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.
Today's podcast episode features Doug Drysdale, CEO of Cybin, a company that is leading innovations in psilocybin, mushrooms that may help people with anxiety and depression.
Listen on Apple | Listen on Spotify | Listen on Stitcher | Listen on Amazon | Listen on Google
These mushrooms have been used for religious, spiritual and medicinal purposes for thousands of years, but only in the past several decades have scientists brought psychedelics into the lab to enhance them and maximize their therapeutic value.
Today’s podcast guest, Doug Drysdale, is doing important work to lead this effort. Drysdale is the CEO of a company called Cybin that has figured out how to make psilocybin more potent, so it can be administered in smaller doses without side effects.
The natural form of psilocybin has been studied increasingly in the realm of mental health. Taking doses of these mushrooms appears to help people with anxiety and depression by spurring the development of connections in the brain, an example of neuroplasticity. The process basically shifts the adult brain from being fairly rigid like dried clay into a malleable substance like warm wax - the state of change that's constantly underway in the developing brains of children.
Neuroplasticity in adults seems to unlock some of our default ways of of thinking, the habitual thought patterns that’ve been associated with various mental health problems. Some promising research suggests that psilocybin causes a reset of sorts. It makes way for new, healthier thought patterns.
So what is Drysdale’s secret weapon to bring even more therapeutic value to psilocybin? It’s a process called deuteration. It focuses on the hydrogen atoms in psilocybin. These atoms are very light and don’t stick very well to carbon, which is another atom in psilocybin. As a result, our bodies can easily breaks down the bonds between the hydrogen and carbon atoms. For many people, that means psilocybin gets cleared from the body too quickly, before it can have a therapeutic benefit.
In deuteration, scientists do something simple but ingenious: they replace the hydrogen atoms with a molecule called deuterium. It’s twice as heavy as hydrogen and forms tighter bonds with the carbon. Because these pairs are so rock-steady, they slow down the rate at which psilocybin is metabolized, so it has more sustained effects on our brains.
Cybin isn’t Drysdale’s first go around at this - far from it. He has over 30 years of experience in the healthcare sector. During this time he’s raised around $4 billion of both public and private capital, and has been named Ernst and Young Entrepreneur of the Year. Before Cybin, he was the founding CEO of a pharmaceutical company called Alvogen, leading it from inception to around $500 million in revenues, across 35 countries. Drysdale has also been the head of mergers and acquisitions at Actavis Group, leading 15 corporate acquisitions across three continents.
In this episode, Drysdale walks us through the promising research of his current company, Cybin, and the different therapies he’s developing for anxiety and depression based not just on psilocybin but another psychedelic compound found in plants called DMT. He explains how they seem to have such powerful effects on the brain, as well as the potential for psychedelics to eventually support other use cases, including helping us strive toward higher levels of well-being. He goes on to discuss his views on mindfulness and lifestyle factors - such as optimal nutrition - that could help bring out hte best in psychedelics.
Show links:
Doug Drysdale full bio
Doug Drysdale twitter
Cybin website
Cybin development pipeline
Cybin's promising phase 2 research on depression
Johns Hopkins psychedelics research and psilocybin research
Mets owner Steve Cohen invests in psychedelic therapies
Doug Drysdale, CEO of Cybin
Immune cells battle an infection.
Measuring immune resilience
The researchers measured immune resilience in two ways. The first is based on the relative quantities of two types of immune cells, CD4+ T cells and CD8+ T cells. CD4+ T cells coordinate the immune system’s response to pathogens and are often used to measure immune health (with higher levels typically suggesting a stronger immune system). However, in 2021, the researchers found that a low level of CD8+ T cells (which are responsible for killing damaged or infected cells) is also an important indicator of immune health. In fact, patients with high levels of CD4+ T cells and low levels of CD8+ T cells during SARS-CoV-2 and HIV infection were the least likely to develop severe COVID and AIDS.
Individuals with optimal levels of immune resilience were more likely to live longer.
In the same 2021 study, the researchers identified a second measure of immune resilience that involves two gene expression signatures correlated with an infected person’s risk of death. One of the signatures was linked to a higher risk of death; it includes genes related to inflammation — an essential process for jumpstarting the immune system but one that can cause considerable damage if left unbridled. The other signature was linked to a greater chance of survival; it includes genes related to keeping inflammation in check. These genes help the immune system mount a balanced immune response during infection and taper down the response after the threat is gone. The researchers found that participants who expressed the optimal combination of genes lived longer.
Immune resilience and longevity
The researchers assessed levels of immune resilience in nearly 50,000 participants of different ages and with various types of challenges to their immune systems, including acute infections, chronic diseases, and cancers. Their evaluation demonstrated that individuals with optimal levels of immune resilience were more likely to live longer, resist HIV and influenza infections, resist recurrence of skin cancer after kidney transplant, survive COVID infection, and survive sepsis.
However, a person’s immune resilience fluctuates all the time. Study participants who had optimal immune resilience before common symptomatic viral infections like a cold or the flu experienced a shift in their gene expression to poor immune resilience within 48 hours of symptom onset. As these people recovered from their infection, many gradually returned to the more favorable gene expression levels they had before. However, nearly 30% who once had optimal immune resilience did not fully regain that survival-associated profile by the end of the cold and flu season, even though they had recovered from their illness.
Intriguingly, some people who are 90+ years old still have optimal immune resilience, suggesting that these individuals’ immune systems have an exceptional capacity to control inflammation and rapidly restore proper immune balance.
This could suggest that the recovery phase varies among people and diseases. For example, young female sex workers who had many clients and did not use condoms — and thus were repeatedly exposed to sexually transmitted pathogens — had very low immune resilience. However, most of the sex workers who began reducing their exposure to sexually transmitted pathogens by using condoms and decreasing their number of sex partners experienced an improvement in immune resilience over the next 10 years.
Immune resilience and aging
The researchers found that the proportion of people with optimal immune resilience tended to be highest among the young and lowest among the elderly. The researchers suggest that, as people age, they are exposed to increasingly more health conditions (acute infections, chronic diseases, cancers, etc.) which challenge their immune systems to undergo a “respond-and-recover” cycle. During the response phase, CD8+ T cells and inflammatory gene expression increase, and during the recovery phase, they go back down.
However, over a lifetime of repeated challenges, the immune system is slower to recover, altering a person’s immune resilience. Intriguingly, some people who are 90+ years old still have optimal immune resilience, suggesting that these individuals’ immune systems have an exceptional capacity to control inflammation and rapidly restore proper immune balance despite the many respond-and-recover cycles that their immune systems have faced.
Public health ramifications could be significant. Immune cell and gene expression profile assessments are relatively simple to conduct, and being able to determine a person’s immune resilience can help identify whether someone is at greater risk for developing diseases, how they will respond to treatment, and whether, as well as to what extent, they will recover.
