The Two-Way Street: Gout’s Impact on Renal Function – and Vice Versa

Gout Rx: Past, Present, and Future

Welcome to the second season finale Kicking Gout in the Acid. This season dove into additional topics of importance to not only those with gout, but for those treating the disease as well. Whether you’ve been recently diagnosed, care for someone suffering, or are a medical professional treating the disease, the Kicking Gout in the Acid podcast can help you learn more. The season finale of Kicking Gout in the Acid features a conversation between Dr. Larry Edwards and Dr. Brian Mandell, rheumatologist from the Cleveland Clinic, and member of the Gout Education Society’s Board of Directors. In this episode, Dr. Edwards and Dr. Mandell will look back at the history of gout treatment, discuss the current state of affairs for medications in development, and look towards the future of disease management.  Key Takeaways: Early treatments focused on symptom relief rather than the underlying disease, delaying recognition of gout as a condition driven by urate deposition that requires targeted, long‑term management. Medications like probenecid and later allopurinol reframed gout as a chronic condition that can be controlled by consistently lowering and maintaining serum urate to a defined target. This strategy opened the door to new options like febuxostat, uricosurics, and uricase-based therapies that allow for more individualized care. The future of gout treatment is bright with options as many are in the clinical pipeline. To Dr. Edwards and Dr. Mandell, an option that not only lowers urate more effectively but also directly targets inflammation pathways could be an interesting area of future research. Gout is treatable and curable when managed correctly. Successful outcomes depend on a team-based approach involving informed patients, appropriate medication use, adherence to treat‑to‑target principles, and consistent follow‑up. Start your journey with gout today via the Gout Education Society website and sign up for the monthly newsletter. Follow the Gout Education Society on X and Facebook Looking for nearby gout specialists? Find rheumatologists, nephrologists and more via the Gout Specialists Network. Educational Materials: Gout Patient Brochure Medical Professional Guide Crystal Clear Checklist Kicking Gout in the Acid is sponsored by Sobi.

Heart Health and Gout: Connecting the Dots

Welcome to season two of Kicking Gout in the Acid. This season will dive into additional topics of importance to not only those with gout, but for those treating the disease as well. Whether you’ve been recently diagnosed, care for someone suffering, or are a medical professional treating the disease, the Kicking Gout in the Acid podcast can help you learn more. This episode of Kicking Gout in the Acid features a conversation between Dr. Larry Edwards and Dr. Ken Saag, rheumatologist, professor, and director in UAB Medicine’s Division of Clinical Immunology and Rheumatology, member of the Gout Education Society’s Board of Directors. The two dive into the link between gout and cardiovascular disease, why flares may increase risk for CV events, and clinical recommendations that medical professionals should consider when someone faces both conditions. Key Takeaways: The link between gout and cardiovascular disease remains complex and often misunderstood. While biological plausibility exists, human data are mixed, creating uncertainty about how strongly uric acid contributes to long‑term heart outcomes. Gout flares themselves may carry cardiovascular risk. Acute flares are highly inflammatory, and emerging evidence suggests they may directly increase the likelihood of cardiovascular events which underscores the need for proactive flare prevention. Those with both gout and heart disease benefit from aggressive management based on the treat-to-target approach. Lowering serum urate, preventing flares, and maintaining overall cardiovascular stability remain key goals for improving outcomes for those facing both conditions. Lifestyle changes can be helpful in those with gout, but medication is essential to treat a majority of cases. Although weight loss and dietary changes provide modest improvements, they rarely reduce uric acid enough on their own. Sustainable management still depends on appropriately titrated urate‑lowering therapy. Start your journey with gout today via the Gout Education Society website and sign up for the monthly newsletter. Follow the Gout Education Society on X and Facebook Looking for nearby gout specialists? Find rheumatologists, nephrologists and more via the Gout Specialists Network. Educational Materials: Gout Patient Brochure Medical Professional Guide Crystal Clear Checklist Kicking Gout in the Acid is sponsored by Sobi.

