Do We Have Kidney Health All Wrong?

Thomas: 
We actually saw a statistically significant increase in kidney function, which is unheard of in the kidney world.

Bret: 
Welcome to the Metabolic Mind Podcast. I’m your host, Dr. Bret Scher. Metabolic Mind is a nonprofit initiative of Baszucki Group where we’re providing information about the intersection of metabolic health and mental health and metabolic therapies such as nutritional ketosis as therapies for mental illness.

Thank you for joining us. Although our podcast is for informational purposes only and we aren’t giving medical advice, we hope you will learn from our content and it will help facilitate discussions with your healthcare providers to see if you could benefit from exploring the connection between metabolic and mental health.

Have you been warned against trying a ketogenic diet because it could negatively impact your kidneys? There’s a common perception all these people are changing their lives with ketogenic therapy. But there’s such a concern medically that ketogenic diets may actually be harmful for someone’s kidney health.

But turns out that’s not the case. And I’m joined by Dr. Thomas Weimbs, who is a professor and vice chair at the Department of Molecular, Cellular and Developmental Biology at UC, Santa Barbara where he has spent his life studying kidney disease and recently the effect of ketogenic diets on kidney function and what he’s found and what others in this field have found goes exactly against this concern that ketogenic diets are harmful for kidney function and actually shows that they’re beneficial for kidney function.

So why the disconnect and how can we get it right and how can we use ketogenic diets to actually improve people’s kidney health? Here’s my interview with Dr. Thomas Weimbs. Many of the interventions we discuss can have potentially dangerous effects of done without proper supervision. Consult your healthcare provider before changing your lifestyle or medications.

In addition, it’s important to note that people may respond differently to ketosis and there isn’t one recognized universal response.

Dr. Weimbs, thanks so much for joining me here at Metabolic Mind. 

Thomas: 
Great to be here, Bret. Good to see you again. 

Bret: 
Yeah, it was very nice to see you in person at Keto Live, which is a conference in Switzerland every year about the medical interventions of ketosis and how they can benefit different health conditions.

And you gave a very good talk about ketosis for kidney disease, and right away, it sparks a lot of controversy because if you just Googled ketogenic diets and kidney disease, you’re probably gonna find a lot of things about how it’s harmful and the high protein and acidosis and worsens kidney disease.

But we have evidence to the contrary, and a lot of clinical practice to the contrary. So I wanna get into all of that, but before we jump into that, now that I’ve just given this big long introduction, before we jump into that, tell us about you. What got you interested in kidney disease research and specifically ketogenic diets for kidney disease research?

Thomas: 
Great question. So we’ve been focused on a genetic form of chronic kidney disease that’s called polycystic kidney disease, or PKD, for short. And we have researched that for about 25 years in my lab, starting out actually at the Cleveland Clinic when I was starting my first lab as an assistant professor there.

And it was a bit of a coincidence that I wasn’t really planning to work on this, but a family with PKD and the family wanted to sponsor PKD research at the Cleveland Clinic and they figured out that this new guy, the new assistant professor, works with kidney cells, and they were very generous in sponsoring, essentially paying money for me to hire a postdoctoral researcher and do some research. And we had some quick success experimentally published a couple of good papers and it went on from there. 

Bret: 
And how did ketogenic diets come into the mix? Like, why ketogenic diets?

Why not vegan diets, vegetarian diets, Mediterranean diets? Why ketogenic? 

Thomas: 
It’s one of these things, we just followed the signs where it led us. We have many different mouse and rat models with polycystic kidney disease. And, I had a maybe somewhat crazy, graduate student, a PhD grad student in the lab.

So he reasoned, oh, let me just give them less food. He puts them on a caloric restriction regimen. Found that it very profoundly stopped the progression of polycystic kidney disease in these mice. And it turns out, when you calorically restrict mice, you very easily push them into ketosis.

And that’s actually overlooked very often in the caloric restriction literature, the mouse literature, I think almost all the papers where people look at calorie restriction and longevity and that kind of thing. What they actually are doing is they’re putting them into ketosis.

And that turned out to be the important part. So we can do this with a ketogenic diet with acute fasting, periodic fasting time-restricted feeding, and so on. So every time we put him in ketosis, it very strongly suppresses the progression of polycystic kidney disease.

So, essentially, that’s a story. We just follow the science, step by step, which it’s trying to lead us. So I’d never really heard much about ketogenic diets or ketosis before. This was all new to the lab. We just did it, and then we had to educate ourselves. What are we even talking about?

