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Biomedicine

Building an Implantable Artificial Kidney

A prototype uses kidney cells to help it perform vital functions.

Nearly 400,000 people in the United States–and as many as two million worldwide–rely on dialysis machines to filter toxins from their blood because of chronic kidney failure.

Under pressure: A bioengineered kidney takes advantage of silicon membranes that allow very low-pressure filtration. The membrane in this image is layered with kidney cells. The cells’ nuclei are shown in blue, their microtubules in red, and a junction protein called ZO-1 in green.

Patients must be tethered to machines at least three times a week for three to five hours at a stretch. Even then, a dialysis machine is only about 13 percent as effective as a functional kidney, and the five-year survival rate of patients on dialysis is just 33 to 35 percent. To restore health, patients need a kidney transplant, and there just aren’t enough donor organs to go around. In August, there were 85,000 patients on the U.S. waiting list for a kidney in the U.S., while only 17,000 kidney transplants took place last year.

A collaborative, multidisciplinary group of labs is working to create the first implantable artificial kidney. The prototype, revealed last week, is compact, no larger than a soup can. It not only filters toxins out of the bloodstream but also uses human kidney cells to perform other vital functions, such as regulating blood pressure and producing vitamin D.

“Dialysis is not only time-consuming, but it’s also debilitating. Many patients don’t feel good, because it’s not doing all the functions of a normal, healthy kidney,” says bioengineer Shuvo Roy, whose lab at the University of California, San Francisco produced the new device and is already testing it in animals. “The kidney doesn’t just filter toxins. It also has metabolic functions and hormonal functions, and dialysis doesn’t capture these abilities.”

Making an artificial kidney small enough to fit inside the body is, however, a big challenge. A healthy kidney filters 90 liters of water each day. Current dialysis machines are the size of a small refrigerator, and require substantial pressure to pump enough water through the machine’s porous membranes to allow contaminants to be filtered out of the blood.

The new implant is a fusion of multiple lines of research, and takes advantage of two recent advances in the field. University of Michigan nephrologist David Humes has shown that human kidney cells could be used in a room-sized filtration machine to greatly improve the health of patients whose kidneys have stopped functioning. Meanwhile, Roy and William Fissell, a nephrologist at the Cleveland Clinic, have produced a nano-pore silicon membrane that–with its dense and precise pore-structure–could help miniaturize dialysis machines.

The prototype is a two-part system: half consists of a toxin-removing filter, in which thousands of silicon membranes are stacked together. Their nano-pores are so dense, and so precisely shaped, that they can filter very precisely using only the force of the body’s own blood pressure. Blood flows in through this filter, where the toxins, sugars, water, and salts are removed as a filtered solution.

The clean blood and watery filtrate are both shunted into the other half of the system: a separate cartridge. Here, they flow over more silicon membranes, these ones coated with a single type of human kidney cell, which helps the device reabsorb some of the water, sugars, and salts, as well as produce vitamin D and help prevent blood pressure from sinking too low–normal kidney functions that are not offered by dialysis. The waste that’s not reabsorbed is shunted to a tube attached to the bladder and removed as waste in the urine–just like a normal kidney would do.

It’s far from a complete system, and the researchers note that they don’t ever expect it to replace kidney transplants. “Your kidney has 20 to 30 cell types in it, all of which accomplish different functions. But we’d like to overcome a critical issue that’s emerged in renal failure,” says Fissell. “If you’re listed for a kidney transplant, you’re far more likely to die on the waitlist than you are to get a kidney.” He says the device could act as a bridge for patients awaiting transplant.

“From a general perspective, any implantable device would sharply reduce the burden that patients now experience,” says Glenn Chertow, the chief of nephrology at the Stanford University School of Medicine. “And if some of the additional magic that a native kidney provides could be added to an implantable device, we could come closer to a restoration of good health.”

The researchers have already worked out some of the more difficult issues: Humes has worked out how to culture kidney cells on the necessary scale (he can culture enough cells for 100,000 devices from a single kidney). He’s also determined the best way to freeze them for future use. And Roy, a TR35 winner in 2003, has tested the implant in a dozen rats and a handful of pigs. They still have to scale up the implant’s efficiency to something that could work effectively in humans, but they hope to start human trials in five-to-seven years. Right now the biocartridge can filter between 30 to 35 liters of water per day, and it needs to be able to filter at least 43. They also have to find ways to ensure that the devices don’t cause blood clots or immune reactions.

Other groups are also working toward alternatives to thrice-weekly dialysis appointments, although most are concentrating on wearable dialysis devices–a difficult proposition in itself, given the challenge of constant filtration at such large volumes without an external pump. One such device is already in the second stage of clinical trials. But even constant dialysis can’t take the place of the kidney’s other functions.

Allen Nissenson, CMO of DaVita, one of the country’s largest dialysis provider, says the implantable concept holds appeal. “It’s a bioreactor kidney, an incredibly innovative concept, and really exciting if it proves to be workable on a larger scale,” he says.

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