COMMENTARY

What to Know About New Hypertension Guidelines in Chronic Kidney Disease

Ileana L. Piña, MD, MPH; Peter A. McCullough, MD, MPH

Disclosures

April 13, 2021

This transcript has been edited for clarity.

Ileana L. Piña, MD, MPH: Hello. I'm Ileana Piña, professor of medicine at Wayne State and at Central Michigan University. I'm a heart failure transplant cardiologist, and this is my blog. We often have interesting guests to talk to us about topics of wide interest. I'm really happy today to have my good friend, Peter McCullough, who is a professor of medicine at Texas A&M School of Medicine, to talk a little bit about other guidelines — not the guidelines that I usually talk to you about, the American Heart Association/American College of Cardiology guidelines. These are the KDIGO guidelines, which I didn't know existed until a few years ago. Thank you to Dr McCullough.

Dr McCullough is a rare species who has really combined in his research interests not only heart failure, but also the kidney. So when I have these questions, Peter is the person I go to. Peter, welcome to the blog and thank you for your time. Tell the audience what KDIGO is.

Peter A. McCullough, MD, MPH: Ileana, thanks for having me. KDIGO stands for Kidney Disease: Improving Global Outcomes. KDIGO is a not-for-profit entity that was spawned by the National Kidney Foundation and centered in Europe, outside the United States. They are charged with holding controversies conferences, which are largely to identify gaps in knowledge, and then put together guidelines bodies that span the entire scope of acute and chronic kidney disease.

Piña: We were together at a KDIGO conference in Greece several years ago with the controversy of heart failure and kidney disease, something that cardiologists battle with — as in, "I've got to call the nephrologist because creatinine went up." We had a publication come out of that that I thought was really very reasonable. But what are the more important guidelines that you could refer our primary care audience and our general cardiology audience to look at?

McCullough: I think the most highly cited guideline is the 2012 KDIGO acute kidney injury (AKI) guideline. This was the first guideline that set the terminology at "acute kidney injury." It used to be called acute renal failure or acute renal insufficiency.

Piña: That's what it was called when I was in fellowship.

McCullough: It's now AKI, as of 2012. It set the stages of AKI: stage 1, 2, and 3. Stage 1 is a rising creatine greater than 0.3 mg/dL. Stage 2 is a doubling of serum creatinine. Stage 3 is a tripling of creatinine or going on dialysis. So it set the stages of AKI and gave us a framework for research. I personally think the AKI guideline was a little premature for clinical practice. And when you round in the hospital, now all the residents want to tell us that everybody has an AKI.

Piña: They also use the term CKD very freely without applying the definitions. Recently I have seen the hypertension guidelines. What drove a hypertension guideline? I'm always fascinated by the fact that we've been talking about hypertension since I was a fellow. It wasn't big on the radar of general cardiologists; we relegated it to the nephrologist. And yet we know — and I want to remind my audience from the SPRINT trial — that if you really reduce that blood pressure as low as 120 mm Hg, you will reduce heart failure incidence by about 50%, something we've been saying for years. Now we have the data that actually show this and how it works in the older patients as well as in the younger patients. So why now hypertension guidelines?

McCullough: Let me just say that I completely agree that the blood pressure–sensitive outcomes in our field are stroke and heart failure. A lot of people don't know this; they think it's coronary heart disease, and it's really not. The controversy in kidney disease is that as kidney disease worsens the kidney disease itself raises blood pressure. So there really was a controversy of whether or not blood pressure control, conversely, can help the natural history of kidney disease. This guideline updated over 200 studies and found that in patients who have a reduced estimated GFR less than 60 mL/min/1.73 m2 and begin to have albumin in the urine, and an albumin-to-creatinine ratio greater than 30 mg/g, that in fact, these patients do benefit from a lower blood pressure, as we knew from the SPRINT trial for heart failure and stroke.

Now in the update, instead of a target blood pressure of 130/85 mm Hg, the target blood pressures is 120/70 mm Hg. KDIGO always had a big push for ambulatory blood pressure monitoring for better diagnosis and management of hypertension, particularly in those with kidney disease. So there are some targets there. But the big news for cardiologists is that we really need to measure the albumin-to-creatinine ratio. And if we need any further evidence that we need to go lower with blood pressure, that measure — which many cardiologists don't measure — really can help us.

Piña: Yeah, it should be part of the standard routine when you're bringing the patient in and you're doing everything else — you're getting their NT-proBNP, for example. It's such an easy test to do, but it's so telling. So, in this guideline, are there recommendations for specific drugs?

McCullough: The RAS (renin-angiotensin system) inhibitors have always been the featured drugs, and they are recommended. For type 1 diabetes with kidney disease, it's the ACE inhibitors. With type 2 diabetes and kidney disease, it's the ARBs because of the clinical trials. The guidelines have not yet taken on SGLT2 inhibitors or the combination of sacubitril/valsartan. Those are really more cardiovascular/cardiorenal applications.

Piña: Yet, whenever the creatinine bumps up, the cardiologists remove the RAS inhibition, from this fear of "Oh, I'm killing the kidney." I think in that conference, we very nicely showed where the data are, and the data are just not there. On the contrary, it's protective.

