Cardio-Renal Disease: New Perspectives and the Cardio-Renal Connections Conference

The Cardio Renal Connections Conference takes place July 20-21, 2018, in San Antonio, Texas. Learn more at www.cardiorenalconnections.org

Can you describe what you mean by the term “cardio-renal disease”?

The construct has been around for probably two decades, but hasn’t entered the mainstream until recently. Part of that is two-fold; first, we now have a better understanding of the pathophysiology of heart disease and kidney disease, and how they overlap and influence each other. They are not separate organ systems. The heart, the vascular system, and the kidney are all interrelated. Second, there is such an epidemic of diabetes in the United States and in other developed countries that we can’t avoid it. With diabetes comes chronic kidney disease, and with diabetes and chronic kidney disease comes heart disease, so the two disease states are in our face every single day when we are seeing patients. The cardio-renal connection is coming more to the forefront in day-to-day practice.

What is the incidence of cardio-renal disease in the United States?

The incidence of heart and kidney disease is really being driven by diabetes. For instance, if you look at projected diabetes rates where I work, in Texas, they are expected to grow considerably. The national average rate of diabetes in the United States is about 8-9%; in Texas, we are in the 9-10% range, and in San Antonio where I practice, we are at 10-13%. If you go into the more Southern region of the United States, there is actually a diabetic belt that runs from Texas all the way to the southeast coast of the United States. You will see that diabetic rates are very high, particularly in minority populations of African-Americans and Hispanics, and in certain parts of the diabetic belt, the rate can be as high as 30% in the general population. That means 1 out of 3 people in these communities has diabetes, which translates to 60% or more of patients in clinical settings having diabetes. As these individuals get older and they have diabetic complications, they will be at risk of developing chronic kidney disease and premature cardiovascular disease as well. Identifying these patients is easy, but we don’t do a good job of it. As cardiologists, traditionally we are so focused on the heart and blood vessels, we often don’t ask questions such as what is the baseline renal function? Is this patient on medications to help prevent progression of chronic kidney disease? Do they have protein in their urine? What does the nephrologist think about the patient? 

What are the ways cardio-renal disease is identified? Is serum creatinine still the gold standard?

If the creatinine is elevated, that patient is at risk, certainly. But there are patients who have less dramatic increases or elevations in their creatinine level that are still at risk of cardio-renal disease. Those patients would be those who have even subclinical decreased glomeluar filtration rate, or GFR. Traditionally we don’t think about calculating GFR. We may look at the serum creatinine, but as cardiologists, we should do a better job of focusing on the GFR rate, particularly as calculated by one of the more contemporary equations such as the Modification of Diet in Renal Disease (MDRD) Study equation or the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. If we understand that the creatinine is just part of the measure of renal function, that will be helpful. If you just look at one creatinine time point, you don’t get a sense of what is going on with the patient. It is helpful to look at the serum creatinine measurements and the GFR rates that preceded us seeing the patient, and what happens to the renal function after we take care of the patient’s heart, so that we can have a better continuity of what is going on with their kidney function.

Once these patients are identified, how do you proceed?

It depends on the context in which we are seeing these patients. Cardio-renal syndromes are present in a variety of different clinical scenarios. For example, a patient comes in with worsening kidney function, then develops worsening cardiac function. Or the patient comes in a really bad cardiac state, with decompensated heart failure, acute coronary syndrome, shock, and then the kidney function gets worse. In fact, a common scenario we see is where the patient comes in with chronic kidney disease, and then needs a cardiovascular procedure, such as a stent, angioplasty, angiography, transcatheter aortic valve replacement, and/or a peripheral artery intervention, and then develops acute kidney injury. It is a heterogeneous mixture of patient scenarios that make up this paradigm of cardio-renal disease. If we are addressing a patient with worsening kidney function in the context of decompensated heart failure, there is a whole approach that involves trying to understand intracardiac filling pressures, management of diuretics, and neurohoromonal modulation. When it comes to patients undergoing stent procedures or revascularization, and with chronic kidney disease, we have a whole other approach to consider in terms of minimizing contrast dye, ensuring that these patients are not volume depleted, and in minimizing nephrotoxic agents. It isn’t one solution for all of these different scenarios; but rather, we have to look at the context of what we are dealing with in terms of cardio-renal disease.

How and when should different clinical specialties be engaged?

In 2017, we published a study in Catheterization and Cardiovascular Interventions that looked at modern cardiovascular medicine in terms of acute kidney injury and kidney outcomes in patients with heart disease who are undergoing procedures.¹ We surveyed several thousand cardiologists, asking them a variety of different questions, and one of the key questions was: when you have a patient who is at risk of kidney injury in the cath lab setting, how often do you call a nephrologist for advice before you do the procedure? We found that upwards of 40% of the respondents don’t get nephrology involved. What we learned was that in general, we could do a much better job of collaboration and communication. What I personally have tried to do is to reach out more to nephrologists and to encourage my colleagues to do so as well. As part of the Cardio Renal Connections conference we started, we emphasize that better communication and collaboration is necessary between cardiologists and nephrologists regarding these patients. Often we may be seeing the patient in one given setting, doing a variety of different interventions. We may be partly responsible for kidney injury with our procedures, but then we can’t just sign off and just have the nephrologist pick up the pieces and deal with it. If we work collaboratively, we might be able to get improved outcomes on these patients. We might be better able to inform patients and families of their risks of procedures and benefits, and then have better follow-up by collaborating earlier and more closely. 

