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May 18, 2023

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Waterless artificial kidney may be the treatment of the future

by University of Arkansas

Every year, more people die of kidney disease than breast cancer. The Centers for Disease Control and Prevention estimates that 37 million people in the United States—15% of U.S. adults—have some form of chronic kidney disease.

Of this population, about 100,000 people will develop end-stage renal disease. The treatment options for this group—hemodialysis, peritoneal dialysis or kidney transplant —have not changed significantly over the past 50 years. According to the CDC, the average duration of patient survival on dialysis is approximately seven years, but most patients have to wait 10 years to receive a donated kidney. A hundred thousand people die each year on dialysis, many waiting for a kidney transplant.

Kidney disease is also a major public health problem. The U.S. government spends more than $100 billion in Medicare payments—almost 10% of Medicare's annual budget of $1 trillion—to care for patients with kidney disease.

A collaboration between engineering researchers at the University of Arkansas and a kidney doctor in Southern California could change all this. If successful, their work will revolutionize treatment for kidney disease and offer hope for something better than dialysis or transplantation.

The power of electrodeionization

Several years ago, a decade into his career at the University of Arkansas, chemical engineering professor Jamie Hestekin received a call from Ira Kurtz, a prominent nephrologist in Southern California. Hestekin's research did not have medical applications, so the call was unexpected and somewhat random. But in other ways, it made perfect sense. At the time, Hestekin had no way of knowing that Kurtz's call would change the direction of his work and eventually dominate his research agenda.

Hestekin specializes in a chemical process called electrodeionization, which is why Kurtz was calling. Used primarily in water treatment , electrodeionization removes or separates ions (electrically charged molecules) from water by applying an electrical charge to specially designed membranes.

Before Kurtz's call, Hestekin had used the technology to remove ions from grape juices, cells from biofuels and organic acids from fermentations. More recently, he was doing consulting research for fracking companies, applying the electrodeionization process to the removal of environmentally hazardous particles from wastewater.

As Distinguished Professor of Medicine and Chief of Nephrology at UCLA Health, Kurtz is a leading basic researcher on the structural biology and physiology of the human kidney. He focuses on proteins that transport various ions in renal and extrarenal tissues. In the kidney, ion transporters play an important role in helping determine the final chemistry of urine.

Kurtz emphasizes that the human kidney is not a simple filter. Rather, it is more like a computer, sensing the chemistry of our blood and keeping it constant, despite all the chemicals that food and beverages introduce into the blood. How the kidney accomplishes this is a major focus of his research.

In addition to studying the ion transport process in the kidney, Kurtz, along with the US Kidney Research Corporation, had been investigating a new, radical idea.

"I'd been thinking about creating an artificial kidney," he said. "So, I looked around to see what was out there. There were a few efforts, but I could see they weren't going to work ultimately. Such a device needed to filter blood, as everyone knew, but compared to the requirement of needing to create a device that could transport ions specifically, the filtration requirement was child's play."

Kurtz started exploring techniques that could transport critical ions, such as sodium and potassium, without using dialysis. The device he envisioned would be implantable and therefore couldn't use water, a dialysate or a dialyzer, which are currently used to treat patients. He ultimately landed on electrodeionization as a technology that could potentially transport ions like the human kidney. After looking at several researchers around the country with a background in this process, Kurtz called Hestekin—because of a paper he had written describing an approach to transporting monovalent cations via electrodeionization.

The kidney as a chemical computer

Kurtz likes to say that the kidney is more complex than a 747. Weighing in at about a third of a pound, each kidney is located toward the back of the upper abdomen. Its microanatomy is particularly complex, containing roughly a million nephrons, each of which is responsible for filtering and transporting ions and other substances that will end up in the urine. Each nephron contains a filter, called a glomerulus, and a tubular transporting part that is further subdivided anatomically and functionally into about 15 segments that contain different cell types. Kidneys also have nerves, arterial and venous blood vessels, and lymphatics that, along with the nephrons, are configured in a complex three-dimensional structure.

They never stop working. Despite the fact that people typically eat and drink three times a day, a process that can significantly affect the chemistry of blood and cells, the kidneys recognize these changes and excrete the exact amount of electrolytes, water and organic compounds to compensate for what is absorbed from the human diet into the bloodstream via the gastrointestinal tract. Kidneys prevent the blood chemistry from changing by excreting electrolytes, water and organic substances in urine.

Potassium, one of the many important electrolytes the kidneys regulate, plays a role in the electrical properties of all cells in the body, including cardiac—pacemaker cells that control the heart rate. Unfortunately, in patients without kidney function, whatever they eat and drink stays in their bodies. In such patients, nephrologists need to control what the kidneys would normally do by artificially removing the necessary amount of water and electrolytes during dialysis treatments.

Briefcase-sized artificial kidney

Creating an artificial device that performs the above functions is an immense and complex task. The call from Kurtz led to a fruitful collaboration. In addition to Hestekin and Kurtz, the team also includes Christa Hestekin, professor of chemical engineering and associate dean of the Graduate School and International Education, and US Kidney Research Corporation, whose Founder/CEO is Roland Ludlow. Kurtz had established ties with this California-based private company before he knew the Hestekins. US Kidney Research Corporation supports the research and plans to market the world's first tabletop artificial kidney, based on a prototype that will ultimately be developed by the Kurtz-Hestekin-Ludlow team.

With $4 million in funding from the company, the research team, including students in the Hestekin laboratory, are building a prototype device that fits on a desktop. It could be used at work or placed on a bedside table and used while a patient sleeps.

The device has four basic components that simulate the filtering and critical ion transport functions of an individual nephron. There is an ultrafiltration module that filters blood. Proteins and blood cells return to the patient's blood, while water, ions, urea and some uremic toxins permeate to the next component in the device. A nanofiltration module helps glucose to return to the blood, while allowing all other substances to permeate. Electrodeionization modules perform the ion transport requirements, and a reverse osmosis module concentrates the synthetic urine and simultaneously controls water excretion, ensuring that the volume of urine approximately matches the patient's water intake.

Early on, most of the work focused on the electrodeionization module, which selectively removes ions from urine and returns them to the blood. This process was achieved by inserting platinum porous meshes between two ion-exchange wafers to create a single wafer that uses an electric field to force ions through membranes. The meshes serve as electrodes when voltage is applied. This enables independent control of transport chambers within the device, which in turn enables the researchers to select different ions and adjust transport rates independently. The researchers have successfully tested this technology with several physiologically relevant ions, mimicking the specific control of ion transport by the kidney.

More recently, an "accidental" discovery has given the research team further reason to be excited. Ultrafiltration membranes used in hemodialysis, the primary treatment for people with end-stage kidney disease, have problems. They tend to clot. In recent years, in the effort to develop a better membrane, biomedical researchers have focused on the so-called "middle molecule," that is, design of a membrane that achieves optimal performance in terms of molecule size and electrical charge, one that filters out uremic toxins without losing critical proteins and ions.

As part of a different project, Jamie Hestekin and students in his lab were experimenting with various types of membranes to use as friction material for surface engineering. They were having success with a membrane made of cellulose. Then, a student decided to try it on blood. The results were encouraging.

"This membrane looks more like nature," Jamie Hestekin says. "It mimics the glomerulus and the tiny fibers connected to it better than anything out there. This was kind of an accidental discovery. We're still not sure why it mimics the glomerulus better."

The researchers have used the cellulose membrane in animal studies, but it has not yet been tested as part of the artificial kidney device. The cellulose membrane could potentially be used in hemodialysis dialyzers as well. Its filtering performance is superior to those currently in use, Hestekin says. US Kidney Research Corporation has licensed the membrane for this purpose and is exploring potential collaborations.

What it means

Developing and marketing an artificial kidney could give patients with kidney disease more options and independence, while potentially reducing Medicare expenditures significantly. Patients using the device would no longer need to go to a dialysis clinic three times a week for treatment. Because their treatment would be done daily at home or in the office, with less stress on the cardiovascular system than three times a week in hemodialysis, there likely would be improvements in both patient quality of life and lifespan.

There's another major benefit—the environment. Billions of gallons of wastewater produced annually by dialysis treatments would no longer enter water treatment facilities. Development of a waterless artificial kidney would significantly reduce the carbon footprint associated with using and manufacturing water-purifications systems, dialysate solutions and dialyzers. This additional advantage of not using water means the system would be optimal in countries where water is scarce.

The team is also trying to scale down components to create a partially or fully implantable device, which would be about the size of two fists. They first need to complete testing the new filtration membrane and make additional refinements to the tabletop device before creating a protype that can be used in animal trials. The Hestekins and Kurtz estimate this will require an additional $5 million in research funding, and they hope to begin animal trials for the prototype in about 18 months.

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The latest advances from Vanderbilt University Medical Center

Creating the First Implantable Bioartificial Kidney

Discoveries in Medicine will present a three-part overview of the work of nephrologist William H. Fissell, M.D. , who, along with Shuvo Roy, Ph.D., a professor of bioengineering at the University of California San Francisco, is spearheading the development of the first implantable bioartificial kidney from concept through to production.

Fissell, a nephrologist and associate professor of medicine at Vanderbilt University Medical Center, reports that the team’s bioartificial kidney is proving viable in preclinical trials – a medical first. This soda-can-sized implantable device was designed to carry out the primary functions of a natural kidney.

Discoveries in Medicine has tracked the device’s development over the past several years. This is part one of a three-part series where we catch up with Fissell and the progress he is making as the bioartificial organ moves toward the manufacturing stage.

Discoveries: Dr. Fissell, tell us about the dream to create an implantable kidney. How did you come to adopt this ambitious initiative?

Fissell : It started when I was an undergraduate studying astrophysics at MIT. I was working with a team on NASA’s Chandra Observatory, a space-based X-ray telescope, to develop an instrument for Chandra that works like a prism, but for X-rays. That instrument is flying in space today.

