Bioengineering innovations to decrease failure rates of arteriovenous fistulas and grafts, improved infection control measures in catheter-based and peritoneal dialysis, and a new hemodialysis system designed for home use were the prize-winning “Redesign Dialysis Phase 2” innovations announced at the recent virtual KidneyX Summit.
KidneyX (the Kidney Innovation Accelerator) is a partnership between the American Society of Nephrology and the US Department of Health and Human Services (HHS) to promote innovations in kidney disease prevention, diagnostics, and treatment. Through a series of monetary prize competitions, KidneyX helps speed the development of new medical products by fostering collaboration among patients, health professionals, industry, innovators, and government experts.
This year’s summit continued the emphasis of the 2019 Redesign Dialysis Phase 1 competition, awarding grants of $500,000 to each prize winner. The competition received 70 submissions, which were reviewed under a rigorous two-phase process.
The need for true, patient-centered innovations in dialysis care is profound. Dialysis itself has changed relatively little in the past several decades, with huge financial impacts on the US healthcare system and on kidney patients’ quality of life.
“It will take collaboration across industries and disciplines to truly redesign dialysis and transform the status quo of kidney treatment, and that is what KidneyX is delivering,” said Eric Hargan, JD, HHS Deputy Secretary. “You have the chance to change not just the face of kidney care in America, but across the whole world.” Kidney health innovation is a top priority for HHS and will help achieve goals outlined in the Advancing American Kidney Health initiative.
Serial entrepreneur Dean Kamen, of DEKA Research & Development Corporation, gave the summit’s keynote address, noting that true innovations are so compelling that people are willing to change the way they do things. “An innovation actually solves a real human need,” he said. “It can be scaled practically. In the medical space, that not only means it has to be safe and reliable, but it has to be affordable.”
“What frustrated me about the kidney health innovation landscape was that everybody was talking in different rooms,” said panelist Sandeep Patel, PhD, the former HHS open innovation manager who played an integral role in establishing KidneyX. “And that doesn’t even get to all the engineers and scientists that don’t even know there is a problem to be solved. To me, that’s the power of KidneyX.” Patel is currently Director of the HHS BARDA Division of Research, Innovation, and Ventures.
KidneyX incorporates patient input at every step of evaluation, and the panelists and award winners highlighted the critical role of such perspectives in their innovations.
Redesign Dialysis Phase 2 award winners
Fistula and graft innovations
The preferred form of dialysis vascular access is an arteriovenous (AV) fistula, which provides lower infection rates and longer functioning lifetime compared to grafts. But not all patients can get AV fistulas. They cannot be utilized as quickly, and sometimes the fistulas never mature. Although less prone to failure than AV grafts, AV fistulas have a 30–40% failure rate at one year. With repeat failures, some patients are forced into catheter-based access, an approach that significantly increases the chances of mortality.
Buddy Ratner, PhD (previous Phase 1 winner), for creation of a new type of AV graft
Ratner is co-director of the Center for Dialysis Innovation at the University of Washington. He and his colleagues created a tubular AV graft with similar mechanical compliance to a native artery. The graft is designed to perform better than those currently available and to reduce the rate of failure.
Although standard Teflon grafts are not toxic, they initiate an inflammatory response, Ratner said, leading to scarring and out-of-control cell growth. This, in turn, leads to partial occlusion of the vessel, and the resultant reduced blood flow leads to clotting. “The scar-like sheath also inhibits the pulsation of the graft with each beat of the heart,” Ratner said. “Teflon grafts do not flex, which disturbs blood flow and further enhances the inflammatory reaction.”
Ratner and his team invented a porous biomaterial where all the pores are 40 microns in diameter and interconnected. Although not bioresorbable, the material heals inside the body without stimulating a chronic inflammatory reaction or creating a scarring sheath. Over time, blood vessels grow into the tiny pores, providing a path to seed the luminal region with protective endothelium. These blood vessels can also allow phagocytic cells to access bacteria, potentially reducing complications from infection.
The team has studied the new graft type, which they call “pro-regenerative access graft” (PRIDE), in sheep models, where they have demonstrated much reduced thrombotic deposition.
“We believe the PRIDE would reduce expensive and painful surgeries while performing as well or better for blood access than the fistula,” Ratner said. They speculate that the grafts might be used to address lower limb complications, as a critical need exists for synthetic vascular conduits for diseased leg vessels less than 5 mm in diameter.
