Faculty: Matthew Bultitude, MD, Kristina Penniston, MD and Kymora Scotland, MD

Moderator:  Sara Best, MD


Matthew Bultitude, MD

Matthew Bultitude is a consultant urological surgeon at Guy’s and St. Thomas’ Hospitals in London. He is Clinical Director for transplantation, nephrology and urology. He previously undertook a fellowship at The Alfred Hospital in Melbourne and has a special interest in the management of stone disease and cystinuria. He has published widely on stone disease and won several prizes for this work. He previously wrote his thesis on “The effect of flexible ureteroscopy on renal function”. He is an editor for the classic textbook ‘Browse’s Symptoms and Signs of Surgical Disease’. He has been an invited speaker at many international conferences and meetings including BAUS, EAU, AUA, WCE and SIU. He has taught on courses at BAUS, EAU, AUA and the WCE on stone disease, hands-on-ureteroscopy and PCNL, metabolic stone management and social media. He has held the post of Senior Secretary of the Urology Section of The Royal Society of Medicine and was Associate Editor for the BJUI for 9 years. He currently sits on the data and social media committees for the Endourological Society.

 

Kristina Penniston, MD

Kris Penniston is a scientist and registered dietitian nutritionist at the University of Wisconsin-Madison. Dr. Penniston earned a PhD in nutritional science from the University of Wisconsin-Madison. She completed a dietetic residency at the University of Wisconsin Hospital and Clinics and is a fellow of the Academy of Nutrition and Dietetics. Dr. Penniston has provided clinical nutrition services to patients with kidney stones and other urologic diseases for >20 years. Her work focuses on prevention of kidney stones. She is specifically interested in developing and testing dietary interventions that prevent recurrent stones; promoting patients' self-efficacy in managing their stone disease; and understanding and improving patients’ health-related quality of life. She was the primary developer of the Wisconsin Stone Quality of Life questionnaire (WISQOL), a stone-specific instrument to assess patients' health-related quality of life. Dr. Penniston leads the North American Stone Quality of Life consortium, a clinical research collaboration comprised of 17 urology centers in the US and Canada, the primary aims of which are to test and validate the WISQOL and understand how kidney stones affects patients’ health-related quality of life. Dr. Penniston is a member of the American Urological Association (AUA) and is a former AUA research scholar (2008-2010). She currently serves as Secretary-Treasurer for the Research on Calculus Kinetics (ROCK) Society.

 

Kymora Scotland, MD

Dr. Scotland is Assistant Professor and Chief of Endourology Research at UCLA. She earned her medical degree from Weill Cornell Medical College of Cornell University  and her doctorate at the Tri-Institutional Cornell/Rockefeller/Sloan Kettering MD-PhD Program. She then completed her urology residency at Thomas Jefferson University and an endourology fellowship at the University of British Columbia. 

Dr. Scotland’s clinical interests include the treatment of kidney stones, benign prostatic hyperplasia and upper tract urothelial carcinoma. Her basic research at UCLA investigates stone pathogenesis and the physiology of peristalsis. She has a particular clinical research interest in developing techniques aimed at improving quality of life for nephrolithiasis patients and has focused recent work on patient engagement with medical management regimens. She is the President of the Collaborative for Research in Endourology (CoRE), an international group of endourologists focused on developing innovative solutions to the care of kidney stone patients.

 

Sara L Best, MD

Sara L Best, MD is an Associate Professor of Urology at the University of Wisconsin School of Medicine and Public Health in Madison, WI. She completed a fellowship in Minimally-Invasive Urology and Stone Disease at the University of Texas Southwestern and serves as co-director of the Endourology Fellowship Program in Wisconsin.

 

Webinar Transcript

Dr. Jared Winoker:

Good morning, good afternoon everyone depending on where you're coming from. We appreciate everyone joining us again for the latest installment of the masterclass in endourology. Of course this is an educational initiative that's brought to you by the Endourological Society. Today, as you all know, we're here to hear from some experts on the medical management for stone disease, specifically a practical approach to the endourologist. We're joined by a star studded faculty panel that's going to be led by our moderator, Dr. Sara Best. Dr. Best is an associate professor of urology at the University of Wisconsin's school of medicine. She completed a fellowship in minimally invasive urology and stone disease at the University of Texas Southwestern and currently serves as co-director for the endourology fellowship at Wisconsin.

Dr. Jared Winoker:

Just a reminder that, like all of our webinars, today's is going to be recorded, so you can feel free to look back at this slide, which is an overview of the CME program for today's webinar. So without further ado, I'll go ahead and turn it over to Dr. Best.

Dr. Sara Best:

Hello everyone. Thank you for the introduction. It is a pleasure to be with everyone today during this unprecedented time. I hope everybody is healthy and safe and we have a really good program lined up for you today with some really excellent speakers. We will have the ability... I'll review and keep an eye on the Q&A portion of where you can type in some questions and we will be able to review those questions. We'll have a few minutes after each talk and then at the end for more discussion as a group to chat about approaches, I think we're really trying to focus especially on a practical approach, which is something I think that's useful to everyone. So with no further ado, I would like to introduce our first speaker, who is Dr. Matthew Bultitude, who is a consultant urological surgeon at Guy's and St. Thomas' Hospital in London. There he's a clinical director for transplantation, nephrology and urology and he completed his fellowship at the Alfred Hospital in Melbourne.

Dr. Sara Best:

He has particular interest in stone disease and specifically cystinuria, which is what he's going to be sharing his expertise, particularly with us today. We'll look forward to that and onto his chat.

Dr. Matthew Bultitude:

Good afternoon from London and good morning to those in other parts of the world. Thank you for the introduction and to the Endourological Society for inviting me to speak today on one of my favorite subjects to talk about. So these are my disclosures, both Retrophin and Advicenne do make medications relevant to cystinuria, so just to disclose that. I thought that I'd start with a little bit of background about cystinuria. A lot of people don't know that much about it. It's a rare orphan disease and thought to affect approximately 1 in 7,000 people around the world, although that number does vary. It's due to failure of reabsorption of cystine and the other three dibasic amino acids across one of two transporters, as you can see in the diagram, that are encoded for by two different genes. It affects transport across the intestine, which has no known effects, and across the proximal tubule, and leads to a build-up of cystine in the urine, obviously crystallization to form stones.

