Pioneering Innovations in Organ Transplant Surgery

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Prab Baliga

rejection rates in the early: 1980

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Kevin Smith

Welcome to the Innovatively Speaking Podcast, a podcast brought to you by the Medical University of South Carolina. In each episode we dive into the origins of the next big things the who, the why and how we explore ideas that are changing what's possible here at the Medical University of South Carolina and in some cases all across the world.

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Kevin Smith

I'm Kevin Smith in the MUSC podcast video with my co-host, the chief innovation officer here at MUSC, Dr. Jesse Goodwin. Good morning.

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Jesse Goodwin

Good morning, Kevin.

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Kevin Smith

Today's guest is the head of the MUSC Department of Transplantation Dr. Prab Baliga. When we talk about the importance of transplantation and how this field has evolved. Set the stage for us, Jesse.

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Jesse Goodwin

So mett Baliga, I think when he joined MUSC as the department chair right around the same time that I started, I think I will have to figure out exactly when we both came. But it's been really exciting to watch what he's done with his department. He is a big supporter of not just really great advancements in terms of innovative clinical care, but has grown his research base within his department and also started a lot of new programs that support innovation, particularly for students and trainees and so it's been really great to have a collaborator and a colleague who believes in fostering it among his own group as well.

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Jesse Goodwin

So, I mean, I'm looking forward with today's conversation.

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Kevin Smith

Fascinating subject matter. Let's let's dove right in Dr. Baliga welcome to the MUSC Innovatively Speaking Podcast.

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Prab Baliga

Thank you so much. Thank you for having me today.

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Kevin Smith

All right. Let's let's start from the beginning. Tell us a little bit about your history in the transplant field, how you got interested in that and how that led you to where you are today.

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Prab Baliga

antation was first started in: 1954

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Prab Baliga

It overnight increased transplant success rates from double the 30-35% to 70%.

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Kevin Smith

Overnight just right away. Wow.

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Prab Baliga

A phenomenal success and more importantly that opened the doors for extra renal organs liver intestines, heart lungs and all the extra-renal organs then became more successful. So everything what people would suggest like an infant to or rather than like in the neonatal ICU of of transplant where it had been kind of stagnated for a long period of time and kind of exploded.

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Prab Baliga

ing during my training in the: 1980

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Prab Baliga

success rate. This is in the: 1980

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Prab Baliga

South Carolina Medicaid had a contract with the University of Nebraska to send children for liver transplantation to Nebraska.

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Jesse Goodwin

It's interesting. I had no idea.

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Prab Baliga

er transplant program here in: 1992

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Jesse Goodwin

I didn't realize. I think we met after you became department chair, so can you talk a little bit about your journey from joining as a faculty member and starting that pediatric program to when you. I stepped into the role as, as the department chair for surgery.

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Prab Baliga

to: 2015

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Prab Baliga

But you could take patients and create models that they no longer needed lifelong immunosuppression and unfortunately, you know, I failed. And the field still requires patients to take anti-rejection medications for a long period of time. And the second part which we initiated in transplant at that point of time is clinical trials, clinical trials of a variety of new medications.

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Prab Baliga

And we were the leaders in the country on several new anti-rejection medications which have now come out and such as what's called L2 receptors a type of a receptor blockade which is still utilized today. We were one of the early and one of the largest recruiters for that clinical trial. We also were the largest recruiters for a clinical trial of a different class of anti-rejection medications, which blocks a completely different pathway called mTOR, and it's a drug called Sirolimus.

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Prab Baliga

So we were the lead... became the leaders in and clinical trials of several newer medications but then introduced to transplantation.

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Kevin Smith

Well, I would just say let's back up a second for for people like myself let's just kind of define what's going on with transplantation. Before we got started, we were talking a little bit about that. Most people don't realize that when you have a transplant, you'll spend a good part of the rest of your life taking these medicines to to keep your body from rejecting the transplant organ. We were discussing that. It seems like most people think it's just you just find a good match and then you transplant in your good. But that's not the case.

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Prab Baliga

Absolutely. So we know the extent that we focus on matching or the importance of matching has decreased over time. So today we just mainly look at typing, you know, blood types and we kind of expand. So, for example, for a living donor transplants today, more than a third of the living donor transplants that we perform are an unrelated patients.

