Dr. Caleb Nelson on pediatric stone evaluation, treatment, and prevention

Caleb Nelson, MD, MPH

Kidney stones are a significant medical problem that continues to grow in severity, yet beyond technological advances in surgical instruments, little development has occurred in basic science/prevention side of stone disease. In this interview, Caleb Nelson, MD, PhD, discusses the current state of evaluation and treatment of stones in pediatric patients. Nelson is the director Clinical and Health Services Research, codirector of the Kidney Stone Program, at director of Quality and Safety at Boston Children’s Hospital and an associate professor of surgery and pediatrics at Harvard Medical School, Boston, Massachusetts.

What is the scope of the problem of kidney stones in children in the US, and how is it projected to change over the next several years?

It's a significant problem, and what's worrisome is that it's become a much more significant problem over the past 10 to 20 years. If you look at the incidence data that have been reported, they consistently show that everybody has seen an increase in pediatric stone disease. It's been looked at in a number of different settings and different methodologies, and it's all been pretty consistent that the number of stones we're seeing is going up. There's always a debate about how much of it is a real increase in disease vs just more diagnoses, because of, say, improved or more frequent imaging tests, more utilization of ultrasounds or CTs, that see stones that maybe would have remained undiagnosed in the past. But I think the general feeling is that even accounting for that, the number of cases has gone up.

Stone disease in the adult world is obviously, incredibly common. Approximately 10% of all adults will get stones in their lifetime. Obviously, it's miserable to have them; they can be very morbid in terms of causing other consequences: kidney failure, infection, things like that, especially if they become recurrent stone problems. But if you're a healthy person who doesn't form their first stone until they're 50, chances are, if that's a one-time thing, you're not going to have a lot of issues. If you're not going to have another stone for another 50 years, we're probably not going to worry about it. But if someone forms their first stone when they're 8, or 12, or 14, we see that as a very concerning sign that it's highly likely to become a recurrent problem, and they've got many years of life left to live during which those stones are going to be an issue. So the stones you have now are obviously a concern, but the lead time, and the future implications of continuing to form those stones, are really significant. That's why we push so hard to do metabolic testing on all the kids and try to figure out why stones are forming because unlike the 50-year-old, if you're 8 and you've got your first stones, there's a very significant chance that there's an underlying situation going on in terms of cause and you're going to keep forming them as time goes by.

What does the current treatment landscape for pediatric stones look like? What sort of treatments are indicated for use with pediatric patients?

It's pretty analogous to how adults are treated. There are 3 primary modalities that we use to treat stones. There is shock wave lithotripsy, which has been around for 40 years now. It started in adults, but quickly followed in kids and for quite a few years was considered the gold standard for the treatment of stones in kids. The second modality is the ureteroscopy procedure, using a scope going retrograde in from the bladder up toward the kidney. That has dramatically increased in utilization over the past 20 years, primarily because of progress with the equipment, just like it has in adults as well. But for kids in particular, the smaller they are, the smaller the equipment has to be, so the availability of some of these really small scopes has made treatment feasible that would not have been 20 or 30 years ago other than through open surgery. The third option is percutaneous nephrolithotomy, which is done through a small hole in the skin, again using scopes and other devices to break up the stones. That, just like in adults, is reserved primarily for patients with very large stones or a stone burden that's so substantial that you'll never be able to clear it by the other modalities. In children, at least in the US, that represents a very small percentage of all the cases that are done, maybe 1% or 2%.

What are some risk factors for stones in pediatric patients?

We're still trying to figure it out. Some of it is analogous to what you see in adults. Poor hydration is clearly a major factor. Things like high-salt diets and sedentary lifestyles happen in kids too, and all those other things that seem to predispose to stones. We know that in any humans with stones, there is a some risk if you do metabolic assessment, you will find things that are abnormal in a percentage of people with stones. But in some people with stones, you don't find any abnormalities. It doesn't mean nothing's wrong, it just means we don't understand the biology enough to figure out why that person is forming stones, but of the identified and known abnormalities that you see, they are significantly more common among kids who have stones compared with adults who have stones. So if you do this work-up, you're much more likely to find something in a child than in an adult. That involves factors like high urine calcium levels, low urine citrate levels, and all sorts of other urine and blood chemistry abnormalities. Those different findings can have different causes. Some of them are environmental, some are genetic, some are medication driven. Part of the work-up is sorting out for any individual kid, what are the factors that are going into this?

In the pediatric population, there's a big chunk of our patient population with severe medical comorbidities, a lot of them related to neuromuscular dysfunctions and mobility problems. So it's conditions like cerebral palsy, spastic quadriplegia, and severe developmental delay, kids who spend almost all of their time on a stretcher or in a wheelchair, and don't move around very much. They have very artificial diets, they are fed by tubes, or have very limited food intake and possibly limited fluid intake, as well. The stone prevalence in that population is pretty significant. And again, it's probably due to multiple factors that are unique to that population: the lack of mobility, the very artificial diet, the fact that many of them are on medications for seizures or other conditions that change their urine chemistry in ways that are not helpful from the urology standpoint. That's a big subpopulation of the pediatric stone world that is unique to what we see. Certainly, we see lots of otherwise perfectly healthy kids who come in with stones, but that is a big chunk of them.

