Recent advancements in engineering mean that the first preclinical trials for an artificial kidney could happen soon.
Still, the devices aren’t ready for testing in humans—yet. But recent advancements in engineering mean that the first preclinical trials for an artificial kidney could happen soon, according to Jonathan Himmelfarb, a nephrologist at the University of Washington.
“It would liberate people with kidney failure,” Himmelfarb says.
An engineering marvel
Compared to the heart or the brain, the kidney doesn’t get as much respect from the medical profession, but its job is far more complex. “It does hundreds of different things,” says UCLA’s Ira Kurtz.
Kurtz would know. He’s worked as a nephrologist for 37 years, devoting his career to helping those with kidney disease. While his colleagues in cardiology and endocrinology have seen major advances in the development of artificial hearts and insulin pumps, little has changed for patients on hemodialysis. The machines remain bulky and require large volumes of a liquid called dialysate to remove toxins from a patient’s blood, along with gallons of purified water. A kidney transplant is the next best thing to someone’s own, functioning organ, but with over 600,000 Americans on dialysis and only about 100,000 kidney transplants each year, most of those in kidney failure are stuck on dialysis.
Part of the lack of progress in artificial kidney design is the sheer complexity of the kidney’s job. Each of the 45 different cell types in the kidney do something different.
Part of the lack of progress in artificial kidney design is the sheer complexity of the kidney’s job. To build an artificial heart, Kurtz says, you basically need to engineer a pump. An artificial pancreas needs to balance blood sugar levels with insulin secretion. While neither of these tasks is simple, they are fairly straightforward. The kidney, on the other hand, does more than get rid of waste products like urea and other toxins. Each of the 45 different cell types in the kidney do something different, helping to regulate electrolytes like sodium, potassium, and phosphorous; maintaining blood pressure and water balance; guiding the body’s hormonal and inflammatory responses; and aiding in the formation of red blood cells.
There's been little progress for patients during Ira Kurtz's 37 years as a nephrologist. Artificial kidneys would change that.
UCLA
Dialysis primarily filters waste, and does so well enough to keep someone alive, but it isn’t a true artificial kidney because it doesn’t perform the kidney’s other jobs, according to Kurtz, such as sensing levels of toxins, wastes, and electrolytes in the blood. Due to the size and water requirements of existing dialysis machines, the equipment isn’t portable. Physicians write a prescription for a certain duration of dialysis and assess how well it’s working with semi-regular blood tests. The process of dialysis itself, however, is conducted blind. Doctors can’t tell how much dialysis a patient needs based on kidney values at the time of treatment, says Meera Harhay, a nephrologist at Drexel University in Philadelphia.
But it’s the impact of dialysis on their day-to-day lives that creates the most problems for patients. Only one-quarter of those on dialysis are able to remain employed (compared to 85% of similar-aged adults), and many report a low quality of life. Having more flexibility in life would make a major different to her patients, Harhay says.
“Almost half their week is taken up by the burden of their treatment. It really eats away at their freedom and their ability to do things that add value to their life,” she says.
Art imitates life
The challenge for artificial kidney designers was how to compress the kidney’s natural functions into a portable, wearable, or implantable device that wouldn’t need constant access to gallons of purified and sterilized water. The other universal challenge they faced was ensuring that any part of the artificial kidney that would come in contact with blood was kept germ-free to prevent infection.
As part of the 2021 KidneyX Prize, a partnership between the U.S. Department of Health and Human Services and the American Society of Nephrology, inventors were challenged to create prototypes for artificial kidneys. Himmelfarb’s team at the University of Washington’s Center for Dialysis Innovation won the prize by focusing on miniaturizing existing technologies to create a portable dialysis machine. The backpack sized AKTIV device (Ambulatory Kidney to Increase Vitality) will recycle dialysate in a closed loop system that removes urea from blood and uses light-based chemical reactions to convert the urea to nitrogen and carbon dioxide, which allows the dialysate to be recirculated.
