George Bakris, MD: CREDENCE Study Delivers on Diabetes Focus

Much of the focus at the American Society of Nephrology (ASN) Kidney Week in Washington, D.C. has been on the CREDENCE study, a landmark trial showing that canagliflozin could help diabetic patients suffering from kidney disease.

George Bakris, professor of Medicine, University of Chicago Medical Center, said in an interview with MD Magazine® the study comes at a good time with an increased push to treat diabetic patients with kidney disease.

MD Magazine: What will the patient impact of the CREDENCE study be?

Bakris: So, CREDENCE is the only study of this SGLT2 inhibitor class in people with advanced kidney disease. It's unique in that regard.

And not only that, it's the only 1 that has gotten an FDA label for not only kidney protection, but also for a slowing heart failure or reducing heart failure events.

So, it's really unique in that regard. It has also taught us a lot about how these agents work in people with advanced kidney disease.

A lot of the early agents because they were done in people with better kidney function, actually thought to be a mild diuretic and glucose lowering agent and turns out they're really cardio renal risk reducing agents with glucose lowering is a beneficial side effect.

Because when you get the GFRs down to levels of 25-30 as was examined in this trial and the bottom line was that you got no glucose reduction and at the same time you got the same benefit that you got when you got glucose reduction.

Of course, it's not surprising because we have heart failure data from the DAPA-heart failure study showing that if you don't even have diabetes you've got protection from this class of drugs.

So, it's not the diabetes that that's really driving this or the glucose lowering, it's other mechanisms. At this meeting, we did a lot of deep dive sub-analyses and looked at the subsections of GFR and we looked at stage 3a, stage 3b CKD.

There's actually late breaker that I presented looking at the subgroup of people that came in with a baseline of less than 130 GFR. That was 174-patients that had the screening visit above 30 of a GFR because that was the inclusion criteria.

Then when the baseline data came the GFR were lower. In fact, the average was around 27, so those people were followed just like everybody else was in a trial.

This dip in GFR that you see or has been come to be known with this class was not seen. There was no reduction hemoglobin A1c and yet the decline in kidney function was the same as the trial overall, heart failure benefit was the same as the trial overall.

Clearly this was another sign that this is not a glucose lowering agent, that its effects are independent of that. The other thing that's interesting was that blood pressure fell to a greater extent than what you saw in people with healthier kidneys and even in the group that had GFR's that were around 60 in the trial.

The question is why is that and there's a study that was not presented here, but it's in press showing that this class of drugs actually causes the type of renal denervation and actually reduce the sympathetic tone and increases nitric oxide. You may hear about that at heart failure meetings or the cardiology meetings.

MD Magazine: Are there any kidney diseases that have been neglected in research?

Bakris: I think the biggest gorilla in the room is diabetes and a lot of work is being done in that area. There's a lot of work being done in focal glomerular sclerosis, which pales in comparison to diabetes.

If you're looking at your numbers of people that have problems, a lot of the kidney diseases are relatively rare relative to diabetes and hypertension.

So, there's a lot of work going on, there there's work going on in other rarer diseases. Polycystic kidney disease is actually a very common disease relative to the other kidney diseases and there's a lot of work going on there.

But there's been no real breakthroughs the way there have been now for diabetic kidney disease.