Overdiagnosis of Kidney Disease; Severity of the Delta Variant

TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine, 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 salt reduction and tight blood pressure control, long-term sequelae of COVID, overdiagnosis of kidney disease in older adults, and is the Delta variant more serious?

Program notes:

0:40 The Delta variant

1:33 Twice as likely to require hospitalization

2:37 Vaccines known to reduce severity

2:48 Salt substitution and tight blood pressure control

3:48 Tight blood pressure control in those with hypertension

4:49 How applicable are these studies?

5:48 Can get blood pressure below 130

6:48 Some not responsive to salt

7:48 6 month consequences of COVID

8:45 Women were twice as likely to have long-term symptoms

9:40 Overdiagnosis of kidney disease in older adults

10:42 Current criterion needs to be modified

11:59 End

Transcript:

Elizabeth Tracey: Is chronic kidney disease overdiagnosed in older adults?

Rick Lange, MD: What are the long-term consequences for people who have been hospitalized with COVID?

Elizabeth: What’s the impact of controlling both dietary salt and blood pressure?

Rick: The Delta variant of COVID is more infectious. Is it more serious?

Elizabeth: That’s what we’re talking about this week on TT HealthWatch, 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, in keeping with our long-standing, now over 18 months, tradition, let’s turn first to the COVID material. So which of those two studies from the Lancet are you interested in starting with?

Rick: Let’s talk about the Delta variant. It was first reported in India in December of 2020 and it marched its way to England in March of 2021. This is an English study that looks at COVID infections over a period of time and asked a simple question — about 20% of their infections during this particular time were due to the Delta variant and about 80% were due to the original one — is the Delta variant associated with more severe disease? And then secondly, can they characterize how severe it is?

They had 43,000 individuals that ended [up] being COVID-positive and they were relatively young. The mean age was 31 years. What they discovered was that the individuals that were infected with the Delta variant were twice as likely to require hospitalization and about 45% more likely to either require hospitalizations or visit the emergency department.

You say, well, that’s because most of those people were unvaccinated. Well, they actually looked at those that had been vaccinated and those that had been unvaccinated. Even in the vaccinated individuals, those with the Delta variant were still twice as likely to be hospitalized as those that had the Alpha — that is, the original variant.

Elizabeth: This, of course, added to the accrual of a lot of data that we’re gathering here in this country relative to the Delta variant, also suggesting that younger people… of course, we are seeing way more unvaccinated people hospitalized, but we’re also seeing vaccinated people hospitalized.

Rick: Right. Again, most of the individuals being hospitalized now are unvaccinated. It places a huge burden on the healthcare systems. Elizabeth, this is the largest trial today that’s reported on the hospitalization risk for the Delta variant. It speaks to the fact that we need to do everything we can to mitigate it — non-pharmacologic measures and mask wearing, but more importantly vaccination as well, because the vaccines are known to help decrease the rate of severe hospitalizations — that is, requiring an ICU stay — and even death.

Elizabeth: From there, then let’s move on to the New England Journal of Medicine. We’re treating these two studies together. One of them is the effect of salt substitution on cardiovascular events and death. The other one is tight blood pressure control in older adults and its impact. Both of these studies are from China.

The first of them is the one relative to the salt. They had 600 villages in rural China. Participants enrolled who had a history of stroke or were 60 years of age or older and had high blood pressure, so a high-risk group. These folks were assigned 1:1 to either your standard stuff or to a salt substitute that contains 70% sodium chloride and 30% potassium chloride. They had almost 21,000 people who were enrolled in this trial and the mean duration of their follow-up was just shy of 5 years. What they showed was that in fact the salt substitution was able to reduce the rates of major cardiovascular events and death in this group.

Before we hear your thoughts about that one, let’s turn to the other one, which is the one relative to intensive blood pressure control. They randomly assigned Chinese patients who were 60 to 80 years of age with high blood pressure to a systolic blood pressure target of 110 to less than 130 millimeters of mercury, or a target of 130 to less than 150 millimeters, the standard treatment.

They have 9,600+ patients who were screened and ultimately ended up with just over 4,000 who were assigned to the intensive treatment group and about that same number to the standard treatment group. Again, what they showed is that in older patients with hypertension, the intensive treatment with a systolic blood pressure target of 110 to less than 130 did result in a lower incidence of cardiovascular events than the standard treatment.

So, both of these turned out to be pretty efficacious interventions. Lots of questions we could ask about them.

Rick: The question is how applicable are these studies? The one with salt substitute may not be quite as applicable in the United States because in the rural parts of China almost all of the salt they intake is added salt. They don’t eat much processed food. In fact, most of the salt that America gets is in processed food.

Nevertheless, we know that diets that are low in sodium or high in potassium are overall beneficial. In underdeveloped countries, where added salt may be a more prevalent part of their diet, using a salt substitute really seems like a very effective way to lower the risk of stroke in patients that have already had a previous stroke.

With regard to the treatment for hypertension, trying to get a tighter control for older individuals. In this particular study, even though they were targeted between 110 and 130, the average blood pressure was about 127 or 128. It wasn’t at the lower end.

We do know that in the elderly, the more intensive the therapy, the more likely you are to get hypotension and that was the case here, although they didn’t develop many of the severe complications of hypotension, like passing out or dizziness or stroke. I think the study is pretty clear that if we can get the blood pressure down below 130, it’s better than letting it inch up above 130.