Aijun Wang, PhD, for a product that could modify existing grafts to reduce graft failure
Wang is associate professor of surgery and biomedical engineering at the University of California, Davis, and co-founder of VasoBio, a medical device startup company. He and his team focused on improving vascular grafts for hemodialysis.
Wang’s group targeted endothelial cells, cells critical for anti-platelet adhesion, anti-inflammatory responses, and other key properties. “Establishment and maintenance of a healthy endothelium is crucial for the prevention of clotting and narrowing of blood vessels,” he said.
Using high-throughput screening technology, the team identified a peptide ligand, LXW7, that possesses high affinity and specificity for endothelial cells and their progenitor cells. They then developed a method to coat grafts already on the market with the ligand. The idea is that the graft would become lined with living endothelial cells that could perform a protective function.
“An innovation actually solves a real human need. It can be scaled practically. In the medical space, that not only means it has to be safe and reliable, but it has to be affordable.”
Dean Kamen
The team verified that endothelial cells do grow and spread more easily on the modified graft. In small and large animal models, the grafts modified with LXW7 maintained significantly higher patency compared to untreated grafts. Those coated with LXW7 displayed a smooth layer of endothelial cells lining the luminal surface, without red blood cell adhesion or platelet clumping.
Although these grafts coated with LXW7 appear identical to uncoated grafts to the naked eye, they work significantly differently at the molecular level, Wang said. They also could be integrated seamlessly into existing surgical protocols. The team posits that the technology might one day successfully be used for such applications as stents, catheters, and chemotherapy ports.
Timothy Boire, PhD, for SelfWrap to reduce AV graft and fistula failure
Boire is the president and CEO of VenoStent. His team developed SelfWrap, a slowly bioresorbable shape memory polymer wrap that provides personalized fit and support at the site of vein-artery or vein-graft junction, the areas most prone to failure as they adapt to an increased blood pressure.
“The main culprit of access failures is inward collapse of the vein through neointimal hyperplasia,” Boire said. “Providing durable but flexible mechanical support reduces the deformation of the vein and provides for more effective outward vein growth.” The support also mitigates hyperplasia and turbulence within the vessel.
SelfWrap is designed to slide up the graft or vein before surgically securing the connection between the artery and vein or the graft and vein. After this connection is secured, the SelfWrap is slid down over the junction. The material becomes slightly sticky and viscous at body temperature, allowing it to close without the need for sutures and in a manner that provides a custom fit to the patient’s specific vessel anatomy.
“The wrap provides mechanical support similar in compliance to that of an artery, and is slowly degraded to improve usability and durability, or maturation and patency,” Boire said. Results from sheep studies showed that use of SelfWrap significantly reduced neointimal hyperplasia while promoting outward remodeling of the vessel or graft, potentially leading to reduced infection, thrombosis, and stenosis.
The team is focusing its preclinical development on use in AV fistulas but hopes to receive FDA approval for use in AV grafts as well.
Reducing infection
Two of the KidneyX winners tackled infection prevention as their primary focus, in two quite different contexts: peritoneal dialysis and catheter-based hemodialysis.
Sarah Lee (previous winner, KidneyX Patient Innovator Challenge)
Sarah Lee is CEO of Relavo, a medical device company founded by students at Johns Hopkins University. She and her colleagues created PeritoneX to help prevent infection due to touch contamination in peritoneal dialysis.
Peritoneal dialysis provides better health outcomes, higher patient satisfaction, and improved patient lifestyle, but only 10% of patients needing dialysis are on it because of the inherent risk of peritonitis, which occurs in 30% of patients annually and necessitates hospitalization in 50% of cases, Lee noted. The Advancing American Kidney Health Initiative aims to dramatically increase the percentage of kidney failure patients on home dialysis. This only increases the need to make peritoneal dialysis safer.
PeritoneX is a two-part connection device consisting of a reusable injection-retraction component and a disposable fluid component containing sodium hypochlorite (an established disinfectant in dialysis catheters.)
“Rather than connecting tubes directly, patients will connect them to our device,” Lee said. “They’ll then push a button to release the antimicrobial solution into the connection space, where it will kill any bacteria on the tube surfaces before being automatically retracted.” This maintains a closed system between disinfection and dialysis treatment. In proof-of-concept studies, the device has been shown to exceed industry standards for catheter disinfection.
