study results are encouraging, and they raise expectations that our new approach may yield a better treatment for life-threatening acute renal failure, for which a high mortality rate has remained unchanged despite years of advances in conventional therapies," says lead study author H. David Humes, M.D., professor of Internal Medicine at the U-M Medical School. "Even more promising, the nature of our new approach - using living cells as therapeutic agents - argues for the feasibility of developing whole classes of new cell-based and tissue engineered therapies."

He notes that despite improvements in acute medical care and advances in dialysis therapy, the mortality rate during the past four decades for patients with acute kidney failure from acute kidney injury has consistently been between 50 to 70 percent.

The phase II RAD trial enrolled 58 critically ill patients with acute kidney failure at 12 medical centers across the country. The patients, ages 18 to 80, were randomly selected to receive continuous venovenous hemofiltration combined with RAD, or continuous renal replacement therapy alone.

Most patients received treatment for up to 72 hours. Several patients were taken off the treatment early due to vascular access, clotting of the hemofilter cartridge, or because of complications related to their other medical conditions.

Renal recovery and mortality for patients who completed treatment was then observed at 28, 90 and 180 days post-treatment.

At day 28, 53 percent of the patients in the RAD group had recovered renal function, 25 percent died, and 20 percent remained on renal support. Additionally, researchers noted that during 180 days of follow-up in the intensive care unit, patients who had received RAD treatment for up to 72 hours had a greatly reduced risk of mortality.

While the study was limited by the small number of patients in this phase II trial, Humes and his colleagues say it offers encouragement that a related device - a wearable kidney that performs natural functions unachievable through man-made technology - can be developed in the near future to treat chronic renal failure.

"The ability to harness vital processes of cells, to target their living molecular machinery on restoring critical substances which have become disordered by disease, has vast implications for the future of medicine," says Humes. "The apparently successful use of living cells in this way validates our approach and should encourage others to investigate cell therapies for a range of disorders."

Humes and his colleagues began developing the bioartificial more than a decade ago, and today the RAD is being developed for future commercial applications under license to Nephrion, a U-M biotechnology spinout company.

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 immune 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.

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. The first human trial of the bioartificial kidney, published in the October 2004 issue of the journal Kidney International showed the device was safe to use and improved kidney function for patients with acute renal failure.

While the initial results are encouraging, the benefits of RAD treatment need to be confirmed in larger trials. Also, still to be met are challenges of mass producing, storing and shipping a living-cell device.

Along with Humes, study co-authors were J. Tumlin, Southeast Renal Associates, Presbyterian Hospital; R. Wali, University of Maryland; W. Williams, Massachusetts General Hospital; P. Murray, University of Chicago; A. Tolwani, University of Alabama; A. Vinnikova, Virginia Commonwealth University; H. Szerlip, Medical College of Gerogia; J. Ye, Western New England Renal and Transplant Associates; E. Paganini, Cleveland Clinic; L. Dworkin, Rhode Island Hospital; K. Finkel, University of Texas; and M. Kraus, Indiana University.