The Challenge of Coordinated Gout Treatment

Welcome to season two of Kicking Gout in the Acid. This season will dive into additional topics of importance to not only those with gout, but for those treating the disease as well. Whether you’ve been recently diagnosed, care for someone suffering, or are a medical professional treating the disease, the Kicking Gout in the Acid podcast can help you learn more. This episode of Kicking Gout in the Acid features a conversation between Dr. Larry Edwards and Dr. Tuhina Neogi, Professor of Medicine at Boston University Chobanian & Avedisian School of Medicine (BUSM), Chief of Rheumatology at Boston Medical Center, and member of the Gout Education Society’s Board of Directors. The two explore the common areas where gout patients are seen, common pitfalls that occur throughout the process of multidisciplinary management, and the importance of promoting the ACR gout guidelines among professionals. Key Takeaways: Gout is still not viewed as an important rheumatic disease by many providers, leading to under-treatment and missed opportunities for proper management. Under-treated gout, or treatment only focused on symptoms, can lead to uncontrolled hyperuricemia, worsening tophi, and patients losing trust in their physicians. There is growing involvement in specialists treating gout, however, inconsistent knowledge on managing the disease can lead to unnecessary medication holds, recurrent flares, and patient confusion. Many myths still hold the attention of those with the disease and medical professionals alike. Notably, the disease shouldn’t be seen as episodic, rather it should be seen as chronic, requiring lifelong therapy that aligns with the treat-to-target approach. Educated patients are advocates for themselves. This can be particularly helpful when their care team has differing opinions. Start your journey with gout today via the Gout Education Society website and sign up for the monthly newsletter. Follow the Gout Education Society on X and Facebook Looking for nearby gout specialists? Find rheumatologists, nephrologists and more via the Gout Specialists Network. Educational Materials: Gout Patient Brochure Medical Professional Guide Crystal Clear Checklist Kicking Gout in the Acid is sponsored by Sobi. Podcast Transcript Ian PonitzHello, and welcome to Kicking Gout In The Acid, a podcast from the Gout Education Society. My name is Ian Ponitz, and I'm your host for this series. Kicking Gout In The Acid features conversations between Dr. Larry Edwards, chairman and CEO of the Gout Education Society, and experts on the disease.  Each episode will dive into important topics that you, the listener, should know about gout. The goal? To feel empowered to get gout under control.  In this episode, Dr. Edwards is joined by Dr. Tuhina Neogi, professor of medicine at Boston University's Chobanian & Avedisian School of Medicine, also known as BUSM. She is the endowed Allen S. Cohen Professor of Rheumatology and professor of epidemiology at BU School of Public Health, and chief of rheumatology at Boston Medical Center. Dr. Neogi is also a member of the Gout Education Society's board of directors.  Today, Dr. Neogi and Dr. Edwards will discuss the gamut of medical care that gout patients may encounter throughout their journey, issues that can be caused when seeing several disciplines of medicine, and the importance of getting medical professionals on the same page when it comes to managing the disease.  Dr. Edwards, take it from here.  Dr. Larry EdwardsThanks, Ian. I'm delighted to have Dr. Tuhina Neogi on today's Gout Education Society's podcast. Dr. Neogi is an internationally recognized expert on many aspects of rheumatology, but especially in the management of gout. Tuhina, can you give our listening audience a bit of your background and how you got interested in gout?  Dr. Tuhina NeogiSure, happy to. Thank you for having me on this podcast.  I'm originally Canadian. I'm from Toronto, and I did all of my medical training in Toronto. When I was a fellow, I didn't have too much interest in gout, but Dr. Adel Pham was one of my mentors. He was well known for the allopurinol desensitization protocol, so we got a lot of gout teaching.  When I completed my fellowship, in order to have a position on the University of Toronto faculty, I needed to get a master's or PhD, for which I moved to Boston to do that research training. And during that research training, I got a PhD, and as part of my PhD, I had to quickly find a set of thesis dissertation topics, and one of my colleagues, Dr. Yuq Ching Zhang, at the time, was just starting an Internet-based gout study in which we were going to study triggers for gout flares. And it was a very cool study design where each person acts as his or her own control over time, and we studied a whole host of dietary and lifestyle factors as potential triggers for gout flares, and that got me hooked.  