Kidney Biology: Simple Diet & Lifestyle Practices for Kidney Health | Thomas Weimbs | #186

About the guest: Thomas Weimbs, PhD is a molecular & cell biologist at UC-Santa Barbara. His lab studies kidney function in health and disease.

Episode summary: Nick and Dr. Weimbs discuss: basic kidney biology; kidney stones and their causes, including dietary oxalates and fructose; the kidney damaging effects of common pharmaceuticals like Ibuprofen; the beneficial effects of BHB and ketosis for kidney health; the myth that high protein intake is bad for the kidney; kidney diseases and their causes; and more.

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Beta-hydroxybutyrate (BHB):

* The primary, most abundant ketone body produced by the liver from fat during fasting, low-carbohydrate intake, or intense exercise.

* KetoCitra: Ketone body BHB with potassium, calcium & magnesium, formulated by Dr. Weimbs with kidney health in mind. Use code MIND20 for 20% off.

*This content is never meant to serve as medical advice

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* Episode transcript below.

Full AI-generated transcript below. Beware of typos & mistranslations!

Thomas Weimbs 1:27

Yeah, it's great to be here. Thank you. Thank you.

Nick Jikomes 1:28

Can you tell everyone a little bit about who you are and what your lab studies?

Thomas Weimbs 1:33

Sure, yeah. So yeah, I'm Thomas Weimbs. I'm a professor of Molecular, Cellular and Developmental Biology at the University of California in Santa Barbara, and we study primarily a genetic kidney disease called polycystic kidney disease, or PKD.

Nick Jikomes 1:53

Okay, we'll get Yeah, we're into that disease and stuff quite a bit, I think. But, you know, I've ever really done any podcast that's had directly to do with the kidneys or the kidney, just kidney biology. And so I want to start out with just some basics on kidney biology. A lot of people will have some general, vagues. Like Me will have some general, pretty vague sense of what the kidney does. It's involved in filtration. But you know, how well would you say we understand the kidney as an organ? Is it an organ that that's considered to be sort of fully solved or fairly well understood, or is it still quite mysterious in certain ways? Well,

Thomas Weimbs 2:33

I would say, you know, scientists you know, have studied it for a long, long time. And obviously, you know, there is a whole discipline called nephrology out there, you know, you know, the kidney doctors, I would say there's a lot of mysteries, but there shouldn't have to be mysteries. So it's, for example, you know, chronic kidney disease, often just called kidney disease, you know, in lay terms. Turns out it's the number one non communicable disease by prevalence. So that's a head of cancer, head of cardiovascular disease, ahead of type two diabetes. So in the US, there's about 14% of the population affected by kidney disease. So it's a pretty insane number. So we're talking 40 plus million people.

Nick Jikomes 3:24

Well, more than one in 10 people has chronic kidney disease. Yeah, yeah.

Thomas Weimbs 3:27

So worldwide, it's, you know, over 10% in the US, it's a little more, it's 14% so the mystery is, to me, not much of a mystery, but for some reason, for everyone you know, for for doctors, it seems to be a bit of a mystery, you know, how does this come all about, what do we do about it? You know? And the numbers have just going up and up and up. So clearly, the treatment is not doing what should be doing. So it's only gotten worse.

Nick Jikomes 4:00

Yeah, I suspect maybe there's some foreshadowing happening here. Maybe it's just another example of where you know, when we treat things, we're often treating the symptoms, the some of the end points of the disease, rather than addressing what's actually causing the disease and removing that before we before we dive into all of that stuff. Can you just give us a basic, concise overview of the major known functions of the kidney. How does it do? What it does, and how does it work?

Thomas Weimbs 4:27

Sure, yes, yeah. So we all have two kidneys, you know, almost everyone, and they're essentially, you know, the the most basic function of the kidneys is to make sure our blood gets purified constantly. So 24/7 the kidneys just essentially filter the blood, and they do it in a way where, essentially, everything, you know, all the small molecules, get filtered out first, and then the kidney decides what to keep and what to reabsorb again. So for example. Uh, you know, waste products, you know, metabolic waste products, you know, the kidney just gets rid of, but something like sugar, amino acids, you know, things that we actually want to keep. They get filtered first, and then the kidney decides, oh, wait, here's sugar, let's keep that, and let's not pee it out. Here's an amino acid. Let's, you know, keep that. And the end product is, of course, the urine that we, you know, excrete, and then, which means, with the urine, we get rid of a lot of the waste products. And in the whole process, the kidney also regulates, you know, the homeostasis. So essentially, the balancing of, you know, many of the the components that we need, you know, to live. You know water homeostasis. Why? Obviously, if we're in the desert wandering around and haven't had a drink in a day or so, the kidneys try their very best to conserve water and not pee out anything. If we're drinking like crazy, obviously the kidney has to get rid of a lot of the water, but just an example. And the same applies to things like sodium, potassium, you know, essentially all of the electrolytes, and they're essentially all handled by the kidneys, and the kidney decides, oh, I have too much sodium, let's pee some out. Or we have too little sodium, let's retain it. So that's in a nutshell what the kidneys do. So if they would fail, however, you know, obviously everything goes out of whack, and, you know, very quickly we would die.

