Kidney IDEAS: The Future OF Renal Replacement Therapy - Part 2

Picking up where I left off last week, let’s talk about the implantable and regenerative options of renal replacement therapy in the pipeline.

An example of a bio-hybrid device is the implantable kidney. This combination of the technological and the biological allows for the elimination of pumps, tubes, dialysis, and immunosuppressive drugs for a permanent solution to renal failure.

• The Kidney Project holds a special place in my heart. One of the very first sessions I ever attended at KHI was a presentation by Shuvo Roy. I had only been on dialysis for a few months, and frankly, the future looked stark. He was talking about an implantable device that could replace kidney function 24/7 without the use of the anti-rejection medications needed with current transplants. What’s not to like? Afterwards, I thanked Shuvo for providing dialyzors with hope, and his reply was genuine: “It is not hope, it is a reality.” So, why is it taking so long? Well, in truth, by research standards, it isn’t.

  The implantable artificial kidney has been a long-term project for study co-authors Shuvo Roy, Ph.D., University of California, San Francisco (UCSF) Professor of Bioengineering and Therapeutic Sciences, and William H. Fissell, IV, M.D., University of Vanderbilt Associate Professor of Medicine—but actually research on the implantable kidney only became a reality about 12 years ago.  

  Much of the technology to implement this complex process already existed, some of it developed by Roy and Fissell, of The Kidney Project. One of the challenges for researchers was to integrate various innovations into one functional, compact—and thus implantable—device. This product will closely mimic normal physiology and duplicate kidney function, providing continuous treatment. A primary advantage is reduced treatment impact for patients (e.g., thirst, diet, work, mobility) and an unlimited, readily available supply of organs when needed.

  Seems simple enough, until I sat in a room with the many of the principle investigators on this project, and realized that each minute detail of the device involved lengthy research to validate its safety and efficacy. Just a discussion on how much processing the bio-reactor should accomplish, or what is an acceptable level of transporting, took hours to review, and years of research!

  And all this must occur before human trials can take place. So the fact that segments of this device have satisfactorily survived in animal trials is significant, and limited human trials are pending. One reason that the anticipated start date for these trials keeps getting moved back is because this is uncharted territory, and the Independent Review Board (IRB), responsible for approving and monitoring these trials, is being extraordinarily cautious.

In full disclosure, Home Dialyzors United has been a partner with The Kidney Project for several years, and I am a member of the Advisory Board for their Quantum grant.

Renal regenerative medicine therapies (RRMTs) aim to regenerate, repair or replace damaged renal tissue using cell, drug or gene therapies as well as tissue engineering in order to restore normal kidney function.

• The Harvard Stem Cell Institute¹ (HSCI) is one research hub developing new therapies to repair kidney damage, reducing the need for dialysis and transplantation. The project with the greatest potential impact on diabetes patients is HSCI’s large, multi-disciplinary effort to create an artificial kidney using stem cells and nanotechnology. Scientists plan to isolate kidney stem cells, mix them with soluble gels, and mold them into the architecture of a nephron. Scientists have already successfully created an artificial rat kidney that produces urine once transplanted into the animal, making artificial organ transplantation a highly possible reality for humans. Another example of regeneration of normalized kidney function might be replacing fibrosis with normal nephrons and vasculature to restore biological kidney function. In this RRT, kidney function can be recovered and maintained, eliminating the impact of disease on patients (e.g., unrestricted diet, return to work).

• 3D bio-printing (3DP) was started by Dr. Anthony Attala from Wake Forest Institute for Regenerative Medicine, who applied 3DP to manufacture organ tissues of the heart and kidney. It is recognized that medical uses for 3D printing, both actual and potential, will bring revolutionary changes. They can be organized into several broad categories, including creation of customized prosthetics, implants, and anatomical models; tissue and organ fabrication; manufacturing of specialty surgical instruments; pharmaceutical research for drug fabrication, dosage forms, delivery, and discovery; as well as manufacturing medical devices. Benefits provided by application of 3D printing in medicine include not only the customization and personalization of medical products, drugs, and equipment, but also cost-effectiveness, increased productivity, the democratization of design and manufacturing, and enhanced collaboration. The future of applications of 3DP in medicine appears optimistic with the extension and refinement of old and development of new spectacular applications. (https://hsci.harvard.edu/kidney-disease-program) New 3-D-printed kidney tissue is the work of the Jennifer Lewis lab at Harvard, which has developed an innovative approach to “bioprinting” tissue using 3-D printing. Their scientists have created tiny, intricate tubes that work like key components of real kidneys. Many more steps are needed before they can make artificial kidney replacement parts, but the result is important, because it means that for the first time researchers have used 3-D printing to make kidney tissue that functions like the real thing. The inventors say that in the near term the artificial tissue could be used outside the body to assist people who have lost renal function, and for testing the toxicity of new drugs.

Researchers have been trying to create artificial kidneys for more than 20 years, but re-creating the complex three-dimensional structure and cellular architecture, which are crucial to kidney function, is extremely challenging.

One thing I am certain of is that previous research efforts in RRT have not always been sufficiently patient-centered. KHI was founded to address this. Their most recent accomplishment, KidneyX, is the collaboration of a public private partnership (ASN and HHS) to fund advances in treating CKD and innovation in RRT technology, all of which must be patient-centric. Recent results from the Standardized Outcomes in Nephrology initiative on hemodialysis (SONG-HD) indicated that, in setting priorities, patients seek more immediate relief from the burdens of dialysis treatment, while physicians focus largely on improved biochemical and clinical outcomes. For example, physicians list the worst possible patient outcome as death, whereas, overall, patients list fatigue. This is a huge disconnect. What the medical profession has failed to understand, from the patient perspective, is that quantity of life is not nearly as important to patients as quality of life. Any device that plans to make it to market cannot successfully do so without taking patient perspectives into consideration.

To Learn More

• Computer simulation Looks at the Problem of Blood Clotting. https://www.nibib.nih.gov/news-events/newsroom/artificial-kidney-development-advances-thanks-collaboration-nibib-quantum

• Third Generation Wearable Artificial Kidney Will be Lighter, More Discrete [Sic] https://www.healio.com/nephrology/artificial-kidney/news/online/%7Bc7e69599-d5f1-4d2f-b67c-2cd3d498f7ba%7D/third-generation-wearable-artificial-kidney-will-be-lighter-more-discrete

• The Wearable Artificial Kidney: An Interview with Dr. Victor Gura https://www.kidneynews.org/kidney-news/practice-pointers/the-wearable-artificial-kidney

• ASN Twitter Feed - https://twitter.com/ASNKidney/status/1026860724356882439

• Gura V, Rivara MB, Bieber S, Munshi R, Smith NC, Linke L, Kundzins J, Beizai M, Ezon C, Kessler L, Himmelfarb J. A Wearable Artificial Kidney for Patients with End-stage Renal Disease. JCI Insight. 2016;1(8):386397, free full-length PDF here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4936831/pdf/jciinsight-1-86397.pdf