Dr. Matthew Bultitude:

Just a little bit of history because it's very relevant to us here in London. The first cystine stone was reported by this guy in 1810. He actually called it cystic oxide at the time because it was a bladder stone and he noted the oxidation process. The picture on the left is taken from a book around that time and here's that picture of that bladder stone and the bladder stone is actually housed in the histopathology museum here at Guy's in London. Over the years, it has turned blue, as you can see. This often causes a lot of confusion, so just to go through it, on the left is cysteine. Cysteine molecules are oxidized to form cystine, with the formation of that disulfide bond that you can see. But that's what gives cystine its strength and also its characteristic sulfur smell when that bond is broken with the holmium laser.

Dr. Matthew Bultitude:

Not much to say about this. There's a very old classification that you often see in literature, which really shouldn't be used. We really should be using the classification at the bottom of the screen, based on genetic classification into either type A, type B or type AB. So what about the challenges of cystinuria? It always affects young patients and these patients are often labeled as non-compliant and drug seeking because they're in and out of the emergency department. They form frequent stones, as we know, and as you can see from that picture, you can try and count up the number of scars on the back of this patient of mine, who's had bilateral open surgery in numerous PCNL procedures over the years.

Dr. Matthew Bultitude:

[inaudible 00:05:00] quickly enough, that image was taken 10 days after insertion. So we really have to be mindful about limiting dwell time in these patients. Renal impairment is very common and 75% of our series at Guy's have abnormal EGFR and 50% have hypertension. So this needs to be managed as well. Stones are often thought to be hard but actually they can be soft. Just to show some work that we presented at the AUA last year, the Hounsfield units aren't really very helpful in judging the hardness of cystine stones, as we might do for other stone types. As you can see, the vast majority of our cystine stones in the range between 400 to 800. So actually, I think if you saw a cystine patient with Hounsfield units greater than 1,000, you should actually be thinking that they're probably converted to calcium phosphate.

Dr. Matthew Bultitude:

Just by way of a recent example, this patient has underwent a PCNL, single stone in one patient. On the top you can see the Hounsfield units measured as 700 and that was the bulk of the stone. That's the stone seen on the left there, which is that characteristic cystine appearance. That was what was shown on stone analysis. At the top of the stone, there was a much harder cap of stone where the Hounsfield units were nearly 1,300 and morphologically, you can see as I said on the right there, that looked very different and that was pure calcium phosphate. Actually you could predict based on measuring those Hounsfield units and knowing what I just said.

Dr. Matthew Bultitude:

My colleague Kate Thomas set up the cystinuria clinic at Guy's in 2008, which is a multi-disciplinary clinic with a urologist, nephrologist, a radiologist, who gets consistency of scans in the clinic, as well as a dietician and a specialist nurse. We have over 200 referrals to our service. Diagnosis of cystinuria is based on at least one of these three things. Stone analysis, observation of cystine crystals in the urine or abnormal excretion of cystine and you can measure the other dibasic amino acids as well. Genetics is not normally needed for diagnosis and that's from the EAU guidelines. It is occasionally useful for diagnosis and potentially very useful for genetic counseling. No major phenotype correlation has ever been identified, however. So in clinic, what do we assess? Well obviously we're going to assess clinically for, have the patients had pain or stone episodes.

Dr. Matthew Bultitude:

Tests we do, I think we should measure blood pressure in these patients every time they come and obviously we check their renal function with a urine dipstick, particularly for proteinuria and pH and we ask all our patients to complete a pH diary and bring that with them so we actually get some real world idea of what their pH is doing at different times of the day with their normal lives. There's different ways of measuring urinary cystine levels, as I'll show in a minute, and we use ultrasound as first line and only use ionizing radiation for patients where it's really needed. I've just listed here the different types of cystine measurements you can make. Obviously you can measure the cystine levels on just a spot urine, which could be in the clinic or an early morning urine. 24 hour urine obviously can be measured and may be the gold standard.

Dr. Matthew Bultitude:

The problem with those measurements are that cystine may have crystallized out to form the stone so the cystine levels may be artificially low and reassuring so people have looked at measuring supersaturation and another way of doing that using a proprietary method called cystine capacity, which is only available in certain parts of the world. You can measure the drug cysteine complex levels to ensure that you're getting good levels of that and you can look at crystaluria as well and there has been a positive association stone formations show. The issues with all these tests are availability, collection issues. Patients often travel long distances, so how do you get them to do a 24 hour urine? And as I mentioned about the cystine crystallizing out into solid forms.

Dr. Matthew Bultitude:

So for medical management, obviously we want to reduce the urinary cystine levels as much as possible and we can assess this either by urinary testing, as I said, or actually by clinical episodes, because of course that's what's going to make the most difference to patients. All patients should follow diet and fluid advice and the majority of patients will also require alkalinization, ideally with potassium citrate. Chelating agents are then really only used for patients who need treatment beyond that, with either tiopronin or D-penicillamine and the reason to try to use these sparingly is because they have significant side effects, as I'll show you.

Dr. Matthew Bultitude:

I've put captopril on the slide because people may have heard of using that. That's no longer recommended any longer but I put it just to make that point. Some dietary considerations for cystinuria, salt is bad for all stones. We're going to hear later. And it's bad for cystine stones. It increases cystine excretion, as you can see from that graph. The effect on stone formation hasn't actually been proven but it certainly makes a lot of sense to try and limit salt where possible. The impact of animal protein methionine, which is then metabolized to cysteine is definitely important and leads to an increase in cystine excretion and then therefore potentially stone formation.

Dr. Matthew Bultitude:

However, methionine is essential for growth so you must ensure you have an adequate alternative protein in your diet and we do not advise limitation at all of protein in children. Fluids of course is the cornerstone of treatment and really patients need to be getting at least three liters of urine per day and will have to drink a variable amount to achieve that. Only rarely really do we ask patients to set an alarm and drink and void at night but sometimes that is needed. The patients can measure the specific gravity themselves to ensure that their urine is dilute. Alkalinization should be done with potassium citrate where possible because you want to avoid the sodium load from sodium bicarbonate and the target pH should be between 7.5 and 8 and really try and monitor this through the day with a pH diary to see if that is being achieved. You can see why in the graph, you want to try and get that pH up as much as possible. The problem going too high is the potential for calcium phosphate formation, although that is only rarely seen but is something to consider.

