Dr. Michael Kraus: Welcome, everyone, to this episode of Field Notes. I'm Dr. Michael Kraus, the Associate Chief Medical Officer at Fresenius Kidney Care, and your host for this discussion today. Here, we interview the experts, physicians, and caregivers who bring experience, compassion, and insight to the work we do every day.

As you may know, April is National Donate Life Month. During this month, we focus on raising awareness about transplantation and donation, and we honor the people who have saved lives through the gift of donation. 

That is why we have a special episode today to give an update on the latest in transplant medicine. Transplantation is the best method of treatment for many people with end stage kidney disease, when it is available and accessible. As a company, we prioritize expanding access to kidney transplant patients, and we work to reduce the challenges facing patients as they move towards getting transplanted. I'm excited to give you some insight on the work that we've been doing as a company in the field of transplantation. 

Here to talk about the vitality of transplantation as a therapy option and how we are working to make it more accessible to all of our patients is Dr. Benjamin Hippen, the Global Head of Transplant and Emerging Capabilities for Fresenius Medical Care.

Ben, Happy National Donate Life. Thank you so much for being here today, and welcome to Field Notes.

Dr. Benjamin Hippen: Thank you, Mike. I appreciate you having me today.

Dr. Michael Kraus: Ben, tell me about the benefits for kidney transplantation for our patients and why is it so important?

Dr. Benjamin Hippen: You said it in your introduction, Mike. Transplantation is really the treatment of choice for the vast majority of patients with advanced chronic kidney disease or end stage kidney disease requiring dialysis. And the reason for that is because for the vast majority of these patients, transplantation improves the quality of life and expands the quantity of life for our patients.

Dr. Michael Kraus: Can you give me some numbers? What do they tell us about transplantation?

Dr. Benjamin Hippen: Right now, there's about 89,000 people on the kidney transplant waiting list in the United States. About half of them are waitlist active, which means that they are eligible for an organ offer. The other 50% are waitlist inactive or status seven, which means that they're actually accruing time on the waiting list but are not currently eligible for an organ offer.

There are many more patients behind those numbers that are in the evaluation process and many, many more behind that who have actually been referred for transplantation. We've had a significant increase over the last several years in the total number of organs procured and actually accepted for transplant. But we're still facing a significant shortage between the number of people who need and would benefit from a transplant and the number of organs that are available.

Dr. Michael Kraus: How many transplants do we do a year? 89,000 people waiting on the list sounds like an awful high number.

Dr. Benjamin Hippen: It is. However, the total number year over year is in the neighborhood of 18 to 20,000 kidney transplants a year. The total number of living donor transplants has been fairly stable over the last several years, but the number of deceased donor kidney transplants has gone up. And I think that is in part related to improved efforts on the part of organ procurement organizations to increase the total number of transplants. But as mentioned, the total number of transplants still are far fewer than the need reflects.

Dr. Michael Kraus: A deceased donor—you mean a patient that has died and their organs have been harvested and then transplanted into one of our kidney patients, correct?

Dr. Benjamin Hippen: That's correct, yeah. In the last year, there were just under 20,000 deceased donor kidneys that were procured from deceased donors and transplanted and just under 6,000 living donor kidney transplants for a total of 25,000.

Dr. Michael Kraus: And we still believe that dialysis remains a great therapy, keeps all those patients on the waitlist alive and functioning and even those that won't be touched by transplant. Why is it important to Fresenius Medical care and even to you personally, to promote transplantation as the best therapy for many? Why not just keep people on dialysis and why should we be moving towards transplantation?

Dr. Benjamin Hippen: The reason to improve our efforts to increase access to transplantation is, as mentioned, it is the treatment of choice for our patients, whether they have advanced chronic kidney disease or end stage kidney disease on dialysis, because it does improve the quality and the quantity of life with this disease. In addition, you know, our ambition here at Fresenius Medical Care is to become the provider of choice for patients across their entire continuum of their kidney disease process and that has to include transplantation.

I think, too, the regulators and payers are moving toward a system that encourages dialysis providers to be more than dialysis providers, to really be comprehensive, end to end care providers for patients with kidney disease. And so that means that Fresenius will have to expand its competencies and its capabilities, not only in making sure that more of our patients have access to transplantation, but that they're also able to keep that transplant for longer and longer periods of time.

