Episode Transcript:

Frank Maddux: Pre-clinical and epidemiological studies have shown an association between acidosis and the progression of chronic kidney disease. Emerging evidence suggests that bicarbonate treatment may slow the progression of CKD and reduce the risk of kidney failure. Nephrologist Professor Dr. Nilufar Mohebbi, is Fresenius Medical Care's Country Medical Director for Switzerland. She's investigating the effect of alkali therapy on graft function in kidney transplant recipients with metabolic acidosis. The goal is to extend the life of transplanted organs in renal patients. Welcome, Nilufar. Thanks for joining me on "Dialogues" today.

Nilufar Mohebbi: Thank you very much, Frank, for inviting me for this interview.

Frank Maddux: The work you're doing now, tell me a little bit about the impact on both CKD and transplant patients and what you think the rolde of acid-based metabolism is in our therapeutic regimen.

Nilufar Mohebbi: Patients with CKD suffer from metabolic acidosis as let's say complication. That has been known for years, for decades, actually. But it was kind of I would say maybe neglected. So people said, "Well, why do they have metabolic acidosis? It's not good for the bone. We will treat it." But it was not, like, of prime importance. And so then a lot has been done then on renal anemia and everything else. But then people realized and these were also from the States. There are a couple of really smart people who do research, epidemiological research. They are-- They have access to these data banks of course, and really large scale data like Kalantarzadeh, who is also Iranian, by the way. And but also Kovesdy and so on. So they have the Veterans' data. And they saw that obviously metabolic acidosis in CKD is associated with mortality. And it's associated with obviously let's say worse outcome regarding kidney function. So these were of course epidemiological data, associations and you never know about cause of that, if it's causal or not or a cause. So then, a guy from London, Professor Yaqoob, he did a study in 2009, published in JSAN, where he just treated open label his patients' CKD stage 4 with alkali. And the interesting thing was, he was not looking into correction of metabolic acidosis. He was not looking into bone first. He was looking on kidney function. And he could, like, save patients life for several years when they were on alkali until they became dialysis patients. So and then of course, these studies were repeated by Donald Wesson, you know him may be from Houston, Texas, and they did it also in patients with better kidney functions. Even for example, CKD stage 2 according to KDIGO Guidelines, even they benefit. So there are, like, a lot of let's say evidence-based data now, interventional randomized trials with placebo control that showed that, okay, if we treat metabolic acidosis in patients, we can delay the progression of chronic kidney disease. And then I was of course fascinated by the data. I know that this data exists. But I was seeing that also transplant patients, they also present with metabolic acidosis. And then I looked a bit more detailed and then I saw that they have even more metabolic acidosis at lower creatinine levels. So and then I saw, I was looking what is the reason maybe? Maybe these are the CNIs, so the calcineurin inhibitors that we are giving to the patients because I did previous work on that in an animal model where I saw that they changed some acid-based transport proteins when you give to the animals Tacrolimus, for example. So then I was fascinated to know why is that and you better know than me that we have a shortage of organs for our patients.

Frank Maddux: Yes.

Nilufar Mohebbi: We know that there's a mean survival of a transplant kidney at least in Europe and Switzerland is at the moment 12 years. So this is not enough for a lot of patients because they are super young. So, everything that could help to also to prolong the graft function and the survival of the graft would be helpful in addition, of course, to better immunosuppressive regimens and so on and so on. But I think it's like a puzzle. You have to use every piece that you have and also the paired kidney donation and everyone is trying. And I thought, okay, let's just-- this is my piece to try. and you know, you cannot compare them. You cannot say, "Okay, because it helps to CKD patients it will also help to transplant patients." You need evidence. And then I was lucky because the Swiss National Science Foundation, which is the governmental organization giving money for research, they had a first call for investigator-initiated clinical studies and I applied for this. It was open for all disciplines like Cardiology, Oncology and so on. But I was lucky to receive the grant and I could start the study that has been started five years ago and just finished this year in July. And we are now performing data bank cleaning, closing the data bank and I can't wait for the first analysis.

Frank Maddux: That's great. In your clinical practice today, do you care for a lot of transplant patients?

Nilufar Mohebbi: Yes. I have my outpatient clinic which is half-half, I would say, half CKD patients and half transplant patients, yes.  I have-- And also my dialysis patients. They are all on the waiting list, you know, if possible. So I think I would say definitely everyone who can walk out of our dialysis unit--  Is almost on the list.  So we are really supportive and I love it that Fresenius as a medical provider it's also supporting this. So this was also very nice for me to see that I can continue to do the best medicine as before. And so yes, so I really talk to the patients. I try to motivate them. so I have a lot of them on the waiting list. I have a lot of patients after transplantation. And they come back, of course, after transplantation. So my dialysis patients, I also try to do living donations, so I see them. I see their relatives. It's very nice.

