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Month: November 2024

People with kidney disease, diabetes may develop heart disease 28 years earlier

People with kidney disease, diabetes may develop heart disease 28 years earlier

According to a recent study, individuals who have type 2 diabetes, chronic kidney disease, or both may be at higher risk for cardiovascular disease (CVD) 8–28 years earlier than those who do not have these conditions. Type 2 diabetes and chronic kidney disease are parts of the cardiovascular-kidney-metabolic (CKM) syndrome, which has a major effect on the risk of CVD.

These findings could aid in the early diagnosis of CVD in patients and aid in disease prevention. Chronic kidney disease, type 2 diabetes, or both may increase the risk of cardiovascular disease (CVD) 8 to 28 years earlier than people without these conditions, according to a recent study presented at the American Heart Association’s Scientific Sessions 2024.

To ascertain the relationship between age and risk factors linked to CKM syndrome, researchers employed simulated patient profiles. These findings could guide early detection and intervention strategies in CVD prevention, even though they haven’t been published in a peer-reviewed journal yet. Type 2 diabetes and chronic kidney disease are two of the four components of cardiovascular-kidney-metabolic (CKM) syndrome, which increase this risk.

According to current CVD prevention guidelines, if a person has a 7 5% chance of having a heart attack or stroke within the next ten years, their risk is elevated. CKM syndrome is defined by the American Heart Association as the relationship among metabolic diseases such as type 2 diabetes and obesity, kidney disease, and cardiovascular disease.

Developing cardiovascular risk profiles
To represent men and women aged 30 to 79 with and without type 2 diabetes and/or chronic kidney disease, researchers created risk profiles. They estimated the age at which each profile would probably reach elevated CVD risk using the Predicting Risk of Cardiovascular Disease EVENTs (PREVENT) calculator from the American Heart Association. Data from the 2011–2020 National Health and Nutrition Examination Survey was used to create the risk profiles.

An estimated glomerular filtration rate (eGFR) of 44.5, which denotes stage 3 kidney disease, was used to categorize chronic kidney disease. A “yes” answer to the PREVENT calculator question, Any history of diabetes, indicated type 2 diabetes. According to the American Heart Association, almost half of all U.S One in three adults has at least three risk factors linked to CKM syndrome, and all adults suffer from cardiovascular disease (CVD) in some capacity. Early identification of high-risk individuals can enhance primary prevention initiatives and reduce the likelihood of early death from CVD.

According to our research, a person’s age and other medical conditions have a substantial impact on their risk of cardiovascular disease. In particular, people with diabetes or kidney disease have a significantly increased risk of heart disease, even in their 30s, which can now be determined using the PREVENT equations. According to Krishnan, the Pooled Cohort Equations, which began at age 40 and excluded kidney function, could not previously be used to evaluate this.

A better understanding of cardiovascular disease risk, which includes heart attacks, heart failures, and strokes, should be made possible by the study, she continued. Even in the absence of a formal diagnosis, people with borderline high blood pressure, glucose, or kidney function may be at risk for unidentified health issues.

For people with CKM (Cardiovascular-Kidney-Metabolic) disorders like diabetes or kidney disease, these risks manifest earlier. For instance, elevated cardiovascular risk can manifest decades earlier in individuals with CKM, particularly when combined with other conditions, whereas it begins around age 68 for women and 63 for men without CKM.

References:
https://www.medicalnewstoday.com/articles/chronic-kidney-disease-type-2-diabetes-may-develop-heart-disease-28-years-earlier#Developing-cardiovascular-risk-profiles


https://mygenericpharmacy.com/index.php?therapy=82

In Conversation: Investigating the power of music for dementia

In Conversation: Investigating the power of music for dementia

There is mounting evidence that music can improve mood, calm people down, and help them regain some aspects of their memory. But why does music have such a powerful effect on our brains, and does this effect last? You may have seen a video of an elderly person suffering from dementia swaying to a piece of music, recalling a plethora of memories, or even playing the notes to a song they used to know on the violin or piano, even though they cannot recall their family members.

