Recent advancements in engineering mean that the first preclinical trials for an artificial kidney could happen soon.
Like all those whose kidneys have failed, Scott Burton’s life revolves around dialysis. For nearly two decades, Burton has been hooked up (or, since 2020, has hooked himself up at home) to a dialysis machine that performs the job his kidneys normally would. The process is arduous, time-consuming, and expensive. Except for a brief window before his body rejected a kidney transplant, Burton has depended on machines to take the place of his kidneys since he was 12-years-old. His whole life, the 39-year-old says, revolves around dialysis.
“Whenever I try to plan anything, I also have to plan my dialysis,” says Burton says, who works as a freelance videographer and editor. “It’s a full-time job in itself.”
Many of those on dialysis are in line for a kidney transplant that would allow them to trade thrice-weekly dialysis and strict dietary limits for a lifetime of immunosuppressants. Burton’s previous transplant means that his body will likely reject another donated kidney unless it matches perfectly—something he’s not counting on. It’s why he’s enthusiastic about the development of artificial kidneys, small wearable or implantable devices that would do the job of a healthy kidney while giving users like Burton more flexibility for traveling, working, and more.
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.
Leaps.org talks with Dr. Tom Oxley, founding CEO of Synchron, a company that's taking a unique - and less invasive - approach to "brain-computer interfaces" for patients with ALS and other mobility challenges.
Listen on Apple | Listen on Spotify | Listen on Stitcher | Listen on Amazon | Listen on Google
In our conversation, Dr. Oxley talks about “Bluetooth brain”; the critical role of AI in the present and future of BCIs; how BCIs compare to voice command technology; regulatory frameworks for revolutionary technologies; specific people with paralysis who’ve been able to regain some independence thanks to the Stentrode; what it means to be a neurointerventionist; how to scale BCIs for more people to use them; the risks of BCIs malfunctioning; organic implants; and how BCIs help us understand the brain, among other topics.
Dr. Oxley received his PhD in neuro engineering from the University of Melbourne in Australia. He is the founding CEO of Synchron and an associate professor and the head of the vascular bionics laboratory at the University of Melbourne. He’s also a clinical instructor in the Deepartment of Neurosurgery at Mount Sinai Hospital. Dr. Oxley has completed more than 1,600 endovascular neurosurgical procedures on patients, including people with aneurysms and strokes, and has authored over 100 peer reviewed articles.
Links:
Synchron website - https://synchron.com/
Assessment of Safety of a Fully Implanted Endovascular Brain-Computer Interface for Severe Paralysis in 4 Patients (paper co-authored by Tom Oxley) - https://jamanetwork.com/journals/jamaneurology/art...
More research related to Synchron's work - https://synchron.com/research
Tom Oxley on LinkedIn - https://www.linkedin.com/in/tomoxl
Tom Oxley on Twitter - https://twitter.com/tomoxl?lang=en
Tom Oxley TED - https://www.ted.com/talks/tom_oxley_a_brain_implant_that_turns_your_thoughts_into_text?language=en
Tom Oxley website - https://tomoxl.com/
Novel brain implant helps paralyzed woman speak using digital avatar - https://engineering.berkeley.edu/news/2023/08/novel-brain-implant-helps-paralyzed-woman-speak-using-a-digital-avatar/
Edward Chang lab - https://changlab.ucsf.edu/
BCIs convert brain activity into text at 62 words per minute - https://med.stanford.edu/neurosurgery/news/2023/he...
Leaps.org: The Mind-Blowing Promise of Neural Implants - https://leaps.org/the-mind-blowing-promise-of-neural-implants/
Tom Oxley
Indigenous people in Australia dig pits next to a honeypot colony. Scientists think the honey can be used to make new antimicrobial drugs.
These hunts have become rarer, as many of the Tjupan people have moved away and, up until now, the exact antimicrobial properties of the ant honey remained unknown. But recently, scientists Andrew Dong and Kenya Fernandes from the University of Sydney, joined Ulrich, who runs the Honeypot Ants tours in Kalgoorlie, a city in Western Australia, on a honey-gathering expedition. Afterwards, they ran a series of experiments analyzing the honey’s antimicrobial activity—and confirmed that the Indigenous wisdom was true. The honey was effective against Staphylococcus aureus, a common pathogen responsible for sore throats, skin infections like boils and sores, and also sepsis, which can result in death. Moreover, the honey also worked against two species of fungi, Cryptococcus and Aspergillus, which can be pathogenic to humans, especially those with suppressed immune systems.
In the era of growing antibiotic resistance and the rising threat of pathogenic fungi, these findings may help scientists identify and make new antimicrobial compounds. “Natural products have been honed over thousands and millions of years by nature and evolution,” says Fernandes. “And some of them have complex and intricate properties that make them really important as potential new antibiotics. “
In an era of growing resistance to antibiotics and new threats of fungi infections, the latest findings about honeypot ants are helping scientists identify new antimicrobial drugs.
Danny Ulrich
Bee honey is also known for its antimicrobial properties, but bees produce it very differently than the ants. Bees collect nectar from flowers, which they regurgitate at the hive and pack into the hexagonal honeycombs they build for storage. As they do so, they also add into the mix an enzyme called glucose oxidase produced by their glands. The enzyme converts atmospheric oxygen into hydrogen peroxide, a reactive molecule that destroys bacteria and acts as a natural preservative. After the bees pack the honey into the honeycombs, they fan it with their wings to evaporate the water. Once a honeycomb is full, the bees put a beeswax cover on it, where it stays well-preserved thanks to the enzymatic action, until the bees need it.
