Onco-Nephrology Program

Podcast Transcript

Dale Shepard, MD, PhD: Cancer Advances, a Cleveland Clinic podcast for medical professionals. Exploring the latest innovative research and clinical advances in the field of oncology. Thank you for joining us for another episode of Cancer Advances. I'm your host, Dr. Dale Shepard, a medical oncologist here at Cleveland Clinic overseeing our Taussig Phase I and Sarcoma Programs. Today I'm happy to be joined by Dr. Roman Shingarev. He's director of Cleveland Clinic's new Onco-Nephrology program at Glickman Urological & Kidney Institute. He's here today to talk to us about that program. So welcome, Roman.

Roman Shingarev, MD: Thank you glad to be here.

Dale Shepard, MD, PhD: So maybe to start, tell us a little bit about your role here at Cleveland Clinic.

Roman Shingarev, MD: So this initiative to build the Onco-Nephrology clinic is the direct continuation of my work at Memorial Sloan Kettering focused on improving outcomes of cancer patients coming from all over the world to receive the best and the latest oncology has to offer. Ensuring the stability of kidney function and preventing kidney failure, which is common with many cancer treatments is integral to the multidisciplinary efforts to improve patient's chances of survival. And this is because reduced kidney function can make some treatments more toxic to the kidneys or other organs. And importantly in our day and age can borrow a patient from participating in a new drug trial.

Dale Shepard, MD, PhD: So this is a relatively new area. Tell us a little bit about how you got involved.

Roman Shingarev, MD: Well, I worked at Sloan Kettering as a dedicated Onco-Nephrologist for the past six years together with a group of more senior people that worked there for decades. This is where I gained the experience, and this is where I learned about the oncology per se.

Dale Shepard, MD, PhD: So when we think about this program you're setting up, what does that program entail?

Roman Shingarev, MD: So probably requires a little bit of background to emphasize the significance of the problem. Cancer is, as you are well aware, is a prevalent problem to which significant resources have been allocated. This led to a tremendous progress in the development of new treatments and led to remarkably improved patient outcomes. Although many of these treatments are proving to be toxic to the kidneys. And the flip side of the improved patient survival is that this kidney toxicity becomes an important issue during the patient's extended lifetimes. So in other words, kidney disease, such as a competing risk factor then becomes apparent when the risk of dying from cancer is reduced.

And there's also been an incredible growth in the novel cancer drugs with the FDA approvals tripling in just over the past decade. Increasing complexity of these novel cancer treatments has led to subspecialization within the oncology practice with most oncologists now specializing in one body organ just to keep up with the current body of research. On the other hand, our understanding and treatment of kidney disease has also been growing rapidly, but this body of knowledge is not necessarily readily available to other specialties including oncology. So my vision for the future of Onco-Nephrology in general, and the program that we're trying to build is to bridge the gap between the two specialties to ensure that patients with kidney disease are safe to get new cancer treatments. And on the other hand, cancer patient survivors needing adequate kidney function to avoid dialysis.

Dale Shepard, MD, PhD: What kind of shift in patients have you seen as we've changed cancer treatment? So we think about traditional cytotoxic chemotherapies and cisplatin and problems with that, for instance, and then now we have immunotherapies and people get more inflammatory problems. So how has that shifted what you're seeing in clinic?

Roman Shingarev, MD: Although immunotherapy and VEGF-directed therapies have become much more prevalent in oncology, we still see a fair share of conventional chemotherapy toxicities that most commonly includes cisplatin, pemetrexed, ifosfamide that result in progressive chronic kidney disease in many patients. And this is when we see them in our clinic. The new drugs certainly added a new level of complexity. And as a specialty, we are struggling to understand the nature of the toxicities and to ascertain the causal relationship between the new drug on the market and the occurrence of acute kidney injury, for example. And this is not very certain. There are plenty of case reports on any given drug that is available that results in some form of kidney injury. But we don't know if there is indeed a causal relationship because we very frequently do not understand the mechanism of that toxicity. So this certainly added a layer of complexity to our clinics in general, but that's what makes it exciting.

