 So what I really want to talk about is a lot of how I am going to put together the diets that we eat, some of the problems that we commonly see in renal clinic, which are some of this is what we call progressive kidney disease, which is due to diabetes and high blood pressure or kidney stones. And how I feel that modification of the diet, much of which goes along with what you guys are calling paleo diets, would probably help make kidney disease better, a lot of kidney disease. And so that's what I just said. So I thought I would start out, we give books to our patients and I love the books because they start out with these questions like what are kidneys? And here I'm gonna actually talk a little bit about what is chronic kidney disease. So there are some kidneys, typically they're about six inches or so. And you can see in the picture, let me see if I can get an arrow here, yeah. So you can see over here, these are the filtration systems in the kidney. So that's half of what the kidney does. These are the glomeruli. And then these are the reclamation and excretion systems, the kidney tubules. And this is a completely healthy kidney where the glomeruli are nice and open. The tubules are nice and open. You don't see any signs of inflammation anywhere. Inflammation is in dark blue. Over here on this side, this is a kidney with advanced kidney disease. So all of the glomeruli, so here are the glomeruli over here. They've all turned into scar tissue. Here are the blood vessels over here. They've gotten really, really thick. And you pretty much don't even see any tubules at all. They've just all disappeared. So when we talk about chronic kidney disease, this is really what we're talking about. Basically, the structure of the kidney has been completely destroyed and replaced with scar tissue. And the vast majority of what we see is due to vascular disease. So while there are some types of kidney diseases that children get due to infections or due to changes in the immune system, the vast majority of what all kidney doctors see is related to progressive vascular disease, which is due to diabetes, number one, high blood pressure, number two, three atherosclerosis and associated with obesity, and which gets worse over time. So that as the decades pass, and you can see over here, so as, where's my little arrow? As the decades pass, the blood vessels get more and more destroyed. The amount of blood getting to the tissues gets less and less, which means the oxygen to the delivery to the tissues gets less and less. And it's the lack of oxygen and which causes, in part, scar tissue. And the progression of damage to the organs, not just the kidneys. Okay, so I will talk about the kidneys, but what happens in the kidneys is happening in the heart, in the brains, in the peripheral vascular system, like in the legs. So this is not a single problem. This is a systemic problem, the vast majority of which is due to the fact that the blood vessels are in terrible shape. And at least part of this, I'm going to argue, is not, is directly related to how much of what we eat is junk food, processed foods, and foods that I'm going to call high acid foods. Because when we say, what can we do to help prevent kidney problems, control the blood pressure, control the diabetes, control the amount of protein in the urine. And then lastly, and we're doing this more and more, control the metabolic acidosis. And the acids in the foods come from the diet that you eat. And so it's not just the fact, as Stefan was talking about earlier today, it's not just the number of calories that we eat, or the lack of exercise. I also believe that it's actually due in part to the actual types of foods. And so as I'm sure you guys have seen this slide very often, as time goes on, people have been getting fatter and fatter, and this is associated with an increasing amount of diabetes in the United States. And is in addition to not just diabetes, but also associated with an increased incidence of high blood pressure. So the fatter you are, the higher your blood pressure is. And as we were talking about earlier today, if you lose, if you tend to be a lot lighter, your blood pressure tends to be a lot lower. And so, and not only are the adults getting fat, but the children are getting fat too, and it's just getting worse and worse. And if you actually look at whether or not we're actually seeing more kidney failure, if you look at the NHANES database, we're seeing more and more severe kidney disease. So when we talk about severe kidney disease, you start seeing a nephrologist somewhere around stage three CKD, which is a glomerular filtration rate of 60 milliliters per minute or less. And so what we're actually seeing in the more severe forms of kidney disease is that as time goes on, we're seeing more and more of them. And as I said, we believe that a lot of this is vascular disease. And so people who have really lower GFRs tend to have heart disease, high blood pressure and diabetes, compared to those who do not have as severe kidney disease or who don't have kidney disease. This is also true independent of what race you are, so it doesn't matter whether you're white or Hispanic or Asian or black, okay? Everything is going up over time through all ethnicities, although