PeritoneX is compatible with Baxter International peritoneal dialysis supplies, where it can slip seamlessly into the existing setup. Currently no other products on the market aim to reduce risk of peritonitis from peritoneal dialysis, and educational efforts about best practices only slightly decrease rates.
Alexander Yevzlin, MD (previous Phase 1 winner), for NitriCap to reduce catheter infections
Over 110,000 patients in the US use a catheter for vascular access each year, resulting in about 30,000 infections.
In response to this need, Yevzlin, a professor of medicine and director of interventional nephrology at the University of Michigan, and his colleagues developed NitriCap, a disposable hemodialysis cap that secretes nitric oxide gas. The nitric oxide is contained in a stable donor molecule that elutes the gas over three days.
“It’s a very simple, unique extension of a regular cap that fits into the hub of a dialysis catheter that can reduce microbial growth,” Yevzlin said.
Nitric oxide is well known to be a potent antimicrobial and antifungal, but it has a half-life of only seconds, eliminating potential systemic effects. Added Yevzlin, “Nitric oxide is produced as a gas, never enters the body, and disinfects the inside and outside of the catheter as it diffuses harmlessly into the air.”
Studies in sheep demonstrated a more than 100,000-fold reduction in bacteria compared to a control cap. Animal studies also showed that the product prevented the formation of biofilm in all four regions of the catheter. In contrast, commercially available antimicrobial caps using chlorhexidine did not.
“Our patients are constantly living in fear of catheter infection and catheter dysfunction,” Yevzlin said. “We think this device can have a huge impact on our patients’ lives
Shuvo Roy, PhD (previous Phase 1 winner), for a new hemodialysis system for home care
Roy is a professor in the department of bioengineering and therapeutic sciences at the University of California, San Francisco, and technical director of The Kidney Project, an effort focused on creating a small, surgically implanted, bioartificial kidney to treat kidney failure.
Unlike the other awardees, who are producing products that can merge into and improve existing dialysis setups, Roy and colleagues are developing the iHemo Dialysis System to provide frequent, prolonged hemodialysis sessions with much greater patient ease.
Roy pointed to evidence that patients receiving more frequent and prolonged hemodialysis treatments have better survival rates, better overall health, and fewer dietary restrictions. Currently only about 2% of people on dialysis receive such treatment. Existing bulky hemodialysis systems approved for home use require complex tasks such as vascular cannulation, and they pose risks such as exsanguination.
With iHemo, a compact hemodialyzer (HemoCartridge) is surgically implanted inside the patient’s abdomen. It is constructed from silicon nanopore membranes that allow it to work under normal cardiac perfusion pressures, without the need of a mechanical blood pump or systemic anticoagulation therapy. The hemodialyzer connects to the blood vessels on one side, creating a permanent blood circuit inside the patient’s body. On the other side, it connects to catheters leading to an external pump.
“From the viewpoint of patients, iHemo fundamentally simplifies the procedure of hemodialysis,” said Roy. “The only external component is a compact pump to recirculate dialysate. No blood ever leaves the body, and patients never have to insert needles into a fistula or graft. Instead, they connect dialysis tubing to a catheter to conduct their treatments.”
Looking ahead
All the recipients emphasized how important these prizes are for furthering their work. The money allows the teams to push their development forward while they raise additional funds from investors.
“This award will help us advance our prototypes to clinically relevant devices that we can test in preclinical disease models and ultimately in clinical trials,” Roy said. “We also hope that the KidneyX award will garner more interest from industry and the investor community to support new innovations to treat kidney failure and kidney disease, because such interest has been significantly lacking for quite some time. It has taken the vision of HHS and ASN to step up.”
KidneyX will soon open two more prize competitions: an artificial kidney prize and a competition for solutions to address challenges caused by the COVID-19 pandemic.
“I hope that KidneyX plays a catalytic function, that we’ll get a self-sustaining innovation ecosystem where we are getting new products on the market constantly and are constantly improving patient care,” Patel said. “Ultimately the measurement of success of KidneyX is not in the programs we create . . . it’s whether we create health and wellness for the people for whom we are innovating.”
