Researchers have identified bacterial biofilms within calcium oxalate kidney stones, the most common type, challenging the established view that these stones are sterile and noninfectious and raising new questions about stone formation and recurrence.

The findings may also one day influence strategies for kidney stone prevention and treatment, according to Kymora Scotland, MD, PhD, assistant professor of urology at the David Geffen School of Medicine at the University of California, Los Angeles, and a co-author of the study.

Historically, bacteria were thought to contribute only to the formation of struvite kidney stones, which are caused by chronic urinary tract infections (UTIs). In contrast, calcium oxalate stones, which account for the majority of kidney stones, have long been considered abiotic, noninfectious, and unrelated to bacterial activity.

Clinical Curiosity Spurs Discovery

In the new study, published in the Proceedings of the National Academy of Sciences, researchers described the identification of bacterial biofilms within the mineral structure of calcium oxalate stones. The discovery stemmed from clinical observations that piqued the researcher’s curiosity.

“I noticed that sometimes patients with no history of UTIs would develop them, or even sepsis, after some stone procedures,” Scotland told Medscape Medical News.

“Similarly, when we cultured the stones obtained from surgical procedures again in patients without a history of UTIs, we would often identify bacteria,” she said. “This led us to hypothesize that bacteria actually play a role in stone formation and were not just bystanders found in the kidney.”

Using electron and fluorescence microscopy, the investigators detected not only live bacteria but also layers, or biofilms, of bacteria integrated into the crystalline mineral layers of calcium oxalate stones.

“The discovery of bacteria in the most common kidney stone type opens up new areas for stone treatment, since bacteria and biofilm components are now potential targets for stone prevention,” Scotland said. “We also believe that these bacteria may account for some of the recurrent UTIs in patients with kidney stones, and we hope to demonstrate this with ongoing studies.”

As a next step, Scotland and colleagues are evaluating the mechanisms by which bacteria influence stone growth, with the goal of developing more targeted treatments for calcium-based stones.

Bacteria’s Undercover Impact

Although the findings do not yet have immediate implications for clinical practice, they raise intriguing research questions, said David S. Goldfarb, MD, clinical chief of the Nephrology Division at NYU Langone Health and professor of medicine and physiology at NYU Grossman School of Medicine, New York City, who was not involved in the study.

“Most stones are not associated with UTIs, and most of the stones studied here have negative bacterial urine cultures,” Goldfarb told Medscape Medical News. “The questions of where these bacteria are living and how they get into the stones remain very interesting.”

“Whether the imaging reveals something about how bacteria contribute to stone pathogenesis or not remains unclear,” he said. “Because the stones are not associated with clear infections, the conventional treatment of UTIs with antibiotics may have no relevance. Antibiotics alter the intestinal microbiome, which could have adverse effects on urine chemistry, and antibiotics could be associated with drug resistance.”

The study highlights the value of applying materials science approaches to kidney stone research, Goldfarb added. However, translating this research into clinical practice poses challenges, primarily the difficulty of examining stone development in vivo over time.

“How these observations could change over time, if the stones were studied longitudinally, is interesting to contemplate,” he said.

The study was funded by the National Institutes of Health, the National Science Foundation, a National Research Service Award, the Air Force Office of Scientific Research, Chan Zuckerberg Biohub Chicago, and a CNSI Voucher Award.

Scotland and Goldfarb reported having no relevant financial disclosures.