Scientists are making machines, wearable and implantable, to act as kidneys
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 as soon as 18 months from now, 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 last year’s 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.
Two-and-a-half year-old Huckleberry, a blue merle Australian shepherd, pulls hard at her leash; her yelps can be heard by skiers and boarders high above on the chairlift that carries them over the ski patrol hut to the top of the mountain. Huckleberry is an avalanche rescue dog — or avy dog, for short. She lives and works with her owner and handler, a ski patroller at Breckenridge Ski Resort in Colorado. As she watches the trainer play a game of hide-and-seek with six-month-old Lume, a golden retriever and avy dog-in-training, Huckleberry continues to strain on her leash; she loves the game. Hide-and-seek is one of the key training methods for teaching avy dogs the rescue skills they need to find someone caught in an avalanche — skier, snowmobiler, hiker, climber.
Lume’s owner waves a T-shirt in front of the puppy. While another patroller holds him back, Lume’s owner runs away and hides. About a minute later — after a lot of barking — Lume is released and commanded to “search.” He springs free, running around the hut to find his owner who reacts with a great amount of excitement and fanfare. Lume’s scent training will continue for the rest of the ski season (Breckenridge plans operating through May or as long as weather permits) and through the off-season. “We make this game progressively harder by not allowing the dog watch the victim run away,” explains Dave Leffler, Breckenridge's ski patroller and head of the avy dog program, who has owned, trained and raised many of them. Eventually, the trainers “dig an open hole in the snow to duck out of sight and gradually turn the hole into a cave where the dog has to dig to get the victim,” explains Leffler.
By the time he is three, Lume, like Huckleberry, will be a fully trained avy pup and will join seven other avy dogs on Breckenridge ski patrol team. Some of the team members, both human and canine, are also certified to work with Colorado Rapid Avalanche Deployment, a coordinated response team that works with the Summit County Sheriff’s office for avalanche emergencies outside of the ski slopes’ boundaries.
There have been 19 avalanche deaths in the U.S. this season, according to avalanche.org, which tracks slides; eight in Colorado. During the entirety of last season there were 17. Avalanche season runs from November through June, but avalanches can occur year-round.
High tech and high stakes
Complementing avy dogs’ ability to smell people buried in a slide, avalanche detection, rescue and recovery is becoming increasingly high tech. There are transceivers, signal locators, ground scanners and drones, which are considered “games changers” by many in avalanche rescue and recovery
For a person buried in an avalanche, the chance of survival plummets after 20 minutes, so every moment counts.
A drone can provide thermal imaging of objects caught in a slide; what looks like a rock from far away might be a human with a heat signature. Transceivers, also known as beacons, send a signal from an avalanche victim to a companion. Signal locators, like RECCO reflectors which are often sewn directly into gear, can echo back a radar signal sent by a detector; most ski resorts have RECCO detector units.
Research suggests that Ground Penetrating Radar (GPR), an electromagnetic tool used by geophysicists to pull images from inside the ground, could be used to locate an avalanche victim. A new study from the Department of Energy’s Sandia National Laboratories suggests that a computer program developed to pinpoint the source of a chemical or biological terrorist attack could also be used to find someone submerged in an avalanche. The search algorithm allows for small robots (described as cockroach-sized) to “swarm” a search area. Researchers say that this distributed optimization algorithm can help find avalanche victims four times faster than current search mechanisms. For a person buried in an avalanche, the chance of survival plummets after 20 minutes, so every moment counts.
An avy dog in training is picking up scent
Sarah McLear
While rescue gear has been evolving, predicting when a slab will fall remains an emerging science — kind of where weather forecasting science was in the 1980s. Avalanche forecasting still relies on documenting avalanches by going out and looking,” says Ethan Greene, director of the Colorado Avalanche Information Center (CAIC). “So if there's a big snowstorm, and as you might remember, most avalanches happened during snowstorms, we could have 10,000 avalanches that release and we document 50,” says Greene. “Avalanche forecasting is essentially pattern recognition,” he adds--and understanding the layering structure of snow.
However, determining where the hazards lie can be tricky. While a dense layer of snow over a softer, weaker layer may be a recipe for an avalanche, there’s so much variability in snowpack that no one formula can predict the trigger. Further, observing and measuring snow at a single point may not be representative of all nearby slopes. Finally, there’s not enough historical data to help avalanche scientists create better prediction models.
That, however, may be changing.
Last year, an international group of researchers created computer simulations of snow cover using 16 years of meteorological data to forecast avalanche hazards, publishing their research in Cold Regions Science and Technology. They believe their models, which categorize different kinds of avalanches, can support forecasting and determine whether the avalanche is natural (caused by temperature changes, wind, additional snowfall) or artificial (triggered by a human or animal).
