TISSUE ENGINEERED KIDNEYS + TRACHEA ARE NEW ON THE BLOCK

Tissue engineers strive to construct whole organs for clinical reconstruction or transplantation from components that did not naturally co-exist or may not even be natural. The world has been in a bit of a tizzy because of two different and unrelated advances that became public within two weeks in April, 2013. In the first, kidneys whose cells were removed but whose microscopic infrastructures were kept intact, were reconstituted with two types of cells (epithelial and endothelial). The kidneys (from rats) exhibited some function both in the laboratory and when transplanted (small amounts of urine in rats). In the second, a 32 month old child whose own trachea did not develop, received the world's first bioartificial trachea  engineered from an artificial nanofiber scaffold and stem cells taken from her own bone marrow. In both cases tissue engineers have accomplished incredible feats.

Just imagine the sequences that could result. Rat kidneys that function after transplantation might lead to the ability to engineer human kidneys following the same principles. Suddenly, there might be a way to help the 100,000 people currently waiting for deceased donor kidneys in the U.S. Others who dared not even dream of trying to qualify for a transplant might now do so.

Clinical success with the bioartificial trachea is even more stunning. Direct application of translational science in a living person. Since the living cellular component is her own, there is no expectation of rejection. No need for immunosuppressive medications. What a win-win situation! How many other ways can you imagine using bioengineered body components to fill in missing body parts caused by congenital defects, disease or trauma? Perhaps now the cause for excitement is clear.

We should also take particular note of the timing of these two announcements. Unlikely that serendipity is involved. Maturation of multiple skills, technologies, concepts and prior developments in a field often combine to make a ripe environment for talented researchers to work in - a sort of perfect scientific storm. These leaps forward could probably not have occurred twenty years ago. But today, the time is right. Let's hope that other exciting announcements follow.

WHY TRANSPLANT A UTERUS?

Roughly half of humanity does just fine without a uterus. The rest of us only experience function during a minor (approximately 12 -48 years of age) portion of our life cycle. While even those years of uterine function remain essential for the survival of our species (despite the amazing reproductive technologies available today), they are not for the individual's survival. For this reason, a uterus- of which there has been one publicly known successful transplant survivor to date - falls into the category of "Quality of Life" transplants. Different from the other organs in that category - the hand, face and larynx-, this is the first vascularized (with a specific reattached blood supply) organ transplant of any type that is intended to be temporary. What a mind boggling concept! It seems that the patient and transplant team expect to stop the anti-rejection medications and remove the uterus following the conclusion of child bearing. Quite logical actually. Why keep a woman on immunosuppression one moment longer than necessary?

Still, this new area raises revolutionary questions.

• Does it make sense to try to control the immune system's response with potent drugs that can cause life threatening infections and cancers just for a few years and to hope for recovery of that system through withdrawal of the medications and (presumably) the uterus? 
• Will the immune system recover back to baseline? Are experiences with failed kidney transplantation an appropriate model?
• Are there long-term consequences for the patient? 
• Who should pay for the privilege of this non-life saving transplant?
•  Are there really enough resources available to support widespread use of a therapy that is not required and may indeed be harmful? 
• If not, and it will only be available to wealthy individuals, should they be permitted to engage the nation's network of donor identification and the organ allocation system in order to find the needed uterus? 
• If not through that means, how will they find a uterus?
• Is it reasonable to intentionally expose a helpless fetus to development while receiving immunosuppressants? To the unknown impact of growth within a transplanted uterus? Who should consent for that fetus?
• Since all nerves to the uterus were cut when it was removed from the donor will the patient/recipient feel contractions (!)?

Yet another typical day in donation and transplantation. A real life situation that could not have been imagined if one had tried. Never a boring day. Trying to achieve equity. Failing to do so because of the resource shortfall. Ethical twists and turns. Learning something every single day.

Those who have never faced infertility issues may not fully understand the strength of the drive for procreation which must be the motivation for a uterine transplant. Among the amazing range of available reproductive technologies, none quite match up to this one. The closest, the use of a gestational surrogate to carry your pregnancy is still not the equivalent of carrying your  own pregnancy, to feeling life within your body, or to delivering your own child. The patient's interest in this transplant is quite understandable. Whether the investigators should perform it when more standard approaches would likely produce a baby with greater certainty is the key, new question on the table.

Thus far, the world has been notified that a first pregnancy has occurred through in vitro fertilization (IVF) and is six weeks along. This patient was also the world's first successful recipient of a uterus transplant. Since then a Swedish team has performed 2 successful mother-to-daughter uterus transplants. Despite the questions and reservations that come to mind, this incredible step in the science and medicine of transplantation now involves a real woman (her name is Derya Sert) and her fetus (with an audible heartbeat). It will be a privilege to provide subsequent comments on even more progress as they share their experiences with the world.

CITIZEN ACTION NEEDED TO HELP KIDNEY PATIENTS - AGAIN

U.S. kidney transplant patients are caught in a political/fiscal Catch-22 that leads to cessation of Medicare coverage for their anti-rejection medications at approximately $10,000 to 20,000 per year, 36 months after transplantation. A proven outcome for some patients has been failure of the transplant with a return to expensive dialysis - again paid for by Medicare, this time at an approximate cost of $70,000 per year. Ridiculous, right?

http://www.govtrack.us/congress/bills/113/hr1428#

Ironically, this dilemma fits well into the mutual history of kidney disease and Medicare. We now take Medicare coverage of dialysis for granted. But it was an individual citizen's definitive and courageous act that helped establish that new entitlement forty years ago. Shep Glazer, a 43 year old husband, father and salesman, supported by the precursor organization to today's American Association of Kidney Patients,  and other stakeholders, opted to be openly dialyzed on the floor of the Ways and Means Committee, stunning everyone on November 4, 1972.  His "excellent testimony" made the point. Chronic kidney failure was adopted into the Medicare program in October 1972.