Less is known about the chemistry of ants’ honey-making. Similarly to bees, they collect nectar. They also collect the sweet sap of the mulga tree. Additionally, they also “milk” the aphids—small sap-sucking insects that live on the tree. When ants tickle the aphids with their antennae, the latter release a sweet substance, which the former also transfer to their colonies. That’s where the honey management difference becomes really pronounced. The ants don’t build any kind of structures to store their honey. Instead, they store it in themselves.
The workers feed their harvest to their fellow ants called repletes, stuffing them up to the point that their swollen bellies outgrow the ants themselves, looking like amber-colored honeypots—hence the name. Because of their size, repletes don’t move, but hang down from the chamber’s ceiling, acting as living feedstocks. When food becomes scarce, they regurgitate their reserves to their colony’s brethren. It’s not clear whether the repletes die afterwards or can be restuffed again. “That's a good question,” Dong says. “After they've been stretched, they can't really return to exactly the same shape.”
These replete ants are the “treat” the Tjupan women dug for. Once they saw the round-belly ants inside the chambers, they would reach in carefully and get a few scoops of them. “You see a lot of honeypot ants just hanging on the roof of the little openings,” says Ulrich’s mother, Edie Ulrich. The women would share the ants with family members who would eat them one by one. “They're very delicate,” shares Edie Ulrich—you have to take them out carefully, so they don’t accidentally pop and become a wasted resource. “Because you’d lose all this precious honey.”
Dong stumbled upon the honeypot ants phenomenon because he was interested in Indigenous foods and went on Ulrich’s tour. He quickly became fascinated with the insects and their role in the Indigenous culture. “The honeypot ants are culturally revered by the Indigenous people,” he says. Eventually he decided to test out the honey’s medicinal qualities.
The researchers were surprised to see that even the smallest, eight percent concentration of honey was able to arrest the growth of S. aureus.
To do this, the two scientists first diluted the ant honey with water. “We used something called doubling dilutions, which means that we made 32 percent dilutions, and then we halve that to 16 percent and then we half that to eight percent,” explains Fernandes. The goal was to obtain as much results as possible with the meager honey they had. “We had very, very little of the honeypot ant honey so we wanted to maximize the spectrum of results we can get without wasting too much of the sample.”
After that, the researchers grew different microbes inside a nutrient rich broth. They added the broth to the different honey dilutions and incubated the mixes for a day or two at the temperature favorable to the germs’ growth. If the resulting solution turned turbid, it was a sign that the bugs proliferated. If it stayed clear, it meant that the honey destroyed them. The researchers were surprised to see that even the smallest, eight percent concentration of honey was able to arrest the growth of S. aureus. “It was really quite amazing,” Fernandes says. “Eight milliliters of honey in 92 milliliters of water is a really tiny amount of honey compared to the amount of water.”
Similar to bee honey, the ants’ honey exhibited some peroxide antimicrobial activity, researchers found, but given how little peroxide was in the solution, they think the honey also kills germs by a different mechanism. “When we measured, we found that [the solution] did have some hydrogen peroxide, but it didn't have as much of it as we would expect based on how active it was,” Fernandes says. “Whether this hydrogen peroxide also comes from glucose oxidase or whether it's produced by another source, we don't really know,” she adds. The research team does have some hypotheses about the identity of this other germ-killing agent. “We think it is most likely some kind of antimicrobial peptide that is actually coming from the ant itself.”
The honey also has a very strong activity against the two types of fungi, Cryptococcus and Aspergillus. Both fungi are associated with trees and decaying leaves, as well as in the soils where ants live, so the insects likely have evolved some natural defense compounds, which end up inside the honey.
It wouldn’t be the first time when modern medicines take their origin from the natural world or from the indigenous people’s knowledge. The bark of the cinchona tree native to South America contains quinine, a substance that treats malaria. The Indigenous people of the Andes used the bark to quell fever and chills for generations, and when Europeans began to fall ill with malaria in the Amazon rainforest, they learned to use that medicine from the Andean people.
The wonder drug aspirin similarly takes its origin from a bark of a tree—in this case a willow.
Even some anticancer compounds originated from nature. A chemotherapy drug called Paclitaxel, was originally extracted from the Pacific yew trees, Taxus brevifolia. The samples of the Pacific yew bark were first collected in 1962 by researchers from the United States Department of Agriculture who were looking for natural compounds that might have anti-tumor activity. In December 1992, the FDA approved Paclitaxel (brand name Taxol) for the treatment of ovarian cancer and two years later for breast cancer.
In the era when the world is struggling to find new medicines fast enough to subvert a fungal or bacterial pandemic, these discoveries can pave the way to new therapeutics. “I think it's really important to listen to indigenous cultures and to take their knowledge because they have been using these sources for a really, really long time,” Fernandes says. Now we know it works, so science can elucidate the molecular mechanisms behind it, she adds. “And maybe it can even provide a lead for us to develop some kind of new treatments in the future.”