Dr. Michael Kraus: Transplant is clearly the best therapy we can offer to so many of our patients. The last I checked, there was about 25% of patients with ESRD ever get touched with transplantation in their lifetime. What's keeping that number so low?

Dr. Benjamin Hippen: Well, there's a number of barriers, and I'm glad you asked. Probably the most important one is, as mentioned, there are not enough organs to meet the current demand. But even before the point of an organ offer, there are a number of barriers for our patients in accessing the transplant waiting list or even the transplant evaluation process. 

There's not much visibility between the dialysis clinic or the nephrology practice that is referring a patient to a transplant center for transplantation. And what happens to that patient between the actual execution of the referral and the procedure of the evaluation process, including testing, multidisciplinary evaluation all the way to the point of waitlisting? 

We are undertaking several efforts here at Fresenius Medical Care to try and shine a light on this process, identify where patients may fall off track and try and get them back on track so that more of our patients who are referred actually make it through the evaluation process successfully and onto the waiting list.

In addition, we're looking at a number of opportunities to try and help our patients identify potential living donor candidates because a living donor kidney transplants of either type of transplantation clearly has additional benefits over and above transplantation more generally for our patients.

Dr. Michael Kraus: Clear benefits to the patients, society, patients’ families, and even to us, I think, as an organization for so many reasons of getting people transplanted. I don't want to leave a false impression that transplant is perfect. It leaves people great. What are some of the risks, the downfalls of being transplanted or being a kidney transplant patient?

Dr. Benjamin Hippen: Kidney transplant surgery is indeed a major surgery requiring general anesthesia, and there's always risks associated with that. In addition, the medications that patients are required to take over the course of the entire lifespan of their graft, medication to suppress their immune system has additional risks, in addition to predisposing patients to opportunistic infections, that is, infections that someone who otherwise was not immunosuppressant would not be as vulnerable to. Those are certainly found at higher prevalence in our patient population and the medications increase cardiovascular risks, though not as much as maintenance dialysis, as well as increased risk for certain types of cancers. However, all things considered, and including the risks of the surgery and immunosuppression, for the vast majority of patients, they tend to do better and live longer with the transplant, even though those long term risks are a perennial challenge for the long term care of these patients.

Dr. Michael Kraus: So it's not a cure of the disease, it's just an improvement of the disease process. I want to shift gears a little bit. We had Dr. Eneanya a couple episodes ago talking about health equity, and she's been very big in the estimated GFR equation. And that's important to when I time people to start the clock, if you will, to be able to get transplant.

So give me an idea of where my eGFR needs to be to get listed for a transplant before I'm on dialysis and what's been done with this calculation to date?

Dr. Benjamin Hippen: Well, it’s a longstanding OPTN policy that a patient is eligible for wait listing when their estimated GFR is at or less than 26 CC/minute. The recent activity and controversies around the calculation of eGFR that you alluded to and that Dr. Eneanya is a subject matter expert in, has recently been the subject of a change in OPTN policy. 

As I'm sure Dr. Enanya elaborated, one of the challenges with a race inclusive eGFR equation is that it tends to overestimate eGFR at the lower end of kidney function. That is, eGFR is closer to end stage and it tends to underestimate eGFR at the higher ends of GFR, which means that it may end up conferring a diagnosis of chronic kidney disease for patients who don't actually have it.

With regard to its implication for access to transplantation in the waiting list, it's this first phenomena with race inclusive eGFR equations that has raised concerns that the use of race inclusive eGFR formulas may actually be inadvertently reducing patients access to the waiting list in the form of changing their time of eligibility for preemptive evaluation in listing for kidney transplantation.

Dr. Michael Kraus: For our audience, I just want to clarify OPTN stands for the Organ Procurement and Transplant Network. Those are the people that help us make sure the organs get to where they're supposed to go. 

I recently also been made aware that UNOS is now expecting transplant centers to adjust waitlist times for people who have been adversely affected by the prior GFR calculations. Can you explain that a little bit to me?

