KIDNEY FUNCTION Explained: Tests, Risks, and Habits That Protect Your Health | Dr. Richard Johnson

What's happened in the last couple decades is the recognition that if you put an animal with kidney disease or a person with chronic kidney disease on a very low protein diet, it actually can make malnutrition worse. And it turns out that low protein diet is not as good as you would think. But high protein diet is bad. When you eat a very high protein diet, the kidney tries to respond by increasing the filtration and that can translate into higher pressure. So it turns out that if you take an animal with chronic kidney disease and you put it on a very high protein diet, the kidney disease will progress. Not only will you get more symptomatic because you're holding on to nitrogen products, but there's an actual worsening of the kidney disease.

So I'll give a little context for the audience. The context of this conversation is it's part of a series that we're doing inspired by the fact that Levels is offering some more kind of expanded uh blood testing. Now, what we're trying to do with this series of shows is look at each of the individual uh systems within the body. So whether that's organ specific, like today we're going to talk about kidneys, we've talked about liver, we've talked about pancreas, um or things like cardiovascular, metabolic, and understanding sort of how what's the importance of that system in your body, how do we measure its health, and then how do we impact its health. And so today we're going to talk about kidneys with the person who literally wrote the book on kidney disease, edited the book, edited the book on kidney disease. Um, and maybe let's just start there for folks who don't know you, a little bit of your background, how did you, where'd you come from, how did you come to focus on kidneys?

Yeah. Okay. Well, I'm a professor, uh, emeritus now because I just recently retired from the University of Colorado, but I've been at a ver number of universities, um, working, uh, as a clinician as well as a researcher, uh, focused primarily on kidney disease. I was trained in internal medicine and nephrology, which is the study of kidney disease. And, um, I've written a lot of papers, uh, hundreds of papers on the science of kidney disease and the clinical aspects of it. And, um, I edit the main textbook, uh, one of the, probably the, well, it's the number one favorite textbook in the US and in internationally. It's called Comprehensive Clinical Nephrology, and it's a textbook for people in training who want to become kidney specialists, as well as for the clinician, and it focuses on the management of kidney disease. Um, and I've been the founding editor. It's in the eighth edition or it's going into the eighth edition, and it's a lot of work to to edit these huge books, I imagine.

So let's start maybe just at the at the very basic level. What is the kidney doing in my body?

Well, the kidney is the barometer for the for the body. Basically, it it's trying to make sure that all the systems are working. It's in charge of excreting the bad stuff, uh, like when you when you, uh, eat food and so forth, they're they're byproducts and waste products that are generated and that have to be excreted. And the kidneys are the professional uh system for cleaning the blood. So the kidneys, uh, you know, every day there's 180 liters of blood rushes through the kidney and gets cleaned. Um, and we put out about a liter of urine, one to one and a half liters of urine a day. Usually, it's about one and a half liters. Um, and that urine output will include all these wastes. So, first and foremost, it cleans the blood. Uh, but it also, uh, can make substances that are very good for us. It it makes the active form of vitamin D. It makes a hormone that helps raise our that produces red blood cells, uh, in the bone marrow. Um, and and it also, um, doesn't just excrete, it reclaims a lot of good things. So it will it will filter, but it will reclaim the stuff that we need to maintain. And what it does is it tries to keep the, um, electrolyte concentrations in the blood within a a range that is good for the function of the body. So it really is the great regulator. It, um, it gets about 20% of the blood supply. Um, it's, uh, it expends much more oxygen than the weight of the kidney, the kidneys would tell you because it does a lot of work to try to reclaim, uh, all the good stuff and to get rid of the bad stuff. So it's a highly energized, uh, organ. It's, there's two kidneys, obviously, and so they're working together, and, uh, and they have, each kidney has about a million filters called glomeruli, that are these little filters that filter the the blood and keep the proteins in and get rid of all the bad stuff.

How did you get interested in the kidneys? Why does, why is this your focus?

Well, it's a good question. I, I, uh, typically kidney disease is can be very complicated, and, uh, a lot of people kind of avoid kidney disease, uh, to study kidney disease because it is complicated, and I was one of those people who was going to avoid it. Um, but when I was a senior resident, um, I had to do, I signed up to do two months on a kidney ward because I wanted to, um, I just wanted to learn it well enough to get by, but not to specialize. Um, but it turned out that, um, the first day, the people that I was supposed to work with told me that they were, the the fellow who was like the expert told me he was leaving for Australia for two months, and that I was going to be the only one on service. And so for two months, I worked every day on service as the resident and fellow, and, uh, pretty much was on call most of the time. And, um, and in during that time, I realized that kidney disease was a very wonderful area to study, that there was a lot to learn. The patients with kidney disease are are quite, you know, they have a lot of health issues, and it's, it was enjoyable taking care of them. There was a little Alaskan boy who fell off a cliff and evulsed his kidneys, and I took care of him, and when he finally got better, I took him sailing with his dad, and his dad donated a kidney to him, and it was, it was great. And after that, I said to myself, you know, uh, I think I'm going to study kidney disease. But I also studied other things. I'm, I have a couple of specialties. My background is in nutrition. I thought I knew everything, but it wasn't until I was tracking that I had to ground truth my assumptions with what was actually happening in my real life. The only way to actually know what works is real data. Using Levels has been life-changing. For one, I've learned how food individually affects me. Even though I know as a physician how stress impacts your glucose levels and your cortisol levels, it was very eye-opening to see right in front of me in real data that my glucose levels go through the roof under certain forms of stress. You can see how food, stress, sleep, and exercise impact you personally to make smarter choices that improve your health. With features like AI-powered food logging, real-time blood sugar tracking, comprehensive blood testing, and personalized dietitian support, Levels gives you everything you need to optimize your health. Whether your goal is losing weight, having more energy, or choosing the right diet for you, Levels gives you the full picture of your metabolic health. Stop guessing, start knowing. Check out Levels and click the first link in the description.

Now, back to the episode. What do we know about the kidneys now? And and we can dive into kidney disease specifically because that's the next place we're going to go is kind of what can go wrong with it. But this, the study of kidneys in general, what do we know now that we didn't know when you started? You've been doing this 40-some years, right?

What don't tell anyone. Oh, the, you know, we're learning things about the kidneys all the time. And one of the things that's come, probably was known by somebody beforehand, but, um, one of the things we're learning is that the kidneys are actually very sensitive to, uh, heat stress. And, uh, because, uh, the kidneys do a lot of work to to help protect you when it's hot, like here in Austin. And, uh, one of the things it does is it concentrates the urine and helps keep the water, uh, helps retain water so that we don't get dehydrated. And, uh, what we're learning is that, um, they are playing a very important role with as temperatures rise, and also because they they do a lot of work to preserve the the water and the electrolytes, they turn out to be very vulnerable to, uh, to severe heat stress. So I've done a lot of work on an epidemic of kidney disease that's occurring in Central America, um, along the Pacific coast. There's a huge epidemic. It's killing a lot of young people, especially manual workers, uh, sugarcane workers, and it's also in Mexico, and it's occurring in India, and it's occurring in Sri Lanka and Thailand. And I've been kind of one of the leaders trying to understand what's causing this epidemic. And one of the things that's clearly involved is chronic recurrent heat stress. And so, uh, we're we're discovering that the kidneys, um, an a target for, uh, heat stress and also for toxins. And so we've identified some agrochemicals and toxins like that are released from sugarcane when they burn the sugarcane, gets into the air, they breathe the workers breathe it in, and it can lead to, um, particulates getting in their kidneys and cause kidney disease. So, uh, so one area that's kind of, um, new is the, uh, the role of the kidneys in cleaning the body is there, but they also can retain some of the toxins. Some of the toxins can be taken up in the kidney, and the effects of heat stress can be hard on the kidneys. So the kidneys are are one of the, what they call it, the canary in the coal mine. Mhm. They they can be one of the first, uh, things to that go abnormal, uh, in the setting of of of any kind of change in the environment. Doesn't have to be heat, but they're they're very sensitive organs.