During and after my college career when I worked as a 911 paramedic, I decided to pursue a career in medicine and earned my M.D. at Case Western. Seeing patients with kidney disease, I was struck by the immense need and the limits of our present treatments. On top of that, I personally had nine (ultimately successful) surgeries over 30 months to correct a congenital renal system defect. Taken together, these experiences provided a foundation, a motivation, and the science to begin seriously bringing new technologies to the prospect of a bioartificial kidney.

Making Transplant Accessible

Discoveries: How would you characterize the problems the implantable bioartificial kidney, termed iBAK, seeks to solve?

Fissell: Our end goal is a bioengineered, mass-produced, universal-donor kidney to overcome the scarcity problem in kidney transplant. Full stop. We want to rescue people from dialysis or death while waiting for transplantation.

Take a look at the state of renal failure and the solutions we have today. A preponderance of renal failure patients depend on dialysis, about 700,000 of them in the United States and 2.5 to 3 million worldwide. Only about one in six of these patients is even healthy enough to qualify for transplant.

“Our end goal is a bioengineered, mass-produced, universal-donor kidney to overcome the scarcity problem in kidney transplant. Full stop.”

Right now, there are roughly 100,000 patients on the transplant list, but due largely to organ scarcity, only about 20,000 transplants are performed a year. Add to this the fact that we have around 105,000 new renal failure cases a year, and you can see there is a huge mismatch between need and fulfillment of that need.

When you see that only 12 percent of those on the waitlist get a kidney, it becomes clear that kidney transplant is not a realistic solution to the problem.

Dialysis comes with its own burdens. There’s the inconvenience of thrice weekly, 3- to 5-hour sessions. There are repeated admissions to hospitals for infections and heart problems. There’s a dependency on others, which patients can find overwhelming and discouraging. There is constant fatigue, a very restricted diet, and travel is difficult.

“When you see that only 12 percent of those on the waitlist get a kidney, it becomes clear that kidney transplant is not a realistic solution to the problem.”

One patient with kidney failure described it like this: “I could not be the kind of husband to my wife, father to my children, or provider for our family that I wanted and needed to be … the awful fate of being half a man.”

Transplantation can rescue people from this situation. A bioengineered transplant like the iBAK will provide the waste excretion and fluid balance functions that a transplant does.

Straightforward Procedure

Discoveries: What would be the patient’s experience in having an iBAK implantation?

Fissell: The iBAK will be implanted just like a kidney transplant, connected to the iliac vessels and draining to the urinary system. Replacement will be simple: disconnect the old one from the vascular grafts and connect the new one. The idea is a bit like how pacemakers are managed: the leads generally stay where they are, but the generator can be replaced as an outpatient minor procedure.

For the physician, there’s the one-time surgery to attach the vascular grafts to the patient’s own blood vessels, and then connecting the cartridge is much easier. We hope that eventually this could become an outpatient ambulatory surgery as well.

Bioartificial vs. Xenograft

Discoveries: Are there other innovations that may solve the dialysis problem?

Fissell: The University of Alabama is working on kidney xenografts from pigs with promising results.

One key advantage with the iBAK, though, is that you don’t have rejection issues. With either an animal or natural human kidney, the patient is on strong immunosuppressants because of rejection risks. Yet these risks are worth it for all the functions it provides.

But whether a xenograft is a riskier proposition for rejection, requires more immunosuppression, or poses greater risks of cancer or heart disease is still unknown.

Ongoing Studies

Discoveries: Where are you now in the testing of the iBAK?

Fissell: We are in preclinical trials now to make sure there is no clotting over time. So far, we are seeing no issues that raise concerns.

NEXT: Challenges Overcome in Creation of Bioartificial Kidney

William H. Fissell, M.D.

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KidneyX Launches New Artificial Kidney Prize with $10.5 Million in Funding

Today, the U.S. Department of Health and Human Services (HHS) and the American Society of Nephrology (ASN) announced a new prize competition from the Kidney Innovation Accelerator (KidneyX) that seeks to further the development of a fully functional bioartificial kidney.

Phase 2 of the Artificial Kidney Prize competition invites submissions focused on developing prototype bioartificial kidneys or a new tool or component that can help enable the development of bioartificial kidneys. Innovators in the fields of regenerative medicine, cellular engineering, tissue engineering, systems biology, and synthetic biology are strongly encouraged to apply.

The 850 million people worldwide who live with kidney diseases include 37 million Americans. In the United States alone, treatment costs total more than $100 billion a year. Each day, 13 people die while waiting for a kidney transplant, while those on dialysis face a 50 percent mortality rate during the first five years of treatment. Communities of color are disproportionately affected with increased incidence, fewer organs available for transplant, and poorer outcomes overall.

Innovation is urgently needed. Through this prize competition, KidneyX is seeking to advance a field that has seen little progress in more than 60 years. The best treatment is a kidney transplant, but the supply of organs only addresses a small fraction of the need.

Assistant Secretary of Health ADM Rachel L. Levine notes, "We are hopeful that KidneyX Phase 2's focus on the integration and advancement of artificial kidney prototypes will result in breakthroughs that ensure a healthier future while reducing health disparities."

Development of a fully functional bioartificial kidney has proven difficult in the past because of the overall complexity of the organ, which is made up of a multitude of cell types and performs several important functions.

A successful bioartificial kidney must be able to perform at least some of the kidney's most vital functions, such as blood filtration, electrolyte homeostasis, fluid regulation, toxin removal and secretion, and the transport and drainage of excess filtrate. However, given the substantial scientific advances that could supplement kidney health, such as adjustments in lifestyle and nutrition, pharmaceuticals, and other interventions that could slow progression of kidney disease or mitigate kidney failure, a bioartificial kidney may not need to replicate the full cellular and tissue complexity of a human kidney.

To encourage revolutionary designs, Phase 2 of the Artificial Kidney Prize consists of two tracks.

• Track One, "Accelerating the Prototype of a Bioartificial Kidney," is open to submissions from innovators with development plans for a prototype bioartificial kidney, including a pathway and future timeline toward first-in-human studies.
• Track Two, "Components and Tools that Enable the Development of an Artificial Kidney," is open to proposals for tools or components that adapt regenerative medicine, cellular engineering, tissue engineering, systems biology, and/or synthetic biology methods to address a challenge currently faced in the development of a fully functional artificial kidney.

Past KidneyX prize winners, as well as any other entrants who meet the eligibility requirements, are invited to enter Phase 2 of this prize competition.

Artificial kidneys may be wearable or implantable options for kidney replacement therapy; xenotransplant, including chimera, or another non-human organ platform may also be considered.

The components and tools solve a specific challenge for developing xenotransplanted, bioartificial, biomechanical, and/or other implantable or wearable platforms for kidney replacement therapy. Examples include tools or components that optimize efficiency and scalability of regenerative medicine, cellular and tissue engineering, systems biology, and/or synthetic biology methodology to enable development of an artificial kidney platform, such as applications of artificial intelligence, machine learning, gene editing, and gene circuits.

"Thanks to the public-private partnership behind KidneyX, innovators have a unique opportunity to create next-generation solutions to help the 850 million people worldwide living with kidney diseases," said John Sedor, MD, FASN, KidneyX Steering Committee Chair. "This competition specifically focuses on the use of regenerative medicine and artificial biology methods to advance the development of bioartificial kidney prototypes or to create enabling tools that overcome barriers slowing innovation. We believe this competition will generate exciting approaches that will accelerate new kidney replacement therapies and improve the lives of people with kidney diseases."

The submission period for both tracks of Phase 2 opens today, with Track One closing on October 28, 2022, and Track Two closing on January 28, 2023. Track Two applicants are encouraged to use the additional time to seek guidance from or collaborate with experts in the kidney field to improve their applications.

Up to $10.5 million in funding will be split among up to nine (9) prize winners, including up to three (3) winners from Track One each receiving $1.5 million and up to six (6) winners from Track Two each receiving $1 million.

For the full rules and eligibility requirements, as well as a list of resources available to applicants, visit kidneyx.org/akp .

About U.S. Department of Health And Human Services

The U.S. Department of Health and Human Services (HHS) enhances and protects the health and well-being of all Americans. HHS fulfills that mission by providing for effective health and human services and fostering advances in medicine, public health, and social services. For more information visit HHS.gov .

About American Society of Nephrology

Since 1966, ASN has been leading the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients. ASN has nearly 20,000 members representing 132 countries. For more information, please visit asn-online.org and follow us on Facebook ,  Twitter ,  LinkedIn , and Instagram .

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Artificial kidney research gets a boost

Development of a surgically implantable, artificial kidney — a promising alternative to kidney transplantation or dialysis for people with end-stage kidney disease — has received a $6 million boost, thanks to a new grant from the National Institute of Biomedical Imaging and Bioengineering (NIBIB), one of the National Institutes of Health, to researchers led by UC San Francisco bioengineer Shuvo Roy, Ph.D., and Vanderbilt University nephrologist William Fissell, M.D.

“We aim to conduct clinical trials on an implantable, engineered organ in this decade, and we are coordinating our efforts with both the NIH and the U.S. Food and Drug Administration,” Roy said.

Roy is a professor in the Department of Bioengineering and Therapeutic Sciences in the Schools of Pharmacy and Medicine, and technical director of The Kidney Project at UCSF, a multi-institutional collaboration. The Kidney Project team has prototyped and begun testing key components of the coffee-cup-sized device, which mimics functions of the human kidney.  

Roy and Fissell will present updates on development of the device Nov. 3-8 at Kidney Week 2015 in San Diego, part of a major meeting of the American Society of Nephrology.

NIBIB is overseeing and funding the continuation of their work for four years under a cooperative agreement through its Quantum Program, created to support the development of “biomedical technologies that will result in a profound paradigm shift in prevention, detection, diagnosis, and/or treatment of a major disease or national public health problem.” This is the second major grant the researchers have received through the program.

