Alan Pao, MD, sees kidney stone sufferers as the proverbial middle child. Although kidney stones are relatively common — about 1 in 10 Americans will have one in their lifetime — and they’re often described as more painful than childbirth, they can be overlooked in both clinical practice and research.
As a practicing nephrologist and an associate professor of medicine at Stanford University School of Medicine, Pao says patients with recurrent kidney stones can find themselves shuffled between two medical specialists: nephrologists, who treat kidney diseases, and urologists, who are surgeons trained to operate on physical blockages of the urinary tract. Therefore, long-term management — and especially the prevention of kidney stones — may fall through the cracks.
“They’re the neglected child,” Pao says.
The guidelines for prevention and treatment have stayed more or less the same for decades, and standard medications have changed little over the past 20 years, explains Charles Scales, MD, an associate professor of urology at the Duke University School of Medicine and a lead investigator for the National Institutes of Health (NIH)-funded Urinary Stone Disease Research Network (USDRN).
But the guidelines may be changing as kidney stones become more widespread. Due to a combination of factors, including changing diet, increasing incidence of obesity and other metabolic disorders, and the warming climate, the prevalence of kidney stones has doubled over the past 30 years. Visits to the emergency department for kidney stones increase with higher temperatures, which can exacerbate dehydration, and kidney stones are more common among people living in hotter climates, Scales explains. Kidney stones are also responsible for significant loss of quality of life and productivity, and, in some cases, can cause life-threatening infections.
The USDRN, which Duke coordinates, brings together a national network of investigators conducting clinical trials on kidney stone disease at several academic health centers.
“We’re entering a new era of clinical trials in kidney stone disease,” Scales says.
Emerging research, both in the lab and in the clinic, is accelerating progress toward a better understanding of why and how stones form, how best to treat them, and, perhaps most crucially, how to prevent them.
Why do kidney stones form?
Kidney stones are made up of minerals and salts that bind together to create pebble-like deposits that can cause pain or obstruction when passing from the kidneys into the bladder. They impact about 11% of men and 9% of women. There are several different types of kidney stones, and they can be caused by a variety of factors, including dehydration, diet, infections, and genetics.
The four main types of kidney stones are:
- Calcium The most common type, these kidney stones account for about 70% of all stones. They are made up of calcium oxalate, which can be found in foods such as spinach and nuts; calcium phosphate, which forms in alkaline (high pH) urine; or a combination of the two.
- Struvite These stones make up about 15% of all stones and are caused by bacteria in urinary tract infections.
- Uric acid These kidney stones comprise about 10% of all stones and are formed when urine is highly acidic. The factors that make urine acidic include a diet heavy in red meat, high-fructose corn syrup, and alcohol. Certain metabolic conditions, such as type 2 diabetes and obesity, are associated with altered chemistry that increases the risk of uric acid stones.
- Cystine The rarest type of stone, the cystine stone is caused by a genetic disorder that makes the kidneys prone to leaking an amino acid that forms crystals.
But some researchers say the current understanding of how and why kidney stones form may be incomplete.
“There’s a lot of received wisdom about how [stones are] formed,” says Kymora Scotland, MD, PhD, an assistant professor of urology and director of endourology research at the University of California Los Angeles (UCLA) David Geffen School of Medicine. “With more and more data, some of these ideas are being updated.”
In January, Scotland and her colleagues published a paper revealing their discovery of bacteria within calcium oxalate stones retrieved from patients, using sterile procedures. The research team used advanced imaging techniques, including X-ray fluorescence, micro-computing tomography, and a scanning electron microscope to prove that the bacteria lived within — not just on the surface — of the stones. Previously, researchers did not believe that bacteria played a role in calcium stone formation, but this discovery calls into question the common understanding that calcium stones are formed exclusively by the oversaturation of calcium and oxalate or phosphate in the urine.
“I’ve always thought that that can’t be the whole story,” Scotland says. She was inspired to research kidney stones during her urology residency at Thomas Jefferson University Hospital in Philadelphia, where she worked with patients who suffered immensely from their recurrent kidney stone disease. “There has to be something happening at the local level causing supersaturation — multiple things contributing to a stone forming.”
