With limited funding, researchers move forward on bioartificial kidneys, xenotransplants
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In a recent editorial, Beatrice Concepcion, MD, wrote despite some challenges, transplantation “remains the treatment of choice for most patients with advanced kidney disease,” offering a better quality of life compared with dialysis.
Administrators of the Medicare End-Stage Renal Disease Program see kidney transplants as more cost effective compared with dialysis and encourage the option through demonstrations that are part of the Advancing American Kidney Health initiative.
But donated kidneys are a limited resource. According to the United Network for Organ Sharing (UNOS), 6,400 living-related kidney transplants were performed in 2022, with an additional 18,600 deceased donor transplants, which pushed the total number of kidney transplants performed in a year past 25,000 for the first time.
Source: Susan Merrell/UCSF
That compares to 93,000 people on the national waitlist for a kidney transplant, according to UNOS.
Alternative options
The short supply of organs vs. the high demand for kidney transplants has created an opportunity for development of alternatives to treat chronic kidney disease before dialysis becomes the likely option.
“There are simply not enough organs available for everyone who needs one,” Robert A. Montgomery, MD, DPhil, the H. Leon Pachter, MD, Professor of Surgery and chair of the department of surgery and director of the NYU Langone Transplant Institute, said in a press release after leading a medical team in performing the fifth xenotransplantation at NYU Langone. “Too many people are dying because of the lack of available organs, and I strongly believe xenotransplantation is a viable way to change that,” he said.
While Montgomery is focused on fine-tuning pig-to-human organ transplants, other researchers are bench-testing mechanical devices that mimic kidney function. Victor Gura, MD, a Los Angeles-based internist and nephrologist and his company, Wearable Artificial Organs Inc., are part of a group of scientists and entrepreneurs who are pursing development of a portable or wearable bioartificial kidney for patients with progressive CKD (see Table).
Gura has conducted three human trials with early versions of his Wearable Artificial Kidney (WAK) and is planning two more trials with a lighter version of the device, which has been reduced from 11 pounds to 2 pounds and was granted a U.S. patent in 2021.
“We need an alternative that provides patients with a better quality of life than being tethered to a dialysis machine,” Gura told Healio | Nephrology News & Issues.
The WAK “will disrupt the dialysis industry and reduce the staggering costs of treating [end-stage kidney disease] ESKD patients,” Gura said in a press release. “Most patients today depend on dialysis clinics to receive their care, but application of the WAK instead will make this unnecessary.”
Gura said patients will use a catheter as a vascular access for his device, which patients will use 24/7. “Since the catheter is in place all the time, it reduces the risk of infection vs. a catheter that has to be accessed for each dialysis treatment,” he told Healio | Nephrology News & Issues.
At the University of Washington Center for Dialysis Innovation (CDI), a research team led by Jonathan Himmelfarb, MD, is developing a wearable, minaturized hemodialysis-based device called the AKTIV (Ambulatory Kidney to Improve Vitality) that is “low-cost, water-efficient, and patient friendly; requires minimal anticoagulation; and offers complication-free blood access,” according to a description of the device on the CDI website.
PD approach
Awak Technologies has taken a different approach to a wearable kidney. The Singapore-based company, which secured more than $20 million in new funding in January, is developing the Automated Wearable Artificial Kidney Peritoneal Dialysis (Awak PD) device, a wearable and portable peritoneal dialysis system.
The technology involves “regenerating and reconstituting waste dialysis fluid into fresh, usable fluid, reducing the volume of dialysis fluid required by up to 90%,” according to a company press release. “This achievement also enables the miniaturization of the dialysis machine to a size that can be conveniently carried in a small bag. As a result, patients experience an enhanced quality of life, benefiting from the convenience and flexibility of Awak’s dialysis technology.”
In October 2018, the company concluded its first-in-human study with no recorded severe adverse events, according to the release. In June, the company enrolled its first patient as part of a pre-pivotal clinical trial to study the safety and efficacy of the Awak PD.
Funding for research
A partner of CDI, dialysis provider Northwest Kidney Centers, is providing $15 million for research and development of the AKTIV. Groups like CDI have also been encouraged by KidneyX, a competition organized by HHS and funded by the American Society of Nephrology and Congress, to encourage development of new devices to treat kidney disease.