Alternative to dialysis

In part because the U.S. population has grown older and heavier and is more likely to develop high blood pressure and diabetes, conditions often associated with kidney failure, the number of individuals diagnosed with kidney failure is growing year-over-year and has risen 57 percent since 2000, according to the National Kidney Foundation. More than 615,000 people now are being treated for kidney failure. U.S. government statistics indicate that kidney failure costs the U.S. health care system $40 billion annually and accounts for more than 6 percent of Medicare spending.

The waiting list for kidney transplants in the United States has grown to more than 100,000 people. The number of available kidneys has remained stagnant for the past decade, and only about one in five now on the list is expected to receive a transplant.

More than 430,000 of those with kidney failure now undergo dialysis, which is more costly and less effective than transplantation and typically requires hours-long stays at a clinic, three times weekly. Only about one in three patients who begins dialysis survives longer than five years, in comparison to more than four in five transplant recipients.

Fissell, associate professor in the Department of Medicine at Vanderbilt and medical director for The Kidney Project, said, “This project is about creating a permanent solution to the scarcity problem in organ transplantation. We are increasing the options for people with chronic kidney disease who would otherwise be forced onto dialysis.”

Along with Roy at UCSF and Fissell at Vanderbilt, a national team of scientists and engineers at universities and small businesses are working toward making the implantable artificial kidney available to patients.

According to B. Joseph Guglielmo, PharmD, dean of the UCSF School of Pharmacy, "The grant from NIBIB is a striking affirmation of the promise associated with this device, as well as NIH confidence in the ultimate success of The Kidney Project. Patients with chronic kidney failure are in real need of alternatives to transplant and dialysis; this School of Pharmacy and campus priority clearly demonstrates the research rewards of working collaboratively."

In September the project was designated for inclusion in the FDA’s new Expedited Access Pathway program to speed development, evaluation, and review of medical devices that meet major unmet needs in fighting life-threatening or irreversibly debilitating diseases. The program evolved from an earlier FDA program called Innovation Pathway 2.0, in which The Kidney Project team was one of three device-development groups selected for a pilot initiative focused on kidney failure. Members of the FDA regulatory staff have continually been in communication with Roy and other project leaders to help guide device testing and criteria for data collection.

The aim of the new program is to speed the FDA’s premarket approval (PMA) process for scientific and regulatory review of safety and effectiveness of Class III medical devices — those with the potential to provide major benefits, but that also might potentially pose major risks.

“The new program brings FDA reviewers, scientists, and leadership together with our team to define a roadmap to regulatory approval and product launch,” Roy said.

Early studies of prototype are encouraging

One component of the new artificial kidney is a silicon nanofilter to remove toxins, salts, some small molecules, and water from the blood. Roy’s research team designed it based on manufacturing methods used in the production of semiconductor electronics and microelectromechanical systems (MEMS). The new silicon nanofilters offer several advantages — including more uniform pore size — over filters now used in dialysis machines, according to Roy. The silicon nanofilter is designed to function on blood pressure alone and without a pump or electrical power.

The second major component is a “bioreactor” that contains human kidney tubule cells embedded within microscopic scaffolding. These cells perform metabolic functions and reabsorb water from the filtrate to control blood volume. A project collaborator, H. David Humes, MD, professor in the Department of Internal Medicine at the University of Michigan, earlier showed that such a bioreactor, used in combination with ultrafiltration in an external device, greatly increased survival in comparison to dialysis alone in the treatment of patients with acute kidney failure in a hospital intensive care unit.

The artificial kidney being developed by Roy and Fissell is designed to be connected internally to the patient’s blood supply and bladder and implanted near the patient’s own kidneys, which are not removed.

Unlike human kidney transplant recipients, patients with the implantable artificial kidney will not require immunosuppressive therapy, according to Roy. Preliminary preclinical studies indicate that the non-reactive coatings developed for device components are unlikely to lead to filter clogging or immune reactions, he said, and that bioreactor cells can survive for at least 60 days under simulated physiological conditions.

The new funding from NIBIB will focus on lab studies on methods for optimizing performance of the bioreactor’s kidney cells. A portion will be used to enable refinements for the mechanical design of the nanofilter unit and investigate biocompatibility of the artificial kidney. The filter will be evaluated in preclinical studies aimed at achieving stable ultrafiltration.

Private philanthropy and UCSF support already have been vital in sustaining The Kidney Project, and even with the FDA’s new and more flexible pathway, additional funding will be required to meet project timelines, Roy said.

Disclosure: Roy and Fissell have ownership in Silicon Kidney, a start-up company that will advance the commercialization of silicon membrane technology.

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Ozempic Cuts Risk of Chronic Kidney Disease Complications, Study Finds

A major clinical trial showed such promising results that the drug’s maker halted it early.

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By Dani Blum

Dani Blum has reported on Ozempic and similar drugs since 2022.

Semaglutide, the compound in the blockbuster drugs Ozempic and Wegovy , dramatically reduced the risk of kidney complications, heart issues and death in people with Type 2 diabetes and chronic kidney disease in a major clinical trial, the results of which were published on Friday. The findings could transform how doctors treat some of the sickest patients with chronic kidney disease, which affects more than one in seven adults in the United States but has no cure.

“Those of us who really care about kidney patients spent our whole careers wanting something better,” said Dr. Katherine Tuttle, a professor of medicine at the University of Washington School of Medicine and an author of the study. “And this is as good as it gets.” The research was presented at a European Renal Association meeting in Stockholm on Friday and simultaneously published in The New England Journal of Medicine .

The trial, funded by Ozempic maker Novo Nordisk, was so successful that the company stopped it early . Dr. Martin Holst Lange, Novo Nordisk’s executive vice president of development, said that the company would ask the Food and Drug Administration to update Ozempic’s label to say it can also be used to reduce the progression of chronic kidney disease or complications in people with Type 2 diabetes.

Diabetes is a leading cause of chronic kidney disease, which occurs when the kidneys don’t function as well as they should. In advanced stages, the kidneys are so damaged that they cannot properly filter blood. This can cause fluid and waste to build up in the blood, which can exacerbate high blood pressure and raise the risk of heart disease and stroke, said Dr. Subramaniam Pennathur, the chief of the nephrology division at Michigan Medicine.

The study included 3,533 people with kidney disease and Type 2 diabetes, about half of whom took a weekly injection of semaglutide, and half of whom took a weekly placebo shot.

Researchers followed up with participants after a median period of around three and a half years and found that those who took semaglutide had a 24 percent lower likelihood of having a major kidney disease event, like losing at least half of their kidney function, or needing dialysis or a kidney transplant. There were 331 such events among the semaglutide group, compared with 410 in the placebo group.

People who received semaglutide were much less likely to die from cardiovascular issues, or from any cause at all, and had slower rates of kidney decline.

Kidney damage often occurs gradually, and people typically do not show symptoms until the disease is in advanced stages. Doctors try to slow the decline of kidney function with existing medications and lifestyle modifications, said Dr. Melanie Hoenig, a nephrologist at Beth Israel Deaconess Medical Center who was not involved with the study. But even with treatment, the disease can progress to the point that patients need dialysis, a treatment that removes waste and excess fluids from the blood, or kidney transplants.

The participants in the study were extremely sick — the severe complications seen in some study participants are more likely to occur in people the later stages of chronic kidney disease, said Dr. George Bakris, a professor of medicine at the University of Chicago Medicine and an author of the study. Most participants in the trial were already taking medication for chronic kidney disease.

For people with advanced kidney disease, in particular, the findings are promising. “We can help people live longer,” said Dr. Vlado Perkovic, a nephrologist and renal researcher at the University of New South Wales, Sydney, and another author of the study.

While the data shows clear benefits, even the researchers studying drugs like Ozempic aren’t sure how, exactly, they help the kidneys. One leading theory is that semaglutide may reduce inflammation, which exacerbates kidney disease.

And the results come with several caveats: Roughly two-thirds of the participants were men and around two-thirds were white — a limitation of the study, the authors noted, because chronic kidney disease disproportionately affects Black and Indigenous patients. The trial participants taking semaglutide were more likely to stop the drug because of gastrointestinal issues, which are common side effects of Ozempic.

Doctors said they wanted to know whether the drug might benefit patients who have kidney disease but not diabetes, and some also had questions about the potential long-term risks of taking semaglutide.

Still, the results are the latest data to show that semaglutide can do more than treat diabetes or drive weight loss. In March, the F.D.A. authorized Wegovy for reducing the risk of cardiovascular issues in some patients. And scientists are examining semaglutide and tirzepatide, the compound in the rival drugs Mounjaro and Zepbound, for a range of other conditions , including sleep apnea and liver disease.

If the F.D.A. approves the new use, it could drive even more demand for Ozempic, which has faced recurrent shortages .

“I think it’s a game changer,” Dr. Hoenig said, “if I can get it for my patients.”

Dani Blum is a health reporter for The Times. More about Dani Blum

A Close Look at Weight-Loss Drugs

Reduced Disease Complications: Semaglutide, the compound in Ozempic and Wegovy, dramatically reduced the risk of kidney complications , heart issues and death in people with Type 2 diabetes and chronic kidney disease in a major clinical trial.

Supplement Stores: GNC and the Vitamin Shoppe are redesigning displays and taking other steps  to appeal to people who are taking or are interested in drugs like Ozempic and Wegovy.

Senate Investigation: A Senate committee is investigating the prices that Novo Nordisk charges  for Ozempic and Wegovy, which are highly effective at treating diabetes and obesity but carry steep price tags.

A Company Remakes Itself: Novo Nordisk’s factories work nonstop turning out Ozempic and Wegovy , but the Danish company has far bigger ambitions.

Transforming a Small Danish Town: In Kalundborg, population under 17,000, Novo Nordisk is making huge investments to increase production  of Ozempic and Wegovy.