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Prab Baliga

So spousal friends, anybody in your social circle, altruistic donation because the anti-rejection medication profile has improved so much and our success rates are so high. So in our I'll just pick on our kidney transplant program we have a 98% patients survival at the end of the year and a kidney graft survival of 96% at the end of one year.

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Prab Baliga

So these are phenomenal outcomes and not really related to any kind of matching. So the focus on matching has completely decreased. So I tell my patients so it's a common misconception of and unfortunately even today we lose some grafts because our patients stop taking the medications, particularly the teenage group who always feel the invincible and so I tell my patients, you know, to think about it like a car that irrespective of how all the car is, unless it's got gas in it, it's going to die in the middle of the highway.

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Prab Baliga

So they've got to take their their gas medicines every day and most patients relate to that and hopefully keeps them well, keep these organs going. Yeah.

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Jesse Goodwin

I guess one of the great things about having so many drugs and the anti-rejection sort of success rate that can be related to that is that it's I would imagine it opens up the world for donors because to find a direct match or to find a family member who is able and willing, you know, would kind of really limit your organ pool.

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Jesse Goodwin

And so I imagine that as you know, as you've had to or been able to decrease the emphasis on matching, you've been able to increase the number of organs that that you've transplanted. Is that correct?

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Prab Baliga

That is true. But still, unfortunately, tremendously inadequate. If you look at the overall picture of this country, about 100,000 patients waiting for a transplant and we perform about 20,000 transplants a year for kidneys. And if you take South Carolina, strictly looking at kidney transplantation, about 10,000 patients on dialysis and overall South Carolina performs about 500 kidney transplants.

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Prab Baliga

So the gap in terms of the need of the population and the number of transplants we are able to perform is still very large. And unfortunately there's still a significant depth on the waiting list. But again, there is a lot of education which needs to get done because patients feel that they can live on dialysis for a long period of time.

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Prab Baliga

They don't do not realize the impact of a kidney transplant and prolonging the lifespan and just not a substitute for dialysis.

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Jesse Goodwin

What do you think some of the biggest barriers are? You know, we can talk nationally or just here in South Carolina on increasing that that organ pool, particularly for something like like kidney, where you could do it as a living donor.

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Prab Baliga

So I think, you know, the two answers to that question, I think one is clearly focusing on an immediate need of and I think that the biggest impact would be education and getting folks to understand the importance and signing a donor card and ensuring donor education. So anyone who's a potential donor that we can utilize those organs would be tremendous.

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Prab Baliga

But I think the long run, I think from an innovation standpoint, we clearly have to go into it as, you know, grafts or bioengineering pathways to create our own organs or have a larger donor pool which is easily available because even today, I would say the logistics of performing a transplant is very complicated where we get kidneys from all over the country, the fly by commercial flights.

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Prab Baliga

It's a complicated algorithm of how kidneys are allocated so a lot of things behind the scenes that folks on the on many, you know, lay people are relate to it. But there's a tremendous amount of complexity of trying trying to fit 100,000 into the 20,000 into the funnel to see who will have the maximum benefit or who has been waiting the longest.

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Prab Baliga

And all of these competing parameters are in we don't have a good answer today.

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Jesse Goodwin

That's really interesting. So I think you pointed to two or three ways that, you know, going forward as we look at like what's next in the field, that we might be able to increase the number of organ transplants that we're doing. And I think the first one that you mentioned was, you know, grafts and the use of those.

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Jesse Goodwin

So can you describe for the listeners like what is a Xenograft and what are our current challenges with using them and sort of where you see the field going with that particular type of organ?

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Prab Baliga

Yes. So Xenografts are taking organs from a different species and one which is extremely popular or the pathway that the transplant field is going in is in porcine a pig organs. The challenge with pig organs is because there are different species that could be rejected immediately. It's called the pulmonology, it's called hyper acute rejection that if you just place a pig kidney into a human within a matter of a couple of few minutes, the kidney will be lost because of a very severe type of rejection.