Himmelfarb says that the AKTIV can be used when at home, work, or traveling, which will give users more flexibility and freedom. “If you had a 30-pound device that you could put in the overhead bins when traveling, you could go visit your grandkids,” he says.
Kurtz’s team at UCLA partnered with the U.S. Kidney Research Corporation and Arkansas University to develop a dialysate-free desktop device (about the size of a small printer) as the first phase of a progression that will he hopes will lead to something small and implantable. Part of the reason for the artificial kidney’s size, Kurtz says, is the number of functions his team are cramming into it. Not only will it filter urea from blood, but it will also use electricity to help regulate electrolyte levels in a process called electrodeionization. Kurtz emphasizes that these additional functions are what makes his design a true artificial kidney instead of just a small dialysis machine.
One version of an artificial kidney.
UCLA
“It doesn't have just a static function. It has a bank of sensors that measure chemicals in the blood and feeds that information back to the device,” Kurtz says.
Other startups are getting in on the game. Nephria Bio, a spinout from the South Korean-based EOFlow, is working to develop a wearable dialysis device, akin to an insulin pump, that uses miniature cartridges with nanomaterial filters to clean blood (Harhay is a scientific advisor to Nephria). Ian Welsford, Nephria’s co-founder and CTO, says that the device’s design means that it can also be used to treat acute kidney injuries in resource-limited settings. These potentials have garnered interest and investment in artificial kidneys from the U.S. Department of Defense.
For his part, Burton is most interested in an implantable device, as that would give him the most freedom. Even having a regular outpatient procedure to change batteries or filters would be a minor inconvenience to him.
“Being plugged into a machine, that’s not mimicking life,” he says.
This article was first published by Leaps.org on May 5, 2022.
Katalin Karikó, pictured, and Drew Weissman won the Nobel Prize for advances in mRNA research that led to the first Covid vaccines.
The work for which they garnered the illustrious award and its accompanying $1,000,000 cash windfall was completed about two decades ago, wrought through long hours in the lab over many arduous years. But humanity collectively benefited from its life-saving outcome three years ago, when both Moderna and Pfizer/BioNTech’s mRNA vaccines against COVID were found to be safe and highly effective at preventing severe disease. Billions of doses have since been given out to protect humans from the upstart viral scourge.
“I thought of going somewhere else, or doing something else,” said Katalin Karikó. “I also thought maybe I’m not good enough, not smart enough. I tried to imagine: Everything is here, and I just have to do better experiments.”
Unlocking the power of mRNA
Weissman and Karikó unlocked mRNA vaccines for the world back in the early 2000s when they made a key breakthrough. Messenger RNA molecules are essentially instructions for cells’ ribosomes to make specific proteins, so in the 1980s and 1990s, researchers started wondering if sneaking mRNA into the body could trigger cells to manufacture antibodies, enzymes, or growth agents for protecting against infection, treating disease, or repairing tissues. But there was a big problem: injecting this synthetic mRNA triggered a dangerous, inflammatory immune response resulting in the mRNA’s destruction.
While most other researchers chose not to tackle this perplexing problem to instead pursue more lucrative and publishable exploits, Karikó stuck with it. The choice sent her academic career into depressing doldrums. Nobody would fund her work, publications dried up, and after six years as an assistant professor at the University of Pennsylvania, Karikó got demoted. She was going backward.
“I thought of going somewhere else, or doing something else,” Karikó told Stat in 2020. “I also thought maybe I’m not good enough, not smart enough. I tried to imagine: Everything is here, and I just have to do better experiments.”
A tale of tenacity
Collaborating with Drew Weissman, a new professor at the University of Pennsylvania, in the late 1990s helped provide Karikó with the tenacity to continue. Weissman nurtured a goal of developing a vaccine against HIV-1, and saw mRNA as a potential way to do it.
“For the 20 years that we’ve worked together before anybody knew what RNA is, or cared, it was the two of us literally side by side at a bench working together,” Weissman said in an interview with Adam Smith of the Nobel Foundation.