Nick Jikomes 6:31

So, so the kidneys are filtering our blood, obviously, the blood, you know, the cardiovascular system. We're pumping blood all throughout our bodies in order to transport electrolytes, to transport oxygen, macronutrients, micronutrients, and we want all of these things to get all over the body, but we want to make sure we don't have too much or too little of some of these things. And we also want to filter out things that shouldn't be there in the first place, like like small molecules or toxins and things like this. Is that more or less how to think about it? That's exactly right, yeah. And what, like, what, to what extent is the kidney hooked up and working in parallel with, like, the liver. So, you know, is the kidney filtering out certain toxins, but certain other toxins go to the liver, like, when we want to get out, like, synthetic compounds, environmental contaminants, things like that. How does the liver stack up relative to the kidney?

Thomas Weimbs 7:24

Right? Yeah. So both organs, the liver and the kidney, are sort of detoxification organs, and that's part of their function. Basically, you could say that the liver is more in charge of detoxifying lipophilic compounds, you know, things that are essentially fat soluble, and the kidney is more in charge of getting rid of hydrophilic compounds, water soluble things, and it just has to do with the nature of, you know, the urine versus the bile, essentially, and things like that. But often there's a bit of a cross talk, because sometimes a lipophilic toxin can get processed by the liver first and turned into something hydrophilic that then the liver spits back out into the blood spray, bloodstream, then it goes into the kidney. The kidney says, whoa, this is a toxin. Let's get rid of it. So there's, you know, collaboration going on, refusing. But

Nick Jikomes 8:16

as a general rule, the kidney is filtering out water soluble stuff from the blood and the liver is detoxifying fat soluble stuff, as a general rule is, is another difference there that, like, when the liver detoxes something, there's there's actual sort of enzymatic transformation of chemicals, whereas it sounds like maybe the kidney is not necessarily chemically transforming things, but but filtering them out and putting them into the urine instead,

Thomas Weimbs 8:43

yeah, I would say that's basically correct.

Nick Jikomes 8:47

And then so we all have two kidneys. Is there anything? What should we know about, like, kidney anatomy? Are there, like, specialized compartments that do different things? What are sort of the major pieces of each kidney,

Thomas Weimbs 8:59

right? Yeah, so each kidney is made up out of sub units that are called nephrons. So the human kidney each has about 1 million nephrons. And so they're obviously tiny, microscopic. And each nephron is essentially a tubular, right? So like a small little tube, it has, you know, beginning and an end. The beginning of the tube is a structure called the glomerulus, which is where the blood essentially comes in, right? So there's, it's a vascular system, and that's where the filtration happens. Once the blood comes in, it gets pressed through a sieve, if you will. And then the fluid enters the beginning of the tubule. It moves all the way along the tubule. That's where all the processing happens, you know, the the good and the bad gets separated. And then at the end, each tubule ends in a collecting duct, which then you. Eventually leads to the bladder, and, you know, that's how we pee it all out. So those are the basic units. So we're born, you know, with about, like, a million nephrons in each kidney. And the goal is we want to keep as many happy as as, you know, for our lifetime, as we can, because they don't come back. They can. They don't, you know, we cannot produce new nephrons if some get damaged.

Nick Jikomes 10:26

I see, so that's different, like, so that's kind of similar to the brain, like we can't regrow parts of our damaged brain. We can't regrow these nephrons, these subunits of the kidney. So I would imagine, just naturally, over time, as we age, some of them start to fail. And we've sort of got, I guess you could think of what? Why do we have a million of them? It's sort of like a lot of backup systems. And eventually, I would imagine enough of them get damaged that the kidney as a whole is no longer filtering things properly, and that's when you can start to run into chronic problems,

Thomas Weimbs 10:55

right? Yeah, that's exactly right. And in fact, even a perfectly healthy individual, you are going to lose some nephrons, you know, here and there. And it's just an age related consequence, you know, of aging that our kidney function slowly declines a little bit, you know, if somebody's like, you know, very old age, you know, and they have 60% kidney function that's actually considered completely normal. So that's not a cause of concern. But of course, if you're if you're young, and you're left with only 60% kidney function, that will be a cause for concern, because it's only going to go downhill from there,

Nick Jikomes 11:35

I see. So your total blood filtration capacity is basically the number of healthy nephrons you have across both kidneys. And I suppose this is why you can often afford to lose one of them if you want to donate your kidney to someone. And even though that won't kill you or anything, it will sort of, it'll decrease your sort of lifetime capacity for filtration, yes,

Thomas Weimbs 11:56

to a certain extent. However, interestingly, the kidneys can actually adjust and can so let's say you donate a kidney, or you lose a kidney, for some reason, the remaining kidney actually grows in size. So it doesn't grow new nephrons. Everything just becomes a little bit bigger. So that's called hypertrophy. So the whole kidney enhances its capacity to filter more. So there's actually some compensation and going on. That's why it's actually all right to donate a kidney. You know, it's not that you suddenly are left with only 50% kidney function, because the remaining kidney cranks things up and then

Nick Jikomes 12:39

grow new kidney, but your your other kidney will get bigger, so, like, the processing capacity of each processor of the kidney will actually get a boost. Exactly.