Making of: Replicating Willem Kolff's artificial kidney for Jekels Jacht

In the summer of 2023 Odyl ter Beek , Assistant Professor of the Department of Advanced Organ Bioengineering and Therapeutics (AOT), received a special invitation from the makers of the television program " Jekels Jacht ". They wanted to dedicate an episode to Willem Kolff, the pioneer behind kidney dialysis.

Odyl ter Beek, Assistant Professor The idea of involving our PhD students in replicating Kolff's historic artificial kidney immediately appealed to me. It allows us not only to learn about the history of our field, but also to take on new challenges as a research group and grow together. Our students test new dialysis filters but do not design the entire device, for example.

Enthusiasm and preparations

The AOT students were immediately excited because the topic of the episode fit seamlessly with their ongoing projects and also offered a fun experience to collaborate on a TV show. Despite the challenging timing due to the summer vacation and graduation period, the AOT team began the preparations full of energy. They immersed themselves in Kolff's thesis, which included detailed drawings, measurements and experiments of his first dialysis machine. They also visited the Rijksmuseum Boerhaave in Leiden, where one of Kolff's first dialysis devices is on display. Dialysis technology has hardly changed in all these years, but today's devices look very different from Kolff's first device.

Approach and execution

The students were given a lot of freedom in their approach and planning. They studied the drawings and measurements themselves, searched for materials in thrift stores and on the Internet, and maintained contact with departments such as TCO and DesignLab. The project was divided into two main parts: (1) the frame with the container for the dialysis fluid and (2) the drum with the membrane through which the patient's “blood” was to flow. Regular work meetings helped evaluate progress and make adjustments as needed. Building the device required several new skills. The students, many of whom had biomedical and chemical backgrounds, had little experience with engineering drawings, wood and metalworking, mechanics and electronics. They had to learn how to rotate the drum with wheels, gears and bearings and how to connect an old motor of the era to the modern electrical grid. Odyl ter Beek: “ It was wonderful to see how the students within the group learned to cooperate and consult effectively with each other and other teams. The realisation that the two parts must eventually become one became clear. I am incredibly proud of the students and the end result they achieved together!”

Collaboration and creative solutions

Cooperation within the group went well, although it was challenging at times because the students picked up this Kolff project alongside their projects and experiments. They had to learn to plan, consult and use each other's skills, even though many of them had no background in mechanics or electronics. Finding and modifying parts and making an old engine work were all new to them. Odyl ter Beek: “ It was nice to see how, despite stressful moments, they remained flexible and understanding.”

One of the biggest challenges was using materials from Kolff's time, such as aircraft metal, sewing machine engines and water pumps from old Ford cars. These parts were hard to find and required a lot of flexibility. These parts were hard to find and required creative solutions. For example, the students used old bicycle wheels for the drum, which required modifying the frame with the dialysis sink. When they had trouble finding the right rotational speed for the drum, they had to experiment with different motors. Because of the time constraints of the TV program, the group chose to build the device “in the spirit of Kolff” rather than making a replica.

Historical research and final results

Historical research played a crucial role because Kolff's invention had to be recreated as accurately as possible with authentic parts. Kolff's thesis provided detailed instructions, and Herman Broers, Kolff's biographer, was involved in the shooting. His knowledge and stories gave the team deep insight into Kolff's work and the context in which he operated.

The students learned a lot about Kolff and his invention, as well as about building devices with all the practical skills involved, not to mention the help of TCO! In addition, they developed important soft skills such as cooperation, planning and communication. They were proud of the result: 

Students AOT Building a replica of Kolff's first dialysis machine was a challenging but immensely rewarding project. It allowed us to delve into both medical and Dutch history and experience firsthand the ingenuity and dedication behind this life-saving invention.

Educational value

This project demonstrated the tremendous value of replicating historical scientific experiments. It gave students insight into the necessity and circumstances of scientific inventions, as Odyl ter Beek emphasised, “I think this is important for education today. It offers students insight into why science is so important! Historic scientific experiments underlie the work we get to do today; that's special and important to realise!” 

Reproducing Willem Kolff's artificial kidney for Jekels Jacht was a challenging but highly educational project. It taught the students not only new technical skills but also a deep understanding of the history and value of scientific research. This adventure enriched and inspired the team to continue working on the medical technologies of the future with the same pioneering spirit.

More recent news

Common sugar substitute linked to increased risk of heart attack and stroke

The safety of sugar substitutes is once again being called into question.

Researchers led by the Cleveland Clinic linked the low-calorie sugar substitute xylitol to an increased risk of heart attack, stroke or cardiovascular-related deaths, according to a study published today in the European Heart Journal.

Xylitol is a sugar alcohol that is found in small amounts in fruit and vegetables, and the human body also produces it. As an additive, it looks and tastes like sugar but has 40% fewer calories. It is used, at much higher concentrations than found in nature, in sugar-free gum, candies, toothpaste and baked goods. It can also be found in products labeled "keto-friendly," particularly in Europe.

The same research team found a similar association last year to the popular sugar substitute erythritol. The use of sugar substitutes has increased significantly over the past decade as concerns about rising obesity rates mount.

“We’re throwing this stuff into our food pyramid, and the very people who are most likely to be consuming it are the ones who are most likely to be at risk” of heart attack and stroke, such as people with diabetes, said lead author Dr. Stanely Hazen, chair of cardiovascular and metabolic sciences at Cleveland Clinic’s Lerner Research Institute.

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Many heart attacks and strokes occur in people who do not have known risk factors, like diabetes, high blood pressure or elevated cholesterol levels. The research team began studying sugar alcohols found naturally in the human body to see if the compounds might predict cardiovascular risk in these people.

In the study, the investigators measured the level of naturally occurring xylitol in the blood of more than 3,000 participants after overnight fasting. They found that people whose xylitol levels put them in the top 25% of the study group had approximately double the risk for heart attack, stroke or death over the next three years compared to people in the bottom quarter.

The researchers also wanted to understand the mechanism at work, so they fed xylitol to mice, added it to blood and plasma in a lab and gave a xylitol-containing drink to 10 healthy volunteers. In all these cases, xylitol seemed to activate platelets, which are the blood component that controls clotting, said Hazen. Blood clots are the leading cause of heart attack and stroke.

 “All it takes is xylitol to interact with platelets alone for a very brief period of time, a matter of minutes, and the platelet becomes supercharged and much more prone to clot,” Hazen said.

The next question is what causes naturally-occurring xylitol to be elevated in some people and how do you lower it, said Dr. Sadiya Khan, a cardiologist at Northwestern Medicine Bluhm Cardiovascular Institute and a professor of cardiovascular epidemiology at Northwestern Feinberg School of Medicine who was not involved in the new study.

Much more research needs to be done, said Hazen. In the meantime, he is telling patients to avoid eating xylitol and other sugar alcohols, whose spelling all end in ‘itol.’ Instead, he recommends using modest amounts of sugar, honey or fruit to sweeten food, adding that toothpaste and one stick of gum are probably not a problem because so little xylitol is ingested.

The report had key limitations. 

First, the study of naturally occurring xylitol in people’s blood was observational and can show only an association between the sugar alcohol and heart risk. It does not show that xylitol caused the higher incidence of heart attack, stroke or death.

Nevertheless, given the totality of the evidence presented in the paper, “it’s probably reasonable to limit intake of artificial sweeteners,” said Khan. “Perhaps the answer isn’t replacing sugar with artificial sweeteners but thinking about more high quality dietary components, like vegetables and fruits, as natural sugars.”

Artificial sweeteners shouldn’t be difficult to avoid, said Joanne Slavin, PhD, RDN, a professor of food science and nutrition at the University of Minnesota-Twin Cities. They are listed on the ingredient list of packaged goods.

“Would I say never eat xylitol?” asked Slavin, who had no connection to the study. For some people who struggle to reduce sugar in their diet, sugar substitutes are one tool, and it comes down to personal choice, she said. 

While Slavin found the study interesting and cause for some concern, she noted that sugar alcohols are expensive and are generally used in very small amounts in gum and sugar-free candies.

Another limitation of the study is that the participants whose xylitol levels in the blood were measured were at high risk for or had documented heart disease, and so the results may not apply to healthy individuals.

Still, many people in the general public share the characteristics of the study participants, said Hazen. 

“In middle-aged or older America, it’s common to have obesity and diabetes or high cholesterol or high blood pressure,” he said.

Barbara Mantel is an NBC News contributor. She is also the topic leader for freelancing at the Association of Health Care Journalists, writing blog posts, tip sheets and market guides, as well as producing and hosting webinars. Barbara’s work has appeared in CQ Researcher, AARP, Undark, Next Avenue, Medical Economics, Healthline, Today.com, NPR and The New York Times.

U.S. Department of the Treasury

U.s. department of treasury releases request for information on uses, opportunities, and risks of artificial intelligence in the financial services sector.

WASHINGTON – Today, the U.S. Department of the Treasury (Treasury) released a  request for information on the Uses, Opportunities, and Risks of Artificial Intelligence (AI) in the Financial Services Sector. Building on Treasury’s recent work on cybersecurity and fraud in AI and recent initiatives by other federal agencies, Treasury is seeking public comment on the uses of AI in the financial services sector and the opportunities and risks presented by developments and applications of AI within the sector. 

“Treasury is proud to be playing a key role in spurring responsible innovation, especially in relation to AI and financial institutions. Our ongoing stakeholder engagement allows us to improve our understanding of AI in financial services,” said Under Secretary for Domestic Finance Nellie Liang. “The Biden Administration is committed to fostering innovation in the financial sector while ensuring that we protect consumers, investors, and our financial system from risks that new technologies pose.”

