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Diabetes Core Update
Special Edition: Understanding Chronic Kidney Disease in People with Diabetes — Epidemiology, Pathophysiology, and Detection - March 2026
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welcome to this special series of Diabetes Core Update where we are going to discuss today chronic kidney disease in people with diabetes. This is a critically important area for all of us in primary care and endocrinology to really understand because CKD is a common consequence of diabetes and there is now a lot of that we can do to help decrease the likelihood of developing CKD and to slow the progression of CKD when it occurs. You know, the problem, though is when there's a lot to do, it's, it's a double edged sword. There's a lot to do, that's a good thing. But you've got to know what to do. And that creates its own set of challenges. You have to detect disease early in its course and then know when to initiate different medicines. I'm your host, Dr. Neal Skolnick, professor of Family and Community Medicine medicine at the Sidney Kimmel Medical College of Thomas Jefferson University. This special series of Diabetes Core Update is sponsored by Bayer. Joining us to discuss this topic is Dr. Holly Kramer. Dr. Kramer is a nephrologist, a professor of public health sciences and medicine in the division of Nephrology and Hypertension at Loyola University in Chicago. She has served as president of the National Kidney foundation, and as of this past December, Holly was appointed editor in Chief of the National Kidney Foundation's journal, Advances in Kidney Disease and Health. Holly, welcome to our podcast.
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Dr. Skolnick, it is so great to be here. I'm a huge fan. You're such a great thought leader and I'm so happy to talk about my soapbox. I'm getting on it right now. You know, only 20% of people with kidney disease are aware that they have it. If we can get people diagnosed earlier and treated, we can really do kidney failure. And kidney failure is hugely costly to our health system. You know, we spend $150 billion almost annually on dialysis and CKD. You know, it would benefit our own pocketbook for the United States if we got more people diagnosed. And so I'm really grateful to whoever is listening to this because they can help so many patients.
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Holly, your passion always comes through. Whenever you talk, you are filled with conviction. Where? Can I just ask you, how did you get into the combination of public health and nephrology is a little bit unusual and your sense of passion and conviction stands out. How did you get into this?
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My mom was a dialysis nurse in the 1970s and started some of the very first dialysis units in northeast Indiana. And back then there was mainly home dialysis and so she would travel to people's houses, and sometimes I would skip school and go with her, and we would go to, like, Cherubusco, Indiana, and walk into a home that had a lot of blue shag carpet and a gigantic dialysis machine, you know, on top of that blue shed carpet. But back in the 70s and the 80s, you know, people didn't live very long. It was really kind of traumatic, actually, to be on dialysis. And her hope was that I would become a nephrologist to prevent people from getting kidney failure in the first place, because back then she was very prescient and she said, we really need to do so much more on prevention. But of course, she didn't realize we were going to then step into an obesity epidemic in the 1990s, which really launched end stage renal disease. And so we've had like a really linear increase in number of people starting dialysis over the past 20 years. But now we have these medications for the first time, you know, starting back like in what, 2017, with the SGLT2 inhibitors that really reduce the risk of kidney failure. But the problem is, if people are not getting diagnosed, they're not getting on those medications, they're not getting the education, they're not getting medical nutrition therapy, and so they still end up on dialysis. I know that, like, I think people feel really comfortable with the estimated glomerul filtration rate, but I think where we are really losing out is the urine album decratinine ratio. Right. So about 95% of people with diabetes get their creatinine measured every year. And I think people feel pretty comfortable. You know, the glomerul filtration rate is given to you in the medical record, but the urine album to creatinine ratio, every health system just has so many different ways to measure it.