Thomas Weimbs 12:48

Yeah, wow,

Nick Jikomes 12:51

interesting. And so I would imagine, like, what are some of the common ways that, like, kidney function can be temporarily compromised, like our states of like, can you go into states of dehydration or electrolyte overload that kind of temporarily throw it off and and mess with, like, your urine composition or something like that? Yes,

Thomas Weimbs 13:11

for sure that can happen. That's called acute kidney injury. And there's, like, you know, 1000 reasons why that could happen. You know, simple way of thinking about is a nephrotoxin, right? So you accidentally ingest something that is a nephrotoxin and starts because many toxins go through the kidney by necessity, because they need to get filtered out so they can get concentrated in the kidney and really affect kidneys more than other organs. And if the toxin starts killing kidney cells, you know, you you end up with acute kidney injury. That can be dramatic. So you know, your kidney function can go down to essentially nothing, which means somebody might need to go on emergency dialysis, you know, to make up for it and in order to survive. But oftentimes the kidneys can actually recover so from acute kidney injury, so they have the kidney has innate mechanisms to repair itself, so there can be new proliferation going on of these kidney tuple cells, and they essentially start replacing these ones that were lost. So acute kidney injury, you know, can, can definitely happen, and oftentimes is recoverable. It can also, you know, common cause is, for example, during what's called ischemic events, you know, during surgeries. But if somebody has a cardiac surgery, it's quite common that the kidneys are affected because the blood supply is compromised temporarily during the surgery, and you end up with acute kidney injury. And it may not be a big problem, because, you know, you just essentially, you. You know, wait for the kidneys to come back up.

Nick Jikomes 15:02

And what So, what is the the direct, immediate source of the blood into the kidney? What is that? What is that vessel and where is it getting the blood from? I would imagine this has to be blood as much as possible, that's not already gone through general circulation. It's probably trying to get pipe in the kidney shortly after the gut is absorbing nutrients and

Thomas Weimbs 15:26

things like that. You know, I'm not the world's best anatomist, but I think it's actually just a regular artery that goes into the kidney, and it has probably to do with, you know, the 24/7 mechanism. You know, the kidneys are always working, right? So they don't just kick in after you consume anything, they just keep filtering. So it's just a constant, you know,

Nick Jikomes 15:49

constant plug in to direct general circulation, right? And so when, so the kidney is dealing with the world of water soluble stuff, primarily, so it's going to affect electrolyte levels in your blood and your urine. It's going to affect, you know, filtering out toxins. For example, when we think about toxins, water soluble toxins that the kidney is filtering out, how does the kidney know when something is a toxin and when it's supposed to be circulating?

Thomas Weimbs 16:19

Yeah. So there, you know, there's many different complicated mechanisms, you know. And you know, the basic principle is usually that everything, just as I mentioned before, everything gets filtered, you know, in the beginning of the tuple, and then the kidney essentially just recovers what it wants. So it works sort of like almost in reverse, but it gets, by default. It gets rid of everything, and then recognizes specific things. Let's say glucose, right? So there's a glucose transport or that says, Oh, you are glucose. Let me bring you back into the through the epithelium, back bring into the blood. So it's not as much that toxins get specifically secreted, you know, they essentially get secreted by default, you know, for the filtering process, but then they're not being recovered because they're not recognized as useful. That actually makes

Nick Jikomes 17:10

sense. It's a pretty elegant way to to for the system to have evolved, because if it had to individually recognize all of the toxin things you don't want, you know, there's, who knows how many, an effectively infinite number of those things. There's sort of no way to bake all of that complexity in, but if you're just filtering everything out by default, then you've got a finite number of things that the body is pre programmed to know should go through glucose, etc, exactly. Yeah, interesting. And you know one thing, fortunately, I've never experienced this, but it's fairly common. You can tell us how common it is, but people talk about kidney stones and how painful they are. What exactly are kidney stones and what causes them?