What about the involvement of primary care physicians?

A patient with chronic kidney disease may see their cardiologist 2 or 3 times a year; if they have stable heart disease, they may see them 1 or 2 times a year. It’s the same thing with chronic kidney disease — patients may see the nephrologist at 6-month intervals. It is the primary care physician who truly needs to play the biggest role in cardio-renal disease, because they may be the ones screening for diabetes, following the patient’s blood pressure, and preventing further renal damage. Primary care physicians are the gatekeepers and are vigilant about using evidence-based therapy for heart disease. We need the primary care providers to be part of this equation. I think just having the subspecialists involved when the disease gets really bad is not going to work. If we truly want to address cardio-renal disease, the primary care physicians have to be very much involved to mitigate the causative factors.

What do you recommend if someone is interested in raising awareness in their general health system?

The best way is to get physician champions who are interested in the disease interaction of heart and kidney disease. That might mean 1 or 2 nephrologists and a handful of cardiologists sit down and say, first, let’s look at how our patients with heart and kidney disease are doing, whether it’s in the clinic or in the hospital setting. What are our outcomes of acute kidney injury? What are our dialysis rates after cardiovascular procedures? What are our heart failure readmission rates and mortality rates? Physician champions need to come together, define cardio-renal disease as an important problem, look at best practices and evidence-based guidance for protocols, and then work with their clinics or hospital administration to bring about change. 

Can you tell us about the Cardio Renal Connections conference you started?

Back in 2015, I decided we needed to have a scientific forum where experts in the field could come together and share their insights into the interaction between heart and kidney disease. I wanted it to be a forum where nurses, physicians, providers, students, and residents could all attend, and we could start discussing some of these issues. The inspiration came to me after I moved to Texas. I saw a fair amount of chronic kidney disease and diabetes in my prior position in California. When I moved to San Antonio, the diabetes rates were really alarming, and obviously along with that came chronic kidney disease. I would routinely be faced with patients who would say, doc, I don’t want this procedure. I don’t want the stent, I don’t want the angiogram, because if it risks me ending up on dialysis or having kidney injury, it’s just not worth it. Paradoxically or conversely, these very same patients are at the highest risk of dying from their heart disease. Often I was left in a scenario where I had to explain to the patient that their risk of dying from a heart attack was much higher than their risk of ending up on dialysis. To be able to have that conversation with the patient, their families, and my nephrology colleagues, was challenging, because the perspectives were different for cardiology and nephrology, and there wasn’t a lot of common ground. The purpose of the conference was, in part, to bring people together to share their data and their experiences, and come up with some evidence-based recommendations for people with heart and kidney disease. We have several great industry partners, one of which is Osprey Medical. I looked on my end for a nephrology partner. I needed someone who could come together to work with me and bring the nephrology component into the conference. Dr. Shweta Bansal was a colleague of mine active in the cardio-renal space. She has a strong interest in heart failure and the heart-kidney interaction. She has proven to be a very dynamic partner, and has helped co-direct and build this conference. We started talking in 2015 and 2016 was our inaugural conference. 2017 marked our second annual conference. Each year, it has grown. We are now planning our third annual conference. Last year, we had close to 300 participants. Attendees came from our region, from all throughout the United States and as far as Canada, and it has been a mixture of nurses, physicians such as cardiologists, nephrologists, and primary care practitioners, students, and residents. We have had world-renowned speakers each year. The conference covers two days. In 2018, it will be July 20-21, in San Antonio. We divide the conference into focused areas related to disease prevention, including chronic kidney disease, diabetes management and prevention, hypertension management, heart failure and chronic kidney disease and the cardio-renal syndromes, acute kidney injury, and management of renal vascular hypertension. We also discuss renal artery denervation and other cutting-edge areas. 

What are you anticipating for the 2018 conference?

Thus far, our meeting has primarily been a CME and CNE-focused educational meeting. As we begin to grow and evolve, our eventual goal is to add scientific presentations, abstracts, and potentially, late-breaking clinical trials. We anticipate that as the meeting gains national recognition and increased attendance, we will be able to do that. This year, 2018, our focus is going to be on obesity, diabetes, and heart and vascular disease. We will be talking about metabolic syndrome, and how diabetes and obesity influence heart and kidney disease. We are going to talk about amputations and vascular disease in patients with chronic kidney disease, as well as amputation prevention and treatment of patients with peripheral vascular disease. 

Is there anything globally that might parallel your work and population?