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I. I think you're right. Let's really focus on that in a few minutes and, and really emphas that in a little more depth. Before we get there, I just want to level set and talk about both the epidemiology and a little bit about the pathophys of CKD for type 1 and type 2 diabetes. And I'm going to add in here, Holly, because I don't think most of us are as aware, as you just emphasized, of how obesity has affected all of this. So if you can also share a bit about how that's fit in. So. So let's start with epidemiology, Both for type 1, type 2, and where obesity fits into all of this for both
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type 1 and type 2 diabetes. You know, about 40% of those people will develop kidney disease during their lifetime. So generally, for a person with type 1 diabetes, if they've had diabetes for at least five years, to go ahead and start screening them, it takes probably about 10, 15 years of exposure to hyperglycemia to really develop the damage in the kidneys that we can detect with our current test. Maybe in the future we'll be able to detect those earlier. So. But usually with type 2 diabetes, you know, we're not really sure when the disease started. So it's recommended that they get tested for CKD as soon as they get a diagnosis of type 2 diabetes, because it's very prevalent.
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Yeah. And there really does seem to be some individual variability about how long it takes. And obviously, part of that's genetic. Part of it has to do with glucose control. And how about for obesity? What should we be thinking of there? Because there aren't currently clear recommendations.
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Yeah, I mean, I think that's a really good point. We don't have clear recommendations. There's a lot of discord about what we should be doing about it. Most of the literature, though, would suggest that really for obesity itself to be a risk factor that's not giving you kidney disease mediated by diabetes and hypertension is gonna occur when the BMI starts to get to be, like, above 40. So especially people who are like, 45, 50, you literally can get so much abdominal visceral adipacity that it can compress the kidney and limit blood flow to the kidney. So a lot of times those patients you might just see is almost like an ischemic form of kidney disease, where they don't have a lot of urine, albumin, excretion. It's just more nephron loss due to ischemia. So most. I think most of the kidney disease from obesity is really mediated by its effects on metabolism. You know, diabetes and hypertension.
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Yeah, that makes sense. Although I'll say, a lot more people in our practice now do have class three obesity. I think you're talking about 5 to 10% of the adult population now has BMIs over 40. 40% have BMIs over 30. So that's another risk factor to be aware of. Any other risk factors you mentioned? Diabetes, hypertension, obesity, Any other things in that cluster of metabolic illness that should raise our concern about even more heightened risk?
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Well, sure. Cardiovascular disease, of course, is a risk factor. Those things all go hand in hand. Right. OBEs, diabetes, heart failure, kidney disease. It's all kind of Clusters together. But other factors to think about would be like family history. So always ask a patient if they have anyone in their family on dialysis. Really should make you think that's unusual because only there's only about 600,000 people who are on dialysis. So it's unusual to have someone who. With kidney failure that they need dialysis. That should make you think that they could have a genetic predisposition to kidney disease. Could be like polycystic kidney disease, or it could be like APOL1 mediated kidney disease. That's something to think about. Another thing to think about is just kind of like nephron number. Nephron number would be like, were they born prematurely so that their nephrons didn't continue to mature all the way up to 40 weeks. So if you're born at, like, 30 weeks, 35 weeks, you may not have a complete nephron numbers as a baby that was born at term. Other thing to think about is, like, previous exposure to medications that could have caused nephron loss, like chemotherapy, or if they've had, like, a nephrectomy because they had kidney cancer or they donated a kidney. Those are all things that you think about. Okay, they have a reduced number of nephrons so that those remaining nephrons have to work a little extra harder. They're gonna be more susceptible to injury. And as you lose more nephrons, chlomeral filtration rate goes down.
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Boy, that's fascinating. There's some. In an. In another area, there's an analogous thing going on that's also relatively new in understanding. In copd, we used to think of it as only happening in people who were smokers, destruction of lung function. And it turned out there's this wonderful study about five years ago showing almost exactly what you said happens with kidneys, that there is a subset of people, and it's a large number that have smaller lung function early in life. And even though they follow a normal trajectory of lung function decline, because they're starting at a lower level, they reach a level where they get short of breath and have COPD earlier. And it sounds very similar to what you're describing with the kidneys. Now, when you talk about nephrons, it clearly leads me then to ask about something I'm a little hesitant to ask you to talk about, which is pathophysiology and mechanism of renal injury and diabetes. And that's one of those things where, at least for us primary care physicians, when you talk about nephrons and tubules, we get A little bit scared. But can you share some of the pathophysiology in a way that makes it understandable without a lot of pictures, since this is just an audio podcast?