Frank Maddux: One of our greatest opportunities I think is to make that transition from transplant back to dialysis therapy safer. It's one of the riskiest times, I think, for patients.  I think one of the things we're looking at is where are there opportunities in the systems of care, whether it's organ availability, whether it's procurement, whether it's management of therapy. So we made, as you know, the company’s made a bunch of investments in this area. We have some clinical studies going on in drugs that prevent, you know, or reduce delayed graft function issues.  And we have a large investment in xenotransplantation through a company called eGenesis.

Nilufar Mohebbi: And I think that's the future, Frank, to my mind. I mean, I'm really not an expert at all, but I think still we have to see in the future and I can't imagine that dialysis is the end, you know. We will have definitely a lot of new therapies, xenotransplantation, new drugs, more targeted,  immunosuppression and longer graft survival hopefully. And so we have to go with the research, with the new developments.

Frank Maddux: Tell me a little bit about the state of transplant care in Switzerland. Are there donor networks? Is there an active paired donation program and other such things?

Nilufar Mohebbi: Swiss people are very lucky because there is a national system. You know countries like Germany or Austria or Netherlands, they have the Eurotransplant, so they are European countries that are connected and have the common donor and recipient pool. Switzerland is on his or her own, so only people that are, like, dialysis patients or have replacement therapy in Switzerland are on the waiting list. And they receive also only organs from other Swiss people. Exceptions are sometimes, like, if they have a collaboration only with France. So if sometimes organs are, like, rejected in France, they ask in Switzerland or if we have, like, high urgency transplants, so they can ask, for example, also for, in France especially regarding liver sometimes. So otherwise, Switzerland is, like, working on its own. And there are five transplant centers in Switzerland. They are all located at the university hospitals, so except one which is in East Switzerland, but the other ones, the four are all connected to the university. They have regular meetings. And you know, although Switzerland is so let's say small, but they are very well-organized so there is the Swiss Transplant Cohort Study that has been initiated years ago and it has been, interestingly, initiated from the infectiologists.  So we have a lot of data on infections, but we have data on like cancer also after this. I was looking, for example, also for bicarbonate. Unfortunately, bicarbonate was not documented. But they have data from all, like, transplant recipients who agree to participate. And this is, like, 90, I would say more than 95 percent of the patients agree, of course, because they are happy to receive the organ. And so we have really nice data, long-term data of the Swiss Transplant patients. We have a very also strong living kidney donation program. This has been also initiated by a nephrologist from Basel = Basle. And he also has, for example, he has made sure that the insurance of the recipient is paying for the donor. And this is not a question, so this is all regulated, all secure, so patients really know that we are committed to take care of them and that everything is well set. And this data of the living donors have also been published, like, I would say 3, 4 years ago in The Lancet. So although we are small, but the data are really nice and we have long-term data. So it's very well-organized. And we do, like, pair kidney donation. We do like ABO-incompatible transplantation. We have, this is also national, so according to the same protocol, that's also important, so not every center does on its own, so it's where all centers agreed on. And we have a common protocol for desensibilization for immunized patients. So I would say it's transplant on a high level.

Frank Maddux: Is your desensitization program with Rituximab-- Or is it a combination of medicine and procedure? Do you use any column-based--?

Nilufar Mohebbi: Yes, it's Rituximab and then they measure the antibodies and then they do also, like, immuno-absorption.

Frank Maddux: Immuno-absorption appears to me to be a much more standardized desensitization component in Europe than in the U.S. and it's always-- It's always been a wonder to me why.

Nilufar Mohebbi: Maybe because of reimbursement. Is that, like, I think so here the reimbursement is well, so, so the staff is well-trained. They are-- they know it, so maybe it's more established. I don't-- I actually don't know.

Frank Maddux: I'm interested in just taking some of the experience that you've had over your career and just letting people understand a little bit more about you. Tell us a little bit about your medical education and your coming from Iran through your training to Germany. I'm just interested in sort of the path you took to your current career.