McCullough: This is probably the single greatest teaching we could ever impart to our colleagues. This stopping the ACE inhibitor, ARB, or the neprilysin inhibitor, or holding it because of an azotemia arise in BUN creatinine, is the biggest mistake any inpatient doctor — or even an outpatient doctor — can make. We should manage patients through the azotemia. There are over 20 published studies that show that when we do this, we hurt the patient, we set the patient backward, and yet that's the very first thing we see in a nephrology consultation or a cardiology consultation. We need to be able to manage patients through azotemia, provided that blood pressure's okay and provided that potassium is manageable. We cannot get faked out with changes in BUN creatinine. Let me say one more thing — I started out with the KDIGO guideline in heart failure. When the BUN creatinine goes up in the absence of sepsis and the absence of shock, it's not AKI; it's what we call worsened renal function, which is a transient hemodynamic change as reflected in the BUN creatinine.

Piña: Right. And in the DOSE trial of Mike Felker, it actually showed that that creatinine bump had no association with increased bad outcomes — mortality, hospitalization. And yet it's being done; it's what our residents learn, and they do it the minute the patient gets into the hospital.

When you go back to SPRINT, it was very interesting to me that in SPRINT they gave a list of medications, but they made no recommendations about what drugs to use. It was left up to the investigator. So I think the point is that we have so many different drugs that work, that can lower blood pressure effectively, many of them generic, which are incredibly cheap. I know enalapril is about $4 for 2 weeks at a place like Walmart or a big grocery store. But, the drugs are just ordered without a sense of a plan. I still think that we need to recommend to our audience that you have to have a plan of what you're going to do. You start off with a drug; you may want to uptitrate that one a bit before you start the other one, but don't give up and don't tell me that a blood pressure of 140 mm Hg every visit is okay, because it's not okay.

McCullough: Just a couple of points: You know the RAS inhibitors are featured; for patients with coronary heart disease, beta-blockers clearly have a role. Remember that the genesis of hypertension is sodium retention. About 80% of African Americans, probably 40% of Caucasians, are salt sensitive. So, the use of a diuretic — not really to cause diuresis, but to actually cause some sodium excretion — makes the body much more responsive to the blood pressure drugs that we have in the program. It's common for patients to need two or three drugs, provided that one of them is a diuretic.

Piña: Part of my teaching of my residents is that I've always said if you have an African American patient with severe blood pressure, until you put them on that thiazide drug, you're just not going to get that blood pressure down all the way, and that it really, really works.

Now, I want to switch over to another point that you made, a very good point, about ambulatory blood pressure monitoring.

McCullough: I was on the very first KDOQI, or Kidney Disease Outcomes Quality Initiative, hypertension guidelines, I think over 20 years ago. I was so impressed with the Europeans, who already had in their guidelines that one needed ambulatory blood pressure monitoring in order to establish the diagnosis of hypertension. It clears up this whole issue of white coat hypertension and all the confusion with patients trying to keep their BP logs. So I'm strongly in favor of it. What the listener needs to know is that when we use ambulatory blood pressure monitoring, we have standards for daytime blood pressure, which is a bit higher. We want to see a nocturnal dip in blood pressure, and overall we want to see 5-10 mm Hg points lower on the mean, as we would in a seated blood pressure in the office.

Piña: As we move on with this chapter, I really want to emphasize the fact that blood pressure doesn't necessarily belong to the nephrologist; it belongs to every specialty, including primary care. And primary care has the privilege of seeing patients very early, often before we see them. Blood pressure targeting, even in the young— when I'm asked, "What do I need to do to keep my health?" I tell them, "Know your numbers, know what your blood pressure is. Have somebody take it." Right now, with the pandemic, a lot of these blood pressure machines in CVS or Walgreens have been covered up because everybody's afraid of the pandemic. But that's very useful: You're shopping, you're in CVS, you stick your hand in there, you get a blood pressure. At least it gives you a sense of a range. We can't just relegate this and say, "Oh, it's a nephrologist issue." No. Every single one of us has to pay attention. We would lower cardiovascular disease so significantly if we could only do that. We could probably eliminate stroke even because most of the stroke parameters happened to be hypertensive.

Anyway, Peter, any parting messages that you'd like to give our audience?

McCullough: I think the future's bright. The single greatest challenge I have with a young person is the recognition that a chronic medication would become part of one's life. When we look at registries of seniors, people over age 80, only 10% of people can make it to over age 80 requiring no medicines; 90% of us need some medicinal aid. It's very common that blood pressure lowering is one of those medicinal aids, and it's a matter of finding something where there can be basically a lifelong relationship between the patient and the medication to keep that blood pressure in a healthy range.

Piña: Getting your medical history of your family is equally important because there's a lot of genetic transmission.

Peter, I want to thank you for joining me today. That was great information. And to you, listeners, I hope that this information is good for you in your office and your practice. This is Ileana Piña, signing off. I hope to see you again soon.

Ileana L. Piña, MD, MPH, is a heart failure and cardiac transplantation expert. She serves as an advisor/consultant to the FDA's Center for Devices and Radiological Health and has been a volunteer for the American Heart Association since 1982. Originally from Havana, Cuba, she is passionate about enrolling more women and minorities in clinical trials. She also enjoys cooking and taking spin classes.

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