Thomas Weimbs 17:51

Yeah, so Kidney stones are fairly common, and they have been getting more common, you know, in, you know, in past decades. So what are kidney stones? So the kidney, you know, as it, you know, does its filtering business, and, you know, excreting of, you know, waste products, it also concentrates a urine. You know, what becomes a urine, right? So you stop of a larger volume, as it's a kidney filters. And, you know, obviously you don't want to lose all the water, because you would dehydrate very, very quickly. So the kidney then needs to recover a lot of the water, which means the solutes that are, you know, to be excreted, they get more and more concentrated over time, you know, as it passes through the kidney. And unfortunately, some of the solutes have the tendency to be not very soluble, which means that along the way, you know, they hit the super saturation threshold and start to crystallize inside the kidney Tubal and that that's what leads to microcrystal formation in these tubules. So it's something we have actually studied in the lab, the most common form of kidney stone in humans is calcium oxalate kidney stones. So that's like, by far the most common and the molecule calcium oxalate. So it's just, you know, like, when calcium meets oxalate, you know, they get together, and that they happen, that happens to be poorly soluble, and in the, you know, once it's concentrated in the kidney, it can crystallize out. And these crystals are, you know, maybe, like, say, a micrometer in diameter, initially, what is a tiny, microscopic but there, there can be very damaging, and they can, because they look like little shards of glass, right? So they have like edges, and they can, they like to get stuck in those kidney tubes. So

Nick Jikomes 19:50

kidney stone is literally a tiny crystal, and it has to eventually, somehow pass through the system of tubes that comprises the kid. Kidney all the way through your urethra?

Thomas Weimbs 20:02

Yeah, it's not yet. So the micro crystal, I would say, is a precursor to a kidney stone. I might still like a bunch of them aggregate together exactly right? So if the kidney somehow is overwhelmed with too much calcium oxalate, forms too many of these micro crystals that can get stuck, that can aggregate. And a big question is, how does the kidney get rid of them? That's actually something we have studied and happy to tell you all about. It is a very cool mechanism, but basically, if the kidney fails to get rid of them, so just keep accumulating their bunch together, and they form bigger and bigger, you know, crystals and which eventually becomes a kidney stone. And then that can cause big problems.

Nick Jikomes 20:45

Yeah. So it sounds like multiple things need to happen. A these micro crystals need to form to begin with. So you need to have calcium meeting oxalates to create calcium oxalate, you probably then have to form a number of these micro crystals, and then the kidney has to fail to get rid of them fast enough so that they can accumulate and aggregate together, and then you've got a kidney stone, which is going to cause you actual symptoms and actual problems. So let's start at the very beginning. If the micro crystals are calcium, oxalate, calcium. You know, we get calcium in our diet. Everybody knows that it's an ion. It's going to be water soluble, pretty straightforward to think about. You know, calcium is used for all sorts of stuff throughout the body. It reacts with these things called oxalates. What are those and where do they come from?

Thomas Weimbs 21:30

Yeah. So, oxalate is a normal metabolic waste product that we make day in, day out. And, you know, it comes from things like hydroxyproline, which is in our collagen, for example, and a few other compounds that turn, you know, get metabolized to oxalate, and you cannot the body cannot degrade oxalate any further, so you have to pee it out. Never get rid of it, mostly for the kidney and usually, the endogenous production of oxalate is not a problem. You know, the kidneys are have evolved to deal with that. The problem comes in if we also eat a lot of oxalate with all food or ingested and it Where does oxalate come from? In nature? It actually comes from plants. So many plants use oxalate, essentially as a defense, as a poison, because plants, it turns out, they don't want to be eaten, most of them, so they try to be toxic to animals. They want to eat them, let's say humans. So if you go out in nature, and you know, to start eating like 100 different species of of plants, you know, probably 95 of them will eventually kill you if you eat enough of it. So usually plants are very toxic. Only very few plants, you know, have become food for us humans, but they still do contain oxalate, just, you know, like lower amounts, but some are still off the charts. You know, things like spinach, for example, that's probably the most common one that can cause oxalate problems. So spinach contains a huge amount of oxalate. I would consider it a non edible, toxic plant, actually. So I'm not quite sure why it is allowed to be, to be, you know, in our food supply, but yep, so yeah, so you can absolutely overeat on, say, spinach. And some people like to make, like, spinach smoothies or spinach juice or something

Nick Jikomes 23:42

that would probably actually just increase the bioavailability of the oxalates. Oh,

Thomas Weimbs 23:45

yes, right. So, and there are many case reports in the literature where you know somebody, you know, consumed, you know, a few too many spinach juices and ends up with acute kidney injury, what we talked about before, and they're in the hospital, and sometimes they might even lose their kidneys.

Nick Jikomes 24:04

So Popeye, the Sailor Man, probably had kidney stones,

Thomas Weimbs 24:10

very possible.

Nick Jikomes 24:12

So okay, so if I'm hearing you correctly, so the oxalates are essentially, they're in most plants to some level. Many plants have them at very high levels, and it's they sort of have them for the reason of defense. They actually don't want, you know, most plants don't want to be eaten most of the time. And if they are eaten by herbivores, you know, herbivores are animals that probably have evolved special adaptations to detox these plants in certain ways. And so in a species like ours, which doesn't have those detox mechanisms, you can run into problems by consuming plants with high levels of things like oxalates. It sounds like you said, basically the things that we consider edible vegetables represent a tiny slice of the plant world that just doesn't have especially high levels of things like oxalates and presumably a lot of other things. But you're saying. In one case, spinach, we do commonly think of this as an edible food plant, but what you're saying is it actually has high enough levels of oxalates that you think that's basically a mistake.