How are stones evaluated in pediatric patients?

The biggest single difference is that in pediatric stone disease, ultrasound is where we always start, and ultrasound is the only thing we do in the vast majority of our patients, unlike with adult stones, where sometimes it seems like everyone who walks through the door gets a CT. We do see kids who were referred to us for their stones but who were diagnosed when they were seen at a community hospital somewhere and were immediately given a CAT scan, even though they're 12 or 14 or 16 years old, because that's just how things work in the adult world. They just CAT scan everybody. Whereas in a stone program at a children's hospital, we almost never start with a CAT scan. Ultrasound is the mainstay of what we image with. To some extent, that's because it's easier, especially in prepubertal kids, because they're small, they're usually thin, and you can image very well with an ultrasound. It's harder, obviously, if you have a 17-year-old who weighs 240 pounds, but we still almost always start with it. Diagnostically, that's the single biggest difference between us and the adult stone area. We certainly still do CAT scans, because there are many situations where they're helpful or necessary, especially for surgical planning, or for cases where you think there might be a stone but the ultrasound is not finding it. But certainly, that's the exception.

The other main difference diagnostically is that we basically recommend metabolic testing for every patient we see after a first stone. That is definitely not the case in the adult world. There are lots of people who have multiple stones over several years and never get a metabolic assessment, just because it hasn't been seen as really necessary in an adult who's formed a stone or 2 or 3, whereas in the pediatric group, the rates of metabolic abnormality are so high and because they're starting so young, we more or less always do it unless the family simply doesn't comply or refuses.

What sorts of preventive measures do you encourage with patients?

Hydration is the foundation of everything. It's not particularly sexy, but that is the key thing that people have to do. That's what we hammer across every time. Almost every kid we test is under hydrated, and so we focus a lot on ways to increase their fluid intake. Nowadays, there are lots of tools. There are apps on your phone that will alert you to when you're supposed to drink. There are smart bottles that have little chips in their lid that record every time you drink. There are a number of ways we can get people to try to drink more. That's true in the adult world too, but it's more challenging in children because they don't necessarily do what we say, and they don't do what their parents say. Teenagers, of course, are a whole different ballgame. They don't do what anyone says. Compliance issues around fluid intake and hydration are really significant. We spend a lot of time around that in the stone clinic.

There are some exciting new medications available for certain indications. One of the metabolic conditions is primary hyperoxaluria, which is a rare genetic abnormality that leads to stone formation. There is a recently approved medication called lumasiran [Oxlumo] that treats that and seems to be very effective in terms of reducing and correcting the metabolic abnormality in the urine, so that those kids hopefully will be much less likely to form stones over time. That's an important group because, although the condition is rare, those kids tend to form stones relentlessly; they have multiple stones a year and need multiple surgeries. There are not a huge number of adults with those conditions, because they tend not to survive that long; they get into things like renal failure and other consequences of that condition. Hopefully, that will be a bit of a game changer for the small subset of kids that we see with that. That's exciting, but it doesn't reflect the needs of the vast majority of stone patients. Huge amounts of research and development have gone into the technology of the surgical interventions—the scopes, the lasers, all the toys we get to use within the OR—which are transformative and night-and-day differences to what stone surgery was like 40 or 50 years ago. That's been revolutionary. But on the prevention side, it's amazing how little there is compared with 20 or 30 years ago. There's just not much that's different.

Cystinuria is one of the other genetic stone conditions we see that, again, is rare, but patients that have it form stones over and over again. The primary medication used for that, tiopronin [Thiola], came out 30 to 35 years ago, and there's been nothing new since then. That's true in a general sense for almost all of this. It's an area that has not been studied enough. The resources and the basic science have not been where they need to be. Look at all of the new drugs in urologic oncology; look at all the new drugs for overactive bladder. There's very, very little in stone prevention. That's something that needs to change in the future. It's hard because stones are a little bit of an orphan area, in that the only people who really deal with it are urologists and a handful of nephrologists who have an interest in stones. Urologists, being surgeons, we spend all our time thinking about the surgeries we do and the equipment we need for that. That's why I think the revolution in stone surgery that has happened over the past 40 years has driven by urologists who wanted better devices and better tools. All this amazing progress has happened. But in terms of the number of urologists who study stone formation in the lab—how the kidney actually produces stones—you can probably count them on 1 hand. Similarly, nephrologists, who would be the natural people to study that since they're medicine doctors, not surgeons, are all focused on glomerular nephritis and diabetes-related kidney failure and all the other conditions that nephrologists deal with. Stones is not a priority for the vast majority of them. That's why it's been so slow in terms of producing new prevention tools. It's unfortunate, but that's where we are. Fortunately, the surgical devices have progressed enormously so we don't have to cut people open for every stone like they used to in the 1970s.