Through this RFI, Treasury seeks to increase its understanding of how AI is being used within the financial services sector and the opportunities and risks presented by developments and applications of AI within the sector, including potential obstacles for facilitating responsible use of AI within financial institutions, the extent of impact on consumers, investors, financial institutions, businesses, regulators, end-users, and any other entity impacted by financial institutions’ use of AI, and recommendations for enhancements to legislative, regulatory, and supervisory frameworks applicable to AI in financial services. Treasury is seeking a broad range of perspectives on this topic and is particularly interested in understanding how AI innovations can help promote a financial system that delivers inclusive and equitable access to financial services. 

Members of the public are encouraged to submit comments within 60 days. Comments responding to this request for information will be publicly viewable  on www.regulations.gov .

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Artificial Kidney Engineering: The Development of Dialysis Membranes for Blood Purification

Yu-shuo tang.

1 Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan; wt.ude.umt.w@631011

Yu-Cheng Tsai

2 Department of Medical Research, Taipei Veterans General Hospital, Taipei 112, Taiwan; moc.liamtoh@928iast

Tzen-Wen Chen

3 Division of Nephrology, Department of Medicine, Wei-Gong Memorial Hospital, Miaoli County 351, Taiwan; wt.ude.umt@nehcwt

Szu-Yuan Li

4 Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan

5 School of Medicine, National Yang-Ming University, Taipei 112, Taiwan

Associated Data

Not applicable.

The artificial kidney, one of the greatest medical inventions in the 20th century, has saved innumerable lives with end stage renal disease. Designs of artificial kidney evolved dramatically in decades of development. A hollow-fibered membrane with well controlled blood and dialysate flow became the major design of the modern artificial kidney. Although they have been well established to prolong patients’ lives, the modern blood purification system is still imperfect. Patient’s quality of life, complications, and lack of metabolic functions are shortcomings of current blood purification treatment. The direction of future artificial kidneys is toward miniaturization, better biocompatibility, and providing metabolic functions. Studies and trials of silicon nanopore membranes, tissue engineering for renal cell bioreactors, and dialysate regeneration are all under development to overcome the shortcomings of current artificial kidneys. With all these advancements, wearable or implantable artificial kidneys will be achievable.

1. History of the Artificial Kidney

The artificial kidney, also known as a dialyzer, is an unreplaceable part of current renal replacement therapy. Without dialysis and kidney transplantation, end stage renal failure meant the termination of a patient’s life in the past. The technology of dialysis has been developed for decades since the early 20th century. In 1928, Haas used a cellulose membrane to treat six patients with dialysis with the anticoagulant of hirudin [ 1 , 2 ]. It ended with no patient survival because of the immature technique.

In 1943, Dutch physician Willem Kolff invented the first practical dialyzer [ 3 ], the rotating drum kidney, which was composed of a 20-m-long rotating cellophane tube wrapped around a 2 m horizontal drum as the semipermeable membrane. A 67-year-old patient with acute kidney failure in the course of an exacerbated bile duct infection was treated with the rotating drum kidney successfully without subsequent renal impairment. This device could remove uremic toxins but not excessive body fluid, mainly because the transmembrane pressure produced by gravitation is not sufficient to provide ultrafiltration. Thus, renal failure with fluid-overload, such as pulmonary edema or hypertension, was still untreatable with the rotating drum kidney.

After the first successful use of dialysis, the artificial kidney developed rapidly. A modified dialyzer withstanding higher transmembrane pressure allowed excessive fluid removal [ 4 ], a parallel plate dialyzer [ 5 ] for lower blood flow resistance and more controllable ultrafiltration, subtractions of heparin [ 6 ] as anticoagulant for dialysis, and advanced shunt for steady blood vessel assessment [ 7 ] all contributed significantly to the development of renal replacement therapy. In 1960, the first chronic dialysis facility was established in Seattle, and end stage renal disease became no longer a fatal disease.

Nowadays, hemodialysis is a standard treatment all over the world for millions of patients with various diseases from acute kidney injury to end stage renal disease. The hollow-fibered dialyzer and more efficient machines replaced the old giant rotating drum kidney. The healthcare industry keeps making new dialyzers to improve patients’ lives.

2. Designs of the Modern Artificial Kidney

Although the new blood purification system is much better in terms of performance, efficiency, and biocompatibility, the basic idea of blood purification is not different from the first-generation rotating drum kidney. The primary goals of dialyzers are removing solutes and excessive fluid from the blood of the patients. To achieve these goals, the designs of dialyzers are based on four fundamental aspects: structure, performance, biocompatibility, and membrane material.

2.1. Structure

Modern artificial kidneys are hollow-fibered dialyzers composed of a blood compartment, dialysate compartment, and semipermeable hollow fibers ( Figure 1 ). Structures of each part of dialyzers influence the fluid mechanism significantly [ 8 ]. Theoretically, a high clearance could be achieved by reduced fluid resistance, membrane thickness, and expanded surface area.

Modern design of the artificial kidney: the geometric designs of the modern artificial kidney are predominantly hollow-fibered. Low fluid resistance and expanded surface area facilitated the efficiency of dialysis. However, the complicated structure creates multiple dead spaces and turbulence within both compartments.

The geometric designs have evolved greatly since the first rotating drum kidney, which was a 20-m-long cellophane tube wrapped around a 2 m horizontal drum and soaked in a tank of dialysate. In contrast, modern dialyzers are hollow-fibered and much smaller. The hollow-fibered structures provide better membrane surface area and less fluid resistance [ 8 , 9 ]. The hollow-fibered design also makes it easier to control pressure in the blood compartment to achieve precise ultrafiltration [ 9 , 10 ].

There are, however, several drawbacks of hollow-fibered dialyzers. The hollow-fibered structure creates complicated space in the dialysate compartment, which produces turbulence and dead space [ 8 ] and impairs the dialysis efficiency and decreases the predictability of each dialyzer’s performance. In clinical practice, the hollow-fibered structure requires careful deaeration before dialysis treatment to prevent air bubbles from staying in the blood compartment [ 11 ]. Considering the advantages of hollow-fibered dialyzers, modern artificial kidneys are still mostly hollow-fibered.

2.2. Performance

The performance of each dialyzer depends on its ability to remove solutes and excessive fluid from the patient’s blood. In regard to blood purification, solutes in the plasma could be classified based on their molecular weights [ 12 ]. In healthy human bodies, small molecular weight solutes (less than 500 Daltons), such as glucose, electrolytes, lipids, urea, and creatinine, are removed by the kidney through ion channels or diffuse across the cell membrane directly. Middle molecular weight solutes (500–15 k Daltons), such as hemoglobulin, β2-microglobulin, and bilirubin, metabolize in human bodies through various pathways. Large molecular weight solutes (greater than 15 k Daltons) cannot pass through most membranes, which create oncotic pressure across semipermeable cell membranes.

To replace the function of the kidney, dialyzers are designed specifically for solutes with different molecular weights. The semipermeable membrane creates the boundary between blood and dialysate. Solutes with different molecular weights behave differently across the membrane on the basis of three main types of clearance: diffusion, convection, and adsorption.

2.2.1. Diffusion

Diffusion is the random movement of particles from a region of high concentration to a region with low concentration. Dialyzer efficiency, the permeability of small molecular weight solutes, is determined by membrane surface area, physical characteristics of the membrane, and temperature [ 13 ]. Since the efficiency remains the same for a specific artificial kidney under fixed temperature. Diffusion is mainly determined by the concentration gradient across the membrane, which is influenced by blood and dialysate flow rates. Diffusion predominantly affects small molecular weight solutes such as electrolytes and creatinine. Clearance of middle molecular weight solutes via diffusion is usually unachievable.

2.2.2. Convection

Convection describes the movement of particles within fluid. The convective clearance or beta-2-microglobulin clearance of a dialyzer, commonly referred to as membrane flux, represents the water flux or permeability of middle molecular weight molecules. In an artificial kidney, the major determinants are ultrafiltration triggered by transmembrane pressure [ 14 ].

Ultrafiltration is a milestone for the development of dialysis, which allows the removal of excessive fluid in uremic patients. Moreover, solutes are also transported through the membrane during ultrafiltration. This phenomenon is called solvent drag. Most middle molecular weight solutes are removed through this mechanism.

2.2.3. Adsorption

Adsorption occurs with the deposition of proteins on the membrane during dialysis, which creates a biofilm over the inner surface of hollow fibers. The involved particles are mostly ranged from middle to large molecular weight solutes. Adsorption clearance would be affected by membrane porosity and charge-dependent selective permeability [ 15 ].

2.3. Biocompatibility and Systemic Effects

During dialysis, interactions between blood and the inner surface of hollow fibers might trigger systemic effects including inflammation [ 16 , 17 ], coagulation [ 18 , 19 ], erythropoietin resistance [ 20 ], and protein malnutrition [ 21 ].

Adsorption during dialysis creates a biofilm which triggers coagulation and inflammation reactions. Coagulation, induced by adsorbed fibrinogen, increases the risk of intra-dialyzer clotting and post-dialysis thrombocytopenia [ 19 ]. Inflammation, triggered by adsorbed C3b and the activated complement pathway [ 16 ], would induce cytokine release, create oxidative stress, and result in epithelial cell injury, arthrosclerosis, and transient granulocytopenia after dialysis [ 22 , 23 ]. Erythropoietin resistance and protein malnutrition are also induced by similar interactions.

In addition to coagulation and inflammation, other systemic effects such as intra-dialysis hypotension, hemodialysis induced amyloidosis, and residual renal function loss are all undesirable complications of blood purification treatment. Improved biocompatibility is one of the most important goals in future dialyzer development.

