Diabetes Med for Kidney Stones? Exercise and Heart Failure

TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine in Baltimore, and Rick Lange, MD, president of the Texas Tech University Health Sciences Center in El Paso, look at the top medical stories of the week.

This week’s topics include catheter material for peripherally inserted central catheter (PICC) lines, a diabetes medication for kidney stones, driver mutation clearance and relapse prediction and exercise and heart failure.

Program notes:

0:44 Exercise and heart failure

1:44 322 patients with heart failure and normal ejection fraction

2:45 What percentage continued?

3:30 Kidney stone prevention with empagliflozin (Jardiance)

4:30 Once daily followed by placebo

5:30 Also effective in heart failure

6:30 Also in gout?

6:40 Driver mutations in myelofibrosis

7:42 Tested blood for mutations in blood

8:42 Looking for driver mutations for other cancers

9:05 Materials for PICC lines

10:05 Rates of device failure

11:05 Clots or infection possible

12:24 End

Transcript:

Elizabeth: Can a medicine used for diabetes help people avoid developing kidney stones?

Rick: Can exercise improve outcomes in people who have heart failure with normal heart function?

Elizabeth: Does it matter what kind of materials we use for central catheters?

Rick: And predicting outcomes in individuals that have a certain type of bone marrow cancer.

Elizabeth: That’s what we’re talking about this week on TTHealthWatch, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I’m Elizabeth Tracey, a Baltimore-based medical journalist.

Rick: And I’m Rick Lange, president of Texas Tech University Health Sciences Center in El Paso, where I’m also dean of the Paul L. Foster School of Medicine.

Elizabeth: I am going to toss the ball to you for our inaugural 2025 issue, exercise and heart failure — it seems like it ought to be a good thing — and that’s in Nature Medicine.

Rick: It should be a good thing. Heart failure is a major public health burden and there are approximately, oh, gosh, almost 7 million people in the United States that had heart failure between 2017 and 2020. Half of these individuals have heart failure because the heart is not pumping adequately. They have a decrease in the ejection fraction, that is, the amount of blood that’s pumped out with each heartbeat. But the other half have normal ejection fraction and that usually indicates that the heart muscle doesn’t relax as well. It’s somewhat stiff.

If you take these people with heart failure and normal heart function, and put them on an exercise program for 12 months, where they do both endurance training, bicycle exercising 3 times a week for 60 minutes, and then throw some weight lifting in 3 times a week as well, will that actually improve their overall outcome, whether they die or not? Are they hospitalized for heart failure? What is their exercise capacity and globally how are they doing?

These investigators took 322 patients that all had heart failure with normal ejection fraction and randomized them to just doing the usual care or to exercise over a 12-month period. There really wasn’t any significant improvement at all. How much exercise were they able to obtain, peak oxygen consumption, and how did they feel? Maybe a slight improvement, but overall kind of disappointing news, Elizabeth.

Elizabeth: Very disappointing news and I’m especially interested in the quality-of-life measure, where they didn’t actually feel better.

Rick: If you ask whether they felt better, they did. If you actually tried to do objective measurements, there really weren’t any significant changes there at all. If you said, “Do you feel better?” Yes, they did. But it didn’t change any of the hard outcomes related to the heart failure.

Elizabeth: Would you speculate that this might be because this strategy wasn’t employed early enough in the development of heart failure?

Rick: A couple of possibilities. One is the fact that these individuals — maybe exercise doesn’t really benefit the overall major heart-related outcomes.

What percentage of people were able to continue and complete all of the exercise program? It was really only about half the individuals. The adherence really wasn’t very good. Is that because the people weren’t motivated? Is that because they had symptoms and couldn’t complete it? It’s hard to know. The fact that adherence was less than 50% tells me that it may not be everything it’s cracked up to be in this particular patient population.

Elizabeth: I would beg that question again: does it suggest that this ought to be employed earlier in the course of the development of heart failure, which, as we know, normally takes quite a while.

Rick: Yep. Elizabeth, it’s hard to know. The average age of these people was 70 years of age. Your point is well taken. They weren’t terribly symptomatic and they hadn’t been terribly symptomatic for a long period of time. If you initiated it earlier, would it help? We need to study that.

Elizabeth: Well, let’s move on to our other study in Nature Medicine and another very common health problem, and that’s kidney stones.

Kidney stones, I learned — the prevalence has risen worldwide in recent decades with a current lifetime risk of almost 20% in men and almost 11% in women. There is a frequent relapse rate that’s seen, with a 10-year recurrence between 30% and 80%.

Now let’s turn to our medicine, which is empagliflozin, an SGLT2 inhibitor, the sodium glucose cotransporter-2 inhibitor that’s used for folks with diabetes. In this study, this medicine was used for kidney stone prevention in non-diabetic patients. This is a phase II double-blind, placebo-controlled, single-center crossover trial with 53 adults with calcium or uric acid kidney stones and at least one previous stone event without diabetes. They were randomized to once-daily empagliflozin 25 mg followed by placebo or the reverse. These stones, of course, were either calcium oxalate or uric acid.

Interestingly, what they did was look at these primary outcomes, which were urine relative supersaturation ratios for calcium oxalate, calcium phosphate, and uric acid, which is a validated surrogate for stone recurrence.

Sure enough, it really did help. In patients with calcium stones, it reduced these parameters that they measured as surrogates by 36% and in those with uric acid stones it did it by 30%. They also did not show a lot of adverse events relative to taking this medicine. Now, admittedly, for a short period of time, only 2 weeks, it sounds like a pretty good outcome to me.

