Hypertension After Kidney Donation; Statins in Old and Very Old People

— Also in TTHealthWatch: fluoride's effect on pregnancy outcomes

Ƶ MedicalToday

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 fluoride in pregnancy and outcomes in children, contagion of mental illness, statins in old and very old people, and hypertension after kidney donation.

Program notes:

0:48 Statins in old and very old

1:48 Increased risk for muscle pain or liver disease

2:48 Started on a statin


4:22 Increase in biomarker results in increased issues in kids

5:20 Parents score behavioral issues

6:16 Hypertension after kidney donation

7:18 Does hyperfiltration compromise?

8:19 Liver attempts to regenerate

9:10 Are mental health issues transmissible?

10:10 713,000+ in cohort

11:10 These issues cluster

12:10 Normalization of mental disorders

13:17 End


Elizabeth: What's the relationship between maternal exposure to fluoride during pregnancy and outcomes among children?

Rick: Is there increased risk of hypertension in adults who donate a kidney?

Elizabeth: Is mental illness contagious?

Rick: And should we be giving statins to old and very old individuals?

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 to Annals of Internal Medicine, this idea of should we continue to give statins to very old people?

Rick: We have decades now of studies that have looked at giving statins for primary prevention of cardiovascular disease -- that is, people who don't have cardiovascular disease, but they have risk factors, things like diabetes or elevated cholesterol. We know that statin therapy is very beneficial in these individuals. It lowers the risk of heart attacks; it lowers the risk of stroke; and it improves survival.

But most of those studies didn't include old or very old people. Now, when I say "old" I'm talking about people 75 to 84 years of age -- and for "very old," more than 85. By the way, that's the definition in this paper; it's not meant to offend anybody. But there are very few studies that have included them.

What these investigators attempted to do to answer this question is they looked at public electronic medical records in Hong Kong and they found a group of individuals who were old and very old, who had indications for primary prevention of cardiovascular disease, some of whom received statins and some of whom did not. Did they benefit from statins? Secondly, because of their older age, were they at increased risk of developing things like muscle pain or liver disease?

What they found is, even in the old and very old, there was a significant benefit for reduction of cardiovascular disease. What they discovered was, if you're going to try to prevent one cardiovascular event in the old individuals, you needed to treat 20 individuals. That's a pretty good number. In those 85 years or older, you just needed to treat eight individuals for 5 years to prevent one cardiovascular event.

Was there an increased risk of muscle pain or tenderness, or an increased risk of liver complications? The answer is no. As you and I have talked before is now they are pennies, is what the cost is. The benefit is pretty substantial and the risk is nil.

Elizabeth: That's a great outcome. How about are these new prescriptions for statins or had these people been on them for a long time and merely aged into these categories?

Rick: That's a great question, Elizabeth. These were individuals who had not been on a statin. They were started on a statin over the age of 74.

Elizabeth: I'm reminded, of course, of the anti-inflammatory properties of statins. Would you suggest that that's the mechanism by which this happens?

Rick: I think that probably is. I mean, at that particular point, you're not long-term preventing atherosclerosis, but you're preventing the inflammatory condition that causes those atherosclerotic plaques to become unstable that lead to a stroke or heart attack.

Elizabeth: It sure sounds like we might be back into that place where we've quipped, "Gosh, are we going to be putting statins in the water because they have such global benefits?"

Since we're talking about what's in the water, let's segue to JAMA Network Open. This is a study that got an enormous amount of media attention. It's looking at exposure of women while they are pregnant to fluoride -- and that's fluoride that's in water in municipal water supplies -- and their child neurobehavior at age 3 years in the United States.

In this study, they looked at largely Hispanic, 263 mother-child pairs who completed their 3-year study. Women who reported prenatal smoking were excluded from this analysis. There were other exclusion criteria as well, including multiple-gestation pregnancies, HIV, or having been incarcerated. They looked at what's called the specific gravity-adjusted MUF (MUFSG), which is a biomarker of prenatal fluoride exposure, and they administered to these children their preschool child behavior checklist, and that is actually filled out by the parents when the child is 3 years of age.

Basically, what they found was that, sure enough, if there was an increase in this biomarker, you did have an increased risk -- nearly double the odds of a Total Problems T score being in borderline range or clinical range, also increases in internalizing problems. Basically, what they show in this study is yep, if the mom has higher levels of fluoride, their child is more likely to have neurobehavioral issues that they identify.

Rick: This study has flaws. How reliable are the results of these and how applicable?

A couple of things. One is, it was a single fluoride measurement, a urinary fluoride measurement. It presumes the fluoride came from water, but they don't talk at all about the water consumption of women. In fact, we know that you get fluoride in toothpaste, for example.

Furthermore, the testing of the children was actually self-reported by the parent. Parents, especially whether they are young or experienced, whether it's the first child or last child, will score some of the behavioral things as normal or abnormal. I don't think it's a very accurate way of assessing whether a child has neurobehavioral problems or not.

Furthermore, it's a fairly small study. Unfortunately, things like this become sensationalized. We know that fluoride in water is particularly helpful for children's teeth. There is no question about that. We need to do some follow-up studies. Your thoughts?

Elizabeth: Well, the other thing that definitely occurred to me was, how do we account for variations in fluoride levels among women who purportedly are consuming the same municipal water supply that would have a pretty consistent level of fluoride? I agree with you that what we really need are some more measurements and to determine whether the fluoride in the water is really the exposure.