there is a genetic component to this, so some people are more affected than others. And if you have kidney disease, you are more likely to die compared to if you don't have kidney disease, even after adjusting for all the factors that we can adjust for. So kidney disease is bad for you. So if we're saying that it's obesity and diabetes and high blood pressure and hyperlipidemia that are causing the problems with the blood vessels, then what kind of information is there out there that says that fixing these problems would potentially help improve kidney function? So there are no studies that have actually looked at this because it actually takes decades to see whether or not kidney failure is progressing and whether or not diets would affect that. But in short-term studies, we and others have shown that if you switch people over to a diet where they get a lot more calories from fruits and vegetables and you take away the grains and the dairy products and you take away the salt, you can show that their blood sugars improve, their blood pressures improve, they can lose weight more, the cholesterol levels improve. And one of the things that we showed in our couch potato study was that the vascular tone improved. So what we were doing was measuring what would they call a flow-mediated dilation where you put a blood pressure cuff on somebody's arm and keep it on for a couple minutes and then you take it off and you see how much the blood vessels dilate. And even after only two weeks on a paleo diet, our couch potato blood vessels got more elastic. And if we're talking about this is a vascular problem, then even short-term studies have shown that maybe there's some improvement in the way the health of the blood vessels. And so I believe, although nobody has proven, but I believe that all of these things would be reasonable things to try to modify if we're trying to take care of people who either have renal disease or have a high chance of having renal disease. The caveat, of course, is that by the time they actually get sent to us most of the time, they have this much kidney function left. And at this point, it's too late to do anything. At this point, we're talking about the last couple of CCs of GFR and how long before I have to put them on dialysis. It is too late to do anything at that point. The kidneys have completely scarred down and you can't treat them with these kinds of approaches. But where you can do something and where I feel it would make the most sense is in the people whose GFRs are still in the 60s or the 50s, where we can potentially do something where there's functional kidney tissue left where hopefully we would be able to actually help people. And so, and right now, that's something that the kidney community is just starting to try to take a look at. And I believe that we will see more and more of this. In the future, but that's where I think we have to put a lot of our effort. Okay, so now I'm gonna change topics a little bit and I'm gonna talk about kidney stones. So what are kidney stones? So any of you who ever had kidney stones, this who has really bad kidney stones because they really, really hurt. And pregnant women or women who've had children who have kidney stones often say that it's worse than labor. So it can be literally excruciatingly painful. And that x-ray is just a plain x-ray. So you can see that these things are actually have the density of bones. I mean, they're just little rocks sitting in there in your kidneys. And there's two really common kinds of stones that form in people who eat Western diets. Calcium oxalate is probably the single most common stone. And you can see here are the little calcium oxalate crystals in the urine. And here are the little calcium oxalate stones. You can see how big they are. And then the other really common one is uric acid stones. And you can see here are the uric acid crystals in the urine. And again, just uric acid stones. And it's extremely common to actually have stones that are made up of both of these things, uric acid and calcium oxalate. So both of them together. And if you say to yourself what factors are important in the formation of kidney stones, hydration, probably the single most important factor. Because these things are crystals and this is just a chemical factor. If you don't have a lot of fluid and you have a really large amount of solute, it'll tend to precipitate. So hydration is probably this one thing that we always recommend for kidney stones. Urine pH, some stones form an acid urine and some stones form an alkaline urine. Western diets, which are acidic, tend to cause acid urine and that's why calcium oxalate stones and uric acid stones are the most common. Depends on the concentration of solute. And so that is how much calcium is in my diet, how much uric acid is in my diet. Which is related to things like how much and what types of protein are you eating, whether or not you have a high fructose intake dependent on how you handle calcium and how much salt you're taking in. And then more and more we're beginning to appreciate that people who have stones tend to be overweight and have metabolic syndrome too. Especially these common kinds of stones like calcium oxalate stones and uric acid stones. And so we're