What does that look like? What is, we talk about kidney disease, and I sort of understand that to be a not necessarily the end stage, but an end stage of of dysfunction that you've got dysfunction builds, and at some point it becomes kidney disease, chronic kidney disease, as opposed to it's not a disease you catch. It's not a sort of virus that comes in and now your kidneys suddenly don't function. But what is building kidney dysfunction look like? What do we mean when we say they start to get stressed, and how does that end up in kidney disease?

Well, yes. So there's there's different, um, ways the kidneys can be damaged. And the classic ways are what we call non-communicable diseases, uh, where it's, it's not an infection. I mean, you can get, there are infections that can hit the kidneys and so forth. They're rare diseases like leptospirosis, and that can really cause kidney damage as an infection. But most ways you get kidney disease, the most common way is to have diabetes. And diabetes, uh, can affect the vision and the eyes is one of the target organs, and the the kidneys are one of the target organs. And so, and blood vessels get damaged by diabetes. So diabetes turns out to be the number one cause of chronic kidney disease. And then the second one is high blood pressure. Now, high blood pressure is a really interesting thing because there was a time in the world when high blood pressure was very rare, but now a lot of people have high blood pressure. And, uh, work suggests that it's that high blood pressure begins as a problem very early on. There's a problem with the kidney getting rid of salt, and the kidney function can be normal. So it's, it's a, it's a type of kidney problem where the kidney function is not affected initially. Um, and, um, but there's a changes that go on in the kidney that make you hold on to salt, and that seems to trigger the development of high blood pressure, and I've studied that extensively. But once you have high blood pressure, the high blood pressure itself can also damage the kidney. So the kidney can become the kind of the cause of hypertension, but then the hypertension can come back and make the kidney disease worse. And so high blood pressure is thought to be maybe the second most common cause of kidney failure. And so you've got diabetes, high blood pressure, and then you can get early evidence of kidney disease with metabolic syndrome, when when you just from, uh, mild obesity and slightly elevated blood pressure and insulin resistance. All these things that we talk about, they can be associated with low-grade kidney disease. Rarely does it cause kidney failure, but it can show evidence of kidney involvement. So, you know, those two, diabetes and hypertension, are like the two big ones. Then there's anatomic causes, like if you have kidney stones that block the the ability to urinate or block block the outflow of urine. Uh, there's, uh, anatomic problems like cysts and things like that that people sometimes, it's induced by trauma, like a car accident or something which damages the kidney. Or you can have a hereditary disease. There's one called, uh, autosomal dominant polycystic kidney disease. It's actually very common, um, and a lot of people have this disease, and it it causes kidney failure over time. There are a lot of people very interested in that disease. We just talked about this epidemic of chronic kidney disease that's occurring from heat stress and and toxins, and that's seems to that may be increasing now over the last, uh, decade, and we're beginning to see some cases in the US. Um, and and, uh, then there's a whole host of immunological causes of kidney disease, what we call autoimmune diseases, like lupus, systemic lupus, and there's a whole variety of them. And and they're they're called oftentimes called glomerulonephritis because they are inflammation of the filters, which is the glomeruli. So, I've just given you a little tutorial on the causes of kidney disease. Um, and usually when people talk about kidney disease, they're talking about, uh, kidney disease associated with reduction in kidney function. You know, the re inability to excrete what we need to excrete. And so, we start to build up things like creatinine and urea in our blood. And so, uh, that's really what a lot of people talk about kidney disease as is types of chronic kidney disease associated with impaired excretion of electrolytes. But, as I mentioned, you can have things like high blood pressure with normal kidney function, but the kidneys aren't normal. The kidneys themselves show changes that lead to, uh, retention of salt, but it, but they're still getting rid of the urea and all those things.

Fine. So look, so the, it's a little bit complicated. That's that's why we have, that's why nephrologists are still looking for more nephrologists. So if anyone out out there wants to become a kidney specialist, please, there's, there's plenty more to understand. There's plenty more to understand.

So when we use the phrase kidney disease, is there a cut-off of kidney function at which it becomes kidney disease, or is any sort of damaging reduced function of the kidney kidney disease?

Well, uh, the nephrology world has classified chronic kidney diseases into stages and stage one, two, three, four, and five. And, um, even very minor changes in kidney function can give you a stage one, for example. The truth is that stage one and stage two kidney disease is very, very mild and really has almost no implications unless it's reflecting a disease that's coming on, right? Uh, it's good for the the kidney specialist to know and for the internist taking care of you to know that you have stage one or two, and it may affect how often you're monitored and things like that. But in terms of regular living, there's no real impact. When you get to stage three, um, it's often in the literature the when people say chronic kidney disease, often they mean stage three or higher, stage four or five. And stage three, um, is usually defined as a a 60 mL per minute divided by the body surface area, which is taken as 1.73 meters squared, but basically, it's, uh, people remember the number 60. And when your GFR or glomerular filtration rate, and it's usually estimated, so it's your eGFR, it hits 60, it's called chronic kidney disease stage three, and it does mean that you have reduced kidney function that's at about half of normal. And that the main effect at that point is with medications. If you're taking medicines that are excreted by the kidney, you have to reduce the dose a little bit to account for the the reduced kidney function. So that's the main association. Um, but when the kidney function gets to 45, which is still stage three, they call it stage 3B, basically, because stage three is from 30 to 60. And right around 45 is when when the problems of of having kidney disease become a little bit more evident. There's a pretty marked risk for high blood pressure, for heart disease, for you start developing anemia, you start retaining phosphate, your bones start getting weaker, you have more trouble sleeping, you know, it that all begins right around that 45. Now, what's confusing to the world, including to nephrologists, is that there is a general decrease in kidney function as we age. And it's greater in males than females, and it begins probably in the when you turn 50, in your 50s as a male, and probably 60s as a female. And there's a gradual reduction in kidney function that occurs with age. And so if you're 75 years old, you know, a kidney, you might reach CKD stage three just from age-associated decline. And so people are saying, is that really, uh, abnormal? It, do I really have kidney disease, or am I just normal for my age? And, uh, there, there's a controversy over that. I'll tell you my take because it relates to what Levels does. Um, so we, we, uh, were interested in what causes aging decline in kidney function, and, and we've been suspicious that aging decline is hastened by the presence of obesity and by insulin resistance and all the things for which you get a CGM to help protect you. And, and in fact, the data is pretty strong that if you have metabolic syndrome, uh, that your aging-associated decline in kidney function is is hastened, is faster. So we took animals and we, we did studies like that where we, we created metabolic syndrome with western diet, and we could accelerate aging. But what was interesting was that we found that just being on a high carb diet without sugar, and I'm a sugar expert, so I, you know, but, uh, we found that, um, if, if animals were on a carb diet of about 50 to 60% carbs, which is very similar to current western diet, that that caught was linked with aging-associated kidney disease. And, you know, some of you may know that I'm an expert on fructose, and that we found that high glycemic diets can produce fructose in the body. Fructose is the active sugar in table, it's one of the sugars in table sugar and high fructose corn syrup. And the body can make it, and it makes it from carbs, and it makes it when your blood glucose goes up, which is why CGMs are so important because you can monitor your blood glucose. And, uh, and what we found is that when we took mice and we gave them a carb-rich diet, they got aging-associated kidney disease. But if we blocked fructose metabolism, even though they weren't being fed fructose, they were protected. They did not get the kidney disease. So I believe that, uh, western diet has a role in driving kidney disease, and, uh, if you develop metabolic syndrome, and you know, insulin resistance, it's going to pro, you're going to get a little bit, if you're diabetic, you're going to get even more, but even just eating a high carb diet probably is doing damage over the years. So I, I'm a, I'm a big fan that low carb diets, um, may be protective to the kidney, and, and, uh, there is a, you know, the the Verata Health people, Jeff Bolic, who's a low carb guy, has fantastic data that low carb diets and keto diets can help some forms of of chronic kidney disease. In fact, we're planning to do a formal study with with Verata, uh, on this. So, I, I believe that, uh, diet is linked heavily with kidney disease, that, uh, the one of the reasons chronic kidney disease has been increasing in the last, uh, century has it relates to the western diet. I think high salt's bad too. High sugar and high carb are at the core, and, you know, and I should say that, um, this is a topic that is a little controversial in the literature, but, um, you know, but I can defend myself, uh, with anybody based on the science, and so I do believe that there's enough evidence out there that I can say this and and defend myself in any situation.