Scotland says that she and her colleagues are using their discovery to develop a new therapeutic approach to stone prevention that doesn’t involve antibiotics, which create the risk of antimicrobial resistance.
The findings support earlier research, published in 2024 from the Cleveland Clinic, that reported that the kidney has its own microbiome — a collection of microorganisms, including viruses and bacteria — and that it can foster or prevent the formation of stones.
“It’s a really exciting time,” Scotland says.
From reactive to proactive
Standard care for kidney stones depends on the size. For small stones, experts recommend drinking two to three quarts of water daily to flush them out and taking over-the-counter nonsteroidal anti-inflammatory medications to manage pain. Larger stones may require procedural intervention, such as shock wave lithotripsy, which uses sound waves to break up the stones; ureteroscopy, using a scope to target the stone with lasers; or percutaneous nephrolithotomy, a surgery that removes particularly large or complex stones directly through an incision in the back.
The technology used for these procedures has advanced in recent years, Scales says. Instruments are getting smaller, lasers are getting more powerful, and surgeons can now use a scope to suction stones out.
But there is a need for more evidence-based guidelines for when to intervene, Scales says. The current standard of care for medium stones, between 4 and 10 millimeters, that are not causing symptoms is to monitor them rather than intervene. However, a recent systematic review of medical literature found that proactively treating even asymptomatic kidney stones could reduce the need for subsequent surgeries, though the authors acknowledged the limitation of a lack of research comparing the two approaches.
“We don’t know which is better,” Scales says.
This problem extends to knowing how best to prevent different kinds of stones, particularly in patients with recurrent disease, Pao adds.
“We, as a field, don’t have high-quality randomized controlled trials to inform guidelines,” he says. “The data hasn’t been generated.”
But some researchers, like Pao and Scales, are working on building up that data repository. The USDRN, for example, is coordinating an ongoing trial studying early intervention on asymptomatic stones.
Looking toward prevention
The dominant advice for prevention is to drink about 12, 8-ounce cups of water a day and to follow a diet that is rich in calcium (which binds to oxalates and lowers the risk of calcium stones), and lower in sodium, protein, and oxalate.
But behavioral interventions have their limitations. The USDRN published findings in March 2026 of the largest behavioral study ever conducted on kidney stone prevention. The researchers, including Scales, spent two years monitoring participants in two groups: one that received the standard advice to drink more water; and one that used smart water bottles that reminded them to keep up with recommended water intake. Despite increasing the amount of water the participants drank, the smart water bottles did not have a meaningful impact on stone recurrence.
Scales says the results show the need for personalized interventions.
Pao’s lab is working on a potential avenue for a drug that would help with prevention for people at high risk for calcium stones. Currently, doctors prescribe potassium citrate or sodium bicarbonate, which binds to calcium and makes urine less acidic, thus helping to prevent the formation of some kinds of stones. But, for some patients, these alkalinizers can increase the chances of forming a different kind of stone that thrives in high-pH urine. His solution is to target a protein, NaDC1, that is responsible for reabsorbing citrate into the kidneys. His lab is currently testing medications in animal models that suppress NaDC1 to allow the kidneys to keep higher levels of citrate to bind to calcium without also increasing the urine pH. Today, patients at risk for both types of stones have limited options.
“We leave them untreated,” Pao says. “These are the patients asking me to do something about it.”
Pao’s lab is also conducting research focused on understanding why certain people experience recurrent stones and how to prevent them.
But even as researchers continue to search for better answers, they emphasize that more awareness of the latest research on kidney stone disease care would improve many lives.
Scotland says that some of her patients have received outdated advice they’d heard from other providers, such as cutting calcium out of the diet to prevent calcium stones.
“I’d encourage [clinicians] to read up on newer information on kidney stones and make sure that what they’re telling patients is up to date,” she says.
Scales also wishes more people knew how serious kidney stones can be. In some cases, they can cause an infection that can flare up into a deadly case of sepsis.
“Last weekend I was on call, I took a couple patients to the operating room right away,” he says. “Infection with a kidney stone can be a life-threatening emergency.”