Dr. Matthew Bultitude:

Chelating agents, so either tiopronin or penicillamine, cleave the cystine and then form a complex with cysteine, which is 50 times more soluble and that is why they work. They're paired that both drugs have similar efficacy and side effects, so choice will really depend on cost and local availability. They do have a wide range of side effects, as many of you will know, which patients have to be counseled about and then monitored for. Monitoring is quite difficult with weekly blood tests for the first three months. Weekly for the first three months and then every three months with full blood count, renal and liver function and patients who also have their urinary protein checked for proteinuria and more rarely, nephrotic syndrome. Specifically with penicillamine, there is a risk of getting vitamin B6 deficiency, so that should either be replaced with pyridoxine or checked with occasional blood tests.

Dr. Matthew Bultitude:

I borrowed this slide from David Goldfarb but it's really to make the point about the importance of monitoring blood pressure. I said earlier how common problems with blood pressure were in this patient population and the detriment that has to long term renal function. I put it to you that all urologists can check a blood pressure. We don't have to be able to treat it because primary care physicians or nephrologists can do that but I think we should at least be thinking about this in our patients.

Dr. Matthew Bultitude:

We believe that patient education and engagement is really important for this group of patients. This helps improve their understanding of the disease and empower them to help themselves. That will improve compliance with diet and weight, adherence to medication, which is often poor in this patient group. We want them to monitor their pH to understand why they're doing it, to want to aim for a target and then try and achieve that and also to measure their urinary volumes and of course, there are apps and different things that could help with that. There are websites for education, we set up a website called cystinuriaUK and the Cystinuria Foundation have a website as well. We have patient information data where patients can meet each other and share stories. Actually, unless you have a dedicated cystinuria clinic, patients very rarely have met another patient with cystinuria. We've created cookbooks, as you can see there, and also there are two patient forums, we set up something called HealthUnlocked, which is a bit like Facebook but for health and the Cystinuria Foundation have a very large Facebook group as well that patients can join.

Dr. Matthew Bultitude:

So in summary, really, cystinuria is a challenging condition to treat for all the reasons that I've said. Diet and fluid advice should be given to all and patients should optimize their weight. Patients are likely to need alkalinization but they should be assessed with pH testing and then monitored and chelating agents should follow if it's needed and keep getting stones. Do remember to monitor as I've described. A regular follow up lifelong is going to be essentially and for that reason, we think it should be with ultrasound rather than ionizing radiation. Really we need to design our services for easy access for patients so they can get back into us to be seen when they have problems because of their frequent stone formation.

Dr. Matthew Bultitude:

I just put for a bit of further reading on this slide, two excellent articles that have both come out this year, which are evidence based but consensus statements on the management of cystinuria and some information about our websites and my contact details if anyone wishes to get any contact. Thank you very much.

Dr. Sara Best:

Great, excellent presentation. We do have a question in from the chatroom. Could you tell us a little bit about your approach to cystinuria in pediatric patients? You mentioned about the dietary, the protein necessity, especially in growing kids but do you have any kids in your practice or any thoughts or insight?

Dr. Matthew Bultitude:

I suppose curiously at Guy's because we are an adult only site, we actually only do see adults so we tend to pick these people up around the age of 17 and 18 and before that, they are managed in the pediatric hospital by the nephrologist there and the urologist there who covers that as well. So we don't actually get involved in the day to day management of that, although it's broadly the same as outlined, as I said. You have to obviously adjust the amount of fluid requirements and the drug doses for their body weight.

Dr. Sara Best:

Then I had a question for you. You mentioned using ultrasound for monitoring for stone burden. There's been a lot of studies that have been published more recently about how the accuracy of ultrasounds can be really variable. Do you have any tips or tricks on how to ensure that you're getting good visualization or have a good ultrasound, things like that for your patients?

Dr. Matthew Bultitude:

This is a challenge, isn't it? All the time. It is a patient population, if you use a CT regularly for them, they're going to get a lot of ionizing radiation throughout their lifetime. I think the way that we have set up our clinic, we have a single dedicated consultant radiologist who attends and does that and that makes a huge difference because part of the problem with ultrasound is the variability in the people who do it, who aren't necessarily used to scanning the kidneys because they do a bit of everything. Our radiologist actually gets to know the patients. So he knows them really well, he recognizes them, knows them by name. So he knows what he's looking for and knows what to monitor. So if he's unsure about something, actually if they're asymptomatic, the thing to do is to monitor that and he repeated himself three months, six months later. Not to get a CT to try and prove that. So very rarely is he wrong. Clearly, people can be wrong with ultrasound and if someone has symptoms at a normal ultrasound, I would still get a CT scan but we've used that judiciously, not just routinely in every patient.

Dr. Sara Best:

We can take one last question here. Another one popped up in the chat. Would you recommend surgical intervention for a cystine stone if it's asymptomatic or maybe a better way of phrasing it would be, when would you intervene if someone's asymptomatic?

Dr. Matthew Bultitude:

Yeah, that's a good question, isn't it? I suppose it does depend on the patient and the patient history and where the stone is. There's going to be a lot of factors that you have to consider in that. We certainly have some patients who have stones in very difficult places to reach that we just leave alone because actually, if you clear them, because those areas don't drain very well, they often reform in that area. So if they're asymptomatic, you leave them. But if someone forms a de novo stone in one of our patients that's of a reasonable size, I think it's probably useful to ask patients what size they can pass. These patients often have much wider ureters and can pass much bigger stones. If they say, "6mm," I often say, "That's nothing. That's fine. I'll pass that if it moves," which other stone forms wouldn't normally feel that way. But I suppose up and around anything bigger than that for a de novo stone, then I would recommend treating that. How you treat it, of course, may be subtly different as well. I actually took the surgical bits out of my talk because this is more about the medical management but we do use shockwave in some people.

Dr. Matthew Bultitude:

I know that gets a bad press in cystinuria but it's not always hard and it does work and we've shown that in some of our patients and often patients will know as well if they've tried it before. Some just won't work and others will. We have a threshold for using flexible urteroscopy beyond where you normally would so you'd probably look to maybe get up to 2cm just to try and avoid repeated insults from having regular PCNLs, which as you saw from that lady's back, often does happen. But there is evidence that being stone free does make a difference. If you get someone stone free, that does make a difference. So that is obviously what you want to achieve and you want to do the right surgery. So you've got a 2.5cm stone, I would say you're likely to have a PCNL for that, not a ureteroscopy.