What are the different ways of putting animals into ketosis? And I learned actually a lot from, I must say from, you and your YouTube, presence because as you really well know, much of the information, it’s not available in like medical textbooks. And I think the real information is really out there on on the grassroots level. Right now it’s well hidden. But on the other hand, people find it. And people like me and my lab, we found the the information there. 

Bret: 
Yeah, that’s really inspiring to hear that you didn’t come at this looking to see if a ketogenic diet had an impact, but you got there, like you said, by finding the science and were able to find enough out there to say, okay, this is how we can do this with a ketogenic diet to study it.

And you found that it was beneficial for treating polycystic kidney disease, which as you said, is a genetic form of kidney disease. Now there’s sort of how do we translate that to the broader scope of kidney disease? Because we often hear if someone talks to their doctor, can I start a ketogenic diet to treat my bipolar disorder?

Schizophrenia, depression, type two diabetes, PCOS, whatever the case may be. Sometimes they will get pushback that now that diet is harmful for your kidneys. So let’s take a minute to just explore why do you think there is this preconceived notion that a ketogenic diet can be harmful for kidney health?

Thomas: 
Really good question. it’s definitely not founded in science, right? So there are no papers, I would say, no clinical studies where anyone, people on a keto diet, and found all their kidneys to fail, right? That doesn’t exist. I think there’s a lot of misunderstanding. Almost everybody in the medical profession seems to confuse ketosis and ketoacidosis.

That’s one weird thing and I think that has to do with it being taught wrong even in medical school, right? Some textbooks even get it completely wrong, and that it’s a mishmash between keto and ketoacidosis. Can’t really blame the doctors necessarily, for getting it, maybe getting wrongly educated, if you will. Another misconception is, of course, the whole protein idea that protein is harmful for kidneys, which blows my mind, that it is ingrained in everyone’s mind because clearly. The number one cause of chronic kidney disease is not protein in excess.

It’s, of course, carbohydrates and excess and type two diabetes, right? Insulin resistance, that’s what’s causing chronic kidney disease, right? So it’s the carbs, not the proteins, and there’s just nothing out there, again, that says that excess protein causes chronic kidney disease.

I think our mutual friend, David Unwin, pointed me to the, he traced back, where does this idea come from that protein is harmful in kidneys? And he traced it back to a key paper from the 1980s by a nephrologist, a very prominent nephrologist, called Barry Brenner, who had just put together a theoretical paper, right? So just a review article. No science, no experiments in there, and he came to the conclusion that, oh, protein is probably, should probably, be restricted. And ever since then, that has been dogma and, unfortunately, Barry Brenner, so this is a person who wrote the standard textbook for nephrologists,

So they all learned it, out of the book, but this was not based on data and in fact, if anything, all the more recent clinical trials show just the opposite, that protein restriction, it’s number one not beneficial really in chronic kidney disease, and number two, causes all kinds of other problems that actually impact, all cause mortality, from other things.

You get, muscle wasting and, so on. There’s a bit of a grassroots movement to overcome this. so some nephrologists are a little bit more, in the know, I would say and but I think the vast majority is still thinking of protein must be harmful to kidney. 

Bret: 
Yeah, which is just wrong on so many levels because it also assumes the ketogenic diet is a high protein diet, which it isn’t, doesn’t certainly doesn’t have to be by any means, but it’s, it’s might be higher than the 0.8 grams per kilogram of the RDA, but that does, that just makes it an adequate protein diet, not a high protein diet. Yeah, very frustrating, especially when it’s not rooted in good science, like you said. And you I think maybe there’s some papers that focus on one thing like the filtration rate or hyper filtration of the kidneys with more protein.

Not the clinical outcome, not how the patient’s doing. And like you said, if you restrict protein, you may have consequences of sarcopenia and decreased muscle mass and worsening metabolic health. And how is that going to impact the kidney function? So it really is you can’t just focus on just one thing.

You have to look at the whole picture and the diet as a whole, which that whole concept just misses. So you referenced, some of the articles and science that is out there supporting that ketogenic diets may actually benefit kidney function. So give us an overview of some of those articles.

