Study Finds Link Between Antibiotics and Kidney Stones

The overall prevalence of kidney stones has risen by 70 percent over the past 30 years, with particularly sharp increases among adolescents and young women. Kidney stones were previously rare in children. This increased incidence is a public health concern.

In a study recently published in the Journal of the American Society of Nephrology, CHOP researchers have found that children and adults treated with some oral antibiotics have a significantly higher risk of developing kidney stones. This is the first time that these medicines have been linked to this condition. The strongest risks appeared at younger ages and among patients most recently exposed to antibiotics.

“The reasons for the increase are unknown, but study findings suggest that oral antibiotics may play a role, especially given that children are prescribed antibiotics at higher rates than adults,” says study senior author Michelle Denburg, MD, MSCE, a pediatric nephrologist at Children’s Hospital of Philadelphia (CHOP). Denburg partnered with lead author Gregory Tasian, MD, MSc, MSCE, a CHOP pediatric urologist.

The study team drew on electronic health records from the United Kingdom, covering 13 million adults and children seen by general practitioners in The Health Improvement Network between 1994 and 2015. The team analyzed prior antibiotic exposure for nearly 26,000 patients with kidney stones, compared to nearly 260,000 control subjects.

They found that five classes of oral antibiotics were associated with a diagnosis of kidney stone disease. The five classes were oral sulfas, cephalosporins, fluoroquinolones, nitrofurantoin, and broad-spectrum penicillins. After adjustments for age, sex, urinary tract infection, other medications, and other medical conditions, patients who received sulfa drugs were more than twice as likely as those not exposed to have kidney stones; for broad-spectrum penicillins, the increased risk was 27 percent higher.

The strongest risks for kidney stones were in children and adolescents. The risk of kidney stones decreased with time from exposure, but remained elevated several years after antibiotic use. 

Study recommendations and future research

Scientists already knew that antibiotics alter the composition of the human microbiome — the community of microorganisms in the body. Disruptions in the intestinal microbiome have been linked to the occurrence of kidney stones, but no previous studies revealed an association between antibiotic usage and stones.

The new findings reinforce the need for clinicians to promote antibiotic stewardship and be careful in prescribing correct antibiotics. They suggest that antibiotic prescription practices may represent a modifiable risk factor — a change in prescribing patterns might decrease the current epidemic of kidney stones in children. One co-author of the current paper, Jeffrey Gerber, MD, PhD, is an infectious diseases specialist at CHOP who leads programs in antibiotic stewardship — an approach that guides healthcare providers in prescribing the most appropriate antibiotic for each patient’s specific infection, with the aims of improving individual outcomes and reducing the overall risk of antibiotic resistance.

The study team is continuing to investigate the microbiomes of children and adolescents with kidney stones in a single-center study at CHOP. Its goal is to expand this research into broader, population-based studies to better understand how variations in microbiome composition may influence the development of kidney stones and how to reduce or prevent them.

In addition to their CHOP positions, Drs. Denburg and Tasian are members of the Center for Clinical Epidemiology and Biostatistics (CCEB) in the Perelman School of Medicine at the University of Pennsylvania. The CCEB holds the license for the database used in the study. The National Institutes of Health (grants DK106428, DK093556, and DK083908) supported this research.

CHOP’s Pediatric Kidney Stone Center was established to meet the increasing need for specialized care for children with urinary stone disease. The Center uses a multidisciplinary approach in the diagnosis and management of stone disease, with a focus on preventing recurrence and improving outcomes. The Pediatric Stone Center offers state-of-the-art treatments, including incisionless stone ablation with laser and shock waves, as well as minimally invasive surgery performed by laparoscopic and robotic techniques. Learn more or refer a patient by calling 215-590-2754.