So I like to say that, you know, gout is kind of my hobby topic for my research career, because it was kind of a passion project that I've been fortunate to continue working in.  Dr. Larry EdwardsYeah. Well, it's more than a little hobby, because you are certainly an internationally recognized expert in the field, and we're delighted to have you on today.  What we're gonna be discussing is the wide range of physicians and medical professionals who may encounter patients with gout, and how they contribute to the overall care. And we're also gonna be discussing how being seen by multiple different care providers may impact the overall level of treatment, and how interaction should take place, and unfortunately, how most of the time they don't.  So let's start off just by discussing at the various stages of gout who might first come in contact with somebody who's suffering from gout.  Dr. Tuhina NeogiYeah. So the vast majority of patients with gout, as you know, are managed in primary care, so that really is the first stop on the patient's journey. And for some patients, they may not be advised adequately about gout and its consequences, and as a result, may not be started on urate-lowering therapy even if they meet the clinical indications for starting such therapy.  Some patients may be simply placed on anti-inflammatory suppressive therapy with colchicine just to try to prevent flares or have flares treated as they occur. Unfortunately, that leads to unabated hyperuricemia to continue on for years. And I'm sure you have a much vaster experience than I do of all the patients that come to us after years of such an approach, where they now have bad tophaceous gout with lots of flares or chronic arthritis where the inflammation is there persistently, and are frankly quite upset that their primary care physician allowed this to occur over the years.  It unfortunately detracts from the trust they have with their primary care physician that if this is what happened with their gout, what else might be happening with their other medical conditions. So that's the majority of it. I would say that I see some patients coming from nephrology or cardiology, where they happen to either check the urate for some reason, or it's one of the visits where the patient happens to mention that they need to take NSAIDs because of their gout.  Dr. Larry EdwardsYeah, might be on any number of drugs that influence the frequency of gout flares or the ability to take certain compounds.  In addition to those, Tuhina, a number of patients get their care from urgent care settings or emergency departments. I think I see a lot of patients. On a typical week, I might get called down to the emergency department maybe a half a dozen times to discuss the differential diagnosis of a single inflamed joint. But the thing with urgent care and with emergency departments is that they're really interested in getting the patient out of their acute facility, and so people can go on for years just following up in that setting and not getting the message.  Really, what we're pushing, and what you've certainly an expert in, is the treat-to-target approach of taking care of gout, and what you're describing from a lot of the primary care physicians is really to avoid symptoms with the use of colchicine or nonsteroidals. Dr. Tuhina NeogiYou made a good point about primary care often using colchicine or NSAIDs on that kind of as-needed basis.  To me, a perspective we could adopt would be for us as rheumatologists to say to cardiologists, "Oh, your patient has cardiovascular disease. There's no need to treat the underlying biology of the cardiovascular disease. There's no need to treat the hypercholesterolemia, the hypertension, the diabetes, obesity, smoking, et cetera. Why don't you just give them sublingual nitroglycerin, and they can just use it as needed or even, you know, use it chronically to prevent the chest pain? But all you need to do is treat the chest pain, not all of the underlying biology."  Or an even perhaps more ridiculous way to drive home the point is telling a pulmonologist for a patient with tuberculosis, "No need to use anti-tuberculous therapy. Just use an antipyretic and an antitussive. Just, you know, treat the fever, treat the cough. No need to treat the underlying bacteria." And I think that's the kind of blunt messaging we might need to explain why treating the underlying hyperuricemia is the cornerstone and foundation of managing gout, not just the clinically evident symptomatic flares.  Dr. Larry EdwardsYeah. Those are excellent points.  Dr. Tuhina NeogiI think over the last few decades, I've queried my primary care friends just about the problems of getting good care for gout. A lot of them will bring up the issues that, you know, they are primary care, so they're not just looking after the occasional gout symptoms that occur, but they have, you know, the same patients might have heart disease, diabetes, various other metabolic problems,...