With smell receptors ranging from 800 million for an average dog, to 4 billion for scent hounds, canines remain key to finding people caught in slides.
With data from two sites in British Columbia and one in Switzerland, researchers built computer simulations of five different avalanche types. “In terms of real time avalanche forecasting, this has potential to fill in a lot of data gaps, where we don't have field observations of what the snow looks like,” says Simon Horton, a postdoctoral fellow with the Simon Fraser University Centre for Natural Hazards Research and a forecaster with Avalanche Canada, who participated in the study. While complex models that simulate snowpack layers have been around for a few decades, they weren’t easy to apply until recently. “It's been difficult to find out how to apply that to actual decision-making and improving safety,” says Horton. If you can derive avalanche problem types from simulated snowpack properties, he says, you’ll learn “a lot about how you want to manage that risk.”
The five categories include “new snow,” which is unstable and slides down the slope, “wet snow,” when rain or heat makes it liquidly, as well as “wind-drifted snow,” “persistent weak layers” and “old snow.” “That's when there's some type of deeply buried weak layer in the snow that releases without any real change in the weather,” Horton explains. “These ones tend to cause the most accidents.” One step by a person on that structurally weak layer of snow will cause a slide. Horton is hopeful that computer simulations of avalanche types can be used by scientists in different snow climates to help predict hazard levels.
Greene is doubtful. “If you have six slopes that are lined up next to each other, and you're going to try to predict which one avalanches and the exact dimensions and what time, that's going to be really hard to do. And I think it's going to be a long time before we're able to do that,” says Greene.
What both researchers do agree on, though, is that what avalanche prediction really needs is better imagery through satellite detection. “Just being able to count the number of avalanches that are out there will have a huge impact on what we do,” Greene says. “[Satellites] will change what we do, dramatically.” In a 2022 paper, scientists at the University of Aberdeen in England used satellites to study two deadly Himalayan avalanches. The imaging helped them determine that sediment from a 2016 ice avalanche plus subsequent snow avalanches contributed to the 2021 avalanche that caused a flash flood, killing over 200 people. The researchers say that understanding the avalanches characteristics through satellite imagery can inform them how one such event increases the magnitude of another in the same area.
Avy dogs trainers hide in dug-out holes in the snow, teaching the dogs to find buried victims
Sarah McLear
Lifesaving combo: human tech and Mother Nature’s gear
Even as avalanche forecasting evolves, dogs with their built-in rescue mechanisms will remain invaluable. With smell receptors ranging from 800 million for an average dog, to 4 billion for scent hounds, canines remain key to finding people caught in slides. (Humans in comparison, have a meager 12 million.) A new study published in the Journal of Neuroscience revealed that in dogs smell and vision are connected in the brain, which has not been found in other animals. “They can detect the smell of their owner's fingerprints on a glass slide six weeks after they touched it,” says Nicholas Dodman, professor emeritus at Cummings School of Veterinary Medicine at Tufts University. “And they can track from a boat where a box filled with meat was buried in the water, 100 feet below,” says Dodman, who is also co-founder and president of the Center for Canine Behavior Studies.
Another recent study from Queens College in Belfast, United Kingdom, further confirms that dogs can smell when humans are stressed. They can also detect the smell of a person’s breath and the smell of the skin cells of a deceased person.
The emerging avalanche-predicting human-made tech and the incredible nature-made tech of dogs’ olfactory talents is the lifesaving “equipment” that Leffler believes in. Even when human-made technology develops further, it will be most efficient when used together with the millions of dogs’ smell receptors, Leffler believes. “It is a combination of technology and the avalanche dog that will always be effective in finding an avalanche victim.”
Living with someone changes your microbiome, new research shows
Some roommate frustration can be expected, whether it’s a sink piled high with crusty dishes or crumbs where a clean tabletop should be. Now, research suggests a less familiar issue: person-to-person transmission of shared bacterial strains in our gut and oral microbiomes. For the first time, the lab of Nicola Segata, a professor of genetics and computational biology at the University of Trento, located in Italy, has shown that bacteria of the microbiome are transmitted between many individuals, not just infants and their mothers, in ways that can’t be explained by their shared diet or geography.
It’s a finding with wide-ranging implications, yet frustratingly few predictable outcomes. Our microbiomes are an ever-growing and changing collection of helpful and harmful bacteria that we begin to accumulate the moment we’re born, but experts are still struggling to unravel why and how bacteria from one person’s gut or mouth become established in another person’s microbiome, as opposed to simply passing through.
“If we are looking at the overall species composition of the microbiome, then there is an effect of age of course, and many other factors,” Segata says. “But if we are looking at where our strains are coming from, 99 percent of them are only present in other people’s guts. They need to come from other guts.”
