Kidney Disease, Gout, Metabolic Syndrome discussed on The Peter Attia Drive
You still actually take care of patients in the inpatient ward and you'd probably spend a quarter of your time in clinic. So how how do you put some of this stuff into practice do you. Liberally use Allah pure and all even for patients who have high uric acid but have not developed gout yet. I do so our data's data's strongly suggests lowering uric. Acid could be beneficial so what I do is the following so it turns out that Allah Pernell is not totally really safe. There's some people who can develop reactions to Allah pure no drug reactions especially Asians about three to four percent of people who are Asian can develop an allergic reaction to Al Appear in all where they can get rashes and it can be pretty severe. And it's about two percent in African Americans and it's about point five percent in Caucasians you can test for it. There's a test called the H. L. E. B. Fifty eight tests. But the point of the matter. Is that no drug is fully safe every drag has side effects so ideally. You'd want to really be certain that your drugs going to provide the benefit that you want and you have to consider the risks versus benefits now. Although in Animals L. appearance totally protective order protects a lot against sugar induced metabolic syndrome the data in humans is suggestive. So there's been for example for pilot studies showing improvement and insulin resistance with lowering uric acid in humans. All four positive as if there is a lot of trials and kidney disease showing that lowering uric acid may benefit kidney disease. There's data on blood pressure. We had a paper in the CHAMMA. Showing that on your gas could improve blood pressure control and adolescence with hyper Uresti Mia. So there's a lot of supporting data. There are some some negative studies too but the overall weight is now in favor of lowering uric acid to benefit. What would the target be? So what I do is when I see a patient in clinic I measure the uric acid and currently we know that the risks start to go up when the Serra Meteoric asses over or five point five so once they serum uric acids over five point five. They really start to have increased risk for prediabetes. Insulin resistance hypertension kidney it is easy etc and what's interesting is most labs like my lab for example doesn't even flag until it hits about six point five as sort of intermediate risk and it's really not until until about seven point five that it says. Well this his high risk but of course that's only through the lens of Gout. I assume yes. That's right. So if a uric acid comes back really high like nine or ten UH. I have no doubt that that based on everything I've done I've no doubt that that's not good. You're not only does it. Increase the risk for Gallup but increases the risk for kidney disease and all all these things and I talked to the patient about the pros and cons of treatment. I talk about the rash at tell him to stop the drug if they get a rash and then call. Oh me but I always start Allah piano when the uric acids like eight or higher and certainly when it's nine or higher when it's between five point five five and eight. I'll talk to them about the pros and cons but we don't have full proof yet but I tend to especially with patients with kidney disease where the data is probably the strongest. Start treating. I'll even do it with your a cast of six and a half for example with chronic kidney disease but anyway it's worthwhile discussing the patient but outside of that the risk of Stevens Johnson Syndrome. Which you've alluded to what are the other potential risks of L. appear and all that's by far the big one? Some people will get get just a mild rash without true Stevens Johnson Syndrome. They're rare cases where liver function test may be elevated but seems to be rare. If if you start at a huge dose right away it can increase Xanthi levels in the urine theoretically there could be representing stones. But but I'm never seen it. So it's really the risk of Stevens Jackson that and do you have to use Allah pure. And how can you use you laurich or other drugs that also lower uric acid well xanten accidents inhibitors of the best because the way uric acid works to cause cardiovascular disease and kidney disease and in all these things appear to be through its actions inside the cell as we said works on my condron. It does all these things. It's not. It's work outside the cell so gout it is really an extra cellular deposition. But when you're thinking about uric acid and it's biologic effects that's an intracellular action so Hosanna in today's makes your gas it inside the cell. So one of the best ways to reduce interest sal. Uric acid is to give his anti oxidation. SASON heavier like for bucks stat now for boxes stat. I think it's probably just as good as Al Paranoia but there was a big clinical trial that was published in the New England Journal Journal. That showed that Alpine was associated with less cardiovascular risk than for boxes sat there seemed to be an increase cardiovascular events in the FA buxom stack group meaning less of a reduction or more events. Let's see the problem was it was no placebo group. Oh yeah that's a disaster. That's a disaster. This is the problem. Yes naproxen yeah. Yeah I mean so. The problem is ella colonels last than for boxes. But there's no placebo groups. Theoretically the Placebo Group would be could be higher in both could be higher than both. And there's actually evidence that that's probably true but because of the care study the way it was designed we don't know so the FDA DA is worried about giving boxes to people with cardiovascular problems because they would prefer to give Al Panel but the travelers. It's not not necessarily it for boxes. Debt is bad. It's just that it's not as good as Al Pure and it's like one hundred thousand times more expensive too. Although it's I think becoming generic Eric now so we may see a change in that. I believe it when I see it. And of course you trust the generics. But that's a whole separate issue exactly so what about Sodium restriction going back to how we started the discussion. I'll tell you a story from a male even told us on the podcast once before but in medical school I remember when we were doing renal physiology. We had a great in nephrology professor. Who is teaching something and I think he was quite ahead of his time because this was more than twenty years ago and he was not part of this salt is bad had bandwagon even though he was in Rajasthan in? I won't do it because I won't do it. Justice but in a beautiful southern accent he made the point that if you lined up all of the a net franz in the world all the functional units of the kidneys in the world from dumbest smartest and then all of the nephrologist in the world from dumbest two smartest. And you took that that dumbest neff Ron and put it next to the smartest