Many people are perplexed by this phenomenon regarding dementia, a neurological disorder. One of the many questions we sought to address in our April podcast, In Conversation: Investigating the Power of Music for Dementia, was how someone could forget the names of their own children while remembering something as intricate as a classical piece of music. Beatie Wolfe, a singer, songwriter, and representative of the nonprofit organization Music for Dementia, and Dr. Kelly Jakubowski, an assistant professor of music psychology at Durham University, joined the discussion this month. This month’s episode is available to listen to below or on your favorite streaming service.

Whether instrumental or lyrical, music is a creative fusion of harmony, rhythm, and emotional expression. Its numerous health benefits have also been confirmed by numerous studies. For instance, a 2013 study discovered that music can help the nervous system recover more quickly and have a calming effect before stressful situations. According to a different study conducted that same year, music therapy helped hospitalized kids feel less anxious and in pain. In addition to its physiological advantages, studies have shown that music has a positive effect on cognitive function.

According to a recent study, individuals between the ages of 62 and 78 may experience a slower decline in cognitive function if they actively practice and listen to music. According to the researchers, playing music enhances the gray matter in certain parts of the brain, increasing neuroplasticity the brain’s capacity to rewire itself which is essential for memory formation and learning. Regarding actively practicing music, a 2023 study also revealed that sustained music training might help maintain the brain’s youth and offer possible functional advantages. According to these findings, music has the potential to be a very effective treatment for dementia, a condition marked by a variety of symptoms such as memory loss and issues with thinking, speaking, and solving problems.

Another way that music can support cognitive health is by serving as a communication tool. Loneliness and social isolation have been linked to accelerated dementia progression in numerous studies. Beatie stated, I think music is the most potent instant connector, almost of any experience and of the arts.. According to the singer/songwriter, the arts in general not just music can be medicinally potent, transcending its use as a kind of amusement. The ubiquitous nature of music does not necessitate one to get up and dance or draw. A person can simply take in the words, the frequencies, and the entire soundscape. Without a doubt, music has always been a strong tool that I use to feel good. You have a great deal of respect and admiration for music after seeing the reactions I’ve witnessed to it, she said.

But just as much, if not more, of an influence on our health, comes from the absence of silence than from sound and music. Silence can be therapeutic and calming, lowering blood pressure and brain wave frequency, according to a 2020 study. Indeed, studies have demonstrated the detrimental effects of excessive noise and loud noises on cognitive function. Chronic exposure to loud noises, like heavy traffic, maybe a particular risk factor for dementia, according to a 2022 study. Beatie, our guest, talked about how she was affected by total silence by sharing her experience recording her Raw Space album in the Bell Labs anechoic chamber, which is the quietest room in the world.

I think it was one of the most profound experiences I’ve ever had, and I keep thinking about it. Even now, it seems to have practically gained more relevance. As the world has become more noisy, both sonically and informationally, we are being inundated with notifications and social media, among other things that are bombarding us and causing us to feel frazzled, she said. You experience silence; it’s almost as if your nervous system relaxes and you hear sound in its most unadulterated form, devoid of echo, reverb, or enhancements. Do you also realize that we use technology far too much these days to fix all of these issues that are fundamentally what makes us human?

Beatie ended up spending quite a few hours in that exact chamber, seemingly enjoying the experience far more than most people do. Because you could hear the blood pounding through your veins and the engineers usually had to take breaks due to the intensity, I was told that I would probably be able to stay in there for fifteen minutes. She claimed that I ultimately spent at least 100 hours.