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Yeah. So the pathophysiology in diabetes is really multiplicative. There's numerous pathways that exist, and they all kind of exist in parallel. But I think one of the main things that people should understand is remember that your each of these nephrons, you have usually about a million nephrons in each one of your kidneys, they are filtering the blood, right? So they're going to be filtering out that glucose, and then the glucose has to get reabsorbed. Right? So if you don't reabsorb that glucose, we would die. Right. So we have to reabsorb that glucose, and that glucose gets reabsorbed in the proximal tubule. But those sodium glucose co transporters, when it gets reabsorbed, if you have really high blood glucose levels, then that means the kidney is reabsorbing a lot of glucose by the proximal tubule, and when it reabsorbs it by the sodium glucose CO transporters, sodium gets reabsorbed with it as well. So if you are reabsorbing a lot of glucose in the proximal tubule, then a lot of sodium gets reabsorbed as well. So now sodium is not getting part to that very end of the loop of Henle distal tubule that loops back what's called the macula densa. So the macula densa is sort of like the thermostat for chlomeral filtration rate. And it's like it's looking at what's in the urine, right? It's looking at what you've. What is still left in the urine. It hasn't been reabsorbed. And it's like, where's all the sodium? What's going on? Like, we are not making enough urine here. Turn up the volume. So it turns up the glomerul filtration rate by vasodilating that afferent arteriole. So glomerul filtration rate, actually in the initial part of kidney disease progression, where your kidney disease is still not noticeable, because glomerul filtration rate looks actually high because you have that hyper filtration, because that afferent arteriole has received a little message to vasodilate to increase glomerul filtration rate. So you see a creatinine of 0.6 and you're like, oh, my patient's doing fine. They're not. They are hyper filtrating. And so that level of hyperfiltration correlates with that hemoglobin A1C. So people who have hemoglobin A1Cs of like 9, 10, 11, they're gonna have really high glomerul filtration rate. So when you're filtering all of this extra glucose and sodium, you're also filtering all of these we call chemokines, or inflammatory markers, right. That increase inflammation in the kidney, and they activate mesangial cells. And mesangial cells are like the glue that kind of hold all the capillaries together in a glomeruli, and they can turn into fibroblast and create collagen and just kind of create those big pink masses of scar tissue in the glomeruli that causes the nephron loss. You also have the issue of the hyperglycemia in your body causes the production of things like advanced glycation end products. So that's when, you know, the. You have the carbonyl product, you know, goes with an amino group on a protein or a lipid, and it creates this irreversible Amadori product. Just like hemoglobin A1C is an Amadori product. And that stuff is like glue, right? It loves collagen. It loves type 4 collagen. And where do you have a lot of type 4 collagen? You have it in your glomeruli, you have it in the back of your eye, and you have it in your skin. And so you. So you have all these things that are causing a lot of scarring in the kidney because of the hyperglycemia.
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Holly, that was absolutely the best and most understandable discussion of this that I have ever heard, because you hear some of these terms thrown around, but you pulled it all together. So thanks so much for covering that. So clearly, let's now get practical. So we know that people with diabetes, people with obesity, people with Type 1, Type 2, are all at heightened risk. We've talked about the pathophysio. What should we do be we be doing in the office coming back to screening for CKD?