Yes, this is a problem in many developed countries, such as England and all of Europe. You can see diabetes and  chronic kidney disease rates rising in places like India and China as well. There is an increasing awareness and interest in heart and kidney disease. We will see that this won’t be an isolated endeavor here, but a broader interest worldwide.

Are there any ongoing trials that are of interest?

Renal denervation was so exciting just a few years ago. It seemed like we would finally have an effective cure for hypertension, and if not a cure, a very robust treatment beyond drug therapy. When renal denervation in SYMPLICITY 3 was put to the test with a randomized, rigorous, controlled trial, involving a background of medical therapy, the results were less impressive. Many people in the field felt like renal denervation was dead. There were a large number of trials that were canceled or put on hold. The next generation of studies is now underway, and the SPYRAL series of studies from Medtronic are ongoing. These studies are very important because they are designed with the knowledge from the previous trials and the trial design, as well as the catheter design, have all been taken into account. The SPYRAL HTN-OFF MED study was published recently.² It was a relatively small study, a randomized, controlled trial that looked at how renal denervation, used in a novel, multifocal ablation technique, would impact hypertension results in patients who had significant but not necessarily refractory hypertension. Patients were off their meds or weaned off their meds for the study. The data were promising, demonstrating that the majority of patients were drug free and had improved blood pressure results. The second set of studies to follow SPYRAL HTN-OFF MED is SPYRAL HTN-ON MED, a study that is ongoing with about 100 patients or so. These individuals will be on their meds, there will not be a wash-out period, and they are going to compare renal denervation against continued medical therapy in this group. If the trial demonstrates a benefit, then we have a chance with a new catheter system and there still might be a place for renal artery denervation. It might encourage other companies and other investigators to start looking again at this technology.

What would be a best-case scenario for cardio-renal disease treatment as we look ahead?

It is probably a three-fold approach. One, if industry recognizes the growing marketplace of diabetes and chronic kidney disease, then the first thing to do is to encourage clinical trials that enroll chronic kidney disease patients. Notoriously, chronic kidney disease patients have been underrepresented in clinical trials. If industry and the government want to get more aggressive with improving outcomes in this context, funding trials that enroll end-stage renal disease patients will also be key. These patients have been excluded from clinical trials, whether it be antiplatelet therapies or transcatheter aortic valve replacement. Second, there is currently not much emphasis on devices or technology to prevent kidney injury. In the cath lab, there are a handful of companies (Osprey Medical, RenalGuard, etc.) that have devoted their efforts to this field, but we need more players involved, particularly the larger companies. Third, we need more basic science and translational research to look at mechanisms of heart-kidney interactions, to look at novel biomarkers, to look at proteomics and genomics, and to see if we can better understand why some patients get kidney injury in the context of heart disease, and some don’t. 

How can nurses and technologists who care for these patients help support this vision?

This issue came up persistently over the last two years as we planned our meeting — we now have two cath lab nurses on our planning committee, and both will be giving talks at the conference. For example, one of the talks our cath lab nurse is giving is “Acute Kidney Injury Prevention and Volume Expansion Protocols: A Cath Lab Nurse’s Perspective.” In many cases, physicians in busy labs may come in, do their procedure, focus on the angiogram, the stent, and closure, and then they are done. But the prevention of kidney injury in the cath lab begins well before the procedure starts. It is appropriate risk assessment and volume expansion with hydration with normal saline, and the nurse plays a key role, because they can identify and emphasize to the physician that this patient is at risk of kidney injury. Nurses can work with the physicians to implement protocol-based hydration before, during, and after a procedure. They can help work with the physician in the hospital to make sure there is adequate follow-up of renal function on these patients. The technologists in the procedure can monitor contrast volume use. They can encourage the physician to consider use of contrast-saving devices. Many times the physician is focused on the procedure and can easily use 100, 200 mls of contrast, and if your technologist or nurse who is next to you is not paying attention, and you are not paying attention, you can exceed the contrast volume threshold for that patient very easily. So our entire staff play a key role in kidney injury prevention. n

References

1. Prasad A, Sohn A, Morales J. Contemporary practice patterns related to the risk of acute kidney injury in the catheterization laboratory: Results from a survey of Society of Cardiovascular Angiography and Intervention (SCAI) cardiologists. Catheter Cardiovasc Interv. 2017 Feb 15; 89(3): 383-392. doi: 10.1002/ccd.26628.
2. Townsend RR, Mahfoud F, Kandzari DE, et al; SPYRAL HTN-OFF MED trial investigators. Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial. Lancet. 2017 Nov 11;390(10108):2160-2170. doi: 10.1016/S0140-6736(17)32281-X.

Disclosure: Dr. Anand Prasad reports the following: research funding: Medtronic, ACIST Medical, Freeman Heart Association; speaking fees: AstraZeneca, Gilead, Abiomed; consulting fees: General Electric, Osprey Medical.

Dr. Anand Prasad can be contacted at prasada@uthscsa.edu.