Thomas: 
Yeah, I wouldn’t say there are like knockout studies yet that have, that would convince every single person in the world. However, the studies that out there, I think are, very compelling. We have done actually a randomized control trial, which is rare. So that was actually done at the University of Cologne, by Dr. Roman Miller and his team. And that was on polycystic kidney disease. And the patients were randomized into a ketogenic diet arm or a control in a no change in diet arm. And was only meant as a pilot study, three months intervention only. So very short term, relatively small study, 63 patients altogether.

But to our surprise, we found not only was the ketogenic diet safe and feasible, but it also led to an efficacy signal. So we actually saw a statistically significant increase in kidney function, which is unheard of in the kidney world. But so when someone has chronic kidney disease, including polycystic kidney disease, the dogma is it only gets worse over time.

Those are relentlessly progressive. They don’t spontaneously ever get better. There’s not a single drug treatment out there that actually achieves remission. So enough, no drug can increase kidney function. All the drugs out there, they only slows the rate of progression, so that’s what it is. What we found is, and was statistically significant looking at different markers of kidney function, same result for all of them, that there’s actually an increase in kidney function. 

Bret: 
Yeah. That’s such a important perspective that it is similar to the way that diabetes type two diabetes has been looked at for so long that it’s just, it’s going to be a chronic progressive disease, and the goal is to slow the progression, slow the worsening as much as possible. And now you’re actually finding, not only is it not worsening, but it’s getting better, which is, it is a totally different concept.

And then to draw the comparison again with type two diabetes, at your talk at Keto Live, you talked about the results of this study, a two year study looking at a ketogenic intervention, not randomized. It was part of the Virta health study. And they looked at again, what happened to kidney function, with a ketogenic intervention.

So tell us about the results of that study as well. 

Thomas: 
Yeah, so this was an amazing study.

And what they have done as Virta, as a company this, they’re focused on remission, putting type two diabetes in remission. By now, they have had over a hundred thousand patients with type two diabetes go through their program already. And it’s a remote ketogenic diet program, essentially, right?

It’s remotely administered, which makes it inherently scalable. So they’ve already published many good papers on reversing type two diabetes. But, of course, many people with type two diabetes also happen to have chronic kidney disease, which is caused by the type two diabetes and one of the major complications.

So it stands to reasons that many patients going through that program came in with chronic kidney disease. So the question was, how does it come out? If you ask random nephrologists out there, probably nine out of 10 would predict that their kidney function declines much more rapidly on a keto diet and they would’ve thought it might kill their kidneys, especially since, patients in the Verta program are usually also deprescribed, SGLT2 inhibitors and the GLP-1 receptor agonists. So that’s part if the package, because the patients don’t need them anymore after some time. So most of them, they’re deprescribed, and those two drugs are also the main drugs now for treating patients with chronic kidney disease.

Right? SGLT2 inhibitors, GLP-1, agonists. So even more reason for a nephrologist to say, whoa, you put them on a keto diet and you get rid of these two drugs that we usually prescribe for chronic kidney disease. All these patients should die of kidney failure. 

Bret: 
Yeah. They’re warming up their dialysis machines as soon as they hear that.

Exactly. They think it’s a foregone conclusions. 

Thomas: 
And as there was not the outcome. The outcome was a gain, a statistically significant increase in kidney function in those patients, and this was a two year study. So we’re looking not at a three month follow up, we’re looking at a much longer term follow up.

And, interestingly, so we stratified the patients in the study by the adherence level to the diet. And as the ketogenic diet is the only diet really where you can objectively measure the adherence because of the ketone levels, right? If someone is in ketosis, you just measure it and you know for sure they didn’t cheat.

You cannot really do this with any other dietary intervention. I think the keto is the only one. There’s an objective measure, and the patients were stratified into those that barely adhered to the diets, they barely had a bump up in ketones, and another group that had a mild level of ketosis, another one with a moderate level and one with a substantial level. So four subgroups, and it turns out there seems to be a dose dependent benefit on chronic kidney disease. So the higher, the better the adherence was to the diet, the better the increase of kidney function, which is interesting and maybe tells us a little bit about the mechanism that maybe is the ketone, beta-hydroxybutyrate itself, could play a role there as well. 

Bret: 
Yeah, so that was leads me to my next question is why does a ketogenic diet not only slow the progression of kidney disease but improve it?

And, to me, there’s a couple obvious answers, right? Because like you said, type two diabetes is a cause of kidney disease. So if you’re improving the blood sugar, the insulin, the type two diabetes, you’re likely going to benefit the kidney. Same for blood pressure, hypertension, a main driver of chronic kidney disease.