Dale Shepard, MD, PhD: And when we think about the cytotoxic-related toxicities, oftentimes those are long-lasting. Are you seeing similar things with newer drugs? Are they more acute episodes?

Roman Shingarev, MD: We probably don't have the continuous experience long enough with the new treatments to assess the chronicity of the problems. Most of the immunotherapy drugs starting with melanoma treatments have been around for six, seven years, give or take. And so I don't think that we are ready to claim that these drugs or the use of these drugs translate into a significant CKD problems. On the other hand, the conventional treatments we know a lot about, and in case of curative regimens like cisplatin, for example, for squamous cell carcinoma, we know a great deal about the long-term effects of that cisplatin. So again, immunotherapies do present acutely to our clinics and require specific treatment, but we're not certain about how chronic these changes are. And it is also dependent on the overall patient survival. We don't gain much information about the outcomes of the patients receiving these drugs as a fourth line of treatment and not surviving long enough for us to make that assessment.

Dale Shepard, MD, PhD: So as this Onco-Nephrology program has been established, is this a multidisciplinary clinic, or what is it like if a patient comes to your clinic?

Roman Shingarev, MD: So we want it to be a multidisciplinary effort for sure, because that's the whole goal of it. But in general, in our practice, any specialist at present or a primary care provider or the oncologist, of course, can send the patient to our clinic, as long as the patient has some form of cancer diagnosis. And we can address a wide range of conditions ranging from high blood pressure to acute or chronic kidney disease. But we would like to establish the clinical relationship with other sub-specialties involved with oncology, like endocrinology, for example, and especially for complex patients, BMT patients in particular, I think that certainly requires a multidisciplinary effort in real time.

Dale Shepard, MD, PhD: So you're mostly seeing patients who may be embarking on a therapy and have underlying kidney disease, or are you more seeing patients that have some toxicities and effects on their kidneys from their treatment, and I guess coupled with that, which ones would you like to see?

Roman Shingarev, MD: We certainly see many more patients with the toxicities arising from cancer treatments, not so much patients with chronic kidney disease going in forward for the treatment at the present. But one of the goals of this program is to actually change that we want to tap into the CKD database and the CKD clinic population that we have at the Glickman Institute and make these treatments widely available to patients with chronic kidney disease. Because as you probably know, chronic kidney disease is considered to be a risk factor for developing certain types of malignancies. And we certainly want to make sure that we get the best treatments for our own patient population.

Dale Shepard, MD, PhD: So one of the frustrations often is that patients might have underlying kidney disease and they may not qualify for certain therapies, or they may not qualify for a clinical trial because of the criteria. Is there work being done to optimize their renal function in order to allow them to get those therapies? Is there research being done in that area?

Roman Shingarev, MD: Yes. There are a research efforts led by MD Anderson that assesses the waste to evaluate the kidney function prior to initiation of pharmacological treatment. We do not have any research efforts established as of yet. That's our long-term goal, but certainly it's part of how our practice. Usually though, we deal with it in the settings of already enrolled patient who presents with an acute kidney injury and gets excluded from the trial at that time. So when we see such patient in the clinic, we try to optimize the kidney function there and we sometimes make a difference because sometimes we discover that the patient is severely hypotensive and taking a lot of anti-hypertensive medications with effects on the kidney function. And we're able to reverse that very readily, and re-enroll the patients very often.

Dale Shepard, MD, PhD: So I guess just to finish out thinking about research, what sort of research are you most interested in setting up within the program?

Roman Shingarev, MD: I think a unique opportunity that Cleveland Clinic has compared to other dedicated oncological centers like MD Anderson or Memorial Sloan Kettering is a large pool of CKD patients and the databases that exist both in oncology and nephrology. My goal would be to try to find a way to link these databases, to discover model risk factors, mechanism of drug toxicity and long-term outcomes. And this combination of two unique patient populations is important to have. And that's one of the reasons why I joined Cleveland Clinic.

Dale Shepard, MD, PhD: How are we engaging with our regional colleagues? Are we getting patients from... A lot of our cancer care actually takes place at our family health centers and our regional hospitals. Is the thought to have those patients come here to main campus for services or is there a thought that this might expand under those areas?

