Saving Evan: The New Transplant Procedure--In-Depth Doctor's Interview
Gerald Lipshutz, M.D., Associate Professor of Surgery at UCLA School of Medicine and Director of the Blood Grouping Compatible Kidney Transplant Program and Desensitization Program talks about blood grouping compatible transplants.
You always hear that there’s such a huge need for donors and it used to be that if you were not an exact match you couldn’t be a donor but that’s not the case anymore, correct?
Dr. Lipshutz: Correct, that is not the case. Often that was not the case in the past. We don’t pay so much attention to matching for the average patient that comes in. They could have people that are completely unrelated to them, have no genetic relationship at all, that would be a good match as you might call it for them. I think what we’re really talking about is a genetic for patients who have other issues and that’s still very important.
Let’s talk about Evan. What was his rare circumstance?
Dr. Lipshutz: Evan was born with no kidneys and also had some other abnormalities such that he was placed on dialysis shortly after birth. He has some antibodies from blood transfusions. These are antibodies against other people. His mom was a pretty good match for him, but her blood type was incompatible, in other words she’s not the blood type that we typically think that people can receive. If you’re blood type O, you usually need to receive a blood type O kidney. If you’re a type A, you can receive an A kidney or an O kidney. People who are type B can receive a B or an O kidney. If you’re AB you can receive anybody’s kidney. But if your blood type O you really can only receive O, so those patients are somewhat limited on what they can receive.
And what was Evan’s blood type, do you remember?
Dr. Lipshutz: I’d have to look it up, but the blood type was incompatible, but they had a good genetic -- what we call HLN match. If I recall correctly, they’re a five out of six match. So really the difference was the blood grouping compatibility for him.
So what needed to be done to make his body accept the kidney?
Dr. Lipshutz: We call the process immunomodulation desensitization. There’s a few centers around the country that do this type of work. This work really began in Japan in the nineteen eighties and has continued in Japan and also in several centers in United States. What this involved was a two armed approach —medications and something to physically remove blood group antibodies from the blood stream and in his situation in particular. The medication are something we called intravenous immunoglobulin, typically abbreviated IVIG, and another medication we call Rituxan or Rituximab it’s an off label use of an FDA approved drug. The other arm of the treatment is plasma pheresis like with this machine here that actually physically removes proteins from the bloodstream of which antibodies are a protein.
And what do those antibodies do?
Dr. Lipshutz: Well, that’s a very interesting question. For blood grouping compatibility I don’t think anybody really knows the purpose of antibodies against blood groups. I don’t think we really know the purpose of them. So they might not have any purpose at all. It turns out that they probably originate from our immune response against bacteria that we have in our intestine that cross reacts with blood types. This would of course never matter except in blood type incompatible transplantation.
And what it does is basically kill any new organ coming in to the body right?
Dr. Lipshutz: That’s right. Antibodies like this that are high enough at the time of transplant would cause in this case a kidney transplant to reject it on the operating room table. The organ would turn purple and it would likely develop blood clots within it. It would need to be removed while the transplant is going on. So our goal for blood grouping compatible transplants is to lower those antibodies to a safe level, perform the transplant and then give time for the body to adjust to that organ. In other words, some type of molecular signaling goes on between the kidney and the immune system that then causes those antibodies to stay low. And if the patients don’t have a problem within the first two weeks after transplant for example in Evan’s case they’ll probably never have an issue with regards to blood grouping compatibility.
What’s the success rate?
Dr. Lipshutz: The success rate is really dependent on the center that you go to and the experience of the center. Our experience here is about a ninety three to ninety four percent one year graft survival. So it’s very high, It’s similar, slightly less, than our overall patient results.
But that’s incredible considering that these patients really don’t have another option.
Dr. Lipshutz: That’s exactly how we like to think about it also. You could present the results as a half empty or half full situation. You maybe have a six or seven percent chance of graft loss or ninety or ninety three or ninety four percent of graft success. I try to think of it as the glass half full instead of half empty.
But basically these patients they don’t have another chance, this is kind of like their last hope that this works?
Dr. Lipshutz: In a lot of those situations it could be that way. Some patients with blood grouping compatibility could get a blood group compatible organ if they knew someone who was willing to donate to them. Sometimes if they want to wait through paired exchange, they may get an organ that way. These processes that you may hear about sometimes called domino transplants or swap transplants but often, not always, will take a lot longer. For a situation like Evan where he was a five of six genetic match and blood group incompatible I’m not sure they would have found a better offer for him.
How does it work?
Dr. Lipshutz: How the equipment works is, we use people’s dialysis access, whether they have a catheter that they dialyze through three or four times a week or what we call fistula or graft on their arm or on their leg. That’s accessed with two cannulas or two needles and blood is withdrawn in to the circuit with the equipment. Proteins are removed from the bloodstream and that is replaced with other proteins that are derived from other people but without antibodies in them and it’s given back to them. So it’s really a two arm process. The first is medications, IVIG, intravenous immunoglobulin and antibodies developed from many people placed in a container and infused in to patients. We believe that helps turn off the production of antibodies or turn off the immune response. We give Rituximab, another medication that helps with this. Then plasma tresis physically removes proteins from the blood stream of which antibodies are a protein. That lowers their antibodies over time. Then they can receive their transplant and are closely monitored. They may require additional therapy after transplant.