Dr. Sara Best:

Great. Well I know that you have important commitments here so we don't want to keep you too long. Do you want to keep moving? There are a couple other questions that popped up if you have a second to look at the chat before you leave for your COVID emergency meeting. Please take care of yourself and be safe and we are grateful as I'm sure all of your patients are as well for all the work that you're doing. Thank you very much.

Dr. Matthew Bultitude:

Thank you for the opportunity today. Thank you.

Dr. Sara Best:

Our next excellent speaker is Dr. Kymora Scotland. Dr. Scotland is an assistant professor and the chief of endourology research at UCLA in Los Angeles. She went to medical school at Cornell and got her doctorate at the tri-institutional Cornell, Rockefeller, Sloan Kettering MD-PhD program and did her fellowship in endourology at the University of British Colombia and she is going to be speaking to us today about calcium stone prevention and thank you for being on the call, Kymora.

Dr. Kymora Scotland:

Thank you so much to the Endourological Society for allowing me to participate. I wanted to start by talking about the two most common types of stones that our patients have to deal with, which is largely calcium stones and uric acid. I will be talking about how we manage these medically. Just a quick primer on calcium stone formation. We know that calcium loss leads to increase stone risk. So what happens with hypercalciuria is that you do have bone loss as well as dietary calcium contributing to the amount of calcium in urine. Urine calcium we know as well is associated with the supersaturation of calcium oxide and calcium phosphate. Now for the purposes of this talk, I will be saying calcium stones but primarily we know that we deal with calcium oxalate stones in most of our patients and so a lot of the information that I'll be giving will have to do with that but I do want to make the point here, because I think it's something that we sometimes miss, that decreased bone density is common in kidney stone disease and it's something that as urologists, we should be taking a close look at in our patients.

Dr. Kymora Scotland:

I also wanted to just touch on the fact that we need to look at some other risk factors for calcium stones, beyond just hyperparathyroidism, it behooves us to think about some of the genetic disorders that might be involved in stone formation, particularly in younger patients. I wanted to start by talking about not just the guideline recommendations but the ones that actually have data to support them and so the things that we do in large part with medical management really have some significant results underpinning them.

Dr. Kymora Scotland:

So thiazides, for instance, are recommended to patients with hypercalciuria and recurrent calcium stones. We recommend alkalinization for patients who are recurrent calcium stone formers as well as those who are hypocitraturic and some of the guidelines recommends allopurinol to patients with recurrent calcium oxalate stones who also are normocalciuric and have hyperuricosuria. Then we'll talk a little bit about what to do in those patients who we really even with 24 hour urines and with workups are not able to find metabolic abnormalities, what the guidelines tend to say is that we should focus on trying thiazide diuretics and potentially potassium citrate in those patients. So for our practical advice, I think it's important for us to first remind ourselves what these things do.

Dr. Kymora Scotland:

So what thiazides really are thought to do is to work by inhibiting the reabsorption of sodium in the distal convoluted tubule. What that has to do with calcium is that calcium really follows sodium. So while calcium inhibits the sodium chloride transporter, what we find is that the uptake of calcium is increased, leading to a decrease of calcium in the urine and then we also, going back to this idea of bone density, we also find that thiazides decrease bone disease and that... I'm sorry, that the importance there of thiazides for calcium stone formers is that they can help maintain bone density. We also think that calcium stones are affected by increases in magnesium and thiazides have been shown to increase the excretion of magnesium, leading to decreased stone formation.

Dr. Kymora Scotland:

So while we're not entirely certain of all of the mechanisms by which thiazides work, it's important to think about all of these potential data points. Then potassium citrate. We know that alkalinization causes an increase in the urine pH and what we found with potassium citrate is that it does this in two ways and then it also complexes with urine calcium and that leads to less free urine calcium but then also prevents the agglomeration of calcium crystals. So that is one of the reasons why potassium citrate is recommended. Briefly we'll talk about allopurinol because what we know is that it blocks uric acid production and we'll talk about that a little bit more when we get to the dissolution of uric acid stones.

Dr. Kymora Scotland:

I wanted to take some time to talk about the fact that really, despite the face that we try to do targeted therapy for our patients, particularly our patients who have recurrent stones and are high risk, a lot of the data that underpins the work that we do is empiric. What I mean by that is this. What we found and what we have data to support is that an increase in fluid intake does in fact decrease stone risk and so that is why we tell patients to make sure that they increase their water intake or their fluid intake so that they have a urine output of greater than 2.5 liters. Data's also shown that a decreased sodium in the diet, less than 2,300mg/d, decreased animal protein intake and maintaining normal calcium can decrease the stone risk.

Dr. Kymora Scotland:

Then there's data that thiazides and potassium citrate will decrease calcium stone risk as well. Now what we do with targeted therapy is we work with 24 hour urines and I just wanted to make the point here that while there is some data that 24 hour urines are very helpful, particularly for a high risk patient, there is not data showing that the use of 24 hour urines results in decreased stone formation. So there has been a wave of folks who are talking about the potential of... focusing on empiric therapy as compared to targeted therapy. Especially for those of us who do not have access to 24 hour urines, as we know the use of 24 hour urines can be quite expensive and is not available everywhere. Dr. Goldfarb just had a recent article in Urolithiasis in 2019 talking about this and I wanted to bring this up because I think, if we're talking about the practical treatment of calcium stone patients, then we really should be thinking about, what are the things that we can do empirically that are data driven?

Dr. Kymora Scotland:

So when we talk about patient engagement, before we start talking to them about these things, I think we need to think about dietary changes and Dr. Penniston will talk about where that might be more appropriate for our patients but when we talk about dietary changes, I think the practical thing to think about is making sure that we gradually decrease our salt, gradually decrease our protein. It's tough for patients to make these changes and when we talk to them about going to on protein a day or when we go to going down to 2300mg, we have to talk to patients about how they can do that and it's our responsibility, I think, as urologists, to work with them to get to that point. It might take a while. Then it's also important for us to talk about the association of stones with other comorbidities, metabolic syndrome, for instance, and the association of stones as a harbinger for other diseases, like cardiovascular disease. That, I think, is one of the ways that we can try to get patients on board when we're trying to encourage them to make these wide scale changes in their lifestyles.