Thomas Weimbs 25:11

Yeah, I would probably say so. And especially since spinach is, you know, promoted as a healthy food and, you know, seed on the internet all day long. You know a nephrologist, friend of mine, you know Toby once that you know he had a patient who, you know, heard on the internet that spinach is good for you. So she said, All right, if a little bit of spinach is good for your health, more spinach is more good for your health. So you eat spinach all day long. And that person, then, you know, showed up at the in the nephrology clinic with acute kidney injury. And that happens with other foods as well. Many nuts are very high in oxalate in almonds, peanuts, for example, another nephrologist friend told me of a person who was binge eating peanuts, which is very easy to do, because it tastes so good, and you end up with acute kidney injury, potentially.

Nick Jikomes 26:06

Yeah, the more I've learned about nutrients and toxins and bioavailability across foods over the years, the more the more I realize how backwards thinking often is so. So for example, just to take the case of peanuts, you're saying, not only do they contain oxalates, so if you more peanuts are going to have more oxalates and a higher chance of getting kidney stones. But people, for example, think of peanuts as a good source of protein, and while they contain a lot of protein, it's not very bioavailable. So there's a lot of people out there eating peanuts, not realizing that they're getting oxalates, which will promote kidney stones, and thinking falsely that they're getting a lot of protein, when in fact, they're only getting a fraction of what's inside of it right Yeah, exactly. Interesting. Any other common foods that have, like, fairly high levels of oxalates that maybe people should know about, besides spinach,

Thomas Weimbs 26:51

yeah? So things like rhubarb, you know, that's not so common in the US, but in Europe. I'm from Germany. You know, when I was a kid, you know, I love to eat rhubarb. You know, when it's rhubarb season, that's pretty high in oxalate, things like dragon fruit, and, you know, many, essentially, you know, I think I would say by default, you know, you would want to suspect that something has is high in oxalate. There's actually, you know, like tables of oxalate content of different foods. So it's, it's a good idea if somebody has kidney stone problem, you probably want to look at a list like that and maybe flag for yourself the things that are kind of very high in oxalate and say, oh, okay, let me stay away from those.

Nick Jikomes 27:35

Yeah, yeah. But it's, it's based on everything you've said so far. Obviously some things have higher levels of oxalates, like spinach, but it sounds like most plants, or a high percentage of plants, are going to have some amount of oxalates. Yeah,

Thomas Weimbs 27:48

yeah, pretty much you know, things like Swiss chard, for example. Again, promoted as a as a health food. It's also very high, yeah. And then you know, if you're that's why juicing may be a bad idea for many people might especially juicing because you end up being you start with a large amount of spinach, whatever it is, and you condense it down to a tiny little drink. You gulp it down all at once. Yeah, right. And maybe you have another one after that, so the intake can be quite, quite high. Wow.

Nick Jikomes 28:25

And so, you know, inevitably, right? There's going to be people out there who've had kidney stones, people who will get kidney stones. Let's say you're one of these people. You know, you're consuming a little bit too much of the oxalates from different plant foods like spinach. These micro crystals start to form calcium and oxalates. Form calcium oxalate they start to form, and then they start aggregating. So the kidneys failing to get rid of these things, failing to clear them out, what is causing that?

Thomas Weimbs 28:53

Yeah, so that's something we have researched. And you know, it used to be pretty mysterious. You know how the kidney gets rid of these micro crystals? So I'd say everybody knows, you know they do form and you know they actually do show up in the urine. So that's called crystalluria, right? So if somebody has, you know, lots and lots of crystals in the urine. That's called crystalluria. And pretty much every normal person even pees out millions of these micro crystals every day of the urine. That's kind of how the kidney gets rid of them. So and as long as they stay small enough, and they get excreted quickly enough for the kidneys, they don't really pose any danger. But every once in a while they do aggregate, and, you know, the kidney gets overwhelmed and they get, you know, lodged in those kidney tubers. And it was actually unknown how the kidney deals with that, you know, with these initial kind of, like blockages of crystals. So we published a paper back in 2019 where we actually figured out how this works. And it's, you know, it's a, I think, a brilliant move. Of evolution, what we found is that, you know, once a kidney tubule is blocked with like an aggregate of crystals, the plumbing essentially widens, right? So the tubal, you know, has usually a very small diameter, but with a crystal stuck in them, the tubule just gets much bigger, right? So you get a, you know, doubling, tripling or so of the of the tubal diameter, and that allows that tubule to flush out the crystal and get rid of it. And then after about a week or so, the tubal is back to the normal diameter. So it will re establish its diameter. And that is actually controlled by signaling pathways in those kidney tubal epithelial cells. And if you block them, for example, the tuber cannot widen, and, you know, you get worse, you will get worse crystal burden, and the kidney cannot excrete them. So it's, you know, it's almost like in your house, you know, your kitchen sink, you know, is connected to the plumbing. You put too much grease and coffee grinds down there, it gets stuck eventually. If you're if you had really smart plumbing, the plumbing would just widen and, you know, let you just flush it all the way out. And that's what, you know, our plumbing is stuck, you know, at one diameter, but the kidney has solved that problem.

