Dialysis technology, which continues to dominate the current treatment of end-stage renal disease patients, dates back to the early 1940s. It also typically proves unable to maintain these patients sufficiently long enough to get them to kidney transplant, which is only available for a fraction of those who need it.

Roseville, Calif.-based US Kidney Research Corp., formerly Curion Research Corp., has been working on its waterless renal replacement technology since its inception in June 2015. Its latest research efforts using its novel blood purifying technology have led to the production of the first ‘synthetic urine,’ which mimics the body’s natural production and the kidney’s filtration capability.

KidneyX validation

The researchers have tested their approach in pigs. That data is slated to be published in a peer-reviewed journal in the next few months; it also was presented as part of the inaugural KidneyX Redesign Dialysis phase I contest. Last spring, US Kidney Research was among the 15 winners of that event, with each receiving $75,000 after a competition against 165 other submissions.

KidneyX, also known as the Kidney Innovation Accelerator, is a public-private partnership between the U.S. Department of Health and Human Services and the American Society of Nephrology. The accelerator was established in April 2018 to help advance the development of innovative solutions that could prevent, diagnose or treat kidney diseases. KidneyX is running phase II of that contest, with submissions due by the end of January 2020; the three winners each will receive a $500,000 prize.

“We've managed to create synthetic urine, which is urine created by artificial means other than the native kidney. No one has ever been able to accomplish that,” US Kidney Research founder and CEO Roland Ludlow told BioWorld MedTech. “We found that making the filtration part of the system was the easier part. Some people have discovered how to do that.

“However, … you have various ions and substances, including sodium, potassium, urea [and] water, that have to be transported, either to the blood or urine stream, and in appropriate amounts over a period of time,” he added. “In order to do that, you need to create an ion transport and water transport system, which we have done. That's why we were able to create the synthetic urine.”

The device includes a pair of electrodeionization units – one dedicated for potassium, as these levels are essential to maintaining cardiac electrical activity, and another for all the other ions. It also has three other modules: ultrafiltration to keep blood cells and proteins in the body, nanofiltration to prevent the excretion of glucose, and reverse osmosis to modulate the amount of water excreted.

It is designed to eliminate urine at a pace that is comparable to a kidney, outputting roughly the same amount of water as is consumed in a given day. It incorporates feedback sensors and customizable software to control changes in blood chemistry.

“Electrodeionization technology was not invented by us. It's been used for … years in the water purification industry. It's also been used in the cosmetic industry and the beverage industry. Because in all these industries, they [must] have water with certain chemistry,” said US Kidney Research science and medical adviser Ira Kurtz, who is also chief of the nephrology division at the University of California at Los Angeles Medical Center.

“We're basically using the same technology. We've modified the device so that we can do multiple ions simultaneously within one unit, which no one has done before,” he added. “That’s how we’re doing the transport as opposed to dialysis. We … have electrodeionization modules that can transport ions. We think it's much more elegant and will allow us … to accomplish our goals without needing a separate dialysate solution and dialysis water infrastructure.”

Standard dialysis machines expose the blood to dialysate via a membrane; the difference between the composition of the dialysate and the blood determines which ions move out of the body and into the dialysate. Unlike dialysis, this approach doesn’t require the purified water or dialysate that add complexity and expense for providers and patients.

Wearable first

The expectation is that US Kidney Research will pursue three iterations of its technology: a standalone machine comparable to existing dialysis devices, a wearable version that could be used throughout the day, and an implantable, miniaturized version that could truly aspire to replacing an organ and providing comparable function.

The company is seeking a corporate dialysis industry partner to advance a standalone device. Its focus for now is on demonstrating human proof-of-concept with a wearable version, which could be worn in a backpack or a fanny pack and would produce bagged urine. After that, it aims to miniaturize and adapt its technology for an implantable version.

US Kidney Research has thus far raised a few million dollars and has the means to continue operations. It is in conversations with potential dialysis industry partners and is considering offers from some of them, Ludlow said.

It aims to be in human trials within about two to two-and-a-half years with the wearable iteration of its technology to be attached to the bloodstream via a catheter inserted into a vein beneath the collar bone. The expectation is that the device could be worn daily and removed and reattached to the catheter by patients.

Artificial kidney prototype. Credit: US Kidney Research Corp.

To get there, the startup needs to continue to improve its technology, miniaturize its prototype and do further biocompatibility testing for safety. “The technical challenges for the next two years are to work on each of the components. For the ultrafilter, we have to work on ways of preventing the patient from needing heparin or an anticoagulant.” said Kurtz. Anticoagulants are standard for long-term dialysis patients.

“We're planning on redesigning the ultrafilter to have components in the filter itself that will prevent blood from clotting. There is technology out there for doing that,” he continued. “The other thing we need to do technically is to improve the electrodeionization units. Right now, we have a selectivity of approximately four to one. We'd like to get that up to 11 or 12 to one. We'd like to get to a point where ion transport modulation involves only a specific ion, without doing any other transport so that we can individually control the transport of each ion without the transport being coupled. There's technology out there that can do it, we just have to incorporate it into our device.”

US Kidney Research isn’t alone in its efforts toward an implantable kidney replacement. For example, researchers from the University of California at San Francisco aim to start clinical testing in 2020 for the Renal Assist Device, which is a bioartificial kidney that combines a membrane hemofilter and a bioreactor of human renal tubule cells.

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