Dr. Kymora Scotland:

So some more practical tips for stone prevention. When we talk to our patients about thiazide administration, it's important to us to remember that thiazides may decrease sodium intake and so we need to know the urine sodium value when we're working with our patients to make sure that they're not taking thiazides but have a high sodium diet. We need to talk to them about the importance of maintaining their calcium intake. So many of our patients are still trying to eat low calcium diets because of data that's since been debunked and then talking to them about alkalinization.

Dr. Kymora Scotland:

I'll just briefly talk about the fact that while we do recommend potassium citrate, in many countries of the world, potassium citrate is quite expensive and we know that our patients have significant side effects of potassium citrate, so it's important to us at some points to think about alternatives to potassium citrate that may work as well and I'll talk a little bit about sodium bicarbonate a little bit later but then I also wanted to just mentioned that especially in patients where it's expensive, we have to think about alternatives and what our patients might be taking, and there are several supplements on the market. Think about genetic causes, as I mentioned, and in terms of supplements, think about what your patients are taking. A lot of our patients are taking things that are very high in vitamin C, for instance, and if we don't ask them, we'll never know.

Dr. Kymora Scotland:

Briefly I'll just talk about shared decision making. Because kidney stones at the end of the day, are a quality of life issue, we really have to get our patients on board and so it's important, even if we're busy, to try to find the time to sit down with our patients and meet them where they are in terms of what they can do on a gradual basis to get to where they need to get to for stone prevention. Talk to them about the medications, talk to them about the side effects and talk about to them about why it is that we're giving them these medications, or recommending them. Then I'm going to move to uric acid, which is an area where there is a lot of work in the past two years that I think is really exciting.

Dr. Kymora Scotland:

So we'll talk about uric acid stone formation and again, we all know that acidic urine pH leads to uric acid crystallization and that in itself leads to uric acid stone formation. But we should also think about some of the other things that might be associated with the formation of uric acid stones in our patients. So we should always be on the lookout for metabolic syndrome and it's something to talk to our patients about. When we see our patients with obesity, diabetes, dyslipidemia, to talk to them about the association of their stones with these different comorbidities. We need to think about the fact that there are other ways that people get uric acid stones, for instance, secondary to chemotherapy. Then we need to talk to them about high purine diets.

Dr. Kymora Scotland:

We know that the Western diet, which is becoming more and more popular worldwide, comes with a high acid load and that in and of itself can cause acidic urine. Now the rationale for dissolving uric acid stones has always been that the solubility of uric acid decreases in acidic urine and it goes from 200mg/dl in a pH of seven, to 7 to 15mg/dl in a pH of five urine. So that is why we alkalinization or our patients, that's why we give them potassium citrate.

Dr. Kymora Scotland:

I just want to mention quickly here that allopurinol works in specific cases, not necessarily for dissolution but in patients who are hyperuricemic and also have gout. Allopurinol can be helpful. So it's something that can help our patients even while we're trying to dissolve their stones. Now potassium citrate and other ways of alkalinizing urine can cause dissolution. It's not something that's very widely practiced and so the idea here, in several teams who have been working in the past two years, has been to look at this.

Dr. Kymora Scotland:

There are now several retrospective as well as prospective studies showing that there is some success to this practice. I just wanted to highlight a recent manuscript by Dr. Knudsen where we're seeing a substantial stone burden disappearing within two months just with the use of potassium citrate. The guidelines do recommend this. They also, as I mentioned, mention allopurinol as a first-line therapy in some patients with uric acid stones. And then we need to talk to them as well about not just using potassium citrate to alkalinize their urine but considering the fact that when you're using a diet that's heavy in animal protein, then you really do need to think about decreasing that in your diet as well.

Dr. Kymora Scotland:

And then we need to remember that we need to do periodic blood testing for our patients. So to end with some practical tips for dissolution therapy, smaller low density stones seem to result in better chemolysis. We need to think about potassium citrate and if it's not tolerated consider things like sodium bicarbonate. Allopurinol as I mentioned. Stress fluid intake as well for these patients for urine volume greater than two and a half liters. And then discuss their diet. Discuss their purines and their salt. Think about stones less than five millimeters. Think about trying passage first. Consider using it for residual stones. If you've already treated the stone and there are some small residual stones, consider doing dissolution therapy instead of another procedure. It can be combined with urinary drainage if there's an obstructing stone.

Dr. Kymora Scotland:

Make sure that you keep the pH over 6.5. The EAU says between seven and 7.2. And then work within a timeframe of three to six months. So give them some time for this to work. All right I went over a little bit but I want to thank you again for the opportunity here to talk about these things.

Dr. Sara Best:

Thank you Dr. Scotland. We are going to save questions for the end, after Dr. Penniston's talk. Dr. Bultitude had to go as I mentioned but we'll save the rest of the questions. We do have a few in the chat. You can look ahead if you'd like. But we should have time at the end to have a discussion. So our next speaker is Dr. Kris Penniston, who is a partner of mine and a wonderful person, I can also shout out there. She is a scientist and registered dietician nutritionist here at the University of Wisconsin-Madison. She earned her PhD in nutritional science from UW and did her follow up work there. She's a fellow of the Academy of Nutrition and Dietetics. In addition to taking care of patients clinically she also has been an amazing researcher, producing a lot of really fascinating work about stone quality of life issues with the WISQOL questionnaire and is also leading the North American Stone Quality of Life Consortium, which has 17 urology centers in US and Canada, looking to look at the effects of quality of life... Or of stone disease on quality of life. With that, we will shift gears and listen to Dr. Penniston. Thank you.

Dr. Kristina Penniston:

Thank you very much. I also appreciate the opportunity to speak to this group here. I'm just kind of looking through the participants and see a lot of people. Some of our former fellows and others who are also experts in this area. So thanks for coming on this... Participating in this class. So yes, we know that nutrition affects stones at all points along the continuum. It can affect the actual supersaturation, which is the nidus or the crystal formation stage. But then it also... Different things in the diet also affect nucleation and growth and aggregation and so on. So it's huge, right? We have all these different dietary risk factors. I'm not going to go through these. I kind of just show this for the wow factor. Many different dietary factors. Some of which Kymora talked about. They all affect, or most of them affect, various things in the urine, which is why we look at them in terms of creating stone risk. So this is a lot of things right? In that all these things are operative in any one person to contribute to his or her stone formation. So if we were to tell patients to do all of these things, it would be overwhelming right?