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Okay, so anyone with diabetes, if they have type 1 diabetes, they should have it at least five years before you would start screening them. Type 2 diabetes, start screening them, you know, at least annually, as soon as you make that diagnosis. And so it's easy. You just get a basic metabolic profile, right? So you get a serum creatinine, you get your Glomerul filtration rate. And what we're looking for there is if the glomerul filtration rate is less than 60, glomerul filtration rate is really kind of correlated with age because as you age, you lose nephrons. So if you have an 80 year old, a normal GFR for an 80 year old can be as low as 60 in a female and as low as 80 in a male. But we don't have age specific GFR cut points because it's just, it's too complex as it is and we want to make it as simplistic as possible. So I think people feel comfortable about that. And then talking to the patient, your GFR is less than 60 or above 60, whatever. The second part is that albumin to creatinine ratio. And the reason why that's so important is because if you look at the progression of kidney disease, remember I talked about that early on in the disease process, you might actually see the glomerul filtration rate is increasing. And most people may not notice that. But at the same time that you're seeing that, you know, because remember, you're, you're, you've got this vacuum cleaner on and you're just sucking up all the glucose and the sodium in that proximal tubule and all these inflammatory markers and all that stuff that's going on that's stressing out the nephron. And the first thing you'll see down that's stress nephron is the albumin in the urine goes up. So that's why measuring that urine albumin to creatinine ratio, that's the earliest way that you can find kidney disease. So if it's above 30 milligrams per gram, that albumin to creatinine ratio, then that's your trigger. That should be your trigger to do something about it. Even if the glomerul filtration rate is
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nano, and that's so important, that indicates how that filter is working essentially. Right. Whereas the EGFR has to do with total nephrons available. Is that a way to think of it?
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Yep.
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And it seems so simple, right? We're getting labs, we send someone for a cmp. It seems simple to send off a urine. But how are we doing with accomplishing that? Is there any data out there on how good we are at using both UACR and EGFR for screening?
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So data suggests that anywhere between 60 to 80% of people with type 2 diabetes are not getting a UACR done annually. But I, you know, but I think really the burden of that is on the nephrologist, because we started calling this microalbuminuria back in the 1980s, which makes it sound like the albumin is small and you need a microscope. What it should have been called is increased urine albumin excretion. But that term was created by someone from the Netherlands who didn't. English wasn't his first language. So that's actually really what happened. And so we're. We're at this battle of. Of words, you know, of trying to explain what it is. But just basically what it means is that normally you don't have hardly any albumin in the urine, but you will have protein in the urine. So those proteins come from, like, the proximal tubule has tons and tons of all these transporters, because 80% of the work in the kidney is done by your proximal tubule. And your proximal tubules actually account for about 50% of the weight of the kidneys. So it's a ton of proximal tubules. So they're constantly sloughing off these transporter proteins in the urine, like beta 2 microglobulin or alpha 1 microglobulin, globulin. All these different weird transporters are in the urine. And then you also have like, Tam's horseball protein, which is secreted by the kidney into the urine. It's like an antimicrobial peptide. You also may have some. A little bit of light chains in your urine as well. So you always have some proteins in urine, but less than 10% of those proteins are albumin. So if you find increased albumin, then that tells you something's wrong, because you have, you endothelium on your glomerul capillary has all these negatively charged glycosaminoglycans and heparin sulfates. Then you have the glomerul mason membrane. And then you have these podocytes, which basically, podocytes are like an octopus. Think of an octopus. Two octopus wrapping around a capillary. And the legs of the octopus interdigitate really, really tightly. So if you're starting to see albumin in the urine, most likely those podocytes are not interdigitating. The legs of the octopus are like, not touching each other there you got these big gaps, and albumin's pouring into the urine.
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Interesting. And, you know, it's still. It still amazes me that we are not better than we currently are at checking urines for albumin because it Just seems simple. And I imagine some approaches that will help now is with many of our electronic records and people with diabetes, we're seeing pop ups around the side in red. A reminder, things like our podcast today that educate clinicians to really think about it. Now, when we think about any screening test, one of the things that we think about is sensitivity of the test specificity and what action it leads to. Let's take that first, the test characteristics. So let's say you get a urine for a UACR and it comes back at 4:40. Is that time for action or does that need to be repeated in order to say this is reflecting what we think it does?