beginning to see a lot of overlap now. So hydration, as things get warmer and warmer. We've always seen a lot of kidney stones at warmer latitudes and as the climate temperature has been going up and the temperatures have been rising, we're actually seeing increased incidence of kidney stones now in more northern latitudes because of the higher temperatures. And presumably because people are not drinking enough fluid and not becoming adequately hydrated. Fructose, this is both total fructose intake and fructose corn syrup or free fructose intake. And pretty much it doesn't matter what group you look at. So NHS one and NHS two, HPFS, these were all large cohorts of younger women, older women and men. And it really doesn't matter what your age is or what your gender is. If you have a very high fructose intake, you're going to have a greater incidence of uric acid stones. And this has to do with the fact that to break down fructose, you have to release a lot of adenosine monophosphate and it's the metabolism of adenosine that leads to the production of uric acid. And I don't expect you to read this slide, but this is those same three groups of people. And if you look at just their BMI, as their BMI increases, their risk of kidney stones increase. So it's not just, and it's not just obesity, it's actually where do you put all the fat? So the people who tend to have the most problems are the ones with the highest waist to hip ratio. So it's not just how fat you are, it's where do you put it. And if you're saying that people who put their fat around the middle are more likely to have metabolic syndrome, again, more evidence that there's something about metabolic syndrome that predisposes you to kidney stones. Now let's talk about calcium intake. This is from the studies of osteoporotic fractures where they actually looked at calcium balance. And what they found is that you could break down people into, even though the dietary calcium intake was more or less the same. If you looked at the people who formed stones, which is in the yellow, versus the people who didn't form stones, which is in the purple, okay? The people who had the highest absorption of calcium in the diet were the ones that were most likely to form stones. And then the other thing that you see about from this slide is that there are really two groups of people here, okay? One group of people who actually, their intestinal calcium absorption doesn't change very much. And another group of people who on a higher, who have a tendency to reabsorb calcium, which you would think would be an evolutionarily advantageous thing in a low calcium environment, but in a high calcium environment might potentially be bad for you. And if you're eating, if you're one of these people who tends to absorb a lot of calcium, if you're eating a low acid diet, in fact, you don't dump a lot of that calcium into the urine. But if you eat a high acid diet and you're a stone former, you're much more likely to put all of that calcium into the urine. And the more calcium that's in the urine, the more likely that calcium is to precipitate and cause stones. So if you're saying what is a Western diet? Well, it tends to be a high dairy product, a high dairy diet, a high acid diet. And if you're one of these people who's predisposed to high intestinal calcium intake and you're eating a highly acid diet, you will be more likely to get kidney stones compared to this other group who in fact don't get kidney stones. And if you actually say, if you actually do a balance experiments, what this shows is that at a very high acid balance over here, these people are actually in negative calcium balance. And this is where the idea came from, that in fact, we're pulling the calcium out of the bones and that if you're in high acid balance, you may be actually dissolving your skeleton away in order to be able to actually buffer the acid in the system and the calcium is just dumped because that's a byproduct of breaking down the base buffer in the bones. And if you say to yourself, where is the acid in the diet coming from? Well, all foods contain acid precursors, which are sulfates and phosphates, but only fruits and vegetables, and that's over here, contain the base precursors that are metabolizable to bicarbonate. So again, if you're eating a Western diet, so high in grains, high in animal foods, low in vegetables, you're gonna be eating a high acid diet. And this just shows you again, these are balanced studies, that high acid diets tend to cause higher urinary calcium excretions compared to lower acid diets. And it turns out, independent of everything else, if you, the more factors you have for metabolic syndrome, and we don't really understand this really well, the lower your urine pH is going to be. And there seems to be a problem with acid excretion in the kidneys. And so something about just the way the more factors for metabolic syndrome you have, the more likely you are to have an acid urine. And the more acid the urine, the more likely you are to get calcium, oxalate, and uric acid stones. And the more factors for metabolic syndrome you have, the more likely you are to be one of those people whose blood pressures go up when you eat a lot of salt. So it turns out that some people can eat all the