Episode 19: Slowing Down the Progression of CKD Through SGLT2 Inhibitors with Dr. Robert Kossmann
Originally developed to treat diabetes, SGLT2 inhibitors are potentially groundbreaking in slowing the progression of chronic kidney disease (CKD). Dr. Robert Kossmann, Executive Vice President, Global Head of Renal Therapies, and Chief Medical Officer of Fresenius Medical Care North America joins Field Notes to examine how this class of drug can be used to intervene earlier with patients and is a key tool within value-based care.

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Brad Puffer: Welcome, everyone, to this episode of Field Notes. I'm Brad Puffer on the Medical Office Communications Team at Fresenius Medical Care, North America, and your host for this discussion today. Here, we interview the experts, researchers, physicians, and caregivers, who bring experience, compassion, and insight into the work we do every day. We're excited to be joined today for an interesting conversation about SGLT2 inhibitors. This class of drug was originally designed to treat diabetes but is showing potentially groundbreaking effectiveness in slowing the progression of chronic kidney disease, as well as to treat a host of cardiovascular issues. SGLT2 inhibitors may also become critical to our efforts to intervene earlier with patients through our nephrologist partners, and a key tool within new, value-based care efforts that aim to improve outcomes and lower the total cost of care. Here to shed further light on SGLT2 inhibitors is Dr. Robert Kossmann, executive vice president, global head of renal therapies, and Chief Medical Officer for Fresenius Medical Care- North America. Dr. Kossmann, it's been a long time coming. Welcome to Field Notes.

Dr. Robert Kossmann: Thank you, Brad, I'm really happy to be here today.

Brad Puffer: I know we wanted to speak to you about this topic because you truly believe this new class of drugs can be a game changer for patients with chronic kidney disease. How does this new class of drugs compare to other innovations in pharmaceuticals in the renal space that you've seen over your career?

Dr. Robert Kossmann: Yeah, it's not often I use the expression, "truly extraordinary," but it's been 30 or more years since there has been something that is going to make as big a difference as this class of agents is expected to be, and that's when we first saw the introduction of ACE inhibitors and subsequently angiotensin receptor blockers.

Brad Puffer: Well, now that we've piqued everybody's interest, I want to back up and better understand what an SGLT2 really is, and how do these new inhibitors actually work?

Dr. Robert Kossmann: I think starting at the beginning is always a good place, and obviously, this is a catchy buzz phrase for this class of agents, but SGLT2 stands for sodium-glucose co-transporter number 2. These are the co-transporters in the cell walls that move sodium and glucose, and they are particularly important in the kidney for reabsorption of filtered glucose in that first segment of the renal tubule.

Brad Puffer: And so, when we think about an inhibitor, what are we preventing and how does this class of drug then work?

Dr. Robert Kossmann: Yeah, so this has really been very interesting. This class of agents was, in fact, designed and first brought forth to treat diabetes and to lower blood sugar, and so because in normal kidney physiology, we all filter 180 liters of fluid a day and a large amount of glucose filters through that initial glomerular filtrate, but then, 90% of it is reabsorbed in the proximal tubule, principally SGLT2-mediated reabsorption and co-transport with sodium. And so these agents, by inhibiting that reuptake, they cause a loss of glucose and secondarily a loss of sodium into the urine. So they cause a level of glycosuria which lowers blood sugar, and it's turned out that this has resulted in pleiotropic beneficial effects.

Brad Puffer: You mentioned how this was originally a diabetes drug. Tell us about that evolution from a diabetes drug to something that's really now being seen as able to slow the progression of kidney disease.

Dr. Robert Kossmann: What's happened is a level of serendipity. People were paying careful attention as these drugs were being developed, and through very large clinical trials with thousands of individuals with diabetes, and in addition to the glucose lowering, it was noted in subpopulations and in substantial trials over time that the progression of diabetic kidney disease was slowed, and there was also a lowering of systemic blood pressure. So very early on, there were indications that there were benefits to these drugs beyond blood glucose lowering.

