Spotlight on Non-Steroidal MRAs for Diabetes-Related CKD

Announcer:
Welcome to Diabetes Discourse on ReachMD. On this episode, sponsored by Bayer, we’re discussing non-steroidal mineralocorticoid receptor antagonists, or MRAs for short, and their impact on the treatment of chronic kidney disease and type 2 diabetes with Dr. Mikhail Kosiborod. Not only is he a Cardiologist and Vice President of Research at Saint Luke’s Health System in Kansas City, Missouri, but he’s also a Professor of Medicine at the University of Missouri-Kansas City. Let’s hear from Dr. Kosiborod now.

Dr. Kosiborod:
Well, I think the nonsteroidal MRA therapy has an important role in the management of patients with diabetes-related chronic kidney disease. First of all, it’s important to keep in mind that patients with diabetic kidney disease are at high risk for a number of deleterious events over a relatively short period of time. Probably the most important risk that these patients experience is that of adverse cardiovascular events. And that’s the risk of both atherosclerotic cardiovascular events or other traumatic events like myocardial infarction and stroke, but they’re also at very high risk of developing heart failure and requiring hospitalization for heart failure as well. And if you actually look at the natural history and what happens to patients with diabetes-related CKD, the biggest risks by far are adverse cardiovascular events like the ones I just mentioned. And then of course the second big risk is progression of kidney disease and everything that comes with that.

So what do we have currently in terms of efficacious therapies that we know can make a positive impact in that regard? We, of course, have the renin angiotensin blockers, so that’s ACE inhibitors, and angiotensin receptor blockers, and they’ve now been a mainstay of treatment in patients with diabetes-related CKD. We know that sodium-glucose cotransporter-2 inhibitors, or SGLT2 inhibitors, provide a significant and substantial additional benefit on both reducing the risk of cardiovascular events, especially heart failure hospitalizations and progression of kidney disease, even in patients already optimally treated with ACE inhibitors and ARMS. And so now, we also have data on nonsteroidal MRAs, such as finerenone from the FIDELIO and FIGARO trials. And the reason that both of these trials are so important is because they address those two key priorities in terms of cardiovascular and kidney disease complications in this patient population, which is what drives morbidity and mortality and poor quality of life in the long term.

So the FIDELIO trial clearly showed a benefit from the standpoint of slowing down and preventing the progression of diabetic kidney disease in a meaningful way, and the FIGARO trial showed cardiovascular benefits, especially when it comes to reducing the risk of hospitalizations for heart failure.

The mechanism of action of nonsteroidal MRAs is important, and of course, as you can glean from the name of these agents, like finerenone which is a nonsteroidal MRA, what these agents do is block the aldosterone receptor. And aldosterone is the hormones that can have a number of noxious consequences both for the heart and the kidney, especially promoting fibrosis and inflammation. And fibrosis and inflammation can have deleterious effects on the progression of both heart and kidney disease, especially when it comes to heart failure and specifically heart failure with preserved ejection fraction on the cardiovascular side of the equation and progression of kidney disease on the kidney disease side of the equation. So nonsteroidal MRAs truly appear to be cardiorenal drugs in that regard, and it’s important to point out that this mechanism of action—interfering with aldosterone receptor and inhibiting the noxious effects of aldosterone, specifically inflammation and fibrosis—is distinct and complementary to other disease-modifying therapies that have been proven to be beneficial in the diabetes-related kidney disease space, such as renin angiotensin blockers and SGLT2 inhibitors.

I think nonsteroidal MRAs are going to really have an important role in patient management and over time be incorporated into these pillars of foundational disease-modifying therapies for this vulnerable patient population.

Announcer:
This episode of Diabetes Discourse was sponsored by Bayer. To access this and other episodes in this series, visit ReachMD.com/Diabetes Discourse, where you can Be Part of the Knowledge. Thanks for listening!