Custom Kidneys
Today, patients who have kidney failure and are waiting for a transplant have one option: dialysis. While other people are working and playing, dialysis patients are sitting in a clinic three times a week while a machine cleans their blood because their kidneys can’t do the job. And there are not enough donated kidneys to go around. According to William Fissell, MD, a nephrologist in the Glickman Urological & Kidney Institute, 80,000 people in the United States are on the wait list, but only 16,000 transplants occur each year. That’s why Dr. Fissell and other Cleveland Clinic researchers are building a bioartificial kidney.
Each of the body’s two kidneys has about a million filters that hold onto things the body needs, such as proteins and antibodies, and filter out waste products, which are smaller. The pores that let out waste products are all the same size, and they’re slit shaped. Conventional dialysis machines are less effective: They use filters with holes that are different sizes — and all smaller than the kidneys’ pores. The process for making the filtering membrane in conventional dialysis machines gives rise to a wide range of pore sizes. “It is exactly this difficulty that led us to explore an entirely new technology for membrane design and manufacturing,” says Dr. Fissell. Cleveland Clinic’s Shuvo Roy, PhD (now at the University of California, San Francisco), developed the bioartificial kidney’s membrane.
The bioartificial kidney employs the same strategy as a real kidney, which has two main parts: a filter called the glomerulus and a bioreactor called the tubule, Dr. Fissell says. The first filters the blood, and the second concentrates a high volume of liquid waste into urine. Cleveland Clinic’s bioartificial kidney is made of silicon with pores that are just the right shape and 1,000 times smaller than a red blood cell. This is more efficient than the unevenly sized and shaped pores of dialysis machines. The silicon also creates a scaffold on which kidney cells, which concentrate the urine after it passes through the pores, can grow. “The cells in the bioreactor, like most cells in the body, grow only when attached to a surface,” Dr. Fissell explains.
Although researchers have been able to grow kidney cells in the lab, the question is whether they’ll be able to grow the cells in a device as compact as the bioartificial kidney, which will be the size of a large cell phone.
There are other challenges as well: “You have to be able to grow the cells in a sterile environment, and you have to be able to pump fluid across the cells at a blood pressure that’s similar to normal blood pressure — and then you need to design some place for the urine to go,” explains Eric Klein, MD, Chairman of the Glickman Urological & Kidney Institute at Cleveland Clinic and holder of the Andrew C. Novick, MD, Distinguished Chair in Urology. The researchers are working fast to overcome these challenges. Says Dr. Fissell, “We have had good success with the building blocks of the bioartificial kidney on the lab bench, and we are starting to integrate the components into a device. We plan on first in-human use at the end of 2015.”
Dr. Fissell expects that the bioartificial kidney will need to be refreshed every six months. The functional components will be replaceable cassettes, allowing doctors to replace failing components and update the technology as research progresses. The plan is to insert the artificial kidney in the same place a transplanted kidney would go — midway between the navel and the hip on the right side — but just under the skin, so that it requires only minor surgery to remove and replace it.
While Dr. Fissell and his colleagues are working on this device, he communicates often with Victor Gura, MD, Associate Clinical Professor of Medicine at UCLA. Dr. Gura is developing a belt-size dialysis machine called the wearable artificial kidney, which will be worn around the waist and connected to a vein in the neck by a catheter that runs under the skin. The initial prototype of the device, which is moving into long-term studies in dialysis patients, weighs about 10 pounds and runs on two nine-volt batteries.
“The idea was to put the component of the artificial kidney into an area of the body that would be ergonomic enough so people can wear it and walk around with it,” says Dr. Gura. “What we did is miniaturize everything we could miniaturize, like the pumps. We typically use about 40 gallons of water to do one dialysis treatment, and with this device we went all the way to less than 400 cc [under 2 cups].”
The wearable artificial kidney will help patients until the bioartificial kidney is ready for use, says Dr. Fissell. “Dr. Gura’s is already in trials — he’ll be treating real sick people long before I will,” Dr. Fissell says. “It’s stepping stones along the way.”