Amino Acids May Protect Kidneys During Surgery; EDTA for Chelation Therapy

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 tranexamic acid for liver resection, edetate disodium (EDTA)-based chelation therapy, suicidality among spouses of people with cancer, and do amino acids protect kidneys during surgery.

Program notes:

0:41 Amino acids for kidney protection during heart surgery

1:40 Intravenous infusion begun at time of surgery

2:40 May increase blood flow

3:20 Use of tranexamic acid during liver resection

4:20 Blood loss similar

5:20 Can reduce blood loss in seepage

6:00 EDTA chelation therapy in people with diabetes and heart attack

7:00 Either placebo or EDTA over 40 weeks

7:46 Suicidality in spouses of patients with cancer

8:45 Suicide attempt higher

9:45 Within a year after diagnosis

10:45 How to improve screening

11:54 End

Transcript:

Elizabeth: Does tranexamic acid help in people undergoing liver resection?

Rick: Does chelation therapy help in people who have had a heart attack with diabetes?

Elizabeth: What’s the rate of suicidality among significant others of people with cancer?

Rick: And to protecting your kidneys during heart surgery with intravenous amino acids.

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: Rick, how about if we turn right to NEJM and let’s talk about this thing that I thought was extremely intriguing. This notion of, “Gosh, shall we give you what amounts to a supplement of amino acids and does that help protect your kidneys?”

Rick: One of the common complications of any type of heart surgery is actually acute kidney injury. During heart surgery, blood flow to the kidney decreases by as much as 50%. It can precipitate acute kidney injury and that’s associated with increased morbidity and mortality and an increased risk you’re going to need to be on dialysis. There are 22 million people that undergo heart surgery every year worldwide.

There were some pilot studies that suggested that people that take increased amounts of protein or amino acids, it actually increases blood flow to the kidneys. For individuals undergoing heart surgery, if we gave intravenous amino acids, it may actually be beneficial in protecting the kidneys.

They performed a multinational, double-blind trial in individuals who were having cardiac surgery that were going to be on a bypass machine, and they received an intravenous infusion of either amino acids or placebo for up to 72 hours. It started at the time of surgery and it continued until either they got discharged from the ICU or if they needed to be on dialysis.

What they discovered in these 3,500 patients at over 22 different centers is that acute kidney injury occurred in about 32% of those that received placebo and only in about 27% of those that received the amino acid infusion, and it decreased the severity of acute kidney injuries as well. When they looked at individuals that needed to be put on dialysis, there was really no difference between the two.

Elizabeth: There is this notion that somehow proteins — which, of course, that’s what are formed by amino acids — are protective to the kidney. I’m just wondering about the biological basis for that.

Rick: I wish we had some more information. There are two possibilities. One is that the kidneys actually undergo some sort of injury and the amino acids protect that. Or it just may mean that it just increases blood flow. One of the shortcomings of this study is they didn’t assess whether there was actually kidney injury and you’d also like to see if 30, 60, or 90 days later, whether there is any difference. Should this be applied to everybody? The answer is no, not yet. but it certainly is a preliminary study that requires further investigation.

Elizabeth: Well, it also sounds like maybe the mix of stuff that is infused previous to surgery and then followed up afterwards might need to be tweaked a little bit. I would finally note that AKI [acute kidney injury] keeps people in the hospital longer. If it also improves that outcome, it would be worth it.

Rick: Right, so these are the additional studies that need to be done.

Elizabeth: Let’s turn to JAMA and something that does not work. This is a look in surgery at the use of tranexamic acid — that’s a super cheap and easily available medication — in patients who are undergoing liver resection for cancer. This is another study that actually is pretty big, undertaken between 2014 and 2022 at 10 hepatopancreatobiliary sites in Canada and one site in the United States. They had a volunteer sample of 1,384 patients. They ended up having 1,245 participants at the end of the analysis. Tranexamic acid was given to these folks during anesthesia at their induction or they were given a matching placebo. Their primary analysis was, did they require transfusion?

Did they require red blood cell transfusion? Yes, 16.3% of the participants in the tranexamic acid group did receive a transfusion while it was only 14.5% of the folks in the placebo group. Intraoperative blood loss was similar and total estimated blood loss over 7 days was similar in both of these groups. Finally, those participants who received the tranexamic acid had significantly more complications — there were a range of those — compared with the folks who received the placebo.

This is disappointing. We have talked about the use of tranexamic acid in hemorrhage relative to childbirth and talked about how very efficacious it can be. Also, other studies have shown that it is helpful in other situations. The authors basically come to the conclusion that when you have bleeding that they call seepage, not dramatic kind of bleeding, maybe that’s different than that from major vessels, which is what we see when we cut into the liver.

Rick: Yeah. This medication blocks the breakdown of blood clots. When blood clots form in small microvessels, the tranexamic acid can actually reduce the need for blood transfusions and reduce the bleeding, but in large vessels — like what occurs when someone is having a liver resection — or in acute gastrointestinal bleeding, or obstetrical hemorrhage with C-section, tranexamic acid has not been proven to be helpful. In fact, there is some concern that it actually may cause venous thrombosis — a clot — to form in other places where you don’t want it. You can’t assume because something works in some surgeries it works across all different surgeries.

