Transcription:
The Importance of Kidney Health for Heart Health

Melanie Cole (Host):  Welcome to Better Edge, a Northwestern Medicine Podcast for Physicians. I'm Melanie Cole and joining me today is Dr. Rupal Mehta. She's an Assistant Professor in the Division of Nephrology and Hypertension at Northwestern Medicine and a Principal Investigator in the Center for Translational Metabolism and Health in the Institute of Public Health and Medicine. She's here to discuss the very close link between kidney health and heart health. Dr. Mehta, thank you for joining us. I'm so glad to have you with us. Please tell us about the connection between heart disease and kidney disease. Is kidney disease, a risk factor for the development of cardiovascular disease? Why should these medical conditions be discussed together?

Rupal Mehta, MD (Guest): So first off, I just want to thank you and all the listeners for having me today on Better Edge podcast to discuss this complex relationship between kidney and heart disease. It's an extremely important topic that I'm very passionate about. And especially as we talk about the prevention, the diagnosis and the treatment of both of these conditions separately, as well as together.

So, I think it's extremely important. Chronic kidney disease affects almost 15% of the US population and almost 850 million individuals worldwide have CKD. So, obviously we're talking about a major public health epidemic, impacting many patients and families. So, having chronic kidney disease increases our patient's risk of developing cardiovascular disease and cardiovascular disease remains the leading cause of death in patients with kidney disease and end-stage renal disease. But it's important to note that the relationship is bi-directional. And so, not only is kidney disease a risk factor for the development of cardiovascular disease, which you asked about, but having heart disease, for example, heart failure is a risk factor for developing kidney disease and for the progression of kidney disease.

And when they occur together, this heightens morbidity, mortality, healthcare resource utilization, and results in poor health related quality of life for our patients. So, each disease state hastens the development and progression of the other, which is just one of the reasons why we should be talking about these conditions together like you asked. They also share common comorbidities, such as diabetes, hypertension, metabolic syndrome. And so, the treatment of these different comorbidities may also improve outcomes for both heart disease and kidney disease. And then finally novel treatments have demonstrated positive results in the treatment of patients with both of these conditions and have targeted both kidney and cardiovascular endpoints. And so, it's important that when we see our patients and talk to our patients, we talk about both kidney and cardiovascular disease together.

Host: Well, thank you for that, Dr. Mehta. So, is kidney disease considered an independent cardiovascular risk factor not a marker? Does impaired kidney function alone up the risk of cardiovascular disease?

Dr. Mehta: Yeah, it's a great question. It's a complex question that has many answers, actually. So, as I said before, kidney and cardiovascular disease share common risk factors, such as high blood pressure and diabetes and uncontrolled conditions such as these worsen both kidney and heart disease. But there are many complications that are unique to chronic kidney disease or that arise as chronic kidney disease progresses that puts our patient population at risk for cardiovascular disease. And these complications are independent risk factors for the development of cardiovascular disease, as you asked. For example, as CKD or chronic kidney disease progresses, many of our patients develop anemia.

And anemia is a risk factor for the development of cardiovascular disease. Similarly, as kidney disease progresses, our patients develop high blood pressure and more difficult to control hypertension. We know that many of our patients, I'm sure many of our listeners have patients with kidney disease and they've noticed that their blood pressure becomes harder to control as CKD advances. This leads to increased risks of coronary heart disease, heart failure, as well as stroke. And then there's also altered mineral metabolism in CKD, and it's something that I've studied, very much in depth and alterations in calcium and phosphate homeostasis, as well as vitamin D, parathyroid hormone, fibroblast growth factor 23 access, all put patients at risk for the development of cardiovascular disease.

These patients have increased risk of vascular calcification, which increases their risk of having heart attacks or myocardial infarctions. Elevations in fibroblast growth factor 23, or FGF 23, and Klotho deficiency are strongly linked to the development of left ventricular hypertrophy and heart failure development.