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Prab Baliga

So now they've genetically engineered some of these organs, so they do not reject. And so that's been a proof of concept. A couple of transplants being performed at in New York. And so we're all waiting to see the continued success in Baltimore. There was a heart transplant performed from a can from a pig. Some of the concerns are just not from a rejection standpoint, but animals contain different types of viruses, as we've seen with COVID so there's a tremendous amount of anxiety that we do not transplant any infection along with the organ.

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Prab Baliga

It's called zoonosis so you're very nervous about in the process of helping somebody you can, you know, potentially create a life threatening situation. And the second component is also the function of the graft, the function of a kidney, you know, in a pig or, you know, is very would be very different. So I think the organ, which is most applicable for, you know, supporting humans would probably be the heart.

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Prab Baliga

And particularly, I would say the most critical need is in pediatric hearts. But it's very difficult to get a small size heart of or an infant or or a small child so I think in that group, it can have a huge impact and save many lives.

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Jesse Goodwin

So when we think about some of the challenges where the sort of operational process we go with, you know, identifying and how to make sure that the right recipient on that really big list gets the right organ, and how do you sort of prioritize and decide make those decisions. Can you talk about some of the advancements in that field and what's being done there to sort of ensure equity and sort of do a better job where, you know, taking that limited pool and making sure that the most deserving are getting it?

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Prab Baliga

rejection rates in the early: 1980

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Prab Baliga

Today our rejection rates are in the single digits are close to like 5-7% at the most. So a significant improvement is because of how we were able to match donors and recipients. So we talked briefly and I can see no graphs of hyper acute rejection or rejecting in a few minutes. You prevent that by what's calling a crossmatch and that's done in the background before we call a patient in for a kidney or pancreas or any of the and mainly for heart, lungs, et cetera, to have what we call antibodies in the system we want to.

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Prab Baliga

And these are not blood type antibodies. These are very specific, which are called HLA antibodies. We are we had to perform a physical cross-match mixing the cells with the I'm sorry, mixing the donor cells with the patient's serum and looking at that reaction under a microscope. Or under flow cytometry was something physically which needed to get done.

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Prab Baliga

But with progress that we've made an understanding population kind of genetics, the entire field has shifted to a virtual platform. So in the vast majority, almost, I would say 99% of our donors today, we do not perform a physical cross-match. We just go buy a virtual cross-match. And that was one of the areas again that MRC was a leader in creating this virtual cross matches.

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Prab Baliga

So and the two important areas of number one that organs are not discarded for because you come in here and, and the patient has a positive crossmatch and the kidney is already got X number of hours and so you cannot utilize the kidneys so that we kind of prevent that from happening and to improve significantly our rejection rates and the graft survival.

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Prab Baliga

So that was one of the area that MSE was a leader in virtual cross-match.

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Jesse Goodwin

It's really fascinating and and it would strike me that, you know, it would help increase the reach of where you're able to get your organs from when you're procuring. Right. Because if you have to bring it on to your point and then do a physical match only to find out that it doesn't work now, you know, it would strike me that you're sort of limited to a very defined geographical area. You can do it virtually.

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Prab Baliga

So today it's completely shifted that out and about, I would say less than ten years ago. 80% of our kidneys used to come from South Carolina. Today, I would say probably about 25% of my kidneys come from South Carolina because of changes in the allocation system. 75% of my kidneys come from outside the state. And so ensuring that we are able to get get to them quickly and safely and transport them quickly has create more pressure on the transplant team.

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Prab Baliga

So Virtual cross match has been a godsend for our group.

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Jesse Goodwin

I can only imagine.

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Kevin Smith

I'm sure I'm guessing it would save obviously on time.

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Prab Baliga

Absolutely.

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Kevin Smith

But also in the discomfort, I would think that making some of these transplants happen with a lot of question marks could be difficult for everybody involved.

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Prab Baliga

Absolutely. No question about it. Gives a surgeon and a lot more comfort. Yeah. And hopefully we relate that to the patient too, in terms of a comfort level. And their anxiety for rejection is significantly decreased.

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Kevin Smith

Figured it out before the organ even gets in the body.