2.4. Membrane Material and Characteristics

As an essential part of the artificial kidney, the hollow fiber membrane divides blood and dialysate compartments with different filtration characteristics. The membrane materials used in artificial kidneys include cellulose derivatives, polysulfone derivatives (PSU), polyacrylonitrile (PAN), polymethylmethacrylate (PMMA), and ethyl vinyl-acetate copolymer (EVAL) [ 24 ]. The initial hollow-fibered membranes were mostly built with cellulose derivatives, but synthetic polymer gradually became the major material because of better biocompatibility and performance. The hydrophilicity of membranes is a major determinant of biocompatibility. Hydrophobic synthetic polymer membranes increase the risk of platelet adhesion [ 18 ], Nevertheless, various addictive materials have been doped in the synthetic materials to improve the biocompatibility [ 25 ].

The semipermeable properties of membranes are mostly determined by pore size, porosity distribution, and thickness, which can be investigated with various methods, such as electron microscopy, gas adsorption, X-ray diffraction, etc. [ 26 , 27 ]. At present, various membranes for biomedical engineering such as artificial lungs, plasma exchange therapy, hemofiltration membranes, and hemoadsorption membranes are contributing to medical treatment around the world. Extracorporeal membrane oxygenation (ECMO) and the artificial liver or pancreas are all possible applications of membranes [ 28 ].

3. Room for Improvement

The development of artificial kidneys and semipermeable membranes for blood purification is still ongoing. The advanced synthetic technique, nanotechnology, accumulated data, and experience of dialysis all contributed to the potential of future dialyzer development.

The current system of blood purification became mature after decades of development. From regular dialysis for end-stage renal disease to continuous venovenous hemofiltration (CVVH) for acute kidney injury in intensive care units, various indications are widely used clinically all over the world. However, there is still plenty of room for improvement. There are three main aspects of problems for the current artificial kidneys: patient’s quality of life, complications of artificial kidneys, and lack of metabolic functions.

3.1. Patient’s Quality of Life

The restriction of life is one of the most unbearable side effects of long-term dialysis. Renal replacement therapy requires three 4-h-long dialysis courses every week. The time-consuming course, frequent hospital visiting, water and food restrictions all reduce the patient’s quality of life, joy of tasting, and freedom of scheduling [ 29 ].

To improve patient’s quality of life, the system of dialysis must be modified greatly. Home dialysis, wearable devices, and even implantable artificial kidneys are all possible solutions. To achieve this goal, the source of dialysate, fresh water supply, energy supplement, the size of the artificial kidney, and financial costs are all challenges on the path toward artificial kidneys that provide better patient quality of life.

3.2. Complications of Artificial Kidneys

The problems of biocompatibility and systemic effects are usually accompanied with hemodialysis. Multiple dialysis-associated complications, such as intra-dialysis hypotension, dialysis-related amyloidosis, and erythropoietin resistance, reflect the fact that the current designs of artificial kidneys require further modification and membrane engineering [ 30 ].

The material compositions of hollow-fibered membranes evolved from the original cellophane to modern synthetic polymer materials or cellulose. Water affinity, a significant determinant of membrane biocompatibility, is one important difference between cellophane and synthetic materials. Hydrophilic materials, such as cellophane, induces the complement pathway more easily. Whereas intra-dialysis coagulation is more common with the hydrophobic inner surface of hollow-fibered membranes [ 18 ]. Hollow-fibered membranes with better biocompatibility could be created by modifying hydrophilicity with modern synthetic technology.

Another method of improving biocompatibility is by adjusting the inner membrane surface with coating materials, such as heparin or vitamin E. Theoretically, heparin can reduce coagulation reaction and vitamin E is able to improve oxidative stress induced by inflammation. Parameters of oxidative stress, erythropoietin resistance, and nutritional status were improved with vitamin E coated membranes in some studies [ 31 , 32 , 33 ]. However, the significance of those coating materials remains debatable [ 34 , 35 ].

Other modifications, such as membrane porosity and geometric designs, can all influence the biocompatibility of hollow-fibered membranes. Although being reduced, complications of artificial kidney still limit the capability of hemodialysis after decades of development.

Rapid fluid removal three times a week, hemodynamic change, oxidative stress, and blood vessel calcification all contribute to the high cardiovascular risk in patients with end stage renal disease. Prolonged dialysis duration with nocturnal hemodialysis has been proved to improve cardiac hypertrophy, blood pressure, and heart function [ 36 , 37 ]. However, nocturnal hemodialysis is practical only if home dialysis or wearable artificial kidneys are easily available for every suitable patient.

3.3. Lack of Metabolic Functions

Natural kidneys are not just organs of filtration, they are also responsible for several metabolic functions, such as synthesis of 1,25-dihydroxyvitamin D (1,25(OH)2 D) [ 38 ], ammoniagenesis [ 39 , 40 ], glutathione metabolism [ 41 ], erythropoietin production [ 42 ], and immunoregulatory support [ 43 ]. Modern designs of artificial kidneys put much emphasis on the efficiency of dialysis and fluid removal but not these metabolic functions. To fully replace renal function, the metabolic functions of the kidney must not be neglected in future developments.

4. Direction of Future Artificial Kidney Development

Although the system of hemodialysis with hollow-fibered membranes is well established, the designs of artificial kidneys are still evolving. There are two major trends of future development: miniaturization and restoration of metabolic functions.

Miniaturization of artificial kidneys is one of the major goals of recent dialyzer development, which enables much easier manipulation of dialysis and allows further wearable or implantable designs of artificial kidneys. To achieve miniaturization, membrane engineering for more efficient membranes is essential. Many projects are currently under development [ 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 ]. With the convenience of wearable or implantable artificial kidneys, patients can have frequent and prolonged dialysis to reduce hemodynamic impact during dialysis courses, which have been proven to improve survival, hospitalization rates, bone mineral metabolism, and medication burden [ 36 , 37 , 54 , 55 , 56 ].

Metabolic functions of natural renal tubular cells are not provided by current artificial kidneys, such as biosynthesis of 1,25-dihydroxyvitamin D (1,25(OH)2 D) [ 38 ], ammoniagenesis [ 39 ], glutathione metabolism [ 57 ], and immunoregulatory support [ 43 ]. Erythropoietin production is provided by renal interstitial cells. Without those metabolic functions, abnormal calcium metabolism, ectopic calcification, and oxidative stress significantly increase morbidity and mortality in end-stage renal disease patients [ 43 ].

5. Key Considerations for Future Dialyzer Membrane Development

Multiple projects and innovative designs for artificial kidneys and membranes are still evolving. To reach the goals of miniaturization and restoration of renal metabolic functions, several technologies could be the key for future dialyzers.

5.1. Nanotechnology

Nanotechnology is widely used in the fields of medicine, consumer products, energy, materials, and manufacturing. However, the application of nanotechnology to blood purification treatment was relatively late compared to other industries.

Microelectromechanical systems (MEMS) are a form of fabrication technology that originated from the microelectronic industry [ 58 ]. Silicon, polymers, or metals could all be fabricated precisely to the scale of nanometers by deposition, lithography, etching process, and sputtering. Conventional artificial dialyzers mostly consist of semipermeable hollow fibers with wide pore size distribution. The pore size variation limits the selectivity and permeability of conventional semipermeable membranes. With microelectromechanical systems, semipermeable membranes with identical pore size could be manufactured. Microelectromechanical systems also allow chemistry modification of membranes to adjust electrostatic charge and further prevent platelet adhesion or protein adsorption [ 59 , 60 , 61 , 62 ], which improves the biocompatibility of membranes significantly. The silicon nanopore membranes modified with polyethylene glycol (PEG) and polyvinylamine (PVAm) polymers showed excellent hemocompatibility in the aspects of surface coagulation, complement and platelet activation, and adhesion [ 63 ], which makes silicon nanopore membranes an option for implant applications.

Silicon nanopore membranes for artificial kidneys have been developed for decades [ 64 , 65 , 66 ]. Scientists have developed a silicon nanopore membrane with an array of rectangular pore slits measuring 2.3 µm × 11 nm with an effective diffusion length of 100 µm [ 64 ]. The rectangular pore was designed to mimic the slit between natural kidney podocytes, which enables higher hydraulic permeability compared with conventional hollow-fibered membranes [ 66 , 67 , 68 ]. Compared with current dialyzers, the silicon nanopore membrane provides a comparable urea clearance under 1/20th of the blood flow rate [ 64 ]. The extremely low requirement of blood flow allows blood purification without a mechanical pump as the patient’s nature circulation is sufficient to drive the system. With an 8 h daily dialysis course and the target of a standard Kt/V(K: urea clearance, t: time of dialysis, V: volume distribution of urea) of 2.0 per week, only 0.17 m 2 of silicon nanopore membrane surface area is required, which is 10 times less than current dialysis membranes [ 64 ]. Uniform pore size also provides strict molecular weight cut-off values [ 64 ] and better middle molecular weight solutes clearance. The nanopore membrane has a 18% beta-2-microglobulin clearance rate, which is much higher than current high-flux dialyzers [ 64 ].

With the aid of nanotechnology, membranes with uniform pore size and extremely thin silicon structures provide better clearance under extremely low blood flow rates. Biocompatibility and clearance of middle molecular weight solutes are also improved. With these improvements, the development of wearable or implantable artificial kidneys is possible.

5.2. Tissue Engineering

Tissue engineering combines the use of cells and materials to create artificial structures with specific bioactivity [ 69 ]. Selective cells are attached to designed scaffolds and further implanted to animal or human bodies. Liver parenchyma, blood vessels, skin, and nerves are all practical targets for mimicking [ 70 , 71 , 72 , 73 ].

The physiological functions of the natural human kidneys include numerous metabolic and endocrinological functions. Erythropoietin generation [ 20 ], vitamin D synthesis [ 38 ], ammoniogenesis [ 39 , 40 ], glutathione metabolism [ 57 ], immunoregulatory support, and cytokine homeostasis [ 43 ] are all crucial for human physiology and potentially associated with elevation of mortality and morbidity of patients under long-term hemodialysis. Many clinical trials are ongoing for the practice of bioartificial kidneys produced by renal tubule cells cultured on semipermeable hollow fiber membranes. Some of them showed promising results such as reduced septic shock [ 74 , 75 ], appropriate inflammatory cytokine response [ 43 ], acceptable safety [ 75 , 76 ], and improved vitamin D metabolism [ 77 ].