Nilufar Mohebbi: Of course, as a child, I had not very much to say. So my parents obviously decided to put me in the German school in Tehran, Iran, where I was born. So I went to this German school, however, after two years the government changed, so the Revolution took place. And then again, it was the decision of my parents what to do with this daughter. And obviously, they wanted to put me away. I was maybe too curious for them. So they decided then to move to Germany and to continue my school education in Germany. And so I when I was actually 11, I moved to Germany and I grew up then in Germany. I went there to high school and then I went to the University actually in the City of Mainz, so which is the city where Pfizer Biontech is located and the vaccine against COVID has been developed. So it's of course just an association, however, it's a very good medical school I would say. And so I did there my medical school and then I was thinking about what to do, what kind of specialty. And a friend of mine, he asked me to come to his clinic. He was in the Cardiology Department and he said that the nephrologists are looking for a fellow. And I was, like, "Oh, my God, Nephrology? Too complicated." And he said, "No, no, no. They are really nice and you will love it." And it was the German Clinic for Diagnostics, which is a kind of similar to the Mayo Clinic in Rochester. So I said, "Okay. So I will try." And I applied for this position and then they invited me. And then they said, "Okay, you can start." And I was like, "Oh, my God. Now I'm becoming a nephrologist probably." And you know what? So they were like, inspiring. So they really showed me nephrology from its best side and after a while, they told me, "Okay. But if you want to become a proper nephrologist, you have to go to Dr. Luft." And I was like, "Okay. Who is this Dr. Luft?" And then I knew that one of my heads at that time, he was writing a textbook in nephrology in German with Dr. Luft, so he knew him, of course, very well. And so he said, "You have to go to Berlin. You have to go." And I have to say, I was very lucky because I had a scholarship also at that time from it's called, it's a very German word, Kuratorium für Heimdialyse, so this is a nonprofit organization in Germany that owns a lot of different dialysis units and has been founded by someone really exceptional, too, because he had at that time in the 1960s when dialysis started worldwide, he went to the States and looked into dialysis units or machines and he founded this in Germany because a friend of his has been becoming a dialysis patient. So I had this scholarship from this company and then I called Dr. Luft and said, "Well, Professor Luft, my name is so and so. I'm a fellow in Nephrology and I would like to come to your department." And he said, "Okay. When are you going to start?" Come and visit us. We will also look at you if you fit into this department and so on." So I went to Berlin. I obviously got accepted by the team. And he had a brilliant team and yes, then I finished my fellowship in Nephrology. And became a nephrologist.

Frank Maddux: I'm interested in just talking a little bit about what it was like being a woman in Nephrology. Were there problems that you had to deal with that were different than the men? And I'm just curious about the experience you've had.

Nilufar Mohebbi: I had interestingly no female, like, role model, I have to say. Because the first nephrologist I trained with, these were four men. But, you know, they are these exceptional men who just don't care about your gender. And that was the case where I started. And then when I was at Dr. Luft's place in Berlin, so at The Charité, it was much more fun here because at one point he said, "Nilufar, you have to do research." And I was like-- Because before I did of course my medical thesis, which is common in the German speaking countries for doctors to become a real doctor, “Dr. Med” it's called, so you have to do some research, so this I did obviously. But I didn't do, like, I didn't continue. So he said, "You have to do research." I said, "Professor Luft, I'm too old." I didn't say, "I'm a woman." I said,, "I'm too old." He said, "No. I was your age when I started doing research in Indianapolis,". So I said, "Yes, okay, but yes, I'm a woman." He said, "I don't care about if you are a woman or a man. I want you to try." And then he asked me, and imagine, this is something really exceptional. He said, "Look into all my groups and see what you are interested in." So he didn't tell which type of research or what kind of research I should do, he said, "Look into the research projects and tell me what you are most interested in." And that's how I started actually with research. So I never experienced, like, to be treated differently because I'm a woman, but-- there's always a but in life and in medicine-- when I was becoming a professor, so regarding becoming a faculty member I think when you want to do, like, this academic career, then it's becoming more hard for females. So I had always the feeling afterwards that especially in Zurich that I have always to be a bit like better than my male colleagues to have the same, like, promotion or so. But interestingly, I never had, like, female role models. I tried, of course, to be a role model when I was an attending physician at the University Hospital for my younger female colleagues, for the fellows. And I always was telling them, "Look at me. I'm a female. I'm doing this job. I'm doing research. And you can still be feminine, you know." Sometimes they are anxious that they have to become like men and I think that's the wrong way. You should-- Because this is the advantage, you know, that we are different than men.