Gout and Genetics: What Your Background Might Mean

Welcome to season two of Kicking Gout in the Acid. This season will dive into additional topics of importance to not only those with gout, but for those treating the disease as well. Whether you’ve been recently diagnosed, care for someone suffering, or are a medical professional treating the disease, the Kicking Gout in the Acid podcast can help you learn more. This episode of Kicking Gout in the Acid features a conversation between Dr. Larry Edwards and Dr. Robert Keenan, Rheumatologist, Chief Medical Officer at Arthrosi Therapeutics, and member of the International Advisory Council for the Gout Education Society. The two explore the broad reach of gout across different demographics, discuss how gout presents differently, and considerations healthcare professionals should be aware of during treatment. Key Takeaways: Gout doesn’t discriminate by age, gender, background, or diet. Doctors should be aware that the signs of gout aren’t always as straightforward. Misdiagnosis is common, so it’s important to take a step back and recognize the subtle symptoms. Genetics play a meaningful, but complex, role. Family history is a significant risk factor, however, research points to polygenic and epigenetic factors than one single genetic mutation. Demographics matter, but not in the way most people think. While men typically develop gout in their 40s-50s, the prevalence is nearly equal in women post-menopause. Start your journey with gout today via the Gout Education Society website and sign up for the monthly newsletter. Follow the Gout Education Society on X and Facebook Looking for nearby gout specialists? Find rheumatologists, nephrologists and more via the Gout Specialists Network. Educational Materials: Gout Patient Brochure Medical Professional Guide Crystal Clear Checklist Kicking Gout in the Acid is sponsored by Sobi. Podcast Transcript Ian PonitzHello, and welcome to Kicking Gout In The Acid, a podcast from the Gout Education Society. My name is Ian Ponitz, and I'm your host for this series. Kicking Gout In The Acid features conversations between Dr. Larry Edwards, chairman and CEO of the Gout Education Society, and experts on the disease. Each episode will dive into important topics that you, the listener, should know about gout. The goal? To feel empowered to get gout under control. In this episode, Dr. Edwards is joined by Dr. Robert Keenan, Chief Medical Officer at Arthrosi Therapeutics, and member of the Gout Education Society's International Advisory Council. Today, Dr. Keenan and Dr. Edwards will discuss how gout affects different populations, the role of genetics and gender on gout, and how medical professionals can better serve diverse communities. Dr. Edwards, take it from here. Dr. Larry EdwardsThanks, Ian. I'm happy to be joined today by Dr. Robert Keenan, internationally recognized expert in the field of gout. He's also the Chief Medical Officer of Arthrosi Therapeutics, and I'm delighted to have us join in our conversation. Can you start off, Rob, by telling a little bit about what your interest in gout has been over the years and what kind of studies and research you've done? Dr. Robert KeenanYeah. Thanks for having me. I appreciate the opportunity to talk about my favorite medical topic or my favorite topic, probably in general, much to my wife's dismay, of gout. Yeah, so I got interested in gout back in medical school, quite honestly, and then my interest further developed in residency, then subsequently in fellowship. I had the opportunity at NYU to start a gout registry with the VA there, and that kind of really kicked off my clinical research interest. From there, I just continued it on as I transitioned to Duke University, and I started a gout clinic and kept up with the clinical research there as a principal investigator for a number of drug studies, as well as principal investigator for some epidemiological studies that were externally funded. So that's kind of how I kept the love of gout and the love of treatment of gout and taking care of this patient population over the last twenty-plus years now. Dr. Larry EdwardsYeah, it's an incredibly interesting disease with a crazy history to it. It certainly is a fun thing to study, and the nice thing is that it's essentially a curable disease if patients listen to the recommendations. We have good medications. We're getting better medications coming down the pipeline, so I think that there's a lot of hope for the future. Let's go ahead, Rob, and start off the discussion today, talking really about the demographics of gout, who gets gout. It's said that there's about 9 to 12 million adults in the United States that have gout, coming to about 4% of the population of adults. What else can you tell us about the demographics of this disease? Dr. Robert KeenanYeah. So I like to tell patients that gout doesn't discriminate. I mean, there's a lot