I spent several hours in there for the first time and found it to be very soothing; perhaps I’m an exception. However, I reacted differently to people’s freakouts, which I believe are also related to being truly alone. You are there very much with yourself, there are no distractions, and there is nothing to pull you out of that internal space, she added, adding, I do think there is an element of it in the chamber. Regarding the issue of dementia patients remembering song lyrics but not their own children’s names, Dr. Dot Guite highlighted the power of repetition and the way that music can simultaneously activate multiple brain networks and regions.

We’ve discussed the universality of music in the brain, but even though a child’s name is repeated throughout their life, the song may only be played once a month or once a year. She inquired, How can we explain that?. Dr. According to Jakubowski, procedural memory is linked to the capacity to fill in the lyrics of songs. When people may no longer have this type of semantic memory for names and places, they still have this type of memory for the motor sequence of singing along lyrics, likely because they have sung along to that song many times before, or at least have sung along to that piece of music in their minds many times before, she explained. Procedural memories are similar to remembering motor sequences, such as being able to ride a bike.

She added that some people with dementia may be able to play an old song on an instrument or remember lyrics because the brain may spare specific areas of this kind of memory. According to her, if a person has played the piano before, they can frequently continue to play those well-known pieces even after they have developed a serious illness. Beatie started a study in 2014 called The Power of Music in a collection of assisted living facilities in the United States. The UK. The Priory Group is in charge.

The video and pictures of that experience make it clear how the dementia patients in those assisted living facilities begin to clap their hands, tap their feet, and sing along to some of them with their eyes shining. She explained to us how it all began when she performed original English-language songs in a Portuguese nursing home. I had intended to perform for my father-in-law alone, but instead, I performed for the entire ward, which consisted of about 100 Portuguese individuals suffering from dementia and Alzheimer’s. Except for this relative, none of them could speak English. Additionally, I was playing brand-new English-language songs that they had never heard before. She added I was witnessing people clapping, waking up, and singing along as much as they could.

Beatie was inspired by this to test the theory that music, whether or not you were already familiar with it, had a powerful effect. In his book Musicophilia, neurologist Oliver Sacks made the prediction that prior knowledge of music was not necessary for its influence, which served as her inspiration. She performed original songs for residents of care facilities in the United States. K. The impact of one song in particular on the audience was noteworthy. Dr. Jakubowski shared her thoughts on why she believes the song Wish was especially popular with the people Beatie visited at the assisted living facility. Beatie, in particular, tends to use brief sentences. The fact that you can practically guess the next word or rhyme is a great way to get people to try singing along. A lot of things are repeated. As a result, you begin to anticipate, and it offers this lovely framework for others to follow along, she said.

Dr. Jakubowski stated that the very obvious beat is an additional contributing element in addition to rhyme and alliteration. The music’s tempo is actually quite similar to what is known as the human-preferred tempo. According to her, if I asked someone to tap a beat without listening to anything, they would typically do so at a pace of about 120 beats per minute, which is comparable to the tempo of that song. This is known as spontaneous motor tempo. We feel at ease clapping at that pace, so it’s a very simple piece to follow along with. I believe that encourages participation as well, she continued. Dr. Jakubowski added that the music’s structure makes it simple to follow. If you don’t have complex lyrics and you have this ‘oh, oh,’ every now and then, that’s pretty easy to understand, she said.

In addition to studying MEAMS (music-evoked autobiographical memories) in general, Dr. Dot Jakubowski thinks there are many implications for its relationship to dementia. She began by discussing the cascade effect of music on memory recall. A memory can be triggered by music or any other cue, which can then trigger related memories. According to her, the theory is that if music can arouse a memory associated with it, it may also aid in reviving other memories from that era or memories that are connected.

Dr. Jakubowski contrasted music with other forms of cues for autobiographical memories in one of her pieces. Across several studies, we consistently discovered that music generally evokes more positive memories from our lives than other cues. Therefore, I believe that music appears to be a particularly powerful cue for recalling happy memories from our past, which is one obvious potential therapeutic benefit. According to her, this actually appears to be further enhanced in older adults. Dr. To determine whether these findings apply to individuals with dementia, particularly those who are in the later stages of the illness, Jakubowski hopes that this will stimulate further research in this field. Dr. Jakubowski also discussed how music can help restore a sense of identity that frequently wanes with memory loss in individuals with dementia.