CDI was one of six winners of a $650,000 grant in an international competition to create components and systems for artificial kidneys funded by the KidneyX Artificial Kidney Prize. The competition, worth more than $10 million in research awards, is divided into phases that include development of bioartificial kidney prototypes toward first-in-human studies and producing components and tools that enable the development of the devices.
The research and engineering costs for these devices are significant, Shuvo Roy, PhD, who leads The Kidney Project, a nationwide biomedical engineering collaboration from the University of California, San Francisco told Healio | Nephrology News & Issues. Roy is working with William H. Fissel, MD, an associate professor in the department of medicine in the division of nephrology and hypertension at Vanderbilt University Medical Center, on development of an implantable bioartificial kidney.
“There are times when I feel like I am part-businessman and part scientist,” Roy said. “The issue for us is not so much about moving the research forward. It’s more about obtaining the funding.” The Kidney Project was awarded a $1 million Artificial Kidney Prize from KidneyX for advancing its prototype bioartificial kidney.
Roy and Fissell co-authored an article in Nature Communications with others recently about the components of the implantable bioartificial kidney.
“Previous success has been reported using an extracorporeal renal tubule assist device (RAD) containing human renal epithelial cells (HREC),” the authors wrote. “Our group has adopted the biohybrid approach of the RAD to develop a completely implantable bioartificial kidney (iBAK); to mimic human nephron physiology, we envision an iBAK composed of a silicon hemofilter to recapitulate the selective permeability of the glomerulus, coupled with an immunoprotective bioreactor containing renal tubule cells to reabsorb solutes and water and recreate the metabolic and endocrinologic function of the renal tubule.”
“In the proposed iBAK, HREC are encapsulated within the bioreactor to continuously process the ultrafiltrate from the hemofilter and selectively return sodium ions and water back to the circulatory system to ensure volume homeostasis,” the authors wrote.
The Kidney Project has successfully tested the two components in a scaled-down version of the artificial kidney, Roy said.
Xenotransplantation
The world’s first genetically modified pig kidney was transplanted into a human on Sept. 25, 2021, at NYU Langone Transplant Institute, which was followed by a second similar procedure on Nov. 22, 2021.
In the transplant procedure performed in July, Montgomery and his surgical team removed a kidney from a 58-year-old man who had been on a ventilator after being declared dead by neurologic criteria and, with permission from the family, replaced it with a kidney from a pig. The study concluded on Sept. 14, when the man was removed from the ventilator and his body returned to the family.
“We have learned a great deal throughout these past 2 months of close observation and analysis, and there is great reason to be hopeful for the future,” Montgomery said in a press release about the study results.
In another xenotransplantation study, 17 cynomolgus monkeys that survived more than 60 days following transplants using genetically modified kidneys from Yucatan minipigs were evaluated for physiological kidney function. The study was done by scientists at eGenesis Inc. and clinicians from the Center for Transplantation Sciences at Massachusetts General Hospital and results were published in Nature Communications.
“The survival period for this group of cynomolgus monkeys was 82 to 642 days,” Susan Low, PhD, director of development for eGenesis, told Healio | Nephrology News & Issues. “Since measures of renal filtration can be somewhat variable in the early post-transplant period, only data from recipients surviving greater than 60 days were included in these analyses.”
Low said data from the study indicate inefficient signaling in the renin-angiotensin-aldosterone system (RAAS) pathway between the porcine kidney and the non-human primate recipient, but “the clinical implications of this finding may be minimal. Patients with [CKD] or [ESRD] often have hyperactive RAAS. Given the high likelihood for significant residual RAAS function in human xenotransplant recipients in a clinical trial, the lack of porcine kidney contribution to the RAAS pathway may mitigate potential deleterious effects for patients” during human trials, she said.
Montgomery said continuing with xenotransplants will bring the technique closer to more extensive human trials. “We think using a pig already deemed safe by the FDA, in combination with what we have found in our xenotransplantation research so far, gets us closer to the clinical trial phase,” he said in a press release. “We know this has the potential to save thousands of lives, but we want to ensure the utmost safety and care as we move forward.”
- References:
- AWAK Technologies and Singapore General Hospital launch pre-pivotal clinical trial of wearable peritoneal dialysis device.
- https://www.prnewswire.com/news-releases/awak-technologies-and-singapore-general-hospital-launch-pre-pivotal-clinical-trial-of-wearable-peritoneal-dialysis-device-301852063.html. Published June 19, 2023. Accessed Sept. 21, 2023.
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- Victor Gura, MD, can be reached at victorgura@gmail.com.
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