Roman Shingarev, MD: We are actually actively working to provide our services to regional patients. We had a meeting with Dr. Hodden who made some very important suggestions of how to achieve that goal. Given the fact that we are a small group of Onco-Nephrologists here in the clinic, we would like to start out by providing these services virtually, which will allow a wider regional coverage. And if this is successful, we will move in to maybe establish the regional clinics as well.

Dale Shepard, MD, PhD: So one of the silver linings, I guess, of the COVID pandemic is our virtual outreach.

Roman Shingarev, MD: Yes, yes. And in fact, I can tell you that I've been pushing for virtual visits for three years before the pandemic hit and didn't move an inch yet in March of last year, it happened overnight.

Dale Shepard, MD, PhD: We mentioned our regional hospitals and systems and patients we're treating, but certainly on the oncology side, I see a lot of patients even from our community partners in the area and it sounds like this is very much something that they could benefit from as well.

Roman Shingarev, MD: Of course, it's a very valuable service. Not only does it allow patients to stay at home, and sometimes they're pretty sick, this also allows us to cover many more patients with the limited resources that we have. So I see it as a tremendous opportunity indeed.

Dale Shepard, MD, PhD: So as people may be listening and interested in having their patients seen, who would you describe as the ideal patient you would like to see in clinic? Who should be coming to see you?

Roman Shingarev, MD: Anybody with an abnormal creatinine, abnormal blood pressure, abnormal urinalysis, who is about to start a treatment, especially the treatment with known renal side effects. So you can think of it in terms of somebody with underlying intrinsic renal pathology, be it diabetic nephropathy or IGA nephropathy. Somebody proteinuric, which is a significant risk factor for acute kidney injury with any form of toxicity. We would like to see these patients in the clinic to help optimize their care before they actually get the treatment. And if we're able to do that before the treatment starts, if we're able to optimize them, we do have a track record of minimizing the subsequent side effects of the chemotoxicity. So this is probably a priority patient for us, but of course the run of the mill patients were presenting with acute kidney injury after a new drug was started, this is our bread and butter.

Dale Shepard, MD, PhD: Sounds like there may be some opportunities for survivorship as well. Patients who have had therapies and may have overcome their cancer, but now need to make sure that they optimize their health.

Roman Shingarev, MD: Right. So this is exactly what I was talking about when I said that once you cure the patients, it's very similar to your "Competition with cardiology." Once you treat the cancer and you extend the patient's survival, all of a sudden we are dealing with a significant risk of needing dialysis in the lifetime of the patient. And certainly we can do a lot on the nephrology side to help minimize the chances of requiring dialysis, but really these survivorship care starts during the treatment. This is where we have our best chance.

Dale Shepard, MD, PhD: And when we think about, we've been talking about a program and we focused on an outpatient setting, but certainly are there a lot of admissions to the hospital with renal complications? Is there a thought that this could expand into an inpatient service as a consult service, for instance?

Roman Shingarev, MD: Yes, this is actually a very active area of clinical interest for us right now. We're figuring out the workflow for referrals from oncology words to come to the Onco-Nephrology clinic for consultations that we can provide in between our outpatient clinic patients or after the clinics are over or sometimes electronically, we're looking to establish that workflow and we're going to trial it with some oncology providers just to make sure that it works seamlessly and doesn't generate confusion and problems. But yes, this is definitely an important direction for us to move in, to provide these sub-specialty consultation service for the inpatient wards.

Dale Shepard, MD, PhD: That's great. Well, it certainly sounds like you're providing a great service and good luck as you continue to develop the program. I appreciate your insights today.

Roman Shingarev, MD: Thank you. It was great talking to you.

Dale Shepard, MD, PhD: This concludes this episode of Cancer Advances. You will find additional podcast episodes on our website, clevelandclinic.org/canceradvancespodcast. Subscribe to the podcast on iTunes, Google play, Spotify SoundCloud or wherever you listen to podcasts. And don't forget you can access real-time updates from Cleveland Clinics Cancer Center experts on our Consult QD website at consultqd.clevelandclinic.org/cancer. Thank you for listening. Please join us again soon.