nephrologist. It's still smarter. His point being of course like the kidney is a brilliant Oregon that is exceptional at auto regulation of everything from flow to house malaria to anti catiline exchange. Again his point being he didn't buy this argument. That salt is the problem. You're saying something much more nuanced than I wanNA Kinda go back to it because I think there are important clinical implications of it. You're saying Komo. Salt does play a role but it's dose timing. Bolas concentration that matters it can also be amplified or mitigated the state of inflammation. So how do you then translate that information to your patients acknowledging that they're a very select group of people by definition may have kidney disease or they wouldn't be seeing you so it's the combination of salt and water. So if you don't drink any water as you eat salt you're gonNA raise your serum sodium. You'RE GONNA they get thirsty and soon as you're thirsty you've triggered that in itself is a sign that you're already making fructose from the salt so when you eat salt. You're you're making fructose in your body and the fructose is then driving a lot of facts now. We know that high salt diets are associated with obesity. Not just best blood pressure. There are associated with the development of diabetes. There's many studies now but high salt looks like it works by producing fructose. So if you drink drink water with salt danger assault is much less if you drink water. And then you you're pretzel you would be safer than if you ate your pretzel and then drink the water better because it would triggers is the rice and salt and so when you see someone that clinic we try to do is to tell them to drink a lot of water and Dan to reduce their salt but it isn't the amount of salt. It's the balance of salt and water. Now that can be sometimes challenging for patients in kidney clinic because because that would be one population in which you do have to be mindful of volume right but most patients with chronic kidney disease they will excrete water normally or just minimally abnormal normal. And so there's actually clinical trials looking at the evidence that water may slow the progression of kidney disease. It might be working in part by blocking the effects of salt and so forth on the kidney and we experimentally show that giving water can slow kidney disease progression so drinking water turns turns out to be good. Here's another thing. It turns out that many animals use fructose to make fat as a means for making water. So when you make fat fat although there's no water stored in the fat. When they burned the fat they make water so Wales? Don't drink saltwater V. or fat because when they break down the factor making the water we call metabolic water so it turns out that fructose drives fat production and impart to preserve water. Not just energy edgy. So animals will use that fat to provide an energy source but also to provide water so it turns out that if you take an animal on fructose and you give it a lot of water. You can suppress some of the obesity. You can suppress some of the effects of Metabolic Syndrome and so the old wives tale that drinking six glasses of water a day is good to help keep you. Skinny is true. It turns out that water suppress some of the effects of fructose. And does it need to be water. Could be tea or coffee or something. That's equally the odds. Malaria waters what serum is about to eighty. Yep Okay so anything with Shirow is malaria. He's good enough. Yes technically a diet soda should have zero added work actually for the record you and I are sitting here drinking just plain walk right and diet. Sugars have their own issues. So we'll come back to that in a few seconds. That's interesting so rick you sort of you. Toss these little nuggets out there. Like they're nothing in but they sound again just based on this sort of breadth of research you put into this. It almost just seems too good to be true and so profound yet used sort of throw it out there like can after the fact. Well look as long as you drink enough water. And don't eat fructose and God forbid. Don't drink fructose manager uric acid levels etcetera etcetera. You make make it seem like a lot of problems could go away from these things. How would you shape that advice for someone with normal kidney disease a normal kidneys? Would you basically just say the same same thing or can you be less restrictive with sodium for example. If we could reduce our fructose intake. I think it would have a huge huge fact but the problem that most people people faces that sugar high fructose Corn Syrup are an almost everything so if you go to the supermarket like seventy percent of processed foods have sugar in it and package foods actually. Seventy percent of packaged foods. Have Sugar High. Fructose Corn Syrup is so it's very hard to avoid it and here's another problem. Our bodies can make for dose so our bodies as I mentioned. We can make fructose from a high salt diet. We can make fructose if we get dehydrated hydrated. We can make fructose high uric. ACID stimulates fructose production. And we're making the fructose out of glucose in situation high glycemic diets. Normally really. If you take an animal and you give it starch. They will not really get fat but we all know that French fries. which don't have sugar in it? They don't have fructose luke dose. They are fattening. But you've got potatoes. Which Raise Your Glucose and what we showed is that if you just give glucose to an animal the high glucose us as it hits the liver induces this enzyme to convert glucose fructose which I miss that? The Converts Glucose Tau redact taste so we took mice and we gave them glucose and we were thinking we might not see much because we were believing that fructose is the culprit but over time these animals really fat. They got insulin resistant. Everything but you had overfeed them glucose. The we put the glucose in drinking water so they were drinking a lot of glucose but they would eat less chow so we gave them Chow and glucose in their drinking water and Chow. Had it was normal. Child wasn't the high fat high sugar chow. No just regular and these animals start getting really really fat and when we looked at the Pardo vein which goes into the glucose levels were high and when we looked in the liver ver- we found that this enzyme was activated. It's also acted in diabetics for example because of the High Glucose in the blood and when that enzyme got activated it started to make fructose so even though these animals were eating no fructose. They were producing for dose in their liver. And then when we blocked there fructose metabolism. They're eating the same amount of glucose no change exactly the suddenly. They're not getting fat they have. I have no fatty liver. They're not insulin resistant. But this suggests rick that a diet in excess carbohydrate. Even if it's not high in sugar could lead to Fatty Audi.