of misnomer about. Oh, it's the over-indulgent rich person who eats too much, you know, meat and drinks too much alcohol, that gets you gout. But really, I mean, just pretty much gout can affect any ethnicity, any race across the spectrum. Of course, men are more likely to get gout earlier on, so you think about the typical gout patient as a man in his fifties, you know, late forties, early fifties when they first initially present with their first flare. But eventually, women do catch up with men post-menopausal. So once they reach menopause, the incidence and prevalence of gout in women starts to catch up with that of men. So by the time they're seventy-five, eighty, it's pretty much almost equal to that of men. Again, it can affect anybody. Now, typically, as far as who gets gout the most, so to speak, there was a recent study that was put out by Yokosi a couple of years ago. I guess it was twenty twenty-three years ago that showed that over the last couple of decades, the Asian population in the US, actually, their prevalence doubled from about 3.3% to about 6.6%. That was a higher increase and a higher rate of increase in prevalence compared to every other ethnic group, including whites and blacks and Hispanics. So I thought that was interesting. If you look at the black population in general, their prevalence of gout is also higher than that of whites. And you can think, “Well, maybe this is something genetic,” and it's probably not genetics, especially when people develop gout in their fifties and sixties. You know, you’ve got to think about a genetic component when they're developing gout in their late teens or twenties, for example. But it's not so much genes as it is just potentially lifestyle, other comorbid illnesses like chronic kidney disease or metabolic syndrome. If you look at that Yokosi study of the Asian population being doubled, you know, it wasn't double. It was actually lower than whites about thirty years ago. So, as with blacks, it could be just a lack of access to care. It could be not being started on urate-lowering therapy when they should. So that kind of pretty much dictates, and if they develop gout and have not started on anything to bring their uric acid down, then they're more likely to have gout longer, more flares, and more severe gout down the road. Dr. Larry EdwardsThere's been a lot of work on the genetics of it, and we can talk about that in a short while. I think other components you've mentioned are the gender, of course, with men predominant early on in the forties, fifties, and sixties, and women becoming much more susceptible to gout as they get into their seventies and eighties. The frequency of gout in that older population, seventy-five, eighty, is actually very high, 20%, 25% percent of the population of adults. Can you talk a little bit about age? You mentioned earlier on, Rob, that the image that most people have of gout is some portly old white guy sitting around drinking some alcoholic beverage or eating a large meal. We know that that's not the primary source of problems. Can you talk about the type of people that you see that would really say that that's not the problem, as far as women, as far as athletes getting it, people that don't drink, people that don't eat meat? All of those are in the spectrum. Dr. Robert KeenanYeah, exactly. So that's where potentially some of those genes kind of come into play in that patient population, especially whether it's women, and just post-menopausal, and especially if they have a strong family history, their father had gout, their grandfather had gout, their brothers have gout, there's a good chance they'll develop gout. A lot of times, in women, they'll present different than men. They won't necessarily present with a big, hot, painful red big toe. They'll present with it in their hands, for example, and it might not even flare like a typical gout flare. It might be a little more subtle. And I think that's important for women to recognize because, you know, I've had patients, women patients who came to me for joint pain in their hands, and, you know, they obviously had some osteoarthritis in their hands, and they came to me saying their pain's just getting worse, and they're having episodes where it's just worse some days than others. Sure enough, I say, "Well, this looks like it could be potentially gout." And, you know, one patient I can think of off the top of my head said, "I don't have gout. My husband has gout, but I don't have gout. There's no way I have gout. He eats too much," et cetera, et cetera. I said, "Well, I think you may have gout. Let's take some X-rays and see what we see, and then check uric acid and see what we see." And sure enough, she had gout on top of her osteoarthritis in her hands. So that patient population certainly is not gonna be necessarily typical in many ways, not only, you know, necessarily what they're eating or not eating,...