That's not just in clinical models, but it's also from basic science work that we see that FGF 23 binds to the receptor on the cardiac myocytes and may cause LVH. And then finally, additionally, in CKD there's upregulation of the sympathetic nervous system, which could lead to worsening heart failure and stroke. There is sodium retention and volume overload, and that can lead to heart failure hospitalizations, and then there's risk of arrhythmias, which may be due to electrolyte abnormalities that happen in advanced CKD.

So, as you can see, there's a multitude of explanations for why patients with kidney disease are at increased risk for cardiovascular disease. It's not a surprise, when I say that one area of large focus in the research arena is on prevention of cardiovascular disease in our patient population. And to do this though, we need to identify cardiovascular disease in our patient population before it's clinically apparent. For example, one of our group's current research focus is on detecting subclinical heart failure and understanding heart failure risk in patients with chronic kidney disease.

Host: So based on what you just said, high risk of heart failure, cardiovascular disease in patients with CKD. Tell us how you approach the management of these patients and Doctor, if someone has heart disease and or kidney disease, are they treated together? Are they treated as two separate conditions? Do they see two separate doctors for their symptoms? Tell us how that works.

Dr. Mehta: Most patients who have cardiovascular disease and kidney disease do see two physicians. They see nephrologists as we manage their kidney disease and the complications of kidney disease and the comorbidities, or some of the co-morbidities that are associated with kidney disease. And they also see cardiologists, whether it be electrophysiologists, whether it be heart failure specialists, or advanced heart failure specialists, they probably, or may have interventional cardiologists that they see. Although our patients see these physicians separately, we co-manage a lot of these conditions together. So for example, in heart failure, we may be as an nephrologists, managing diuretics, but so will heart failure specialists and general cardiologists. And so we sometimes manage these patients together as well. We are in an exciting time for the nephrology community right now.

And there's novel agents that are being developed or have been developed that treat both cardiovascular disease and kidney disease. And it's resulted in a treatment paradigm shift for our patient population. There's a lot of new trial data, which we can discuss if you'd like, that look at new therapies that act on the kidney that have both improvement in cardiovascular and kidney outcomes.

Host: Well, yes, I would like you to get into some of that, because this is an exciting time for nephrology and for your community. Can these therapies be used in patients on dialysis? Tell us about some of the emerging therapies for patients with chronic kidney disease and heart failure or heart disease. And what's exciting in your field right now.

Dr. Mehta: Yeah, I can't emphasize enough where we are in the last five years in nephrology and how excited we are with new trial data that is coming out. So, for example, three sodium glucose co-transporter 2 inhibitors or SGLT 2 inhibitors, canagliflozin and empaglaflozin, dapaglaflozin, have been studied in numerous completed cardiovascular and kidney disease outcomes trials. And these trials demonstrated improvement in both cardiovascular events and hospitalizations, as well as kidney related outcomes.

And then two of these trials, the CREDENCE and the DAPA-CKD trial were conducted in patients with CKD where the primary outcomes were actually dedicated kidney outcomes. And then additionally, the DAPA-CKD trial that I just mentioned included patients with and without type 2 diabetes. And I mention this because originally, these drugs were meant, as therapies for patients with diabetes.

But we've learned more that these drugs not only improve diabetic parameters, but improve cardiovascular outcomes and now renal outcomes as well. Both the CREDENCE and DAPA-CKD trials demonstrated efficacy in protecting against kidney related outcomes. And those outcomes they vary and they may be a composite of serum creatinine doubling or end-stage renal disease or sustained EGFRs less than a certain threshold like 15 or death from renal or cardiovascular causes. So, hard outcomes.

And I think that's extremely important. DAPA-CKD also demonstrated improvement in these outcomes. In the last trial, we're still waiting on is EMPA-CKD, which Northwestern and our group is actually enrolling patients into. This trial is great because not only is it enrolling patients with and without diabetes who have CKD, but they're going to a GFR as low as 25 millimeters per minute. And I think that is extremely important because there's times where we feel like the GFR cutoffs for these therapies exclude many of our patient populations who are at highest risk for cardiovascular disease. And so hopefully with the results of these major kidney trials being published, we'll see a new indication for this class of drugs, not just for the prevention of cardiovascular disease, but for the prevention of CKD progression in patients with CKD, with, or without diabetes.