In 2005, the duo made their 2023 Nobel Prize-winning breakthrough, detailing it in a relatively small journal, Immunity. (Their paper was rejected by larger journals, including Science and Nature.) They figured out that chemically modifying the nucleoside bases that make up mRNA allowed the molecule to slip past the body’s immune defenses. Karikó and Weissman followed up that finding by creating mRNA that’s more efficiently translated within cells, greatly boosting protein production. In 2020, scientists at Moderna and BioNTech (where Karikó worked from 2013 to 2022) rushed to craft vaccines against COVID, putting their methods to life-saving use.
The future of vaccines
Buoyed by the resounding success of mRNA vaccines, scientists are now hurriedly researching ways to use mRNA medicine against other infectious diseases, cancer, and genetic disorders. The now ubiquitous efforts stand in stark contrast to Karikó and Weissman’s previously unheralded struggles years ago as they doggedly worked to realize a shared dream that so many others shied away from. Katalin Karikó and Drew Weissman were brave enough to walk a scientific path that very well could have ended in a dead end, and for that, they absolutely deserve their 2023 Nobel Prize.
This article originally appeared on Big Think, home of the brightest minds and biggest ideas of all time.
With conventional fuel cells as their model, researchers learned to use similar chemical reactions to make a fuel from microbes in pee.
Plus, urine contains water, phosphorus, potassium and nitrogen, the key ingredients plants need to grow and survive. Human urine could replace about 25 percent of current nitrogen and phosphorous fertilizers worldwide and could save water for gardens and crops. The average U.S. resident flushes a toilet bowl containing only pee and paper about six to seven times a day, which adds up to about 3,500 gallons of water down per year. Plus cows in the U.S. produce 231 gallons of the stuff each year.
Pee power
A conventional fuel cell uses chemical reactions to produce energy, as electrons move from one electrode to another to power a lightbulb or phone. Ioannis Ieropoulos, a professor and chair of Environmental Engineering at the University of Southampton in England, realized the same type of reaction could be used to make a fuel from microbes in pee.
Bacterial species like Shewanella oneidensis and Pseudomonas aeruginosa can consume carbon and other nutrients in urine and pop out electrons as a result of their digestion. In a microbial fuel cell, one electrode is covered in microbes, immersed in urine and kept away from oxygen. Another electrode is in contact with oxygen. When the microbes feed on nutrients, they produce the electrons that flow through the circuit from one electrod to another to combine with oxygen on the other side. As long as the microbes have fresh pee to chomp on, electrons keep flowing. And after the microbes are done with the pee, it can be used as fertilizer.
These microbes are easily found in wastewater treatment plants, ponds, lakes, rivers or soil. Keeping them alive is the easy part, says Ieropoulos. Once the cells start producing stable power, his group sequences the microbes and keeps using them.
Like many promising technologies, scaling these devices for mass consumption won’t be easy, says Kevin Orner, a civil engineering professor at West Virginia University. But it’s moving in the right direction. Ieropoulos’s device has shrunk from the size of about three packs of cards to a large glue stick. It looks and works much like a AAA battery and produce about the same power. By itself, the device can barely power a light bulb, but when stacked together, they can do much more—just like photovoltaic cells in solar panels. His lab has produced 1760 fuel cells stacked together, and with manufacturing support, there’s no theoretical ceiling, he says.
Although pure urine produces the most power, Ieropoulos’s devices also work with the mixed liquids of the wastewater treatment plants, so they can be retrofit into urban wastewater utilities.
This image shows how the pee-powered system works. Pee feeds bacteria in the stack of fuel cells (1), which give off electrons (2) stored in parallel cylindrical cells (3). These cells are connected to a voltage regulator (4), which smooths out the electrical signal to ensure consistent power to the LED strips lighting the toilet.