Dr. Kristina Penniston:

So we try not to. And the message of my talk today, where I'll be trying to deliver what I call best practices as well as sort of give you some sense of what's on the horizon as I go through this, we try to be very selective. As Kymora said, we want to give targeted therapy when possible. Because not all of these dietary factors are operative in any one person. So the approach that a dietician uses, probably similar to approach that surgeons use and others is, we want to assess the problem. And in this case we're assessing the diet. We get all this other information about their stone type and about their urinary risk factors. We get information about diet as well. Then we want to diagnose whether there are any risk factors in that diet. The one thing I want to point out and you'll hear me talk about is that there really isn't any sense to tell patients to lower say, their salt intake, if it's already very low. You will know that when you assess the diet.

Dr. Kristina Penniston:

Granted there aren't that many people who have very low salt intakes. But there are some. Same with animal protein. It makes no sense to tell someone to limit animal protein if their intake is already very low. I have seen people who have tried to adhere to what they think are recommendations and then actually gotten too low for their protein intakes. So we want to diagnose the specific risk factors that we see in a diet that contribute to those urinary risk factors or the stone composition. And then of course we want to design interventions that are individualized to each patient. And then as I say here, look and see whether there are changes. If there are, great. If there are not, did we apply the wrong therapy? Did the patient not adhere? Many factors to consider. So I like to use this term minimally invasive nutrition therapy. I borrowed that from you urologists who use minimally invasive surgical techniques. I use that term here as well because I think in the same way that we don't just prescribe all possible medications to a therapy for high blood pressure for example, we don't perform all possible surgeries on a stone, we pick the ones that are most likely to affect change.

Dr. Kristina Penniston:

So in counseling patients I try to look at the four Es. I know that you don't have time necessarily to devote to all of these things when you're counseling patients, because you don't have that much time with them, but these are still things to think about. And certainly things to train a dietician that you might be working with. There's a strong link in nutrition literature and other literature for education and self-efficacy. So we know that the more uptake of knowledge patients have, the more education they have, the more likely they are to be able to manage their disease. So education. What is wrong? Helping patients understand what is wrong in their diet or aberrant in their diet and what they might be able to change.

Dr. Kristina Penniston:

Engagement. Engagement with providers in all aspects of health also improves self-efficacy. So how does this help in our counseling? I think we can interpret this as explaining why therapy will help. Engage with patients and tell them, "If you do this, this is likely to happen." And then empowering, that's an approach that we use in self-motivation techniques but it helps the patient's adherence. There's a lot of literature to support that. So telling them how to change, as Dr. Scotland said. It's not just enough to say, "Here do this." But also, how to do this. And this is where dieticians can be very helpful. And then expectations. I think managing expectations is very important. Not just for quality of life as Dr. Best alluded to but also with other disease end points. There is literature suggesting that the greater... The more accurate patients' expectations are about therapy, the more likely their disease end points are to be improved as well.

Dr. Kristina Penniston:

What are some tips for managing expectations in patients with stones? I think it's important, and this might be funny for me to say as a dietician, but it's important to say that diet doesn't cause or even contribute to all people's stones. So if they think that they're going to change their stone outcomes, i.e. not form new stones by changing their diet, but if diet isn't causing their particular stones, could be as Dr. Scotland said some genetic cause, then we have to realize that they can't expect dietary changes to work. Now that may be a minority of cases but if we do identify dietary contributors I think managing expectations sort of makes us realize that we should counsel patients on how to correct them and what they could expect when they do correct them. And then of course no one is perfect all the time. I think managing patients' expectations are important in this regard. No one does the right thing or does perfect things all the time.

Dr. Kristina Penniston:

I think we need to give patients the liberty to experience that. And then in some patients we may never get them to form... To never form a stone again. But we might be able to get them to form fewer stones. And I think that's an important expectation. So I have a few slides where I'll talk about best practices. These are from my 21 years of experience as a nutritionist and patients with stones. I think it's important to link the physiology. You can judge this on a patient by patient basis. There are some patients who really like the science and really want to know more and others who might not. You can judge this. But when we educate patients about biochemical links to their diet and their stone risk factors, I think it makes more sense to them. And so in fluids for example, helping them understand that the more dilute their urine, the less likely it is to form a stone. In counseling, helping patients understand that it's not just about water. That all fluids count towards their beverage intake. So expanding the fluid repertoire is something I've found to be a best practice.

Dr. Kristina Penniston:

And then addressing barriers and challenges. Using techniques like special water bottles or even these rubber bands that we purchased that people put around their wrists and then took one off every time they drank a container full of water. Little tips and tricks that help people get over some of those hurdles, whether it's forgetfulness or whatever. So there is some literature on best strategies for increasing fluid intake. Some of these involve monitoring tools or specific instructions. Self-efficacy tools. One of our former fellows, Dr. Nicole Streeper is working, just got funding to work on a really neat technological device to increase fluid intake and of course there's the PUSH study, which many on this call probably know about. They're accepting new enrollees. So check out their website if you want to refer your patients to them.

Dr. Kristina Penniston:

What about hypercalciuria? As Dr. Kymora said, salt intake certainly does play a role. But so does the acid load of diet. My best practice here is talk about the biggest contributors of these things in patients' diets. Don't give them a whole list of everything that contains salt or of all the foods that are acidogenic, as this table shows. But rather focus on the biggest contributors to those things in their diet. And in some cases, I even will say let's not limit foods, if we can't get them to stop their intake of cheese, we're in Wisconsin after all, or grains, which are acidic for example, or meat, then let's add. Let's overbalance the situation with bicarbonate precursors from fruits and vegetables. So that's a popular strategy, because it doesn't involve limiting anything. Same with salt. If a person wants to have a high salt meal, fine. Then follow that with lower salt meals. So we can allow for that, must have cheese at every meal, or must have a deli meat sandwich once a day. And then help patients understand how we can manipulate the equation to overbalance that or counterbalance that.

