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Dr. Janani Rangaswami on Cardiovascular Risk Reduction in the Patient with Nephropathy

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Dr. Janani Rangaswami presented the research at the 78th Scientific Sessions for the American Diabetes Association(June 22–26) in Orlando, FL.

Doximity discussed the research with Dr. Rangaswami at ADA 2018. Below is a transcript of the video interview.


Doximity: What is the newest or most important clinical understanding of reducing CV risk in Nephroathy?

Rangaswami: I think it's such a wide-open topic, but if you want to zoom in on a couple of really important innovations, I think we can look at it in two ways.

One is what have we done traditionally so far that has brought us up to this point, like diabetes control itself, blood pressure control, lipid control, and so forth. On that note, there has been a lot of recent interest in what are optimal blood pressure targets. There have been conflicting results from major clinical trials. One in diabetes known as the ACCORD Trial, which showed that very tight blood pressure control with a systolic blood pressure of less than 120 millimeters surprisingly did not really protect the heart and heart related bad outcomes.

Now, when you look at it in patients who are not diabetic_-the SPRINT Study-_showed the opposite, wherein they accrued significant benefits when blood pressure was more tightly controlled.

When you try to look at this data altogether, what emerges is [the result that] tight blood pressure control appears to be beneficial, but in the right patient. We choose the right patient by trying to assess what the impact is on the ability of the kidneys to filter in patients with pre-existing kidney disease, which may be impaired, and if we identify the right subset of patients then blood pressure control becomes a little more manageable.

In terms of the development of novel anti-diabetic agents, there are classes of drugs, such as the SGLT2 inhibitors and the glucagon-like peptide receptor agonists, that have shown promise in terms of reducing not just heart related risks, heart failure related risks, etc. But they also independently seem to protect the kidney and have a benefit in terms of slowing down kidney damage_-_which, I think, is very exciting news for the very vulnerable patients that experience a combination of diabetes as well as chronic kidney disease.

Doximity: What is the most significant learning from your presentation that you want other physicians to know?

Rangaswami: I think the audience should understand the diabetic patient with chronic kidney disease represents the highest risk. Both these diseases amplify the cardiovascular risk of each other.

Many proven therapies that are seen in the general population where diabetics cannot automatically be pulled into the patient with chronic kidney disease and you can't expect them to have the same efficacy. This has been shown in multiple cardiovascular trials wherein patients without kidney disease, a certain therapy may work great. [Yet] the moment you try it in a patient with kidney disease the results don't look so impressive.

However, what is really nice is even with drugs such as the SGLT2 inhibitors, while you can use them in patients with very severe kidney disease, in patients with mild to moderate kidney disease they actually appear to work.

There was a study in circulation in 2018 by Christoph Wanner's group that showed that in EMPAREG OUTCOME, which is one of the big cardiovascular outcome trials, when you look at the patients with kidney disease in particular they accrued the same benefits. [This] is very exciting because chronic kidney disease patients who traditionally excluded from just about every cardiovascular trial finally we're beginning to offer them some novel therapies that may actually change not just the risk for heart disease, but also their own kidney disease progression.

Doximity: How do you see risk reduction changing in the future?

Rangaswami: I think we are kind of moving away from just offering what are called traditional risk reduction, such as controlling diabetes itself or controlling blood pressure. We're now moving towards using some of these novel anti-diabetics for primary risk reduction in heart and in kidney disease. They're even pushing it to see it if this is applicable even in non-diabetic patients [and] in patients that have known elevated heart and kidney risks.

I think we're going away from just saying what is this patient's a1c or what is their blood pressure or what is their cholesterol. [We are] looking at mechanisms of prevention, focusing on how these drugs target the kidney and heart tissue, [taking] that as the primary focus with the metabolic benefits almost being a secondary aspect, and [offering] them to patients at the highest cardiovascular and kidney risk.

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