Beyond that, I believe the significance of autobiographical memories lies in the fact that recalling a small portion of our lives really strengthens our sense of personhood and identity, reminding us of our origins and identity. According to her, that’s crucial for those who experience some form of memory loss because it keeps them from connecting with their former selves and makes them feel trapped in the present, which can harm their mental health.

Family members and carers are also impacted by this sense of past, personhood, and reconnecting. Therefore, it’s crucial to catch a glimpse of the person you once knew. This supports family members and caregivers in realizing that this person is still a person with a rich past. Dr. While the immediate health benefits of music are obvious, Jakubowski pointed out that regular exposure is necessary to discuss long-term benefits. You can’t expect to benefit from listening to music for years on end just because you heard one song three years ago. According to her, listening to music for a longer period has more advantages than just hearing it once and then never hearing it again. People can interact with music in a variety of ways, she added.

For those with dementia, even regular, recorded music listening has long-lasting benefits, such as lowering agitation, lowering apathy, elevating mood, occasionally strengthening a sense of identity, and more. According to her, there are various ways to interact with music. Dr. Jakubowski emphasized that there might be drawbacks to using music therapy to treat dementia. Regardless of whether a person has dementia or not, there are possible drawbacks to music because, on occasion, it may be connected to a traumatic memory from their past, she said.

It might remind someone of a funeral or the death of a family member, even if it isn’t a traumatic memory. Therefore, she added, we must exercise caution when choosing music and consider these factors. She also discussed personal taste and the wide variety of musical styles available. Unwanted consequences could result from this, particularly for those suffering from dementia. According to her, choosing the music for sessions requires careful consideration on the part of music therapists.

Music is less likely to be useful for controlling agitation and mood if someone despises it. This relates to our discussion at the outset, which was that noises in our surroundings can occasionally be harmful and bothersome. According to her, we don’t want to force people to listen to music they don’t particularly enjoy or that they don’t relate to because that could cause them to react negatively.

Regardless of preferences, these experiences demonstrate the positive effects of music on health and well-being. Further research is necessary to determine whether it can truly slow the progression of dementia, but before I go, I would like to ask our readers this: What is the one song that always makes you feel something, whether it’s a reminder of a heartbreaking heartbreak or the happiest day of your life?

References:
https://www.medicalnewstoday.com/articles/in-conversation-investigating-the-power-of-music-for-dementia#Can-music-be-detrimental-to-people

In Conversation: How to understand chronic pain

In Conversation: How to understand chronic pain

In recent years, chronic pain has gained recognition as a medical condition in and of itself. This is because chronic pain is a disease process that is so complicated that we are only now beginning to understand what triggers it. However, what is it like to live with chronic pain, and how do the body and brain cope with it?

People often describe their pain as aching, dull, gnawing, burning, sharp, shooting, and piercing. Imagine having to deal with some of this every day until you have no idea what it’s like to go about your day without this constant pain that gradually saps your physical and mental stamina. For many people who suffer from chronic pain, that is their reality.

It could be an internal struggle concealed behind gritted teeth and fake smiles, and some days might be fantastic and some days awful. However, how does chronic pain become, well, chronic? In the most recent episode of our Pain Awareness Month-themed In Conversation podcast, Medical News Today delves into the science of chronic pain with Drs. Tony L. and Hilary Guite. As Joel Nelson, a longtime patient and advocate for psoriatic disease and arthritis, Yaksh, a professor of anesthesiology and pharmacology at the University of California, San Diego, talks about his experience with pain.

