“That is essentially what diabetic kidney disease is: it is damage to the structures of the kidneys, specifically that filter, that occurred due to diabetes. ” “We’re talking about moving from the ‘one size fits all’ approach to individualized diabetes and diabetic kidney disease care.”
In this episode we speak with Dr. Christine Limonte about her insight on diabetic kidney disease. Dr. Christine shares how diabetes affects kidney health and what individuals with diabetes can do to keep their kidneys healthy
Christine Limonte is a nephrologist at the University of Washington. Her research focuses on mechanisms underlying diabetic kidney disease.
Shireen: In this episode, we speak with Dr. Christine Limonte about her insight on diabetic kidney disease. Dr. Limonte shares how diabetes affects kidney health and what individuals with diabetes can do to keep their kidneys healthy.
Dr. Christine Limonte is a nephrologist at the University of Washington. Her research focuses on mechanisms underlying diabetic kidney disease. Welcome, Dr. Limonte.
Dr. Limonte: Hi. Thank you for having me. Excited to be here.
Shireen: Absolutely. So, Dr. Laimonte first, I would love to understand just what is your inspiration for learning about and then treating diabetic kidney disease.
Dr. Limonte: Yeah. So you know, my main motivation behind my research in diabetic kidney disease, my passion for diabetic kidney disease is that it is just such a major health problem. So putting it into perspective, diabetic kidney disease affects 30 to 40% of people with diabetes and is actually the leading cause of kidney failure in the United States. You can really appreciate the scope of this problem. When you think about how worldwide there are 537 million people with diabetes and a third of these people are going to develop diabetic kidney disease. Also both diabetes and diabetic kidney disease, disproportionately impact racial and ethnic minorities. So, improving the care of diabetic kidney disease is really an important step towards mitigating health care disparities overall.
Shireen: That is that is so helpful to know and to be contextualized for how big of a, like how large of a problem this is. Can you first explain to us the different types of diabetes? Let’s just take it back a little bit basic here and how they might develop then into kidney disease. Like how does that progression happen? How are they related?
Dr. Limonte: Yeah. Yeah, absolutely. So, the major types of diabetes are type one diabetes and type two diabetes. And both of these are conditions where the body essentially does not have enough insulin or sense insulin, which is the hormone that is responsible for letting glucose into cells to be used for energy. Without insulin, cells cannot take in glucose for energy and glucose or blood sugar accumulates in the blood.
Type one diabetes typically presents in childhood. Type one diabetes is caused, it’s an autoimmune condition that’s caused by the body attacking the specific cells in the pancreas that are responsible for producing insulin. So, in type one diabetes, the pancreas is not producing insulin at all.
In contrast, type two diabetes can really occur at any age. And it occurs when cells develop resistance to insulin. So your pancreas is still able to produce insulin. The cells just can’t sense it’s there. Gestational diabetes is another term that people may be familiar with. And this is a term that is used to describe diabetes that occurs during pregnancy due to insulin resistance and gestational diabetes can either go away at the end of pregnancy or persist into, as you know, type two diabetes. And even in people who develop gestational diabetes that resolves by the end of pregnancy or after pregnancy, just having had gestational diabetes is a risk factor for developing type two diabetes later in life.
So that’s something that’s important for people to keep in mind. But when we talk about diabetic kidney disease, what we really think about is type one and type two diabetes as being the causes of this.
So I’ll talk about diabetic kidney disease, but take a step back and just talk about what the kidneys do and why they’re so important. So the kidneys are essentially a structure that filters blood. So it’s a filter attached to a series of tubes that connect to your bladder. And so you’re filtering your blood. So toxins are excreted through those tubes, make it into your bladder and out of your body. So, diabetic kidney disease or diabetic nephropathy, these are terms that essentially mean the same thing that people may be hearing is kidney disease that is caused by diabetes.
The way that we diagnose diabetic kidney disease is by identifying protein in the urine, which would occur if that filter I was talking about is disrupted. Normally, that filter is just, you know, the holes in that filter are just small enough to let the toxins out. But keep important things like your red blood cells and proteins in your body. So, if that filter is disrupted, due to diabetes, you may see protein in the urine, and over a long period of time as that filter is experiences injury and formed scar, it may not work as well in cleaning the blood of toxins. So that is essentially what diabetic kidney disease is, it is damage to the structures of the kidney, specifically that filter, that occurred due to diabetes.
And so the way that we diagnose it is either by identifying a protein in the urine again, as an indicator that the filter is disrupted or through a blood test called creatinine, which we plug into an equation and generate a percent kidney function, which we call the glomerular filtration rate. So the amount that your kidney is able to clear the blood of toxins is what that creatine tells us.