What about preexisting immune response to other people?
Dr. Lipshutz: That’s living donation. So many times we have people that have developed an immune response most easily thought of against other people. That is they developed antibodies against other people. We more commonly see this in women, it’s really a major problem for women who’ve had multiple pregnancies, people who’ve had blood transfusions, people who had a prior transplant. In fact this is one of the most difficult problems that we see today in solid organ transplantation is the preexisting immune response to other people. We call it sensitization. It’s as if you’ve been immunized against tetanus and then someday you say, I want to get tetanus, how do you reverse the immune response so someone could get tetanus. Well your body is very smart, your immune system is very smart and very advanced. Your immune system has memory to these foreign elements in our environment. So we need to work with patients to try to decrease their immune reactivity against other people so they can receive hopefully a successful kidney transplant.
What causes the them to be sensitized?
Dr. Lipshutz: The typical situation is people who have had multiple pregnancies and or multiple blood transfusions or a prior transplant that causes them to be sensitized. When they reach the top of the transplant list, if they don’t have a living donor, they have all these antibodies that basically prevent them from getting transplanted. So when they’re offered an organ from someone who is brain dead we look at six, eight, ten markers. If they have antibodies against those markers that are a significant strength, we know the transplant will be rejected and that organ has to be declined for them. Some patients will wait years and years and years and never get an offer. So we approach them when we see them at the top of the list when they have immune sensitization to say, listen we can see a problem, it’s going to be in your future. I think we need to work with you to try to see if we can lower your immune response so that hopefully you’ll get transplanted.
How does this work in the fact that they come in every day for two weeks or how many times do they do this?
Dr. Lipshutz: What we typically do for people with plasma pheresis is three times a week. A Monday, Wednesday, Friday schedule. The treatments are roughly one and a half to two and a half hours. There are other people that we have considered an inpatient treatment of five days in a row to see if we can get their antibodies down more quickly. But this is not without potential for side affects. We need to be careful and we need to monitor people’s immune responses also.
How long would they do that, whether it’s three or five days, for one week or until they get the transplant?
Dr. Lipshutz: Unfortunately these treatments are only temporary. In other words if people have had an immune response and their antibodies are high we can continue the treatments and hopefully we’ll see they have an anti response and their level will become low. But if we stop the treatments and they do not get a transplant their antibodies will go right back up. The real process that needs to occur is they need to get a transplant and their body needs to have this signaling process that goes on between the transplanted organ and their immune system that will hopefully will keep the antibodies that are specific for that organ low. We call that process accommodation. That’s what we’re waiting for to develop for each patient.
What are the side effects to this?
Dr. Lipshutz: The side effects are thinning of the blood. If people have a cut, it can bleed longer. It also does suppress their immune system so they need to be careful so they don’t get an infection from other people such as a cold or flu. So we recommend for people to wash their hands frequently, carry some type of hand disinfectant, avoid touching their eyes and nose.
Is it hard to find compatible living donors?
Dr. Lipshutz: We have patients that have a living donor that have very high antibodies against their living donor. So we call this a panel reactive antibody, PRA for short. If it’s a hundred percent that means they have antibodies against a hundred percent of people out there. You can think of it that way. If they have antibodies against four percent they have antibodies against four percent of the people out there. So clearly somebody who has antibodies against four percent of the people out there has a ninety six percent chance that we’re going to find a living donor, hopefully we’ll have a living donor that will be compatible with them. But if someone has a hundred percent really they have almost no chance. So let’s say that I have a cousin who needs a kidney transplant and they have a ninety nine percent sensitization. When we look at the markers between myself and the antibodies that my cousin might have they have six out of six very strong antibodies against me. But I’m able to donate my kidney to someone else and someone else’s relative may be able to donate a kidney to my cousin and they may have two or three antibodies against my cousin. So what we can do is now in this situation we know what we’re working against. We know what the markers are, we know what the antibodies are, we know how strong those antibodies are so we can plan a course of therapy to hopefully lower the antibodies down against those three markers and then have to be transplanted. We call this paired exchange with desensitization. So we believe now that we’ve been able to find ways to get people transplanted through blood group incompatibility. We’ve been able to find ways to getting people transplanted through paired exchange. But there’s another group of patients, often re-transplanted patients, often women who’ve had blood transfusions, pregnancies and also prior transplants that will be very difficult to ultimately get transplanted. But by combining these processes blood group incompatibility, desensitization and paired exchange we can hopefully find a match or some compatibility for every patient who has a living donor. That’s really the process together. That’s where I think these kidney transplantations is going in the future, is the programs working together to get people transplanted who have these immune responses.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
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If you would like more information, please contact:
Gerald Lipshutz, M.D., Associate Professor of Surgery
UCLA School of Medicine
To read the full report, Saving Evan: The New Transplant Procedure, click here.