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Prab Baliga

Yeah. So and again, you know, the treatment for rejection takes a big toll on their bodies where you're giving massive doses of steroids, for example, or an increasing anti-rejection medications, then impact opportunistic infections like viruses and different types of infections that you do not normally see in healthy human beings. So those infection rates have also significantly decreased and our overall anti rejection dosage has significantly decreased because we're able to create these virtual platforms and ensure you know, maximal and optimal outcomes.

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Jesse Goodwin

So I think one of the other avenues for that you mentioned for potentially increasing the number of of donors would be by engineering tissues. And I know here at MUSC we have a whole Department of Regenerative Medicine looking at doing that. But can you describe sort of what that looks like, you know, present state and then where potentially in the future we could be able to go with that?

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Prab Baliga

Yeah, it's still in its infancy and I think there are several pathways that you can take. One pathway is which I think has more immediate promise, is better preservation of organs and understanding the tissue metabolism. So recently there's been significant improvements in organ preservation. So for example, when your human on patients was hard to have stopped being able to utilize the heart and lungs and other organs which is by placing them on a special pump.

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Prab Baliga

So that's now commercially and FDA approved and it's now come to clinical practice and that's a huge impact in terms of increasing the number of organs that we can utilize. The second component would be, again, at the cellular level that you can use islets for pancreas or liver cells for, you know, for patients who need a liver or even kidneys just scarred can you can regenerate or the ones which are, you know, which is more further along as in hearts we have some scarring and you can inject heart cells and regenerate so that's one pathway instead of having entirely whole organs.

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Kevin Smith

a little bit. You were saying: 1984

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Prab Baliga

I think there are kind of a couple of different, you know, I think the opportunities, number one, are endless. Yeah. So I think the immediate needs for example or we talked about a lack of tolerance of not, you know, taking a lifelong anti-rejection medication. There's some very interesting clinical trials coming in terms of getting bone marrow along with your kidney and preventing lifelong immunosuppression by simultaneous bone marrow and kidney transplant and the living donor situation.

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Prab Baliga

That's one which is coming up and seems very promising, blocking multiple receptors in the same concept that the time that your body is exposed to this, what we call foreign antigens of the donor, then blockading them at what one stretch at one time point that again will create these pathways. So minimizing some of the complications of transplant is one pathway I think the biggest promise is, as everybody talks about today, is what do would do with artificial intelligence and the application of artificial intelligence in this complex area of transplant is simply I think it's going to be have a huge impact and an early impact probably within the next five, ten years.

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Prab Baliga

And impacting every single aspect of transplant for MUSC. I think we were very fortunate. We recruited a surgeon more recently who was leading our artificial intelligence work, Arman Killic, and he's won a few grant in that area. And it ranges from health care delivery aspects and how do we maximize organ distribution, et cetera. So on the other parts, which we just talked about in terms of regenerative medicine and Xenos, is A.I. being applied to creating what are these proteins and creating these protein structures that can overcome some of the barriers of XENO or some of the barriers of regenerative medicine?

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Prab Baliga

I think to accelerate the progress in those fields by several years or several decades with the applications of A.I..

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Kevin Smith

It's exciting.

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Jesse Goodwin

It's really exciting.

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Prab Baliga

I think the MUSC Department of Surgery Investment is and in a couple of different areas, we are trying to create our own within the Department and a nucleus for accelerating research. So we have we were fortunate to have gotten a donation and from a grateful patient and created a Schiller Innovation Center, which where A.I., Human Centered Design, Clinical Outcomes, research is in one area, right in the center of the department that then facilitates and allows us to ask these questions and we've hired a few machine learning PhDs, scientists and master scientists to then take our ideas and accelerated.

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Prab Baliga

So we're hoping that along with many of the other universities across the country, that we will be on the cutting edge of the future of A.I. and just not in transplantation, but across into our surgical sciences. So that's a major focus for us and another major focus for us is a very different, you know, line of focus is ensuring that we create equity and everybody benefits from it.

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Prab Baliga

And I think that's an area in South Carolina that we need to particularly pay attention to. And again, in my field of kidney transplantation on the field I'm sorry, in the population it has 28% blacks, almost 65% of the dialysis populations black. So the disparity and of kidney failure in that population is so high. So as we approach these innovations, we also have to ensure the equity and ensure that the entire population is benefiting from these from the progress that we make.