Rick: By the way, when you do a single measurement, it depends on not only how much fluoride you have in, but how much consumption of other fluids you've had and dietary stuff. It's an interesting study and it deserves follow-up, but it's certainly not conclusive in my opinion.

Elizabeth: Let's turn to JAMA and let's look at, are there consequences to donating a kidney?

Rick: This study stems from the fact that there are recent guidelines that actually asked for better evidence about health outcomes from people that have actually donated kidneys. We are aware that there are a tremendous number of individuals that need transplants -- about 90,000 a year. Those kidneys that are donated can either be from living kidney donors or from cadaveric donation and about 35,000 people worldwide become living donors each year.

What happens to those donors over the subsequent years? Since they now have one kidney, what's their risk of developing high blood pressure? Because that can affect the remaining kidney. How does it affect their ability to filter toxins out of the system -- what's called a glomerular filtration rate, which assesses kidney function? Is the kidney more likely to spill albumin, which indicates that it's dysfunctional? The thought being is that now that you have one kidney you're asking it to filtrate more. Does this hyperfiltration actually cause kidney dysfunction over a period of time?

The investigators looked at 924 living kidney donors that donated kidneys between 2004 and 2014 in 17 different transplant centers, and they paired those with about 396 non-donors. They assessed their likelihood of developing hypertension, their filtration rate, and they also assessed how much albumin they spilled out in the urine.

What they discovered is that over the median follow-up of 7 years, about 17% of those that donated a kidney developed high blood pressure. By the way, 17% of the individuals who didn't donate a kidney developed high blood pressure as well. When they looked at those who did not donate a kidney, each year their kidney function declined a little bit and those who donated a kidney, their kidney function actually got a little bit better each year.

When they looked to see whether there was an increased risk of spilling albumin, there was no difference between the two. There is really not a significant difference overall between those that donated a kidney and those that did not.

Elizabeth: It reminds me of liver function in live donation where when people get a portion of their liver taken out, gosh, that liver just really attempts to regenerate and take over for that part that's gone.

Rick: That's right, a normal filtration rate between 90 and 120. When you take out a kidney, you decrease that by about 30% immediately. The kidney function, the filtration rate, continues to increase over the next several years as opposed to declining in the normal population. You're right; it does take over and those individuals overall seem to do well.

Elizabeth: It sounds encouraging, then, for those folks who are considering live donation.

Rick: It does. Now, Elizabeth, this obviously requires longer follow-up. This was a follow-up of about 7 years. We need to know what happens over the next 10, 15, and 20 years, so those studies should be coming out.

Elizabeth: Well, what I'm actually hoping for is that we're going to come up with some really viable option for creating kidneys that would allow us to not have to rely on donation.

Let's turn now to JAMA Psychiatry. Are mental health issues transmissible? This is a study that's looking at the transmission of mental disorders in adolescent peer networks. Clearly, a study that had to be done in one of our Scandinavian countries where they look at enormous amounts of data about their citizenry all of the time.

Sure enough, in Finland they took a look at all of the citizens born between January 1, 1985 and December 31st, 1997. They collected, of course, everything they possibly could about them. Then they looked at a cohort that were followed up from August 1st in the year they completed 9th grade, which for most of them was about 16 years of age, until a diagnosis of mental disorder, emigration, or death until December 31, 2019. Their exposure was one or more individuals diagnosed with a mental disorder in the same school class while they were in 9th grade.

They had 713,000+ cohort members. 47,000+ had a mental disorder diagnosis by the 9th grade. 167,000+ had a mental disorder diagnosis during the follow-up. They did find what they called a dose-response association. They found a 5% increased risk with more than one diagnosed classmate. They also found that this risk was highest during the first year of follow-up, showing a 9% increase for one diagnosed classmate and an 18% increased risk for more than one diagnosed classmate. These were largely mood, anxiety, and eating disorders. They say, "Let's talk about this social contagion. Is it possible that we would actually transmit mental illness from one to another?"

Rick: This present study is the largest and most comprehensive investigation of this to date. We know that these things cluster, these mental-behavioral issues. Do they cluster together because people kind of assimilate that have similar problems? But in this particular one, you don't get to choose which school you go to. You don't pick your class; you don't pick your classmates. This is people being randomized to their association with individuals that may have neurobehavioral issues. Once you're exposed to somebody like that, it increases the other individual's risk. The more individuals you are exposed to, the higher the risk.

Let's talk about mechanisms for a second. It may be just due to the fact that now we're doing more reporting. There are peer social influences and adolescents are particularly susceptible to that. That's another possible mechanism. A third is that there is interpersonal contagion. Long-term exposure to, for example, a depressive individual could lead to the gradual development of depressive symptoms through what the authors call well-established neural mechanisms of emotional contagion.

Elizabeth: The authors also note something that I think is really important. They say that one plausible mechanism is normalization of mental disorders. I think that we see an enormous amount of that, especially in social media, where if everybody is reporting that they are feeling symptoms of anxiety, or depression or whatever, it's just normal. It just sort of comes with the territory. Then is it a surprise, then, that especially adolescents would adopt that?

Rick: One of the things that lends credence to this is the risk of having it transmitted is highest in the first year after it's discovered, and that speaks to the fact that normalization may be a prominent mechanism.

Elizabeth: I don't think we understand all of this. I'm not trying to minimize or disparage the fact that we are seeing an enormous amount more depression and anxiety among adolescents.

Rick: Right. Again, a very interesting study. I'm glad you picked that because it's the first time we've talked about this in our almost 20 years of providing podcasts.

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.