If we could better understand this process, we might be able to control and use it; perhaps hospital patients could avoid infections from other patients when their microbiome is depleted by antibiotics and their immune system is weakened, for example. But scientists are just beginning to link human microbiomes with various ailments. Growing evidence shows that our microbiomes steer our long-term health, impacting conditions like obesity, irritable bowel syndrome, type 2 diabetes, and cancer.
Previous work from Segata’s lab and others illuminated the ways bacteria are passed from mothers to infants during the first few months of life during vaginal birth, breastfeeding and other close contact. And scientists have long known that people in close proximity tend to share bacteria. But the factors related to that overlap, such as genetics and diet, were unclear, especially outside the mother-baby dyad.
“If we look at strain sharing between a mother and an infant at five years of age, for example, we cannot really tell which was due to transmission at birth and which is due to continued transmission because of contact,” Segata says. Experts hypothesized that they could be caused by bacterial similarities in the environment itself, genetics, or bacteria from shared foods that colonized the guts of people in close contact.
Strain sharing was highest in mother-child pairs, with 96 percent of them sharing strains, and only slightly lower in members of shared households, at 95 percent.
In Italy, researchers led by Mireia Valles-Colomer, including Segata, hoped to unravel this mystery. They compared data from 9,715 stool and saliva samples in 31 genomic datasets with existing metadata. Scientists zoomed in on variations in each bacterial strain down to the individual level. They examined not only mother-child pairs, but people living in the same household, adult twins, and people living in the same village in a level of detail that wasn’t possible before, due to its high cost and difficulties in retrieving data about interactions between individuals, Segata explained.
“This paper is, with high granularity, quantifying the percent sharing that you expect between different types of social interactions, controlling for things like genetics and diet,” Gibbons says. Strain sharing was highest in mother-child pairs, with 96 percent of them sharing strains, and only slightly lower in members of shared households, at 95 percent. And at least half of the mother-infant pairs shared 30 percent of their strains; the median was 12 percent among people in shared households. Yet, there was no sharing among eight percent of adult twins who lived separately, and 16 percent of people within villages who resided in different households. The results were published in Nature.
It’s not a regional phenomenon. Although the types of bacterial strains varied depending on whether people lived in western and eastern nations — datasets were drawn from 20 countries on five continents — the patterns of sharing were much the same. To establish these links, scientists focused on individual variations in shared bacterial strains, differences that create unique bacterial “fingerprints” in each person, while controlling for variables like diet, demonstrating that the bacteria had been transmitted between people and were not the result of environmental similarities.
The impact of this bacterial sharing isn’t clear, but shouldn’t be viewed with trepidation, according to Sean Gibbons, a microbiome scientist at the nonprofit Institute for Systems Biology.
“The vast majority of these bugs are actually either benign or beneficial to our health, and the fact that we're swapping and sharing them and that we can take someone else's strain and supplement or better diversify our own little garden is not necessarily a bad thing,” he says.
"There are hundreds of billions of dollars of investment capital moving into these microbiome therapeutic companies; bugs as drugs, so to speak,” says Sean Gibbons, a microbiome scientist at the Institute for Systems Biology.
Everyday habits like exercising and eating vegetables promote a healthy, balanced gut microbiome, which is linked to better metabolic and immune function, and fewer illnesses. While many people’s microbiomes contain bacteria like C. diff or E. coli, these bacteria don’t cause diseases in most cases because they’re present in low levels. But a microbiome that’s been wiped out by, say, antibiotics, may no longer keep these bacteria in check, allowing them to proliferate and make us sick.
“A big challenge in the microbiome field is being able to rationally predict whether, if you're exposed to a particular bug, it will stick in the context of your specific microbiome,” Gibbons says.
Gibbons predicts that explorations of microbe-based therapeutics will be “exploding” in the coming decades. “There are hundreds of billions of dollars of investment capital moving into these microbiome therapeutic companies; bugs as drugs, so to speak,” he says. Rather than taking a mass-marketed probiotic, a precise understanding of an individual’s microbiome could help target the introduction of just the right bacteria at just the right time to prevent or treat a particular illness.
Because the current study did not differentiate between different types of contact or relationships among household members sharing bacterial strains or determine the direction of transmission, Segata says his current project is examining children in daycare settings and tracking their microbiomes over time to understand the role genetics and everyday interactions play in the level of transmission that occurs.
This relatively newfound ability to trace bacterial variants to minute levels has unlocked the chance for scientists to untangle when and how bacteria leap from one microbiome to another. As researchers come to better understand the factors that permit a strain to establish itself within a microbiome, they could uncover new strategies to control these microbes, harnessing the makeup of each microbiome to help people to resist life-altering medical conditions.