salt they want, and it doesn't do anything to their blood pressure. And other people, they eat just a little bit of salt, and their blood pressure goes way up. And so when you're talking about kidney stones, especially these kinds of kidney stones, it turns out that salt is bad for you. And it's actually both the sodium and the chloride in the salt, that's the problem. So the chloride in the salt actually exchanges with the bicarbonate. And so the higher the chloride level, the higher the chloride intake, the lower the bicarbonate level, and the lower the blood pH level. And by definition, okay, this means that you're tending to maintain your blood systemic levels at a higher acid level than you would otherwise. When you take the salt away, then the acid levels decrease, and the blood pH and bicarbonate go back to their previous range. So chloride in and of itself is bad for you. And then the sodium, it's well known that when you deliver a lot of sodium to the distal tubules in the kidney, you exchange that sodium for a lot of calcium. So the higher your sodium intake, the higher your urinary calcium excretion. And in people who are predisposed to develop high blood pressure when they eat a lot of salt, it turns out that there's another whole system, which they've been talking about recently, about how does this modify blood pressure? And it turns out that there's a nitric oxide system which causes your blood vessels to dilate. So as long as you're making a lot of nitric oxide, you'll tend to have low blood pressure. People who have salt-sensitive hypertension make a lot of this blocker, ADMA. And so the more salt they eat, the more ADMA they make. ADMA blocks the production of nitric oxide, and so they can't lower their blood pressure and their blood pressures go up. And that's what this slide over here shows. But this is important for kidney stones because it also turns out that the people who are salt-sensitive, the more salt-sensitive they are, the higher their urinary calcium excretion is. So again, salt-sensitive people tend to have metabolic syndrome. People who have metabolic syndrome tend to have lower urinary pHs. People who are obese tend to have kidney stones. People who are obese, especially around their center are more likely to have kidney stones. So all of these things that we think where the diet can be a contributing factor are people who are predisposed to kidney stones are potentially making you even more likely to get kidney stones. And that's what I said here. And the higher your blood pressure is in these rats that have been genetically bred to develop high blood pressure, you can show that when you give them a lot of salt, their blood pressures go up and their kidneys turn into scar tissue. And by giving them enough base to neutralize the acid in their system, you actually keep their blood pressures under better control, and this helps contribute to keeping their kidneys healthier. And we also now have found from epidemiologic studies that people who are more likely to have stones are more likely to develop kidney failure. So the stones themselves cause you to have kidney failure. And my personal belief, the factors that predispose you to have kidney stones predispose you to having vascular disease too. And so it's a combination of both the specific things that are related to having kidney stones plus the more common things that cause you to have vascular disease that cause you to have kidney failure. And so what we're seeing now more and more is increases in the number of people who have kidney stones, as well as the number of people who have kidney failure. And there's been a couple of recent articles on climate change and the incidence of kidney stones and kidney disease. And so in sections near the equator and say India and Sri Lanka and Central America, they're now have especially in agricultural workers who tend to be out in the sun for long periods of time and are not getting, presumably not getting enough hydration. There's been a marked increase in the incidence of both kidney stones and kidney failure in these people. And so really we think that this is going to become more and more of a problem as the climate gets worse and worse. And so if I had to say, do I believe that a diet where you can help improve blood sugar control, help improve blood pressure control, you know, possibly that would help you not be as fat. Especially if you happen to be those people who are predisposed to having these things, especially if you eat a lot of salt, then a paleo diet might be something that would not only improve your chances of kidney stones if you're predisposed to that, but also progression to kidney disease. And in fact, the only, just today, I just saw a new study that came out that showed that in the dash diet, which is a diet which is low in salt and higher in fruits and vegetables, they followed like 14,000 people over 25 years. And it showed that the people who followed, who most followed the dash diet were the ones who had the lowest incidence of progression of kidney disease. And that actually is the best data that I know to say that perhaps this really is something that we should really be trying, we as me as a kidney doctor, and people who are taking care of relatively healthy