To achieve good cell adhesion, different extracellular matrices, including laminin, pronectin, gelatin, collagen IV, or L-3,4-dihydroxyphenylalanine, are coated on the outer surfaces of hollow-fibered membranes [ 78 , 79 , 80 , 81 ], nevertheless, the coated materials could block the dialyzer membrane pores and impair the hemodialysis efficiency. Various addictive materials in synthetic membranes have been used in an attempt to overcome this problem. Graphene oxide (GO) or d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) doped hollow-fibered membranes showed excellent cell adhesion and dialysis performance [ 82 , 83 , 84 , 85 ].

In addition to extracorporeal hollow-fibered bioartificial kidneys, implanted cell bioreactors are also under development. Cell source is a major challenge for cell bioreactors. Autologous and non-autologous renal cells are both reasonable choices theoretically. Autologous renal cells eliminate the issue of rejection induced by host immunity. However, the individualized cell incubation process increases the costs and unpredictability of bioartificial kidney performance. Non-autologous renal cells allow more standardized production after stable cell line establishment. To protect the implanted renal cells from host immunity, a barrier to prevent host immunity is necessary. The barrier needs to be a semipermeable membrane, which is crossable for oxygenation, nutrients, cytokines, or substances metabolized by the implanted renal cells. Meanwhile, antibodies and immune cells from patients must be blocked out of the cell bioreactor. Cell encapsulation with ultrathin synthetic membranes to prevent entry of antibodies and immune cells is a possible solution, but the encapsulation also limited the long-term cell viability [ 86 ]. Short-term renal cell therapy with hollow-fibered bioreactors is used in some clinical projects [ 43 , 87 ]. Silicon nanopore membranes fabricated with microelectromechanical systems also provide good protection from host immunity [ 88 ]. Except cell protection and cell sources, the challenge of uniform and steady cell production, good cell adhesion, and nutritional support of cells are all focuses of future development.

5.3. Dialysate Regeneration

To achieve miniaturization of blood purification systems, the large volume of dialysate is the most important challenge. In a 4 h hemodialysis course, up to 120 L of dialysate is needed. Requirement of mechanical pumps for high dialysate flow, stable source of dialysate, and large amount of clean water limits the possibility of miniaturization of the blood purification system.

To reduce the dialysate volume requirement in hemodialysis, dialysate regeneration is a crucial part for the miniaturization of blood purification systems. The REcirculation of DialYsate (REDY) system was first introduced in 1970 [ 89 , 90 , 91 ] to regenerate dialysate and reduce the required volume of water during dialysis. The water-efficient and portable features made the REDY system a promising dialysis mode.

During dialysis, dialysate and blood pass through artificial kidneys in a counter current pattern. When dialysate leaves the artificial kidney, multiple uremic toxins and excessive fluid from the blood compartment are withdrawn with dialysate. In a conventional single pass dialysis, the waste fluid is usually abandoned directly. Compared to single pass dialysis, the REDY system recirculates the waste fluid to an exchangeable sorbent cartridge to remove excessive solutes and regenerate dialysate ( Figure 2 ). The sorbent cartridge contains materials such as charcoal, urease, or zirconium phosphate to eliminate the substance through chemical break down, ion exchange, or adsorptions [ 92 ]. The dialysate regeneration reduces the water requirement from 120 to 6 L per treatment [ 92 , 93 ].

Comparison of the single pass system and the REDY system: dialysis with the single pass system requires a steady water source and used dialysate is abandoned after dialysis. In comparison, the REDY system regenerates fresh dialysate with sorbent cartridge.

The REDY system is not a new idea. Early versions of the REDY system were abandoned because of aluminum release, ammonia spill over, slow increase in sodium concentration of dialysate, and expensive cost of the system [ 92 ]. However, with the introduction of zirconium as ion exchangers and sorbent material, the adjusted size of sorbent cartridge, and modified dialysate components, these disadvantages could be overcome. In combination with the utility of nanotechnology, the dialysate requirement could be reduced to a greater extent.

Nanotechnology, tissue engineering, and dialysate regeneration encompassed the three key components for future artificial kidneys. With nanotechnology, artificial kidneys could be much smaller, more efficient, and driven by blood circulation without mechanical pumps. Combined with the REDY system, the fluid requirement for dialysis could be reduced significantly. Tissue engineering with renal tubule cells provides bioactivities which are essential to human bodies but can never be provided by conventional hemodialysis.

6. Next Generation Artificial Kidneys

6.1. wearable artificial kidneys.

After decades of development, the system of hemodialysis evolves gradually to a routine treatment. However, the limitation of a patient’s lifestyle and frequent visits to dialysis facilities still bother patients greatly. Thus, home dialysis was developed and improved patient quality of life significantly [ 94 , 95 ].

Compared to home dialysis, wearable artificial kidneys put dialysis treatment to another level with more convenience and less hemodynamic impacts. To be truly wearable, the artificial kidney must be light and small. In addition to miniaturization, the requirement of steady blood vessel access, better biocompatibility (including cytocompatibility, immunocompatibility, and hemocompatibility), and patient education are all barriers for the development of wearable artificial kidneys. When being wearable, the dialysis device needs to be operated by the patients themselves. During the dialysis treatment, a patient’s activity might lead to disconnection of the device from blood vessels and monitoring for blood leakage is required for safety concerns.

Because of prolonged dialysis, the importance of biocompatibility also increases. Blood clotting and complement pathway activation caused by membranes would increase complications after prolonged dialysis. Membrane engineering for excellent biocompatibility is crucial. The Center for Dialysis Innovation (CDI) at the University of Washington, WA, USA, are developing two possible solutions for biocompatibility [ 96 ]. Fluoropolymer, a material used in blood content devices, can bind fibrinogen in an inactive form and albumin tightly to avoid further clotting and immune reaction. Another solution is to create surfaces with super non-fouling properties that repel proteins so that protein fouling and coagulation do not occur [ 97 ]. Modification of the membrane surface with microelectromechanical systems to prevent protein fouling is also ongoing [ 59 ].

A wearable hemodialysis device is under development by Gura and his colleagues at the University of California, Los Angeles (UCLA) [ 46 ]. A hollow-fibered dialyzer with a surface area of 0.2 m 2 , dialysate regeneration system, heparin and electrolyte reservoirs, and 375 mL of dialysate are all contained in a wearable dialysis device ( Figure 3 ) with a weight of less than 4.5 kg.

Basic concepts of a wearable hemodialyzer and a peritoneal-based wearable artificial kidney: within a wearable hemodialyzer (upper), the pumps, battery, safety system, and REDY system are all installed in a vest. During dialysis, the REDY system regenerates dialysate and reduces the requirement of water. A bubble detector, blood leak detector, and flowmeter monitor all fluid compartments and shut off the system in the case of an emergent condition. The peritoneal-based wearable artificial kidney (lower) is connected to the patient’s peritoneal cavity and regenerates dialysate fluid. The disposable part of the device is exchanged after dialysis.

In 2016, Gura conducted an FDA-approved human trial of the wearable artificial kidney. A 24 h dialysis with the wearable device was performed successfully in five patients without adverse effects. Mean urea, creatinine, and phosphorus clearances over 24 h were 17 ± 10, 16 ± 8, and 15 ± 9 mL/min, respectively. Mean β2-microglobulin clearance was 5 ± 4 mL/min [ 98 ]. Although the trial was discontinued due to device-related technical problems, including excessive carbon dioxide bubbles in the dialysate circuit and variable blood and dialysate flows, the trial still proved the possibility of wearable artificial kidneys.

Another design of wearable artificial kidneys is a modification based on the treatment with peritoneal dialysis. Although peritoneal dialysis is associated with less life-style restriction for patients compared with hemodialysis, storage and transportation of dialysate are still an issue for patients and limit their daily activities. Several peritoneal dialysis-based wearable devices are under development currently including the AWAK project by AWAK Technologies (Singapore) [ 53 ], the WEAKID project by Nanodialysis Inc (Oirschot, The Netherlands) [ 52 , 99 ], and CarryLife project by Triomed (Lund, Sweden) [ 51 ].

Peritoneal dialysis-based wearable artificial kidneys are composed of portable a sorbent cartridge and a dialysate reservoir ( Figure 3 ). When connected to the filled peritoneal cavity, wasted dialysate flows into the sorbent cartridge and regenerates fresh dialysate intermittently. Without complicated parts needed for hemodialysis, the peritoneal dialysis based wearable artificial kidney could be miniaturized to purse size. Several human trials for peritoneal dialysis-based wearable devices are still under study. Current published research revealed sufficient dialysis clearance without severe adverse events [ 53 , 99 ]. Abdominal discomfort is the most common side effect [ 53 ].

6.2. Implantable Artificial Kidney

Among all renal replacement therapies, kidney transplantation offers the best quality of life, total financial costs, and survival rate [ 100 , 101 , 102 ]. However, the supplies of donated kidneys are far less than the demands. Most patients with end stage renal disease therefore sustain their lives with hemodialysis or peritoneal dialysis.

The implantable artificial kidney is a promising and challenging idea that emerged with the development of renal replacement therapy. The artificial kidney needs to fit several properties to be implantable and replace the function of human kidneys.

First, the requirement of energy supply needs to be as low as possible. An experiment in pigs revealed that the high efficiency of the silicon nanopore membrane allows the dialysis to be performed without mechanical pumps for blood compartments [ 64 ]. Blood circulation is one of the most sustained power sources in human bodies. If the artificial kidney is still depending on a battery for energy supply, the battery should be able to function for years to avoid frequent surgery to exchange the batteries.