We know ketogenic diet improves hypertension, improves blood pressure, so can improve kidney disease. But it seems like there’s more than that. So you’re saying maybe there’s an actual effect of the ketones themselves. So tell us about that. 

Thomas: 
Yeah, so you’re absolutely right in all the things.

Essentially, if you take away what injures the kidneys in the first place, that should be a given that any treatment starts with that. It is almost if you would treat a toxicity by not taking away the toxic insult, ethically you couldn’t do that, but for some reason in diabetes, that’s how it is. Yeah, anyway, so if you take all this away by putting people on a ketogenic diet, you lower the insulin, you get rid of the insulin resistant, you stabilize the blood sugar levels, which can actually also directly impact the vasculature and the kidney. So that’s, I think, a given that this should be beneficial.

But, the ketone, in particular beta-hydroxybutyrate, I think is really interesting and that’s something we are researching in my lab at UC, Santa Barbara. What does BHB actually do to kidneys? And, as you know, BHB, is a potent anti-inflammatory molecule, and inflammation is one of the main drivers of chronic kidney disease anyway, so it stands to reason if you, essentially reduce inflammation in the kidneys with BHB, that should be beneficial. And that’s something that we see in animal models where you can study things mechanistically. We’re trying right now to find out exactly which immune cell type is most affected with beta-hydroxybutyrate in the kidneys.

So that’s something, I don’t have a final answer yet, and it’s probably that all of them are affected because the BHB is such a broad, a molecule of broad effects. 

Bret: 
Yeah. And this is fascinating because there is some pushback saying, oh, their kidney function did better because they lost more weight or their kidney function did better because their diabetes got better.

Or which is, in and of itself, great like anything you can do to improve kidney function. But this is gonna be fascinating research to say no, there may be more to it. So I find that very interesting. 

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So one more point I wanted to clarify about the study, the two year study from Virta Health, and I think in one of your social media posts, you mentioned that there was remission of chronic kidney disease in this subset of people, and there was some pushback. Can you really call it remission?

Was that really the case? So, tell us about this subset and why you’re saying there was remission. 

Thomas: 
Yeah, so I guess, maybe they’re different definitions in the dictionary for what remission is. But, usually it means, you are reversing a certain disease, outcome, improving it and especially if you do it in a sustained way, like in a two year study, and it’s another that you have a quick bump in kidney function and then it goes back down again, anything like that. So this was really sustained for two years. I think the pushback comes from the fact that typical kidney doctors don’t see that, have not ever seen that, in their normal daily practice. Because they have very limited tools, those drugs, that we talked about, and they don’t achieve remission, right? So that they’re just achieve a slowing of the progression and it has become dogma that even chronic kidney disease can never be improved and you can only slow the progression.

Bret: 
Yeah, and in this case, in this case, not only did they improve, but they normalized. Wasn’t that the key? They actually normalized their kidney function and their GFR to the normal standards, so they no longer had evidence of kidney disease, which, like you’re saying, people just don’t see so they probably really doubt and question, but the data was there.

Thomas: 
Yeah, the data was there. Do doctors believe it? I think oftentimes, and I dunno, I cannot speak for the kidney doctors, but sometimes I feel like they don’t want this to work because then they would have to use dietary interventions with their patients. And if this became standard of care, which nobody wants to do, right?

So there are many disincentives to using nutritional approaches, I think. 

Bret: 
That is so depressing, but unfortunately, I think fairly accurate, even if it is disheartening. So what about one other thing, people talk about acid-based status, right? And that if you’re in ketosis or on a ketogenic diet, it’s a quote unquote acidic diet, which is going to be bad for the kidneys, right?

So clearly the evidence you’ve just presented shows that as a whole, it is not bad. It’s actually good for the kidney. So what about this concern about acid based status? 

Thomas: 
Yeah, so I think that is probably a bit of more of a concern in people with chronic kidney disease than in people with normal kidney function because that is one of the things that happens in chronic kidney disease, that the metabolic acidosis gets worse and worse over time. So I can see that people are concerned about this probably realistically. We have to distinguish whether somebody’s on a ketogenic regimen or on a carbohydrate type of food regimen, right? So I think, as metabolic acidosis in the context of a high carb diet is probably a bad thing, but metabolic acidosis, all an acidifying environment in the context of a ketogenic diet, is probably what we all evolved to be optimized for.