Because chronic pain is not life-threatening, it is frequently disregarded as merely a symptom of a more serious issue or not given the attention it deserves. Chronic pain, however, has a social as well as a personal cost. According to studies (), individuals who experience chronic pain may find it difficult to carry out daily tasks and activities and may also have worse general health. Chronic pain sufferers may also experience unemployment or unstable employment.

Chronic pain was not recognized or diagnosed until 2018 when the International Classification of Diseases (ICD) assigned it a code in the draft version of the new ICD-11 coding system. The two types of chronic pain currently recognized by the World Health Organization (WHO) are chronic primary pain and chronic secondary pain.

According to this classification, primary pain is defined as pain that cannot be attributed to or explained by another medical condition. Fibromyalgia and persistent primary low back pain are a couple of examples. A widespread pain disorder that affects at least four to five body parts and lasts for at least three months, but typically longer, fibromyalgia varies from person to person. Since there is no other explanation for the pain, Dr. Dot Guite clarified that it is a form of primary chronic pain.

Conversely, secondary pain results from or is a result of an underlying medical condition. This would include pain from ulcerative colitis, cancer, or arthritis. I began experiencing chronic pain when I was ten years old. And ever since, Joel Nelson told MNT’s In Conversation, “Chronic pain has kind of been an intermittent part of my life right up until the present day. Joel, who is currently 38 years old, has experienced chronic pain for several decades.

I experienced pain for the first time when I had a gravel-like burning sensation in my hip. And the more I used the joint, the worse it got; at one point, he claimed, I was losing some of my mobility. He decided to seek help at that point, just like the majority of people do. Joel asserted that the best way to describe his persistent pain is noise. I have always referred to it as noise because, on the days when the pain is severe, I simply lose the capacity to take in additional information and manage several tasks at once, he said.

In light of my current condition, I believe that the experience’s fluidity is its most significant lesson. In the end, my mobility and limits can vary from anything to the point where I can do more than just walk, and I might be able to run and cycle a little bit like I do now, to possibly needing crutches again the following week. Pain dictates a lot of that. I get a lot of stiffness in the mornings from arthritis, but the pain is what keeps me from doing things. Joel said it’s difficult to predict what will happen next with his chronic pain, likening it to a series of chapters. Researchers have discovered that a gateway receptor known as Toll-like receptor 4(TLR4) may be a governing factor behind the development of chronic pain from acute pain.

We are aware that signaling that is typically linked to what is known as innate immunity can be activated in response to various types of tissue or nerve damage. And the toll-like receptor is one of the mediators of that. It turns out that although those receptors are typically present to detect the presence of foreign bugs, like E. coli, those insects contain a substance known as lipopolysaccharide, or LPS, in their cell membrane. According to Dr. Dot Yaksh, bacteria are the source of that, which is not typically present in our system.

You don’t need to acquire it; you are born with it. It is constantly present. Over the past few years, we’ve discovered that your body releases a variety of substances that will activate those same toll-like receptors, he continued. The central immune system may be primed for elevated pain states by toll-like receptors. The body begins to release products from inflammatory cells in response to damaging stimuli, stressors, or tissue damage, particularly in the gastrointestinal tract or microbiome.

According to him, when this occurs, the products that are expelled from our bodies can activate toll-like receptors. One such receptor is called TLR4, and it is found on both sensory neurons and inflammatory cells. Dr. According to Yaksh, TLR4 activation makes the nervous system more reactive but doesn’t actually cause as much pain.

In addition to this priming, Dr. Dot Guite noted that if additional stressors are present at the time, such as poor diet or psychological distress, this can trigger a series of events that can accelerate the transition to chronic pain. TLR4 activation initiates a cascade, a series of events that will result in increased expression of numerous receptors and channels capable of enhancing the system’s response. When this occurs, the initial tissue damage is followed by this improved response. It only makes the system more reactive; it doesn’t really cause the pain condition. According to him, Joel’s circumstances are consistent with the idea that people can experience different kinds of pain.