Dr. Kristina Penniston:

And then certainly providing ways to cheat I think is a best practice as well. You can't avoid pizza sometimes and so if you do then help patients understand that, okay, then the next day you're going to be really low in salt. So best practices I think always involve things like adding foods as opposed to eliminating foods if at all possible. Just a shout out about calcium supplements. Dr. Scotland talked about supplements. People are over supplementing with calcium in many cases. Certainly they need it, if they're not getting enough in their diet. But they only need as much as is needed to reach the goal of say, 1,000 or 1,200mg a day. So anyone supplementing with that amount is likely risking toxicity. Because any nutrient, whether it's a vitamin or mineral, is toxic and certainly can cause hypercalciuria.

Dr. Kristina Penniston:

There are some on the horizon sort of things. There are some medications, which are known to reduce urinary calcium excretion. Bisphosphonates, a nice paper was written about this recently in the Clinical Journal of American Society of Nephrology. There's also some ideas about maybe bedtime dosages of thiazides to help reduce urine calcium might be better than morning dosages. And then as Dr. Scotland noticed, potassium citrate could be used as a calcium... As a way to lower urine calcium. I'm going to move on quickly to some other things. I want to talk about oxalate for a minute. This is something that is common. Relatively common. Although I would say probably only 20 to 30% of patients who form calcium oxalate stones actually have hyperoxaluria. So I always want to look for hyperoxaluria before I really kind of focus on oxalate because it may not be the main thing.

Dr. Kristina Penniston:

But we certainly know that a low calcium intake, or a calcium intake that is insufficient to counterbalance the oxalate in their diet, that's a cause. We know that excessive vitamin C is a cause as Dr. Scotland said. We know that an insufficient prebiotic intake can actually also increase oxalate stone risk because then you don't have enough bacteria in your gut because you haven't given them sustenance to degrade oxalate. And this is something where there's a growing body of literature around this. So just a thing about oxalate. I like, as I said before, to try not to limit foods but to add foods. So if a person does have a high oxalate diet, it's not necessarily an unhealthy diet. We know from studies we've done and from others, that you can simply increase the calcium intake, timing it with meals for example. And in this case we pushed everybody from having high urine oxalate, everybody moved towards the left. Some people even achieved normal urinary oxalate excretions.

Dr. Kristina Penniston:

And this was just with diet changes alone or combination of supplements and diet. Why might we not want to go right towards a low oxalate diet? Well there was one study that showed that it does also lower urinary inhibitors of calcium oxalate stones. So I think we need to be careful. And when we look at lists of foods that are high in oxalate, as you see here, these are also foods high in magnesium and fiber and alkali potential. So again, I want to be judicious when I limit these foods. And if I can correct hyperoxaluria by balancing or increasing calcium intake, that's what I'll do. That's simply what this slide shows. I want to move to a close because I know that we want to leave time for discussion. On the horizon for hyperoxaluria there's some really great options that I think might be emerging. Medications. RNA inhibitors, RNA interference agents, enzymes that degrade oxalate in the gut. So these are very interesting studies in a growing body of literature.

Dr. Kristina Penniston:

And then for hypocitraturia, we also want to address this. Because it reduces the risk of all calcium stones. Increasing fruits and vegetables simply, can achieve higher urine citrate in many people. Some will need that extra help that Dr. Scotland talked about, in terms of potassium citrate. But eating more fruits and vegetables has another benefit and that benefit is that it increases urine volume because fruits and vegetables are mostly water. And there actually are some studies, not in the stone literature, but in other literature, showing that urinary output can actually be about 30% from fruits and vegetables and not just fluids. So again, eating more fruits and vegetables might help to overbalance or counterbalance a diet that is otherwise high for acid load. And as Dr. Scotland said, baking soda can be used as an alternative. We've looked at this. We've looked at some of these over the counter things. Currently we and others are studying these drinks and these powders to see if they really are useful as a way to prevent having to use potassium citrate.

Dr. Kristina Penniston:

And there was a great article in Scientific Reports just recently that looked at a longer lasting oral alkali formulation of potassium citrate and potassium bicarb. The longer lasting action is very important. And then finally I just want to talk about magnesium. Urine magnesium is an inhibitor of calcium oxalate stones because it keeps magnesium soluble. And in a lot of patients who are taking PPIs, their magnesium absorption may be reduced. What we're finding, this is unpublished data but we're going to be publishing it shortly, that when we addressed people's low urine magnesiums, their urine citrates also went up. So you can see here, the magnesium went up because they were supplemented with it, but so did their urine citrate. And there's some renal explanations for that, which I don't have time to get into. So lastly I'll just say, uric acid stones, we know that patients with diabetes are more prone to these.

Dr. Kristina Penniston:

Here's where you really might want to get a dietician involved. Because helping them control their diabetes might help to reduce their uric acid stone risk. And there's some good evidence for this. Some of which Dr. Best has presented. So finally, in my minimally invasive approach, I look at diet as a prescriptive sort of thing. Trying to get as few changes as possible. We studied this and found that patients receiving more than three dietary recommendations had a harder time remembering them let alone adhering to them. So I try to limit to this if possible, or as Dr. Scotland said, do it in sort of staged approaches over multiple clinic appointments. And a handout that I use is prescriptive in that I can check exactly which things I want patients to do to help them understand what might be the highest priority. So thank you very much. I hope there's ample time for questions. Thanks to the society for letting me speak.

Dr. Sara Best:

Excellent talk as always, Kris. If I had to make a disclosure it would be that I am the president of the Kris Penniston fan club. So we do have, let's see, about 10 minutes for a discussion.

Dr. Kristina Penniston:

There's a question about turmeric supplements and their oxalate load. That's a great question. A lot of people are taking turmeric. It's associated with anti-cancer properties. It has a high oxalate load. We studied this. We presented it at an AUA meeting and haven't published it yet. I was talking to Dr. Scotland recently about a way we can combine our data to maybe publish that. Yes. I would be very careful about turmeric. If I see a patient with high urine oxalate on turmeric, first thing I might do is say let's try getting off of it and see what that does.

Dr. Kymora Scotland:

I should add to that. It really behooves us to ask patients what they're taking. Because there are all kinds of things online. And Kris and I are going to be working on a manuscript and I'll be doing another one as well, just sort of pointing out some of the things that are available. A lot of vitamin C, a lot of oxalate in some of these things that are supposedly stone breakers. And so it's really important for us to talk to our patients. Because they don't necessarily come with this information. A lot of times they don't even know what's in the things that they take. There are a few more questions as well. One of which is, does chronic use of thiazide predispose to calcium phosphate stones? So there have been some papers that have suggested this.