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Kevin Smith

Can you talk a little bit about that equity portion and how that actually is taking place here in South Carolina?

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Prab Baliga

Currently, we are focused on on the health service research aspects of ensuring access to care with the utilization of telehealth and telemedicine and patient navigators across the across the state. So and second component of that is education I would like just like we talked about in a current situation, medication adherence is a huge concern. So again, we just recently one of our transplant pharm D, David Taber, won a $3 million grant from the NIH on a medication adherence app with pharmacy.

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Prab Baliga

You know, intervention. So those are some of the current, you know, initiatives that are ongoing on the challenges as we continue to progress, we need to ensure that we continue to maintain that equity.

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Jesse Goodwin

Out of curiosity of the discrepancy in our our population versus the percentage that is on dialysis. So that. 28 to as you know over 64%. Yeah. Is that largely due to diabetes.

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Jesse Goodwin

Yeah. So today the number one reason or etiology for renal failure is diabetes. So I have to end with saying that you just can't solve everything with innovation. A large component of this has to be preventive medicine and preventing the progress of the impact of diabetes, hypertension and obesity is extremely critical to our population.

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Kevin Smith

Does does South Carolina have a unique history in transplants?

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Prab Baliga

For the longest time, we were the only transplant program in South Carolina, so we were a first for all organs here in South Carolina. I think the unique organ that we transplant and for a lot of it, we are the first in the southeast was intestinal transplant so children who have lost their small intestines or they could not absorb food can be, you know, can receive a small ball transplant.

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Prab Baliga

So we were the first in the Southeast to perform that.

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Jesse Goodwin

I had no idea that that was a transplanted organ. So, yeah, I just not only do I not know that we were the first to do it, I had no idea that that was actually one of the organs on the list that could be transplanted. That's cool.

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Prab Baliga

The surgical technique for each of them has significantly changed you know, for, you know, speaking a little bit about liver transplant, which we talked about earlier, the surgical technique involved putting them on bypass because we had to clamp just below your heart and above your kidneys to cut the old liver out. And so we used to place patients on on a bypass by making a an incision in the groin and taking the blood out from below and making another incision in the armpit and circulating the blood and giving it back in the armpit.

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Prab Baliga

So now I'd say we haven't done a liver on bypass probably for the last decade. We've also understood the coagulation pathways better. So the blood transfusion requirements, when I started a liver transplant patient to receive about maybe 25 units of blood today, probably less than five in most cases, maybe, you know, three to five would be the the mean.

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Prab Baliga

So the duration of surgery used to be about a good 18 hours. So today is probably about four or 5 hours because the improvements in anesthetic anesthesia management and trough management. So several areas have improved so much so I feel like an old dinosaur.

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Prab Baliga

orm a liver transplant in the: 1980

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Jesse Goodwin

I mean it was cutting edge for that time right yeah.

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Prab Baliga

So it's really exciting for patients come out I'd say probably a good third of the patients are what we call extubated or taken off the breathing machine in the operating room whereas in the old days they'd be on the breathing machine for a couple of days so lots and lots of improvements at every level and it's really exciting to see and looking forward to the big improvements of, you know, organ preservation and availability of organs and, you know, further improvements in anti-rejection medications.

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Jesse Goodwin

It feels like we've come so far in a relatively short amount of time and there still like so much more exciting work ahead. Right? We're kind of just on the cusp of what's next.

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Kevin Smith

Yeah. And all these improvements are because of innovation on your part in a lot of ways. And so we just want to say thank you so much for spending some time with us here at Innovatively speaking today.

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Prab Baliga

And thank you so much for having me.

00;30;48;03 - 00;30;49;06

Jesse Goodwin

Yeah, thank you very much.

00;30;51;23 - 00;31;12;21

Kevin Smith

You've been listening to the Innovatively Speaking Podcast with the Medical University of South Carolina. If you enjoyed this episode and would like to support the show, leave a rating and review to hear more innovative ideas and to share your own. Subscribe to the show or visit us on our web page. Web Dot MUSC Dot Edu Slash Innovation.

00;31;12;28 - 00;31;15;24

Kevin Smith

And remember, don't hesitate to innovate.