Frank Maddux: You didn't have a lot of role models for your own career, but you certainly have the opportunity to be a role model for others. And we have quite a few in our medical office early to mid-career women that I think actually benefit from some of the women that have had very successful careers like yourself within the field. Was it while you were working with Professor Luft that you got your interest in acid-based disturbances and the issues that you're studying now?

Nilufar Mohebbi: At that time, I looked into three groups. One was doing research in vasculitis. But these were all people from Chapel Hill, you know. They had trained in Chapel Hill, so super good. The second group was doing autonomous stuff, very successful with nice publications. And the third group was a one-man group with a student, a medical student, who came just back from Yale University. So he did some research. Of course, you know Yale University has a long tradition in renal physiology. So Yale had Gerhard Giebisch and so on and so on. And so he had done research on a gene in a fly which is called, the gene is called INDY. INDY is for I'm Not Dead Yet. So this is just the abbreviation. And this fly was able-- it is a drosophila. There's this mutation of this INDY gene and this fly was able to live longer and this was because, and that's what was my first publication, actually, because it is a citrate transporter in the kidney, let's say, or similar to the ones that we have in the kidney and it's about energy metabolism and so that if you use less energy and  they are data from primates and so on, that you live longer. And so this was the first project and I got fascinated. And I loved the student. He was super motivated. He was very smart and now he's also a professor for Nephrology in Berlin. His name is Felix Knauf. So I started research then and then of course Professor Luft told me, "There is this professor, Heini Murer, in Zurich who cloned the sodium phosphate co-transporter. So what do you think about this?" I was like, "Okay. Switzerland? Sounds good. It's close “And so I started a post-doc in Zurich in the Institute of Physiology. So that's how the research started and I became fascinated about transport because this is very logic, you know. These transport proteins you know what they do and you know what had happened. You can measure everything in urine. You can measure everything in blood. So it's much more precise to my mind than immunology, you know, where you don't really measure what happens.

Frank Maddux: So did you get involved at all in sort of the early micropuncture techniques to look at sort of electrolyte movement and patch clamps and other things like that at the bench?

Nilufar Mohebbi: I did not do patch clamp but I collaborated in studies where these have been done because patch clamp, we did it in Zurich in the lab where I was, but this was done by a colleague of mine because this is really to patch the piece of tubule this is really difficult. So I watched it for a long time. I did a lot of immunofluorescence microscopy on kidney tissue and kidney cells, but I didn't do the patch clamp.

Frank Maddux: Well, before we end here, I thought I might ask you, how COVID has impacted your dialysis environment and the work that you do day to day. How are things for you right now in Switzerland with regard to the pandemic?

Nilufar Mohebbi: You know, the good thing in Switzerland is they are small. Sometimes it's good to be slow, you know. So they did not immediately follow all the measures that all other countries did like the neighboring countries, let's say. So we did-- We had, of course, all the lockdowns, but it was never too long. And still, you know, you could always go to the supermarket, so I never felt like by myself very, bad just say. And regarding patients, first, we were super lucky. We didn't have any cases. And then, of course, with the second wave especially, so the autumn last year, in November, we had, like, a couple of patients. And then we had to organize another shift for them because we didn't want to have them of course in parallel to our non-infected, like, healthy patients. And then we had to do more hours, of course, because we had to come in in the night and also our nurses. But I have to say, also, our nurses, they did a really nice job. There was no complaint. Nobody said, like, "No, I'm not, you know, I'm not doing more hours," and so on. So,  we managed really to get the patients out of this pandemic or it's still continuing, but out of the second wave. We lost one patient, unfortunately. But all in all, we are, of course, following all measures still now. Sometimes people ask, "Ah, still the mask?" Staff, patients, whoever.

Frank Maddux: Right.

Nilufar Mohebbi: Still we don't allow any other people coming into the unit. So, we are following some measures. But I think with these measures if everyone is doing well, why not?

Frank Maddux: Have most of the patients accepted vaccination and what's the vaccination status?  In your population?

Nilufar Mohebbi: Yes. We are super lucky because, I have the number compared to all the EMEA countries that Stefano is providing us. Dr. Stuard, the head of the EMEA, and I'm very lucky if I see my country, like, within the good numbers. So we have I think the last time I got the statistics it was, like, 92 percent.

Frank Maddux: Oh, that's fantastic. I'm here today with our Country Medical Director from Switzerland, Dr. Nilufar Mohebbi. It's been great to talk to you and thank you so much for giving us some insight in getting to know you just a little bit better.

Nilufar Mohebbi: Thank you very much.