Elizabeth: Exactly, and that’s a good thing because I think that temptation would be quite high to try to apply it in all comers who have bleeding. On to your next one and that’s staying in JAMA.

Rick: Elizabeth, you talked about something that doesn’t work. I’m going to talk about another thing that doesn’t work, and that’s what’s known as chelation therapy.

About 10 years ago, there was a study done in individuals that had recent heart attack. There was a suggestion that giving chelation therapy — that’s a medication that binds minerals like calcium, lead, and cadmium — the thought was, if you gave that, it could leach some of the calcium out of the arteries and the heart, and it could reduce the risk of heart attacks. But the study was done poorly. But it suggested that it could be helpful. If so, it would really be most helpful in those that had a heart attack and diabetes because those are the ones who are most at risk to have another heart attack.

They embarked upon another study, in 88 different sites in the U.S. and Canada, giving either placebo or chelation therapy. Another one is going to look at placebo versus high doses of multivitamins and then the combination of chelation therapy and multivitamins. Well, this particular study just reports on the chelation therapy. There were almost 1,000 participants. They all had a heart attack and diabetes. They were randomized to receive infusions of either placebo or chelation therapy (EDTA) over 40 weeks.

What they discovered is, even though the chelation therapy reduced blood levels of lead and cadmium, it was not effective at all in any of the outcomes — heart attack; it didn’t prevent stroke.

Elizabeth: I wonder if we attempted to do chelation therapy in folks who just originally present with coronary artery disease.

Rick: This therapy is not beneficial in people at a high risk. There is really no reason to believe it would be beneficial in people that are lower risk. It’s not the calcium in coronary arteries that causes heart attacks. There is no good evidence that giving chelation therapy actually leeches that out either. I think this is actually going to put the nail in the coffin for chelation therapy with regard to preventing cardiovascular disease.

Elizabeth: Finally, let’s turn to JAMA Oncology, an issue that I was totally unfamiliar with and it sounds like a lot of other people were also. This was a look at suicide attempt and suicide death among spouses of patients with cancer — I also said [it included] this notion of partner or significant other because this study also does look at those folks.

It was a nationwide cohort study in Denmark. It looked at data from 1986 through 2016. They had individuals who had a spouse with cancer diagnosed in that time period compared with individuals whose spouse did not have a cancer diagnosis during that same period. They identified both suicide attempts and suicide deaths from their national registries, 409,000+ exposed individuals — those folks who had a spouse with cancer — and over 2 million unexposed individuals, so almost a 5:1 ratio relative to those two groups that they compared.

What they found was that cases of suicide attempt among those who did have a spouse with cancer were 62.6 per 100,000 person-years and among the folks who did not have a spouse with cancer it was 50.5. Suicide completion among the exposed individuals was 16.3 per 100,000 person-years while the unexposed was 11.4.

Clearly, the outcome of this is, “Hey, we really need to be assessing what’s going on with the spouses of patients with cancer,” especially if this was true in the first year after the cancer diagnosis, and some of the other social determinants also impacted that. Folks with higher incomes, for example, or greater education had less of an impact relative to suicidality when they had a spouse with cancer.

Rick: I agree with you. This is the first time I thought about it. Think about individuals that receive a diagnosis and you don’t think about how it affects the spouses as well as — at least I hadn’t until this. The fact that the suicide rate is higher in individuals within a year after their spouse has been diagnosed. It’s higher in those that have metastatic disease. The suicide risk is about 50% higher in individuals whose spouse has a cancer versus those without.

Here is the thing that’s even more sobering. This study was done in Denmark. Denmark has a high literacy rate, high income, and universal healthcare. If this happens in those circumstances, one can imagine in more limited circumstances where the rate could be and should probably be even higher there. Paying attention to not only the person that received the diagnosis, but screening their spouses as well, I think, is essential.

Elizabeth: I agree with that. I would also point out that the editorialist talks about the role in caregiving for the patient that the spouse is expected to really perform. If that person is depressed or is at risk for suicide, that’s an important thing for the patient also.

This notion of screening spouses, though, I’m wondering: we are not terribly good at screening everyone just in general for rates of depression and potential suicidality. I’m wondering about the resources that would be necessary in order to do that screening and then to actually provide some sort of service relative to it.

Rick: Yeah. No, it will clearly put an additional strain on an otherwise burdened system. What I would say is that in places where the screening is already done on the patient that receives a diagnosis of cancer, it would make sense to do it on the spouse at the same time, and then we can plug that spouse into either counseling or group sessions. Over the next 15 years, there are going to be 26 million people living with a diagnosis of cancer. It behooves us, if we’re going to care for that patient, to care for their spouse as well, who will be caring for that patient.

Elizabeth: 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.