Life without properly functioning cells can be hell, and no one knows that better than a dialysis patient. People with chronic kidney disease-400,000 in the United States alone-plug into dialysis machines three to six times a week. The machines pump their blood through permeable tubes, squeezing out plasma (the fluid and proteins making up the bulk of blood) and dissolved wastes, which are tossed out. Then the oxygen-carrying red blood cells and the white blood cells of the immune system are mixed with fresh plasma and returned to the body. Such periodic flushing extends the lives of those with diseased or damaged kidneys, but it doesn’t make them healthy. Regardless of age, life expectancy for most patients on dialysis is capped at five years. “There’s no question that dialysis in its current mode is an insufficient treatment,” says Harmon. Dialysis is even less effective for the more than 120,000 Americans every year whose otherwise healthy kidneys are suddenly knocked out by infection, toxins, or strokes. Even with continuous dialysis, 60 percent of those facing acute kidney failure descend into multiple organ failure and death.
There are few if any options. Transplantation of a healthy, compatible kidney is the only reliable means of escape from dialysis. But those in acute failure are seldom stable enough to endure transplants; and while transplants rescue 14,000 people with chronic kidney disease in the U.S. each year, more than 50,000 languish on waiting lists, thousands of whom die waiting. Meanwhile, a fully artificial replacement for the kidney is unlikely any time soon. Bioengineers lack a complete understanding of what the organ does. And compared to cells, even the most ingenious mechanical device is woefully unsophisticated. “Cell therapy is based upon a billion years of Mother Nature’s research and development. We’re not that bright,” says Humes.
The promise of Humes’s bioartificial organ is to deliver the full range of kidney functions, even tasks such as regulating the immune system that are barely understood by medical science. Though the fix is temporary, patients who survive acute kidney failure have a good shot at a normal life, free of dialysis. For patients in chronic failure, cellular support could supplement traditional dialysis, arresting their slide into heart disease and infection, improving their quality of life, and increasing their life span.
Ten years ago Humes was one of the few nephrologists who believed that temporary support with living kidney cells was desirable. He was an early advocate of the theory, now gaining ground, that the organ helps to control inflammation and that the loss of this control is what makes acute kidney failure so deadly. In the early 1990s, Humes made the breakthrough that enabled the bioartificial kidney: he found a source of cells. Humes discovered how to isolate the immature cells that form the kidney’s tubules-its functional center. Within a few years, he had figured out how to coax these cells to form mature tubule structures in the lab.
To make the devices that Humes and Nephros are testing, technicians harvest immature kidney cells from donor organs deemed unsuitable for transplantation and seed them into hollow, plastic fibers (see “Bioartificial Treatment,” below). There the cells multiply and organize to form a continuous blanket of tissue just one cell thick, transforming each fiber into a living, working kidney tubule. “It’s basically what you would see in a kidney,” says Humes. “It’s their natural architecture.”
The first human tests showed that Humes’s kidney is safe. What is more exciting is that the device also appeared to pull a few of its first patients out of acute kidney failure, even though the U.S. Food and Drug Administration limited treatments in this initial trial to 24 hours. How such brief support from living tubules could save someone in such desperate condition isn’t clear. Humes believes that among the substances that the tubule cells add to blood are molecular signals that instruct the patient’s immune system to reign in the inflammation ravaging blood vessels throughout the body. By smothering this inflammatory “forest fire,” suggests Humes, the tubule cells stabilize blood pressure, oxygenating and rejuvenating the patient’s organs. “We view this treatment as almost like a drenching rain for 24 hours,” he says.