In your view, what are some important areas in need of research?
Dr. Moe: There are many areas in nephrology where more research is needed, such as dialysis delivery. This filtration process hasn’t changed in decades and is ripe for innovation.
Dialysis only removes toxins and doesn’t replicate any of the other functions of kidney tubule cells, like breaking down metabolites and synthesizing hormones. In theory, renal tubule cells could be regenerated using progenitor stem cells, and could be made to function.
The challenge would be placing them on a wearable or implantable matrix or use them as a truly biocompatible membrane.
The process of dialysis uses a lot of water, which is not recycled. Some studies have shown that this water could be potentially recycled, which would be a great improvement cost and environmental benefits.
More research is also needed in vascular access. Although fistula and graft use has become common, there isn’t a mechanism to avoid needles. New insights are needed on how to treat some vascular access complications, and the difficulties patients experience with those complications.
A lack of standardized end points for clinical trials in this area has hampered research. The Kidney Health Initiative (KHI), a joint ASN-FDA partnership, will address this in a new project.
Finally, the problem of health disparities needs to be addressed. African Americans, Native Americans, and Hispanics are far more likely to have progressive kidney disease, and there is an understanding of some of the genetic associations involved.
However, the roles these genes play are less well understood. If we could harness research to understand how those genes alter progression in different ethnic groups, we might be able to do more personalized or targeted therapy. That, in and of itself, is really critical for slowing the progression of kidney disease and keeping people off of dialysis altogether.
Any thoughts about the research needs in kidney transplantation?
Dr. Moe: When dialysis was first developed, it was designed to be a bridge toward transplantation. A kidney transplant will always be the number one choice of therapy for end-stage renal disease.
But many patients die on dialysis before they get a kidney simply because there’re not enough organs. If we can give those patients more hope and better a therapy, perhaps a cell-based therapy, maybe they’ll stay healthier longer and even do better with transplantation.
What about implantable kidneys?
Dr. Moe: One of the barriers to getting new technologies approved is how you define the end points for approval. Moving forward from improved duration of life to improved quality of life is a major step. Another project within KHI is looking at how patient preferences may be included in the FDA approval process for devices.
Engaging patients in the design of a clinical trial or definition of the end point is one way to encourage the approval of therapeutics that patients (not industry or clinicians) feel will impact their quality of life and/or function. Implantable kidneys are very viable options, and are receiving serious consideration by by the FDA. However, there first has to be investors who are willing to take on these projects.
If you’re going to invest in the dialysis space, you also need to have a return on your research and development costs. That means a potential change in the reimbursement model, which currently does not support innovation.
Do you think the pharmaceutical and medical device companies have cut back on research funding since the debut of bundling?
Dr. Moe: The uncertainty of whether or not a drug or device will be considered as a treatment within the bundle probably has led some companies to decide not to enter into the dialysis space.
A large investment of time and money are put into development of drugs, devices, and biologics, and companies don’t want to make that investment if they don’t know if these are going to get reimbursed many years from now. All of those uncertainties do discourage companies from entering into the renal space. This may be why there’s been a lot more focus on the predialysis space, where there is a little more certainty on coverage.