Brad Puffer: And that sounds like big benefits also for cardiac issues in the heart.

Dr. Robert Kossmann: Absolutely, and perhaps one of the great findings for these agents has been their cardiovascular benefits. So not only does it turn out that they have lowered blood pressure some, and it appears that part of that is by decreasing blood volume a little bit, the loss of sodium in the urine and this effect. But as trials progressed, there was an observation that there was a reduction in congestive heart failure complications, so specific trials then went on to look at cardiovascular events and the effect on heart failure and showed quite substantial improvements in MACE (major adverse cardiovascular events) -- those are major adverse cardiovascular events-- and cardiovascular death and heart failure.

Brad Puffer: Well, based on these studies and the benefits we're seeing, when you have benefits for diabetes, when you have benefits for cardiac, benefits for renal disease, who should be prescribing these drugs and is, in fact, the nephrologist perhaps the best one to consider prescribing it?

Dr. Robert Kossmann: So, my feeling about this, very strongly, is that nephrologists play a very important role in prescribing these drugs, particularly in any patients with chronic kidney disease. So as these large trials have been published and come forward, trials such as CREDENCE and other trials including DAPA-CKD, what we have seen is that not only do patients with diabetic kidney disease and cardiac risk factors benefit, but also some with non-diabetic kidney disease, and certainly with cardiac disease not related to diabetes. And so since the nephrologists often serve as the principal care physician for many of the patients with advanced chronic kidney disease, there's clearly a role for the nephrologist to be one of the prescribing physicians here.

Brad Puffer: Well, the science you've been describing is pretty compelling. Is that therefore translating into an uptick in use by nephrologists? Are people catching on?

Dr. Robert Kossmann: So, I think it's beginning, and as I've talked to some neurologists in the field, both in small practices, medium practices, and then in further conversations with a couple of the large practices, but it boils down to the individual physician. Nephrologists are beginning to prescribe these drugs. Given the pleiotropic effects, there has been some question of how to best coordinate the care, and it turns out that this is another great opportunity to remind all of us that what's really key is the communication among providers. The patient really is at the center of what it is that we are all doing in health care, so it certainly can be appropriate for the primary care physician to prescribe these agents. It can be certainly appropriate for the endocrinologist or diabetologist. Cardiologists are also beginning to prescribe these, and so, that handoff of the patient from one visit to another among different physicians, who may be caring for that patient, is important. But again, clearly, there is not a reason for the nephrologist not to be taking an active role in prescribing here. The benefits can be reduction in progression of kidney disease on the order of 35% to 40% reduction in progression, and that is on top of the benefit patients will get from their ACE inhibitor or angiotensin receptor blocker. And these studies, in fact, when they were done, were looking at standard of care being in place which included ACE inhibitor or ARB and then use of these agents.

Brad Puffer: That's a pretty dramatic drop that you're describing there. In a lot of ways, these have the potential to really change how we treat patients before they reach kidney failure, which is what we're trying to do. If it's this compelling, what will it take for more nephrologists to then begin prescribing them? So in your personal experience as a practitioner, do you sometimes see different stages of adoption before a drug takes off?

Dr. Robert Kossmann: Absolutely, yes, and indeed, there's a science of change, and certainly some studies over time about what it takes to help encourage change in medical management to be adopted. One of the first things is education, and so opportunities to not only read but then hear about and learn from others, whether it's in meetings or from colleagues in less formal settings. And so I think one of the things is that disseminating the understanding and the knowledge from these clinical trials, and the degree to which this benefit really exceeds most of the other interventions that we have available to help patients, and it is our focus as a company. It is our focus as a profession to improve the quality of life as well as the length of life of our patients. And this class of drugs is very much a class of drugs for patients with CKD before they reach dialysis. In fact, patients with GFRs below 15 are not appropriate at all, and below 30, there is caution and different drugs are at different stages with respect to their-- indications with respect to their FDA labeling. That said, however, this is a population of patients where four out of five patients with CKD and with progressive CKD die of cardiovascular complications before their CKD ever progresses certainly as far as end stage. And so what we have here is an opportunity to really improve quality of life, reduce complications, improve length of life, so we are really very excited about what this means for patients going forward.