Nick Jikomes 31:22

I see, well, yeah, so it can just, you can just dynamically adjust its size, right?

Thomas Weimbs 31:27

Yeah. And for some reason that that hadn't been realized before, so and that that also then tied in to this whole problem of polycystic kidney disease that we can get into later, but we think that's actually kind of what, what is causing these cysts to form. And

Nick Jikomes 31:50

when someone has, like, full blown kidney stones, and they talk about having to pass the stones, how are they normally removed? If someone has to go into the Doctor, are they? Are the procedures that can be done to go in and, like, disintegrate the crystals, or do they have to, like, let it pass all the way out of their body? Yeah.

Thomas Weimbs 32:05

It totally depends. You know how big the stone is and where it is stuck. So sometimes, you know if it's too big, yes. So with ultrasounds, that can be essentially broken into tiny pieces, sometimes that's not if that's not possible, you know, they might have to go in surgically to remove a kidney stone, but you know, the best way is always preventing it from from happening in the first place, and usually when somebody has had a Kidney stone. I've never had one, luckily, but I've heard, you know, bad stories about how painful this is, and people compare it to, you know, a woman giving birth, you know, the same level of pain. So I think people that had kidney stones are highly motivated not to get another one. Yeah. And prevent them. Yeah, yeah.

Nick Jikomes 33:00

So basically prevention here is basically about avoiding oxalate containing foods. So

Thomas Weimbs 33:05

yeah, that's one way, and it depends a little bit. So there are some kidney stones that are not made up of oxalate. So another class is calcium phosphate, and another one is uric acid. There are kind of two other somewhat common ones, but most of them is calcium oxalate. So if someone is a calcium oxalate stone former definitely they would reduce the intake of oxalate. You can also actually increase the intake of calcium with your food. And that sounds counterintuitive. What do we think? Oh, wait a second, eating more calcium, shouldn't that give me more calcium kidney stones? But actually the opposite is the case, because the calcium that you ingest with your food, let's say, from a dairy product. You know, eat some yogurt with your spinach, the calcium from the food will actually bind to the oxalate

Nick Jikomes 34:01

from the preemptively bind to it before it gets inside, exactly so

Thomas Weimbs 34:05

it gets essentially neutralized in the GI tract, and you just get rid of it harmlessly nice as a way of preventing it,

Nick Jikomes 34:13

I see. So if you really love peanuts or spinach or stuff with oxalates, or let's say you're a vegetarian or vegan, and it's harder to avoid eating high oxalate levels if you are just careful about CO consuming high calcium foods with high oxalate, foods that can help solve the

Thomas Weimbs 34:29

problem, exactly, right? Yeah, that's and you know one, the one, the number one recommendation to prevent kitten any kidney stone of any chemical composition is just drink more water. And because I will always keep things more diluted in the kidney and, you know, and prevent these super saturation problem for any type of kidney stone. And that's, you know, the number one recommendation for anyone you know to prevent kidney stones, just drink more water. You know, lots of people don't like to do. More water, and that can be a challenge. But, you know, something like two or three liters a day is usually kind of the recommendation there I

Nick Jikomes 35:10

see. So the the stack of recommendations here to minimize kidney stone, the probability of getting kidney stones, stay hydrated with plenty of water, avoid oxides as much as possible and or consume high enough levels of calcium together with foods that contain oxalates.

Thomas Weimbs 35:26

Yeah, yeah, exactly.

Nick Jikomes 35:27

What about, um? Are there any like food components or toxins or chemicals that are particularly problematic for the kidney, that can damage the kidney like, you know, by analogy, we often talk about liver or liver damage, certain, like, if you drink a lot of alcohol, this is really hard on your liver, in particular, because the liver is what's detoxing the alcohol. Are there any common things in foods or in medications or anything like that that people are exposed to that is especially problematic for the kidneys? Right?