That can be made worse by “psychological” stressors, which can intensify a pain state that may actually have a physiological component that we don’t fully comprehend, he continued. Dr. Yaksh, for instance, proposed that Joel’s condition was likely made worse by the stress (and joy) of becoming a father and all the other factors involved, making it more difficult to manage the pain. He emphasized that this did not lessen the reality of the pain.

I believe that Joel’s situation was likely associated with a very strong, emotional component. He explained that the pain condition and the events related to the psoriatic diagnosis and other aspects may have actually established the transition from one state to another, which we call an acute to chronic or chronification of the pain state. According to current theories, pain occurs where the body and brain meet.

The way you mentioned that pain is in the brain is exactly right; Dr. Dot Yaksh stated that everything’s output function originates from the higher centers. It all comes down to how tissue damage affects how the brain perceives pain. Our bodies use pain as a warning system to notify us when there is damage or illness, which is why it is so important to our survival. Following a disease or injury, the surrounding nerves begin communicating with the brain via the spinal cord, urging us to seek medical attention and prevent additional harm.

Following an injury, the body’s organs and tissues suffer damage, which sets off an acute inflammatory response involving blood vessels, immune cells, and other mediators. But occasionally, the nervous system may continue to be distressed or reactive even after the body has healed from the initial injury phase. The body may become overly sensitive to pain as a result. Peripheral sensitization is the term used to describe this increased sensitivity to touch or heat near the injured area.

Dr. Yaksh explained that if I were to jam my finger or if I were to experience something that causes a local autoinflammation of the joint, as Joel did, then that inflammation actually causes the release of factors that make the innervation of that joint more sensitive. Dr. According to Yaksh, everyone goes through this, even if they don’t have chronic pain. He clarified that an otherwise harmless activity, like wriggling one’s finger, can become extremely unpleasant following an injury.

He defined this as a sensitization brought on by inflammation and injury to the periphery, which is subsequently transmitted to the brain via the spinal cord. The brain is now perceiving what would otherwise be a harmless occurrence, producing a signal that suggests, as we say, that bad news is on the horizon. On the other hand, this prolonged reaction to the initial injury can occasionally result in persistent pain that is not restricted to the injured area. Central sensitization is the term for this ().

Joel’s situation is intriguing because it is evident that he has a peripheral problem, whether it be skin inflammation, joint inflammation, or abnormalities in peripheral nerve function. Therefore, Dr. Yaksh explained, that in addition to changes in joint morphology and other similar things, you also get changes that alter how information enters the spinal cord and then travels to higher centers. Additionally, you’ve activated particular populations of sensory fibers that are typically only activated by severe injury.

The spinal cord, which is currently, in a sense, organizing the input-output function from the periphery to the brain, may become reorganized. This would be similar to turning up the volume on a radio; the signal would remain the same, but the volume would increase. The spinal cord can therefore be thought of as a volume regulator.

Additionally, it states that there is bad news. However, we now know that some of the input that travels through the same pathway actually goes to parts of the brain that are unrelated to the source of the pain just that it is severe,” he said. The brain receives information about the location and severity of the pain from these outputs that ascend the spinal cord. According to Dr. Yaksh, the limbic system, also known as the smell brain, is one region where these are processed. He continued by saying that these are brain regions that are actually linked to emotionality in humans.

In addition to causing muscles to tense or spasm, this stress can also alter how the body perceives pain and raise cortisol levels of the hormone. Over time, this could result in pain and inflammation. Over time, this can worsen the pain by contributing to an already stressed nervous system and causing sleep issues, irritability, exhaustion, and depression. Even though acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), and opioids are frequently used to treat acute pain, there are relatively few options for managing chronic pain.

We began by stating that pain originates in the brain. Additionally, your views of the world have a direct impact on you and alter how your brain functions in ways that can be defined experimentally. Therefore, I am not implying that pain is any less real in any manner, shape, or form when I say that it is in the brain. Dr. Yaksh asserted that it is a reality. We now instruct medical students that, you know, a patient may have a condition other than a swollen joint, even if that isn’t the primary diagnosis, he said.

