Oral Antibiotics May Increase Risk for Kidney Stones

Diana Swift

May 10, 2018

Five classes of antibiotics are associated with an increased risk for kidney stones, results from a nested case-control study suggest. The risk is particularly pronounced with sulfa drugs and among children and adolescents, researchers report in an article published online today in the Journal of the American Society of Nephrology.

"These findings suggest that exposure to some oral antibiotics is a novel risk factor for nephrolithiasis, one that may be modifiable for the 30% of patients who receive inappropriate outpatient prescriptions for antibiotics," write Gregory E. Tasian, MD, MSCE, a pediatric urologist at Children's Hospital of Philadelphia (CHOP) in Pennsylvania, and colleagues. "These results have implications for the pathogenesis of the disease and for the rising incidence of nephrolithiasis, particularly among children."

Kidney stone prevalence has increased by 70% over the past 30 years and parallels the widespread use of antibiotics. In 2011, 262 million antibiotic courses were prescribed in the United States, Tasian and colleagues point out, with the highest rates in women and in children under age 10 years.

Kidney stones were previously rare in children. "The reasons for the increase are unknown, but our findings suggest that oral antibiotics play a role, especially given that children are prescribed antibiotics at higher rates than adults," coauthor Michelle Denburg, MD, MSCE, a CHOP pediatric nephrologist, said in an American Society of Nephrology news release.

To assess the potential effect of antibiotics on nephrolithiasis risk, Tasian and colleagues analyzed data from the February 2015 version of The Health Improvement Network (THIN), a registry of 13.8 million patients receiving care in 641 general practices in the United Kingdom between 1994 and 2015. They included 25,981 patients with kidney stones and 259,797 unaffected control participants, with a medium follow-up time of 5.4 years. Approximately 35% of cases and controls were women, and the median age at first stone was 51.6 years. The mean body mass index in both groups was more than 27 kg/m2.

Outpatient antibiotic prescriptions were most commonly written for cough and tonsillitis, as well as chest, upper respiratory tract, and urinary tract infections.

Looking at 12 classes of antibiotics, the investigators found an association between nephrolithiasis risk and five types taken 3 to 12 months before the index kidney stone date. The excess relative risk ranged from 27% for broad-spectrum penicillins to 133% for sulfa drugs.

Table. Risk Associated With Antibiotics, by Class

Antibiotic Type Adjusted Odds Ratio (95% Confidence Interval) P Value
Sulfas 2.33 (2.19 - 2.48) <.001
Cephalosporins 1.88 (1.75 - 2.01) <.001
Fluoroquinolones 1.67 (1.54 - 1.81) <.001
Nitrofurantoin/methenamine 1.70 (1.55 - 1.88) <.001
Broad-spectrum penicillins 1.27 (1.18 - 1.36) <.001


The highest risks were associated with antibiotic use at younger ages (P < .001) and use in the 3 to 6 months before the index date (P < .001). Kidney stone risk for all classes except broad-spectrum penicillins remained statistically significant for 3 to 5 years from exposure, although risks declined over time.

In 2016, Medscape Medical News reported on a study by Tasian's group showing a 16% rise in the annual incidence of  kidney stones in South Carolina between 1997 and 2012, with the greatest increase in adolescents, women, and blacks.

Scientists suspect that antibiotic-induced reductions in the microbiome, the body's community of microorganisms, and subsequent alterations in macronutrient metabolism, may promote nephrolithiasis. Antibiotic exposure has been associated with inflammatory bowel, lung disease, and, as in patients with asthma, the gut microbiota of kidney stone patients has been found to be less diverse.

But while perturbations in the intestinal and urinary microbiomes have been linked to kidney stones, no prior studies had specifically linked them to antibiotic usage.

This study was supported by research grants from the National Institute of Diabetes and Digestive Diseases and Kidney Diseases of the National Institutes of Health, which played no role in any aspect of the study. The authors have disclosed no relevant financial relationships.

J Am Soc Nephrol. Published online May 10, 2018. Abstract

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