Year in review: 2022 highlights in stone disease

SAP Partner | <b>UCSF Health</b>

Thomas Chi, MD, discusses 2022 milestones in stone disease and looks ahead to what might be on the horizon for the field in the coming year.

The past year has brought about some incredible strides in urology, spanning everything from advances in treatments to changes in practice management. To celebrate these achievements, Urology Times® is closing out 2022 by highlighting some of the clinical and research milestones from different areas of urology over the past year.

In this installment, Thomas Chi, MD, discusses some of the highlights from 2022 regarding stone disease and looks ahead to what might be on the horizon for the field in the coming year. Chi is a professor and associate chair at the University of California, San Francisco.

Could you describe your clinical practice?

I am a professor and associate chair at the University of California in San Francisco [UCSF]. My practice is at an academic tertiary referral center where we see a lot of complex cases around kidney stones, minimally invasive surgery, and enlarged prostates. As a result, I see a lot of patients that end up needing percutaneous kidney stone surgery, ureteroscopy, and I do a fair amount of holmium laser enucleation of the prostate, so we have big prostates over here. It's a mixture of different types of things.

As an academic urologist, I spend a lot of my time in research and teaching. It's a lot of fun helping to develop that next generation of urologists and thinking about how we can advance the frontiers of clinical care for our patients.

Over the past year, what have been some clinical and research highlights in stone disease?

There are a lot of neat things. The fun thing about stone disease is that there's a lot that we don't know. As a result, there are a lot of amazing areas where people are innovating and thinking about different ways to approach stone disease.

I think if I were to break down the different areas where there's excitement to me, one area would be a basic understanding of how stones form. There's a lot of work in microbiomics, and [looking at] how the microbiome affects kidney stone formation and where kidney stones come from. We're doing a lot of work in our lab on genomics and trying to understand how genes and people's genetic disposition puts people at risk.

There's also been exciting work in pharmaceuticals in the past 5 to 10 years, after a long spell of having no new drugs for kidney stones. We've seen some things develop in drugs, like new drugs for people with hyperoxaluria, or high oxalate in the urine, and for cystinuria. For example, we're doing a clinical trial now on a drug target that came out of our lab to try to treat cystinuria. There's been a recognition that some of the worst versions of stone disease like cystinuria and bad hyperoxaluria may be areas where we can develop drugs and help the worst hit patients with kidney stones. So, pharmaceuticals have been very interesting in the past several years.

Related tangentially to that, people have developed a few new medical grade foods. You could think of these as supplements; you can buy them over the counter. There is a product called Moonstone, for example, that was developed by one of my partners, Marshall Stoller [, MD], who has been in the stone business for a long time. Him and several colleagues from across the country—Brian Eisner [, MD], for example, at Massachusetts General Hospital—have come up with a drink to prevent patients from forming kidney stones. It works by changing people's citrate levels and their PH. Those medical foods supplements have seemed to be effective and are readily available to patients. There's also LithoLyte and a couple others that are out there now that are readily accessible, which is exciting. I think our ability to prevent stones is key because the recurrence rates are so high. That's what I have seen on the basic science portion and the pharmaceutical side.

There's always a lot of big interest in technology. Endourologists and stone specialists in general, we tend to be tinkerers. The current status quo is never good enough. We're always looking for the next best thing to try to advance the way that we do things. In that space, there's some neat technology on the horizon. People have developed some ways for non-invasive breaking up of stones. Some things that come to mind, there's a company has spun out of University of Washington, SonoMotion is the name of the company, and they're developing ultrasound technology to try to break up stones or push stones around non-invasively for patients, which is really neat. There's some amazing microbubble technology. Full disclosure, it's connected to some work being done at UCSF, but [it looks at] ways to enhance our ability to break up stones non-invasively. Those are things that are on the horizon that are really neat.

I think that it's an exciting time for stones because for many years, we've [been] like the carpenter. You see a nail, you're a hammer, and so we see a stone, we just get rid of the stone. Now we've got a lot of movement in terms of understanding how stones form, some pharmaceutical interventions that we can use to prevent stones, and then how we can get even less invasive to try to get stones in the least morbid way for our patients. There's a lot of excitement in the past couple of years in stones.

What advances are you expecting in 2023 in stone disease?

For stone disease, I think that the advances that we should be looking forward to in the next year or 2 is in understanding how pressure in the kidney, for example, changes and affects our ability to take care of our patients safely. There are some terrific labs across the country—University of Michigan, Massachusetts General Hospital, Duke University all come to mind—where they're doing some really neat studies, both in animal models and now moving towards clinical translation in people, to understand how it is that pressure during the time of surgery can affect risk of infection and pain after surgery.

