KidneyX Summit Highlights Innovative Approaches to Kidney Care

Transplanting pig kidneys into humans

Two of the prize winners are trying to make it possible to transplant genetically modified pig kidneys into humans. Xenotransplantation researcher David K.C. Cooper, MD, PhD, FRCS, of Harvard University, believes this is the solution to increasing the supply of available kidneys for transplant. His team has successfully transplanted pig kidneys into primates, with the kidneys functioning for more than 1 year in several of the animals and one kidney functioning for 4 years. But the results are not consistent enough yet for the U.S. Food and Drug Administration to allow human trials, he explained. To improve success, his team needs to develop a better immunosuppressant regimen, Cooper said. He is hopeful they will see success in a couple of years, which would open the door for human trials.

Cooper pointed out that 45% of patients receiving dialysis are taken off the transplant waiting list because they have died or have developed co-morbidities that make them unsuitable for transplant. He believes those patients should be the first to be offered a pig kidney. “One day, organ transplantation from deceased human donors, I think, will be of historic interest only,” Cooper said. “People at a meeting like this in 30 years' time will say, ‘Once upon a time, they actually transplanted kidneys from dead people—can you believe that?’”

Like Cooper, Matt Tector, PhD, chief scientific officer at Makana Therapeutics, is also working on using pig kidneys for humans. Tector's team is trying to solve the challenging fact that every human has antibodies to every pig, which would cause the human body to destroy a transplanted pig kidney in minutes or hours. His team selected 44 patients on the kidney transplant waitlist to evaluate how their antibodies bind to the cells in genetically modified pigs. They discovered that knocking out one or two genes was not enough. But by knocking out three genes, the human anti-pig antibodies fell to an acceptable level. Next, they tested the three-gene-knockout pigs on 822 patients and found that 40% of the patients fell into the detectable but manageable level, whereas 30% of patients had no detectable anti-pig antibodies. “We're very excited that these triple-knockout pigs can be useful for 70% of patients in need of an organ transplant,” Tector said, “and we're hoping to move forward with clinical trials in the near future.”

Tools to develop artificial kidneys

Nephrologist William Chang, MD, PhD, of Yale University, proposes improving care of patients with end stage kidney disease (ESKD) by combining innovations in stem cell technology and tissue engineering with the established clinical practice of peritoneal dialysis. “Kidney organoids can now be generated from patient-derived stem cells,” Chang explained. But the question is how to use them therapeutically. “I believe you can implant these in the abdomen as an augmentation of peritoneal dialysis,” Chang said. “You can then drain fluid and allow filtration to occur.” Advantages include that the stem cells are derived from the patients, reducing infection risk, and that peritoneal dialysis is well-established and is the preferred form of dialysis by many patients with ESKD, Chang noted.

Bioengineer Shuvo Roy, PhD, of the University of California, San Francisco, is aiming to provide patients with a small, implanted, bioartificial kidney. Roy's team has developed a bioartificial kidney that uses a mechanical hemofiltration unit and a bioreactor with engineered renal tubule cells. Importantly, patients with the device would not need treatment of immunosuppressive drugs, he said. The team has successfully implanted and operated the device in pigs for 7 days without immunosuppression. Roy estimated his team needs approximately $20 million and 3–4 years to get through the first clinical human trials. “If we do that, we're able to get to something that will provide patients a better quality of life and save costs and allow us to change how end stage renal disease is treated,” he said.

Vascular biologist and tissue engineer Ben Shepherd, PhD, is co-founder and chief executive officer of Trestle Biotherapeutics. His team focuses on regenerative medicine. They aim to develop implantable therapeutic tissue that would replace the kidney, using a patient's own stem cells to grow more cells and then a new kidney in the laboratory. This would be a solution “that restores renal function, that provides freedom of mobility, that doesn't come with an increased risk of infection, [and] that doesn't come with an increased risk of cancer,” he said.

Shepherd explained that all of the technology his team needs already exists; the challenge is putting it all together. “[At Trestle, we are] taking newly formed stem cells and creating cells that will become the kidney, organizing those into miniature organs that contain blood-filtering units that are essential to renal function. And we're now using 3D bioprinting techniques to make larger tissue with interconnected, fluid-filled channels so that we can mature that tissue and get it ready for transplantation. But to be clear, there's a long way to go,” Shepherd continued. “Some of these things are more advanced than others. Some simply require more capital and research and development. And some, we must understand much better before we could ever safely administer them to a patient.”

As the KidneyX Summit came to a close, Rush reiterated the importance of developing technology that would realistically work with patients' lives and their needs. “With all the exciting things on the horizon—it's great to see all the technical stuff and scientific things, [but we need to marry] the two between the patient and the technology, making sure that the technology equals some of the patients' needs and some of the needs of the people involved in the patients' lives,” Rush said. “We need both of them to co-exist.”

2023 KidneyX winners

Track 1 participants each received $1.6 million, and Track 2 participants each received $1 million.