Future of kidney replacement. Am I on the right track here?

[PaulBC]

When my daughter was diagnosed with ESRD, I spent a good deal of time trying to answer what her life will be like 20 years from now. The short term (dialysis) and medium term (transplant) are very clear, but I really want a much better answer. Here is a summary of what I came up with. I have a lot of links in my source document that are omitted here.

To put this in context, I would have thought that regenerating new organs was farther along than I now believe it is. However, at least some transplant recipients may benefit from establishing immune tolerance using bone marrow from the donor, and that is not just speculation. I'm less certain about work on the artificial implantable kidney (Shuvo Roy, UCSF). I'd like to know more about how it is progressing.

Is this reasonable? Am I missing anything? My summary:

There are two main approaches to permanent kidney replacement to eliminate reliance on scarce human organ availability and solve rejection issues:

• An implantable artificial kidney that would be much smaller than current dialysis machines and would carry out other kidney functions (renal assist device).  It could be bioartificial, meaning it would have a component containing live cells. There are devices under development, but it is unclear when they will be small enough and suitable for implantation. (Clinical trials are planned in a few years, so this may become available within the next decade, assuming the trials go well.)
  
• A means of growing a new, fully compatible organ, preferably from the patient’s own cells. Some ideas include using a decellularized kidney (either unusable human kidney or pig kidney) as a scaffold for stem cell growth. The work in this direction looks very preliminary. It’s unclear if this can be put in clinical practice in the next two decades.

Some other developments that could help, but don’t solve the whole problem:

• Improvements in anti-rejection therapy, particularly using bone marrow (or stem cells) to establish a chimeric immune system that would tolerate new organ. Does not solve scarcity problem (does it help at all?). This has been accomplished in some cases, but it’s unclear if it is generally applicable.
  
• Xenotransplantation, e.g. from pigs. This has been considered for over a century but never carried out successfully. Would hypothetically solve scarcity problem. It’s unclear if this is possible at all, and if so, rejection would still need to be handled with medication.
  

In situ kidney regeneration:

• It’s commonly understood that once scarring occurs, the glomeruli cannot regenerate. While this is generally true, some signs of repair have been seen, at least when damage is not as severe. Could a stem cell treatment be developed that actually repairs a damaged kidney? I have no way to guess at the feasibility. From a research article: “It is unlikely than any organ-based repair process will overcome the extent of damage that is seen in a patient who has reached end-stage renal failure.” I have seen some suggestion that repair can occur but the condition of the kidney before treatment is unclear.

Incremental results in treatment:

• Mostly improvements in dialysis. Machines are getting smaller and more available for home use. The wearable artificial kidney (WAK) is a miniaturized hemodialysis machine. Significantly, it does not require a plumbing connection. While this should improve quality of life and provide benefits of continual dialysis, it does not replace all kidney function. It seems like it would also have the same risk of infection as any kind of catheter placement. This looks most suitable for adults who are not good transplant candidates or have a very long wait.

[Michael Murphy]

There is new work on using 3d printers to create the collagen frame work that cloned cells are attached to build new kidney.  What I understand there is currently testing on rats with rat kidneys built this way.  There is also research on using these printers to build kidneys directly with cells applied by the print heads. 

[PaulBC]

Yeah, I had heard about 3d printing of organs, though I can't think of anything specific that came up in my reading. As soon as I read about using decellularized kidneys as a scaffold, I thought that sounded like a more direct approach to the structural problem, but you still need to get the cells to organize, and individual nephrons are very complex. The cells know how to self-organize during development, but you need to put them in the right context.

The main sense I get reading about kidney generation for rats and so forth is that they are not quite fully functional kidneys and don't have the same level of filtration (let alone replacing other kidney function). So I wonder how long it would take to get something that really replaces a kidney and passes clinical testing.

The optimist in me says that stem cell research is accelerating rapidly, and 20 years is a long time. The pessimist wonders what has really advanced in the past 20 years. I think all the current therapies are the same as in 1994, though I don't doubt there have been improvements in outcomes. I am hoping for a much better next two decades.

[Michael Murphy]

There is several promising approaches being worked at the same time.  It appears that one should eventually work.  At the same time work is also going forward on better dialysis technology better filters and new methods of creating dialysate which would require less water.  It appears that with all the work going on one of the approaches will pay off before your daughter is too old.  I go to one of the few pediatric dialysis centers in my state.  And while I would hope that a transplant would arrive for each of these kids.  They all seem to be doing well.  Also the new transplant rules are aimed at providing the best kidneys to the youngest patients.  I know it would be best if your child was not in this position but there is real hope in the next decade.