In conjunction with that, there are now devices that can measure pressure at the time of surgery, in particular for ureteroscopy. When you're up in the kidney, and you have irrigation coming in, how much does the pressure inside the kidney affect people's risk of developing infection afterwards or having really bad pain? One company that comes to mind would be Boston Scientific, where they've created the next generation of a disposable ureteroscope, that has a pressure monitor on the end. They've done some first in human clinical evidence gathering now in Canada to show whether that seems to make a difference for patients. That could be an exciting development in the future as we understand the clinical characteristics that maybe we never measured before. Can we do surgery safer for people? I think that's going to be exciting work in the next year or 2.

There's also been a focus on a related field in temperature. As we put fluid in the kidney, how much do we need to worry about temperature? We've had a lot of development of new and higher-powered lasers, new energies like thulium fibers, and new lasers that have different pulse modulation. As we use bigger energy in the kidney, how can we make sure that it's safely delivered and effective, so we can remove stones, but also do it safely for our patients? Some of the labs right now in Michigan and a couple other places are doing some high-level work to try to understand how much we should be worried about the heat generated from these lasers. I think it'll help us to figure out the boundaries between pressure and temperature in the kidney and how we can be safer for our patients. I think that's going to be important for us.

In the other areas that are clinically relevant, we've talked a little bit about the different technologies that are coming around, and my hope is that we're going to see some things that are going to move towards FDA approval and get these in people's hands in the next couple of years. One area where there's a lot of excitement is how can we look towards robotics. As you can imagine, robotics has transformed many areas within urology: pelvic surgery, prostate cancer, women's incontinence work. People are starting to develop new robots that can change the way that we do stone surgery. As people think about how we can do stone surgery more effectively, less morbidly for our patients, and less invasively, I think we're going to see robots enter our picture. A lot of those companies are starting to move things towards production and FDA approval. Hopefully, that's going to end up in our operating rooms soon. And by “soon,” if we could see something in our hands the next year or 2, I think that'd be exciting for all of our patients.

Could you describe your own research interests?

I run a translational lab here at UCSF, and we run the gamut of looking at many things, from the benchtop all the way to the bedside. One of the things that makes me passionate is trying to prevent kidney stones. When you have a stone, we know that half of the people are going to get another one within 5 years without good prevention. If we can get an understanding of why stones form and how to knock it out of the park before they even get inside the body, I think that's going to serve our patients well.

We do a lot of studies on genomics to understand the gene sequencing and the gene profiles for patients that might result in high risk for stones. We're also doing a lot of work on what we would call a microarchitecture understanding of kidney stones. If you take a microscopic picture of a kidney, but then zoom down 100x, 1,000x, even smaller and smaller at the nano level—so micrometers and nanometers, not meters and feet—can we understand what's going on at that microscopic level, the interface between calcium and minerals, and the meat of the kidney? What drives those stones to form? We're zooming in on those areas and how we can understand where stones come from. Then, the next step is going to become, “well, if we know where stones are coming from, how can we identify the areas that we can put an intervention into to prevent the stones from either coming back or forming in the first place?” That's one area where we're looking at.

As we move towards translational work, we've got a big registry now that's multi-institutional and collecting prospective data on our patients. It's called ReSKU, or the Registry for Stones of the Kidney and Ureter. This has been a fun experience going on 7 years now, where we're constantly collecting information about patients. We've got it live at UCSF, and we've got it live at Oregon Health & Sciences University as well as the University of California, San Diego. We're building out to more and more institutions, so on an ongoing basis, we're collecting data on patients so we can understand what patients experience. How do they feel? Then we can bring that data back to the lab to link it to things that we're seeing in the lab to understand how those 2 things come together.

One example of where that's been successful for us is that we're now developing things like biomarkers. If we look in urine, what types of things can we find in there that might help us to predict who's at highest risk for having a new stone in the future? And how can we identify stones non-invasively without imaging? Those are the types of things that we're working on that link that benchtop work to the bedside in many ways. Using clinical data that's collected at a high quality, ongoing prospective way has helped us.

On the clinical end, as we move towards surgery, we're doing a lot of things in device innovation, as well as improving our techniques with surgery. A lot of our clinical work here is teaching people how to use ultrasound in order to do things like percutaneous nephrolithotomy more effectively, easily, and have urologists get their own access. We've been lucky to have new courses at the American Urological Association National Meeting. We had a course this year at the World Congress for Endourology and Uro-Technology in San Diego. We're bringing education to our communities so we can teach people how we can use ultrasound as a tool to treat the kidney, to remove stones, and to safely operate on patients with less radiation. It's been a lot of fun. We've had great partners from across the country. The feedback has been very positive, and it has brought new tools to urologists’ hands. These are some of the things that get me excited and have made a big difference for our patients and for the urology community.