I have a few questions on that. Do you, do you find that the, the diet-related, the fructose-related damage, is it, is there an independent aging-related mechanism that is being accelerated by these other factors, or is it that they're all sort of damaging, it's all being damaged in the same way, and that it's the accumulation of sort of poor lifestyle habits by the time we hit our 60s and 70s that have now created that damage? In other words, if I never ate fructose, would my kidney function still decline? Not, not even never ate fructose, but let's say I maintained a low carb diet all my life.

So, I was very fortunate to be a friend of William Oliver, who was the chief of pediatric nephrology at the University of Michigan for a long time. And Oliver, back in the 1990s, 80s, went to, uh, the jungles of southern Venezuela where there are hunter-gatherer groups called the Yanomamo Indians, and he studied these people and found that their kidney function stayed stable as they aged. They did not lose kidney function with age. He also found that their blood pressure was always was very low, and that they were on a very low sodium diet. They were eating fruits. So they were, but they weren't eating huge amounts of sugar, or they weren't eating refined sugar, and they weren't eating a high carb diet, and they weren't eating a lot of salt, and they, their kidney function maintained. So, I, of course, there was one problem with this study, and the problem was was that the oldest subjects tended to be like 55 or 60 because they tended to kill each other in in violent wars. But, um, so, so we can't really say, you know, what, what was the GFR of an 80-year-old Yanomamo Indian, but, uh, there was, it was just beautifully flat, um, over the age, uh, that we're studying, anyway. Um,

And has that, has that been validated in other kinds of animal studies or other human studies that absent the excessive salt, fructose, glucose over a lifetime, that there's not some independent mechanism that's just going to decline my kidney function simply because I got older?

Well, so, so I'll tell you a little bit about this. Um, this gets into the general mechanisms driving aging. And, um, when when you eat sugar, you induce oxidative stress to the mitochondria. And, uh, and the mitochondria are what keep, you know, make all the energy and keep us healthy. And, uh, if you eat sugar chronically, the mitochondria will fission, and you'll start showing evidence of a loss of mitochondria. And when you age, you also see a loss of mitochondria. And when the mitochondria, uh, start decreasing, um, the tissues don't work as healthy, and particularly the blood vessels to the kidney, for example, don't constrict as well. And this is called autoregulation. And, uh, what happens is it's easier to to damage the kidneys because the blood vessel normally constricts when your blood, if you get excited and your blood pressure shoots up, the kidney squeezes its vessels down so that the high pressure doesn't hurt the kidneys. But as we get older, that autoregulation starts to get impaired. So you start getting damage to the kidney. And it's all linked with mitochondrial function and health and vascular health. And, um, one of the issues is is that, um, diet, uh, animals in the wild like to have a little bit of of, um, extra fat on board to protect them. And so animals in the wild, and all animals, try to maintain some fat stores for protection. And so they're creating every time there's a little bit of fat, there's this mitochondrial oxidative stress. So someone figured out years ago that if they did caloric restriction in an animal so that it maintained almost no fat stores, you could reduce mitochondrial oxidative stress, and the animals live longer. And, uh, and so, you know, I believe that mitochondrial oxidative stress is kind of at the center, and, and there's always going to be a little, and so there is an aging process that will happen to all animals. But if you do, uh, caloric restriction, try to keep the fat stores down, uh, is is going to last longer. Maybe if you took vitamin C or other things that could block that oxidative stress, maybe you'd even live longer, right? But if you have no fat stores, what's happened with these caloric restriction studies is you have to restrict like 70% for the animals to really get a benefit. But if you put them in the wild, um, you know, in the 70% environment where they're getting 70% of their calories, they have no fat stores, but you're feeding them every day, so they live longer. But if you put them in the wild where suddenly there's no food for a week, you know, because this is the way it is, now they're vulnerable and they'll die quicker, right? So anyway, bottom line, I is I do believe that aging is a process that probably is inevitable. Um, and, uh, but the, you know, how well you age and how long you age can be modified.

Right. So you, you mentioned that there's maybe some controversy in the literature around the notion of, uh, the the diet impact on kidney function and maybe as you age. Is the, maybe just unpack that debate a little bit. Is it a mechanistic debate, or is a debate around the matter of degree?

Well, so historically, um, it was shown decades and decades ago that, um, you know, when you go into kidney failure, you hold on to nitrogen wastes, nitrogen products like urea is a nitrogen product, right? So we measure blood urea or BUN as a marker of kidney function. And years ago, it was shown that, um, you know, most BUN is generated from the breakdown of protein. You know, not from carbs and fat so much, but but most of the nitrogen-containing foods we eat are protein. And when the protein breaks down, you get this nitrogenous, that's called nitrogenous or nitrogen-containing waste that you get rid of. So it was found that if you were in kidney failure and you ate a high protein diet, that your BUN could go up pretty significantly, and that was a sign that the kidneys could be getting worse. And then it was shown that it wasn't just because you're retaining the nitrogen products, but when you eat a very high protein diet, it tends to cause a reflex and increased pressure to the for filtration. There's the the the kidney tries to respond by increasing the filtration of when the nitrogen compounds go up in the blood, and that can transfer into translate into higher pressure. So it turns out that if you take an animal with chronic kidney disease and you put it on a very high protein diet, the kidney disease will progress. Not only will you get more symptomatic because you're holding on to nitrogen products, but there's an actual worsening of the kidney disease. So, when I was in training, the focus was to low protein diets for chronic kidney disease. And what was really shown was that high protein diets could make things worse. And in fact, we could make animal models of kidney disease by putting an animal on a high protein diet, it was a trick to to accelerate kidney disease. What's happened in the last couple decades is the recognition that if you put an animal with kidney disease or a person with chronic kidney disease on a very low protein diet, it actually can make malnutrition worse. You, and, and it turns out that, uh, low protein diet is not as, uh, good as you would think, but high protein diet is bad. So what's happened is there's been a shift towards recommending, um, you know, a normal protein diet in patients with chronic kidney disease. Uh, and, you know, we try to avoid eating a lot of steaks and things like that if you have chronic kidney disease. Um, so the for the carnivore diet people, you know, if you have chronic kidney disease, be a little careful because a lot of a lot of protein, high protein is a bad thing. On the other hand, uh, what we've realized is that things like carbs are much more in some respects worse than than the the protein component because sugar and high glycemic carbs really can accelerate diabetes, can accelerate chronic kidney disease, um, can cause, you give high sugar diets to an animal, you can show changes in the kidney right away. Um, and so, uh, I think that the bottom line is is that, um, we're eating too much carbs and and, uh, sugar. Uh, we need to cut the carbs down. And we should try to maintain a normal protein, not super high. And, uh, so that means the fats have to go up. And that's sort of, you know, counterintuitive to what people were saying 15 years ago, right?