The Two-Way Street: Gout’s Impact on Renal Function – and Vice Versa

Welcome to season two of Kicking Gout in the Acid. This season will dive into additional topics of importance to not only those with gout, but for those treating the disease as well. Whether you’ve been recently diagnosed, care for someone suffering, or are a medical professional treating the disease, the Kicking Gout in the Acid podcast can help you learn more. This episode of Kicking Gout in the Acid features a conversation between Dr. Larry Edwards and Dr. Richard Johnson, board-certified nephrologist and member of the Board of Directors for the Gout Education Society. The two explore the connection between gout and kidney health through topics like uric acid regulation through the kidneys, treatment options, and considerations for medical professionals in charge of care should keep in mind. Key Takeaways: The kidneys play a central role in uric acid regulation. About two-thirds of uric acid is excreted by the kidneys, and one-third by the gut. When kidney function declines, uric acid retention occurs, increasing gout risk. Kidney disease and gout are closely linked to one another. Chronic kidney disease (CKD) is a major cause of gout because impaired kidney function leads to uric acid buildup. Conversely, high uric acid may contribute to CKD progression, creating a vicious cycle. In those with kidney disease, treatment can look a bit different. Notably, NSAIDs may not be an option due to their harmful impact on the kidneys. For those with kidney disease looking for pain relief from a gout flare, options like steroids should be considered. Also, historical dosing restrictions for allopurinol in CKD have led to undertreatment, but recent evidence supports gradual titration to higher doses when monitored. For medical professionals, it’s important to screen those with gout for kidney disease and vice versa. Medications known to raise uric acid should also be reviewed, namely, diuretics. Comorbidities should always be considered when treating gout. Start your journey with gout today via the Gout Education Society website and sign up for the monthly newsletter. Follow the Gout Education Society on X and Facebook Looking for nearby gout specialists? Find rheumatologists, nephrologists and more via the Gout Specialists Network. Educational Materials: Gout Patient Brochure Medical Professional Guide Crystal Clear Checklist Kicking Gout in the Acid is sponsored by Sobi. Podcast Transcript Ian PonitzHello, and welcome to Kicking Gout In The Acid, a podcast from the Gout Education Society. My name is Ian Ponitz, and I'm your host for this series. Kicking Gout In The Acid features conversations between Dr. Larry Edwards, chairman and CEO of the Gout Education Society, and experts on the disease. Each episode will dive into important topics that you, the listener, should know about gout. The goal? To feel empowered to get gout under control. In this episode, Dr. Edwards is joined by Dr. Richard Johnson, board-certified nephrologist, professor emeritus at the University of Colorado Anschutz Medical Campus, and board member of the Gout Education Society. Today, Dr. Johnson and Dr. Edwards will discuss the connection between gout and kidney health, how uric acid is regulated, and the challenges patients face when both conditions exist. Dr. Edwards, take it from here. Dr. Larry EdwardsThanks, Ian. I'm happy to be joined today by Dr. Richard Johnson, who's a board-certified nephrologist, an internationally recognized researcher, and a member of the board of directors of the Gout Education Society. Welcome to you today, Rick. What I'd like to do is ask you to just briefly here talk about your interest in gout, how that came about, gout and uric acid. Dr. Richard JohnsonYeah. Well, first off, thank you, Larry, for inviting me to be on this podcast. It's a real delight to see you again and to interact with the people who are interested in gout. I'm a kidney doctor, and gout is very common in kidney disease. And so, just by nature, I've seen many patients with gout. But what happened was, in my research, where I was investigating mechanisms of kidney disease and high blood pressure, I became interested in the role of uric acid in kidney disease and blood pressure. Over the years, I have studied this with National Institutes of Health (NIH) funding and other grants to try to understand if uric acid might have a biologic role in diseases, not just gout, but in diseases such as high blood pressure, chronic kidney disease, metabolic syndrome, and so forth. It's a controversial topic, but that's where I've spent much of my research career over the last twenty-plus years. Dr. Larry EdwardsYou've certainly been at the forefront of that area of investigation over that time period. Can I get you to just do a brief overview of the role the kidneys have in regulating uric acid? Dr. Richard JohnsonYes. It's a very important role