According to Dr. Dot Yaksh, fibromyalgia is frequently treated or managed with mindfulness in therapy. According to him, this does not imply that fibromyalgia lacks a physiological component, and in fact, new research indicates that it is most likely an autoimmune disease, just as real as the presence of antibodies that indicate the existence of an arthritic joint.

Although it’s not something you could become mindful enough to say have surgery done, mindfulness can help the person respond to the type of afferent traffic that’s coming up the spinal cord. However, it may lessen the intensity of some of the factors that are actually causing this heightened reaction. A prime example is fibromyalgia. According to him, mindfulness shows that altering your perspective on your pain condition can help you manage it, but it doesn’t make the pain state any less real.

Joel continued by saying that, from the viewpoint of someone who has chronic pain, it is a journey to see how the body and brain cooperate to maintain pain: Talking about pain and how it resides in the brain is a really delicate conversation, and as someone who has gone through the entire process of being appalled when it was first suggested to undergo pain management, I have also had to understand it to better process it. For me, it completely altered everything.

It’s still unclear what the future of chronic pain treatment will bring. Nonetheless, there is hope that medications will be created to affect receptors like TLR4 in a way that might prevent acute pain from turning into chronic pain and that as time goes on, we will learn more about how psychological processes interact with the neuro-immune interface.

References:
https://www.medicalnewstoday.com/articles/in-conversation-how-to-understand-chronic-pain?utm_source=ReadNext#Mindfulness-and-the-neuroscience-of-pain
https://mygenericpharmacy.com/index.php/therapy,82

Empagliflozin Effects Subside With Discontinuation

Empagliflozin Effects Subside With Discontinuation

SAN DIEGO The significant kidney and cardiovascular benefits of people with chronic kidney disease (CKD) show over 2 years of treatment with empagliflozin begin to subside within about a year after treatment discontinuation, suggesting the need for ongoing treatment.

We know that empagliflozin is safe we know it works and now we know we need to keep people on the treatment to maximize the benefits, said first author William G. Herrington, MD, of the Renal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, UK, at a press briefing at the American Society of Nephrology (ASN) Kidney Week 2024.

The New England Journal of Medicine published the study at the same time. Empagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that was discontinued early in the EMPA-KIDNEY trial because of its effectiveness in lowering the risk of kidney disease or its progression in patients with a variety of kidney disease causes and kidney function levels. The study demonstrated that empagliflozin decreased the primary outcome of kidney disease progression or cardiovascular death by 28% compared to a placebo, with no significant safety concerns, over a median follow-up of two years.

Herrington and colleagues examined data on 4891 (74 percent) of the 6609 CKD patients who participated in an extra 2-year post-trial observational period to better examine the changing effects of the medication following discontinuation. Adult patients with CKD-EPI estimated glomerular filtration rate (eGFR) of 20 to 45 mL/min/1.73 m2 or 45 to 90 mL/min/1.73 m2 plus urine albumin-to-creatinine of ≥ 200 mg/g were specifically included in the study. In the post-trial randomization, the average age was 63 years, 34% of the participants were female, and roughly 57% of both groups had never had diabetes before. About 35% of each group had a mean eGFR of less than 30 mL/min/1.73 m2, while the mean eGFR was 37 mL/min/1.73 m2.

Patients were randomized to receive a matching placebo or 10 mg of empagliflozin once daily. During the post-trial phase, neither placebo nor trial-related empagliflozin was given. However, open-label SGLT2 inhibitors, such as empagliflozin, were administered to patients as directed by their physicians. Similarly, during the post-trial phase, open-label SGLT2 inhibitors were utilized by 40% of the placebo group and 43% of the empagliflozin group.