So, if the, if the mechanism around the protein damage is is related to the nitrogen because you're going to get that nitrogen from the breakdown and that's going to, you're going to hold on to more of it because your kidneys aren't functioning, what's the mechanism on the carb side? What's causing that damage?

Well, it's, I think it's related to the stimulation of blood glucose, the post, what we call, you know, uh, the postprandial or the rise in blood sugar, blood glucose after a meal when you eat carbs. And I think it's related to the fructose and, uh, and, uh, chronic insulin stimulation. And it's, uh, again, it's probably related to mitochondrial oxidative stress as well as other things. But, um, but yeah, and it, there's an inflammation pathway that's activated. So it's a, so it's a multifactorial way that the carbs are are interacting in your body and then leading to the kidney damage.

That's right. Okay. Okay. And one of the things is probably uric acid gets involved, uh, because, uh, high protein diets will generate uric acid, and, uh, fructose will generate uric acid, and we have pretty good evidence that uric acid is, uh, is the cause of gout, as people know. Uric acid is in our blood, and when it's high, it can cause the disease gout, but it can also be increased by these foods and alcohol and sugar and purines like in meats. And when the uric acid goes up, it seems to be associated with an inflammation and increased risk for heart disease and kidney disease and high blood pressure and other conditions.

Right? So, we've talked a lot about the the lifestyle factors. How much of a role does genetics play in my kidney health?

Uh, well, if you have polycystic kidney disease, everything, because that is the genetic, the main genetic disease that causes kidney disease. There are a lot of genetic, uh, rare genetic diseases, uh, involving the kidneys. There's tens of them, 20, 30 types of disease out there. They're pretty rare, and, but you could have a genetic cause, and, uh, there's even genetic forms of glomerular disease, you know, affecting the filters. Uh, there's one that's very common in Finland, for example, and, uh, it's called the Finnish nephrotic syndrome, congenital nephrotic syndrome. So there are genetic causes, and there are genetic risk factors. So people can carry, uh, genetic polymorphisms that may increase your risk for kidney disease. But in general, most kidney diseases are probably linked more with diet than with genetics.

Do we see individual variation in susceptibility to the impact of those lifestyle factors?

Oh, yeah, sure. Yeah. No, that for sure. There's genetic, uh, factors that, uh, are involved with every disease, basically. There are risk factors that increase your risk, uh, and those that decrease your risk. So, a little bit of is the lottery, right? But the truth is, we can do a lot by, uh, trying to exercise and do healthy living and eat right. And, um, and there are people who take supplements that can help, uh, different aspects of kidney disease, likely, and we can talk about that too. There are there are supplements, there are artificial sugars, there are all kinds of things or natural sugars that aren't fructose that people are using, but, yeah, there's different ways to approach it, but it begins with healthy diet.

Right. Right. So everybody will benefit from the same, uh, changes, but in terms of, if if you and I were to eat the same sort of diet, the amount of damage that that causes to our kidneys over time might vary because of our individuality.

I think you're right on the money there.

Okay. I want to touch on before we get into some of the specific markers that we do want to walk through, the relationship of the kidney to some of the other systems of the body. So what do we know about how kidney function impacts or is impacted by, we talked a lot about the metabolic functions, um, but maybe other things like cardiovascular health. Is there a relationship between kidney health and cardiovascular health?

Oh, absolutely. I think we, we've already talked about the link through high blood pressure, and pretty much everybody who has chronic high blood pressure has, uh, some things going on in their kidney. It's typically, it's low-grade inflammation that leads to retention of salt. Um, and, and so chronic kidney disease is hugely linked with high blood pressure, which is associated with stroke, heart failure. Uh, those are the three big ones. But it's, you know, associated with, um, coronary artery disease. It's associated with all these different cardiovascular type and vascular diseases. Um, the kidney, uh, makes the hormone associated for, it's called erythropoietin, and it's a hormone that stimulates red blood cell production. So it's very common to develop anemia as the kidney function continues to progress or to fail. And, uh, so anemia, you know, is a hematologic issue, but it's really linked with kidney disease. Um, kidney disease, you know, as it progresses, can affect your ability to excrete fluids, and you can retain fluids, and you can start swelling, and it can cause heart failure and lung problems and, you know, fluid there. Um, you know, so the kidney is so important, you know, it governs all the electrolytes, and, and when the electrolytes get imbalanced, it can affect just about every organ, including how well we think, and, um, you know, so the kidneys are really important. Um, uh, they're they're really used to help, pretty much every organ gets a little help from the kidneys because the kidneys are so important at keeping the the the blood clean and healthy and etc.

So before we get into some of the specific markers, I want to just talk broadly about sort of assessing kidney health. We, we touch on this a little bit, but are there any sort of obvious symptoms or signs before I get any kind of a blood test that my kidneys are not functioning the way they should be?

The kidneys can be invisible to, uh, to people from the standpoint of symptoms and signs. And so you could have chronic kidney disease and not know it. And most people do, right? I've read that that a large portion of kidney disease is undiagnosed.