Elizabeth: Let’s return just for a moment to the salt study because I think that this ratio of 70%/30% is also something that calls questions to mind. Would it be more effective to make that ratio even more almost parity or even more potassium versus sodium? I wonder about the inclusion of those kinds of formulations in manufacturing so that we could change that ratio of salt that we consume here in the U.S., for example.

Rick: That’s an interesting thought. I think that’s something that’s worth studying.

Elizabeth: The other thing about the salt study that’s worth mentioning is we’ve talked an awful lot about salt over these many years we’ve been recording. I am wondering about sort of the genotype-phenotype and who is salt-sensitive and who isn’t when it comes to cardiovascular events.

Rick: It is clear that there are some people that are very salt-sensitive in terms of their blood pressure going up. In fact, some it would go up as much as 10 millimeters of mercury with a little bit of salt, and other people are unresponsive at all to salt in terms of their blood pressure.

Speaking of blood pressure, I want to go back to the previous study, Elizabeth. I think a very important part of that study was they didn’t just use the blood pressure measurement taken in the office. They used the home blood pressure measurements that were automated and it could be transmitted via a smart app on a phone to the doctor’s office. Because all of us that take care of patients know that their blood pressure is oftentimes elevated in the doctor’s office, but in the home setting it’s oftentimes not quite as high. I think one of the reasons they were able to avoid some of the complications associated with intensive blood pressure measurement was they used home blood pressure measurements as well as office blood pressure measurements.

Elizabeth: It will be really interesting adopting that model here to see if that would impact on the recidivism that so many people seem to demonstrate when they are on multiple agents to manage their blood pressure.

Rick: Having it at home, putting it in your smartphone, automatically transmitting it to the doctor’s office really gives a lot of information about how well people are doing and sometimes whether they are taking their medications or not.

Elizabeth: Right. Let’s go back to the Lancet.

Rick: Elizabeth, this is a look at the 6-month consequences of COVID-19 in patients that have been discharged from the hospital, over 1,700 patients that were discharged in Wuhan, China over a 5-month period. Now we’re looking at the 6 months after they were discharged to see if they had any residual side effects.

In fact, three-fourths of individuals 6 months after they have been discharged still continue to have symptoms related to the COVID infection. Fatigue and muscle weakness is the most common. It occurred in about 63%. About a fourth of them had sleep difficulties and a fourth of them had anxiety or depression. A fourth of them couldn’t walk as much as the lower limits of normal and somewhere between 25% and 60% had abnormal lung tests or abnormal CT scans. You say, “Well, that range is pretty broad.” Well, that’s because the sicker the person was, the more likely they were to have abnormal pulmonary function tests or abnormal CT scan afterwards. Women were more likely to have residual symptoms. They were twice as likely.

Elizabeth: How does this compare to the post-ICU syndromes that we see in so many people already? Irrespective of what your illness was that got you in there, there is a lot of sequelae on the heels of an ICU stay. Then my other question is, gosh, if it was this with Alpha, what are we going to see with Delta?

Rick: Your point is well taken though. Those that were sicker in the hospital were more likely to have these side effects and they were more likely to be in an ICU, but there were many people that were hospitalized who were never in an ICU and still had residual symptoms. I think it’s important for our listeners to realize when you talk about a COVID infection you’re not just talking about the acute complications, hospitalizations, ICU stay, even death. We’re talking about residual effects as well. Those that are reluctant to be vaccinated because they’re concerned about vaccination side effects fail to consider the side effects related to COVID infection and ongoing side effects.

Elizabeth: Indeed. Finally, let’s turn to JAMA Internal Medicine. This is taking a look at the definition of chronic kidney disease in older people. This issue of chronic kidney disease is a big deal. Many people, as they age, are getting diagnosed with this and it turns out that maybe they really shouldn’t be.

The editorialist brings out the fact that in 2002 this definition of what is chronic kidney disease was established and really wasn’t modified a whole lot. Previous to that, it was kind of a free-for-all. They welcomed the definition of it and now it really looks like what we really need to do is modify this based on people’s age.

This study included 127,000+ folks. They all had chronic kidney disease. They took a look at this fixed threshold cohort and an age-adapted cohort. They looked at 5-year risks of kidney failure and death in these older people and in everybody else. Basically, the cohort study of adults suggests that the current criteria really needs to be modified based on the estimated glomerular filtration rate or eGFR. That has to be age-stratified so that it can be predictive because way too many older people are being identified as having this.

Rick: The whole reason why in 2002 we tried to identify and specifically define kidney failure is because, as you mentioned, it does impact mortality and morbidity, how long you’re likely to be alive and what other diseases you might get. If you have kidney disease, we want to provide treatments or avoid things that could potentially make it worse.

With age, a lot of things decline: our cognitive function, our muscle strength, our heart rate, our cardiopulmonary fitness, and even our kidney function. Some of these are just normal aging effects. They don’t really need treatment. And as you identified, Elizabeth, if we went by the old definition, a third of the individuals that are older, who were thought to have kidney disease, in fact, don’t have it at all. As a result, they really don’t need specific treatments.

Elizabeth: That is welcome news indeed. On that note, 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.