Thomas Weimbs 35:59

Yeah, I would say number one is probably anything that can form micro crystals in the kidney. We talked about the oxalate. Another one is phosphate, for example, calcium phosphate. And unfortunately, ultra processed foods contain a lot of inorganic phosphate food additives, and they are. They're not added for nutritional value. They're just added for, you know, industrially processing value, essentially to make it more, you know, your foods more, you know, palatable, or to as a preservative and things like that. So they're in there for the wrong reasons. And the inorganic food additives, they actually get absorbed much more than, you know, phosphate that comes with meat, for example, so you end up with a high phosphate load, and that has to get through the kidney. Can give you calcium phosphate kidney stones. Another source is actually a uric acid. So that's not something you eat, but the uric acid is sort of a metabolic consequence most of the time of eating too much fructose, right? So the sugar and fructose and fructose is like half of of the table sugar, sucrose is actually fructose. So every time you eat 100 grams of you know, table sugar, you're actually eating 50 grams of of fructose. And the way that fructose is metabolized in the body, that actually leads to the generation of uric acid by the liver. And that's a problem because that all that uric acid has to be excreted through the kidneys, and uric acid is another one of these compounds that are tend to be highly insoluble and can quickly overwhelm the kidney, so we can end up with uric acid micro crystals. That's also something we are studying in the lab, how these micro crystals can really injure the kidneys quite dramatically. So we see, you know, like strong inflammatory pathways turning turning up and so on.

Nick Jikomes 38:10

I see, so the uric acid can become a problem with respect to the kidneys and the formation of kidney stones, ultimately, for the same physio, chemical reason that the oxalates were a problem. You're forming a you're forming something that's not quite as soluble as as you would like. And so these micro crystals can can precipitate out of solution and then ultimately lead to kidney

Thomas Weimbs 38:32

stones, right? Yeah, yeah.

Nick Jikomes 38:34

And so you're Go ahead. Sorry.

Thomas Weimbs 38:36

I was just going to say a whole nother class are medications, drugs, because many of them, then, oftentimes, you know, a very common side effect of many drugs is nephrotoxicity, and even something over the counter, very simple, you know, ibuprofen, for example, right? So, you know, everyone has that, probably in their household, in their cabinets and medicine cabinet, you don't think twice about it. You know you got some back pain, you pop some ibuprofen. And, you know you got more back pain. You pop more. It's, it's actually quite nephrotoxic. And many, many cases of acute kidney injury from ibuprofen, you know, over consumption, and that can also lead to chronic kidney disease, and so you essentially, you know progress and might lose your kidney function that way. Is

Nick Jikomes 39:27

that ibuprofen specifically, or is it that class of drugs? Generally,

Thomas Weimbs 39:31

it's a whole class, but maybe ibuprofen might be the most common one that people just have around the house. Unfortunately, I don't think there's, there's any big warnings on the labels that I've seen. You know, you buy the stuff, like a 500 pill bottle at Costco, for example, that's where I get it from. And I've never seen a warning label saying, Oh, you can get, you know, kidney toxicity from it. But. Wow.

Nick Jikomes 40:00

Yeah. So one possible title for this podcast is why you should stop taking ibuprofen and eating spinach. There you go. So what is it about? I mean, we don't need to go into like, gory mechanistic detail, but is ibuprofen are drugs that are nephrotoxins like ibuprofen are they basically just slowly but surely destroying the nephrons, the processing units of the kidney,

Thomas Weimbs 40:23

right? Yeah, that's basically it. There's even some drugs that also form crystals again, you know, we're back to the crystals. I've heard this from, let's see vancomycin, you know, one of the common antibiotics that are administered in hospitals, that also has a pretty high rate of acute kidney injury, and that can actually precipitate, you know, because that has to be eliminated for the kidneys. And in fact, many of those drugs and that that have nephrotoxicity, the particular impact the kidneys because they get essentially concentrated in the kidney during the detoxification.

Nick Jikomes 41:04

Wow. So, so the uric acid thing, uric acid is one of the things, like oxalates, that can cause these little crystals to form and eventually give you kidney stones. The uric acid, one's interesting because you're saying it's a byproduct of fructose metabolism. And so one of, one of the problems of the uric acid here that's coming from fructose is, is what you mentioned. It's, it's the ability to form these little crystals and then kidney stones. But I've heard that, you know, it's problematic for other reasons as well. I've read and I've had people on the podcast who talk about the sort of metabolic chain of events that happens, taking you from fructose to uric acid. And then, you know, there's the case you just talked about with the kidney stuff. But there's also, you know, it can basically go another direction and basically promote things like fatty liver.

Thomas Weimbs 41:45

Yeah, absolutely. And if maybe you've had Rick Johnson on your on your podcast, if you haven't, he's a great guy to invite. So he has done, you know, all the research on fructose and uric acid and how this leads to metabolic diseases and so on, which collaborating with him as well on our project. And, you know, yes, uric acid is bad in the sense of, you know, it really triggers a whole metabolic change in the body, and which probably has, like, ancient evolutionary reasons, yeah, but we used to be good thing, you know, when we were hunter gatherers and we had to gorge ourselves on fruit, for example, you know, just before the winter comes, so we can fatten up. So there's a whole switch that actually makes us become fat for good reasons. But of course, nowadays, you know, we It doesn't matter anymore if it's winter or summer. You know, we have food available, yeah, any day of the week. So if we keep consuming all that fructose constantly, you know, we keep triggering this fat switch, and, you know, we're just accumulating body fat that way. Yeah,