Yeah. Exactly. Absolutely. And when it's very mild, it probably doesn't have much consequence. So that's the other side of the coin. But yeah, there's a lot of people who don't know they have kidney trouble. Um, the earliest sign, one of the earliest signs is, uh, what we call, uh, nocturia, and which means you when you get up at night to go to the bathroom. Now, everybody has their own pattern, you know. Uh, some people get up two times, some people get up not at all. But if there's a change in pattern, like let's say you normally go to the bathroom once at night, you wake up, and now you're doing it three or four times a night, that is a sign of that you might be getting developing chronic kidney disease or some other health issue that needs to be addressed. And, uh, so nocturia, of increased frequency of urination, but I don't want to scare people because everybody has their own normal pattern. So if you're a person who normally goes three times and you've been doing it all your life, that doesn't mean you have chronic kidney disease. But so that's one. Another one would be if you see changes in the color or other aspects of the urine that you, you like foam can be a sign of kidney, of protein in the urine. So if you suddenly see a lot of foam when you're urinating, or or if it looks like it might be bloody, or or if there's a big change where you're peeing much less, those can all represent kidney disease. Um, if suddenly your blood pressure is high and it's like really high, um, remember that the kidney has a major role in blood pressure, and you might be developing kidney disease that's causing the high blood pressure. So getting the kidney function tested when when your blood pressure is really high is a very wise move, and I think most physicians will do that too. Um, you know, if you have really blurred vision, uh, it, the eyes, that could reflect the high blood pressure and kidney trouble too. Um, you know, um, kidney disease can be associated with other organ dysfunction, but the, you know, the typical, typically it's relatively silent, and then, uh, what happens is you, you just feel fatigued, and you, you feel really tired. Uh, you may have trouble sleeping at night. Uh, you might be falling asleep during the day and then staying up all night. So changing patterns, um, when it's quite significant, you can start itching, and, uh, so that can be a sign, bone disease, you start, um, you might, uh, the bones get weak as you develop chronic kidney disease, sort of a late manifestation though, but I think the main ones would be, uh, anemia where you can't explain it, you know, uh, yeah, I would say, yeah, the the usual way it's found out is by having a blood test and someone calling you and say, hey, your creatinine, what is 2.4, and normally it's should be like 1.2, two or less, and someone will call you and, oh my god, you know, that's how it's usually discovered.

Given how much of kidney disease is undiagnosed, but also as you said, that the early stages don't seem to have a lot of physiological effect and aren't, and don't necessarily mean that they're going to progress to later, more damaging stages. Should we be doing more kidney testing? Should just as a society, should we be screening for more things, or are we just going to catch a lot more early stage that and scare people when they don't really need to worry about it, or should you be, is it helpful to know you have stage one, you have stage two, oh, I should start to get some serious about some lifestyle changes to prevent that kind of progression?

I don't want to scare people, um, but I do think that, um, you know, when you have your yearly exam, just have your kidney function tested, have your urine checked. If, if there's something that's beginning early, um, often times it's not that important, but it's also might be relatively easy to fix. And if you don't fix it, and it's one of the, it's the beginning of something that's going to be get worse and worse, that wouldn't be good. So I, I think it's always good to know, but I don't want to scare people, too. There are a lot of people who get scared when they, you know, they find out that their GFR is 62, and it's almost chronic kidney disease stage three, and they go, "Oh my god, you know, I'm I'm going to die." And it's not true at all. But, but it, you know, if you do have a, you know, a GFR 65, and, uh, you know, it's good to kind of just do some basic investigation and just make sure that you know, maybe this is age-associated decline. Maybe it's, uh, you know, there's a lot of chronic kidney disease that's relatively benign. It's a very slow process, and, but one of the keys is to look at the urine. If the urine is filled with protein and blood, it's usually a sign of active disease going on in the kidney, and that's not good. And so when I, when I see a kidney function like a GFR of 65 or 48 or so, my first question is, what, what does the urine show? Because if the urine is completely benign, uh, it, it suggests a slow, slow process. Whereas if you see protein and blood and white cells, it means that there's something going on that needs really to be addressed pretty quickly.

And is kidney damage always progressive, or is it can it be transient? Can I reverse kidney damage?

Yeah. Oh, yeah. There's, there's it's called acute kidney injury. Okay. And, uh, it's fairly common to have that. So there's chronic, chronic kidney disease means that it's like a permanent change, although we can sometimes reverse chronic changes. But acute means that there's some recent insult, like you, let's say you, you, uh, got hospitalized and, uh, because you had a bacterial infection go into the blood, what we call sepsis, and your blood pressure got low, and you had to come into the hospital, and they're put in the intensive care unit, and they're filling you up with fluids and giving you medicines to bring your blood pressure up, and they're giving you antibiotics, and you're sick as can be for like three or four days, and then you recover because the infection was treated, and, you know, they figured out where it came from. All is good. But they look at your kidney function. They go, "Wow, you know, two weeks ago when you were seen by the outside doctor, you had normal kidney function. Right now, your kidneys are almost completely shut down." That's acute kidney injury. And it can be to the point where some people need dialysis, but it, uh, it can also be very mild. Can vary, right? And, uh, you know, depending on how severe it is, you might have to have dialysis associated with this infection. Um, and, and the trouble with a kid, acute kidney injury is, um, it can take two to six weeks, eight weeks to recover. So you could be in a situation where they treat the infection, and you're feeling good. Five days later, the infection's gone. You're talking. You're, you're no longer, you're just getting antibiotics, otherwise good, but they want to keep you in the hospital because your kidney function is bad. And in fact, they're going to want to dialyze you for, uh, 10 more days until the kidneys recover. But the kidneys do recover. So with acute kidney injury, they recover. There's a little bit increased risk for developing chronic kidney disease later in life, but, you know, most of these will recover, and you get off dialysis, and you go home, and everything's good. But you now you've had an episode of acute kidney injury, and so they'll try to, they'll keep an eye on your kidney function a little bit more than they would normally, right?

But in in chronic, it's the damage is done. It's not sort of coming back. So, if I make some lifestyle changes, I might be able to arrest or to slow the progression, but I'm not going to, I'm not going to go from stage three back to stage one.

Well, you know what? Uh, we used to say that all the time, but I mean, truthfully, we see, we're seeing, um, slight improvement in kidney function over time with good management. It used to be like when I was in training and, you know, my early years, what you just said is exactly true. We, we could stop it, slow it, but we couldn't reverse it. But really, I see patients, um, improving their kidney function over several years, uh, significantly, and, like they may have, like a, remember a normal creatinine is 1.2, two, or or lower. Um, and, uh, they might have a creatinine of three, but with good diet, blood pressure control, all these great things, the creatinine will go from three to 2.8 to 2.6 to 2.4, and maybe get down to like two, three, or I mean, it doesn't go back to normal generally, but, it's amazing.

There's even a few diseases where you can be on dialysis for like a year and then suddenly come off. Um, the classic is malignant hypertension, scleroderma. There's these rare diseases, but, um, but yeah, there are cases where people can recover. This, uh, the E. coli syndrome, Jack in the Box syndrome, where you eat a hamburger and it's been got this E. coli and you develop this horrible kidney failure, and, uh, it can kill you, actually. And but if you, you, you can be on dialysis for maybe two months, three months and suddenly come off. That's another one. So that's, um, not everyone has permanent kidney disease from, that's more of an acute, anyway, but, but, uh, but yeah, interesting.

So we've referenced a lot of the markers. Let's, let's dive into those a little bit more specifically, and maybe eGFR is the place to start. So, estimated glomerular filtration rate, as I understand it. This is one of our sort of best indicators of kidney, uh, function. There's different ways to measure it. I see it with creatinine, and I see it with cystatin C. So what is it? Why are there different algorithms for how we estimate it?

Well, creatinine was the one that everyone liked because it was the first one that would was figured out. Everyone has creatinine that's comes from the muscle. Uh, and its excretion is dependent largely on kidney function. So as your kidney function reduces, the amount of creatinine that's excreted, um, stays, this, it's, it's sort of, uh, complicated because it's called clearance, but basically, um, what happens is the kidney function gets worse, the creatinine will go up in the blood, but it won't keep going up. It will go up until the excretion equals what it was before. But be, but because you're filtering less, but now you're filtering at a higher concentration. So it will, it will go up and stabilize when the excretion equals the generation. M, so it's kind of complicated, but basically the, if your kidney function drops in half, the creatinine will double. And if the kidney function goes down by a third, the, the kidney, the creatinine will go up by about threefold, you know, it's pretty close. And then they, they have better equations to, to, to do that. But, but basically, so creatinine can be used as a marker of kidney function, but there are, there are issues with.

