Around a hospital’s intensive-care unit it is often called the spiral of death. Chemotherapy or an infection knocks a patient’s kidneys out of service, and within a day or two, inflammation spreads throughout his or her blood vessels. Blood pressure crashes, starving the body of oxygen, and in short order the lungs, liver, and other organs begin to fail. Replacing the kidney’s most basic function by using conventional dialysis to clear urea and other wastes from the blood is of little help. More than half of those caught in the grip of acute kidney failure die.
But in a small clinical trial completed last winter, a novel treatment offered the first real hope for patients in acute kidney failure. Six out of the 10 critically ill patients beat the odds and survived; all but one had been judged to have no more than a 10 to 20 percent chance of living.
What appears to have saved them is a plastic cartridge the size of a pair of stacked soda cans containing an unconventional active ingredient: one billion human kidney cells thriving inside 4,000 translucent, hollow, plastic fibers. It’s called a bioartificial kidney. Developed after a decade of research by University of Michigan internist David Humes, this hybrid of living cells and artificial structure is at the forefront of a pragmatic effort to find an effective treatment for people whose organs have failed. Though the research may not be as glamorous as attempts to develop an all-artificial heart or other completely synthetic organs, the strategy has a distinct advantage: it seems poised to save lives now. “It’s clearly a very promising technology,” says William Harmon, a transplant physician at Children’s Hospital in Boston and president of the American Society of Transplantation.
Bioartificial organs’ most compelling use may be for kidney failure patients. While a strictly artificial device such as a dialysis machine can cleanse the blood, it can’t replace or mimic the subtler metabolic functions of a large, complex organ like the kidney. Dialysis machines just don’t do enough to save most patients in acute kidney failure. Nor, in the long term, do they do enough for the hundreds of thousands of people with chronically diseased kidneys. “Patients who are undergoing chronic dialysis become malnourished, and they sort of wither,” says Harmon. The solution, believes Humes, lies in harnessing kidney cells themselves-cells that can rapidly react to changes in the body’s environment in a way that machines simply can’t.
The kidney-in-a-cartridge, which is being developed by Lincoln, RI-based University of Michigan spinoff Nephros Therapeutics, could be ready for widespread use in as little as three years. And it’s only one example of the increasingly popular strategy of using living cells to do the heavy lifting in artificial organs. Several academic labs are developing similar devices packed with liver cells to chew up the toxins that accumulate in the blood when the liver suddenly fails. Already in human trials, these bioartificial livers could help patients in acute liver failure, whose only chance today is a rare organ transplant.
While bioartificial organs offer benefits that purely mechanical devices can’t match, they still have some severe limitations. For now at least, they are external devices, and the cells inside them stay healthy for no more than a few weeks. Even such temporary support could be a boon for medicine, sustaining thousands of patients and enabling them to regain the function of their own organs or survive until transplant organs become available. But the real revolution will come with the development of permanent, implantable bioartificial organs. That will require new materials that allow the cells to receive nourishment from the body but still protect them from attacks by the recipients’ immune systems. Such devices are years from fruition, but Humes and other researchers developing living temporary devices have started laying the groundwork for them-with the potential for eventually saving hundreds of thousands of lives (see Bioartificial Potential).