And so those are the two measures that we use in the clinic when you see your doctor to detect diabetic kidney disease. But the only way that it could be definitively diagnosed, you know, no doubt this is diabetic kidney disease is with a kidney biopsy which your doctor may want to do if there is some uncertainty behind the potential causes of kidney disease.
Now, to answer your original question, which was how does diabetes result in diabetic neuropathy. So, persistent high blood sugar causes direct injury to these kidney cells in the filter as well as changes in how blood flows through the kidneys through the filter. And over time, those injuries from high blood sugar result in like I, I’ve discussed leakiness of the filter and scarring of the kidney and in its, you know, ultimate final stages, a scar builds up in the kidney. The kidneys can’t do their job of filtering the blood of toxins, getting rid of extra salt and water.
Shireen: And so what does it look like at the different stages? So you’ve mentioned like it’s this progression of this filter, you know, mechanism getting severely damaged through high blood sugar and then just not being able to filter, right. But are there, are there symptoms that one can look for? Are there ways that one can know you mentioned the lab test as well? How does one sort of go about understanding how far along they are and what, what that looks like?
Dr. Limonte: Yeah. That’s a great question. And you know, the thing about kidney disease is that in its early stages, it is silent. There are no symptoms that a person may be feeling that may say, hey, that may tip them off to think, you know, something is wrong. I should see my doctor about this. In the very early stages of diabetic kidney disease, the only sign may be the presence of a small amount of protein in the urine indicating that the filter is disrupted.
The word that we use to describe that small amount of protein in the urine is microalbuminuria. Over time, as kidney disease progresses in the setting of diabetes, the amount of protein in the urine may increase to very, very large amounts. And when you have those very large amounts of protein in the urine, that’s when you could start to develop symptoms of fluid retention, swelling in the arms legs, abdomen, fluid build up in the lungs and high blood pressure.
In parallel to this protein appearing in the urine, we also see a decline in the glomerular filtration rate. So that is the amount that your kidneys are able to clear the blood of toxins. And we use this blood test called creatine to determine that. So as your creatine in the blood goes up, it means that your kidneys are cleaning the blood less and less.
So, I’ve mentioned the symptoms that folks may see if they have a lot of protein in the urine. What about symptoms of a high creatine in the blood again, in the early stages? There really aren’t any when the creatinine is a little bit high in the blood suggesting that there is a little bit less filtration in the kidney from diabetes, there may be no symptoms at all. It’s actually when the creatinine is so high in the blood that the percent kidney function is, I want to say about 30% or less, that people may start having symptoms, again, of fluid retention, higher blood pressure or abnormalities in electrolytes.
So, you know, to summarize in the early stages, no real symptoms. But when you get to some pretty severe kidney dysfunction, like 30% of your kidneys working from 100% or a lot of protein in the urine. And that’s when you may start to experience fluid retention and other symptoms. This is why it is so important that people with diabetes see their doctor regularly and have urine testing done when they see their doctor at least once a year or more to screen for the presence of diabetic kidney disease.
Shireen: So it’s very important, especially as listeners hear someone may have diabetes themselves or a loved one. This is an important part of that screening. We always hear, get your, you know, get your feet checked, get your eye checked, eyes checked. I mean, this is just as important to look at your kidney function and then just really to, to hone in on that protein number as well.
You know, we as we’re, as we’re sort of talking about this, could you also help us understand can diabetic retinopathy, excuse me, diabetic nephropathy be prevented? Are there things that someone with diabetes can do today to say, ok, I have diabetes, but these are things that I can do to absolutely prevent? This lifestyle modifications come to mind medications. What other kind of interventions are available to, to someone who has diabetes?
Dr. Limonte: Yeah. So the biggest factor in primary prevention of diabetic kidney disease, we think of prevention in, in different ways. So, primary prevention is preventing diabetic kidney disease from occurring and secondary prevention is once you have diabetic kidney disease, how do you slow its progression?
So, for primary prevention of diabetic kidney disease, blood glucose control is one of the most important things that you can do to reduce your risk of developing kidney disease. This has been shown by multiple studies that controlling your, you know, having your, your blood sugar as close to normal for as long as possible will have impacts on your kidney health long term for decades out.
It’s also important to maintain a healthy weight because obesity can contribute to kidney disease to treat high blood pressure, often, a lot of people with diabetes also have high blood pressure. So controlling high blood pressure, keeping that in normal, in normal ranges, puts less strain on the kidneys. And you know, other general lifestyle measures such as quitting smoking, there are no medications you know to, to prevent diabetic kidney disease from coming on if you if you have it, but these lifestyle measures can really make a big impact in one’s long term health.