Rick: This drug is used primarily to treat diabetes and in the studies that we’ve talked about before it’s effective in reducing hemoglobin A1c levels. We know it’s also effective in treating people who have heart failure. Now, it can improve some of the parameters associated with kidney stones. The reason why it was even tested in this population is because when it was used in diabetes the individuals that took it had less recurrence of kidney stones and there is some biologic plausibility of why that could be. This is really good news. We need to do longer-term studies.

Elizabeth: I absolutely agree. Interestingly, they suggest that mechanisms might include anti-inflammatory effects, which we’ve talked about with regard to these medicines before. To me, it kind of begs this whole question about metabolic syndrome, which we know one of the hallmarks is inflammation. I’m just wondering about how this all works. Of course, we’ve been quipping about some of these diabetes meds and putting them in the water because they have such profound global effects.

Rick: It could be anti-inflammatory. It also increases the excretion of uric acid, fewer stones forming inside the kidney if you can get rid of it in the urine. My question is would this also be useful in people with gout, for example? Because we know that that’s associated with an increased amount of uric acid in the bloodstream, and if we can excrete that more, we may be able to use it for another indication.

Elizabeth: Let’s turn now to the New England Journal of Medicine, this notion of driver mutations in myelofibrosis.

Rick: This is a bone marrow disorder in which there is excessive scar tissue that forms in the bone marrow and it disrupts the production of blood cells. This fibrosis causes a decrease in all of those cells. People get tired. They have difficulty breathing. They bruise easily. It can ultimately be fatal.

It’s driven primarily by 3 different mutations: JAK2 mutations, which occurs in about three-fourths of individuals; about a fourth have what’s called a CALR mutation; and about 4% have MPL mutations. It doesn’t respond well to chemotherapy. Almost all these patients have to undergo bone marrow transplantation.

We try to predict who is at higher risk of relapsing by which mutation they have, because those individuals at higher risk, we’re more likely to give them a higher dose of chemotherapy in the very beginning. Is there a better way of trying to decide who will recur?

They took individuals that are going to be treated with myelofibrosis with bone marrow transplant and then they tested their blood, seeing if these mutations recurred in the blood. We now have machines that can, with a high sensitivity, detect these three mutations and they were able to detect them at 30 days in the bloodstream.

What they discovered was if they were unable to detect them, over the course of the next year the relapse rate was about 6%. If they were able to detect them at 30 days, the relapse rate was about 21%. The same thing at 60, 120, and 180 days. This was a better predictor of outcome than any of the single mutations.

What this will allow us to do is very early on to determine whether someone is likely to relapse and, perhaps at that point, begin to intervene in those individuals. Those that aren’t going to relapse, it’s just to continue them on their course.

Elizabeth: Well, it’s really great that this is something that can be detected in the peripheral blood, so it doesn’t require a bone marrow aspiration, which nobody enjoys having that. I think that this is tantalizing in looking for driver mutations for other forms of cancer, and particularly I think this is going to point the way toward that.

Rick: Right, and so there are other bone marrow cancers besides myelofibrosis — we’re thinking about things like leukemia. The question is, will detection of driver mutations in the bloodstream after they have been treated also predict outcome? Hopefully, additional studies will follow from this.

Elizabeth: Our last one, of course, is also in the New England Journal of Medicine. This is something that I bear witness to a lot: PICC lines, the peripherally inserted central catheters that people get sometimes when they are in the hospital. When they’re going to need to have infusions of various things, they place this thing to make that a lot easier for everybody concerned — not just for the clinicians, but also for the patients.

For this study in Australia, they were looking at, does it make a difference whether we have that catheter made out of a hydrophobic material, the catheter be coated with chlorhexidine as an antibacterial, or a standard polyurethane? They had adults and children who were referred for PICC line placement. They randomized them into these three groups to receive it.

Clearly, what they were trying to do was avoid device failure due to infections, thrombotic events, and catheter occlusion events. There were around 365 in each one of the groups. They looked at rates of device failure and these other outcomes that I described.

Basically, what they found out was that there really wasn’t much in the way of difference between the hydrophobic catheter and the standard polyurethane catheter. It turned out that some of the outcomes for the chlorhexidine group were actually worse than they were for the other ones. It’s sure looking like standard polyurethane PICC lines are probably just perfectly fine.

Rick: For our listeners that may not be aware, you described the PICC line — these are people that need to have some intravenous infusion, chemotherapy or antibiotic, or some other agent that you don’t want to put into just a vein in the arm because either it can irritate or damage the vein, or because the patient may need to have an IV infusion for weeks or months.

They put in a long line. This about a foot to a foot and a half long. It goes kind of through the veins in the arm, but it circulates all the way up into the more central circulation, closer to the heart. The long-term consequence of that is people can develop clots on them or people can develop an infection. These newer catheters with these coatings were trying to prevent those things, but as you highlighted it doesn’t look like they prevent them at all. We don’t want to be putting in through a PICC line that has a higher complication rate, as you mentioned the one with chlorhexidine. This is a really well-done study in over 1,100 patients and I’m glad they did it.

Elizabeth:A priori I think we would have all assumed that, sure, chlorhexidine will be a great thing to put in there to reduce the rates of infection relative to these devices. Sure enough, it was not. In fact, it was significantly worse. I’m very glad they actually tested it.

Rick: The other thing that does is it looks at the patient population and says, “What are the complications from these PICC lines?” It ranges between about 20% of them experienced a complication over the 8 weeks that they had the line in and, with the chlorhexidine, as much as almost 40%. They are not innocuous. We have to be very fastidious about how we take care of them and make sure that there is a proper indication for them in patients.

Elizabeth: Exactly. More of that welcome.

On that note then, that’s a look at this week’s medical headlines from Texas Tech. I’m Elizabeth Tracey.

Rick: And I’m Rick Lange. Y’all listen up and make healthy choices.