Dr. Kymora Scotland:

But the jury's still out. What we do know is that when you're treating patients with thiazide it's really important to continue to do serum studies. Even if you're not doing 24 hour urine... Do try to do some urine studies so you see where things are going with them. Because obviously if you're moving your urine pH and you're all the way up to 7.5 or so then you need to start thinking about what could be happening to your patients down the line. So I think the thing for us to pay attention to as urologists is that sometimes we put patients on these medications and then we don't check back. And so it's important for us to do these routine studies and make sure that all is well.

Dr. Sara Best:

I would say too that getting 24 hour urines can be a great way to engage patients in their care as well. So not only informing what you're doing as a provider but it can also really give a benchmark for patients to look forward to. I tell folks, if you're going to take a medication every day over the long term, you probably would want to be really sure that you're on the right dose of that medication. And that sort of thing. So it can really be helpful for them to see, "Look your calcium is 450. And now you've got your sodium down and you're taking the med. This is great." Because it may take a while for them to see a different in stone events. Because whatever stones they have they may continue to pass and it can be frustrating for folks if they don't have an end point that they can see in the short term.

Dr. Sara Best:

We do have a few other questions. I think some themes through the questions here and then maybe we can take a peek at the poll. There's a question about, does low protein diet actually work on acidic urine once metabolic syndrome is present in a patient?

Dr. Kristina Penniston:

You know, diet I think has some role in addressing urine acidity as pH. But it's limited. And we need to be aware of its limits. It's used in dog and cat foods right? We can manipulate urine pH in those foods. But that's because they're concentrated. It's hard to do that in such a magnitude in humans given the variable diets on a day to day basis that we eat. So yes it can be done but in really severe cases, medication has to be used to help.

Dr. Sara Best:

We also have another question about mineral water while we have you on here. Is there a concern about your water source?

Dr. Kristina Penniston:

So I was just typing an answer to that. Mineral waters are bicarbonate. They confer a bicarbonate load. And they usually have magnesium in them as well, which is an inhibitor of calcium oxalate stones. So I favor the use of bicarbonate waters in addition to other beverages. As I said, not any single beverage is going to be a panacea. But I certainly favor the use of these beverages.

Dr. Sara Best:

And a quick question for both of you, what are your approaches for home monitoring of urine pHs in patients with stones? Do you recommend that? Do you find that effective? How do you go about doing that?

Dr. Kymora Scotland:

So I think for uric acid stones, we're doing uric acid dissolution. That's particularly helpful. And it's actually not that expensive, at least in the US and in North America, to get the pH strips that patients... And patients really... They [inaudible 00:54:59] onto this because it's something that they can do. And they can see exactly what they're doing and if there's a change based on the medication that they're taking. So that's one of the ways to follow up and get patients involved.

Dr. Kristina Penniston:

Dr. [inaudible 00:55:17] who's our nephrologist in our stone clinic here, he and I did a study where we gave patients hydrometers, which are commonly used if you have fish tanks. So we purchased a bunch of these and we had patients use them to measure their specific gravity. It was just a fancy way of doing what Dr. Scotland just said. It was a little bit of a gimmick. People kind of liked it. But the same thing can be achieved with dips.

Dr. Sara Best:

I'm taking a peek through the poll results here and pretty interesting here. It looks like about half of our participants use 24 hour urines in high risk or recurrent stone patients. Only about a third are using them routinely. 14% not at all. Which I think is probably very reflective of overall practice, maybe even showing more use of 24 hour urines by our audience who selected for themselves to attend this talk. And then we have, for medical management, which I'm presuming is mainly medications, we've got about looks like 44% getting targeting therapy for high risk patients and about a quarter of folks participating are using empiric therapy routinely. That might be a good target for Dr. Scotland and Dr. Penniston to tell us, when are times that you are likely to just go with empiric therapy? Or do you really try to talk everybody into doing a metabolic evaluation?

Dr. Kymora Scotland:

I have to say that I do metabolic evaluations of almost all of my patients. I do think, for the reasons that you mentioned that it is helpful. Especially if you can afford it. It's helpful for patients to know and it really helps them to become a partner with you when you're making these decisions. So I very much routinely will do it. But for patients how we do 24 hour urines and we don't see anything, then we start doing empiric therapies for patients who can afford to do it. So unfortunately a lot of my patients in the county system are not able to do this. And for patients who are just sort of like, you know, a little bit older. So when you've got the 74 year old patient who's coming in to you with stones and a history of stones, we can start talking about what are sort of the basic things that you can do.

Dr. Kristina Penniston:

For diet I guess I would say, if I'm going to see a patient I'm going to assess his or her diet and I'm going to really try to target in on the specific things that they need to do. Rarely do I give I guess what empiric would be sort of all the recommendations that are possible, I would be-

Dr. Sara Best:

All right well thank you everybody very much. We've got Dr. Winoker is going to summarize here and talk about other offerings from the society. Thank you everybody for your time and best of luck.

Dr. Jared Winoker:

Great. Thanks again to all our panelists and our moderator. Just a couple of housekeeping slides before we let you go. Just a reminder of course you should join us again next week as the masterclass rolls on. We're going to be led by our moderator Dr. Amy Krambeck, who'll be leading an expert panel on overcoming the learning curve associated with prostate enucleation. This webinar, you can sign up for it on our endourology website. There you can also see all the previous recordings including today's webinar and all of our webinars over the past year. As a reminder, regarding CME, you're going to be receiving a survey from Michele Paoli at the email address that you have on record. When you do get it, just go ahead and indicate which seminars you've actually attended and then the CME certificate will be sent to you at that address. Please do take not that it's important to actually fill out the questionnaire and that this and each of our seminars as it is important for securing your CME credit.

Dr. Jared Winoker:

For those who are not already signed up as members, we do encourage you, visit our website for more details, for the many member benefits including but not limited to full text online access to all of our journals. And finally, just want to go ahead and remind everyone to save the date, as of right now, we're going to be proceeding with the World Congress of Endourology and Technology, which will be taking place this fall in September, Hamburg, Germany. Thanks again for joining us and we look forward to seeing you again.