And once you know, people develop diabetic kidney disease, we do have great medications to slow the progression of diabetic kidney disease and reduce the risk of ultimately developing kidney failure. And those medications, we can start the second that we identify protein in the urine at that very early stage of diabetic kidney disease when someone doesn’t even have symptoms or feel unwell.
So, you know, that’s another plug for following really closely with your primary care doctor, your endocrinologist and, and getting all of these, you know, screening measures done, as you were saying, foot checked, urine checked, eyes checked, in addition to ensuring that you’re on the best glucose lowering regimen for for you.
And because you did mention diabetic retinopathy, I do want to also acknowledge that all of these other diabetes complications, like diabetic retinopathy, neuropathy, disease of the nerves and nephropathy, disease of the kidneys, all kind of occur together. So if you have diabetes, affecting your eyes, high blood sugar, affecting your eyes, then you are at higher risk for having diabetes, affecting your kidneys. So, important for treating, you know, all of diabetes and its potential complications.
Shireen: And the connecting factor here being that blood sugar, right, that high blood sugar is impacting the eyes, the you know, the you mentioned the neuropathy with the nerves. And then of course, we’re talking about neuropathy here. So it’s that high blood sugar that we don’t sort of think about it, this annoyance that we have to manage every single day, but at the heart of it, what we’re really saying is that this has implications that ripple across multiple organs just not a specific one.
Dr. Limonte: Right. And it’s not just, you know, we we the root here is high blood sugar, but what it is really is everything that’s downstream of that. When your cells are constantly exposed to high blood sugar, it triggers inflammatory pathways. It causes injury to the structures within cells that handle energy metabolism.
For example, mitochondria and generates oxidative stress. And this cycle of high blood sugar inflammation, oxidative stress ultimately leads to scar formation in the kidney cells. And there are similar mechanisms for these other organ systems, the eyes, the nerves, et cetera.
Shireen: This is a very helpful Dr. Limonte. This, you know, another question that I have for you is really being able to understand what, what is some of the research look like in this space as it stands today. So could you really touch on some of the outgoing research efforts focused on understanding the linkage really between the you know, multiple chronic diseases and just emerging breakthroughs that you can share with our listeners here.
Dr. Limonte: Yeah. So I’d say what folks in the diabetic kidney disease space are probably most excited at the emergence of new drug classes in the last 5, 10 years that have been shown to reduce the risk of diabetic kidney disease progression and incidence of kidney failure by 30% or more. And those drugs are SGLT-2 inhibitors glp-1 receptor agonist agony are some of those drug classes up until the last decade, there was really just a diabetic kidney disease was kind of a one size fits all treatment approach with limited drug options. And with the emergence of these drugs and research for new drugs, we’re finding that we can develop more, we can, we can have better care for people with diabetes and slow disease progression. And we can also target therapy to the individual so they are on the drugs that are best for them.
And that is where a lot of ongoing exciting research about understanding diabetic kidney disease is going for example, through consortiums like the kidney, the Kidney Precision Medicine Project, where groups are trying to understand the exact molecules and pathways involved in diabetic kidney disease and try to answer questions like why is one person with diabetic kidney disease developing disease faster and more and more severe disease than another person with diabetes and kidney disease? And how do we target drugs to, you know, person A versus person B? So that’s where I think this field is heading, which is really exciting and very promising.
Shireen: So this opens up opportunities for more personalization, customization known, you know, in, in terms of the intervention and the level of that intervention itself.
Dr. Limonte: Exactly. We’re talking about moving from a one size fits all approach to individualized diabetes and diabetic kidney disease care.
Shireen: With that Doctor Monte, we are toward the end of the episode. However, at this point, I would love for our listeners just to know how they can connect with you and learn more about this incredible work that you do.
Dr. Limonte: So listeners can learn more about all of the research being done on kidney disease at the University of Washington on our kidney research institute website. That’s kri.washington.edu. And listeners should also look up the kidney precision medicine project because a lot of really exciting groundbreaking work is going on there.
Shireen: Lovely. Ok. And we’ll link by the way, all of this up in the show notes below. So to our listeners, head over in our show notes to find that information, but that Dr. Limonte, thank you so very much for your time here today with us to our listeners, thank you for tuning in on another episode.
You know, the drill at this point, we’re gonna head over to social media next, head over to Facebook, Instagram, find this podcast post and comment below to tell us: What is your personal experience with managing diabetes for yourself, for a loved one? And then how are you thinking about the progression of kidney disease? And how are you managing that for yourself or for a loved one?
Again, head over to our Facebook, our Instagram and comment below this podcast supposed to tell us how again: what is your personal experience with managing diabetes along with kidney disease? We’ll continue the conversation there. Thank you so much for joining us and thank you again, Doctor Almonte. It was an absolute pleasure.
Dr. Limonte: Thank you.
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