And one is very common with people who, uh, are interested in levels and CGM, and that is, um, that, uh, some people take creatine supplements, and creatine supplements are used to help boost muscle size and muscle strength. And, um, but when you take creatine supplements, some of the creatine gets broken it down to creatinine, which is very similar, but they're different substances. But if you're on a high creatine diet for muscle, your serum creatinine will go up just from that. And it's, it's fake because it's not due to, uh, it's not due to reduced kidney function. It's due to just eating more creatine that's being converted to creatinine. So, um, so if you're, if you, if I get a young guy who is like lifting weights and, you know, and he comes in and he gets referred by a physician to me because they think he has chronic kidney disease and his creatinine is like 1.8, uh, you know, I ask him, "Do you take creatine supplements?" And they, they go, "Oh, yeah, I do." And I go, "Okay, well then we won't measure creatinine on you because that's not going to be an accurate test. And we'll measure cystatin C, which is a different kidney function marker that is not affected by creatine. And then we go, oh, it's normal. Or if it's abnormal, then we go, there is something going on here." So, um, anyway, so the eGFR is the actual measure, uh, the calculation for how well the kidney is filtering, uh, the creatinine is used to, to calculate the eGFR.

Um, the creatinine is imperfect for a variety of reasons. What we just explained, one of them, but it's also reflected by muscle mass. If you're, uh, an NFL football player and you have tons of muscle, your creatinine is probably going to be 1.5, which would be considered abnormal, but it's just that you have a large muscle mass. And if you are a 84 pound year old lady with very little muscle mass, your normal creatinine is probably 0.5. And if you go to 1.0, that's abnormal. You might have kidney dysfunction. You might have bad chronic kidney disease with a normal serum creatinine, but it's because your muscle mass is so low. In fact, there was a study done of of these of people who are anorexic and, you know, they, they have kidney failure when their creatinine is 1.2 to, you know, so, um, so creatinine's imperfect.

So then they use cystatin. Cystatin is another marker that, uh, also gets filtered pretty much along with the fil, with kidney filtration. And so when, uh, when your kidney function decreases, the cystatin also rises, but it's an expensive test. And, uh, people tend to like to continue to use creatinine. So almost all, um, physicians are still using creatinine as their primary way to measure kidney function, as opposed to cystatin C. And then they, there's formulas to convert that to eGFR. And, uh, one of the interesting findings is that I, you know, I told you that like when a creatinine doubles, it's more or less like a reduction of your kidney function by half. So when your creatinine gets up to like, if normal is one, just a creatinine of two is, is quite a significant reduction in kidney function. Uh, but like if you have a creatinine at 1.4, it seems very close to 1.2 too. But it, it when you do the eGFR, it will show a, a kind of a significant drop because when the creatinine is low, um, a smaller change actually means more significant change in GFR than if it, like if it was goes from four to 4.2, that's now no real change in GFR. But what if you go from 1.4 to 1.6? That's a bigger change. Okay? Because it's to the inverse.

Anyway, uh, bottom line is, um, the eGFR is a more sensitive measure, but it can also be more alarming because people go, "Oh my gosh, you know, my GFR is 62," but actually my creatinine is only 1.44. And, uh, you know, and the, if you look at the creatinine, it doesn't look like it's very significant, but when you look at the GFR, it looks like, you know, your kidney function's at half. And so it will scare people more. But so GFR is, is looking. So there's serum creatinine, right? We can just look at the, the, the sheer amount of creatinine that is in the blood, right? That might be misleading for all the reasons that we just talked about. So what's that algorithm doing, the calculation that's giving me GFR context? Is that giving me that I'm not just getting from the serum creatinine?

So this, the serum creatinine, um, is, is, uh, just reflecting, you know, uh, the steady state of the creatinine in the blood. And, um, and, and it, it can be shown to follow a, a pretty good trajectory with the, with the how much is being filtered. And so, uh, but, but it's, it's pretty unique for each individual. So like if you're, as we said, muscular, you're going to have a higher creatinine and so forth. So the, the GFR is meant to help corrections for body mass and male, female, and all that kind of stuff to try to make it more accurate. So if you're, you know, to help correct, and it doesn't correct it perfectly, but so all these formulas are kind of aimed at trying to give you a more accurate measurement of your kidney function. So it's a little bit like what, given all of these other factors that we're going to put into this, this calculation, what would we expect your creatinine to be? And that's going to tell us a little bit. Then what we're trying to calculate is, is kidney function. How well? Yeah. If you look at age, gender, all these things, you can kind of, um, factor in correction factors to try to figure out what your kidney function is. And, and if you know, and as I mentioned, um, when they do this, they find that there's a lot of people who have some level of kidney disease. And, um, and it, you know, if you do have kidney disease, it is important to see a doctor and just to make sure that, you know, is it something to be worried about or not.

And now how do you make sense then of when you get discordant numbers back, right? If you've got a, a higher, I mean, we talked about creatinine could vary a lot by individual, but even something like a cystatin, which is going to be less sensitive to something like muscle mass or some of those factors, if one of them suggests a problem, but my GFR suggests not, or vice versa, how do I make sense of those kind of discordant results in my blood labs?

Well, um, you know, so things like creatinine, I mean, I, I do tend to not view it as as, uh, critically when, uh, when the individual has a huge re issue of muscle mass or so forth like that. Then I'll favor the cystatin. Cystatin C can be affected as well by inflammation and so forth, not as much, but, uh, you know, basically, uh, in some respect effects. The most important thing is to use the same method on repeated testing. Okay? And, um, you know, if I see somebody and they have a GFR of 70, but they have a lot of protein in, in the urine, as I was talking about, I'm going to work that person up for kidney disease. I'm going to try to figure out what's going on. Right? If the G, the urine shows no blood, no protein, no white cells, and it's benign, what we call benign urine, and the GFR is, is 70, and the person is 70 years old, um, I'm going to assume that this is probably, uh, not anything serious, but I might have them come back and get repeat tested, you know, in three months or six months, or maybe, you know, I'll look for factors like, you know, is the blood pressure under good control? What's the diet like? Is the, what's the blood sugar? You know, I look for the fixable things, but I, it's not like I'm going to be worried that this guy, this patient's going to get into trouble. Um, I don't view it as a, as a serious issue at that stage. And in fact, I think of it as is that the person has, um, stable chronic kidney disease, what of whatever cause, maybe diet and so forth, but not one that is likely to progress. I don't think this guy will go on dialysis. I don't think that he's going to die from kidney disease. I, I don't see any evidence of activity. Uh, it's true his kidney function is a little reduced. I might modify his medication, but, um, but that, you know, will I'm not really bothered. And I, if I measured it with creatinine based or cystatin based, it doesn't really matter, but the key is to use the same method, right, uh, on repeat.

Do you ever see a scenario of, you know, serum creatinine or cystatin being fine, urine being benign, but your GFR is, is not 70, it's 40? Um, and in that case, are you, are you more worried? Are you getting a clear indication of of worrisome kidney dysfunction?