Dr. Benjamin Hippen: Yeah, that's correct, Mike. So very recently the OPTN published a policy that was initiated by the Minority Affairs Committee of the OPTN that was ultimately approved by the OPTN Board of Directors that requires transplant centers for patients on their waiting lists that are African-American or Black to make inquiries with their referring nephrologist and/or look at health information exchange records to see if they can identify an eGFR calculation for these patients where the race inclusive eGFR equation was used and to see if a race neutral eGFR equation using the same values, the same lab values that the race inclusive eGFR equation was, was used to calculate an EGFR to see if those patients actually have an eGFR with the race neutral equation that's less than 20 CC/minute. So if before they had an eGFR with the race inclusive equation that was greater than 20 CC/minute and with the race neutral EGFR equation, it was less than 26 CC/minute, those patients would have an opportunity to have their waiting time recalculated to reflect that corrected EGFR.

We don't know exactly at this point what impact that's going to have on the waiting time for how many patients. There are a handful of studies that were published, concomitant with many of the studies that were published on proposing the change to the eGFR equations to move to a race neutral calculation that suggests there's probably 3% or so of the population that would have had an eGFR using a race inclusive formula that was above 20 CC/minute, that using the race neutral GFR would reduce it to less than 20 CC/minute.

And for some context, currently on the waiting list, there are about 30,000 African-Americans on the waiting list. A little less than 50% of them are waitlist active. A little more than 50% are waitlist inactive. So, you know, 3% of 30,000 would probably be in the neighborhood of a thousand or 1100 patients. So, you know, if this past modeling actually reflects the reality, this may only change the waiting time for a fairly small number of total patients on the waiting list for those patients.

Dr. Michael Kraus: For those patients, not a small number, right?

Dr. Benjamin Hippen: Oh, absolutely right. Yes. I mean, it may make a substantial difference in their actual calculation of waiting time. But again, and this is just retrospective modeling as an effort to try and protect the prospective effects of this new policy. We don't really know, and we won't really know until it's actually implemented.

Dr. Michael Kraus: I want to move into something that your heart and soul is in. We talked earlier about the barriers and the difficulty of getting to the transplantation and getting to waitlist. You're working on a platform of Fresenius Medical Care to speed line or smooth out that transplant referral process. Explain some of these changes in the process to me. What do you have planned?

Dr. Benjamin Hippen: Thanks for asking, Mike. Yes, this has been a work in progress for more than a year with a dedicated team of folks in our IT arm as well as a number of social workers and transplant professionals who've all come together to try and create a referral packet of information that is complete but not overwhelming for our transplant centers.

Right now, many transplant programs still require, in the 21st century, a transplant referral form that has to be filled out by hand and has to include a number of additional documentation pages that ultimately have to be collated and faxed manually to a transplant center. What we've tried to do making use of our existing internal databases within our FKC clinics is create a fairly streamlined approach where a social worker who's executing a transplant referral has to click a mouse a couple of times to assemble 167 different demographic, clinical, psychosocial, laboratory, as well as regulatory data items, including a signed 27, 28 form and proof of insurance, all assembled in a clinical packet as a PDF that ends up being about 10 to 15 pages. 

The other thing that we're adding to this is many of our patients don't have a current complete history and physical or discharge summary available on file and for those patients that don't have that with sufficient currency, we've actually tasked a team of Fresenius RN case managers, to go into the health information exchange and create by hand a tailored, curated, transplant focused clinical summary that would then be sandwiched into this automated transplant referral packet and that would be what is delivered to transplant centers. 

And this has a number of virtues. First of all, it results in a single document sufficient information for a transplant center to be able to look and identify very quickly the key clinical facets of a potential transplant candidate and make some initial triage decisions without having to spend the time or the expense of trying to secure a lot of clinical records, much of which may not be relevant to the initial triage decision making. So we're hoping that rolling this out will actually improve the efficiencies of the transplant center's workflow process and shorten the time between when we refer a patient from one of our clinics to when the transplant center is actually able to make an initial triage decision about whether this patient is appropriate for evaluation. 

We also hope that this will create an electronic paper trail, as it were, so that we can identify across all of our clinics that a referral was executed when it was executed, and we actually have the completed packet available as an electronic file so that we can start to do population level trends in terms of tracking our patients once they're actually referred. So, we can see ultimately what happens to them. 