I can't emphasize enough the enormous impact this will have on our patient population. And it's not just SGLT-2 inhibitors. I focused on that, but there's other therapies as well that have been shown to benefit our patients from both a cardiovascular and renal perspective. So GLP-1 receptor agonists have also been shown to demonstrate efficacy and the prevention of CV outcomes or cardiovascular outcomes and kidney outcomes in patients with type 2 diabetes and CKD.

All of this underscores the importance of continuing to perform clinical trials in patients with chronic kidney disease. And whether that be trials in populations of kidney disease or it just means including our patients into larger cardiovascular trials, both would be necessary. And I'd encourage all physicians out there listening to discuss enrollment of their patients into national trials and registries.

We have a number of clinical trials ongoing here at Northwestern for our patients. And we find that patients are excited to be a part of these clinical trials, not just because of possible improvement in their own clinical status, but patients really enjoy helping the scientific community answer questions better critically important to themselves and their health or things that are affecting their families.

Host: What an informative episode, really fascinating, dr. Mehta. Leave us with one parting piece of information for providers who are listening, what would you like them to know about heart health, kidney health, how these two things not only work together, but run counter to each other. And when you feel that it's important that they refer to the specialists at Northwestern Medicine.

Dr. Mehta: So, I'll say two things. One, I'll go back to a question you had asked about end stage renal disease and these therapies and end stage renal disease. And I'll say this, it was an important question and it's an important point. These clinical trials that I've referred to have all been performed in patients with chronic kidney disease, but they exclude patients on hemodialysis or peritoneal dialysis. And kidney transplantation remains the most important therapy or intervention we can advocate for in patients with end stage renal disease. There are emerging therapies that we didn't consider before, that we're starting to see used in patients with end stage renal disease. For example, we're seeing implantation of left ventricular assist devices in patients with advanced heart failure and end stage renal disease. And we're seeing utilization for example, of CardioMEMS devices to help guide volume status in some patients with end stage renal disease.

But it's important to note that these therapies are not being done everywhere, nor are they the standard of care. And that there's a very specific patient population that these therapies are offered to. Regarding one final piece of information, I'd like to emphasize that implementation remains crucial. So, we have all this clinical trial data, which is wonderful. But we know that a large proportion of our patients, both either with cardiovascular disease or heart failure or kidney disease are not on therapies we know that they would benefit from. And so, the reasons behind this are complex. It's important that we continue to work towards understanding why patients aren't getting the therapies they should be on, based on clinical trials and what the barriers to implementation of new therapies and treatments are. And this could include access to therapies, drug pricing, our formulary medications, our own physician inertia, infrastructure, or a lack of infrastructure support to manage these complex medical diseases and comorbidities.

The list can go on and on. And although we have the trial data translating these clinical trials, our clinical trial data to our clinics remains critical. And so, I think we're beginning to make a case for multidisciplinary integrated care models that include nephrologists, cardiologists, endocrinologists, primary care physicians, anybody else who would want to be involved, including the patient.

This can be implemented both on the inpatient and outpatient settings. And so, I think I'll end with saying that and that we need to kind of work together with subspecialists and primary care doctors to treat our patients. And I believe we're now in an era to use Guideline Directed Medical Therapy or GDMT, which is being very much intensified and aggressively pursued in the heart failure realm, but not only for patients with heart failure and cardiovascular disease, but we're in an era of GDMT for patients with kidney and heart disease.

Host: Wow. What great points you made Dr. Mehta. Absolutely a fascinating episode. So informative. Thank you again for joining us. I hope you'll join us again and update us as more of your research comes to fruition. To refer your patient, please visit our website at nm.org/nephrology to get connected with one of our providers.

That concludes this episode of Better Edge, a Northwestern Medicine Podcast for Physicians. Please remember to subscribe, rate and review this podcast and all the other Northwestern Medicine podcasts. I'm Melanie Cole.