Yes. You know, if, for example, like this epidemic of chronic kidney disease that's going on in Central America. Uh, many of these patients will have very high creatinines that are, you know, it isn't like a GFR 70 with a creatinine of 1.2. It's a GFR of 40 with a creatinine of 2.2. And, um, and that is an abnormal creatinine, right? That is not just from slow aging or, you know, or diet. That, you know, the creatinine 2.2, there's something going on. And although many of these patients will have a little bit of blood in the urine, a little tiny bit of protein in the urine, some of them have benign kidneys or benign urines, I'm sorry. But they have a thing called tubulointerstitial disease. They have disease of the tubules, not of the filters. And that can be from toxins, that can be, and that is a, a real disease where it can progress even with a benign urine. So there is, there are these circumstances where you can have a bad disease without a lot of activity in the urine. Um, uh, you know, most kidney diseases will have an active urine associated with active disease, but this, this thing called chronic tubular disease, which can be due to toxins and stuff like that, can, can be a, a scary one.

So if, if you're, if you know, like if you're 70 years old and your creatinine is 1.44 and your GFR is 60, that might well just be aging associated CKD. It might be from diet. I think it is, but I'm not worried about it. But if you're 22 years old and you have a, you know, a creatinine of 1.8 and you're not on creatine supplements and, you know, there's something going on because you shouldn't have mild. I mean, that's a fairly significant reduction in kidney function and you're young. So those people will get worked up.

You know, here's a good example. Um, you can have a car, you know, in a car accident, you could have, uh, trauma to your, you know, to to your abdomen where you could, uh, lose the blood supply to a kidney. The, you know, when you hit the, the kidneys are kind of like, you know, with it's almost elastic. They, they can bounce a little bit inside and if they bounce too much, they can, what's called an avulsion, but basically they, they can tear the blood supply. The artery can have an internal tear where it doesn't bleed out, but it, it basically, uh, the blood supply to the kidney can go to zero. And if it, that happens and there's no blood supply to the kidney, the, the, there's no urine coming out. So you won't see any abnormal urine because it's the kidney is all knocked out. So you suddenly are working with one kidney and you could have elevated creatinine develop without much in the urine and it's because you've had a significant injury to a kidney that could be identified with correct imaging and, you know, potentially, you know, people could potentially do surgery to to try to recover the kidney if they can do it early. Right? So, so there are situations where you don't have to have an active urine, um, you know, act, you know, abnormal urinalysis and you could have significant kidney disease. That's why we have kidney doctors so we can help figure that out. But anyway, but yeah, so yeah, there's the, there's the issue.

You know, I have a GFR of 75. Am I going to die, doctor? And I, you know, the usually that's benign, but there are these situations where you're not supposed to have a kidney function that low and it means that we need to investigate. Right.

Well, on that point, how you mentioned the notion of retesting. How much can I learn from a single point in time testing versus how important are patterns over time?

Oh, you just named it. You just said it. I mean, patterns over time is really a key. I, I mean, if you come in and your creatinine is nine and you're not making urine, we only need one, one measurement to know what's going on. But, but yeah, no, um, so much, uh, in medicine involves, um, developing differential diagnosis and trying to figure out what, what is the most likely cause. And, um, sometimes, uh, it's really assisted by getting a repeat measurement, uh, sometimes right away, sometimes, uh, you know, after a period of time to help, uh, provide convincing evidence that your management plan is right and your, what you're thinking about the diagnosis is right.

And I would imagine then to understand what we were talking about earlier of of how if you have some damage, how quickly is it progressing versus sort of how stable is it?

Right, right. Yeah. And what are some of the other markers that that sort of fall on a kidney panel? So, we talked a little bit about urea nitrogen or BUN. BUN, people might see. Um, what's that telling me and what's its relationship to some of these other markers we've been talking about?

Yeah. So, it's a, a marker of kidney function. So, when, uh, when the kidneys are not working very well, you'll start to retain blood urea nitrogen and it's, it's fostered or it's accelerated by eating a high protein diet. We mentioned that, you know, if you, so, um, it's also tends to, to, you know, it's made a lot of it comes from the liver. So if the liver function is not very good, you may have a, a lower BUN than expected for the kidney function. Um, and also, um, BUN is, uh, often when you, when you start getting dehydrated, your BUN level will go up faster than the creatinine. And that's because you tend to reabsorb urea, uh, with along with the water. So when you get dehydrated, you're trying to hold on to the water and it, you, you pull in the urea a little bit as a consequence. And, and, uh, so if you see a high BUN level relative to the creatinine, it usually reflects, um, you know, it often reflects dehydration. So we use the BUN for a lot of, uh, measurements. I mean, for a lot of, uh, assessment, but yeah, you don't, a lot of people, uh, it's not uncommon to have a mildly elevated BUN, but if the BUN's really high, that's a bad mark, that's a bad sign.

And what about albumin? So albumin is the measuring the protein in your blood. And, uh, you know, you have a lot of protein in your blood, but the, the major protein in our blood is albumin. And it's a real sign of overall health, vascular health, nutritional health. Um, and a low albumin can be a, a sign of, of, of liver disease. It can be a sign of kidney disease, um, and, uh, malnutrition. So the albumin turns out to have a lot of prognostic information. You, you can, and, and it can be related to the kidney disease because some kidney diseases are associated with losing protein in the urine. And, uh, and sometimes the protein loss in the urine can be massive. It's seen with certain diseases and in those people, the albumin tends to be low in the blood. So the albumin is a very important measurement and measuring in both the blood and the urine. If you have a lot of albumin in the urine, it's a real sign of kidney disease.

And would we expect albumin to move in relation to some of the other markers? Right? If we've got fatty GFR, if we've got high creatinine, might that affect albumin, or that's something that might be an independent?

So the GFR is measuring how well you're filtering the electrolytes and urea. But normally when you're filtering these things like sodium and water, proteins don't get across. Okay? But in certain kidney diseases, the proteins, the barrier is so leaky that proteins get across. So then, um, the problem is, uh, if you get a lot of albumin in the urine, the serum albumin goes down because it's, you're losing it in the urine. And the albumin is really important in helping keep the blood vessels full. And when the albumin goes down, the fluid starts to seep out into the tissues and you start getting swelling in your feet. And, um, so the albumin is measuring a different thing. It's measuring the fil, the, the, you know, in terms of the kidney, it's a sign that the, that the filtration barrier is becoming leaky to protein, whereas the GFR is measuring how effective is the barrier at allowing the filtration of electrolytes. So it's a different thing. So you know, when the filtration barrier goes down or is reduced, the GFR falls. But with the basement membrane normally, or with a filtration barrier normally, no protein gets across or very little. So when it breaks down, you're actually getting more protein into the urine. And so that's bad.

Got it. And so the last sort of set of markers then I want to talk about is the electrolytes. We talked a little bit about what are the electrolytes doing and what's the relationship to kidney function.