Courtesy Ioannis Ieropoulos
Key to the long-term success of any urine reclamation effort, says Orner, is avoiding what he calls “parachute engineering”—when well-meaning scientists solve a problem with novel tech and then abandon it. “The way around that is to have either the need come from the community or to have an organization in a community that is committed to seeing a project operate and maintained,” he says.
Success with urine reclamation also depends on the economy. “If energy prices are low, it may not make sense to recover energy,” says Orner. “But right now, fertilizer prices worldwide are generally pretty high, so it may make sense to recover fertilizer and nutrients.” There are obstacles, too, such as few incentives for builders to incorporate urine recycling into new construction. And any hiccups like leaks or waste seepage will cost builders money and reputation. Right now, Orner says, the risks are just too high.
Despite the challenges, Ieropoulos envisions a future in which urine is passed through microbial fuel cells at wastewater treatment plants, retrofitted septic tanks, and building basements, and is then delivered to businesses to use as agricultural fertilizers. Although pure urine produces the most power, Ieropoulos’s devices also work with the mixed liquids of the wastewater treatment plants, so they can be retrofitted into urban wastewater utilities where they can make electricity from the effluent. And unlike solar cells, which are a common target of theft in some areas, nobody wants to steal a bunch of pee.
When Ieropoulos’s team returned to wrap up their pilot project 18 months later, the school’s director begged them to leave the fuel cells in place—because they made a major difference in students’ lives. “We replaced it with a substantial photovoltaic panel,” says Ieropoulos, They couldn’t leave the units forever, he explained, because of intellectual property reasons—their funders worried about theft of both the technology and the idea. But the photovoltaic replacement could be stolen, too, leaving the girls in the dark.
The story repeated itself at another school, in Nairobi, Kenya, as well as in an informal settlement in Durban, South Africa. Each time, Ieropoulos vowed to return. Though the pandemic has delayed his promise, he is resolute about continuing his work—it is a moral and legal obligation. “We've made a commitment to ourselves and to the pupils,” he says. “That's why we need to go back.”
Urine as fertilizer
Modern day industrial systems perpetuate the broken cycle of nutrients. When plants grow, they use up nutrients the soil. We eat the plans and excrete some of the nutrients we pass them into rivers and oceans. As a result, farmers must keep fertilizing the fields while our waste keeps fertilizing the waterways, where the algae, overfertilized with nitrogen, phosphorous and other nutrients grows out of control, sucking up oxygen that other marine species need to live. Few global communities remain untouched by the related challenges this broken chain create: insufficient clean water, food, and energy, and too much human and animal waste.
The Rich Earth Institute in Vermont runs a community-wide urine nutrient recovery program, which collects urine from homes and businesses, transports it for processing, and then supplies it as fertilizer to local farms.
One solution to this broken cycle is reclaiming urine and returning it back to the land. The Rich Earth Institute in Vermont is one of several organizations around the world working to divert and save urine for agricultural use. “The urine produced by an adult in one day contains enough fertilizer to grow all the wheat in one loaf of bread,” states their website.
Notably, while urine is not entirely sterile, it tends to harbor fewer pathogens than feces. That’s largely because urine has less organic matter and therefore less food for pathogens to feed on, but also because the urinary tract and the bladder have built-in antimicrobial defenses that kill many germs. In fact, the Rich Earth Institute says it’s safe to put your own urine onto crops grown for home consumption. Nonetheless, you’ll want to dilute it first because pee usually has too much nitrogen and can cause “fertilizer burn” if applied straight without dilution. Other projects to turn urine into fertilizer are in progress in Niger, South Africa, Kenya, Ethiopia, Sweden, Switzerland, The Netherlands, Australia, and France.
Eleven years ago, the Institute started a program that collects urine from homes and businesses, transports it for processing, and then supplies it as fertilizer to local farms. By 2021, the program included 180 donors producing over 12,000 gallons of urine each year. This urine is helping to fertilize hay fields at four partnering farms. Orner, the West Virginia professor, sees it as a success story. “They've shown how you can do this right--implementing it at a community level scale."