Bio-artificial kidney Milestone

For millions of people around the globe, end-stage renal disease (ESRD) is a life-altering diagnosis that brings with it a grueling, time-consuming regimen of medical treatments and an agonizing wait for a potential organ transplant. The physical, emotional, and financial burdens of total kidney failure are immense. However, a glimmer of hope is steadily growing on the horizon. The Kidney Project, a national, collaborative research effort, is diligently working to develop an implantable device that could forever change the landscape of nephrology. In a major presentation at the American Society of Nephrology Kidney Week 2019 conference in Washington, DC, researchers announced a significant breakthrough: the successful implantation of a prototype bioreactor into pigs without triggering immune rejection or blood clots. This remarkable achievement brings the medical community one giant leap closer to a fully functional bio-artificial kidney for human patients.

Bio-artificial kidney: A Collaborative Effort to Eliminate Dialysis

The Kidney Project is a highly ambitious initiative spearheaded by leading scientific minds, specifically Shuvo Roy, PhD, a faculty member in the Department of Bioengineering and Therapeutic Sciences at the University of California, San Francisco (UCSF), and Dr. William H. Fissell, MD, a prominent nephrologist from Vanderbilt University Medical Center. For over a decade, this cross-country partnership has been driven by a singular, life-saving goal: to create a viable, surgically implantable bio-artificial kidney that completely eliminates the need for dialysis and eases the devastating, urgent shortage of donor kidneys.

To fully understand the gravity of this project, one must examine the staggering statistics surrounding end-stage renal disease. In the United States alone, nearly 750,000 Americans are currently being treated for ESRD. Worldwide, that number swells to over two million individuals. With rates of chronic kidney disease growing at a rapid, alarming pace, the medical system is facing a severe shortage of available organs for transplant. Data from 2016 highlights the severity of this crisis: there were roughly 100,000 patients languishing on the national kidney transplant waiting list, yet only about 21,000 donor kidneys became available that year. For many patients, the anticipated wait time for a matching organ stretches anywhere from five to ten long years.

While they wait, the vast majority of these patients are kept alive by dialysis, a medical procedure that artificially filters toxins from the blood. However, dialysis is incredibly cumbersome. Patients must tether themselves to machines for several hours a day, multiple times a week. Furthermore, while dialysis clears out immediate toxins, it is an imperfect substitute for a real organ. It does not replace many of the essential, continuous functions of a healthy human kidney. As a result of these physical limitations and the heavy toll the treatment takes on the human body, the long-term prognosis for dialysis patients remains grim; on average, only 35 percent of patients on dialysis survive past the five-year mark.

Beyond the human cost, the financial toll of standard ESRD treatments is astronomical. In 2016, the cost of dialysis and other related treatments—which are universally covered by Medicare in the United States—reached a staggering $35 billion. This single disease state accounted for a massive seven percent of Medicare’s total annual budget. A successful bio-artificial kidney would not only give patients their lives back but also relieve an enormous financial burden on the national healthcare system.

Bio-artificial kidney: How the Two-Part Implant Operates

The genius of The Kidney Project’s device lies in its sophisticated, two-part design, carefully engineered to mimic the complex physiological duties of a natural organ while fitting into a form factor roughly the size of a standard deck of playing cards. This compact size is crucial, as it allows the device to be surgically implanted into the patient’s abdomen in a manner very similar to a traditional kidney transplant.

The first major component of the device is the hemofilter. This acts as the primary filtration system, mirroring the function of the glomerulus in a biological kidney. As blood flows into the hemofilter, it passes through advanced, micro-machined silicon membranes. These membranes are fabricated with precisely shaped, nanometer-scale pores. As the blood pushes through these microscopic grates, harmful toxins, waste products, and excess water are effectively filtered out, while essential blood cells and vital proteins are retained in the bloodstream. Following promising studies in large animal models, this hemofiltration component is currently awaiting approval from the U.S. Food and Drug Administration (FDA) to begin initial clinical trials specifically evaluating its safety in human subjects.

The second component, and the subject of the recent breakthrough, is the bioreactor. While a mechanical filter can remove waste, a healthy kidney does much more than act as a sieve. Kidneys are highly active chemical processing plants that regulate blood pressure, maintain adequate fluid volume, balance critical salt and electrolyte levels, and produce essential hormones that the body needs to survive. To replicate these complex biological tasks, the researchers developed the bioreactor to house a culture of living human kidney cells. As the filtered fluid from the hemofilter passes through the bioreactor, these lab-cultured cells perform the necessary metabolic and endocrine functions to keep the patient healthy.