Second, hemofiltration should be the modality of renal replacement rather than hemodialysis. Without the demand of dialysate, the implantable artificial kidney could be designed without mechanical pumps for dialysate. The requirement of a steady supply of dialysate, implanted inlet for dialysate, and large amount of fresh water will not exist anymore, then the artificial kidney could be truly implantable.

Third, the device should be extremely biocompatible. The replacement therapy with implantable artificial kidneys performed continuously all day after implantation. Coagulation and complement activation would be more severe than conventional intermittent hemodialysis. Continuous infusion of heparin is also impractical. Modification of the membrane surface should be done to absolutely prevent such reaction. Fluoropolymer material or membranes with super-non-fouling properties are possible solutions [ 59 , 96 , 97 ].

Last but not least, metabolic functions of natural renal cells have long been ignored in renal replacement therapy. The lack of metabolic function leads to multiple comorbidities in patients with end stage renal disease. Bioreactors with renal cells protected by nano-structured materials have been built for implantable artificial kidneys [ 103 ]. Moreover, the excellent protection from host immunity eliminates the requirement for immunosuppressants.

With these four properties, a truly implantable artificial kidney could be manufactured. The Kidney Project led by Shuvo Roy at the University of California San Francisco (UCSF) is currently developing a fist-sized implantable artificial kidney [ 50 ]. The artificial kidney consists of a bioreactor and a hemofilter connected to blood circulation with the common iliac vein and artery ( Figure 4 ). The waste fluid is drained to the patient’s bladder as urination. The driving force of hemofiltration is based on the pressure difference between arterial and venous systems. After implantation, patients could theoretically live without any further hemodialysis.

Implantable kidney: driven by the pressure difference in the artery and vein, blood passes through the implantable kidney, which is composed of a hemofilter and cell bioreactor. With a nanopore silicon membrane, waste fluid (yellow) created by hemofiltration flows into the patient’s urinary bladder. Dialyzed blood is transferred to the cell bioreactor after hemofiltration. Natural kidney metabolic function is restored by protected renal tubule cells in the cell bioreactor.

7. Conclusions

The design of artificial kidneys has developed dramatically over decades after invention in the early 20th century. Hollow-fibered dialyzers overwhelmingly replace other artificial kidneys currently for the advantages of less fluid resistance and better surface area. However, patient’s quality of life and complications of artificial kidneys remain challenges of modern dialyzers. However, the time-consuming treatment course limits the patient’s quality of life significantly. Hemodialysis-related complications also highlight the unmet need for better biocompatible dialyzers. Multiple attempts, such as geometric designs and modified synthetic materials, have been made to overcome these challenges; nevertheless, there is still plenty of room for improvement. Miniaturization and restoration of kidney metabolic functions are the goals of new artificial kidneys. With the introduction of nanotechnology, tissue engineering, and the REDY system, the designs of modern artificial kidneys have changed dramatically. Although many technical problems still exist, wearable and implantable artificial kidneys are the next promising milestones in blood purification therapy.

Acknowledgments

We sincerely thank the editors and reviewers for their hard work on the manuscript and their constructive suggestions.

Author Contributions

Conceptualization, S.-Y.L.; investigation, Y.-S.T. and Y.-C.T.; writing—original draft preparation, Y.-S.T. and S.-Y.L.; writing—review and editing, S.-Y.L.; supervision, T.-W.C.; project administration, S.-Y.L. All authors have read and agreed to the published version of the manuscript.

This research is supported by MOST 110-2314-B-075-028-MY3.

Institutional Review Board Statement

Informed consent statement, data availability statement, conflicts of interest.

The authors declare no conflict of interest.

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

University of Memphis touts $1M investment into artificial intelligence research amid xAI news

J ust a day after the reveal that the Elon Musk-company xAI would build the "world's largest supercomputer" in the Bluff City, the University of Memphis has announced a new investment in artificial intelligence.

University of Memphis is poised to inject a million dollars into academics and research focused on artificial intelligence. This initiative is aligned with community efforts to bring xAI to Memphis , and it’s being led by Provost David Russomanno and Jasbir Dhaliwal, executive vice president of research & innovation.

“The arrival of xAI is a perfect fit with the technology innovation ecosystem of Memphis, which is centered around the University as a top-tier Carnegie R1 research institution,” President Bill Hardgrave said in a press release. “We have much to offer in terms of talent, workforce training, and cutting-edge research.”

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Added Russomanno: “We will offer a wide range of educational experiences across the University, including degree programs and stackable micro-credentials customized by context and topic, reflecting student and workforce needs. Going forward, we will provide opportunities for all our students to understand and apply AI.”

 Already, U of M has supported and launched AI initiatives; it isn’t an unfamiliar area to the university.

For more than 30 years, it’s focused on applying AI to major local sectors, like education, healthcare, and transportation. It recently founded the Center for Electrified and Autonomous Transportation and Agile Freight Supply Chain; U of M’s FedEx Institute of Technology houses an array of AI-oriented groups.

901 AI, for example, offers a place for local professionals to engage in AI-based work, and it’s paired with the Data Science Research Cluster, and the upcoming AI research Cluster. The FedEx Institute also leads the Next Generation Supply Chain and Innovation Challenge, which is an industry-aligned AI effort partnered with the National Science Foundation.

TN leaders: Planned supercomputer in Memphis may help with crime, add job diversity

U of M also has one of the largest computer science programs in the state; and in the past three fiscal years, enrollment in its AI-oriented departments – including management information systems and electrical and computer engineering – has doubled. A significant chunk of that growth has come from master’s level candidates.

Now, the university is poised to use the work it’s done to incorporate AI into more academic areas – an effort that school leaders believe could attract more students.

On Wednesday, the Greater Memphis Chamber announced that xAI would be coming to Memphis . Chamber President and CEO Ted Townsend said it would represent a multibillion-dollar investment and is the largest by a new-to-market company in Memphis history. Final job counts and total investment are still being calculated by the company, but the project is expected to open this year.

John Klyce covers education and children's issues for The Commercial Appeal. He can be reached at [email protected]

This article originally appeared on Memphis Commercial Appeal: University of Memphis touts $1M investment into artificial intelligence research amid xAI news

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• 08 March 2023

Researchers tackle chronic kidney disease

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Every 30 minutes, the kidneys filter all the blood in the body. This round-the-clock removal of toxins is hard work, and over a lifetime of purification, these vital organs can falter. The result is a progressive condition that affects roughly 10% of the world’s population — an astonishing 800 million people. In fact, chronic kidney disease (CKD) has become one of the leading causes of death worldwide. The stakes are high, and research is advancing on multiple fronts .

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Nature 615 , S1 (2023)

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Liquid metal-based electronic logic device that mimics intelligent prey-capture mechanism of Venus flytrap

New insight on embodied intelligence inspired by plant.

A research team led by the School of Engineering of the Hong Kong University of Science and Technology (HKUST) has developed a liquid metal-based electronic logic device that mimics the intelligent prey-capture mechanism of Venus flytraps. Exhibiting memory and counting properties, the device can intelligently respond to various stimulus sequences without the need for additional electronic components. The intelligent strategies and logic mechanisms in the device provide a fresh perspective on understanding "intelligence" in nature and offer inspiration for the development of "embodied intelligence."

The unique prey-capture mechanism of Venus flytraps has always been an intriguing research focus in the realm of biological intelligence. This mechanism allows them to effectively distinguish between various external stimuli such as single and double touches, thereby distinguishing between environmental disturbances such as raindrops (single touch) and insects (double touches), ensuring successful prey capture. This functionality is primarily attributed to the sensory hairs on the carnivorous plants, which exhibit features akin to memory and counting, enabling them to perceive stimuli, generate action potentials (a change of electrical signals in cells in response to stimulus), and remember the stimuli for a short duration.

Inspired by the internal electrical signal accumulation/decay model of Venus flytraps, Prof. SHEN Yajing, Associate Professor of the Department of Electronic and Computer Engineering (ECE) at HKUST, who led the research, joined hands with his former PhD student at City University of Hong Kong, Dr. YANG Yuanyuan, now Associate Professor at Xiamen University, proposed a liquid metal-based logic module (LLM) based on the extension/contraction deformation of liquid metal wires. The device employs liquid metal wires in sodium hydroxide solution as the conductive medium, controlling the length of the liquid metal wires based on electrochemical effects, thereby regulating cathode output according to the stimuli applied to the anode and gate. Research results demonstrate that the LLM itself can memorize the duration and interval of electrical stimuli, calculate the accumulation of signals from multiple stimuli, and exhibit significant logical functions similar to those of Venus flytraps.

To demonstrate, Prof. Shen and Dr. Yang constructed an artificial Venus flytrap system comprising the LLM intelligent decision-making device, switch-based sensory hair, and soft electric actuator-based petal, replicating the predation process of Venus flytraps. Furthermore, they showcased the potential applications of LLM in functional circuit integration, filtering, artificial neural networks, and more. Their work not only provides insights into simulating intelligent behaviors in plants, but also serves as a reliable reference for the development of subsequent biological signal simulator devices and biologically inspired intelligent systems.

"When people mention 'artificial intelligence', they generally think of intelligence that mimics animal nervous systems. However, in nature, many plants can also demonstrate intelligence through specific material and structural combinations. Research in this direction provides a new perspective and approach for us to understand 'intelligence' in nature and construct 'life-like intelligence'," said Prof. Shen.

"Several years ago, when Dr. Yang was still pursuing her PhD in my research group, we discussed the idea of constructing intelligent entities inspired by plants together. It is gratifying that after several years of effort, we have achieved the conceptual verification and simulation of Venus flytrap intelligence. However, it is worth noting that this work is still relatively preliminary, and there is much work to be done in the future, such as designing more efficient structures, reducing the size of devices, and improving system responsiveness," added Prof. Shen.

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