We think that this is going to be the first step in uncovering a number of other barriers that our patients face along the way, because we know that well, getting a complete dataset is an important first step. It's not the only step to really assuring that our patients make our way through what ultimately can be a fairly tangled, convoluted, and difficult process for them.

Dr. Michael Kraus: I talk to patients all the time, and despite the fact that it's 2023, the ability to get on a transplant list is a large burden to the patient and to our social workers and nurses, as well. So, anything we can do to reduce that is important. Do you think we'll make progress? I mean, I have patients all the time to try to get multiple listed, more than one center, and each center has a different sheet of paper. Each center has a different set of equations and things that they desire. Will this help? I mean, we are a large provider of transplant patients.

Dr. Benjamin Hippen: Well, we hope so. It's certainly going to become an initial point of conversation with transplant programs about the extent to which they are clinically comfortable in changing their transplant evaluation process to provide a level of uniformity, which I think will make a lot of things easier for the patients, and certainly on its face suggests that there's opportunities for realizing more efficiencies across the system.

Transplant centers, however, are practicing medicine, and I think we have to respect the unique facets that they think are really important about getting patients listed in a safe and responsible way. But as much as we can, we're going to try and bring a level of uniformity to the process and to our referral package, in particular. 

We're trying to approach this with a spirit of humility. While we've had several months to pilot this with transplant centers and have received a lot of valuable feedback, we know that we're not done. So, as we roll this out, enterprise wide starting on April 17th, we are preparing for additional feedback from transplant centers, and we hope to iteratively make this overall referral packet better so that really does serve the needs of our transplant center partners.

Dr. Michael Kraus: A lot of transplant centers are now getting into some automated programs and one of them is, for instance, the Transplant Referral Exchange, or TRex, as they like to call—I like dinosaur names—so, the TRex, then I know there's another one or two out there, how does our program match with theirs?

Dr. Benjamin Hippen: It has never been our intention to compete with any particular transplant referral platform, and in fact we designed our transplant referral packet to be fully compatible both with TRex as well as TxAccess. So, our referral packet, again as a single discrete PDF can be sent to transplant centers who prefer to use one or the other of those platforms.

It's also helpful that by virtue of being a PDF, it is by definition compatible with any of the transplant centers’ electronic medical records. We're not at the point where we can transmit information seamlessly electronically to another electronic medical record using APIs, but that is sort of a perennial challenge for medical records that I'm not sure will necessarily be solved in either of our professional lifetimes.

But in the meantime, we're not going to be hamstrung by it. This is at least a way in which we are able to communicate uniformly with our transplant center partners.

Dr. Michael Kraus: I'm going to have to bring it back because we have to talk more about educating patients, getting them ready for transplant. And I'd really love to spend some time talking about the future, like xenotransplantation or even 3D printing of organs. Is there anything else you want to share for today?

Dr. Benjamin Hippen: Just to say that we're very excited about rolling out this first step in improving the communication pathway and the visibility and the transparency of the referral process. And we really do envision this as a first in many steps for Fresenius Medical Care to make access to transplantation more widely available and easier to navigate for our patients.

Dr. Michael Kraus: We'll continue to try our best to educate the patients on how to get to home dialysis as well as transplantation, reduce those barriers and make it easier for them as well. And I think that's the future, that's where we're clearly headed as a company, and I'm thrilled to hear about the progress we're making, and we’ll continue to make transplant more equitable and accessible.

Thanks again for being here today to talk about what's going on, this has been a fascinating discussion.

Dr. Benjamin Hippen: Thanks again. I appreciate you having me.

Dr. Michael Kraus: To our audience, again, Happy National Donate Life Month, and thank you for joining us today. If you have questions about transplantation, please reach out to us at Fresenius.Office@FreseniusMedicalCare.com and we can assist you.

If you're new to Field Notes podcasts, you can download past episodes at the Apple Store, Google Play, or wherever you download your favorite podcast. Please remember to subscribe and receive the latest updates as they happen. 

Until next time, I'm Dr. Michael Kraus, and you've been listening to Field Notes by Fresenius Medical Care. Take care, everyone. And let's begin a better tomorrow.