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So that's a great question. I'd say the sensitivity is high, the specificity is not. So even if you get a positive test, it's likely it may not truly be positive. So if you find a positive test, always repeat it like in two months. The urine album to creatinine ratio is really noisy. It's influenced by illness. Anything, any kind of inflammation or illness will increase it. So that's why people always have a little bit of protein when they come in for heart failure or pneumonia. It also is going to be influenced by like high blood pressure. So if the person has really uncontrolled blood pressure, get their blood pressure controlled, repeat it, it probably would go away. So you do want to repeat it. And you should not give a diagnosis of moderate or severely increase your albuminin excretion unless you do show that it's persistent. So I think your point's extremely well
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taken and that that's important. And so we talked about test characteristics, importance of repeating it, and then the next step is always action. What does it lead to? And, and let me say, Holly, we're gonna spend a lot more time on the medicines available in a future podcast. We're gonna go over this in detail, but I'd like to just make sure our audience hears a brief overview of the pillars of care, because there used to be not much you could do and now we actually have pillars of care. Can you briefly go over that and we'll come back to it in detail at another podcast?
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Sure. Well, I would say definitely, you know, blood pressure control. If the urine album to creatinine ratios are elevated, you know, use an ACE or arb. I don't think it's necessary to use an ACE and ARB if they don't have increased urine albin excretion. Just get the blood pressure controlled and then medical nutrition therapy. I think, you know, getting the patient to eat better. Of course it should be considered a pillar. But then you have the sodium glucose co transporter inhibitors, so that's a pillar. You have the non steroidal monocorticoid receptor antagonist, that's another pillar. And then you have the GLP one with or without the glucose dependent insulinotropic polypeptide, but that's also another pillar. So that itself I say, like weight loss should be viewed as a pillar. However that happens. The kidneys love weight loss.
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Interesting. So that's so helpful and that gives us a sense because we're getting toward the end of our podcast of the fact that there is so much we can do now and this is very different than even just 10 or 15 years ago. The world of slowing progression of kidney disease has changed enormously. We're about out of time. Holly, any final thoughts? Thoughts that you have for our listeners?
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The urine alba to creatinine ratio. I find that people struggle with this. I just want to just remind everybody that everyone excretes a gram of creatinine a day, even if the glomerul filtration rate is bad. Remember, creatine goes to creatinine and creatinine is what you urinate out every day. You urinate about a gram every day. That's why we standardize the albumin for the creatinine urine albumin to creatinine ratio. Remember that bad things happen in threes. So you know, if you, if you get a flat tire in the morning, probably your oven's gonna break and your window's gonna break. Right? Bad things happen in threes. So it's 3 milligrams per gram of creatinine a day is ideal. Normal. That's normal. Ten times that or 30 milligrams per gram is the moderately increased serum albinocretinine ratios. And 10 times that is 300 milligrams per gram or severely increased serine, albumin and creatinine ratios. So just remember, everyone excretes a gram of creatinine a day. That's normal. And then we standardize the albumin by thinking of the. That rule of threes, right? 3, 30, 300. And that's in milligrams. Whereas everyone excretes a gram of creatinine a day. So 3:30, 300 milligrams per gram.
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Holly, you are such a great teacher. Dr. Holly Kramer, thank you so much for joining us today.
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Thank you. It's always great to be here.
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And Holly, I can't get the image of you as a little girl joining your mother and the blue shag running
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every house had blue sag carpets where,
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oh, gosh, I remember that. Most of all, I want to thank our listeners. As always, thank you for joining us on this special edition of Diabetes Core Update, discussing CKD in people with diabetes. This special edition of Diabetes Core Update is sponsored by Bayer. We thank you for listening. We are going to do a deep dive on treatment in a future episode, so tune back in. For the American diabetes association, I'm Dr. Neal Skolnik. Till next time, stay safe and keep learning.
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Sam.