It appears that Congress may now finally be committed to fixing this medication coverage problem.  Another step has just been taken on the legislative pathway, but a few major ones are still required (make it out of House and Senate Committees, approval by House, approval by Senate, negotiation + agreement by House + Senate members, Presidential signature). Kudos to Representative Michael Burgess from Texas who introduced the Comprehensive Immunosuppressive Drug Coverage for Kidney Transplant Patients Act of 2013  
into the House of Representatives on April 9, 2013. The House Bill was referred directly to the House Ways and Means Committee on the same day and matches the Senate Bill previously introduced on February 13, 2013 by Senators Durbin and Cochran. Both would remove the medication coverage cliff awaiting patients at 36 months following kidney transplantation.

Noted clearly on the government website is the low percentage of bills that make it out of Committees for consideration by the entire House or Senate; only 13% of House bills and 1% of Senate bills succeed to the next procedural step. If our dual immunosuppressive bills don't make it out of their respective committees, they will be "dead" and the Catch-22 will continue. This is where your help is needed - really. We must help push these bills out of committee for consideration by the entire legislative bodies.

Politicians respond to their constituents, especially when significant numbers of citizens make the effort to respectfully express an opinion through the system. To date, it appears that only 35/435 Representatives have signed on as co-sponsors of the Burgess bill, and 5/100 Senators have signed on as co-sponsors of the Durbin bill. Many of our legislators need to hear directly from us about these bills.

Spend some time now confirming the identity and contact information for your own Senators and Representative.   If your politician has already "signed on" to the appropriate bill (the Senate bill for a Senator, the House bill for a Representative), call or e-mail to say; "Thank- you for signing on to the Comprehensive Immunosuppressive Drug Coverage for Kidney Transplant Patients Act of 2013".  If the individual has NOT YET signed on, indicate that you believe that signing on is important - and why.

Special effort should come from constituents who live in the districts and states of the House Ways and Means and Senate Finance Committee members. They include:

You will be joining an important and proud tradition of citizen voices shaping Congressional action. Shep Glazer's personal action was considered "excellent testimony" and made a real difference. Your personal phone calls and e-mails will be too.

< SIX DEGREES OF TRANSPLANT

Organ donation and transplantation have steadily become so intertwined with the cultures of the developed world that it is difficult NOT to find connections to our own lives. Just this weekend while spending time away with family, I personally fell upon two different and poignant true life transplant tales.

In the first, the woman arranging the new lease on my daughter's (a college freshman) first apartment was unusually helpful - almost motherly in her patient approach. We had established an easy working relationship on the prior day when I scouted the building ahead of my daughter. Despite being kind, her thoroughness and professionalism had provided me with confidence and reassurance that my daughter would be in a well run facility. I was therefore stunned when her placid face and smooth toned voice changed suddenly as she looked at my responses to the form on which I promised to back up my daughter's credit. The words she spoke made no sense; "I pray for you every day", she said.  I did not understand the sudden appearance of tears either. But then she asked; "Are you really a transplant surgeon?" and her story spilled out.

I had been right in my assessment of her maternal nature. Her own daughter was a transplant recipient, having received her father's kidney 30 years ago at the age of 8. The family had traveled to the U.S. seeking the transplant that was unavailable at home. Tragically, the donor/father/husband was murdered by terrorists back at home a few years later. Subsequent successful life led to the young transplant recipient's natural desire for procreation which carried risk for the potential mother and her kidney. So, the woman/leasing agent became a surrogate mother for her own grandchild, to protect their daughter and the transplant. Years later the kidney still functions well, the daughter works full time as a professional and is the mother of a successful young person. Now I believed this woman's description of her daily prayer for all transplant surgeons.

Secretly hoping that my daughter was as moved by this woman as I was, I returned to find my young niece back at home. Again amazed, I listened while she recounted the adventures of a classmate who had recently missed many weeks of school because of a live donor kidney transplant. Now she was happy that he was back most of the time, except for doctor's visits. He was even well enough to join her in physical education activities approximately 50% of the class time!

Either I have the same type of powerful, natural attractant for people connected to transplantation + donation that I do for mosquitoes, or these fields of medicine/translational science have had enormous impact on society. The facts clearly support this success. Just in kidney transplantation, recent data show growth to an incredible number of prevalent (currently alive with a functioning transplant) patients just in the U.S. of 179,000 patients in 2010. (By the way, note that only 15,000 recipients were alive in the era of the leasing agent daughter's transplant - a rare and marvelous success story stoked by the support of her mother/gestational carrier.) There is no simple means of equivalent, accurate tracking for patients with other types of transplants.

My own experience in speaking to audiences about these topics is that roughly 25% will raise hands to indicate that they have personal contact with these worlds. Still more subjective confirmation that it would take less than 6 degrees to connect most of us to transplant. Would that just as many people will join organ registries, especially during this April - Donate Life month. I WILL love to fall upon and recount even more dramatic - and true - stories yet to come.

I am currently grateful to the leasing agent for permitting me to share her story with you.