Nick Jikomes 42:59

I've heard this type of idea articulated before by others that you know obviously, not only do total calorie consumption that matters, total sugar consumption matters, but also things like the glucose fructose ratio can tip the body down different metabolic pathways. And it could very well be that, I think what you're saying is that in the past, perhaps due to seasonal changes in food supply that signaled the onset of winter and the need to fatten ourselves up, we may have started consuming things seasonally, such that the say, the fructose glucose ratio increases. This promotes fat gain, and that's actually adaptive in the context of seasonality, where you know starving is is a real concern, but in today's world that Starvation is no longer a concern, and everything has high fructose corn syrup in it. Now,

Thomas Weimbs 43:42

exactly, yeah, and that's, you know, another very common complication of high uric acid level. This gout. You know, gout simple symptoms, you know, essentially joint problems, where the uric acid actually leads to crystal formation. Again, in this, this case, it's not the uric acid itself, but it is mono sodium urate. So the sodium salt of uric acid, which also happens to be poorly soluble, and that, that is the one that crystallizes in the joints, you know, in the toes and hands and so on, so and you know, the gout, you know, used to be called the disease of the kinks, because back in the day only, the Kings could afford to eat a lot of sugar all day long and consume alcohol and so on. Wow.

Nick Jikomes 44:30

So oxalates can be a problem spinach, peanuts, certain other plant foods, certain medications, like ibuprofen, can be a problem for the kidneys. High Fructose consumption can also be a problem for for reasons we just discussed tied to uric acid any other so well, let me ask you this. What? What? What about other dietary components? So for example, do certain fatty acids or the total amino acid? Concentration of your diet matter. I've heard things before in my life where people would say things like, very high protein diets where you're consuming a lot of amino acids can be problematic for the kidneys.

Thomas Weimbs 45:11

Is that true? Well, that's a very old myth, almost, I would say. And that actually originates from a paper you know, from the 1980s I want to say, by a very prominent nephrologist, Barry Brenner. So it's called the Brenner hypothesis. Oftentimes, you know, and Barry Brenner went on to, you know, to write the Z textbook on nephrology that every single nephrologist in the country has studied. And it's a very interesting story. So the it was, it's almost was a theoretical paper, right? So there were some indications from like, different species of animals. You know that, yes, if you eat some protein, your kidney filtration goes up. That all makes sense. And Brenna essentially postulated that, you know, if you just to eat more protein, your kidney filtration, you know, goes into overdrive and you hyperfiltrate, and that that ultimately would be detrimental to kidneys, and you end up with chronic kidney disease that way. So that was essentially the dogma for many decades. And, you know, has made it into all the clinical guidelines. And you know, oftentimes people with kidney disease are advised, you know, to cut down their the protein intake. And oftentimes, dramatically, you know, the threshold of malnutrition, for protein intake, is about 0.8 grams per kilogram body weight. You know, that's essentially what the government says. You gotta be above that. But people with kidney disease often are advised to be below that, and then sometimes even, like, way below that, you know, I'd say point six or point five and so on, all

Nick Jikomes 47:00

because of this guy. This guy had a hypothesis, and he wrote a textbook, yeah,

Thomas Weimbs 47:03

yes, yeah. And, you know, I mean, there were some studies done, but I think nothing actually ever really proved anything. But it turns out, more recent studies have pretty much across the board, shown that, you know, protein consumption is not really associated with chronic kidney disease, and that as you as you know, but it takes something like 20 years for studies to make it into clinical practice. So we're still behind there. And, you know, unfortunately still people, many people with kidney disease, are advised to cut down their protein intake, but then they end up with, you know, being malnourished. They end up with sarcopenia, muscle wasting, and actually can cut down the overall mortality. There was a recent paper that looked at at patients with chronic kidney disease, you know, that were either on a low protein or normal protein diet, and overall mortality was actually much better. You know, they lived longer on a higher protein diet. Yeah. I

Nick Jikomes 48:08

mean, it's just amazing. This is just, it's one more example out of many that we could talk about in the history of medicine, in the US, at least, where, you know, we normally like to think that everything that's in clinical practice has sort of gone through this rigorous chain of vetting, going from basic research to clinical research to sort of proven bona fide stuff that's in the textbooks, and then we put it into practice. But not always, but in many cases, there are things that are put into practice that are not only wrong, but they're based on ideas that often can be traced back to a single socially influential person and that never really had strong evidence to back them to begin with.

Thomas Weimbs 48:49

Yeah, yeah. Unfortunately, that has happened many times. Yeah. So you know, most nephrologists, I would say, have actually never really gone back and read this Brenna paper in detail. So I actually went back recently and said, Okay, then let's read what exactly is in there, and stumbled on something really interesting. So the whole premise of this hypothetical paper was that ancient humans, you know, during our evolutionary days, and when we were hunter gatherers that, you know, ancestral humans would have consumed food only every two days, right? So he just hypothesized, okay, you know, we were on an in