Before the November 2019 presentation, this bioreactor technology had performed beautifully in controlled laboratory experiments but had never been successfully implanted into an animal model. The successful integration of these two components—the hemofilter and the bioreactor—represents the realization of a completely self-contained bio-artificial kidney.

Overcoming the Twin Hurdles of Rejection and Clotting

One of the most persistent and dangerous challenges in the field of organ transplantation and long-term medical implants is the body’s natural immune response. When foreign tissue is introduced into the human body, the immune system instinctively attacks it. To prevent this, traditional kidney transplant recipients must take a strict regimen of heavy immunosuppressive drugs for the rest of their lives.

“It has been a holy grail of transplant therapies to find ways to avoid the need for lifelong immunosuppressive drugs that are often required to prevent immune rejection,” explained Dr. Shuvo Roy. These drugs severely compromise a patient’s immune system, leaving them highly vulnerable to opportunistic infections and viruses. Over time, these toxic medications can also cause harmful side effects, directly damaging the transplanted cells and eroding the therapeutic benefits of the new organ.

Cost is another devastating factor linked to these medications. While Medicare uniquely covers standard dialysis treatments for life, it generally covers immunosuppressive drugs for only the first three years following a transplant surgery. This creates a tragic paradigm where many patients who are lucky enough to receive a biological kidney transplant ultimately lose the new organ simply because they can no longer afford the expensive medications required to keep it from being rejected.

During the Kidney Week conference, UCSF Surgical Innovations Fellow Dr. Rebecca Gologorsky presented the team’s elegant solution to this problem. The silicon membranes inside the bioreactor act as an impenetrable physical shield. The nanometer pores are perfectly sized to allow essential nutrients to reach the enclosed human kidney cells, but they are too small for the host’s large, blood-borne immune cells and aggressive antibodies to pass through. By keeping the immune system out, the bio-artificial kidney protects the cultured cells from attack, entirely eliminating the need for toxic, costly immunosuppressive drugs.

The team also had to tackle a second massive hurdle: blood clots. Any artificial material introduced into the bloodstream carries a high risk of triggering a coagulation cascade, leading to potentially fatal complications like a pulmonary embolism or a stroke. Standard blood-friendly coatings used on heart valves and catheters were much too thick; they would clog the delicate nanometer pores of the silicon membranes. To circumvent this, the engineers painstakingly developed a novel surface chemistry. They coated the blood-contacting surfaces of the silicon filters with specialized, biologically friendly molecules at a microscopic level. Furthermore, the internal geometry of the device was precisely mapped and engineered to ensure a smooth, continuous flow of blood, avoiding the turbulent eddies and stagnant pools that typically trigger clot formation.

The results from the pig trials were outstanding. The animals housed the prototype device without suffering from blood clots, and the cells inside remained healthy and functional without the use of blood thinners or anti-rejection medications.

The Road Ahead: Scaling Up for Human Trials

“This is the first demonstration that kidney cells can be implanted successfully in a large animal without immunosuppression and remain healthy enough to perform their function. This is a key milestone for us,” stated Dr. Roy.

With this critical safety data in hand, The Kidney Project has proven that they are steadily advancing toward a clinical “trifecta.” Their ultimate vision is a surgically implanted device that requires no external batteries or tethers (which carry high infection risks), runs entirely on the natural pressure of the patient’s own beating heart, and cleans the blood flawlessly without the crutch of anti-rejection drugs or dangerous blood thinners.

The researchers’ next immediate objective is scaling up the device. The prototype bioreactor tested in the pigs must be expanded to hold a much larger volume of cultured cells to fully supplement kidney function in animals experiencing complete renal failure.

Moving a complex, cell-based medical therapy from the laboratory into active human clinics is an arduous journey. “Advancing a complex cell therapy like this into the clinic will not be a trivial task,” Roy cautioned. “For instance, it will require substantial investments in cell production and characterization in controlled GMP [Good Manufacturing Practice] facilities to avoid any possibility of contamination. Now we’ve confirmed that we’re on the right track to move forward with these efforts.”

If successful, the bio-artificial kidney will not just represent a triumph of modern bioengineering; it will mean a second chance at a full, unhindered life for millions of people worldwide currently tethered to dialysis machines.