Yeah. So the, the, the fluid, our blood doesn't just have water and red cells and white cells, but it has, um, electrolytes. And these are mainly sodium and potassium and other things, calcium. And they are used as part of, they're, they're really important in how cells function. And, um, cells use electrolytes for many different reasons, but like inside the cell, we try to maintain, uh, slightly negative charge and we tend to have, uh, a fairly high level of potassium in the cell. Whereas outside the cell, we tend to have a lot of sodium. And the sodium and the, these electrolytes are involved in all kinds of cell processes. I mean, so we try to maintain this, the, these electrolytes within very careful levels. So for example, potassium is a great example where we try to keep it between like three and a half and five point two, um, milliequivalents per liter. So, and, and when it's, when the potassium gets really high, it can actually slow the conductivity of the heart. If it gets really high, it can cause the heart to stop. And if it goes really low, it act, it, uh, irritates the heart and increases its, uh, ability to have arrhythmias. And if it gets really low, it can trigger ventricular tachycardia or even, uh, fibrillation. So the potassium is like really important that you want to maintain it within a certain range. And they did studies like people who suddenly drop dead tend to have a low potassium, you know. So potassium is really, really important.

Sodium is a reflection of it. It, it really helps, uh, ma, keeps the water electrolyte balance. It, it's what controls what we call osmolality, which is, um, how salty the, the, the blood is. The blood needs to be a certain level of saltiness. And if it, if the salt concentration goes up too high, it will pull water out of the cells and the cells will shrink and it can cause really significant dysfunction where, uh, even cognitive function and all that can be really impaired. And, and we know that when you get thirsty, that's when the serum sodium starts to go up, uh, and then you drink water and you dilute the sodium back down to that normal range. And likewise, if the sodium gets very low, uh, it's often a sign of chronic diseases and it's associated with, you know, bad outcomes. So the sodium, it turns out to be really, really important, um, and maintaining the serum sodium between like 136 and 144, um, is considered the normal range. What's happened in the last five years has been the discovery that if your serum sodium is high, but still in the normal range, that that's associated with increased risk for disease and it's associated with increased risk for, uh, dementia and strokes and cardiovascular disease and chronic kidney disease. And, uh, we've been looking at this as well. And so it turns out that, um, there are a lot of people who are not drinking enough water. And if you don't drink enough water, your serum sodium tends to be on the upper end of normal. And what's amazing is we do as doctors, we used to say, well, if it's in the normal range, don't worry about it. But now we actually are have papers coming out showing that if you're in the upper range of normal, it correlates with not drinking enough water and it correlates with an increased risk of disease. And so the aging institute at the National Institute of Health recently published a beautiful paper on this showing that upper end of normal serum sodium is associated with chronic diseases or, you know, with the development of it. So my recommendation, uh, is for you when you get your blood work from your doctor to look at everything and what's normal, what's abnormal, but also just look at the serum sodium, which is Na, and look at the number, and if it's like 143 or 144, it's still normal, but it, you know, so it's on the high end and that means you're not drinking enough water. And I recommend drinking six to eight glasses of water a day. Uh, you can overdrink water, but, um, I do think that, uh, trying to keep your serum sodium in the normal range and ideally in the mid range is, is perfect.

And the relationship with the kidneys there is that the kidneys are basically doing that regulation. They're filtering. Yes. And, and reabsorbing the electrolytes. So if your electrolytes are off, it might be a sign that your kidneys are not functioning as well.

Yeah. So there's, there is a disease where the kidneys don't concentrate, uh, correctly and so you, you spill a lot more urine and your serum sodium goes up because you're, you're losing a lot of water. Uh, it's called diabetes insipidus. And there's, there's some that are due to the brain not making enough vasopressin, which is the hormone that helps to do this. And you can have a primary problem in the kidney where you're not reabsorbing the water, uh, sodium, and being dehydrated and, you know, increased risk for diseases.

So, where we wanted to, to kind of end was on some of the lifestyle choices, some of the things you can do to support a healthy kidney. And I think we've talked about a lot of them through here, but I just want to hit on them as we finish. Maybe let's just start with hydration because we just talked about that.

Yeah. Why is hydration helpful? We talked about the sodium impact, but why else is hydration helpful for your kidney health?

Well, I, um, hi, I believe that, um, so what we're learning is that, um, an increase in osmolality or the salt concentration, uh, leads not only to dehydration but also activates, uh, blood pressure and sympathetic nervous system activity. So people, we, we have shown that the concentration of serum sodium when it's high, is associated with an dramatically increased risk of hypertension, not only to develop it, but your blood pressure will go up as you raise your serum sodium. It, when we did a study where we gave salt in the soup, you can mask how much salt you put in a soup, and so these guys were getting a fair amount of salt, and if they brought their serum sodium up, their blood pressure shot up and they turned on cortisol and all these bad actors, bad actors. And they, if they took the salt with water, that didn't happen. Now, the kidneys will fix the problem, but they take a to to do that. So if you, rather than bring your serum sodium up and have the kidneys activate and try to hold on to the water to bring it down, it's much better to drink the water with the salt or not to eat the salt at all to to keep your serum sodium in balance. So the kidneys got a really important role in keeping it normal, but it takes a while for them to fix it. So, uh, staying well hydrated is just a wisdom. It will help in so many ways. And you can overhydrate, but, and, you know, if your serum sodium is low, talk to your doctor because maybe you're drinking too much water. And so hydration is really important.

Uh, a second thing, uh, we've talked about is the importance of not eating a lot of sugar and carbs, especially high glycemic carbs, and to not eat a super high protein diet. You don't want to be on a high protein diet. A normal protein diet, like one gram per kilogram, point eight to one gram per kilogram, that's good protein in the diet. Um, you know, I, I would look at your uric acid. I, I do think there's a relationship of uric acid with kidney disease and a high uric acid is a major risk factor. There's debate on whether or not lowering uric acid can benefit patients with chronic kidney disease. I'm in the group that believes it does, but, uh, I, you, I think you should discuss with your doctor and depending on how bad your uric acid is or if you have gout, please try to get that uric acid down.

Mhm. And how sensitive are the kidneys to other lifestyle factors besides diet like sleep, stress, exercise? How much do those impact kidney function?

It's an area that's being studied. I believe it's probably, uh, important, but, uh, I, I don't think that we have a lot of, uh, data to really support that, uh, at this point, but I do believe it's very likely to be important. Sleep patterns are so important, and stress, and stress is so important in blood pressure and vascular tone. It's, they've got to be linked with kidney disease. But I do know that people with chronic kidney disease often have poor sleep patterns. And so we do know it goes the other way, that sleep disorders can come out of kidney pro, uh, disease. But, um, but I suspect that sleep disorders are probably not good for the kidney function either. Right. Yeah.

I wonder if there the connection also just through the mitochondrial functional function, the oxidative stress. Right. Anything that's going to induce that is going to ultimately come back and bite the kidneys. I think you're right. Right.

Great. Well, uh, anything we didn't cover about kidneys that you want folks to know?

There's two things to that may be important to emphasize again. And the first one is, um, if you get back slightly abnormal kidney function, don't necessarily, don't panic. You know, there's a lot of people who have, you know, chronic kidney disease, stage two or or very mild chronic kidney disease, and it's really not going to affect your life at all. But, um, it is important if you do think you have chronic kidney disease to be evaluated by a doctor and to make sure that you don't actually have an important dis, you know, a disease that's that's developing that could be acted on, uh, you know, early. There's a lot of panic in the literature, you know, and people said, "Oh my God, I got a GFR 75. What does that mean?" And so there's, I see a lot of that, but I also don't want to tell you to ignore it. So, you just, uh, you need to probably just show it to your, your physician and have them evaluate. And, and probably in, in the majority of cases, you just need to be seen once a year and follow wisdom of good health, good diet, um, and making sure your blood pressure is under good control.