Brad Puffer: Some people may say, well, why is the chief medical officer of a company that primarily provides dialysis so excited about this, but we're also more and more taking responsibility and helping lead the way for patients who have late-stage CKD, who haven't even reached kidney failure yet. Does this really play into helping with our mission, especially around value-based care?

Dr. Robert Kossmann: Very, very much so, and not inconsistent, in the least, with our core mission in our traditional core activity of taking the best care of patients with advanced chronic kidney disease requiring dialysis, but in the last many years now, we've been involved in the care of patients with CKD through our physician partners and never more so than now. And these agents represent an opportunity to improve, again, the quality of life and the length of life for patients. And for many of these patients, it will delay not only their cardiovascular complications, but their renal disease, and may prevent them from progressing at all. Other patients will have longer survival without needing renal replacement therapy, but when they do reach a point where they need a transplant or they need dialysis, that they should be in better health, and we should be able to help these patients live better longer even when they come to the need for transplant or dialysis.

Brad Puffer: Well, a lot has happened around the science of SGLT2 inhibitors in just the last couple of years. What is the future? What is the trajectory? Do you see us turning a corner where 5 to 10 years from now, these new drugs are widely used to slow the progression of kidney disease?

Dr. Robert Kossmann: That is absolutely what I see. I think this is the most exciting class of agents in decades. We have FDA approval for three agents now, empagliflozin, canagliflozin, and dapagliflozin, and there are others that are in the wings, at least one other that's in use in Europe. The benefits of these agents are clearly powerful benefits for patients for improving quality of life and length of life. The pleiotropic effects assist with management of several complications for those patients who indeed have diabetic kidney disease, and lest I give the impression that these are a panacea, they are not, but they are clearly an exciting development here. A recent publication by Dr. Ralph DeFronzo, a well-known endocrinologist, points out that once there are established complications of diabetes including cardiovascular and renal effects, no single agent, no single class of agents is likely to be sufficient to control all of the complications. But certainly the SGLT2 inhibitors provide us with a tool unlike any other tool that we've had before to really make a difference.

Brad Puffer: It's going to be really exciting to see what happens over the next few years, Dr. Kossmann, and whether more and more physicians and especially neurologists get involved with prescribing these. And hopefully, we'll see also insurance companies and others making it even easier to prescribe them because I assume that can also be a barrier as well.

Dr. Robert Kossmann: It is, and with any new class of agents, it takes a little time for it to work through some of the processes, including insurance coverage. Some of these agents are expensive and significantly so, and that is a barrier, but as the data is as strong as it is, and the benefits are as strong as they are, I'm confident that over time, the hurdles that exist will be overcome and that we will see widespread adoption and utilization.

Brad Puffer: Well, Dr. Kossmann, this has been a really interesting and, I think, important conversation. I hope there are some people who will want to learn more or even begin prescribing these new drugs after listening to this, and certainly the more people we can help to live fuller, healthier lives, the better, so thanks for being here.

Dr. Robert Kossmann: Thank you for having me, Brad. It's been a real pleasure.

Brad Puffer: And to our audience, thank you for joining us. Please know that your feedback is always welcome. If you have any comments on today's episode, topics of interest to you, or speakers you want to hear from, let us know by clicking the feedback link featured on the Field Notes website on FMCNA.com. Don't forget, you can find Field Notes on the Apple Store or Google Play or right here at FMCNA.com where you can also find our annual medical report and other featured articles. We hope you'll come back and join us as we have many more topics to discuss in the weeks ahead. Until next time, I'm Brad Puffer, and you've been listening to Field Notes by Fresenius Medical Care. Take care, everyone, and stay safe.