Gregory Tasian, MD, MSc, MSCE, Attending Urologist at the Children’s Hospital of Philadelphia talks about the increase of kidney stones in children and what the reason for it might be.
Interview conducted by Ivanhoe Broadcast News in May 2018.
You’re a Urologist but then you drifted over in to research for this particular story, what was the germination of the idea to get you on to that?
Dr. Tasian: I view clinical care and research as being complimentary as opposed to being two opposing forces. And I think all good research starts with a clinical question and those come out of my everyday interactions with patients and their families. And with respect to antibiotics and kidney stones it came about probably five to ten years ago with the question of, why are we seeing such a tremendous increase in the incidence of kidneys stones particularly among children and adolescents.
How much of an increase were you seeing? Was it dramatic?
Dr. Tasian: It’s a dramatic increase. I really describe it as an epidemic. When I was training in medical school finishing in early two thousand and then residency training kidney stones were a rare phenomenon in childhood; it was often genetic conditions that caused an early onset of kidney stones. But then over the last twenty years we’ve seen this tremendous rise over a very short period of time. Over that twenty years the incidence has doubled among adolescent girls in particular, the rate is increasing at about five percent per year. It’s a dramatic increase.
I’m thinking about this, my son is twenty three and the whole antibiotic thing came about, kids were getting ear infections back in the late nineties and stuff. Is that about when the antibiotic prescriptions really ramped up to the point they are now?
Dr. Tasian: It’s an interesting question: who are the populations, who are the groups of patients who are prescribed the most antibiotics, how has that changed over time? And you look historically over the last twenty years, it’s younger patients, pediatric patients, who have been prescribed, proportionately, the greatest number of antibiotics. There was a recent article in Jama just one or two weeks ago that I think gives us some hope that some of those trends are changing and that antibiotic use has started to decrease. We don’t know, per se, what particular classes of antibiotics but we’re starting to see some positive trends to more judicious use of antibiotics.
Do you think that’s the parents that read articles and read about the dangers of over prescribing, is it a combination of the physicians and the parents or are the physicians scaling back?
Dr. Tasian: I think it’s probably three things. One, there is increased awareness amongst parents, two, increased awareness among physicians and three, a greater public health awareness that may hopefully drive practice patterns in the right direction.
You found certain classes of antibiotics. How did you key in on that in research?
Dr. Tasian: It started with the question of, are antibiotics associated with kidney stones? And if so which antibiotic classes? We went in with the hypothesis that it may be those antibiotics that are active against this particular type of bacteria called Oxalobacter which is a microbe that degrades oxalate which is a major constituent of kidney stones. At the end of the study it turned out there are these five classes associated with kidney stones. Some of these classes are active against Oxalobacter, but some aren’t. I think that speaks to the fact that it’s rarely a single bacterium that causes a disease such as kidney stones. If kidney stone disease is mediated, in part, by the gut microbiome or the urinary microbiome or both, it’s most likely that this community of organisms, many of which are interdependent on each other, that could be driving this association.
You’re talking about when somebody is prescribed antibiotics for something unrelated to kidney stones it’s destroying the proper bacteria in the gut and you were trying to figure out which portions of that were getting hit by those and then there’s all kinds of combination.
Dr. Tasian: I think those are the next steps. Right now we know that there are these five antibiotics that are associated with kidney stones. The five classes are 1) cephalosporins like cefdinir, 2) broad spectrum penicillins which include augmentin, 3) fluoroquinolones like cipro, 4) nitrofurantoin which is used to treat urinary tract infections and 5) sulfa drugs like Bactrim or septra. These classes of antibiotics all have different mechanisms. The next steps are to understand what effect they’re having on the gut microbiome and urinary microbiome and what is actually mediating the effect of antibiotics.
So by mediating you mean that there has to be some sort of a catalyst that starts that change?
Dr. Tasian: Yes, the causal mechanism between antibiotics and kidney stones. Most likely it’s due to the effect on the microbiome either in our intestinal tract and/or our urinary tract. But we don’t know what those shifts are. You had spoken about this destruction of the microbial community. It’s more likely a shift, and that shift may be over a prolonged period of time, over the course of months to years. We noticed that the greatest effect was within three to six months after the antibiotic exposure, but it persisted but at a lower level for up to three to five years afterward. There’s likely some shifts that are going on and there may be some restoration with time, but it persists for a great period of time after the exposure.
It’s almost like a nuclear half-life if I’m hearing you right. Parents who are administering these and physicians dispensing the antibiotics, what would you say to parents about giving too much to their children for example?
Dr. Tasian: Well I think antibiotics without question have saved millions of lives and, when used appropriately, they are an extremely important and effective part of what we do in medicine. But the question becomes if antibiotics are prescribed unnecessarily, for example, for a viral illness that’s where I think we need to focus our efforts. We should be using antibiotics judiciously and appropriately rather than for conditions in which they provide no benefit and now appear to cause harm.
This used to be kind of an old person’s disease, you got kidney stones. How is it different in kids, what symptoms do they manifest?