Herrington stated that an evaluation for any carry-over effects is made possible by the absence of a between-group difference in SGLT2 inhibitor use after the trial. The primary outcome, a composite of kidney disease progression or cardiovascular death, was observed in 865 out of 3304 patients (26.2 percent) in the empagliflozin group compared to 1001 out of 3305 patients (30.3 percent) in the placebo group when the effects from the active and post-trial periods were combined (hazard ratio [HR], 0.79; P < .0001).

The hazard ratio for the primary outcome was still significant during the post-trial period. Still, it was less so at 0.87 (P = .04). Regarding other specific outcomes, the risk of kidney disease progression during the combined periods was 23 percent for the empagliflozin group and 27 percent for the placebo group; the risk of cardiovascular death was 3 point 8 percent and 4 point 9 percent, respectively; and the risk for the composite of death or end-stage kidney disease was 16 point 9 percent with empagliflozin and 19 point 6 percent with placebo. The percentage of deaths from noncardiovascular causes (5.3% in both groups) did not differ between the groups.

According to Herrington, the carry-over effect was only about a year long and reduced the risk for the primary outcome by 13 percent overall, which was less than the 28 percent reduction that occurred while taking empagliflozin during the active trial. According to the authors, the effects of empagliflozin were seen after the follow-up regardless of the degree of albuminuria, diabetes status, kidney function level, and primary kidney diagnosis. According to the study, analyses of the long-term eGFR slope from the active-trial period also revealed that empagliflozin slowed the progression of all albuminuria subgroups.

Finally, they conclude that the results show that the benefit after the trial was less than the benefit during the study treatment and seemed to be transient. Therefore, long-term CKD treatment is necessary to optimize the cardiorenal clinical benefits of SGLT2 inhibitors. Emily Chang, MD, an associate professor of medicine at the University of North Carolina, Chapel Hill’s Division of Nephrology and Hypertension, commented on the study and agreed that the results offer valuable information about the possible consequences for patients, irrespective of their disease stage, who stop taking empagliflozin.

Chang told Medscape Medical News, “I think it is important to know that these are probably lifelong drugs, although I have already been operating under that premise in my practice at least.”. However, knowing that this is probably the best course of action is comforting. Regarding comparable effects with other SGLT2 inhibitors, Chang speculated that this effect would hold true for all SGLT2 inhibitor classes, though we can’t be certain until more research is conducted. A patient’s ability to take the medication will be limited if they are unable to tolerate it, she continued. Otherwise, I intend to keep these patients taking this medication for the rest of their lives if it is tolerated.

Pietro Canetta, MD, an associate professor of medicine in the Division of Nephrology at Columbia University Irving Medical Center in New York, added that while there is a wealth of information about the advantages of SGLT2 inhibitors during treatment, this study was noteworthy for demonstrating that a significant portion of the benefits appeared to last for at least a year after the study populations stopped taking the prescribed medication.

Although we cannot definitively determine the mechanism from this trial, the strong effect that persisted even after stopping the drug highlights that there appear to be advantages beyond its immediate effects. For instance, he said, they might be promoting better vascular health or beneficial remodeling.

Important disclaimers were mentioned by Canetta, who told Medscape Medical News that patients with a history of ketoacidosis or recent immunosuppression were not included and that patients had to be taking an adequate dosage of an RAS [renin-angiotensin system] inhibitor. Furthermore, he added, it’s critical to remember that the advantages were different when taken off a drug than when taken on one. Although the group that initially received empagliflozin outperformed the group that initially received a placebo, the difference was more noticeable while both groups were taking the study medication.

This is significant because, according to Canetta, the trial’s message shouldn’t be taken to imply that you can quit after a year and still anticipate the same advantages indefinitely. The main takeaway from this is that there is more proof that these medications are a great addition to our toolbox for slowing the progression of kidney disease and cardiovascular consequences.

References:
https://www.medscape.com/viewarticle/empagliflozin-effects-subside-discontinuation-2024a1000jm9