And so one thing we have been doing in the lab, and that’s not published yet, we actually just submitted the papers and review. Right now, what we found is That uric acid, one of our normal waste products that we excrete for the kidneys, uric acid seems to be a driver of chronic kidney disease, by mechanism.

That actually explains a lot of things because uric acid is insoluble under acidic conditions. So if the urine is acidic, let’s say pH five, the kidney has a hard time excreting uric acid out of the body because the uric acid wants to precipitate in the form of microcrystals in the kidney.

And that can be very harmful to the kidney. It causes massive inflammation. And we can test this of course in animals as well, but the interesting part is that uric acid is only harmful under acidic conditions. As soon as you alkaline the urine, the kidneys are able to excrete the uric acid without the danger of precipitation.

So I think there’s something to it, but my point is, that somebody on a ketogenic diet would naturally not have that uric acid burden, right? Because they’re staying away from fructose and they’re staying away typically, hopefully, from alcohol. and those are some of the main drivers of, uric acid.

Bret: 
Yeah, and it’s interesting with a keto diet because frequently uric acid will go up initially, presumably from a decreased renal excretion, but then after a couple weeks, maybe month, it comes right back down to normal. So there isn’t this concern of uric acid. But if you only check that, two week or three week blood test, you’re gonna think that right there is a chronic hyperuricemia or, hyper uric acid, but it’s not, it actually normalizes.

And that’s really important. Yeah. 

Thomas: 
One quick thing to add is, I think someone with chronic kidney disease being put on a ketogenic diet would probably benefit a lot from a urine alkalizer and what we have been using is citrate, alkaline citrate, and that’s actually also part of the medical foods that we have created for people with chronic kidney disease and for that exact purpose, right?

So that we want to prevent a strong acidification, and it makes a urine more alkaline, which other people oftentimes do with plant focused, plant-based diets. You can use that for that. And that might be, it’s tricky, I think, because then you are sabotaging the rest of the keto diet there as well.

But what we’ve been doing is, and we have this, we have created a nutrition and lifestyle program for people with polycystic kidney disease that combines a ketogenic diet with this medical foods that also helps to alkalinize the, urine and prevents these micro crystals from forming.

Bret: 
Yeah. Very interesting. Yeah, and that’s the Santa Barbara Nutrients, is that right? 

Thomas: 
Yeah, that’s our startup company. 

Bret: 
All right. So, to wrap it up, look you’re a researcher, you’re a scientist, you’re a professor. If you came, into this with no preconceived notion.

So if someone came into this field and had knew nothing about it. Knew nothing about kidneys, knew nothing about diet, and just looked at the research, looked at the science and the published papers. Would there be any concern about ketogenic diets and kidney disease? 

Thomas: 
Great question. I always ask those types of questions myself.

If an alien from space comes to visit us, and looks at what’s going on here, they would scratch their head about how we’re treating chronic kidney disease, right? So they would scratch their head about the fact that we don’t try to reverse the type two diabetes first right before doing anything else, but that should be a given. They would scratch their head that we keep patients with chronic kidney disease on a high carb, yeah, diet that causes insulin spikes all day long, causes hypertension all day long. It just makes no sense. It’s really backwards. So I think you’re absolutely right an objective observer without biases, should come to the conclusion that a very low carb, ketogenic type of diet must be the way to go. Hopefully, one of these days, the message gets across, and turns into widespread clinical practice. 

Bret: 
Yeah. but it’s such a powerful message and could help so many people with type two diabetes and kidney disease or just kidney disease without the type two diabetes as well, just can be so impactful that we really need to get out of our own way and get away from our own biases to realize how we could help people. So, thank you for all the research you’re doing to really, help this be known and, for talking about it.

So if people wanted to follow you and learn more about the work you’re doing? Where can we direct them to go? 

Thomas: 
Yeah, a couple of places, if anyone is on Facebook, I have a pretty large Facebook group called WMS Lab, and a few other words behind that. Anyone is welcome to join. There’s about 4,000 people with policies to kidney disease on there.

Lots of discussions going back and forth. They can also, go to santabarbaranutrients.com, to learn about this medical food that I mentioned that we created based off of the research from my lab. So those are probably the places to go. 

Bret: 
Great, thank you so much.

I really appreciate you joining me. And you mentioned so many papers that are not yet published so we’ll have to have you back when those are published to talk more about the details. 

Thomas: 
Awesome, love to. Thank you, Bret. 

Bret: 
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