Dr. Tasian: You’re absolutely right in that historically kidney stones was a disease of white middle aged men. And then over the last twenty years we’ve seen the shift to an earlier onset of the disease where it’s happening in the teenage years or early twenties. And with that shift, we’ve seen more of a predominance among females. Among adolescents the typical patient is a fifteen year old or so girl. Whereas in adulthood it’s still about a forty year old man. Why we’re seeing this shift in age and sex is something that we’re actively investigating. What that means for that child who has a stone earlier in life is that they have a long lifetime over which stones can occur. With each episode, you have pain, you have nausea, vomiting, blood in the urine. But even more than those symptomatic events that bring you to the emergency room, kidney stones are associated with decreased bone mineral density, increased risk of fracture, increased risk of high blood pressure, and among adults, increased risk of cardiovascular disease. Younger women have the greatest risk for many of these conditions associated with stones. What makes me concerned as both a urologist and an epidemiologist is that as we’ve seen the shift to young adult life or adolescence is that all those conditions may be more prevalent over a lifetime because kidney stones are starting earlier in life.
The kidney stones which recur frequently have a long lifespan to really attack that person. The kid who gets it because their tubes are smaller, they’re not fully developed, does it impact them on a greater basis?
Dr. Tasian: It can. When there is a stone in the ureter, which is the tube between the kidney and the bladder, the question is: “is that stone going to pass on its own or is it going to require surgery?”. And a good number of patients do require surgery. When a stone is in a child there are technical considerations and the size of the instruments is very important, even more so than adults, because the urinary tract is just simply smaller. It’s an area where there’s an emerging need for specialists in this area because we need to be able to treat our patients effectively, giving them the state of the art care. And that’s certainly why we’ve developed our Kidney Stone Center at the Children’s Hospital of Philadelphia- so we can provide children surgical care when necessary and then also from the medical side prevent stones from occurring.
When you see kids who come in and present with kidney stones what are some of the things that you see with them?
Dr. Tasian: The way a child would typically present with a stone is in a younger patient for example, five or six, he or she may just simply have belly pain, blood in the urine, maybe some nausea. As you get older in to adolescence, after puberty, and young adulthood, they have those typical signs of a kidney stone, pain in the flank, often with nausea or vomiting. But it can be a little bit different in a younger child.
You said five or six?
Dr. Tasian: Certainly. The youngest patient that I’ve had to treat surgically for a kidney stone was eight weeks old.
How is that even possible, was that related, it couldn’t be related to antibiotics right?
Dr. Tasian: I think in this case it was multifactorial and I think it speaks to the need to treat every child individually and to be able to understand what the risk factors are so you can prevent a stone after you’re removed it surgically. But that’s the entire reason that we developed our Kidney Stone Center at CHOP so we can bring together that expertise in Urology, nephrology, radiology, nephrology, and emergency medicine so we can provide comprehensive care and deliver the most effective safest care possible for every child.
Because of your research is that one of the first questions that you ask when the kids come in with stones?
Dr. Tasian: What we want to do in both the research side and the clinical side is understand what those factors are that cause a stone to form at this moment in time. And both clinically and in research we understand that there’s probably a genetic background, a certain genetic susceptibility that doesn’t change over time. But then it’s all these other exposures that interact with the genetic susceptibility to cause stones to form – and those exposures could be diet, it could be antibiotics, it could be other medications, it could be environmental influences. Our group focuses on the effect of temperature and humidity on stones in their incidence. And then moving into how do we take that information to prevent stones? For example, a lot of our work is focused on adherence to best practices. We know what’s good for us. We know, for example, that drinking a lot of fluids prevents stones, but it’s very hard to do that. There is an ongoing multicenter randomized trial of strategies to maintain a high fluid intake. Using things like smart water bottles, using things like financial incentives and coaching so we can personalize ways to overcomes those individual barriers to maintain a high fluid intake and then decrease stone recurrence over a lifetime.
Just a random question here, before bottled water came out and we were turning on the faucet and drinking water, I don’t remember drinking a ton of water like they tell you to do. Have you seen an increase, does the bottled water have anything to do with it? Expense, the plastic?
Dr. Tasian: Certainly there are environmental concerns with the amount of bottled water that we consume. The question becomes what about the content of that water. It’s an area of where there’s not a lot of evidence and something that we’re examining at a population level. We are investigating the quality of water, the content of water, the minerality of water, and what effect that may have on areas that may have a high prevalence of stones. The rationale for focusing on water hardness is that we know a diet that is moderate to high in calcium content is protective against stones. That’s something that, on the surface, runs counter to logic but has been shown very convincingly some twenty years ago.
Now we find out that the gut is kind of the magic skeleton key of the kingdom?
Dr. Tasian: I think the concept of the microbiome certainly is something that we’re examining more and more in medicine, including within kidney stone disease. So when you look at all of the cells in our body only about one tenth of them are human. The other ninety percent are microbial cells. And a lot of those are the gut microbiome, all those communitues of organisms that live within our intestinal tract. But we also have a skin microbiome, there’s a urinary microbiome. The more that we understand about various diseases, the more we understand that changes or shifts in these microbiome may be an important factor for the development or the severity of the disease.
Just one summary statement about your research.
Dr. Tasian: Our research is focused on understanding the determinants of kidney stone disease among children and adolescents so we can better develop prevention strategies to decrease the morbidity of this growing disease across a lifespan.
END OF INTERVIEW
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