people who have some of these common problems, that this is something that we should really be trying to work on more. Unfortunately, most of the time, by the time I see them, it's too late to do anything. So it's just sort of my plea for those of you out there who actually do take care of healthier people to try to do this. And I'm speaking not to the people in the audience, but to the people who might be out there and online who are watching this, who want to say, do I want to do this? And I think this is really something that we could really help people with. And then I just want to thank all of my collaborators. And this is what San Francisco looked like when I left the other day. So, you know, miserably cold and foggy. So anyway, thank you very much. I appreciate everybody listening. So, questions? Yeah, so if I understood you correctly, you talked about vascular diseases being the primary cause of, or increasing chances of getting kidney disease. And kind of in the first portion of your talk, I wrote a note down of you saying something about controlling the amount of protein in the urine. So my question is, does a high protein diet contribute to the higher chances of getting chronic kidney disease? And if so, how does that happen? I don't think it's the higher amount of protein in the diet. I think it's the balance between the amount of protein and the other things that you eat. But the protein in the urine seems to be because of damage to the glomerular filtration membrane, which is due to, for example, the high pressure inside the glomerulus, or actual damage from the high blood sugar damaging the membrane, which then allows the protein to leak through. So those are the factors that we try to control in an attempt to try to make the membrane as healthy as possible. Hello. I've just finished my first year of medical school, and one of the things they taught us was that gout, the majority of people with gout are under excreting uric acid. With the links between gout and Western disease, that got me thinking as to what your thoughts might be on how that was coming about. So it's, if you under excrete uric acid, that's probably a problem with uric acid transport into the kidneys, which may be a specific transporter problem, not specifically something you can do anything about. What you can do something about is how much uric acid you actually take in. And so that's where I think the ability to modify your chances of getting gout actually come from. Okay, thanks. Hi. I was wondering if you could speak to people who do have kidney disease, whether that be stage one to stage three or four, not necessarily on dialysis and animal protein for those people. So I get in prevention models, that's different, but when somebody already has existing kidney disease, is that you see studies where that becomes an issue, but in the context of a paleo diet or a lower carb diet, is that trying to figure out, tease out those studies? So if you have advanced enough kidney disease, we actually limit your protein intake to somewhere around 0.8 grams per kilogram per day. I don't actually believe it makes a difference where the protein comes from. I think that as long as you don't have stage four kidney disease and a problem with potassium excretion, then if you can then also make sure that you're getting enough base so that you can modify the acid in the diet from the proteins that you're probably going to be okay. Thank you. Hi, thank you for your talk. I wanted to talk to you more about salt because I don't know if you differentiate between salt that's in processed food, regular table salt, sodium chloride with iodine added, and unrefined sea salt with a lot of people that are in the paleo community eat. So for what I've read, and I use a lot of unrefined sea salt because it's got a lot of minerals in it other than just sodium. Is there, what do you think about that? I'm talking about sodium chloride. Sodium chloride, so you're okay with, because a lot of people in the paleo community have reduced inflammation, we don't retain a lot of water, we tend to not retain a lot of salt, and we also tend to be low on minerals generally just as a population, so I like to use unrefined sea salt. Right, and again, there is a population of people who can eat a great deal of salt and it doesn't seem to bother them. The older you get, the fatter you get, and the more likely you are to have metabolic syndrome, the more likely you are to have a problem with salt intake. Gotcha, gotcha. I agree, I think your comment though about paleo in general probably leading to more kidney stones, it's sort of weird to just generalize paleo, because you got Dr. Wal's paleo, which is very, not high in protein at all, and loaded with vegetables, and I wouldn't think a diet like that, what all would lead to higher kidney stones. Okay, so kidney stones is a complicated issue, some of it is genetic, some of it is related, and a lot of it is related to urine pH, so I didn't talk at all about the kinds of stones that form an alkaline urine, so that's a completely separate topic. All I'm talking about are stones that form where the diet is a potentially modifiable factor in the production of these specific kinds of stones. Understood, thank you. Okay, thank you.