for the kidney. Uric acid is a breakdown product of purines, which are nitrogen-containing substances that are in our cells, DNA, and other RNA. And just as we have to get rid of waste, when the purines break down, they form uric acid. In many animals, there's an enzyme that degrades uric acid, and so that's the main way you get rid of uric acid, you know, like most mammals do. But humans and some other species, like apes and also birds, and reptiles, lost this enzyme. And so we have to get rid of uric acid from our body a different way. We don't have the enzyme to degrade uric acid, and so we have to get rid of it typically through the urine. And about two-thirds of the uric acid we get rid of goes out through the kidneys into the urine. One-third is removed by the gut. So the gut, or intestines, especially the large intestines, have bacteria that degrade uric acid. There's some movement of uric acid in and out of the intestines, and about one-third of uric acid is removed by the gut. When people start developing kidney disease, they'll start to have some problems with excreting uric acid through the kidneys because with less kidney function, there's less filtering, and it's harder to get the uric acid out. And so the intestines increase their workload to remove uric acid a little bit in response to that. But it's usually not enough, and so uric acid starts to be retained in our blood. As the uric acid levels go up, we become at risk for gout and other complications associated with high uric acid. But when the kidneys are not working, the uric acid levels tend to go up. In people who start dialysis, for example, about half of them will have a uric acid level of greater than seven. It's very, very common to develop gout with kidney disease because you're retaining the uric acid. So, kidney disease is a major cause of gout because as you get worse kidney disease, your uric acid tends to go up, and as the uric acid levels get over seven, the risk increases for the uric acid to crystallize into joints and to cause gout. It's been known for a long time that you can develop gout because of your diet, you know, from eating foods very rich in purines. Beer and alcohol will generate uric acid. Sugar can generate uric acid. So you can raise your uric acid by diet, but the two other major risk factors are genetics, if you have a genetic predisposition to have gout, and the other is if you develop kidney disease, because as you develop kidney disease, you retain uric acid. So, kidney disease is very important in people with gout, and everybody with gout should have their kidney function tested. Dr. Larry EdwardsAnd genetic mutations in these transport systems, both in the gut and in the proximal part of the kidney, I think, are very important and have been researched extensively here for the past fifteen years. I have always been impressed over the last thirty, forty years that I've been looking at these things that uric acid was so tightly regulated by multiple transport systems in the kidney transport systems in the gut that you talked about. Why do you think uric acid has that much influence as far as the body is concerned? Dr. Richard JohnsonWell, you know, there is this problem where if the uric acid levels go up really high, and this is particularly seen in some animals that also lack this enzyme. So we lack this uricase enzyme that, if we had that enzyme, it would protect us if our uric acid levels go up. It would degrade the uric acid, and it wouldn't matter if you had kidney disease or not. But in some animals, especially reptiles and birds, for example, if their kidney function gets worse, they can retain very high levels of uric acid, where the crystals don't just form in the joints, but also in the kidneys and in the heart and throughout the body, and it's actually got the name visceral gout. It's fatal, basically. It's really massive crystallizations associated with aneurysms and severe high blood pressure. Visceral gout is a problem. Now, in humans, we rarely see visceral gout, but there are reports. I was on a paper that described a couple hundred cases of uric crystals forming outside of joints. And usually these are people with kidney disease, and the uric crystals just overwhelm. You can find them in the heart, in the blood vessels, in the kidneys, in the skin, in the eyes. And I've seen a few patients with this over the years, and it's really a horrible syndrome often associated with uric acid levels of fifteen or higher. So the kidneys, though, become so important for getting rid of uric acid. And it's controlled in the tubules. So what happens is after the blood is filtered in the filters of the kidneys, we have millions of filters called glomeruli. And then the urine runs down tubules until it gets into the ureter and then goes into the bladder. It's full of urine, and then you excrete it. But the urine is initially partially filtered. It's first filtered,...